International Council

of Nurses

TB
GUIDELINES
for Nurses in the Care
and Control of Tuberculosis
and Multi-drug Resistant
Tuberculosis

3rd Edition
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Copyright © 2015 by ICN - International Council of Nurses,

3, place Jean-Marteau, 1201 Geneva (Switzerland)

ISBN: 978-92-95099-31-9
International Council of Nurses

TB GUIDELINES

for Nurses in the Care and Control of

Tuberculosis and Multidrug-Resistant
Tuberculosis

3rd Edition
Table of Contents
Preface........................................................................................................................ 1
Introduction................................................................................................................ 2

Chapter 1: Tuberculosis: the Clinical Context ........................................................ 3

History of tuberculosis ................................................................................................. 3
Epidemiology of tuberculosis ....................................................................................... 4
Pathology..................................................................................................................... 6
Pulmonary TB .............................................................................................................. 7
Extrapulmonary TB ...................................................................................................... 8
Signs and symptoms of pulmonary and extrapulmonary TB ....................................... 8
Risk factors for TB ....................................................................................................... 9
Managing and preventing risks .................................................................................... 9
TB and HIV ................................................................................................................ 12
Isoniazid preventive therapy ...................................................................................... 14
Co-trimoxazole prophylaxis therapy ......................................................................... 14
TB and diabetes ........................................................................................................ 15
TB in children............................................................................................................. 15
TB in women.............................................................................................................. 16
Drug-resistant tuberculosis ........................................................................................ 16

Chapter 2: Global Measures for Tuberculosis Control......................................... 21

The End TB Strategy (Post-2015 Global Tuberculosis Strategy) ............................... 21
The Stop TB strategy (2006 – 2015) ......................................................................... 23
The DOTS strategy (1995 – 2005) ............................................................................ 24

Chapter 3: Diagnosis of Tuberculosis ................................................................... 29

Screening tests for TB ............................................................................................... 29
Diagnosis of pulmonary TB........................................................................................ 30
Diagnosis of extrapulmonary TB................................................................................ 32
Diagnosis of drug-resistant TB .................................................................................. 32
Diagnosis of TB in children ........................................................................................ 34
Contact investigation ................................................................................................. 35
TB Classification ........................................................................................................ 35

Chapter 4: Treatment of Tuberculosis ................................................................... 40

TB treatment: Essential drugs against TB ................................................................. 40
TB treatment regimens for children ........................................................................... 44
Treatment of MDR-TB ............................................................................................... 45
New drugs to treat drug-resistant TB ......................................................................... 49
Monitoring TB treatment ............................................................................................ 50
Treatment outcome definitions .................................................................................. 50
Medication adverse effects ........................................................................................ 52
Treatment Adherence ................................................................................................ 53

Chapter 5: Guidelines for Patient Care: Nursing Principles and Processes ...... 55
Role of Nurses in TB Care and Management ............................................................ 55
Patient-centred approach to TB control and care ...................................................... 56
DOTS strategy ........................................................................................................... 57
ii
Patient-centred care and treatment adherence ......................................................... 60

Chapter 6: Organisational and Workforce Issues ................................................. 63

Organisational issues ................................................................................................ 63
Workforce issues ....................................................................................................... 63
Infection prevention and control................................................................................. 64
Maintaining a healthy workforce ................................................................................ 66
Social mobilisation and advocacy .............................................................................. 70
DOT treatment support .............................................................................................. 72
Conclusion ................................................................................................................. 73

ANNEXES ................................................................................................................. 74
Annex 1: Algorithm for Screening for TB among Adults and Adolescents ................ 75
Annex 2: TB Symptom Screening Tool Sample........................................................ 76
Annex 3: Algorithm for Diagnosing TB in Children .................................................... 77
Annex 4: TB Drugs used for MDR-TB in Five Groups .............................................. 78
Annex 5: Adverse Effects, Suspected Agents and Management Strategies
in MDR-TB Treatment............................................................................... 80
Annex 6: Factors Affecting Adherence ..................................................................... 90

References ............................................................................................................... 91

iii
List of Tables
Table 1.1: Differences between latent TB infection and TB disease ............................ 7
Table 1.2: Signs and symptoms of TB ......................................................................... 9
Table 1.3: Causes of inadequate anti-tuberculosis treatment .................................... 18
Table 2.1 The WHO End TB strategy indicators and selected targets ....................... 23
Table 3.1: TB Diagnostic tests and procedures ......................................................... 32
Table 3.2: Definitions of TB case classifications ........................................................ 38
Table 4.1: Essential first-line anti-TB drugs and recommended doses ...................... 40
Table 4.2: Fixed-dose combination of first-line drugs ................................................ 41
Table 4.3: Recommended treatment regimens for new and presumed TB patients .. 42
Table 4.4: TB treatment regimens for previously treated patients based on
availability of access to DST ..................................................................... 44
Table 4.5: Recommended treatment regimens for new paediatric patients in HIV
endemic settings ....................................................................................... 45
Table 4.6: Recommended doses according to weight for children ............................ 45
Table 4.7: Conventional groups of second-line anti-tuberculosis agents used to
treat MDR-TB............................................................................................ 47
Table 4.8. Updated anti-TB medications for the treatment of RR-TB and MDR-TB... 48
Table 4.9: Monitoring of TB treatment by smear microscopy for new pulmonary
TB patients ............................................................................................... 50
Table 4.10: WHO treatment outcomes for TB patients (excluding patients treated
for RR-TB or MDR-TB) ........................................................................... 51
Table 4.11: Treatment outcomes for RR-TB/MDR-TB/XDR-TB patients treated
using second-line treatment .................................................................... 52
Table 5.1: The role of the nurse in relation to the five elements of the ...................... 57
Table 6.1: Infection prevention and control measures ............................................... 66
Table 6.2: Key nursing capabilities in TB control and prevention .............................. 70

List of Figures
Figure 1. Map of global estimated TB incidence rates 2014 ........................................ 6
Figure 2. Post-2015 global tuberculosis strategy: Pillars and Principles .................... 22

iv
Abbreviations
AFB Acid-fast bacilli
ART Antiretroviral therapy
BCG Bacille Calmette Guerin
CPT Co-trimoxazole prophylaxis therapy
CT Computer tomograph
DOT Directly observed treatment
DOTS The internationally recommended strategy for TB control
DRS Drug resistance surveillance
DST Drug-susceptibility testing
EPTB Extrapulmonary TB
FDC Fixed-dose combination
G Gram
GLC Green Light Committee
HIV Human immunodeficiency virus
ICN International Council of Nurses
IGRA Interferon-gamma release assay
ILO International Labour Organization
IPC Infection prevention and control
IPT Isoniazid preventive therapy
IRIS Immune reconstitution inflammatory syndrome
LPA Line probe assay
LTBI Latent TB infection
MDR-TB Multi-drug resistant tuberculosis
Mg Milligram
MRI Magnetic resonance imaging
NGO Non-governmental organisation
NTP National TB Programme
PPE Personal protective equipment
PTB Pulmonary TB
RR-TB Rifampicin-resistant TB
SL-LPA Second-line line probe assay
TB Tuberculosis
TST Tuberculin skin test
The Union The International Union Against Tuberculosis and Lung
Diseases
UVGI Ultraviolet germicidal irradiation
WHO World Health Organization
XDR-TB Extensively drug-resistant tuberculosis

v
Anti-tuberculosis drug abbreviations
Am Amikacin
Bdq Bedaquiline
Amx/Clv Amoxicillin/Clavulanate
Cfx Ciprofloxacin
Cfz Clofazimine
Clr Clarithromycin
Cm Capreomycin
Cs Cycloserine
Dlm Delaminid
E Ethambutol
Eto Ethionamide
FQ Fluoroquinolone
Gfx Gatifloxacin
H Isoniazid
Imp/Cln Imepenem/Cilastatin
Km Kanamycin
Lfx Levofloxacin
Lzd Linezolid
Mfx Moxifloxacin
Mpm Meropenem
Ofx Ofloxacin
PAS Para-aminosalicylic acid
PAS-Na Para-aminosalicylate sodium
Pto Protionamide
R Rifampicin
Rfb Rifabutin
S Streptomycin
T Thioacetazone
Trd Terizidone
Z Pyrazinamide

vi
vii
Preface

Tuberculosis (TB) has reached epidemic proportions in many parts of

the world. Nearly one and a half million people die every year from a
disease that is curable and preventable in most cases, even in very
resource poor settings. Everywhere in the world, nurses encounter
patients with TB, suspected TB and those who have symptoms of the
disease.

The information in these guidelines by the International Council of

Nurses (ICN) is intended to help nurses in their important role of
detecting TB cases, providing care and managing TB treatment. It sets
out a nursing approach to planning and delivering patient care, aimed
at improving access and quality of care throughout the treatment
period.

These guidelines offer a review of TB and multi-drug resistant TB

(MDR-TB). The new End TB Strategy (2016 – 2035) has been
developed to replace and to continue the successes of the previous
Global Plan to Stop TB (2011-2015) and the Stop TB strategy (2006-
2011). Also included is an overview of organisational issues that can
have an important impact on TB control programmes.

This publication is a continuation in a series of ICN products on TB and

is intended to be a comprehensive guide for the busy nurse. Other ICN
publications on TB address practice development with regard to TB
care, TB-related stigma, infection prevention and control, and
occupational issues. ICN trusts that the series will provide a complete
understanding of TB and MDR-TB and strengthen nursing competence
in tackling this growing epidemic.

The second edition of these guidelines was prepared by Gini Williams,

former ICN TB Project Director. The revision of this third edition was
prepared by Carrie Tudor, ICN TB Project Director, and Gini Williams.

This publication is supported in part by a grant from United Way

Worldwide made possible by the Lilly Foundation on behalf of the Lilly
MDR-TB Partnership.

1
Introduction
The International Council of Nurses (ICN) prepared these guidelines to
strengthen nursing capacity related to TB and to enhance the
effectiveness of TB control measures worldwide. Because nurses play
a crucial role in TB control programmes, it is essential for them to have
a solid understanding of TB: its aetiology, pathogenesis, epidemiology
and treatment, as well as the best practices for TB control. This
strengthened understanding is essential in the light of the current
resurgence of TB and drug-resistant TB in many countries.
Undetected and improperly treated cases of tuberculosis resulting from
ineffective TB management are major reasons for the spread of the
disease and the development of MDR-TB. More recently the
emergence of extensively drug-resistant TB (XDR-TB) has added to
the complexity of TB care and treatment. Ineffective TB management
of this type often results from a scarcity of adequately trained
personnel, poor capacity at a management level, and/or inadequate
resources to sustain treatment.
If they are properly informed and mobilised, nurses can positively
influence TB disease prevention and management, particularly
because of their close involvement with patients. Some nurses
specialise and work solely with TB programmes, but the vast majority
work within general health services, encountering patients for a wide
variety of reasons – pregnancy, injury, illness, or to receive
immunisations. Thus, nurses are in an ideal position to detect
previously unsuspected cases of TB, since the patients they see for
other reasons may also have symptoms of TB.
This publication approaches TB control from a best practices
perspective and provides practical TB information for nurses in their
day-to-day work. A section on organisational issues gives the reader a
useful perspective for managing TB control.
ICN believes that information is only valuable when it is utilised at the
local level. Blending the measures of the expanded TB control strategy
with local customs enhances nursing practice and provides the best of
both worlds – standardised care that is individualised to meet the
constraints and the needs of local nursing practice. ICN sincerely
hopes that the best practice approach offered in these guidelines
enhances TB control programmes in your local community and
strengthens your own individual nursing practice.

2
Chapter 1: Tuberculosis: the Clinical Context
History of tuberculosis
Mycobacterium tuberculosis (TB) is as old as the human species.
Fragments from the spinal column of Egyptian mummies dating from
2400 BC show definite pathological signs of tubercular decay. The
name “tuberculosis” has been used from the middle of the last century.
Tuberculosis, also called phthisis or consumption, and nicknamed
"white plague", first appeared in Greek literature. At around 460 BC
Hippocrates described it as the most widespread disease of its time.
Exact aetiological and pathological descriptions of TB began to appear
in the 17th Century when the earliest references to the infectious nature
of the disease appeared in Italian medical literature. Although this
allowed for some progress to be made towards prevention, a cure was
still not within sight.
The introduction of the sanatorium provided the first hope for a TB cure.
These special centres were located in areas with a healthier climate,
where patients were continuously exposed to fresh air. Improving
social and sanitary conditions and ensuring adequate nutrition were all
that could be done to strengthen the body’s defence against TB. It is
still unknown whether sanatoria really helped people with TB. There
were also many people with TB who could not afford to go to a
sanatorium, and who died at home.
In 1865, a French military doctor, Jean-Antoine Villemin, demonstrated
that TB could be passed from humans to cattle and from cattle to
rabbits. On the basis of this evidence he postulated that TB was
contagious and a microorganism was the cause of the disease.
In 1882, a German scientist, Robert Koch, discovered the
Mycobacterium tuberculosis under the microscope and the fight
against TB really began.
A further milestone came in 1895, when Wilhelm Konrad von Roentgen
discovered radiation. Now the progress and severity of a patient’s
disease could be followed and reviewed.
The French bacteriologist, Albert Calmette, worked together with
Camille Guérin to develop a vaccine against TB. By 1921, they had
developed a bacillus harmless to man, yet with the ability to stimulate
the production of antibodies. From 1924, the vaccination of newborns
was practiced. The Bacille Calmette Guérin (BCG) vaccine is still used
in immunization programmes today.
In 1943, in the middle of the Second World War, an American scientist,
Selman A. Waksman, discovered streptomycin, an antibiotic that could

3
kill TB bacteria. In the following years, a rapid succession of anti-TB
drugs appeared. This was essential because with streptomycin mono-
therapy, resistant mutants began to appear, endangering the success
of antibiotic therapy. Following streptomycin, isoniazid (1952),
pyrazinamide (1954), ethambutol (1962) and rifampicin (1963) were
introduced as anti-TB agents. These anti-TB drugs are still used today
and their application will be described later in greater detail. The effects
of TB on the population during the last centuries and its current global
situation and epidemiological trends will be described in the next
section - Epidemiology of Tuberculosis.

Epidemiology of tuberculosis
TB caused great public concern in the 19th and early 20th centuries as
the endemic disease of the poor. After the development of the antibiotic
streptomycin in 1943, medical treatment rather than prevention
became a possibility. Prior to this medical treatment, only surgical
intervention was possible along with the purported benefits of
sanatoria.
Following the development of effective treatment for TB in the 1950s
the general view, especially in industrialised countries, was the disease
no longer posed a public health threat (Raviglione, 2003, Frieden et al.,
1995). In industrialised countries there was a steady decline in TB
incidence from the1950s to the 1980s. Due to the drop in TB cases
many countries decreased funding for TB control programmes. As a
result, there was a decline in successful treatment outcomes which
gave rise to drug-resistant TB.
Increases in TB figures, seen in both the United States and Europe,
were alarming in the late 1980s, highlighting the need to refocus efforts
on TB control. The reasons for the increases in the USA were largely
attributed to the rising rates of human immunodeficiency virus (HIV),
worsening poverty in urban areas, decrease in funding for TB control
programmes, and poor TB control practices. Hopes that TB could be
completely eliminated have been dashed since the rise of multi-drug
resistant strains in the 1980s. In Europe, the increases were mainly
associated with urban poverty. In recognition of the fact that, in both
the United States and Europe, increases in TB prevalence were
associated with immigration from countries with high rates of TB, the
disease had to be addressed as a global issue (Raviglione, 2003). In
order to intensify efforts to limit its spread, in 1993, TB was declared a
“global emergency” by the World Health Organization (WHO).
TB remains a major public health problem worldwide and is the second
leading cause of death due to an infectious disease, second only to
HIV/AIDS. While much progress has been made over the past 20 years
since TB was declared a public health emergency, there is still much
funding needed and work to do to control the disease. Since 1995,
more than 56 million patients have been treated for TB resulting in an

4
estimated 22 million lives saved. In addition, the global TB mortality
rate has decreased by 45% compared with 1990 rates. While progress
has been made, TB will continue to remain a major killer for many years
to come (World Health Organization, 2013c). The following figures from
the WHO’s Global tuberculosis report 2015 (World Health
Organization, 2015c) highlight the current state of the global TB
epidemic:
 Two billion people, i.e. one-third of the total human population, are
estimated to be infected with M. tuberculosis.
 9.6 million new cases of TB occurred globally in 2014 including
among 1.2 million living with HIV.
 TB remains a disease of poverty. Of the 9.6 million new TB cases
in 2014, approximately 85% lived in Africa and Asia. The majority
of TB cases (80%) occur in 22 countries and 95% of TB cases and
deaths occur in low-resourced countries.
 In 2014, 1.5 million people died worldwide from TB including
400,000 individuals co-infected with HIV.
 In 2014, there were an estimated 480,000 new cases of multidrug-
resistant TB (MDR-TB) worldwide however, only 110,000 were
registered on treatment. It is estimated that there were 190,000
deaths due to MDR-TB globally in 2014.
 Between 1990 and 2012, the TB mortality rate decreased by 47%.
 TB is one of the leading causes of death among women of
reproductive age and in 2014 nearly 3.2 million TB cases were
among women resulting in approximately 480,000 deaths due to
TB. Moreover, it is estimated that 140,000 women with TB/HIV
died.
 In 2014 an estimated 1 million children were diagnosed with TB
and 140,000 died from TB (HIV-negative children).

5
Figure 1. Map of global estimated TB incidence rates 2014

Source: (World Health Organization, 2014d, World Health Organization, 2015c)

Pathology
TB is a bacterial infection caused by Mycobacterium tuberculosis (M.
tuberculosis) also referred to as tubercle bacilli. The M. tuberculosis is
a Gram-positive aerobic bacterium. It is a small rod-like bacillus with a
complex cell wall, which can withstand weak disinfectants and survive
in a dry state for weeks, but can only grow in a host organism.
It most commonly affects the lungs, producing pulmonary TB.
However, transported by the blood or lymphatic system, the TB bacilli
can infect almost any part of the body, including lymph glands, joints,
kidneys, and bone - extrapulmonary TB. It is critical to understand the
disease, its aetiology and its epidemiology to develop a strong TB
control programme.
Early symptoms of pulmonary TB are often vague and easily
attributable to other conditions, with the result that many cases of
active, infectious TB can remain undetected for some time. Thus, the
disease spreads from one person to another.
TB is spread when an infectious person coughs, sneezes, talks or
sings, releasing droplets containing the bacilli into the air. However, TB
can also be spread when TB bacilli are aerosolised by treatments, such
as irrigating a wound that is infected with TB, organ transplants, or
bronchoscopy. In either case, a susceptible person inhales the airborne
droplets, which then traverse the upper respiratory tract and bronchi to
reach the alveoli of the lungs. Once in the alveoli, alveolar
macrophages take up the TB bacilli, holding some in the lungs, and

6
transporting others throughout the body. Usually within 2-10 weeks, the
immune response limits further multiplication and spread of the bacilli.
Some patients may go on to active disease from this stage while others
may be able to contain the infection and may never develop active TB.
In the patients who contain the infection some may eliminate all the
bacteria; however, in many of the patients, the bacilli remain dormant
and viable for many years, resulting in a condition referred to as latent
TB infection (LTBI). Persons with LTBI usually have positive TB skin
tests but have no symptoms of the disease and are not contagious.
See Table 1.1 for a list of differences between latent TB infection and
active TB disease (Centers for Disease Control and Prevention, 2012).
In fact, most people who are infected with TB never go on to develop
active disease and therefore present no risk to the people around them.

Table 1.1: Differences between latent TB infection and TB disease

Latent TB infection TB disease (active TB)
 No symptoms  Symptoms are present, which may
include:
o Bad cough that lasts ≥ 2
weeks
o Pain in the chest
o Coughing up blood or sputum
o Weight loss
o Fever
o Night sweats
o Weakness or fatigue
o No appetite
 Does not feel sick  Usually feels sick
 Not contagious  Contagious
 Tuberculin skin test (TST) or blood  Tuberculin skin test (TST) or blood
test (IGRA) results will be positive test results will be positive indicating
indicating TB infection TB infection
 Chest x-ray is negative and a  Possible abnormal chest x-ray, or
negative sputum smear positive sputum smear, Xpert®
MTB/RIF or culture
 Treatment for latent TB infection to  Treatment to treat active TB disease
prevent active TB disease
Adapted from (Centers for Disease Control and Prevention, 2012)

Pulmonary TB
Pulmonary TB (PTB) is the most common and potentially most
contagious type of active TB. Small areas in the lung infected with the
bacilli gradually merge to form a bigger lesion filled with infected
material. This material can become liquid, which is then coughed out,
leaving a cavity in the lung (Rieder et al., 2009). The process continues
causing extensive damage to the lung tissue and its blood vessels,
generating more infectious material and inflammation – the damage to
blood vessels can result in some patients coughing up blood

7
(haemoptysis). Some healing may occur in parts of the lung resulting
in scar tissue.
In the early stages of this process, someone with pulmonary TB may
well not be infectious and have few easily definable symptoms. As the
disease progresses and causes more damage, they will become
infectious and experience worsening symptoms. The challenge is to
identify people in the early stages to prevent transmission.

