Federal Republic of Nigeria

NATIONAL GUIDELINES FOR DIAGNOSIS AND TREATMENT

OF MALARIA

Federal Ministry of Health

National Malaria and Vector Control Division
Abuja-Nigeria

March 2011

2
 FOREWORD
Malaria has consistently topped the list of the public health diseases in the
country, contributing significantly to high morbidity and mortality.
Over the years, the Federal Government has put several interventions in place to
control the scourge of the disease, one of which is the improvement of malaria
case management at all levels. A major threat to these efforts however was the
emergence of resistance to available antimalarial medicines such as chloroquine
and Sulphadoxine-Pyrimethamine. The Drug Therapeutic Efficacy Tests (DTET)
on chloroquine and Sulphadoxine-Pyrimethamine in the six epidemiological
zones in 2002 evidently showed the inability of these medicines to completely
clear malaria parasites in the blood.
The introduction in 2005, of Artemisinin based Combination Therapy (ACTs) as
treatment of uncomplicated malaria following the failure of chloroquine and
Sulphadoxine-Pyrimethamine revolutionalized the treatment of malaria in the
country. Presently ACTs are the most efficacious antimalarial treatment available
globally.

In a renewed effort to control, the disease, emphasis has shifted from the
vulnerable groups to the entire population at risk. In this case, colour coded and
pre-packaged antimalarial medicines will now be deployed to the public sector
and also at highly reduced cost to the private sector. By so doing, the medicines
will be made available and affordable to the general populace.
One of the major highlights in the newly reviewed policy is the promotion of
parasite based diagnosis in all age groups; in which case, all suspected cases of
malaria shall be appropriately diagnosed where available, before treatment. This
is expected to protect the medicine while also saving cost.
This updated guideline provides comprehensive information on
chemoprophylaxis, preventive treatment, diagnosis and treatment of malaria as
recommended by the country's National Policy on Diagnosis and Treatment of
Malaria. The use of this document is therefore expected to provide information
that will lead to the improvement in the management of malaria illness both at
the health facility and at community levels.
The guideline would be widely disseminated to health care facilities; both private
and public across Nigeria as an important step in standardizing their prescription
practices. Accordingly, it is imperative for the health care providers in the country

National Guidelines for Diagnosis and Treatment of Malaria 3

 to strictly comply with this guideline to harmonize malaria management
practices within the country.

I would therefore encourage all health care providers at the various health
facilities and within the community to avail themselves of the opportunities
offered by this guideline with a view to “rolling back” malaria from Nigeria.

Prof. C.O. Onyebuchi Chukwu

Honourable Minister of Health

National Guidelines for Diagnosis and Treatment of Malaria 4

 ACKNOWLEDGEMENT
The Federal Ministry of Health, hereby specially acknowledges the contributions
of the various organizations, institutions and their staff towards the successful
review and finalization of this document.
We also thank the Roll Back Malaria partnership, for its unflinching and
continued support to the malaria control programme both at the national and
the state levels.

It is worthy to mention the support provided by the World Bank Malaria Booster
Project. In the same vein, we are grateful for the contribution from experts from
World Health Organization, Support for National Malaria Programme (SuNMaP),
Yakubu Gowon Centre (YGC), United States Agency for International
Development (USAID), Society for Family Health (SFH), Malaria Action
Programmes for States (MAPS), Clinton Health Access Initiative (CHAI) etc.
We also appreciate the contribution of representatives of academic institutions
and research centres for their quality inputs to the development of this
document.
It is our hope that this document will provide the necessary guide required for
the effective management of malaria in Nigeria.

Dr. Babajide Coker

National Coordinator,
National Malaria Control Programme

National Guidelines for Diagnosis and Treatment of Malaria 5

 EDITORIAL TEAM
Dr Babajide Coker National Malaria Control Programme, Abuja
Dr Bellay Kassahun USAID, Abuja
Dr David Durojaiye National Malaria Control Programme, Abuja
Dr Ernest Nwokolo Society for Family Health, Abuja
Dr Evelyn Patrick Support to National Malaria Programme
Dr Femi Ajumobi National Malaria Control Programme, Abuja
Dr Godwin Ntadom National Malaria Control Programme, Abuja
Dr Ibrahim Kabir State Malaria Control Programme, Dutse,
Jigawa State
Dr Moriam Jagun World Bank Malaria Booster Project, Abuja
Dr Ngozi Mbanugo Yakubu Gowon Centre, Abuja
Dr Olusola Oresanya National Malaria Control Programme, Abuja
Dr Peter Olumese World Health Organization, Geneva
Dr Tolu Arowolo World Health Organization, Nigeria
Dr Uwem Inyang Malaria Action Programme for States, Abuja
Mr Jide Banjo National Malaria Control Programme, Abuja
Mrs Comfort Ubah National Malaria Control Programme, Abuja
Mrs Nkoyo Onnoghen National Malaria Control Programme, Abuja
Pharm Ewomazino Ogedegbe Yakubu Gowon Centre, Abuja
Professor Akinwande Sowunmi University College Hospital, Ibadan
Professor Francis Useh University of Calabar Teaching Hospital
Professor Uche Okafor University of Nigeria Teaching Hospital, Enugu
Professor Wellington Oyibo Lagos University Teaching Hospital, Idi Araba,
Lagos
Professor William Ogala Ahmadu Bello University, Zaria

National Guidelines for Diagnosis and Treatment of Malaria 6

 © National Malaria Control Programme
All rights reserved.
Publications of the Federal Ministry of Health, Nigeria
Available at <nmcpnigeria.org>
The responsibility for the interpretation and use of the material in this
guideline lies with the reader, however, all issues arising from this
document should be appropriately directed to:
Case Management and Drug Policy Branch
National Malaria Control Programme
Abia House, Central Business District, Abuja, Nigeria
E-mail: [email protected]