Extrapulmonary TB
Extrapulmonary TB (EPTB) is TB that occurs outside of the lungs and
it is estimated to account for 20 to 25% of all TB cases globally (World
Health Organization, 2009a). EPTB can affect any organ in the body
including:
 cervical lymph glands (most common)
 bone (particularly the spine)
 pleural cavity (causing pleural effusion)
 kidney and genitourinary tract
 intestines and peritoneum
 pericardium
 meninges
 skin

Although extrapulmonary TB is treatable in most forms, the lasting

damage may be permanently crippling (in the case of spinal TB) or
even fatal (in TB meningitis). Bacillary load, extent of disease and
anatomical site determine the severity of EPTB. One of the most lethal
forms of tuberculosis is TB meningitis.
Some forms of extrapulmonary TB are more common in particular
geographical areas, ethnic groups or age groups. By knowing the most
common types of EPTB in the local community, the nurse is more alert
to the symptoms and may detect a case of extrapulmonary TB that
would otherwise have gone unnoticed. Extrapulmonary TB is also
common in patients infected with HIV.

Signs and symptoms of pulmonary and extrapulmonary

TB
The symptoms of pulmonary and extrapulmonary TB may differ but
some are common to both. Most people have only a few of these
symptoms. It is recommended that anyone reporting a cough which
has lasted for two or more weeks should have their sputum tested for
TB. However, for patients living with HIV, it is recommended to test
their sputum for TB if they have had a cough of any duration. As a
general rule, the presence of three or more symptoms for two or more

8
weeks increases the suspicion of any form of the disease. Common
signs and symptoms of both pulmonary and extrapulmonary TB are
detailed in Table 1.2.

Table 1.2: Signs and symptoms of TB

General symptoms Pulmonary symptoms Extrapulmonary
symptoms

Fever Dry or productive cough Localised pain/swelling

(depending on site of
disease)
Night sweats Chest pain
Weight loss Shortness of breath
Fatigue Traces of blood are
coughed up in the
sputum (haemoptysis)
Loss of appetite

Risk factors for TB

Risk factors combined with TB symptoms are strong indicators for
further diagnostic workup and early detection of the disease.
Some of the main risk factors for TB include:
 history of TB
 contact with a known TB case, e.g. family member or friend
 compromised immunity due to illness, e.g. HIV infection, cancer or
diabetes
 compromised immunity due to medications such as steroids
 migration from a country with a high incidence of TB
 history of travel to an area with a high incidence of TB
 smoking
 alcohol and/or drug abuse
 malnutrition
 homelessness

Managing and preventing risks

Those who are responsible for managing TB programmes must
consider the five levels that can be ascribed to the risks of TB
transmission and progression. The risks must be considered in
relation to the population of the region and local community, but also
how they apply to the nurses and other TB programme staff. The risk
levels are the following (Rieder, 1999):

9
1) the risk of exposure
2) the risk of infection
3) the risk of developing active disease
4) the risk of developing drug-resistant TB (MDR-TB/XDR-TB), and
5) the risk of death
The number and severity of risk factors present in any given community
affects the epidemiology of TB disease in that community. Successful
TB control programmes recognise, assess and manage these risk
factors effectively.
Risk of exposure
The risk of exposure is associated with the frequency and
duration of contact with an infectious case of TB/MDR-TB.:
 Exposure is very much linked to time spent with potentially
infected individuals in confined and poorly ventilated spaces, and
overcrowded accommodation due to poverty or social norms of
living together in extended family groups; working conditions; and
other social habits and behaviours, e.g. communal drug-taking.
 A higher risk of exposure to TB is also associated with urban
areas where people are living, travelling and working in cramped
conditions.
 TB is more prevalent in residential institutions such as prisons,
hostels, and healthcare facilities where accommodation may be
overcrowded.
 The higher the prevalence of the disease in a community, the
greater the likelihood of contact with an infected person, and the
higher the risk of exposure to TB bacilli.
Risk of infection
The risk of infection depends on:
 numbers of TB bacilli inhaled
 duration of the exposure
 virility of the bacilli
 strength of the person’s immune system (Rieder et al., 2009,
Centers for Disease Control and Prevention, 1994).
For example, some people exposed to just a few TB bacilli may be
naturally more susceptible and will develop active TB disease. Others
when exposed to a large number of bacilli will only develop a latent TB
infection. Others may be exposed, but develop neither a latent TB
infection nor active TB disease.
The longer a person with active TB who is smear positive remains
undetected and untreated, the higher the likelihood that others will be
10
exposed and infected. The more people there are living in overcrowded
conditions with a person with undetected TB, the higher the risk of
someone contracting the infection. It is estimated that individuals with
active TB disease can infect between 10 to 15 people a year if not
placed on appropriate treatment (World Health Organization, 2015f).
Risk of developing active disease
WHO estimates that one-third of the world's population is infected with
Mycobacterium tuberculosis (World Health Organization, 2015f). In
general, people who become infected with M. tuberculosis have
approximately 5 to 10% risk of developing active disease in their
lifetime and as high as 50% among those living with HIV (World Health
Organization, 2015f). This risk is greatest during the first two years after
infection. The risk of developing active disease relates to the
individual’s health status, and most particularly to the status of the
immune system. HIV increases the risk of developing active TB once
infected.
WHO estimated that approximately one-third of the 35 million people
living with HIV at the end of 2012 had latent TB infection and were
roughly 30 times more likely to develop active TB disease compared
with persons without HIV (World Health Organization, 2014e). Other
factors contributing to the risk of developing active disease, once the
TB infection takes hold, are smoking (more than 20% of TB incidence
may be due to smoking) (World Health Organization, 2009b); diabetes
(World Health Organization and The International Union Against
Tuberculosis and Lung Disease, 2011); exposure to smoke from
biomass stoves (Perez-Padilla et al., 2001); Vitamin D deficiency
(Wilkinson et al., 2000); malnutrition often associated with poverty,
alcohol and substance abuse, and other debilitating conditions (Crofton
et al., 1999). Internally displaced people, asylum seekers, migrant
workers and refugees all face difficulties compounding their
vulnerability to TB, including crowded and poorly ventilated housing,
poor access to health and social care, and reduced personal security.
Risk of developing multi-drug resistant TB (MDR-TB)
The WHO estimates that approximately 3.5% of all new TB cases and
up to 20% of retreatment cases worldwide have MDR-TB. Roughly
10% of all MDR-TB cases are estimated to be extensively drug-
resistant TB (XDR-TB) cases. However, incidence of MDR-TB varies
greatly by region and country. More than 50% of all MDR-TB cases in
2014 occurred in China, India, and the Russian Federation (World
Health Organization, 2014d). Given the increasing trend toward
globalisation, trans-national migration and tourism, all countries are
potential targets for outbreaks of MDR-TB.
Risk factors for developing MDR-TB are:
 improper use of first-line anti-TB drugs;

11
 inadequate laboratory capacity to diagnose MDR-TB;
 patients who failed previous first-line treatment;
 new TB patients who remain smear positive after two or three
months of anti-TB treatment;
 close contact with known MDR-TB case;
 poor infection control especially in healthcare facilities; and
 people who are living with HIV or other immunosuppression
disease (diabetes).
Risk of death
Among infectious diseases, TB is a leading cause of adult mortality,
resulting in more than one million deaths a year worldwide (World
Health Organization, 2015c). In addition, TB kills more people with HIV
than any other associated disease or opportunistic infection. Two main
factors are the principal determinants of TB case fatality: 1) the site and
type of disease; and 2) the appropriateness and timeliness of the
intervention and care provided. Inadequate treatment is likely to result
in early death: 30-40% of untreated sputum smear-positive TB cases
will die within a year, and 50-60% will be dead within five years (Rieder,
1999). HIV infection, malnutrition and severe pulmonary disease are all
associated with a greater risk of death from TB. Inadequate treatment
for those suffering from drug-resistant TB (MDR/XDR-TB) also
increases the risk of death.

TB and HIV
HIV is one of the main risk factors for developing active TB from both
recently acquired and latent TB infection and poses one of the greatest
challenges to TB control. In addition, TB is the most common
opportunistic infection among people living with HIV. In 2014, WHO
estimated that there were 1.2 million new cases of TB among people
living with HIV worldwide and approximately 75% of these cases
occurred in sub-Saharan Africa. More people living with HIV die from
TB than any other condition accounting for about 24% of all HIV-related
mortality (World Health Organization, 2015c). The association between
the two diseases is so significant that one cannot be managed without
consideration of the other.
With better care and treatment opportunities becoming available to
those infected with HIV, there is now a greater incentive for individuals
to know their HIV status. With adequate treatment, a TB patient who is
co-infected with HIV is as likely to make full recovery from TB as a HIV-
negative patient. The top priority must be early diagnosis of TB and
effective and efficient treatment for both HIV and TB in order to give
him/her the best chance of recovery. In recent years, many countries
have begun to integrate TB and HIV care services to better treat co-
infected patients. It is important for patients to know their HIV status
and therefore all TB patients should be tested for HIV and all people

12
living with HIV should be regularly screened for TB and offered
preventive therapy such as isoniazid preventive therapy (IPT) and co-
trimoxazole prophylaxis (CPT) (World Health Organization, 2014e).
Those in the early stages of HIV infection are more likely to develop
sputum smear-positive pulmonary disease and present in a similar way
to their immuno-competent counterparts. In the later stages of HIV
infection, due to suppression of the immune response, patients are
more likely to be smear negative, or suffer from EPTB and present with
less definable symptoms. Immuno-compromised patients with TB may
present different clinical pictures, according to their level of
immunodeficiency (Raviglione et al., 1997). In addition, TB skin tests
may be negative and x-rays may not show the typical TB picture. In
fact, in rare cases, x-rays may appear as normal (Centers for Disease
Control and Prevention, 1994).
The WHO recommends regularly screening people living with HIV for
the following four most common symptoms: (World Health
Organization, 2013a)
 current cough
 fever
 weight loss
 night sweats
If a patient living with HIV presents with any one of the above four
symptoms, they are to undergo further screening for active TB. Those
patients living with HIV diagnosed with active TB should be screened
for drug-resistant TB and started on appropriate anti-TB treatment as
soon as possible. If it is determined that the patient does not have
active TB, they should be counselled and offered IPT to protect them
against developing active TB described below (World Health
Organization, 2011a). See Annex 1 for an algorithm for diagnosing TB
in HIV-positive adults and adolescents.
For more information, please see: Guidelines for intensified tuberculosis
case-finding and isoniazid preventive therapy for people living with HIV in
resource constrained settings. WHO, Geneva, Switzerland. 2011:
(http://who.int/tb/challenges/hiv/ICF_IPTguidelines/en/) and Consolidated
guidelines on the use of antiretroviral drugs for treating and preventing HIV
infection: recommendations for a public health approach. WHO, Geneva,
Switzerland June 2013:
http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf?
ua=1

Numerous studies have found that starting TB patients co-infected with

HIV on antiretroviral therapy (ART) within eight weeks of starting anti-
TB treatment irrespective of CD4 count significantly improves TB
treatment outcomes and significantly reduces mortality among co-
infected patients compared with deferring the initiation of ART until
after completion of TB treatment (Abdool Karim et al., 2010, Abdool

13
Karim et al., 2011, Blanc et al., 2011, World Health Organization,
2013a). Therefore, the most recent 2013 WHO guidelines recommend
initiating ART naïve TB/HIV co-infected patients within eight weeks of
starting anti-TB treatment including patients co-infected with MDR-
TB/HIV. For patients with a CD4 count < 50 cells/mm3, it is
recommended to initiate ARTs within the first two weeks of starting anti-
TB treatment. However, it has been shown that co-infected patients
with a CD4 <50 cells/mm3 starting ARTs within two weeks of starting
anti-TB treatment are more likely to experience immune reconstitution
inflammatory syndrome (IRIS) (Abdool Karim et al., 2011, Havlir et al.,
2011, World Health Organization, 2013a).
Please visit the following link for more information:
http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf?ua=1

As TB and HIV are becoming increasingly common co-infections,

nurses must follow national TB and HIV treatment guidelines and
recommendations for treatment with ART and anti-TB treatment of co-
infected patients. In addition, nurses should be familiar with preventive
therapy such as IPT and CPT.

Isoniazid preventive therapy

Isoniazid preventive therapy (IPT) – the use of isoniazid to prevent
latent tuberculosis infection from developing into active TB disease –
has been shown to be effective in treating LTBI and has been used
globally for many years in HIV-negative individuals (Comstock et al.,
1967). More recently, IPT has been promoted for the prevention of TB
among people living with HIV (World Health Organization, 2011a,
World Health Organization and UNAIDS, 1998, World Health
Organization, 2008b) and is estimated to reduce the incidence of TB
among people living with HIV taking IPT by 32% (Akolo et al., 2010).
Current WHO guidelines call for the provision of IPT for all individuals
living with HIV regardless of TST results (World Health Organization,
2011a). The most recent WHO HIV guidelines released in 2013
recommend providing at least six months of IPT for any HIV-positive
patient with either known positive TST or unknown TST with no signs
and symptoms of active TB (World Health Organization, 2013a).
However, individual national guidelines may differ and IPT should be
provided based on current national guidelines.
For more information please visit:
http://whqlibdoc.who.int/publications/2011/9789241500708_eng.pdf?ua=1
http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf?ua=1

Co-trimoxazole prophylaxis therapy

Co-trimoxazole is a broad-spectrum antibiotic comprised of
sulfamethoxazole and trimethoprim used to treat a range of common
opportunistic and bacterial infections among people living with HIV

14
such as Pneumocystis jirovecii (carinii) pneumonia (PCP),
toxoplasmosis, etc. (World Health Organization, 2006b). The WHO
recommends that all TB/HIV co-infected patients should be given co-
trimoxazole (480 mg 1 tablet twice daily or 960 mg 1 tablet once daily)
regardless of CD4 count. Co-trimoxazole prophylaxis therapy (CPT)
has been shown to substantially reduce mortality among TB cases
living with HIV (Harries et al., 2009, World Health Organization, 2006b,
Uyei et al., 2011, Nunn et al., 2008).
It is important for the nurse to check for allergies to sulpha drugs and
patients with such allergies should not be given co-trimoxazole
prophylaxis therapy. Dapsone is the recommended alternative drug for
those with sulpha drug allergies (World Health Organization, 2006b).
For more information please visit:
www.who.int/hiv/pub/guidelines/ctxguidelines.pdf?ua=1

TB and diabetes
Diabetes is estimated to affect 422 million people worldwide and
approximately 80% of deaths due to diabetes occur in low- and middle-
income countries – in many cases the same countries with a high
burden of TB. The global prevalence of diabetes is expected to
continue to increase in the foreseeable future. WHO estimates that
roughly 15% of all TB cases also have diabetes and those with
diabetes have a three-fold greater risk of TB compared with those
without diabetes. In addition, patients co-infected with TB and diabetes
are more likely to die while on TB treatment and are more likely to suffer
a relapse following TB treatment than those who do not have diabetes.
All people with diabetes should be screened regularly for TB, especially
in settings with a high burden of TB, in order to diagnose and treat TB
early as a means to improve treatment outcomes and the control of
both diseases. It is also recommended that TB patients should be
screened for diabetes (World Health Organization and The
International Union Against Tuberculosis and Lung Disease, 2011,
World Health Organization, 2016b).
For more information please visit
http://whqlibdoc.who.int/publications/2011/9789241502252_eng.pdf, and
http://www.who.int/tb/publications/diabetes_tb.pdf.

TB in children
In recent years there has been an increasing awareness of the major
impact TB has on childhood morbidity and mortality worldwide,
especially in high TB burden countries. According to the latest WHO
estimates, the annual global burden of TB in children aged less than
15 years in 2014 was approximately one million cases, and that up to
140,000 children died from TB in 2014 – equating to approximately 200
children dying of TB every day. However, it is likely that the true burden
15
of childhood TB is underestimated, because in areas with a high HIV
burden, children co-infected with TB and HIV are often classified as an
HIV death (World Health Organization, 2015c).
The majority of TB cases among children occur in those less than five
years of age. While infants and children are likely to suffer from more
severe forms of TB, such as TB meningitis, the majority of children will
suffer from pulmonary TB. Additionally, infants and children are more
likely to experience a faster onset of disease than older children or
adults and it is expected that 90% of children under five years old who
become infected with TB will progress to TB disease within one year of
infection. TB can often be difficult to diagnose in children because there
is often considerable overlap of TB symptoms with other common
childhood diseases resulting in many TB cases being missed, including
the more severe and often fatal cases that present as severe
pneumonia, malnutrition or meningitis. In countries with a high burden
of TB, it is estimated that between 10 to 20% of all TB cases occur in
children (World Health Organization, 2013c, World Health
Organization, 2013e, The International Union Against Tuberculosis
and Lung Disease, 2010).

TB in women
Women are greatly affected by TB, which is one of the top five causes
of death among women of reproductive age. WHO estimates that the
global burden of TB disease among women in 2014 amounted to
approximately three million cases and 480,000 deaths. Women from
Africa and Southeast Asia are most affected accounting for nearly 70%
of all TB cases among women. Approximately 140,000 TB deaths
among TB/HIV co-infected individuals were among women –
approximately 50% of all such deaths in 2014 (World Health
Organization, 2015c). In addition, it is believed that in 2012
approximately half of the estimated cases of TB among women were
undetected which is greater than the estimated number of undetected
cases in the general population (World Health Organization, 2014d).
It is important for nurses to routinely screen women of reproductive age
for signs and symptoms of TB especially in high TB burden settings
regardless of their HIV status. This can be done through prenatal and
well-baby check-ups as well. It is important to get women diagnosed
and on treatment as a means to protect them, but to also protect other
family members including children (World Health Organization, 2014g).

Drug-resistant tuberculosis
Among the bacteria multiplying and causing disease in someone with
TB, there will always be a few bacteria that will be resistant to any one
of the anti-TB drugs. If only one drug is used, a population of bacteria
resistant to this drug will develop. If more than one drug is used, then

16
any bacteria resistant to one drug will be dealt with by another. This is
why it is recommended that TB is treated with multiple drugs.
A person may become infected with a TB strain that is already drug
resistant. This is termed primary drug resistance. This is the principal
reason why patients fail the standard six-month TB treatment regimen
when properly administered. If multi-drug resistance develops while the
person is receiving drug therapy, the resistance is called acquired drug
resistance. It often develops because a patient is treated incorrectly or
the patient is not able to adhere to the treatment regimen. In both
cases, the patient has not been receiving a strong enough dosage of
the drugs over a long enough period of time to kill the bacilli, so the
organisms are given time to develop resistance to one or more of the
drugs.
Drug-resistant TB can only be defined through laboratory confirmation
of in vitro resistance to one or more anti-TB drugs. Results are defined
according to the pattern of resistance – please see page 29 for more
details.

Multi-drug resistant tuberculosis (MDR–TB)

Although MDR-TB varies widely across regions, it occurs in all
geographical settings able to produce data and is therefore a significant
global public health threat. WHO estimated the global prevalence of
MDR-TB cases was roughly one million with approximately 480,000
new incident cases in 2013. China, India and the Russian Federation
account for more than 50% of the annual incidence of MDR-TB cases
(World Health Organization, 2014d). Of the estimated 480,000 new
cases of MDR-TB in 2013, roughly 3.6% were new TB patients (primary
drug resistance) and up to 20% had been previously treated for TB
(acquired drug resistance) although these percentages can vary
greatly by country. It is estimated that the average MDR-TB patient
may infect up to 20 other people in her/his lifetime. In 2013,
approximately 48% of MDR-TB patients who started treatment in 2011
were treated successfully (World Health Organization, 2014d).
Drug resistance can emerge from the improper use of first-line anti-TB
agents in the therapy of drug-susceptible TB patients and is found in
all countries. Some programmes do not yet have adequate laboratory
capacity and resources for treating MDR-TB cases. Nonetheless, all
TB programmes in poor-resourced areas should develop, in
conjunction with a good TB control programme, adequate laboratory
facilities to diagnose MDR-TB and an effective strategy for MDR-TB
treatment. Treatment for MDR-TB is effective, feasible and cost-
effective. Table 1.3 lists some of the most common causes of
inadequate anti-TB treatment which may contribute to drug resistance.
Aside from the clinical care, the importance of maintaining a positive
attitude towards patients and ensuring strong support for them
throughout diagnosis and treatment cannot be underestimated.
17
Extensively drug-resistant tuberculosis (XDR-TB)
Extensively drug-resistant TB (XDR-TB) is a rare type of drug-resistant
TB resistant to first- and second-line drugs. As a result, patients with
XDR-TB are left with treatment options that are more toxic and less
effective. However, if XDR-TB can be identified early, it can be treated
and cured under proper TB control conditions. Successful treatment
outcomes depend on the extent of the drug resistance, the severity of
the disease and the immune response of the patient.

Table 1.3: Causes of inadequate anti-tuberculosis treatment

HEALTHCARE HEALTH SYSTEM ISSUES: PATIENTS:
PROVIDERS: INADEQUATE SUPPLY INADEQUATE DRUG
INADEQUATE REGIMENS /QUALITY INTAKE
 Inappropriate  Poor quality  Poor adherence
guidelines  Unavailability of certain (or poor direct
 Noncompliance with drugs (stock-outs or observed treatment
guidelines delivery disruptions) (DOT))
 Absence of guidelines  Poor storage  Lack of information
 Poor training conditions  Lack of money (no
 No monitoring of  Wrong dose or treatment available free
treatment combination of charge)
 Poorly organized or  Lack of transportation
funded TB control  Adverse effects
programmes  Social barriers/stigma
 Malabsorption
 Substance dependency
disorders
(World Health Organization, 2008a)

XDR-TB strains have been found in all regions of the world and, as of
late 2014, 100 countries had reported at least one XDR-TB case. While
XDR-TB remains rare, in some parts of the world 19% of MDR-TB
cases had XDR-TB and in 2013 WHO estimated that globally
approximately 10% of all MDR-TB cases are XDR-TB (World Health
Organization, 2015c). This percentage varies by country and region
and is likely an underestimate based on the lack of second-line drug-
sensitivity testing capabilities in many countries.
XDR-TB remains a grave global public health threat, especially in
populations with high rates of HIV and drug-resistant TB. In 2013,
approximately 3,000 XDR-TB patients worldwide were reported to be
on treatment (World Health Organization, 2014d). XDR-TB is most
often a result of a poorly functioning TB control programme and poor
management of MDR-TB. The best way to prevent XDR-TB is to
ensure prompt diagnosis of pulmonary TB and drug-resistant TB (both
RR-TB and MDR-TB) in the early stages of disease and successfully
manage, treat, and cure patients with both drug-susceptible and drug-
resistant TB. Effective infection prevention and control measures in

18
health facilities play a key role in preventing nosocomial transmission.
Moreover, there is a need for the development of new TB diagnostics,
treatments and vaccines, since the current tools are outdated and
insufficient. In 2008 an international response to the XDR-TB
emergency began with the establishment of a WHO Global Task Force
on XDR-TB. The recommendations of this Task Force can be found at
the following website:
http://whqlibdoc.who.int/hq/2007/WHO_HTM_TB_2007.375_eng.pdf

19
20
Chapter 2: Global Measures for Tuberculosis
Control

The End TB Strategy (Post-2015 Global Tuberculosis

Strategy)
While wealthy industrialised countries with good public healthcare
systems can be expected to keep TB under control, in much of the
developing world the disease remains an urgent public health problem
and is the second leading cause of death globally.
A concerted effort has been made by the WHO together with national
TB programmes to expand the coverage of effective TB control
measures based on first the DOTS (Direct Observed Therapy Short
Course) strategy and then the broader Stop TB Strategy through the
Global Plan to Stop TB 2006-2015. This concerted effort has meant
that since the 1990s the TB mortality rate has decreased by 45%
resulting in an estimated 22 million lives saved and 56 million patients
cured. However, even though the incidence of new cases is coming
down, the decline is still too slow and there remains an alarming
increase in all forms of drug-resistant TB, so there is no room for
complacency.
The WHO has approved a new strategy to continue the fight against
TB – The End TB Strategy. This new strategy builds on previous
strategies with a much greater emphasis on patient-centredness and
the need to work with a much broader range of partners to address
ongoing challenges. It will form the basis of a new Global Plan to Stop
TB which is being devised under the leadership of the Stop TB
Partnership.
The incidence of TB currently is declining at a rate of 2% per year and,
in order to meet the target of a 90% reduction in incidence by 2035,
this rate of decline will need to be increased to approximately 10% per
year (World Health Organization, 2015a). The End TB Strategy also
calls for a 95% reduction in mortality due to TB compared with 2015
and no families or patients afflicted with TB should suffer catastrophic
costs due to TB. In order to reach these targets the WHO has adopted
the following principles: 1) government stewardship and accountability,
with monitoring and evaluation; 2) a strong coalition with civil society
organisations and communities; 3) protection and promotion of human
rights, ethics and equity; and 4) adaptation of the strategy and targets
at country level, with global collaboration.
The strategic framework is comprised of three main pillars and
components (World Health Organization, 2015a):
1. Integrated, patient-centred care and prevention

21
 a. early diagnosis of TB including universal drug-susceptibility
testing and systematic screening
b. treatment of all people with TB (including drug-resistant TB)
and patient support
c. collaborative TB/HIV activities and management of co-
morbidities
d. preventive treatment of individuals at high risk
2. Bold policies and supportive systems
a. political commitment with adequate resources for TB care and
prevention
b. engagement of communities, civil society organisations, and
public/private care providers
c. universal health coverage policy, and regulatory frameworks
for case notification, vital registration, quality and rational use
of medicines, and infection control
d. social protection, poverty alleviation and actions on other
determinants of TB
3. Intensified research and innovation
a. discovery, development and rapid uptake of new tools,
interventions and strategies
b. research to optimise the implementation and impact and
promote innovation

Figure 2. Post-2015 global tuberculosis strategy: Pillars and

Principles (World Health Organization, 2015b)

Source: WHO Gear up to end TB: Introducing the End TB Strategy (World Health Organization,
2015b)

For more information on the current global TB strategy, please visit:

www.who.int/tb/End_TB_brochure.pdf?ua=1. The WHO has also
published an implementation guide on how to implement the new End
22
TB Strategy titled: Implementing the end TB strategy: the essentials
(http://www.who.int/tb/publications/2015/end_tb_essential.pdf) (World
Health Organization, 2015d).

WHO has declared MDR-TB a global health risk and drafted priority
actions to address this threat (World Health Organization, 2014c).
Five priority actions to address the global MDR-TB crisis are to:
 prevent MDR-TB through strengthening drug-susceptible TB
treatment control programmes
 scale up rapid diagnosis of drug-resistant TB cases
 ensure immediate access to MDR-TB treatment
 prevent transmission through effective infection prevention and
control
 ensure political will and funding

Table 2.1 The WHO End TB strategy indicators and selected targets
A world free of TB
Vision (zero deaths, disease and suffering due to TB)
Goal End the global TB epidemic
Milestones Targets
Indicators
2020 2025 2035
Reduction in number of TB deaths
35% 75% 95%
compared with 2015 (%)
Reduction in TB incidence rate 20% 50% 90%
compared with 2015 (%) (<85/100,000) (<55/100,000) (<10/100,000)
Percentage of TB-affected families
experiencing catastrophic costs due to 0 0 0
TB
Source: The WHO End TB strategy (World Health Organization, 2015a)

The Stop TB strategy (2006 – 2015)

While new tools such as drugs and vaccines were recognised as
essential to combating TB in the longer term, WHO understood that the
targets set for 2015 would only be achieved if more people had access
to existing good quality diagnosis and treatment. For this reason, The
Global Plan to Stop TB 2006 - 2015 adopted the WHO-recommended
Stop TB Strategy which consisted of the following six key elements:
1. Pursue quality DOTS expansion and enhancement (based on the
five elements of the DOTS strategy), improving case-finding and
cure through an effective patient-centred approach to reach all
patients, especially the poor.
2. Address TB/HIV, MDR-TB and other challenges, by scaling up
TB/HIV joint activities, DOTS-Plus, and other relevant
approaches.
23
3. Contribute to health system strengthening by collaborating with
other health programmes and general services, for example in
mobilising the necessary human and financial resources for
implementation and impact evaluation, and in sharing and
applying achievements of TB control.
4. Involve all care providers, public, nongovernmental and private, by
scaling up approaches based on a public-private mix, to ensure
adherence to the International Standards for TB Care (TB CARE
I, 2014).
5. Engage people with TB and affected communities to demand, and
contribute to, effective care. This will involve scaling up community
TB care; creating demand through context specific advocacy,
communication and social mobilisation; and supporting
development of a patients’ charter for the TB community.
6. Enable and promote research for the development of new drugs,
diagnostics and vaccines. Research will also be needed to
improve programme performance.
While the Stop TB Strategy ends in 2015, the need to provide care to
all TB patients, whether the disease is caused by drug-susceptible or
drug-resistant bacilli continues. Nurses are absolutely crucial to
ensuring the successful treatment of patients continues.
The DOTS strategy (1995 – 2005)
The DOTS strategy (1995 – 2006) remained at the heart of the Stop
TB Strategy and continues to be a guide for good TB management and
is consistent with many components of Pillar 2 of the new End TB
Strategy. It combines five elements or essential principles that must be
fully implemented to achieve effective TB control:
1. Political commitment to effective TB control.
2. Case detection by bacteriological confirmation (sputum
smear microscopy, Xpert MTB/RIF, culture, etc.) among
symptomatic people.
3. Standardised treatment regimen of six months with first-line
anti-TB drugs, administered under proper case management
conditions.
4. Uninterrupted supply of all essential anti-TB drugs.
5. Standardised recording and reporting system, allowing
monitoring and evaluation of treatment results.
1. Political commitment
Only political commitment to the TB control programme can ensure its
successful implementation. Political support at community, regional,
national and global level will provide technical guidance, and required
financial and human resources. Sustainable partnerships will guide the

24
achievement of short, middle and long-term goals in fighting TB.
Concerted efforts of communities, non-governmental organisations,
faith-based organisations and patient groups can improve political
commitment and increase access to care.
2. Case detection and monitoring by sputum smear microscopy
In order to control TB effectively, it is necessary firstly to reduce the
infectious pool in the community by finding and treating the most
infectious cases. While sputum smear microscopy remains a reliable
and cost-effective method of identifying infectious cases of TB, the
Xpert MTB/RIF test is becoming more widely used as the initial method
for diagnosis. This varies between and within countries and in all
circumstances nurses need to be aware of and follow local policies.
Some countries and settings have rolled out the Xpert MTB/RIF for
initial diagnosis.
3. Standardised treatment regimen
The objective of anti-TB treatment is to cure as high a percentage of
smear-positive patients as possible. Well-run programmes can cure
greater than 90% of all detected smear-positive cases.
The main requirements for adequate anti-TB treatment are the:
 right combination of anti-TB drugs,
 right dosage,
 right schedule, taken regularly without interruption,
 right length of treatment,
 patient entry is not in a critical or severe condition, and
 bacilli are not resistant to isoniazid and rifampicin.
Establishing a treatment regimen that is adequate and adapted to the
situation of the individual patient can be facilitated by placing each
patient on appropriate TB treatment. The diagnostic classifications are
used for each new or current TB patient, and they can be modified to
account for culture and drug-susceptibility testing (DST) results
obtained.
4. Regular, uninterrupted drug supply
Since it is imperative for a TB patient to complete a full, uninterrupted
course of treatment to prevent drug resistance, and since in most
countries TB drugs are procured centrally with a nation-wide system
for ordering and distribution, the government must commit to organise
and manage resources to ensure a consistent supply of drugs. Enough
medication to effectively treat all patients is based on the number of
cases detected and on the roster, including a reserve amount. This is
imperative to prevent treatment interruptions. Thus, accurate reporting
and recording systems are vital. Also, security is essential for storage

25
and transport of supplies. Drugs must be protected from adverse
conditions, such as extreme temperatures, water damage, accidents,
animal interference, etc. Governments must ensure that they are
procuring quality medications from trustworthy manufacturers. The
Global TB Drug Facility (GDF) is available to help governments and
non-governmental organisations procure a continuous supply of quality
TB drugs.
5. Standardised recording and reporting systems
Standardised recording and reporting systematically evaluate patient
progress and treatment outcome and give a picture of how the
programme is performing overall. There are four essential
components: the laboratory register, the patient treatment card, the TB
register and quarterly reports. These components should be able to be
cross-checked to evaluate completeness, accuracy and promptness of
record keeping, and programme accountability.
 The laboratory register logs all patients who have submitted a
sputum sample for analysis by biological examination (smear,
Xpert MTB/RIF) or by culture and sensitivity testing. Completed by
the laboratory technician, it includes basic patient details, dates of
the tests and results.
 Patient treatment cards contain basic patient details and clinical
information, including the medication, dosage and dates
prescribed for each patient. The card has a calendar grid for
recording each dose of medication, allowing the nurse and the
patient to see the treatment status, get timely sputum tests and
ensure adequate medication supplies. The treatment card is an
important indicator of treatment completion and is particularly
important if the patient is unable to produce a sputum specimen at
the end of the treatment or if the TB was extrapulmonary. If
medications are self-administered or supervised at home, the
patient or a family member maintains the card and needs training
to use it.
 The TB patient register lists all persons who have been
diagnosed with TB, including drug resistance (RR-TB, MDR-TB,
or XDR-TB), HIV status, anatomical site of TB, and previous
history of TB and who are under treatment at a particular facility. It
is maintained locally and allows the facility to monitor its own
performance. This register feeds into a district registry that
enables monitoring of the TB situation at district level, as well as
consolidating information about the overall epidemic.
 Quarterly cohort analysis includes data on all TB patients
registered during a three-month period. This type of report enables
health facilities to monitor their performance, identify and address
local problems, and order appropriate quantities of drugs and
supplies. At a district and national level, cohort analysis compares
TB programme progress to TB control targets.

26
The DOTS strategy and drug-resistant tuberculosis
The DOTS framework with its five elements also applies for the
management of drug-resistant TB. DOTS programmes ensure that
second-line drugs are used safely and appropriately within a
comprehensive management system. Without this strategic approach,
drug supplies may become erratic, recording is likely to be inadequate,
and the use of second-line drugs risks inconsistent, which can lead to
second-line drug resistance. Second-line drugs should only be used by
a project that follows the published WHO protocols for standardised or
individualised DOTS treatment regimens for MDR-TB (World Health
Organization, 2009a, World Health Organization, 2011b). Effective TB
control based on the DOTS strategy is the first step in the fight against
drug resistance.

27
28
Chapter 3: Diagnosis of Tuberculosis

Screening tests for TB

Systematic symptom screening for active TB is recommended to
detect TB early and get patients initiated on appropriate treatment as
soon as possible. In general clinical settings in high-burden TB and
TB/HIV settings, it is recommended to use a standard screening tool
for all patients at each clinic visit (or hospital admission) to screen for
common symptoms of TB (cough, unexplained loss of weight, night
sweats, and persistent fever) and to collect sputum samples from those
with symptoms for testing. (World Health Organization, 2013f). See
Annex 2 for a sample screening tool.
For more information on the systematic screening of patients for
active TB, please visit:
www.who.int/tb/publications/Final_TB_Screening_guidelines.pdf.
Tuberculin skin test (TST): In this test, a substance called tuberculin
is injected into the skin of the arm. Tuberculin is protein derived from
tubercle bacilli that have been killed by heating. In most infected
people, the immune system will recognise the tuberculin because it is
similar to the tubercle bacilli that caused infection. This will cause
reaction to the tuberculin. A positive TST reaction does not distinguish
between TB infection and active TB disease and a negative TST
reaction alone does not rule out TB disease.
The TST is read by measuring the induration in millimetres. A TST is
considered to be positive if:
≥ 5 mm induration ≥ 10 mm induration

 patients living with HIV or those  children irrespective of BCG

who are severely malnourished immunisation

 those who have a history of recent  those who work in high-congregate

contact with a known TB case settings (like prisons, healthcare
facilities, etc.)

o TST results take 48 -72 hours and require two patient visits
(once to have the TST set and again 48-72 hours later to
have the TST read).
o The test is inexpensive and does not require special
laboratory infrastructure.
Interferon-gamma release assay (IGRA): The WHO also
recommends this blood test to screen for latent TB infection. The IGRA
29
tests for an immune response to the TB bacilli from a prior exposure to
TB but does NOT detect actual TB bacilli.
o IGRA results take 24-48 hours.
o It is more expensive and technically challenging than TST
requiring special laboratory resources.
It is important to note that while both TST and IGRA can be useful in
identifying patients who have been exposed to TB and may require
additional work-up to rule out active TB, the TST and IGRA should
not be used to diagnose active TB. Additionally, these tests do not
predict which patients will develop active TB disease (World Health
Organization, 2011c).

Diagnosis of pulmonary TB
Several measures are used to diagnose pulmonary TB, the most
common and infectious form of the disease. The most common method
used to diagnose pulmonary tuberculosis is sputum smear microscopy
which will diagnose the most infectious cases, i.e. those that are
sputum smear positive. A new molecular diagnostic test is now being
used called Xpert MTB/RIF (also called GeneXpert) which can confirm
the presence of M. tuberculosis as well as rifampicin resistance. If
facilities are also available for drug-sensitivity testing, it will be possible
to identify drug resistance. Culture remains the gold standard for
diagnosing TB. Different methods for diagnosing TB are described
below.
For accuracy of diagnosis, at least two quality sputum specimens
should be taken from someone presumed to have TB. Ideally, the initial
specimen is collected at the first patient interview under the nurse’s
supervision and, if possible, it is recommended for the other sputum
specimen to be an early morning specimen. Depending on the
availability of laboratory services, if acid-fast bacilli (AFB) are seen on
direct microscopy, the specimen should be cultured to confirm the
identity of the bacilli and check their sensitivity to first-line anti-TB
drugs, especially isoniazid and rifampicin. If AFB are not seen and
laboratory services allow, the sputum specimen should be cultured
before being considered negative, or evaluated using Xpert MTB/RIF,
if available (World Health Organization, 2009a). In countries and
settings where Xpert MTB/RIF is used as the initial test, these
recommendations may vary and it is important to follow the national
guidelines.
The tubercle bacillus has a number of unique properties. It has an
unusually thick cell wall, which is impermeable by acids, alkalis and
detergents, and it is very slow growing. This means that specific tests
are required to investigate TB. To confirm active disease, the patient’s
sputum must be examined.

30
 Sputum smear microscopy: M. tuberculosis is identified
microscopically by its staining characteristics: it retains certain
stains after being treated with acid solution. Therefore, it is
classified as an “acid-fast bacillus” (AFB). The most common
staining technique is the Ziehl-Neelsen stain. AFB are stained
bright red, which stands out clearly against a blue background.
Auramine staining followed by fluorescence microscopy is faster
although not universally available.
 Xpert MTB/RIF: The newest diagnostic test for TB, Xpert
MTB/RIF is a rapid molecular diagnostic test useful for detection
of M. tuberculosis and rifampicin resistance which is used as a
proxy for MDR-TB. This test can provide results within two hours.
Introduced in 2010, the Xpert MTB/RIF was available in more than
100 countries as of June 2014. This test is also helpful in
diagnosing TB among patients living with HIV who are more likely
to be sputum smear negative (World Health Organization, 2014f,
World Health Organization, 2014d).
 Molecular-amplification assays
o Line probe assay (LPA): A molecular test used for rapid
detection of MDR-TB. Results are available within one to
two days and include drug-sensitivity testing for isoniazid
and rifampicin.
o MTBDRsl or second-line LPA (SL-LPA): A rapid
molecular DNA-based test that can detect genetic
mutations in MDR-TB strains which make them resistant to
fluoroquinolones and injectable second-line anti-TB drugs.
This test can also be used to detect XDR-TB. Results are
available within one to two days; much faster than current
culture methods which can take up to two months (World
Health Organization, 2016c).
 Culture: In addition to smear microscopy and Xpert MTB/RIF, all
specimens should also be isolated and identified by means of a
sputum culture. Culturing the specimen means growing the
mycobacteria on media, substances that contain nutrients, in the
laboratory. When the mycobacteria have formed colonies, they
can be identified. Liquid culture is the preferred culture method
over solid culture as it is more sensitive in detecting mycobacteria
and provides more rapid results to drug-sensitivity testing.
 Chest x-ray: This is helpful to look for cavitations areas of
consolidation and infiltration, enlargements of the hilar lymph
nodes and pleural effusion in symptomatic patients found to be
smear negative (World Health Organization, 2016a).
 Computer tomography (CT) and magnetic resonance imaging
(MRI): These are useful for guiding the diagnosis process in some
difficult cases, but frequently are not available.

31
Examples of the most commonly utilised tests and procedures to
diagnose TB are listed in Table 3.1.

Table 3.1: TB Diagnostic tests and procedures

Pulmonary Extrapulmonary
 Sputum smear microscopy  Biopsy at site
 Sputum culture  Fine needle aspiration at site
 Xpert MTB/RIF  Lumbar puncture
 Line probe assay (LPA) (if TB meningitis is
 Chest x-ray suspected)
 Bronchoscopy  Imaging, e.g. by CT or MRI
 Imaging, e.g. by CT or MRI  Tuberculin skin test (TST)
 Tuberculin skin test (TST) (most valuable in children)
(most valuable in children)
 Gastric washing (or gastric
aspirate) (in children)

Children are often treated empirically since it is harder to get a sputum

specimen. Gastric lavage and/or bronchoscopy are not often used
since it is not always fruitful and is difficult to do in many resource-poor
settings (Shingadia and Novelli, 2003). See more information on the
diagnosis of TB in children on page 33.