National Guidelines for Diagnosis and Treatment of Malaria 7

 TABLE OF CONTENTS
FOREWORD.......................................................................................................................... 3
ACKNOWLEDGEMENT.......................................................................................................... 5
EDITORIAL TEAM.................................................................................................................. 6
TABLE OF CONTENTS............................................................................................................ 7
GLOSSARY............................................................................................................................. 10
LIST OF ABBREVIATIONS....................................................................................................... 13
EXECUTIVE SUMMARY.......................................................................................................... 15
1.0. INTRODUCTION.............................................................................................................17
1.1 OVERVIEW OF THE GUIDELINES FOR DIAGNOSIS AND TREATMENT OF MALARIA......... 19
1.1.1 Objectives
1.1.2 Target audience
1.2 HEALTH CARE LEVELS AND THEIR ROLES IN MALARIA MANAGEMENT.......................... 19
1.3 EPIDEMIOLOGY AND CLINICAL DISEASE......................................................................... 20
2.0 HISTORY.......................................................................................................................... 21
3.0 DIAGNOSIS OF MALARIA.................................................................................................22
3.1 Clinical diagnosis
3.2 Parasitological Diagnosis
3.2.1 Microscopy
3.2.2 Malaria Rapid Diagnostic Tests (RDTs)
3.3 The Choice between Rapid Diagnostic Tests (RDTs) and Microscopy
4.0 TREATMENT OF UNCOMPLICATED MALARIA................................................................. 27
4.1 Treatment Objective
4.2 Artemisinin based Combination Therapies
4.3 Recommended treatments
4.4 Practical Issues in Management of Uncomplicated Malaria
5.0 TREATMENT OF UNCOMPLICATED MALARIA IN SPECIAL
GROUPS............................................................................................................................ 30
6.0 COMMUNITY MANAGEMENT OF MALARIA............................................................... 31
6.1 Children less than 5kg
6.2 Pregnant women and Lactating mothers
7.0 ASSESSMENT AND MANAGEMENT OF SEVERE MALARIA..................................... 36
7.1 Definition
7.2 Explanatory notes on the features of severe malaria
7.3 Who are the people at risk for severe malaria?
7.4 History
7.5 Physical Examination
7.6 Differential Diagnosis
7.7 Laboratory Investigations
7.8 Treatment
7.8.1 Life threatening emergencies
7.8.2 Specific Antimalarial Treatment
7.8.3 Supportive Treatment
7.8.4 Treatment not recommended

National Guidelines for Diagnosis and Treatment of Malaria 8

 8.0 NURSING AND QUALITY OF CARE..................................................................................... 47
9.0 PRE-REFERRAL TREATMENT............................................................................................ 48
10.0 PREVENTIVE TREATMENTS AND CHEMOPROPHYLAXIS................................................ 50
10.1 Intermittent Preve Treatment
10.2 Malaria Chemoprophylaxis
10.3 Non immune Visitors
11.0 ANTIMALARIAL DRUG RESISTANCE...............................................................................52
11.1 Antimalarial drug resistance in Nigeria
11.2 Impact of resistance
12.0 BRIEFS ON PHARMACOLOGY OF ANTIMALARIAL DRUGS............................................54
ANNEXURES..........................................................................................................................59
ANNEX 1 QUALITY ASSURANCE FOR MALARIA DIAGNOSIS WITH MICROSCOPY...............59
ANNEX 2 SUMMARY OF CHECK-LIST FOR INTERNAL QUALITY ASSURANCE FOR MALARIA
MICROSCOPY.......................................................................................................60
ANNEX 3 QUALITY ASSURANCE FOR MALARIA DIAGNOSIS OF MALARIA..........................67
ANNEX 4 BLOOD SMEARS FOR MICROSCOPY.....................................................................67
ANNEX 5 ISSUES WITH RDTS IN THE FIELD.........................................................................72
ANNEX 6 PHARMACOVIGILANCE........................................................................................75

National Guidelines for Diagnosis and Treatment of Malaria 9

 GLOSSARY

Artemisinin-based combination therapy (ACT): A combination of

artemisinin or one of its derivatives with an antimalarial or antimalarials
of a different class.

Asexual parasitaemia: The presence in host red blood cells of asexual

parasites. The level of asexual parasitaemia can be expressed in several
different ways: the percentage of infected red blood cells, the number of
infected cells per unit volume of blood, the number of parasites seen in
one microscopic field in a high-power examination of a thick blood film, or
the number of parasites seen per 2001000 white blood cells in a high
power examination of a thick blood film.

Cerebral malaria: Severe P. falciparum malaria with cerebral

manifestations, usually including coma (Glasgow coma scale < 11,
Blantyre coma scale < 3). Malaria with coma persisting for > 30 min after a
seizure is considered to be cerebral malaria.

Cure: Elimination of the symptoms and asexual blood stages of the

malaria parasite that caused the patient or caregiver to seek treatment.

Drug resistance: The World Health Organization (WHO) defines resistance

to antimalarials as the ability of a parasite strain to survive and/or to
multiply despite the administration and absorption of a medicine given in
doses equal to or higher than those usually recommended but within the
tolerance of the subject, provided drug exposure at the site of action is
adequate. Resistance to antimalarials arises because of the selection of
parasites with genetic mutations or gene amplifications that confer
reduced susceptibility.

Gametocytes: Sexual stages of malaria parasites present in the host red

blood cells.