Diagnosis of extrapulmonary TB
The diagnosis of extrapulmonary TB can be difficult as it is less
common than pulmonary disease and there may be numerous
differential diagnoses. It is therefore essential to recognise the general
symptoms of TB that are common to both pulmonary and
extrapulmonary TB. Specific symptoms for extrapulmonary TB vary
according to the site of disease but severe pain is common – this can
be excruciating when it causes destruction in bones and joints.
In some cases, particularly with regard to TB of the lymph node, it may
be possible to collect pus by aspirating the infected site. Biopsies may
also be useful, but it is important to remember to send specimens for
both histo-pathological as well as microbiological examination. If at all
possible, diagnosis should be based on a culture-positive specimen, or
historical or strong clinical evidence consistent with active TB, followed
by a decision by a clinician to treat with a full course of anti-TB
treatment. A list of diagnostic tests is included in the table above. There
is likely to be varied availability of these tests especially imaging and
culture, according to local resources.

Diagnosis of drug-resistant TB
A multidrug-resistant organism requires treatment with second-line
drugs. While treatment of MDR-TB is more complicated, expensive and
longer than treatment with first-line drugs, it has been proven

32
efficacious. Patients who are identified early with MDR-TB can have
greater than an 85% chance of cure. The treatment is also feasible in
low-resourced areas. It is extremely important to treat MDR-TB patients
both to prevent their deaths and to prevent those who remain infectious
from spreading drug-resistant TB in the community.
Good history taking is essential when people present with TB
symptoms to determine previous TB treatment, its length and the drugs
used. In addition, during history taking, the patient may reveal contact
with someone who suffered from drug-resistant disease. This patient’s
sputum should be examined by Xpert MTB/RIF or cultured for drug-
sensitivity testing when risk factors for MDR-TB are detected. In some
areas there are no resources for culture and sensitivity testing, but in
those settings, a history of inadequate treatment, or past treatment with
only one drug, or a past default on treatment, followed by a return of
symptoms, may be considered as reasonable suspicion that one is
dealing with MDR-TB.
Drug-resistant TB can only be defined through laboratory confirmation
of in vitro resistance to one or more anti-TB drugs. In well-resourced
settings all specimens are sent for culture and drug-sensitivity testing,
in areas where there are fewer resources, specimens of high-risk cases
may be sent for further investigation but in some areas it is not possible
to offer any culture and sensitivity testing. Results are defined
according to the pattern of resistance as follows:
 Mono-resistant TB: TB in patients whose infecting isolates of M.
tuberculosis are confirmed to be resistant to one first-line anti-TB
drug.
 Poly-resistant TB: TB which is resistant to more than one first-
line drug, other than isoniazid and rifampicin.
 Rifampicin-resistant TB (RR-TB): Active TB resistant to
rifampicin, with or without resistance to isoniazid or other anti-TB
drugs. This is a newer description following the rollout of the Xpert
MTB/RIF rapid molecular diagnostic test.
 Multidrug-resistant TB (MDR-TB): Active TB which is resistant
to at least both isoniazid and rifampicin, the two most powerful
anti-TB agents; an MDR-TB strain can be resistant to more than
these two antibiotics and in many cases patients are resistant to
other first-line drugs as well.
 Extensively drug-resistant TB (XDR-TB): Active TB resistant to
at least rifampicin and isoniazid, in addition to any fluoroquinolone
(FQ), and to at least one of the three following injectable drugs
used in anti-TB treatment: capreomycin (Cm), kanamycin (Km) or
amikacin (Am).

33
Diagnosis of TB in children
Diagnosing TB in children can be difficult as many of the symptoms are
similar to other more common childhood diseases like pneumonia. The
most important role nurses can play in diagnosing TB in children is
careful history taking. It is important to ask about symptoms of TB, as
well about a history of a household or other close contact with a known
or presumed case of active TB or contact with an adult who has had a
chronic cough. Children less than five years old are more likely to have
a household contact with active TB than older school-aged children
who could potentially have been exposed to TB outside of the home
(The International Union Against Tuberculosis and Lung Disease,
2010, World Health Organization, 2006a).
The most common symptom and clinical sign of pulmonary TB in
children is a persistent cough and poor weight gain or failure to thrive.
Younger children (less than one year of age) and children who are
HIV-positive often present with acute pneumonia. Below is a list of the
most common signs and symptoms of TB in children under 10 years
old.
The approach to diagnosing TB in HIV-positive children is similar to
that for HIV-negative children.
Common symptoms of TB in children < 10 years old
 persistent cough ≥ 2 weeks that does not improve on its own or with
antibiotics
 loss of weight or failure to thrive
 persistent fever > 10 days
 night sweats
 fatigue which may present as reduced playfulness
 respiratory distress – in severe cases
Because many children less than five years of age do not cough and
produce sputum effectively, culture of gastric washings obtained by
nasogastric tube lavage or induced sputum has a higher yield than
spontaneous sputum (Shingadia and Novelli, 2003). Tuberculin skin
tests (TST) can also be useful in supporting a diagnosis of TB in
children with clinical symptoms suggestive of TB, but who are not
able to produce sputum (The International Union Against
Tuberculosis and Lung Disease, 2010).
Signs and symptoms and diagnosis of pulmonary TB among children
under 10 years old and adolescents are similar to the symptoms
present in adults. It is important to note that TB disease can be more
severe and have a much faster onset in younger children and infants.
Just as with adult TB cases, child TB cases should be screened for HIV
in settings with high HIV prevalence (The International Union Against
Tuberculosis and Lung Disease, 2010, World Health Organization,
2014a).

34
Box 1. Recommended approach to diagnose TB in children (World Health
Organization, 2006a)
1. Careful history (including history of TB contact and symptoms consistent with
TB)
2. Clinical examination (including growth assessment)
3. Tuberculin skin testing
4. Bacteriological confirmation whenever possible
5. Investigations relevant for suspected pulmonary TB and suspected
extrapulmonary TB
6. HIV testing (in high HIV prevalence areas)

For more information on diagnosing TB in children, please visit:

www.theunion.org/what-we-
do/publications/technical/english/pub_tbdeskguide_eng.pdf,
http://whqlibdoc.who.int/hq/2006/WHO_HTM_TB_2006.371_eng.pdf?ua=1,
and www.who.int/tb/challenges/Child_TB_Training_toolkit_web.pdf?ua=1.

Contact investigation
In some countries, contact tracing is initiated at the initial assessment.
The patient provides a list of those people closest to him/her. These
people are then invited for screening: a symptoms check, a TST or
sputum examination if TB symptoms are present. If resources are
scarce, the patient is encouraged to identify anyone he/she knows who
is showing signs or symptoms of the disease and to encourage them
to come to the health clinic for investigation. At a minimum, all children
under the age of five living in the patient’s household are examined.
Whatever the circumstances, this is a distressing process, since the
patient may not want others to know that he/she has TB. Contact
tracing offers a good opportunity to educate others about TB, infection
control in the home, and address stigma, thus increasing the patient’s
support system. Contact tracing must always be conducted
sympathetically, with the greatest possible effort to maintain
confidentiality.
TB Classification
Once diagnosed, patients should be classified by whether they have
had previous treatment for TB, and the outcome of this treatment. This
helps to identify patients at increased risk of drug resistance and to
prescribe appropriate treatment. In 2013, the WHO updated TB case
definitions and reporting recommendations and now recommends
national TB programmes use the following definitions detailed below
and in Table 3.2 (World Health Organization, 2009a, World Health
Organization, 2013b).

35
TB case definitions
 Presumptive TB refers to a patient who presents with symptoms or
signs suggestive of TB (previously known as a TB suspect).
 A bacteriologically confirmed TB case is a case with a confirmed
biological diagnosis by smear microscopy (smear positive), Xpert
MTB/RIF or other diagnostic tests, such as culture or LPA.
 A clinically diagnosed TB case is a case which cannot be
confirmed bacteriologically but has been diagnosed with active TB
by a clinician or other medical practitioner and the medical provider
has prescribed a full course of TB treatment. This definition includes
cases diagnosed on the basis of X-ray abnormalities or suggestive
histology and extrapulmonary cases without laboratory
confirmation. If a clinically diagnosed case is later confirmed to have
TB by bacteriologic means either before or after starting TB
treatment, they should be reclassified as a bacteriologically
confirmed TB case (World Health Organization, 2013b).
Bacteriologically confirmed or clinically diagnosed cases of TB are
further classified according to:
 anatomical site of disease
 history of previous treatment
 drug resistance
 HIV status
Classification based on anatomical site of disease
Pulmonary tuberculosis (PTB) refers to any bacteriologically
confirmed or clinically diagnosed case of TB involving the lung
parenchyma or the tracheobronchial tree. Miliary TB is classified as
PTB because there are lesions in the lungs.
Patients with pulmonary TB are referred to as either smear
positive or smear negative
This is an important distinction as smear-positive patients tend to have
more advanced disease with more damage to their lungs so they cough
up more infectious material and are therefore more contagious. Without
treatment, the outcome of their disease is poorer than that of smear-
negative patients.
Pulmonary TB; sputum smear positive (PTB+)
 is the most infectious form of TB
 refers to patients who have enough TB bacilli (AFB) in their sputum
that they can be identified under a microscope when a Ziehl-
Neelsen or auramine stain is used:
o at least two initial sputum smear examinations need to be
positive for AFB; or
36
 o one sputum specimen AFB+ and radiographic abnormalities
consistent with active pulmonary TB; or
o one sputum specimen AFB+ culture positive for TB bacilli
o one sputum specimen bacteriologically confirmed with Xpert
MTB/RIF
Pulmonary TB; sputum smear negative (PTB-)
If a patient has symptoms suggestive of TB, at least two sputum
examinations negative for AFB, and radiographic abnormalities
consistent with active PTB, the patient should receive a full course of
anti-TB therapy. Individuals living with HIV are more likely to be smear
negative. If available, Xpert MTB/RIF should be used to diagnose TB
in those living with HIV.
Knowing whether the patient is smear negative or smear positive
is important for two reasons:
1. Sputum conversion from smear positive to smear negative or vice
versa is one of the key indicators of a patient’s progress and
response to treatment.
2. The status of the sputum smear can determine how to allocate
scarce resources. In such situations smear-positive patients take
priority in treatment over less infectious smear-negative cases
although every effort must be made to treat all cases of TB as soon
as possible.
Extrapulmonary tuberculosis refers to any bacteriologically
confirmed or clinically diagnosed case of TB occurring outside of the
lungs and involving organs other than the lungs, e.g. pleura, lymph
nodes, abdomen, joints and bones, meninges, etc.
A patient with both pulmonary and extrapulmonary TB should be
classified as a case of pulmonary TB.
Classification based on HIV status
HIV-positive TB patient refers to any patient diagnosed with TB by
bacteriologic or clinical means who is known to be HIV-positive or who
has tested positive to an HIV test at the time of TB diagnosis. An HIV-
positive TB case may or may not be on antiretroviral therapy.
HIV-negative TB patient refers to any bacteriologically confirmed or
clinically diagnosed case of TB who has a negative result from HIV
testing conducted at the time of TB diagnosis. If a HIV-negative TB
patient is later found to be HIV-positive, they should be reclassified as
a HIV-positive TB case.
HIV status unknown TB patient refers to any bacteriologically
confirmed or clinically diagnosed case of TB who has no result of HIV
testing and has no evidence of being enrolled in HIV care. If the

37
patient’s HIV status is subsequently determined, he or she should be
reclassified accordingly.

Classification based on drug resistance

Cases are classified in categories based on drug-susceptibility testing
of clinical isolates confirmed to be M. tuberculosis and include: mono-
resistant, poly-drug resistant, multidrug resistant, extensively drug-
resistant, and rifampicin resistant. Any patient with drug-resistant TB
can fit into more than one of the above categories. For example, if a
patient is diagnosed with RR-TB they must also be recorded as being
either MDR-TB or XDR-TB. (World Health Organization, 2013b)
It is important for nurses to be familiar with the case definitions,
reporting and classification definitions in the national TB Programme
(NTP) guidelines of their country. For more information on the WHO
classification and reporting guidelines, please see
http://apps.who.int/iris/bitstream/10665/79199/1/9789241505345_eng.pdf.

Table 3.2: Definitions of TB case classifications

Type of case Definition
New patient No previous treatment for TB or treatment for
less than one month
Previously treated patients Have previously received at least one month
or more of anti-TB treatment including the
outcome of the most recent course of anti-TB
treatment.
Relapse patients Previously treated and declared cured, or
treatment completed in the past, and now
diagnosed with smear-positive or culture-
positive TB. (This can be either true relapse
or a new episode of TB caused by
reinfection).
Treatment after failure patients Previously treated for TB and whose
treatment failed at the end of treatment, e.g.
remained smear positive after five months of
treatment.
Treatment after loss to follow-up A patient returning to treatment who is smear
patients or culture positive, after being classified as
lost to follow-up at the end of their most
(Previously referred to as treatment recent TB treatment.
after default)
Other previously treated patients Patient previously treated for TB without any
documented history of treatment outcome.
Patients with unknown previous TB Patients who do not fit into any of the other
treatment history categories.
*New and relapse cases of TB are incident TB cases.
Source: Definitions and reporting framework for tuberculosis – 2013 revision (World
Health Organization, 2013b)

38
39
Chapter 4: Treatment of Tuberculosis

TB treatment: Essential drugs against TB

More than 10 million bacteria exist in the actively multiplying bacterial
population in any given patient, and there are always a few
mycobacteria resistant to one or another of the anti-TB drugs. If only
one drug is used, bacteria resistant to that drug will continue to develop
and multiply. However, if more than one drug is used, the bacteria that
may be resistant to the first drug are killed by the second drug – this is
the rationale behind the use of multiple-drug therapy.
Anti-TB drugs have three main actions: bactericidal activity, sterilising
activity and the ability to prevent resistance. Isoniazid and rifampicin
are the most powerful bactericidal drugs. Rifampicin is the most potent
sterilising drug and pyrazinamide and streptomycin are also
bactericidal. Ethambutol is used in association with more powerful
drugs to prevent the development of resistant TB bacilli. Table 4.1
below shows (World Health Organization, 2009a) the main first-line TB
drugs and recommended dose. The range is shown in parentheses.
The WHO still recommends the use of fixed-dose combination (FDC)
tablets for the treatment of TB. Details are provided in Table 4.2 below.
Standard code for TB treatment regimens
TB treatment regimen should have a standard code. Each anti-
TB drug has an abbreviation:
Isoniazid H
Rifampicin R
Pyrazinamide Z
Ethambutol E
Streptomycin S
Table 4.1: Essential first-line anti-TB drugs and recommended doses
Recommended dose
Daily 3 times per week
Dose and range Maximum Dose and range Daily
Drug (mg/kg body (mg) (mg/kg body maximum
(abbreviation) weight) weight) (mg)
5 10
Isoniazid (H) 300 900
(4-6) (8-12)
10
10
Rifampicin (R) 600 (8-12) 600
(8-12)
25 35
Pyrazinamide (Z) 2000 2000
(20-30) (30-40)
15 30
Ethambutol (E) 1200 1200
(15-25) (20-35)
15 15
Streptomycin (S) 1000 1000
(12-18) (12-18)

40
*WHO no longer includes the use of thioacetazone as a first-line drug because of the risk
of severe toxicity in HIV-infected individuals (World Health Organization, 2009a).
Source: Treatment of tuberculosis: guidelines - 4th ed (World Health Organization,
2009a)

Table 4.2: Fixed-dose combination of first-line drugs

Drug Dose form Strength for daily Strength for use 2-3
use times weekly
Isoniazid + Tablet 75 mg + 150 mg; 150 mg + 150 mg
rifampicin 150 mg + 300 mg

Tablet or pack of 30 mg + 60 mg 60 mg + 60 mg
granules*
Isoniazid + Tablet 150 mg + 400 mg --
ethambutol
Isoniazid + Tablet 75 mg + 150 mg + 150 mg + 150 mg +
rifampicin + 400 mg 500 mg
pyrazinamide
Tablet or pack of 30 mg + 60 mg + --
granules* 150 mg

Isoniazid + Tablet 75 mg + 150 mg + --

rifampicin + 400 mg + 275 mg
pyrazinamide +
ethambutol
*For paediatric use.
Source: Treatment of tuberculosis: guidelines - 4th ed (World Health Organization,
2009a)

For new patients with PTB and EPTB, treatment with the drugs
recommended by WHO is divided into two phases:
1. Intensive phase – four drugs given daily (isoniazid (H), rifampicin
(R), pyrazinamide (Z), and ethambutol (E)) in fixed dose
combination, and directly observed for at least two months. This
rapidly improves clinical symptoms and reduces the bacterial
population without allowing drug resistance to develop.
2. Continuation phase – a combination of two drugs (isoniazid and
rifampicin) in fixed-dose combination, daily or three times per week,
for four more months to eliminate remaining bacilli and prevent
relapse. The WHO now recommends drug treatment regimens
containing at least six months of rifampicin for new TB patients.
In the standard code, the number before a phase is the duration of the
phase in months. Letters in parentheses indicate fixed-dose
combinations of those drugs. A number in subscript (e.g. 3) after a
letter or letters in parentheses indicates the number of doses of that
drug per week. If there is no subscript number, treatment is daily (or 6
times weekly, excluding for instance Sundays). One example is shown
below:
2 (HRZE) / 4 (HR)3
41
The initial phase is 2 (HRZE). The duration of this phase is two months.
Drug treatment is daily, with isoniazid (H), rifampicin (R), pyrazinamide
(Z) and ethambutol (E) in FDC.
The continuing phase is 4 (HR)3. The duration is four months, with
isoniazid and rifampicin, in fixed-dose combination, three times per
week.
The current WHO recommended standard anti-TB treatment
regimens for new and presumed TB patients are detailed in Table 4.3
below. For more information, please visit the latest WHO Treatment
of tuberculosis: guidelines – fourth edition:
http://whqlibdoc.who.int/publications/2010/9789241547833_eng.pdf?ua=1.

Table 4.3: Recommended treatment regimens for new and presumed

TB patients
TB treatment regimen
TB case classification Dosing frequency Initial phase Continuation
phase
Presumed, or new
patients known, to have PREFERRED
drug-susceptible TB treatment regimen
(includes smear-negative, 2 HRZE 4HR
smear- and culture- Daily for initial and
positive patients), both continuation phases
HIV-positive and HIV-
negative patients, and Daily for intensive and
those with EPTBa (except three times per week for
TB meningitisb, CNS, continuation phase
joint and bone).
2 HRZE 4 HR3
Acceptable if patient
receives directly
observed therapy for
continuation phase
Three times per week
for intensive and
continuation phase

Acceptable if patient is
receiving directly
observed therapy 2 HRZE3 4 HR3

NOT recommended for

patients living with HIV
or patients living in
areas with high
prevalence of HIV
New TB patients in areas
where isoniazid
Daily 2 HRZE 4 HRE
resistance among new
TB patients is high

42
Notes:
a Except for the following types of EPTB cases: TB meningitis, TB of the bone, joint or TB of the

CNS. WHO recommends treating EPTB for 9 – 12 months (TB meningitis) and 9 months (for TB
of bone or joint) with standard regimen – 2 HRZE / 4 HR) (World Health Organization, 2009a).
b In TB meningitis ethambutol should be replaced by streptomycin.

Source: Treatment of tuberculosis: guidelines - 4th ed (World Health Organization, 2009a)

For previously treated patients with access to DST or rapid

molecular tests and who have drug-sensitive TB, the initial phase
is two months of daily drug treatment with isoniazid (H), rifampicin (R),
pyrazinamide (Z), ethambutol (E), and streptomycin (S) followed by
one month of isoniazid (H), rifampicin (R), pyrazinamide (Z), and
ethambutol (E). The continuation phase is five months with isoniazid
(H), rifampicin (R), and ethambutol (E) for a minimum of eight months
of treatment.
The WHO recommends that DST be done for all patients (new and
previously treated) before starting anti-TB treatment to ensure that
each patient is placed on appropriate therapy. With the rollout of Xpert
MTB/RIF many countries now have the ability to test for rifampicin
resistance at the initial diagnosis and can perform confirmatory DST
prior to starting anti-TB treatment. However, many countries and
regions still do not have access to this rapid diagnostic test. Therefore,
WHO recommends that all previously treated patients especially
among those who failed prior treatment and all patients living with HIV
have DST performed for at least isoniazid and rifampicin prior to
starting anti-TB treatment. In addition, DST is recommended for new
patients with a history of contact with a known MDR-TB case and in all
new patients living in countries or settings where more than 3% of new
TB patients are expected to be MDR-TB. Table 4.4 below details the
WHO recommended treatment regimens for previously treated
patients.