National Guidelines for Diagnosis and Treatment of Malaria 10

 Malaria pigment (haemozoin): A dark brown granular pigment formed by
malaria parasites as a by-product of haemoglobin catabolism. The
pigment is evident in mature trophozoites and schizonts. They may also be
present in white blood cells (peripheral monocytes and
polymorphonuclear neutrophils) and in the placenta.

Monotherapy: Antimalarial treatment with a single medicine (either a

single active compound or a synergistic combination of two compounds
with related mechanism of action).

Plasmodium: A genus of protozoan vertebrate blood parasites that

includes the causal agents of malaria. Plasmodium falciparum, P.
malariae, P. ovale and P. vivax cause malaria in humans. Human infections
with the monkey malaria parasite, P. knowlesi have also been reported
from forested regions of South-East Asia.

Rapid diagnostic test (RDT): An antigen-based stick, cassette or card test

for malaria in which a coloured line indicates that plasmodial antigens
have been detected.

Recurrence: The recurrence of asexual parasitaemia following treatment.

This can be caused by a recrudescence, a relapse (in P. vivax and P. ovale
infections only) or a new infection.

Recrudescence: The recurrence of asexual parasitaemia after treatment

of the infection with the same infection that caused the original illness.
This results from incomplete clearance of parasitaemia due to inadequate
or ineffective treatment. It is, therefore, different to a relapse in P. vivax
and P. ovale infections, and it differs from a new infection or re-infection
(as identified by molecular genotyping in endemic areas).

Relapse: The recurrence of asexual parasitaemia in P. vivax and P. ovale

malaria deriving from persisting liver stages. Relapse occurs when the

National Guidelines for Diagnosis and Treatment of Malaria 11

 blood stage infection has been eliminated but hypnozoites persist in the
liver and mature to form hepatic schizonts. After variable intervals of
weeks to months, the hepatic schizonts burst and liberate merozoites into
the bloodstream.

Severe anaemia: Haemoglobin concentration of < 5 g/100 ml

(haematocrit < 15%).

Severe falciparum malaria: Acute falciparum malaria with signs of

severity and/or evidence of vital organ dysfunction.

Uncomplicated malaria: Symptomatic infection with malaria

parasitaemia without signs of severity and/or evidence of vital organ
dysfunction.

National Guidelines for Diagnosis and Treatment of Malaria 12

 LIST OF ABBREVIATIONS
AA: Artesunate - amodiaquine
ACTs: Artemisinin-based Combination Therapy
ADR: Adverse Drug Reaction
AL: Artemether - lumefantrine
CSF: Cerebrospinal fluid
DHP: Dihydroartemisinin - piperaquine
DOT Directly Observed Therapy
ECG: Electrocardiogram
FCT: Federal Capital Territory
GIT: Gastrointestinal Tract
G6PD: Glucose 6-Phosphate Dehydrogenase Deficiency
Hb: Haemoglobin
HBSS: Sickle Cell Haemoglobin
HIV: Human Immunodeficiency Virus
HRP-2: Histidine Rich Protein-2
IM: Intramuscular
IPT Intermittent Preventive Treatment
IV: Intravenous
LGA: Local Government Area
LLIN: Long Lasting Insecticidal Nets
MAPS: Malaria Action Programme for States.
MP: Malaria Parasite

National Guidelines for Diagnosis and Treatment of Malaria 13

 NAFDAC: National Agency for Food and Drug Administration and
Control
NGT: Nasogastric Tube
PCR: Polymerase Chain Reaction
PCV: Pack Cell Volume
PMVs: Private Patent Medicine Vendors
QA: Quality Assurance
QC: Quality Control
RDTs: Rapid Diagnostic Test
RMCs: Role Model Care-givers
SOPs: Standard Operating Procedures
SuNMaP: Support for National Malaria Programme
TNF: Tumor Necrosis Factor
USAID: United States Agency for International Development
WBCs: White Blood Cells
WHO: World Health Organization

National Guidelines for Diagnosis and Treatment of Malaria 14

 EXECUTIVE SUMMARY
Malaria case management remains a vital component of the malaria
control strategies. This entails early diagnosis and prompt treatment with
effective antimalarial medicines recommended for use in the country. As
part of the activities to scale up the diagnosis and treatment of Malaria in
Nigeria, the National Malaria Control Programme reviewed the National
Policy on Diagnosis and Treatment of Malaria in line with WHO
recommendations. This guidelines has therefore been reviewed to reflect
the changes and recommendations in the new policy document

This third edition of the guidelines emphasizes the importance of

parasitological confirmation of malaria cases through microscopy or
Rapid Diagnostic Test and also provides clear and easy-to-understand
steps required in carrying out the listed procedures.

The summary of the key recommendations provided in these guidelines is

presented below.

 Prompt parasitological confirmation by microscopy or RDTs is

recommended in all patients suspected of malaria before
treatment.
 Treatment solely on the basis of clinical suspicion should only be
considered when a parasitological diagnosis is not accessible.
 Artemisinin-based combination therapies (ACTs) are the
recommended treatments for uncomplicated P. falciparum
malaria.
 The following ACTs are recommended for use in Nigeria
Artemether-lumefantrine, Artesunate-amodiaquine,
 Artemisinin and its derivatives should not be used as monotherapy
in the treatment of uncomplicated malaria
 Oral Quinine is the recommended medicine for the treatment of
uncomplicated malaria in the first trimester and in children less
than 5kg, however, ACTs can be used under supervision by the

National Guidelines for Diagnosis and Treatment of Malaria 15

 health care provider
 ACTs is the recommended treatment of uncomplicated malaria in
the second and third trimesters of pregnancy.
 Severe malaria is a medical emergency. After rapid clinical
assessment and confirmation of diagnosis where feasible,
commence immediate treatment with parenteral medication.
Intravenous artesunate is preferred for the treatment of severe
P.falciparum malaria
 Parenteral quinine or artemether is an acceptable alternative if
artesunate is not available.
 Parenteral antimalarial medicines in the treatment of severe
malaria should be administered for a minimum of 24 hours once
started (irrespective of the patient's ability to tolerate oral
medication earlier) and thereafter, complete treatment with a
complete course of an ACT.
 In settings where complete treatment of severe malaria is not
possible, patients should be given pre-referral treatment and
referred immediately to an appropriate facility for further
treatment. The recommended pre-referral treatment options
include any of these; artesunate IM or rectal, and quinine IM.
 The recommended chemoprophylaxis for non immune visitors will
be as available in the visitor's country of origin or as recommended
in Nigeria.
 Sulphadoxine-Pyrimethamine is the recommended medicine for
Intermittent Preventive Treatment in Pregnancy.

National Guidelines for Diagnosis and Treatment of Malaria 16

 2.0. INTRODUCTION

Malaria remain a major public health problem in Nigeria; children under

the age of five and pregnant women are still the most affected. More than
60% outpatient visits in Nigeria are due to malaria. The disease has
impacted negatively on the economy with about 132 billion Naira lost to
the disease as cost of treatment and loss in man-hours.

The launching of the Roll Back Malaria initiative in April 25, 2000 and the
commitment of all African leaders to fight the disease which kills over one
million children and pregnant women every year was commendable.

One of the key strategies to control malaria is effective case management.

Unfortunately, this has received a major setback in the past years because
of the high level of resistance to the first and second line antimalarial
medicines; Chloroquine and Sulphadoxine-Pyrimethamine.

In 2005, the National Malaria Treatment Policy was reviewed during which
the Artemisinin based Combination Therapies were introduced. These
medicines are presently the most efficacious antimalarial treatment
available. The therapeutic efficacy study in 2004 and a repeat test in 2009
has continuously demonstrated high efficacy of these artemisinin
combinations. In addition, the Federal Ministry of Health is aware of the
development of new potent combinations that are also highly effective
and may deploy some of these as pilots in selected sites.

Until recently, in areas of high malaria transmission such as Nigeria,

malaria treatment has been based mainly on clinical diagnosis which was
presumptive, because malaria was considered one of the commonest
causes of fever.

With the deployment of several other control interventions such as Long

Lasting Insecticidal Nets (LLIN) and Indoor Residual Spraying (IRS),

National Guidelines for Diagnosis and Treatment of Malaria 17

 Intermittent Preventive Treatment (IPT) etc, there has been emerging
evidences of decline in the incidence of malaria in some regions. These
have further been corroborated by the reduced rate of parasitaemia in the
recently concluded Drug Therapeutic Efficacy Test in the six
epidemiological settings in the country.

With the availability of new tools such as parasite-based rapid diagnostic

kits, which compliments the standard microscopy, it is imperative to
provide targeted treatment and, accurate estimation of true malaria
cases. However, in cases where parasitological confirmation is not
available, highly vulnerable groups (including children under five years
and those suspected with severe malaria) can be treated on a clinical
basis.

This guideline has been produced to provide information on the use of

some antimalarial medicines approved for use in Nigeria to reflect the
changes that have been incorporated into the reviewed National
Antimalarial Treatment Policy.

National Guidelines for Diagnosis and Treatment of Malaria 18

 1.1 OVERVIEW OF THE GUIDELINES FOR DIAGNOSIS AND
TREATMENT OF MALARIA

1.1.1 Objectives
The objectives of this document are to provide guidelines for:
 the diagnosis of malaria using rapid diagnostic tests (RDTs) and
microscopy
 treatment of uncomplicated malaria
 management of severe malaria
 chemoprophylaxis and preventive treatment of malaria

1.1.2 Target audience:

 Health care providers at all levels

1.2 HEALTH CARE LEVELS AND THEIR ROLES IN MALARIA

MANAGEMENT

Community based Care

Informal health care providers in the communities are Role Model Care
Givers (RMC) and the Patent Medicine Vendors (PMVs). These are trained
to recognize basic symptoms of uncomplicated malaria and treat them.

Management of malaria at health facilities occur at three levels:

Level I
This includes such facilities as the Primary Health Care Clinics,
Dispensaries and Health posts and is expected to be available in all the
political wards and communities in the country. The cadre of staff found in
this level include Nurses, Community Health Officers, Community Health
Extension Workers, Pharmacy technicians etc. These are trained to
provide comprehensive management for uncomplicated malaria and also

National Guidelines for Diagnosis and Treatment of Malaria 19

 initiate appropriate treatment before referring suspected cases of severe
malaria to higher facilities. Occasionally, there may be medical officers
and pharmacists and trained microscopist at this level of health care
delivery. The main form of diagnosis is the use of Rapid Diagnostic Test
kits.

Level II
This level consists of Comprehensive health centres, Cottage hospitals,
General hospitals and some private hospitals. At this level, there is
capacity to carry out microscopy and other basic laboratory services and
also to treat severe malaria in addition to providing in-patient care. Each
LGA is expected to have at least one of these.
The cadre of staff found at this level are medical officers, pharmacists,
medical laboratory scientists, nurses, Community Health Officers etc.
Parasite based confirmation with microscopy shall be used to confirm
suspected cases of malaria; however RDTs may be used at this level as
appropriate.

Level III
This represents the highest level of medical care in the country. The
facilities include Teachinghospitals, Specialist hospitals, Federal Medical
centres. Some General and private hospitals belong to this category. At
least, one of these categories is found in each state of the Federation and
provide specialized health care services. The cadres of health workers
found here include specialists in various health disciplines.
Parasite based confirmation with microscopy shall be used to confirm all
cases with febrile illnesses; however RDTs may be used at this level as
appropriate.