Nurses must be familiar with the adverse reactions of anti-TB drugs

and refer to WHO and national tuberculosis programme (NTP)
guidelines on essential drugs and national treatment guidelines.
For more information on WHO recommendations for TB treatment, please
visit: http://whqlibdoc.who.int/publications/2010/9789241547833_eng.pdf?ua=1.

43
Table 4.4: TB treatment regimens for previously treated patients
based on availability of access to DST
Likelihood of MDR-TB
(based on patient registration group/classification)
High likelihood of MDR- Low or medium
DST availability
TB (i.e. patients who likelihood of MDR-TB
have failed first-line (i.e. relapse or loss to
treatment) follow-up patients)
Xpert MTB/RIF If not RR-TB start
If RR-TB to be started on
retreatment regimena
empiric MDR regimen
2 HRZES / 1 HRZE / 5
*Regimen to be revised
HREb
once confirmatory DST
results become available
Rapid molecular-based DST results available DST results available
method (line probe assay) within 1 – 2 days to confirm within 1 – 2 days to
or exclude MDR to guide confirm or exclude MDR to
choice of regimen guide choice of regimen
Conventional method While waiting for DST
results 2 HRZES/ 1 HRZE /5
(liquid or solid culture) HREa
Empirical MDR regimen for full course of treatment

*Regimen to be revised *Regimen to be revised

once DST results become once DST results become
available available
DST not available 2 HRZES/ 1 HRZE /5
Empirical MDR regimen
HREa
for full course of treatment
*Regimen to be revised
once DST results or drug-
*Regimen to be revised
resistant survey (DRS)
once DST results or DRS
data become available
data become available
a This is based on international guidance and policies regarding regimens may vary between
countries. It is essential that nurses are familiar with and follow locally recommended treatment
regimens and policies.”
b Daily regimen – intermittent or thrice weekly regimens of first-line drugs are not recommended

for previously treated patients.

TB treatment regimens for children

The standardized treatment regimens for children are similar to those
for adolescents and adults with the exception of certain types of
extrapulmonary TB as shown in Table 4.5 below. Intermittent anti-TB
treatment is not recommended for children with HIV. Table 4.6 provides
information on daily dosage of anti-TB medications for paediatric TB
cases.
As of late 2015, child-friendly formulations or doses of anti-TB
medications are available. The new child-friendly formulations are

44
available in FDC making it simpler and easier to give the correct dose
to children weighing < 25 kg without having to cut or crush pills. The
new formulations can be dissolved in water making it easier to give to
younger children (World Health Organization, 2015e). However, there
are still no child-friendly formulations or doses of second-line anti-TB
medications for children with drug-resistant TB.
For more information on treatment regimens for paediatric TB patients
please visit: http://www.who.int/tb/FDC_Factsheet.pdf, and
www.theunion.org/what-we-
do/publications/technical/english/pub_tbdeskguide_eng.pdf.

Table 4.5: Recommended treatment regimens for new paediatric

patients in HIV endemic settings*
Recommended regimen
TB disease category Intensive Continuation
phase phase

All forms of PTB and EPTB except

2 HRZE 4 HR
TB meningitis & osteoarticular TB

TB meningitis & osteoarticular TB 2 HRZE 10 HR

*An HIV endemic setting is a setting/country where prevalence of HIV adult pregnant women is
greater than 1% or the prevalence of HIV among TB patients is more than 5%.

Source: (World Health Organization, 2010, The International Union Against Tuberculosis and
Lung Disease, 2010)

Table 4.6: Recommended doses according to weight for children

Drug Daily dosage in mg/kg

(range)
Isoniazid (H) 10 mg/kg (range 7-15)
Rifampicin (R) 15 mg/kg (range 10-20)
Pyrazinamide (Z) 35 mg/kg (range 30-40)
Ethambutol (E) 20 mg/kg (range 15-25)
Source: (World Health Organization, 2010, The International Union Against Tuberculosis and
Lung Disease, 2010, World Health Organization, 2015e)

Treatment of MDR-TB
When MDR-TB is confirmed by DST (rapid molecular or culture
methods), is suspected based on the patient’s history, or rifampicin
resistance is identified by Xpert MTB/RIF the first phase of treatment
should include at least four second-line drugs susceptible to the
infecting strain. This intensive phase should include pyrazinamide
(Group 1), a parenteral agent (Group 2), a fluoroquinolone (Group 3),
and ethionomide or prothionomide (Group 4), and cycloserine (or PAS
if cycloserine is not available). Drugs listed in Group 5 in Table 4.7
45
below may be used, but these drugs are not recommended as they are
of unknown efficacy. It is no longer recommended to add additional
second-line drugs to the standard MDR-TB regimen of four
second-line drugs. The first phase, which uses an injectable agent,
should be a minimum of six to eight months and many programmes
extend treatment if the patient has not converted both smear and
culture. However, the duration of the intensive phase may be modified
based on the patient’s condition, for example, if the patient converts
before eight months the intensive phase may be modified to less than
eight months. The evidence to support this is not of high quality
however. The entire treatment period should not be less than 20
months past smear and culture conversion (World Health Organization,
2011b, World Health Organization, 2014b).

Box 2. Example of a standardized MDR-TB regimen

8Km6-Lfx7-Eto7-Cs7-Z7/12Lfx7-Eto7-Cs7-Z7

The initial phase consists of five drugs and lasts for eight months in most patients.
Kanamycin is given six days a week and all other drugs are given seven days a week.
The continuation phase in this example - the phase without the injectable - continues
all the oral agents for a minimum of 12 months. The total minimum treatment will last
at least 20 months.

Patients with MDR-TB take more tablets for a longer period of time,
may experience more adverse effects and require increased support to
continue treatment and/or to monitor adverse effects. Detecting and
controlling adverse effects in a timely manner prevents adherence
problems and patients defaulting treatment. Nurses play a critical role
in the rapid detection of adverse effects, management and adherence
issues. See Annex 5 for common adverse effects of essential and
reserve medications used in treating drug-sensitive and drug-resistant
TB. Patients co-infected with HIV and MDR-TB often experience more
adverse effects in addition to drug to drug interactions between
second-line TB medications and antiretrovirals. See the WHO’s
Companion handbook to the WHO guidelines for the programmatic
management of drug-resistant tuberculosis (World Health
Organization, 2014b) for more information.
http://apps.who.int/iris/bitstream/10665/130918/1/9789241548809_eng.pdf?ua=1
&ua=1

46
Table 4.7: Conventional groups of second-line anti-tuberculosis
agents used to treat MDR-TB
Group name Anti-tuberculosis agent Abbreviation
Group 1: First-line oral drugs Isoniazid H
Rifampicin R
pyrazinamide Z
ethambutol E
rifabutina Rfb
Group 2: Second-line parenteral kanamycin Km
agent amikacin Am
(injectable anti-tuberculosis drugs) capreomycin Cm
streptomycinb S
Group 3: Fluoroquinolonesc levofloxacin Lfx
moxifloxacin Mfx
gatifloxacind Gfx
Group 4: Oral bacteriostatic second- ethionamide Eto
line anti-tuberculosis drugs protionamide Pto
cycloserine Cs
terizidone Trd
para-aminosalicylic acid PAS
para-aminosalicylate PAS-Na
sodium
Group 5: Drugs with limited data on Bedaquiline Bdq
efficacy and/or long term safety in the Delamanid Dlm
treatment of MDR-TB clofazimine Cfz
linezolid Lzd
amoxicillin/clavulanate Amx/Clv
thioacetazone Thz
clarithromycin Clr
imipenem/cilastatin* Ipm/Cln
High-dose isoniazid High-dose H
meropenem* Mpm
a Rifabutin has similar microbiological activity as rifampicin. Rifabutin is not on the WHO list of
essential medicines, however it has been added here as it is used routinely in patients on
protease inhibitors in many settings.
b There are high rates of streptomycin resistance in MDR-TB; therefore it is not considered a

second-line anti-TB injectable agent.

c Ofloxacin is considered a weaker fluoroquinolone against TB and is no longer recommended.
d Gatifloxacin is known to have life-threatening side effects including serious diabetes

(dysglycemia) and has been removed from the formula in several countries.
e Terizidone has limited programme data and effectiveness data as compared to cycloserine.
f Clavulanate (Clv) is recommended as an adjunctive to imipenem/cilastatin and meropenem.
g Limited data on the role of thioacetazone and clarithromycin in MDR-TB treatment has
resulted in many experts not including these drugs as options for Group 5.
Source: Companion handbook to the WHO guidelines for the programmatic management of drug-
resistant tuberculosis (World Health Organization, 2014b)

New shortened treatment for MDR-TB

As of May 2016, WHO recommends a shortened treatment regimen for
patients with MDR-TB (World Health Organization, 2016d). The new
MDR-TB regimen shortens the MDR-TB treatment course from 20 to
24 months to nine to 12 months. The new recommended regimen
47
should contain a second-line injectable plus a fluoroquinolone
(moxifloxacin), prothionamide (or ethionamide), clofazimine, high-dose
INH, pyrazinamide, and ethambutol for an initial phase of four months.
This is to be followed by five months of four drugs (moxifloxacin,
clofazimine, pyrazinamide, and ethambutol). Please see Box 3 for a
sample regimen. More detailed information can be found at
http://www.who.int/tb/MDRTBguidelines2016.pdf?ua=1 (World Health
Organization, 2016d).

Box 3. Example of new shortened MDR-TB treatment regimen (World

Health Organization, 2016d)

4-6 Km-Mfx-Pto-Cfz-Z-Hhigh-dose-E / 5 Mfx-Cfz-Z-E

The WHO has revised the list and grouping of medications for the
treatment of MDR-TB and RR-TB. Please see Table 4.8 below for the
updated groupings.

Table 4.8. Updated anti-TB medications for the treatment of RR-TB

and MDR-TB
Group name Anti-TB medication Abbreviation
A. Fluoroquinolonesa Levofloxacin Lfx
Moxifloxacin Mfx
Gatifloxacin Gfx
B. Second-line injectable agents Amikacin Am
Capreomycin Cm
Kanamycin Km
(Streptomycin)b (S)
C. Other core second-line agents Ethionamide / Prothionamide Eto / Pto
Cycloserine/Terizadone Cs / Trd
Linezolid Lzd
Clofazimine Cfz
D. Add-on agents D1 Pyrazinamide Pza
Ethambutol E
High-dose isoniazid Hh
D2 Bedaquiline Bdq
Delamanid Dlm
D3 p-aminosalicylic acid PAS
Imipenem-cilastatinc Ipm
Meropenemc Mpm
Amoxicillin-clavulanate Amx-Clv
(Thioacetazone)d (T)
a Medications in Groups A and C are shown by decreasing order of preference for use.
b Streptomycin is not appropriate for substitution for other injectable agents. Please see the text
for more detailed information. (http://www.who.int/tb/MDRTBguidelines2016.pdf?ua=1)
c Carbapenems and clavulanate are meant to be used together; clavulanate is only available in

formulations combined with amoxicillin.

d HIV status must be tested and confirmed to be negative before thioacetazone is started.

48
New drugs to treat drug-resistant TB
Bedaquiline
Bedaquiline (TMC207) is the first new drug to be approved for
treatment of tuberculosis in 40 years. A WHO expert panel has
recommended that bedaquiline may be added to a standardized MDR-
TB treatment regimen for pulmonary MDR-TB in adults only. There
remains limited data available on the use of bedaquiline and long-term
adverse effects among other safety issues. Therefore, the use of
bedaquiline is very limited and controlled as of late 2014. There are five
conditions that must be met for use of bedaquiline to be used to treat
MDR-TB patients and it is not yet available in most countries. The five
conditions are:
1 Treatment is administered under closely monitored conditions.
2 Proper patient inclusion (pulmonary MDR-TB patients > 18 years
old).
3 Informed consent from patient.
4 Adherence to WHO recommended standardized MDR-TB
regimen.
5 Management of adverse drug events (World Health
Organization, 2013g).
For more detailed information on bedaquiline please visit:
www.who.int/tb/challenges/mdr/bedaquiline/en/index.html.

Delamanid
Delamanid (OPC-67683) is another new drug which has been
approved in several countries as of 2014. WHO convened an expert
panel to develop recommendations for the use of delamanid for the
treatment of pulmonary MDR-TB in adults. At present there is limited
data available on the use delamanid, safety issues and long-term side
effects.(World Health Organization, 2014h)
The conditions for use of delamanid are:
1 Proper patient inclusion (adults ≥ 18 with pulmonary MDR-TB –
including those with HIV).
2 Adherence to WHO recommended standardized MDR-TB
regimen.
3 Treatment is administered under closely monitored conditions.
4 Active pharmacovigilance and management of drug adverse
events including drug interactions.
5 Informed consent obtained from the patient.
For more detailed information on delamanid please visit:
http://apps.who.int/iris/bitstream/10665/137334/1/WHO_HTM_TB_2014.23_eng.p
df?ua=1&ua=1&ua=1

49
Monitoring TB treatment
During the course of TB treatment, sputum smears must be taken at
least three times for monitoring purposes for new smear-positive
pulmonary TB/MDR-TB cases (see Table 4.9).

Treatment outcome definitions

The 2013 revised WHO definitions and reporting guidelines now
make a distinction between drug-susceptible and drug-resistant TB
patients (those taking second-line drugs) and the reporting should
reflect this. For example, if a patient initially started first-line treatment
and is then later found to have drug-resistant TB, they must be
removed from the drug-susceptible TB register and outcome cohort
and added to the drug-resistant register and outcome cohort.

Treatment outcome definitions are described in Table 4.10 for drug-

susceptible TB patients and Table 4.11 for drug-resistant TB patients
(RR-TB and MDR-TB).

Table 4.9: Monitoring of TB treatment by smear microscopy for new

pulmonary TB patients (6-month regimen)
Time of New smear-positive pulmonary TB Retreatment smear-positive
sputum patients pulmonary TB patients
collection (6-month regimen)
At the end of the 2nd month of At the end of the 3rd month of
treatment when 75-85% of initially treatment when sputum smear-
sputum smear-positive patients positive patients should be
should be sputum smear negative sputum smear negative (sputum
(sputum conversion) conversion)
st
1 time
If smear positive – repeat sputum If still smear positive at the end
again at the end of month 3 and of month 3, request culture and
if still smear positive at the end of DST
month 3, request culture and DST

At the end of the 5th month of At the end of the 5th month of
treatment in order to confirm TB cure. treatment in order to confirm TB
cure.
2nd time If smear positive – request culture
and DST If smear positive – request
culture and DST

At the end of the 6th month of At the end of the 8th month of
treatment in order to confirm TB cure. treatment in order to confirm TB
cure.
3rd time
If smear positive – request culture
and DST If smear positive – request
culture and DST

50
Source: Treatment of tuberculosis: guidelines - 4th ed (World Health Organization,
2009a)

Conversion (to negative): A patient is considered to have converted

to negative if two consecutive sputum smears (drug-susceptible TB or
cultures (RR-TB and MDR-TB), taken at least 30 days apart, are found
to be negative. The date the specimen of the first negative culture was
collected is used as the date of conversion.
Reversion (to positive): A patient is considered to have reverted to
positive when, after an initial conversion, two consecutive sputum
smears (drug-susceptible TB) or cultures (RR-TB and MDR-TB), taken
at least 30 days apart, are found to be positive. For the purpose of
defining treatment failure, reversion is considered only when it occurs
in the continuation phase (World Health Organization, 2009a, World
Health Organization, 2014b).

Table 4.10: WHO treatment outcomes for TB patients (excluding

patients treated for RR-TB or MDR-TB)
Outcome * Definition
Cured A pulmonary TB patient with bacteriologically confirmed
TB at the start of treatment who was smear- or culture-
negative in the last month of treatment and on at least
one previous occasion.
Treatment completed A TB patient who completed treatment without evidence
of negative sputum smear or negative culture results in
the last month of treatment and at least on one previous
occasion and without evidence of treatment failure. This
may be because tests were not done or because results
are unavailable.
Treatment failed A TB patient whose sputum smear or culture remains
positive at the 5th month or later during treatment.
Died A TB patient who dies for any reason before starting or
during the course of treatment.
Lost to follow-up A TB patient who did not start treatment or whose
treatment was interrupted for 2 consecutive months or
more.
Not evaluated A TB patient for whom no treatment outcome is
assigned. This includes cases “transferred out” to
another treatment unit as well as cases for whom the
treatment outcome is not known.
Treatment success The sum of cured and treatment completed.
Adapted from WHO Definitions and reporting framework for tuberculosis – 2013 revision
(World Health Organization, 2013b)

*All bacteriologically confirmed and clinically diagnosed TB cases should have a recorded
outcome from the above list except those with RR-TB or MDR-TB, who are placed on a
second-line drug regimen – see treatment outcomes for RR-TB and MDR-TB patients below
in Table 4.11.

51
Table 4.11: Treatment outcomes for RR-TB/MDR-TB/XDR-TB patients
treated using second-line treatment
Outcome Definition
Cured Treatment completed without evidence of failure AND
three or more consecutive cultures taken at least 30
days apart are negative after the intensive phase.

Treatment completed Treatment completed without evidence of failure BUT

no record that three or more consecutive cultures
taken at least 30 days apart are negative after the
intensive phase.
Treatment failed Treatment terminated or need for permanent regimen
change of at least two anti-TB drugs because of:
 lack of conversiona by the end of the intensive
phase, or
 bacteriological reversion in the continuation
phase after conversion to negativea, or
 evidence of additional acquired resistance to
fluoroquinolones or second-line injectable
drugs, or
 adverse drug reactions (ADRs).
Died A patient who dies for any reason during the course
of treatment.
Lost to follow-up A patient whose treatment was interrupted for two
consecutive months or more.
Not evaluated A patient for whom no treatment outcome is assigned
– includes cases who ”transferred out” to another
facility and whose treatment outcome is unknown.
Treatment success The sum of cured and treatment completed
Source: Definitions and reporting framework for tuberculosis – 2013 revision (World Health
Organization, 2013b)
a The terms “conversion” and “reversion” of culture are defined as follows:

Medication adverse effects

Minimising medication adverse effects helps ensure patient adherence
to treatment. The nurse should teach every patient about the possible
adverse effects and encourage them to report any symptoms as soon
as possible. Adverse effects fall into two groups depending on their
severity, minor and major.
Minor adverse effects include:
 discolouration of urine
 nausea, occasional vomiting, abdominal discomfort, loose stools
 lack of energy
 mild rash, itching
The patient experiencing minor adverse effects needs support to
complete his/her treatment. The nurse may need to think of ways to

52
help alleviate suffering such as changing the medication time, diet
and/or offering mild anti-emetics, antacids or anti-histamines.
Treatment is usually stopped if the patient suffers any of the
following major adverse effects:
 persistent vomiting
 hepatic toxicity/jaundice
 peripheral neuropathy
 severe rash
After a short break in treatment to permit some recovery from the
adverse effects, each drug is reintroduced, one at a time, to identify the
problem drug. Once identified, the problem drug is replaced with an
alternative. This does mean that the treatment period is extended.
For more detailed guidance, please see Adverse Effect Management
in Annex 5 (page 80).

Treatment Adherence
To encourage adherence to treatment protocols, TB services must be
flexible enough to give the patient a choice about where they receive
treatment, e.g. at home, in the clinic or in the workplace (TB CARE I,
2014, Williams et al., 2007). If the patient chooses to take the drugs in
his home or workplace, treatment observers, other than those
associated with the clinic, are encouraged. These observers can be
anyone who is willing, trained, responsible, acceptable to the patient
and accountable. Close family members, such as spouses, may not
always make the best treatment observers as they may be manipulated
by the patient and caution is needed to ensure adherence.
Failure to adhere to standardised treatment due to adverse effects or
other reasons can lead to treatment failure and the emergence of MDR-
TB. Therefore, the patient’s commitment to the prescribed therapy
plays a key role in successful treatment outcomes. Nurses must listen
to patients’ concerns and provide information and education that is
tailored to each patient’s needs. The importance of treatment
adherence and obtaining patient commitment are vital for treatment
success.
Please see Annex 6 (page 90) for more information on factors affecting
adherence and suggestions to improve adherence.