1.3 EPIDEMIOLOGY AND CLINICAL DISEASE

Malaria is an infectious disease caused by the parasite of the genus
Plasmodium, transmitted mostly by the bite of an infected female

National Guidelines for Diagnosis and Treatment of Malaria 20

 anopheles mosquito. There are four identified species of the parasite
causing human malaria, namely, Plasmodium falciparum, P. vivax, P. ovale
and P. malariae. In Nigeria, the species most responsible for the severe
form of the disease that leads to death is P. falciparum. P. vivax does not
occur in indigenous Nigerians.
Malaria transmission is stable in Nigeria. Children under the age of five,
pregnant women and non-immune visitors from non-endemic areas are
particularly more susceptible than the general population.

Based on clinical and laboratory profiles, malaria can be classified as

uncomplicated or severe. Patients with malaria can die when the disease
is not appropriately classified. Failure to recognize severe malaria may be
fatal.

a. Uncomplicated malaria:
This is symptomatic malaria that has no vital organ dysfunction or
life threatening manifestations.
b. Severe malaria:
This is when there is P. falciparum asexual parasitaemia and no
other confirmed cause of their symptoms with the presence of life
threatening clinical or laboratory features.

2.0 HISTORY

A complete history should include:

 General information such as age, place of residence and recent
history of travel within or outside the country.
 Enquiry about the following symptoms:-
* Fever
* Chills (feeling cold) and rigors (shaking of the body)
* Headache
* Joint weakness or tiredness

National Guidelines for Diagnosis and Treatment of Malaria 21

  Also ask for the symptoms of other common childhood diseases
* Cough or respiratory distress
* Diarrhoea
* Ear pain and skin rashes in the last three months.

3.0 DIAGNOSIS OF MALARIA

Malaria can be diagnosed based on clinical and laboratory evaluations.

3.1 Clinical diagnosis

The signs and symptoms of malaria are non-specific. However, clinical
suspicion is based on fever or history of fever in the last 24 hrs and/or the
presence of anaemia. It is important to note that clinical diagnosis alone
may result in over-diagnosis of malaria; hence, parasitological
confirmation is strongly recommended.

Clinical signs may include amongst other symptoms:

 Raised body temperature ≥ 37.5°C.

 Enlarged spleen or liver, especially in children.
 Pallor (children/pregnant women)
 Exclude signs of severe disease.

3.2 Parasitological Diagnosis

The changing epidemiology of malaria due to scale up of interventions and
the introduction of ACTs have increased the urgency of improving the
specificity of malaria diagnosis. Parasitological diagnosis has the following
advantages:

 Improved patient care in parasite-positive patients;

 Identification of parasite-negative patients in whom another
diagnosis must be sought;
 Prevention of unnecessary use of antimalarials, reducing

National Guidelines for Diagnosis and Treatment of Malaria 22

 frequency of adverse effects, especially in those who do not need
the medicines, and drug pressure selecting for resistant parasites;
 Improved malaria case detection and reporting;
 Confirmation of treatment failures

Parasitological confirmation is recommended in all suspected cases of

malaria. However, in areas of high transmission such as Nigeria, children
under five years can still be treated on clinical basis where parasitological
confirmation is not feasible. This is also applicable in cases of suspected
severe malaria.

Prompt and accurate diagnosis is part of effective disease management.

High sensitivity of malaria diagnosis is important to identify those positive
cases in all settings. High specificity is vital to identify negative cases,
which can reduce unnecessary treatment with antimalarial medicines and
improve differential diagnosis of febrile illness.

The two methods in routine use for parasitological diagnosis are Light
Microscopy and Rapid Diagnostic Tests (RDTs). The latter detect parasite-
specific antigens or enzymes and some have a certain ability to
differentiate species. Deployment of microscopy and RDTs must be
accompanied by quality assurance.
Other tests outside the routine clinical setting such as Polymerase Chain
Reaction (PCR)-based techniques are used for parasite diagnosis under
special circumstances in tertiary institutions and research (for instance
resistance testing)

Antimalarial treatment should be limited to test positive cases. The

negative cases should be reassessed for other common causes of fever.
The benefit of parasitological diagnosis depends entirely on health-care
providers adhering to the results in managing the patient. However, the
severity of the disease justifies the use of antimalarial medicines in test
negative cases, considering the possible small risk of false negative tests.

National Guidelines for Diagnosis and Treatment of Malaria 23

 The risk of false negative microscopy is higher if the patient has received a
recent dose of an artemisinin derivative.

The results of parasitological diagnosis should be available within a short

time (less than two hours) of the patient presenting.

3.2.1 Microscopy:
Microscopy is the standard method for parasitological diagnosis of
malaria. This is done by examining a stained thick or thin blood smear for
the presence of malaria parasites.
Thick films are recommended for parasite detection and quantification
and can be used to monitor response to treatment. Thin films are
recommended for species identification.

Microscopic examination of stained blood films by a highly skilled

microscopist has a sensitivity range of 86-98% with a lower sensitivity in
detecting low parasitaemias (≤ 320/µl). Various factors such as the stage
of the malaria infection and previous medication may reduce
parasitaemia below the detectable threshold and necessitate repeat
examination.

3.2.2 Malaria Rapid Diagnostic Tests (RDTs)

Malaria Rapid Diagnostic Tests (RDTs) is a device which detects specific
antigens (proteins) produced by malaria parasites. The RDT signifies
presence of the antigens by colour change on nitrocellulose strip (test
strip)
They provide a useful guide to the presence of clinically significant malaria
infection. They complement microscopy based diagnosis where such
services are not available. However, RDTs should not replace microscopy
as the sole means of malaria diagnosis.