53
54
Chapter 5: Guidelines for Patient Care:
Nursing Principles and Processes
Role of Nurses in TB Care and Management
Nurses make up by far the largest group of healthcare workers in any
part of the world and as in most areas of healthcare they often
undertake the bulk of the work in TB control. According to the ICN Code
of Ethics, “Nurses have four fundamental responsibilities: to promote
health, to prevent illness, to restore health and to alleviate suffering.
The need for nursing is universal.” (International Council of Nurses,
2012) In relation to TB, nurses promote health in order to prevent
people becoming vulnerable to the disease in the first place; they
prevent illness by reducing transmission of TB in the community by
finding and treating active cases; they restore health by ensuring
patients receive the treatment they need; and alleviate suffering by
organising support for patients according to their individual needs.
Many people are extremely shocked when they are told they have TB;
some refuse to accept it; and others simply take it in their stride. The
reaction depends on many factors including cultural beliefs and values,
previous experience, and knowledge of the disease. TB sometimes
has a high profile in the media; the reports are often alarmist and a
stigma still remains attached to the disease. Even though TB is more
common among vulnerable groups, it can affect anyone and it is
important for patients to be able to discuss their concerns. Nurses are
well-placed within communities, working closely with patients and their
families, to play a crucial role in providing a caring environment for all
patients suffering from TB. This is essential to the success of TB control
programmes which need to offer good access to effective diagnostic
and treatment facilities. With the inclusion of patient-centred care as
one of the three main pillars of the End TB Strategy, the WHO has
recognised the vital importance of this approach to the success of any
TB programme. Individualised patient-centred care underpins the
nursing process and, as such, should encourage nurses to take the
lead in this area.
The nurse’s role in relation to national TB control strategies
The roles that nurses play in TB management and control vary
according to their work setting. While some will be involved in all of the
activities described below, others will take on various elements. Nurses
with additional qualifications may change their job titles thereby
becoming less visible as nurses, but continuing, nonetheless, to carry
out nursing activities. With the new WHO End TB Strategy as described
in Chapter 2, there is now a larger role for nurses to play in ensuring
care is patient-centred from the moment a patient seeks diagnosis to
the very end of their treatment. There is also a larger emphasis on
working with a broader range of partners, something which nurses are

55
well-placed to do with their understanding of the needs of their clients
and their potential to identify and work closely with other clinical
partners and community organisations.
Nurses working in primary healthcare settings are often first to see
people who present with symptoms and are crucial to the early
identification and management of presumed TB and MDR-TB cases.
To ensure a high level of case detection, a cornerstone of TB control,
nurses working with individuals, families, communities and other
services need to understand their role in controlling this preventable
disease.
The nursing process, DOTS and MDR-TB management
strategies
The nursing process is a systematic approach to providing
individualised, patient-centred care through a cycle of assessment,
planning, implementation and evaluation. It offers a scientific basis for
decision making and improves the quality of planning. Actions made
explicit during the planning phase allow for evaluation of the
effectiveness of the interventions undertaken.
Like the nursing process, DOTS and MDR-TB management strategies
have quality and effectiveness at their core. The DOTS strategy in
particular offers a standardised approach for the control and
management of TB. The management of MDR-TB is much more
complex although there are some opportunities for standardising
certain aspects such as elements of diagnosis and treatment
monitoring. Although the technical aspects of TB control are
standardised, to be effective, TB services must be flexible and based
on the needs of the patient, their family and the local community (Table
5.1).

Patient-centred approach to TB control and care

The patient-centred model links nursing process with the DOTS and
MDR-TB management strategies, identifying case finding and patient
holding as intertwined cycles of intervention. Cases are constantly
being found, prompting further investigation, which leads to more cases
being discovered. Since the individual patient’s needs may change
during the time they are on treatment, the nurse’s constant evaluation
and reassessment ensures appropriate care at each stage and
enhances the patient’s adherence to TB treatment protocols.
Case finding
Patients enter the patient roster through passive case finding or active
case finding. Active case finding is TB screening of populations,
recommended only in areas where treatment success is at least 85%
and where treatment and follow-up services are available. Screening
can be expensive, so it is more cost effective to target the highest risk

56
groups based on epidemiological trends within a local population.
Often screening is targeted at hard-to-reach groups, which means
identified cases are a challenge to treat (Williams et al., 2007).

Table 5.1: The role of the nurse in relation to the five elements of the
DOTS strategy
Element Strategy and rationale Nurses’ role
Political Investment essential at Advocacy and lobbying
commitment national and local levels to Experience of working closely with
implement and sustain a patients and communities can inform
successful TB control policy and strategic decision making
programme and assist implementation

Case detection by Most cost-effective option Identification of presumed cases

smear microscopy Identifies infectious cases Support for worried patients
(and other Advise patients on how to produce a
bacteriologic tests good sputum sample
e.g. Xpert Access for delivery of sample
MTB/RIF) Documentation (dates & results)

Standardised To ensure effective Ensuring equitable access

treatment with treatment prescribed and Individualised care planning
DOT good adherence to Education of patient and family
medication Monitoring and documentation
Treatment observers of medication and progress
should be willing, trained, Support for patient, family and
responsible, and treatment observer
acceptable to the patient
Standardized Systematic evaluation of Clear, accurate and prompt record
reporting and a) patient progress and keeping
recording treatment outcome –Laboratory register
b) overall programme –Treatment cards
performance –TB register
Communication re individual and
collective progress

Regular Minimising the possibility Ensuring there is a sufficient supply

uninterrupted drug of treatment interruption for patients seen according to level of
supply responsibility (manager of a TB Unit
to DOTS supervisor)

Additional Vital to ensure quality and Personal professional development

logistical aspect: proper management of Provision of education for patients
Training and actual and possible TB their families, communities and
supervision cases volunteers etc.

Additional The range of geographical, Nurses play a key role in providing

operational environmental and cultural flexible TB services by providing
aspect: Flexibility contexts requires flexibility individualised patient-centred care
in the implementation of
DOTS components

57
Passive case finding occurs when people present themselves with
symptoms. It relies on good public information and accessible services
for people to recognise TB symptoms and know where to get help. If
TB is suspected, the person is tested.
If diagnosed with active TB, the nurse registers the patient and starts
him/her on treatment. Diagnosis usually leads to an investigation of the
patient’s contacts to see if any of them have active TB (active case
finding). Those with TB are registered and treated, and so on.
Patient holding
Once diagnosed, the patient enters the patient holding cycle and
remains there until TB cure or treatment is complete. In this cycle, the
nurse ensures that the patient can adhere to the drug treatment as
easily as possible. She assesses his/her status, implements the
treatment plan, and continuously evaluates progress and problems.
To ensure appropriate assessment, planning and implementation, the
nurse needs a range of skills: clinical skills; detecting and managing
adverse effects; counselling; communication and teaching; as well as
organisational skills for co-ordinating the patient’s care, especially if a
number of different care givers are involved, e.g. advocates,
community workers, volunteers (Williams et al., 2007).
Assessment
Assessment includes evaluating the patient’s physical, psychological,
social and nutritional status in relationship to the management of
his/her TB care by collecting data from medical notes, and
communicating with and observing the patient. The nurse must listen
to the patient and assess what is important to him/her, what he/she is
trying to achieve, and how the TB diagnosis has affected him/her.
The TB patient often cares for him/herself and may not appear to have
problems. Yet, there may be something happening that prevents
adherence to treatment – depression, financial difficulty, pregnancy,
alcohol or drug dependency, working illegally, bereavement,
homelessness, poor nutrition, etc (Williams et al., 2007).
Planning
Defining treatment goals and expected outcomes at the beginning of
treatment reduces confusion and misunderstandings. Planning as a
team, the nurse and the patient agree on short term, intermediate
and/or long term goals with specified and measurable outcomes.
Including his/her personal goals in the treatment plan gives the patient
a vision beyond the absence of disease.
Planning must be realistic and achievable, and services promised must
be accessible. To do this, each person must understand his role and

58
the role of the others, know the available services, and have an
accurate understanding of the treatment goals.
A clear understanding of the patient’s situation is key. For instance, if
the patient has to work from early in the morning until late at night or
has to leave home for several weeks during his treatment, directly
observed treatment at the clinic will not be successful. The nurse and
patient must establish a different treatment plan. Once the patient’s
concerns are known, the nurse can work with him/her to develop an
individualised plan including support systems. Doing so minimises
disruption in his/her life, motivates adherence and enhances
completion of drug treatment.
Implementation
Having assessed and planned care with the patient, it is essential to do
what was agreed. A range of skills is required to provide care for
patients, only few of which are manual such as tuberculin testing,
injections, wound care and so on. Core skills include counselling,
communication and teaching. As discussed below, good organisational
skills are also required to ensure, for instance, that the correct
medication is available and provided as prescribed.
The nurse should record the patient’s progress promptly, clearly and
accurately and any changes or problems should be referred as
appropriate. Obviously, the availability of support services will vary
from place to place and best use needs to be made of local resources.
Evaluation
During long-term TB treatment (especially in patients with MDR-TB),
many factors could change so the nurse must evaluate the patient’s
progress at regular intervals as agreed with the patient. This may
involve a weekly review to begin with, followed in later stages by
fortnightly or even monthly follow up. Any changes in the patient’s
clinical condition, personal circumstances, mood, attitude and
appearance should be noted.
In addition, the patient should be assessed and their progress
documented at specific intervals in accordance with the local TB control
programme:
 Usually after two months of treatment to ensure progression to
non-infective condition, sputum conversion from smear positive to
smear negative.
 With MDR-TB patients:
- usually at 3-4 months to ensure the patient’s sputum has
converted to negative; and
- 8 months after this point (when the injectable medication, which
is used in the first phase of treatment for a minimum of 8 months,
is stopped) as this is the point when many patients move from
inpatient to outpatient treatment settings.
59
 At the end of treatment, to evaluate and record the treatment
outcome.

Patient-centred care and treatment adherence

While emphasising the need for a patient-centred approach, it is still
imperative to stress the importance of treatment adherence – both the
adherence of healthcare workers to following correct protocols as well
as the adherence of the patient to the treatment prescribed. Adherence
to TB treatment, a major factor in the successful outcome of TB
treatment, reduces the potential for developing acquired MDR-TB and
is the main reason the DOTS strategy was developed in the first place.
Adherence is the extent to which a person’s behaviour – taking
medication, following a diet, and/or executing lifestyle changes –
follows the agreed healthcare recommendations (World Health
Organization, 2009a).
Adherence is complex, with a number of factors that can adversely
impact treatment completion including: socio-economic factors and
issues related to the organisation of TB treatment in the community;
patient variables; treatment variables; treatment of adverse effects;
disease variables; and organisational variables. The nurse must
understand the barriers for adherence to treatment regimens and
reduce or eliminate these barriers. A patient-centred approach which
includes facilitating access to treatment, deciding with the patient the
most convenient time and place for direct observation of treatment
(DOT), and when possible providing other social and medical services,
is more effective than tracing patients lost to follow up (World Health
Organization, 2009a). DOT is a key element of the policy package for
TB control and requires that an observer watch the patient swallow the
medicines. The observer can be a health worker or a trained and
supervised member of the community.
Best adherence indicators include:
 smear conversion from positive to negative,
 improvement in symptoms, and
 clinical improvement.
The use of incentives to motivate the TB patient to adhere to treatment
can be effective and enhance the patient/nurse relationship. Some
ideas for incentives are: support groups; award ceremonies on
successful completion of treatment; reimbursement for travel, food,
visits and phone calls; “Thank you teas” for patients and their families;
and birthday or anniversary greetings. In many countries, malnutrition
is a serious problem and food is considered an enabler – necessary for
treatment success – rather than an incentive.
Giving incentives carries responsibility for both the patient and the
nurse. Both must keep their promises. If the nurse promises the
60
incentive and does not deliver it, the relationship with the patient and
credibility in the community may be adversely affected. To effectively
use incentives, the nurse must also get to know the patient and
recognise the difference between the nurse’s perception of the
patient’s needs and his/her reality.

61
62
Chapter 6: Organisational and Workforce
Issues

Organisational issues
Organisational issues related to a successful TB control
programme include:
 human resource issues, such as staffing and worker protection
 practice development issues including training and quality
assurance
 programme evaluation and TB research
 social advocacy and community mobilisation
Some of the most common and important organisational issues
were identified by WHO in the 2002 survey of National TB Programme
Managers in 22 high-burden countries. These issues are: (World
Health Organization, 2003)
 lack of qualified staff
 weak political commitment
 inadequate health infrastructure
 non-compliance of the private sector with DOTS

Workforce issues
While no further study has been undertaken since then it is clear from
the WHO’s progress report on Strengthening Nursing and Midwifery
that there are many challenges still affecting the healthcare workforce
(World Health Organization, 2013d). The following issues remain in all
six regions of WHO although the severity of each may vary from
country to country. Key challenges to strengthening nursing and
midwifery services were identified as:
 inadequate human resources at all levels of the health-care
system
 difficulty in retaining healthcare workers in rural areas after
completion of training
 increased migration within countries, regions and globally
 low salaries, lack of career incentives, an ageing workforce, poor
professional image
 poor working conditions/environments
 difficulties implementing and reinforcing existing policies
 lack of high-quality local education programmes

63
 delayed or inadequate responses to crises and/or disasters
 limited access to information and communication technologies
 funding and training resource constraints exacerbated by the
global economic situation
By understanding the problems and potential resolutions, nurses can
advocate for strong TB control programmes at a local, regional or
national level.
In addition to these general issues which disproportionately affect lower
and middle income countries where TB is more common, there are a
number of additional challenges associated with the disease namely:
 unsafe work environment through poor or lack of infection control
measures
 stigma
 work-related stress
 lack of protective devices such as filtering facepiece respirators
(N95 or FFP2)
Some of the main issues are discussed here as they relate to TB.

Infection prevention and control

Effective infection prevention and control (IPC) in healthcare facilities
plays an important role in providing a safe environment for both
patients and healthcare workers. The hierarchy of infection control
measures consists of: 1) managerial/facility level controls, 2)
administrative controls, 3) environmental controls, and 4) personal
protective equipment (Table 6.1).
Managerial and administrative controls are at the top of the hierarchy
and are the most effective and often the least expensive IPC measures.
The most effective way to protect staff and patients from TB exposure
is to be alert to potential cases and to separate coughing patients and
patients with suspicious symptoms until a diagnosis of active TB can
be ruled out. The healthcare facility should institute a policy allowing
the nurse to place a patient in a separate waiting area or isolation if
he/she suspects that the patient has active TB. This helps minimise
exposure that can occur while waiting for a diagnosis.
Since patients with active TB are the most infectious, they should
remain separated from patients who do not have TB for the first two
weeks of treatment. Patients being treated for MDR-TB generally
convert by the third or fourth month. In facilities where there are a high
number of patients with HIV infection, it is particularly important to
separate TB patients and TB suspects from HIV-positive patients. After
two weeks of treatment, most patients with TB are no longer infectious
(Rouillon et al., 1976). However, if there is a suspicion that the patient

64
has MDR-TB, he/she should be separated from other patients until
there are good signs of clinical improvement and, if possible, until
sputum becomes smear negative. Prompt diagnosis and initiation of
appropriate treatment are also an effective method of decreasing and
preventing transmission.
Environmental controls are the next level of the infection control
hierarchy and include measures to maximize natural ventilation (open
windows and doors) to reduce the amount of airborne droplet nuclei to
decrease the risk of transmission. Other environmental controls include
mechanical ventilation, such as negative pressure isolation rooms and
ultraviolet germicidal irradiation (UVGI). In most low-resourced settings
natural ventilation will be the only environmental control available and
it is important for environmental controls to be implemented in
conjunction with administrative controls. Natural ventilation is
inexpensive while mechanical ventilation and UVGI are much more
expensive and require considerable monitoring and maintenance
(World Health Organization, 2009c).
The lowest level of the infection prevention and control hierarchy is
personal protective equipment (PPE) such as wearing filtering
facepiece respirators like N95 or FFP2 respirators. Respirators should
not be used alone, but rather it is recommended they be used as part
of an overall infection control strategy, especially in addition to effective
administrative control measures. Moreover, it is important for
healthcare workers to be fit-tested prior to using respirators as a one
size respirator does not fit all face shapes (World Health Organization,
2009c).
More resources on infection control are available at the following links:
http://whqlibdoc.who.int/publications/2009/9789241598323_eng.pdf
www.tbcare1.org/publications/toolbox/tools/ic/TB_IC_Implementation_Fra
mework.pdf (Tuberculosis Coalition for Technical Assistance, 2010)
Infection prevention and control is the responsibility of everyone
working in health facilities and it is important for nurses, physicians,
support staff and management to all work together to ensure a safe
environment for patients, healthcare workers and visitors. ICN has
created a toolkit to help guide inter-professional collaboration in
healthcare facilities on infection control (International Council of
Nurses, 2011). The toolkit can be found at the following link:
www.icn.ch/es/tb-mdr-tb-project/training-resources/training-
package/tb-infection-control-toolkit.html.

65
Table 6.1: Infection prevention and control measures
Type of control Examples
 Conduct a risk assessment plan of facility
infection control measures
 Create a multidisciplinary infection control
committee
Managerial controls
 Develop and implement a comprehensive
(facility-level controls)
infection control plan
 Monitor and evaluate infection control plan
 Surveillance of TB among healthcare workers

 Triage coughing patients and TB suspects

(routinely ask patients about cough upon
entering facility/hospital) and separate coughing
patients from others
 Minimize time spent in health facilities (fast track
patients with cough)
 Separate HIV-positive patients from TB
patients/suspects in waiting areas and in wards.
 Ensure patients are not crowded in hallways or
waiting areas (casualty, etc.).
Administrative controls  Educate patients on cough hygiene (coughing
into tissue, ask patients to wear a surgical mask,
etc.)
 Provide tissues, cloths or surgical masks for
patients to cough into
 Sputum samples are collected in a designated
area (i.e. outside)
 Separate smear-positive and smear-negative
patients in wards
 Rapidly diagnose and start patients on
appropriate treatment
 Natural ventilation (open windows and doors)
 Mechanical ventilation (negative-pressure
Environmental controls
isolation rooms, extraction fans, etc.)
 Ultraviolet germicidal irradiation (UVGI)
 Filtering facepiece respirators (N95 or FFP2)
Personal protective equipment
 Fit testing
(PPE)
 Gowns, aprons, gloves, eye protection
Adapted from: WHO Policy on TB infection control in health-care facilities, congregate
settings and households (World Health Organization, 2009c).

Maintaining a healthy workforce

A healthcare facility is a workplace as well as a place for giving and
receiving care. Nurses need protection from workplace hazards. Yet,
protection and safety of nurses and other health professionals is often
a neglected area. In order to protect themselves from TB infections and
to maintain a continued high level of patient care, it is important for
nurses to understand the risks of contracting TB and to know the
recommended methods of protection.
66
Given the global prevalence of TB, protection of the nurse’s health is
pertinent to every TB discussion. The prevalence of disease in the
wider community has always been a significant factor in determining
occupational exposure for nurses. Historically, TB has long been a
recognised hazard for healthcare workers, especially nurses. In fact, it
has been reported that entire nursing classes had been infected with
TB within the first year of nursing training (Israel et al., 1941). It is
estimated that more than 50% of healthcare workers globally have
LTBI placing them at a greater risk of developing active TB. Moreover,
healthcare workers are two to three times more likely to develop active
TB than the general population (Joshi et al., 2006, Menzies et al.,
2007).
Although it is important for countries to establish regulations and
legislation to protect nurses, with or without that legislation, employers
still have a responsibility to protect their workers. In most countries,
according to the International Labour Organization (ILO), the employer
is responsible for occupational safety and health programmes.
Moreover, ILO contends that disease and injury are not inevitable
consequences of work, and poverty does not excuse an employer’s
disregard for his employee’s safety and health. This is true for nurses
as well as other workers.
While some measures recommended to protect nurses are costly,
others can be implemented at a low cost including:
 pre-employment and routine (annual) screening for TB symptoms
 checking BCG status
 TB skin testing
 giving BCG vaccination
 taking a chest x-ray, if indicated
 educating nurses about the signs and symptoms of TB and
encouraging them to seek medical attention promptly if signs
appear
 confidential and voluntary HIV counselling and testing
 reassigning HIV-positive healthcare workers to work in areas with
low risk of being exposed to TB patients or TB suspects
 provision of HIV treatment services including IPT for healthcare
workers living with HIV.
In 2011, the ILO/WHO/UNAIDS released a guidance note on improving
healthcare workers’ access to prevention, treatment and care for
HIV/AIDS and TB. Below are several actions recommended to be
implemented in the workplace to protect healthcare workers affected
by TB and/or HIV.

67
 Make occupational health services available for all healthcare
workers to ensure access to HIV and TB prevention, treatment,
support and care can be attained.
 Strengthen existing IPC programmes, especially with respect to TB
and HIV to ensure a safe work environment.
 Provide regular, free, voluntary and confidential HIV counselling
and testing, and TB screening, as well as general wellness
services including screening of family members of health workers
with TB.
 Implement good practices in occupational health and the
management of HIV and TB in the workplace
 Provide information on benefits and risks of post‐exposure
prophylaxis (PEP) to all staff and provide PEP free of charge for all
exposed health workers in a timely manner.
 HIV and TB treatment should be provided free of charge for
healthcare workers in need. Services for healthcare workers
affected by HIV and TB should be provided in a confidential, non-
stigmatizing, and patient-centred manner.
 Provide universal access to prevention and care services for all
HIV-positive health workers, such as isoniazid preventive therapy
and co-trimoxazole prophylaxis.
 Provide training for all healthcare workers on TB and HIV
prevention, treatment, support, and care including information on
the rights of both employers and workers and measures to reduce
stigma. (International Labour Organization, 2011)
For more information, please visit: www.ilo.org/wcmsp5/groups/public/---
ed_protect/---protrav/---ilo_aids/documents/publication/wcms_149714.pdf.

Practice development
Practice development encompasses a broad range of interventions
designed to improve practice and patient care services (Bryar and
Griffiths, 2003). Training and quality assurance are essential
elements of practice development.
Staff training
Training and supervision of health personnel are essential to the
success of any TB control programme. They are equally important at
all levels of nursing – those working specifically in TB control
programmes as well as primary healthcare workers, who are often the
first to identify suspect cases. Participatory education with regular
follow-up is usually more effective than didactic approaches that simply
disseminate information (Centers for Disease Control and Prevention,
2005). The best training provides ongoing support and helps integrate
the learning into practice.

68
Evaluation is essential to reinforce, maintain and disseminate best
practices. Developing new practices requires establishing measures
for evaluating change. Since changes in community nursing practice
may have a far reaching impact on a variety of stakeholders, no
developments should be planned without outlining expected
measurable outcomes, including looking downstream at the impact on
the wider community.
The type of data collected during an evaluation should also reflect the
purpose of the evaluation. If the purpose is to influence physicians and
TB coordinators, quantitative data may be most appealing. However,
for nurses and patients, qualitative data may be more meaningful.
Data collection is absolutely intrinsic to the DOTS programmes –
gathering the right data is essential for correctly identifying a problem,
developing a practice to resolve the problem, and evaluating the impact of
the change:
 Quarterly cohort analysis gives regular feedback about overall
programme performance and highlights rates of sputum
conversion, defaulting, etc.
 Comparing laboratory records with the TB patient registry shows
how many sputum smear positive cases started treatment, and
within what time period.
 Treatment outcome data demonstrates rates of success, default,
failure or death.
 Patient record cards illustrate treatment adherence patterns.
 In addition to evaluating nursing practices and patient outcomes,
worker health protection must be regularly evaluated to determine
if it is successfully protecting healthcare workers from contracting
TB. In most settings, TB skin tests are done when new staff is first
employed, every six months or annually thereafter (based on the
level of TB found in the community and in the health facility), and
whenever an employee has signs and symptoms of active TB
(World Health Organization, 2009c). In addition, mechanical
ventilation and negative-pressure isolation rooms are routinely
checked to ensure that the controls are functioning properly.
Nurses wearing respiratory protection must also perform fit tests
regularly to ensure that the respirator fits their faces appropriately.
If a respirator does not fit correctly, its protection is compromised.

69
Table 6.2: Key nursing capabilities in TB control and prevention
CAPABILITY REQUIRED KNOWLEDGE
 recognise a suspect case  signs and symptoms of TB
 describe the local TB situation  local and national statistics
 explain how TB is spread  how TB is transmitted
 discuss the main principles of TB  local and national policy for
management treatment and management of TB

Primary/Community Care facilities

In addition to the above: In addition to the above:
 order appropriate tests  diagnostic tests available for TB
 give the patient / family basic  support required by patient when
information, e.g. TB is curable suspected of having TB
 refer to the appropriate service  local services responsible for TB
 complete appropriate  recording and reporting procedures
documentation associated with TB management

Acute hospital services

In addition to the above: In addition to the above:
 apply hospital infection control  infection control strategy for
procedures appropriately inpatient facilities
 observe treatment given during  treatment for TB
patient’s stay in hospital  adherence issues
 recognise and report adverse  range of adverse effects from TB
effects medication
 discuss treatment with patient (and
family)
 plan discharge to local TB
services/unit

TB Units
In addition to the above:
 support and monitor patients In addition to the above:
throughout their treatment  recommended TB control and
 order subsequent tests at the management procedures
correct time and record results  complexity of patients’ needs;
accurately methods to maximise adherence
 refer or manage adverse effects as  essential monitoring issues, e.g.
appropriate patient progress; sputum
 liaise with other support services conversion
according to patient need  TB treatment, possible minor and
 complete reports as appropriate severe adverse effects
 reporting procedures

Social mobilisation and advocacy

Social mobilisation, the active recruitment of patients and community
members to support TB control strategies, is necessary to sustain
support for TB control. TB affects whole communities and has social
and economic as well as physical consequences. Social mobilisation
means that community representatives become partners in the TB

70
control programme and work closely with the health services involved.
It requires a strong relationship between the community and the TB
control programme.

The four main activities of social mobilisation are:

 advocacy
 health education
 DOT treatment support
 programme support

Not all activities have to be implemented to achieve successful social

mobilisation. In fact, the local community and the setting determine
which activities are appropriate.
Advocacy
A suitable environment can be created for sustainable TB control when
a community has strong and effective leadership and mobilises to
demand appropriate services and political commitment. Advocacy can
happen on many levels from high-level international lobbying to local
advocacy to improve services and working conditions. Patient
advocacy is an important part of a nurse’s role as many nurses have
demonstrated in the field of TB. Over the years, numerous examples
have been given by nurses attending training reviews where they have
made significant changes to their services and improved patient care
as well as staff and patient safety. Changes have been made from the
provision of the correct respirators, to separation of infectious from non-
infectious patients, to the building of entirely new clinic areas. By
identifying problems and targeting efforts real practical changes can be
made and, ultimately, lives can be saved.
More details about nurses’ achievements through advocacy can be found at
www.icn.ch/tb-mdr-tb-project.html

The common thread was that they all

 knew what was required to make an improvement
 presented the suggestion to the right people who could help
 involved all the key partners and colleagues
 were patient and persistent
 made a personal commitment
Events, such as World TB Day on March 24th each year, raise TB
awareness and help establish the need for commitment to effective TB
control, adequate government funding and appropriate organisation of
services.

71
Health education
Education of the public about TB is important. It should be part of an
effective control programme that has a good cure rate and raises
awareness about access to care and treatment. Increasing the
knowledge of TB usually increases the demand for services and can
result in advocacy for people’s right to treatment and improved quality
of care.
The health education plan must be relevant to available services and
community needs. Before initiating a campaign, planners must
carefully consider who should be involved and clarify the aim of the
education. For example, one area for educational campaign could be
to combat the stigma associated with TB patients. Stigma can be
attached to any number of falsely held beliefs and myths. People may
believe, for instance, that TB is incurable, runs in the family, is caused
by having a dirty household, or is the result of a curse. The stigmas
must be exposed and addressed before public TB education will be
successful.
DOT treatment support
As mentioned earlier, members of the community can often provide
invaluable support to patients on treatment. With appropriate training
and support from the nurse, they can supervise a patient’s treatment
using the patient’s treatment card and drugs provided by the TB
service. Receiving treatment from a community member is often a very
convenient alternative to the health clinic. This can enhance the
patient’s adherence to the treatment regimen and facilitate successful
completion and cure. For example, in South Africa, local pharmacists
and shopkeepers are trained to offer DOT and, in Malawi, volunteers
act as guardians for TB patients. In Peru, for the two-year treatment of
MDR-TB in 2002-2004, community volunteers were trained to observe
two or three patients. In return, the volunteers received a basket of
staples each month valued at US$ 30. Nurses trained and supervised
the volunteers.
Programme support
Community-based approaches rely on good organisation and support
from the health services responsible for treating TB patients and
require strong support from the district and national level.
The types of support needed for a successful community
programme are:
 ongoing training and supervision of involved community members;
 a mechanism for providing essential supplies, such as TB drugs and
sputum containers; and
 good communication between the community and the local health
service to address questions and concerns.

72
Conclusion
Nurses play a significant role in the control of drug-sensitive and drug-
resistant TB all around the world. To be effective, the nurse must
understand the disease, recognise the signs and symptoms of TB, and
support patients’ adherence to TB treatment. By adapting the best
practice standards described in the next section of this guide to local
settings and advocating for strong TB control programmes, nurses can
maximise their role and have a real impact on TB control practices.
However, nurses must also be protected while they care for others, and
worker protection programmes must be instituted to enhance the
nurse’s ability to provide high quality care. On-going programme
evaluation ensures programme effectiveness and enables continuous
process improvement.
TB control involves all levels of the health system – international and
national policy makers, regional and district TB coordinators and TB
specialty nurses, as well as primary care nurses working in a variety of
settings. The general practice nurse is the first line of defence in TB
control worldwide, and this important role must be recognised and
strengthened. ICN encourages you to learn more about TB in your
community and to actively participate in establishing effective TB
control programmes.

73
ANNEXES

74
Annex 1: Algorithm for Screening for TB among
Adults and Adolescents

a Every adult and adolescent should be evaluated for eligibility to receive antiretroviral therapy,
infection prevention and control measures should be implemented to reduce TB transmission in
all healthcare settings.
b Chest radiography can be done if available, but is not required to classify patients into TB and

non-TB groups. In settings with high HIV prevalence and a high TB burden among people living
with HIV, strong consideration must be given to adding other sensitive investigations.
c Contraindications include: active hepatitis (acute or chronic), regular and heavy alcohol

consumption and symptoms of peripheral neuropathy. Past history of TB and current pregnancy
should not be contraindications for starting IPT. Although not a requirement for initiating IPT,
tuberculin skin testing may be performed as part of eligibility screening in some settings.
d Investigations for TB should be performed in accordance with existing national guidelines.

Source: Consolidated guidelines on the use of antiretroviral drugs for treating and
preventing HIV infection: summary of key features and recommendations (World Health
Organization, 2013a)

75
Annex 2: TB Symptom Screening Tool Sample

Source: National tuberculosis management guidelines 2014 (Department of Health

Republic of South Africa, 2014).

76
Annex 3: Algorithm for Diagnosing TB in Children

* The clinical and CXR signs suggestive of TB are listed on page 26.

Source: Desk-guide for diagnosis and management of TB in children 2010 (The

International Union Against Tuberculosis and Lung Disease, 2010)

77
Annex 4: TB Drugs used for MDR-TB in Five Groups
Medication Weight Class
(drug abbreviation), (common
presentation)
Dose range (use in patients ≥ 30 kg)
Daily dose 30-35 kg 36-45 kg 46-55 kg 56-70kg >70 kg
Isoniazid (H) 4–6 mg/kg
150 mg 200 mg 300 mg 300 mg 300 mg
(100, 300 mg) once daily
Rifampicin (R) 8-12 mg/kg
300 mg 450 mg 450 mg 600 mg 600 mg
(150, 300 mg) once daily
Pyrazinamide (Z) 20-30 mg/kg
800 mg 1000 mg 1200 mg 1600 mg 2000 mg
(500 mg) once daily
Ethambutol (E) 15-25 mg/kg
600 mg 800 mg 1000 mg 1200 mg 1200 mg
(100, 400 mg) once daily
Rifabutin (Rfb) 5-10 mg/kg
300 mg 300 mg 300 mg 300 mg 300 mg
once daily
Group 2: Injectable anti-TB drugs
Daily dose 30-33 kg 34-40 kg 41-45 kg 46-50 kg 51-70 kg >70 kg
Streptomycin (S) 12-18 mg/kg
500 mg 600 mg 700 mg 800 mg 900 mg 1000 mg
(1 gram vial) once daily
Kanamycin (Km) 15-20 mg/kg
500 mg 625 mg 750 mg 875 mg 1000 mg 1000 mg
(1 gram vial) once daily
Amikacin (Am) 15-20 mg/kg
500 mg 625 mg 750 mg 875 mg 1000 mg 1000 mg
(1 gram vial) once daily
Capreomycin (Cm) 15-20 mg/kg
500 mg 600 mg 750 mg 800 mg 1000 mg 1000 mg
(1 gram vial) once daily
Group 3: Fluoroquinolones
Daily dose 30-35 kg 36-45 kg 46-55 kg 56-70kg >70 kg
Levofloxacin (Lfx) 750-1000 mg
750 mg 750 mg 1000 mg 1000 mg 1000 mg
(250, 500 mg) once daily
Moxifloxacin (Mfx) 400 mg 400 mg 400 mg 400 mg 400 mg 400 mg

78
 (400 mg) once daily
Gatifloxacin (Gfx) 400 mg
400 mg 400 mg 400 mg 400 mg 400 mg
(400 mg) once daily
Group 4: Oral bacteriostatic second-line anti-TB drugs
Daily dose 30-35 kg 36-45 kg 46-55 kg 56-70kg >70 kg
Ethionomide (Eto) 500-750 mg/day in
500 mg 500 mg 750 mg 750 mg 1000 mg
2 divided doses
500-750 mg/day in
Prothionomide (Pto) 500 mg 500 mg 750 mg 750 mg 1000 mg
2 divided doses
Cycloserine (Cs) 500-750 mg/day in
500 mg 500 mg 500 mg 750 mg 750 mg
(250 mg) 2 divided doses
p-aminosalycilic acid (PAS) 8 g/day in 2 divided
8g 8g 8g 8g 8-12 g
(4 gram sachets) doses
Group 5: Anti-TB drugs with limited data on efficacy and/or long term safety in the treatment of drug-resistant TB (This group
includes new anti-TB agents)
Daily dose 30-35 kg 36-45 kg 46-55 kg 56-70kg >70 kg
Bedaquiline (Bdq) 400 mg once daily for 2 weeks then 200 mg 3 times per week
Clofazimine (Cfz) 200-300 mg (2 first months) then 100 mg
Linezolid (Lzd) 600 mg once daily 600 mg 600 mg 600 mg 600 mg 600 mg
Amoxicillin/clavulanic acid 80 mg/kg/day in 2
2600 mg 2600 mg 2600 mg 2600 mg 2600 mg
7/1 divided doses
Amoxicillin/clavulanic 80 mg/kg/day in 2
3000 mg 3000 mg 3000 mg 3000 mg 3000 mg
acid 8/1 divided doses
16-20 mg/kg once
High-dose isoniazid 600-1000 mg 1000-1500 mg 1500 mg 1500 mg 1500 mg
daily
Imipenem/cilastatin 1000 imipenem / 1000 mg cilastatin twice daily
Meropenem 1000 mg three times daily (alternative dosing is 2000 mg twice daily)

Adapted from the Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis (World Health
Organization, 2014b) and Tuberculosis: Practical guide for clinicians, nurses, laboratory technicians and medical auxiliaries. 2014 edition
(Médecins Sans Frontières and Partners In Health, 2014).

79
Annex 5: Adverse Effects, Suspected Agents and Management Strategies
in MDR-TB Treatment
Adverse Reaction Suspected Agent(s) Suggested management strategies Comments

Rash, allergic Any drug 1) For serious allergic reactions, stop all therapy until the 1) History of previous drug allergies should be carefully
reaction and reaction is resolved. If the patient experiences reviewed and any known drug allergies should be noted
anaphylaxis anaphylaxis, follow standard emergency protocols. on the treatment card.
2) Eliminate other potential causes of allergic skin 2) Flushing reaction to rifampicin or pyrazinamide is
reaction. usually mild and resolves with time. Antihistamines can be
3) For minor rash – agents such as antihistamines, used. Hot flushes, itching, palpitations can be caused with
hydrocordisone creams, low dose prednisone (10 to 20 isoniazid and tyramine containing foods like cheese and
mg/day for several weeks), and moisturizing lotion for red wine. If this occurs advise patients to avoid these
dry skin. foods.
4) Once rash resolves, reintroduce drugs one at a time 3) Any of the drugs can cause hives (urticaria). To identify
with the most likely to cause the reaction last. the drug, introduce the drugs one at a time. In the case of
5) Suspend any drug permanently identified to be the hives a desensitization attempt can be made.
cause. 4) Any drug that resulted in anaphylaxis or Stevens–
Johnson syndrome should never be reintroduced.
Arthralgia Bedaquiline (Bdq), 1) Initiate therapy with NSAIDs (indomethacin 50 mg 1) Symptoms of arthralgia generally diminish over time,
Pyrazinamide (Z), twice daily or ibuprofen 400 to 800 mg three times a even without intervention.
Fluoroquinolones (FQs) day). 2) Uric acid levels may be elevated in patients on
2) Lower dose of suspected drug (most commonly pyrazinamide. Allopurinol should be used if gout is
pyrazinamide), if this can be done without compromising present.
regimen. 3) If acute swelling, redness and warmth are present in a
3) Discontinue suspected drug without compromising joint, consider aspiration for diagnosis of gout, infections,
regimen. autoimmune diseases, etc.
4) Initiate exercise regimen.
Dysglycaemia and Gatifloxacin (Gfx), 1) Stop gatifloxacin and replace with different later
hyperglycaemia Ethionomide / generation fluoroquinolone like moxifloxacin.
Prothionomide (Eto/Pto) 2) Treat diabetes as needed. Good glucose control is
important during treatment.

80
Adverse Reaction Suspected Agent(s) Suggested management strategies Comments
Gastritis and Para-aminosalicylic 1) Abdominal pain can also be associated with serious 1) Severe gastritis, as manifested by blood in the vomit or
abdominal pain acid (PAS), adverse effects, such as pancreatitis, lactic acidosis and stool is relatively rare.
Ethionomide (Eto), hepatitis. If any of these are suspected, obtain 2) Dosing of antacids should be carefully timed so as to
Protionomide (Pto), appropriate laboratory tests to confirm and suspend the not interfere with the absorption of anti-TB drugs (take two
Clofazimine (Cfz), suspected agent. hours before or after anti-TB medications).
Fluoroquinolones (FQs), 2) If symptoms are consistent with gastritis (epigastric 3) Stop any nonsteroidal anti-inflammatory drugs
Isoniazid (H), burning or discomfort, a sour taste in mouth associated (NSAIDS) the patient may be taking.
Ethambutol (E), and with reflux) initiate medical therapy with the use of H2- 4. Diagnose and treat for Helicobacter pylori infections.
Pyrazinamide (Z) blockers (ranitidine 150 mg twice daily or 300 mg once 5. Severe abdominal distress has been reported with
daily) or proton-pump inhibitors (omeprazole 20 mg once clofazimine. Although this is rare, if this occurs,
daily). Avoid the use of antacids as they decrease clofazimine should be suspended.
absorption of fluoroquinolones. 6) Reversible upon discontinuation of suspected agent(s).
3. For severe abdominal pain stop suspected agent(s)
for short periods of time (1 to 7 days).
4. Lower the dose of or discontinue the suspected agent,
if this can be done without compromising the regimen.
Diarrhoea and/or Para-aminosalicylic 1) Educate patients that some degree of loose stools 1) Consider other causes of diarrhoea:
flatulence acid PAS), and flatulence may occur. • Pseudo-membranous colitis related to broad-spectrum
Ethionomide (Eto) 2) Encourage fluid intake. antibiotics (such as the FQs) is a serious and even life
Prothionomide (Pto) 3) Treat uncomplicated diarrhoea (no blood in stool and threatening condition. Fever, bloody diarrhoea, intense
no fever) with loperamide 4 mg by mouth initially abdominal pain and increased white blood cells are
followed by 2 mg after each loose stool to a maximum of warning signs of possible pseudomembranous colitis.
10 mg per 24 hours. •parasites and common waterborne pathogens in the area
4) Check serum electrolytes (especially potassium) and should be evaluated in the patient and treated.
dehydration status if diarrhoea is severe. •lactose intolerance, especially if patient has been
5) Fever and diarrhoea and/or blood in the stools exposed to new foods not normally part of their diet.
indicate that diarrhoea may be secondary to something 2) Loperamide can be used in children over two years of
other than an adverse effect of anti-TB drugs. age.
Lactic acidosis Linezolid (Lzd) 1) Stop linezolid if lactic acidosis occurs. 1) Lactic acidosis can be monitored with a blood test that
measures lactic acid.