The general management of a malaria patient should base treatment

decisions not only on results but also other clinical parameters. In case of
uncomplicated malaria, the rationale of treatment for a MP slide/RDT
negative should be clearly defined by the managing clinician.

National Guidelines for Diagnosis and Treatment of Malaria 24

 Like all laboratory procedures the accuracy of an MP slide /RDT is
dependent on the care and expertise with which it is prepared and
interpreted.
Quality assured Histidine Rich Protein 11 (HRP 2) based RDT is the
recommended for the diagnosis of malaria in all age groups. Most RDTs
have a sensitivity of 95% at parasite densities of 200/μl of blood.

The sensitivity of malaria RDTs is determined by the:

 Species of parasite
 Number of parasites present in the blood
 Condition of the RDT
 Correctness of technique used to perform the test.
 Correctness of interpretation by the reader
 Parasite viability and variation in production of antigen by the
parasite.

3.3 The Choice between Rapid Diagnostic Tests (RDTs) and

Microscopy
The choice between RDTs and microscopy depends on local
circumstances, including the skills available, patient case-load,
epidemiology of malaria and the possible use of microscopy for the
diagnosis of other diseases. Where the case-load of fever patients is high,
microscopy is likely to be less expensive than RDTs, but may be less
operationally feasible. Microscopy has further advantages in that it can be
used for speciation and quantification of parasites, and to assess response
to antimalarial treatment. Microscopy can also be used in the
identification of other causes of fever.
However, a major drawback of light microscopy is its requirement for well-
trained, skilled staff and, usually, an energy source to power the
microscope. In many areas, malaria patients are treated outside of the
formal health services, e.g. in the community, in the home or by private
providers; microscopy is generally not feasible in many such
circumstances, but RDTs may be possible.

National Guidelines for Diagnosis and Treatment of Malaria 25

 Although RDTs for detection of parasite antigen are generally more
expensive, their deployment may be considerably cost effective in many
of these settings. The sensitivities and specificities of RDTs are variable,
and their vulnerability to high temperatures and humidity is an important
constraint. Despite these concerns, RDTs make it possible to expand the
use of confirmatory diagnosis
In the diagnosis of severe malaria cases, microscopy is a preferred option;
it not only provides the diagnosis of malaria, but it is useful in assessing
other important parameters in a severely ill patient. In situations where an
RDT has been used to confirm malaria, this allows for a rapid institution of
antimalarial treatment, however, where possible a microscopic
examination is recommended to enhance the overall management of the
patient.

Summary Box 1: Diagnosis of Malaria 4.0

 Prompt parasitological confirmation by microscopy or RDT

is recommended in all patients suspected of Malaria before
treatment is initiated.

 Treatment solely on the basis of clinical suspicion should only

be considered when a parasitological diagnosis is not
accessible

National Guidelines for Diagnosis and Treatment of Malaria 26

 TREATMENT OF UNCOMPLICATED MALARIA
4.1 Treatment Objective:
The objective of treating uncomplicated malaria is to cure the infection as
rapidly as possible. Prompt treatment will prevent both progressions to
severe disease and the additional morbidity associated with treatment
failure. Cure of the infection means eradication from the body of the
parasite that caused the disease. Additional objectives are to prevent
transmission, and the emergence and spread of resistance to antimalarial
medicines.

4.2 Artemisinin based Combination Therapies

The treatment of choice for uncomplicated malaria is Artemisinin Based
Combination Therapy (ACT). ACTs are combination medicines consisting
of an artemisinin derivative and another effective long acting
schizonticidal antimalarial medicine.

4.3 Recommended treatments

The recommended ACTs for treatment of uncomplicated malaria in
Nigeria are Artemether-Lumefantrine and Artesunate-Amodiaquine. The
2009 Drug Therapeutic Efficacy Tests carried out on these medicines in the
country have confirmed that they remain efficacious.

Artemether-Lumefantrine
It is available as co-formulated. Each tablet contains 20mg artemether and
120mg lumefantrine.

National Guidelines for Diagnosis and Treatment of Malaria 27

 There are 4 different packet sizes (see table below); some children packs
containing six and twelve tablets come in dispersible tablet form.

Dosage regimen

Weight Number of tables/dose

5 - < 15kg 1 tab twice daily X 3days

15 - >25kg 2 tabs twice daily x 3days

25 - <35kg 3 tabs twice daily x 3days

>35kg 4 tabs twice daily x 3days

It is important to emphasize that the 6 doses must be taken by the patient.

The first two doses should be taken between 8 to 12 hours apart.
Absorption of the medicine is enhanced by fatty meals.

Artesunate-Amodiaquine
It is available as co-formulated and co-packaged. The co-formulated
medicines are however preferred.

National recommended Artesunate and Amodiaquine combination

Medicines Dosage form Presentation

Artesunate - Tablet Co-formulated
Amodiaquine

National Guidelines for Diagnosis and Treatment of Malaria 28

 Dosage regimen for co-formulated Artesunate-Amodiaquine

Weight/Age Tables strength Dosage regimen

4.5kg - <9kg 25mg/67.5mg 1 tab once daily for three days
2months - 11months
>9kg - <18kg 50mg/135mg 1 tab once daily for three days
>1 year - 5 years
18kg - >36kg 100mg/270mg 1 tab once daily for three days
>6 years - 13 years
36kg and above 100mg/270mg 1 tab once daily for three days
14 years and above

If the patient shows evidence of inadequate response (persistence of

fever, parasitaemia or deterioration in clinical condition), do the following:
 Evaluate the patient and review diagnosis
 Exclude sub optimal dosing or inadequate intake
 Investigate further
In the absence of clinical improvement and persistence of positive
parasitaemia, despite adequate treatment, quinine should be used.
(Please see below for the dosage regimen of quinine).
Monotherapy with any artemisinin derivatives and other antimalarial
medicines are not recommended in the treatment of uncomplicated
malaria. It should be noted that Sulphadoxine-Pyrimethamine is not a
combination therapy and should not be used as such. In Nigeria, the use of
Sulphadoxine-Pyrimethamine is restricted to pregnant women as
Intermittent Preventive Treatment.