81
Adverse Reaction Suspected Agent(s) Suggested management strategies Comments
Hepatitis Rifampicin (R), 1) Stop all therapy pending resolution of hepatitis. 1) History of prior hepatitis should be carefully analyzed to
Isoniazid (H), 2) If enzymes are more than 5 times the upper limit of determine most likely causative agent(s); these should be
Pyrazinamide (Z), normal, stop all hepatotoxic drugs and continue with at avoided in future regimens.
Ethionomide (Eto), least 3 non-hepatotoxic medications (for example, the 2) Viral serology should be done to rule out other
Prothionomide (Pto), injectable agent, fluoroquinolone and cycloserine). If aetiologies of hepatitis if available, especially to hepatitis
Para-aminosalicylic hepatitis worsens or does not resolve with the 3-drug A, B and C.
acid (PAS), regimen, then stop all drugs. 3) Assess patient for alcohol abuse and refer for treatment
Ethambutol (E) 3) Rule out other potential causes of hepatitis (viral if appropriate.
Fluoroquinolone (FQs) hepatitis and alcohol induced hepatitis). 4) Generally reversible upon discontinuation of suspected
4) Consider suspending most likely agent permanently agent.
Re-introduce remaining drugs, one at a time with the
most hepatotoxic agents first, while monitoring liver
function.
Hypothyroidism Para-aminosalicylic 1) Most adults will require 100–150 mcg of levothyroxine 1) Symptoms of hypothyroidism include fatigue,
acid (PAS), daily. Start levothyroxine in the following manner: somnolence, cold intolerance, dry skin, coarse hair, and
Ethionomide (Eto), and Young healthy adults to be started on 75–100 mcg daily. constipation, as well as occasional depression and
Prothionomide (Pto), • Older patients should start treatment with 50 mcg daily. inability to concentrate.
especially when given • Patients with significant cardiovascular disease should 2) Do not start treatment unless TSH is above 1.5 – 2.0
in combination. start at 25 mcg daily. time of the upper normal limit.
2) Monitor TSH every one to two months and increase 3) It is completely reversible upon discontinuation of PAS
the dose by 12.5–25 mcg until TSH normalizes. Adjust and/or Eto/Pto.
the dose more slowly in the elderly and in patients with 4) The combination of ethionamide/protionamide with PAS
cardiac conditions. is more frequently associated with hypothyroidism than
when each individual drug is used.
Optic neuritis Ethambutol (E), 1) Stop ethambutol (E) and do not restart. 1) Usually reverses with cessation of ethambutol (E).
Ethionomide (Eto), 2) Refer patient to an ophthalmologist. 2) Improve diabetes control in diabetic patients.
Prothionomide (Pto),
Linezolid (Lzd),
Clofazimine (Cfz),
Isoniazid (H),
Rifabutin (Rfb)

82
Adverse Reaction Suspected Agent(s) Suggested management strategies Comments
Nausea and vomiting Ethionomide (Eto), 1) Assess for dehydration Initiate rehydration therapy if 1) Nausea and vomiting are common in early weeks of
Prothionomide (Pto), Indicated and correct any electrolyte disturbances. If therapy and usually decrease with time on treatment and
Para-aminosalicylic there is blood in the vomit, check haemoglobin (Hgb) supportive therapy. Some nausea and vomiting may be
acid (PAS), and treat for possible bleeding ulcers. unavoidable in the initial period.
Bedaquiline (Bdq), 2) Electrolytes and creatinine should be monitored if
Amoxicillin/Clavulanate 2. Initiate a stepwise approach to manage nausea and vomiting is severe. Give intravenous fluids and replace
(Amx/Clv), vomiting. electrolytes as needed.
Isoniazid (H), Phase I: 3) Reversible upon discontinuation of suspected agent.
Ethambutol (E), ––Give Eto/Pto at night 4) Ondansetron is a serotonin 5-HT3 receptor antagonist
Pyrazinamide (Z), ––Give Eto or PAS twice or three times daily and considered to have strong antiemetic properties. It is
Clofazimine (Cfz) ––Give a light snack (biscuits, bread, rice, tea) before on the WHO essential drug list. A number of other
the medications antiemetics from this class of serotonin 5-HT3 receptor
––Give PAS two hours after other anti-TB drugs. antagonists exist. Trying different antiemetics, even if from
Phase 2: Start antiemetic(s): the same class may be helpful for some patients.
––Metoclopramide 10 mg, 30 minutes before anti-TB Ondansetron prolongs the QT interval; avoid with
medications. bedaquiline.
––Ondansetron 8 mg, 30 minutes before the anti-TB 5) Another strategy is to stop the responsible medicine for
drugs and again eight hours after. Ondansetron can two or three days and then add it back gradually
either be used on its own or with metoclopramide. (If increasing the dose (advise the patient that the medicine
ondansetron is not available, promethazine can be will be increased back to a therapeutic dose in a manner
used.) For refractory nausea give 24 mg, 30 minutes that will be better tolerated).
before the dose. 6) For patients particularly anxious about the nausea, (and
Phase 3: Lower the dose of the suspected drug by one with “anticipatory nausea and vomiting”) a small dose of
weight class if this can be done without compromising an anti-anxiety medicine (5 mg of diazepam) can help
the regimen. It is rarely necessary to suspend the drug when given 30 minutes prior to the intake of anti-TB drugs.
completely.
Metallic taste Ethionomide / 1) Educate patients about this possible side effect. 1) Resolution occurs after treatment is stopped.
Prothionomide 2) Sucking hard candy or chewing gum can be helpful.
(Eto/Pto),
Clarithromycin (Clr),
Fluoroquinolones (FQs)

83
Adverse Reaction Suspected Agent(s) Suggested management strategies Comments
Vestibular toxicity Streptomycin (S), 1) If early symptoms of vestibular toxicity appear, 1) Ask the patient about tinnitus and unsteadiness every
(Tinnitus and Kanamycin (Km), change the dosing of the injectable agent to twice or week.
dizziness) Amikacin (Am), three times a week. Also, consider using Cm if an 2) Fullness in the ears and intermittent ringing are early
Capreomycin (Cm), aminoglycoside had been the prior injectable in the symptoms of vestibular toxicity.
Cycloserine (Cs), regimen. 3) A degree of disequilibrium can be caused by Cs, FQs,
Fluoroquinolones 3. If tinnitus and unsteadiness worsen with the above Eto/Pto, H or Lzd. Some clinicians will stop all drugs for
(FQs), adjustment, stop the injectable agent. This is one of the several days to see if symptoms are attributed to these
Isoniazid (H), few adverse reactions that cause permanent intolerable drugs. Symptoms of vestibular toxicity generally do not
Ethionomide (Eto), toxicity and can necessitate discontinuation of a class of improve on withholding medications.
Linezolid (Lzd) agents.
Hearing loss Streptomycin (S) 1) Document hearing loss and compare to baseline 1) Patients with prior exposure to aminoglycosides may
Kanamycin (Km) audiometry. have baseline hearing loss. In such patients, it may be
Amikacin (Am) 2. If early symptoms of hearing loss are documented, helpful to obtain audiometry at the initiation of MDR-TB
Capreomycin (Cm) change the dosing of the injectable agent to twice/thrice therapy.
Clarithromycin (Clr) a week. Also, consider using Cm if an aminoglycoside 2) Hearing loss is almost always permanent.
had been the prior injectable in the regimen. Continuing the injectable agent despite hearing loss
3) Discontinue the injectable agent if hearing loss almost always results in irreversible deafness.
continues despite dose adjustment and add additional 3) The risk of further hearing loss must be weighed with
drugs to reinforce the regimen. Even when additional the risks of stopping the injectable in the treatment
drugs are not available, stopping the injectable agent regimen.
can be considered based on the patient’s desire to 4) While the benefit of hearing aids is minimal to moderate
maintain hearing. in auditory toxicity, consider a trial use to determine if a
patient with hearing loss can benefit from their use.
Electrolyte Streptomycin (S) 1) Check Potassium 1) If severe hypokalaemia is present, consider
disturbances Kanamycin (Km) 2) If Potassium is low also check magnesium (and hospitalization.
(hypokalaemia and Amikacin (Am) calcium if hypocalcemia is suspected) 2) Amiloride 5-10 mg daily or spironolactone 25 mg daily
hypomagnesaemia) Capreomycin (Cm) 3) Replace electrolytes as needed. Dose oral may decrease potassium and magnesium wasting and is
electrolytes apart from FQs as they can interfere with FQ useful in refractory cases.
absorption. 3) Oral potassium replacements can cause significant
nausea and vomiting. Oral magnesium may cause
diarrhoea.

84
Adverse Reaction Suspected Agent(s) Suggested management strategies Comments
Seizures Cycloserine (Cs), 1) Suspend suspected agent (Cs, H, FQs) pending 1) Anticonvulsant is generally continued until MDR-TB
Isoniazid (H), resolution of seizures. treatment is completed or suspected agent discontinued.
Fluoroquinolones 2) Initiate anticonvulsant therapy (carbamazepine, 2) History of prior seizure disorder is not a contraindication
(FQs), phenytoin or valproic acid). to the use of agents listed here if a patient’s seizures are
valproic acid 3) Consider increasing pyridoxine to maximum daily well-controlled and/or the patient is receiving
dose (200 mg daily). anticonvulsant therapy (Do not include Cs if an
4) Check serum electrolytes including potassium, alternative drug is available).
sodium, bicarbonate, calcium, magnesium and chloride. 3) Patients with history of prior seizures may be at
5) Restart suspected agent or reinitiate suspected agent increased risk for development of seizures during MDR-TB
at lower dose, if essential to the regimen. Cycloserine therapy.
should not be restarted unless it is absolutely essential 4) Always check creatinine in patients with new onset
to the regimen. If Cs is reinitiated, start a dose one seizures. A decrease in renal function can result in high
weight band lower. blood levels of Cs, which can cause seizures. Adjusting
the dose of Cs in the presence of low creatinine may be all
that is needed to control the seizures.
Peripheral Cycloserine (Cs), 1) Correct any vitamin or nutritional deficiencies. 1) Patients with co-morbid disease (e.g. diabetes, HIV,
neuropathy Linezolid (Lzd), Consider increasing pyridoxine to 300 mg daily. alcohol abuse) may be more likely to develop peripheral
Isoniazid (H), 2) Initiate therapy with NSAIDS or acetaminophen (may neuropathy, but these conditions are not contraindications
Streptomycin (S), help alleviate symptoms), tricyclic anti-depressants, to the use of the agents listed here.
Kanamycin (Km), gabapentin (300 mg three times per day), 2) Neuropathy may be irreversible; however, some
Amikacin (Am), carbamazepine (100 – 400 mg twice per day) if patients may experience improvement when offending
Capreomycin (Cm), available. agents are suspended. The neuropathy associated with
Ethionomide 3) Rarely, medication may be discontinued, but only if an linezolid is common after prolonged use and often
/Prothionomide alternative drug is available and the regimen is not permanent. For this reason, suspension of this drug
(Eto/Pto), compromised. should be strongly considered when neuropathy develops
Ethambutol (E), 4) Consider whether the dose of Cs can be reduced due to linezolid.
Fluoroquinolones (FQs) without compromising the regimen. If isoniazid is being
used (especially high dose isoniazid), consider stopping
it. If possible, switching the aminoglycoside to Cm may
also be helpful.

85
Adverse Reaction Suspected Agent(s) Suggested management strategies Comments
Renal failure Streptomycin (S) 1) Discontinue suspected agent. 1) History of diabetes or renal disease is not a
(Nephrotoxicity) Kanamycin (Km) 2) Consider using Capreomycin if an aminoglycoside contraindication to the use of the agents listed here,
Amikacin (Am) had been the prior injectable drug in regimen. although patients with these co-morbidities may be at
Capreomycin (Cm) 3) Consider other contributing aetiologies NSAIDS, increased risk for developing renal failure.
diabetes, other medications, dehydration, congestive 2) Renal impairment may be permanent.
heart failure, urinary obstruction, etc.) and address as
indicated.
4) Follow creatinine (and electrolyte) levels closely,
every one to two weeks.
5) Consider dosing the injectable agent two to three
times a week if the drug is essential to the regimen and
the patient can tolerate (close monitoring of creatinine).
If the creatinine continues to rise despite twice/thrice a
week dosing, suspend the injectable agent.
6) Adjust all TB medications according to the creatinine
clearance.
Haematological Linezolid (Lzd) 1) Stop linezolid if myelosuppression (suppression of 1) Haematological abnormalities (leukopenia,
abnormalities white blood cells, red blood cells or platelets) occurs. thrombocytopenia, anaemia, red cell aplasia, coagulation
Consider restarting with a lower dose of linezolid (300 abnormalities, and eosinophilia) can rarely occur with a
mg instead of 600 mg) if myelosupression resolves and number of other anti-TB drugs.
if linezolid is considered essential to the regimen. 2) There is little experience with prolonged use of linezolid
2) Consider nondrug related causes of the
haematological abnormality.
3) Consider blood transfusion for severe anaemia
Suicidal ideation Cycloserine (Cs), 1) Hospitalize the patient and put under 24-hour 1) Keep the patient in the hospital until risk of suicide has
Isoniazid (H), surveillance. passed.
Ethionomide / 2) Discontinue cycloserine. 2) If no improvement occurs after stopping Cs, hold H
Prothionomide (Eto/Pto) 3) Request psychiatric consultation. and/or Eto/Pto.
4) Initiate antidepressant therapy.
5) Lower the dose of Eto/Pto to 500 mg daily until the
patient is stable.

86
Adverse Reaction Suspected Agent(s) Suggested management strategies Comments
Psychotic symptoms Cycloserine (Cs), 1) Hold suspected agent for a short period of time (one 1) Some patients will need to continue anti-psychotic
Isoniazid (H), to four weeks) while psychotic symptoms are brought treatment throughout MDR-TB therapy.
Fluoroquinolones (FQs) under control. (The most likely drug is cycloserine 2) Prior history of psychiatric disease is not
followed by high dose isoniazid.) contraindicated with Cs, but may increase the likelihood of
2) Initiate anti-psychotic drugs (haloperidol) if severe development of psychotic symptoms developing during
symptoms persist. treatment.
3) Hospitalize in a ward with psychiatric expertise if 3) Some patients will tolerate Cs with an antipsychotic
patient is at risk to himself/herself or others. drug but this should be done in consultation with a
4. Increase pyridoxine to the maximum daily dose (200 psychiatrist, as these patients will need to be under
mg per day). special observation; this should only be done when there
5) Lower dose of suspected agent (most commonly is no other alternative.
cycloserine 500 mg/day), if this can be done without 4) Psychotic symptoms are generally reversible upon
compromising regimen. completion of MDR-TB treatment or cessation of the
6) Discontinue suspected agent if this can be done offending agent.
without compromising regimen. 5) Always check creatinine in patients with new onset
7. Once all symptoms resolve and patient is off Cs, psychosis. A decrease in renal function can result in high
antipsychotic therapy can be tapered off. If Cs is blood levels of cycloserine, which can cause psychosis.
continued at a lower dose, antipsychotic therapy may
need to be continued and any attempts of tapering off
should be done after referring to a psychiatrist trained in
the adverse effects of second-line anti-TB drugs.
Gynaecomastia Ethionomide / 1) Breast enlargement can be a troublesome side effect 1) Resolution occurs after treatment is stopped.
Prothionomide (Eto/Pto) of Eto/Pto therapy, especially for male patients.
Galactorrhoea has also been reported.
2) Educate patients about this potential side effect.
Superficial fungal Fluoroquinolones (FQs) 1) Topical antifungal agents or short-course oral
infection and thrush and other antibiotics antifungal drugs are helpful.
with antibacterial 2) Exclude other diseases if response to treatment is not
properties prompt (such as HIV).

87
Adverse Reaction Suspected Agent(s) Suggested management strategies Comments
Depression Socioeconomic 1) Assess and improve socioeconomic conditions. 1) Importance of socioeconomic conditions and chronic
circumstances, 2) Group or individual counselling. illness should not be underestimated as a contributing
chronic disease, 3) Initiate anti-depressant drugs (amitryptiline, fluoxetine factor to depression.
Cycloserine (Cs), or similar). Tricyclic antidepressants and selective 2) Depressive symptoms may fluctuate during therapy and
Fluoroquinolones (FQs), serotonin reuptake inhibitors should be given may improve as illness is successfully treated.
Isoniazid (H), together and should not be given to patients on 3) History of prior depression is not a contraindication to
Ethionomide / linezolid. the use of the agents listed here, however, these patients
Prothionomide (Eto/Pto) 4) Lower dose of suspected agent, if this can be done may be at increased risk for developing depression during
without compromising the regimen. (Example: reduce MDR-TB treatment. If significant depression is present at
the dose of Cs and Eto to 500 mg daily to see if the the start of treatment, avoid a regimen with Cs, if possible.
depression improves) 4) Question the patient regarding suicidal ideation any
5) Discontinue suspected agent if this can be done time the depression is judged to be more than mild.
without compromising regimen.
6). Assess patients for coexisting substance abuse and
refer to treatment if appropriate.
QT prolongation Bedaquiline (Bdq), Any patient found to have a QTc value greater than 500 1) The QT interval is measured from the end of the QRS
Fluoroquinolones ms should be managed carefully. complex to the beginning of the T wave on a standard
(FQs), • Repeat ECG and confirm the prolongation. ECG. The QT is corrected for heart rate, which is referred
Clarithromycin (Clr), • Bedaquiline should be stopped for QTc value greater to as the QTc and calculated by most ECG machines. A
Clofazimine (Cfz) than 500 ms. Consider stopping other drugs that prolong normal QTc is generally <440 ms.
the QT interval. 2) Values above QTc 440 ms are referred to as prolonged.
• Check potassium, calcium and magnesium levels. Patients with prolonged QTc are at risk for developing
Electrolyte levels should be maintained in the normal cardiac arrhythmias like torsades de pointes, which can be
range. life threatening. Patients with QTc greater than 500 ms are
• It is suggested to maintain potassium levels of more at the greatest risk for developing these arrhythmias.
than 4 mEq/l and magnesium levels of more than 1.8 3) The fluoroquinolones cause prolongation of the QTc.
mg/dl. Moxifloxacin and gatifloxacin cause the greatest QTc
• Avoid other drugs that increase the QT interval. prolongation, while levofloxacin and ofloxacin have a lower
Monitor the patient’s renal and hepatic function and risk.
adjust the dose of fluoroquinolones if impairment is 4) Currently, ECG monitoring prior to initiation and
present. during MDR-TB therapy is only required with the use
Consider suspension of fluoroquinolone if risk of of bedaquiline.
torsades de pointes outweighs the benefits of the drug.

88
 Adverse Reaction Suspected Agent(s) Suggested management strategies Comments
Headache Cycloserine (Cs) 1) Rule out more serious causes of headache including 1) Headaches are common during the initial months of
Bedaquiline (Bdq) meningitis, and other infections of the central nervous MDR-TB treatment. They can present as migraine or
system. cluster headaches.
2) Start analgesics like ibuprofen (NSAID) or 2) To minimize headaches at the start of treatment,
paracetamol. Also encourage good hydration. cycloserine can be started at a lower dose of 250-500 mg
3) Consider low dose trycyclic antidepressants for and gradually increased over one to two weeks to achieve
refractory headaches. the target dose.
3) Headaches due to cycloserine and bedaquiline are
usually self-limited.
4) Pyridoxine should be given to all patients receiving
cycloserine to help prevent neurotoxicity. The
recommended dose is 50 mg for every 250 mg of
cycloserine prescribed.
Alopecia Isoniazid (H), 1) Hair loss can occur or there can be significant thinning 1) Significant cosmetic change has not been reported.
Ethionomide / of the hair, but this is temporary and not progressive
Prothionomide (Eto/Pto) during treatment.
2) Educate patients about the possibility of hair loss.

Adapted from Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis (World Health
Organization, 2014b).

89
Annex 6: Factors Affecting Adherence
Tuberculosis Factors affecting adherence Interventions to improve adherence
Social/economic ( - ) Lack of effective social support Assessment of social needs, social
Factors networks and unstable living support, housing, food tokens, and legal
circumstances; culture and lay beliefs about measures; providing transport to
illness and treatment; stigma; ethnicity, treatment settings; peer assistance;
gender, and age; high cost of medication; mobilization of community-based
high cost of transport; criminal justice organizations; optimizing the cooperation
involvement; involvement in drug dealing between services; education of the
community and providers to reduce
stigma; family and community support

Health system/ ( - ) Poorly developed health services; Uninterrupted, ready availability of

healthcare team factors inadequate relationship between healthcare information; training and management
provider and patient; healthcare providers processes that aim to improve the way
who are untrained, overworked, providers care for patients with
inadequately supervised or unsupervised in tuberculosis; support for local patient
their tasks; inability to predict potentially organizations/groups; management of
non-adherent patients disease and treatment in conjunction with
the patients; multidisciplinary care;
( + ) Good relationships between intensive staff supervision; training in
patient and physician; availability of adherence monitoring; use of DOT
expertise; links with patient support
systems; flexibility in the hours of
operation
Condition-related ( - ) Asymptomatic patients; drug use; Education on use of medications;
factors altered mental states caused by substance provision of information about
abuse; depression and psychological stress tuberculosis and the need to attend for
treatment
( + ) Knowledge about TB Education on use
of medications; provision of information
about tuberculosis and the need to attend
for treatment
Therapy-related factors ( - ) Complex treatment regimen; Education on use of medications
adverse effects of treatment; toxicity and adverse effects of medications;
adherence education; use of fixed dose
combination preparations; tailor treatment
support to needs of patients at risk of non-
adherence; agreements (written or verbal)
to return for an appointment or course of
treatment; continuous monitoring and
reassessment
Patient-related factors (-) Forgetfulness; drug abuse; depression; Therapeutic relationship; mutual
psychological stress; goal-setting; memory aids and
isolation due to stigma reminders; incentives and/or
reinforcements; reminder letters,
(+) Belief in the efficacy of treatment; telephone reminders or home visits for
motivation patients who default
Adapted from International Standards for Tuberculosis Care (ISTC) (Tuberculosis Coalition for
Technical Assistance, 2006).

90
References

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