4.4 Practical issues in Management of Uncomplicated Malaria

 Antipyretic measures
If temperature is > 38.5°C, give Paracetamol 10 - 15 mg/kg in children
or 500-1000 mg in adults every 6 8 hours or when necessary or advice

National Guidelines for Diagnosis and Treatment of Malaria 29

 to tepid sponge (wipe the body with towel soaked in lukewarm water)
and avoid over=clothing.
 Persistent Vomiting
If a patient vomits the medicine within 30 minutes, repeat the dose. If
this is vomited again and the vomiting becomes persistent, the patient
should be considered as having severe malaria and managed
accordingly.
 Febrile Seizures
If a patient has a seizure and does not recover within 30 minutes from
that seizure, it should be considered as severe malaria.

5.0 TREATMENT OF UNCOMPLICATED MALARIA IN SPECIAL

GROUPS
5.1 Children less than 5kg
Malaria in children less than 5kg can be serious and may progress to
severe disease with increased risk of dying if not treated promptly.
Artemisinin derivatives are safe and well tolerated by young children. ACTs
can be used for the treatment of uncomplicated malaria in infants and
young children but attention must be given to accurate dosing and the
providers must ensure that the administered dose is retained. Oral
quinine 10mg base /kg every 8 hours for 7 days and other supportive
therapy can also be used for treatment.

5.2 Pregnant women and Lactating mothers

Falciparum malaria in pregnancy carries a high mortality for the foetus and
increased morbidity for the pregnant woman. Quinine is safe for the
treatment of malaria in all trimesters of pregnancy. In the second and third
trimester ACTs can be used. However there should be proper monitoring
and documentation in all cases.
In the first trimester the safety of the ACTs has not been ascertained for a
categorical recommendation on their use. However, should be used if it is

National Guidelines for Diagnosis and Treatment of Malaria 30

 the only effective antimalarial medicine available.
Lactating mothers should also be treated with recommended ACTS.

6.0 COMMUNITY MANAGEMENT OF MALARIA

One of the strategies introduced to improve access and rapidly scale up
malaria diagnosis and treatment is the introduction of community
management of malaria. Role Model Caregivers and Private Medicine
Vendors (PMVs) in remote communities where access is difficult are
identified and trained to recognize basic symptoms of uncomplicated
malaria in children less than five years, carry out diagnosis where feasible
with malaria Rapid Diagnostic Test and initiate appropriate treatment.
They also recognize symptoms of severe malaria and support the referral
process.

Recommended medicines for the treatment of malaria at community

level is as recommended for the treatment of uncomplicated malaria.

Key Messages for Oral Medicines at Home

 Tablets are preferred as oral medication
 Determine the appropriate medicine and dosage according to
weight and age
 Tell the patient or the caregiver the reason for giving the medicine
 Demonstrate how to take or give the correct dose
 Watch the patient taking the medicine
 Explain that the treatment course must be completed even when
the patient feels well
 Advise them on when to return
 Check that the patient or caregiver has understood the
instructions before leaving the clinic

Follow up
 Counsel the patient to return immediately;

National Guidelines for Diagnosis and Treatment of Malaria 31

 * if condition gets worse or develops symptoms of severe
disease,
* if fever persists for two days after commencement of
treatment
 When patient returns,
* Check that the treatment regimen was complied with,
* Do a complete assessment to exclude any other
possible cause of the fever,
* Repeat or do blood smear for malaria parasites and
* Refer or manage as necessary

Summary Box 2: Treatment of uncomplicated malaria

 Parasitological confirmation of diagnosis is recommended

in all age groups.

 Artemisinin Combination Therapy (ACT) is the recommended

medicines for the treatment of uncomplicated Malaria.

 Artemether-Lumefantrine (AL) and Artesunate-Amodiaquine

(AA) are the recommended ACTs for programmatic use in
Nigeria.

 The use of monotherapies is not recommended

National Guidelines for Diagnosis and Treatment of Malaria 32

 ALGORITHM FOR FACILITY BASED MANAGEMENT OF MALARIA AT DIFFERENT LEVELS OF HEALTH CARE IN NIGERIA

Fever (Temp > 37.5°C)

Or History of fever in the last 24 hours

Health Centre/OPD

Signs of Severe Malaria S

P
Yes E
No C
I
- Pre-referral General Hospital
treatment A
RDT L
I
REFER S
Signs of Severe Malaria T
Positive
Negative
Yes
No H

National Guidelines for Diagnosis and Treatment of Malaria

- Give ACT - Assess for other causes O
Or Microscopy/RDT S
REFER for further - Assess for other P
investigations causes for fever I
Neg T
Pos
- investigate further A
Capacity to treat? L
Give ACT S
Yes No REFER

Treat as appropriate

33
 ALGORITHM FOR COMMUNITY TREATMENT OF MALARIA

History of fever / Fever by touch /

Temperature of > 37.5°C)

GENERAL DANGER SIGNS

Less than 5 years
 CONFUSION/UNCONSCIOUS
 VOMITING EVERYTHING Yes
 CONVULSION
 NOT PASSING ENOUGH URINE RDT No
 NOT RESPONDING TO ACT
 EXTREME WEAKNESS Positive Negative
 YELLOWNESS OF THE EYES/
BODY IN INFANTS
 PALLOR General Danger Signs

No Yes

National Guidelines for Diagnosis and Treatment of Malaria

- Give ACT
Health Education

No improvement after 2 days or Health Facility

getting worse
Develop other infection(s)
Reacting to medicine

34
 ALGORITHM FOR MANAGEMENT
OF SEVERE MALARIA

SEVERE MALARIA

PREGNANT?

IMPAIRED CONSCIOUSNESS?
ND RD
2 &3
TRIMESTER
YES NO

ST
1 TRIMESTER
IV/IM ARTESUNATE IS ORAL
OR ADMINISTRATION OF
IM QUININE DRUG FEASIBLE?

& OTHER
SUPPORTIVE CARE
NO YES

IV/IM QUININE
COMPLETE TREATMENT
(Give IV/IM WITH ACT ONCE GIVE ACT AND TREAT
ARTESUNATE PATIENT CAN TOLERATE
if Quinine is
MAIN COMPLICATIONS
ORALLY
not available)

National Guidelines for Diagnosis and Treatment of Malaria 35

 7.0 ASSESSMENT AND MANAGEMENT OF SEVERE
MALARIA
Management of severe malaria should be carried out in secondary
facilities with adequate facilities to manage complications or at specialist
facility.

7.1 Definition
A patient has severe malaria when there is P. falciparum asexual
parasitaemia and no other confirmed cause of their symptoms, in the
presence of one or more of the following clinical or laboratory features:
a
Clinical Manifestations or laboratory findings Frequency

Children Adults
 Prostration (i.e. Generalized weakness or inability to sit, stand or +++ +++
walk without support)
 Impaired consciousness (confusion or drowsiness or coma) +++ ++
 Respiratory distress (difficulty in breathing, fast deep breath) +++ +
 Multiple convulsions (>2 generalized seizures in 24 hrs with +++ +
regaining of consciousness)
 Severe anaemia (Hb <5g/dl) +++ +
 Circulatory collapse (shock) + +
 Hypoglycaemia (Less than 40mg or 2.2 mmol/l)
 Pulmonary oedema (respiratory distress/radiology) +/- +
 Abnormal bleeding (disseminated intravascular coagulopathy) +/- +
 Jaundice (yellow discoloration of the eyes) + +++
 Haemoglobinuria (Coca-cola coloured urine) +/- +
 Hyperparasitaemia b ++ +
 Renal failure (Urine output of less than 400 ml in 24 hours or +/- ++
<12ml/kg per 24 hours in children and a serum creatinine of more
Than 265 u mol/l (> 3.0 mg/dl), failing to improve after rehydration)

A
on a scale from + to +++; +/- indicates infrequent occurrence.
b
Density of asexual forms of P. falciparum in the peripheral smear exceeding 5% of
erythrocytes (more than 250,000 parasites per µl at normal red cell counts)

National Guidelines for Diagnosis and Treatment of Malaria 36

 7.2 Explanatory notes on the features of severe malaria
a. Anaemia
Anaemia occurs as a result of destruction of parasitized red blood cell by the
spleen, TNF mediated depression of erythropoiesis and immune mediated
haemolysis.
b. Cerebral Malaria:
For a diagnosis of cerebral malaria, the following criteria should be met:
i. Deep, unarousable coma: Motor response to noxious stimuli is non-
localising or absent. However management should be instituted once
there is an altered consciousness.
Ii. Exclusion of other encephalopathies:
Iii. Confirmation of P. falciparum infection:

c. Abnormal neurological manifestations:

Convulsions may be as a result of very high temperature, hypoglycaemia,
hypoxaemia, severe anaemia or the effect of herbal concoction.

d. Hypoglycaemia:
This may occur as a result of decreased intake, increased glucose
utilization; antimalarial mediated reduction, glycogen depletion or
impaired gluconeogenesis.

e. Acidosis:
This is due to elevated levels of lactic acid which results from tissue
anaerobic glycolysis, particularly in skeletal muscles.

f. Breathing difficulties:
Patients with severe malaria may present with difficulty in breathing as a
result of any of the following:

National Guidelines for Diagnosis and Treatment of Malaria 37

  Heart failure resulting from severe anaemia.
 Pulmonary oedema (following administration of excessive fluids)
usually there is frothing from the mouth and marked respiratory
distress.
 Acidosis causes deep and rapid respiration.
 Aspiration

g. Renal Failure:
Renal failure develops due to low blood pressure as a result of dehydration
or shock.

H. Haemoglobinuria:
This occurs as a result of excessive breakdown of red blood cells by
parasites or drugs like sulphonamides and primaquine, especially in G6PD
deficiency patients.

7.3 Who are the people at risk for severe malaria?

 Children < 5 years
 Pregnant women
 People returning or coming to Nigeria after living in malaria free areas
 People who have had splenectomy

7.4 History
In addition to the general history taken in patient with uncomplicated
malaria you should ask about the following
In all patients ask about:-
 Extreme weakness (Prostration): inability to eat and drink or do
anything without support. Progressive weakness should
immediately alert you that the patient may be developing

National Guidelines for Diagnosis and Treatment of Malaria 38

  Severe malaria.

 Abnormal behaviour or altered consciousness: ask relatives to tell

you any observed changes in the patients' behaviour since the illness
started or when the unresponsiveness started.
 Convulsions: ask about the number of episodes, part of the body
involved, previous history and time onset of last episode. Focal or
multiple convulsions over a period of 24 hours is indicative of severe
disease.
 Drowsiness or deteriorating level of consciousness.
 Time of last drink or food since the onset of the illness.
 Fast breathing which may occur due to pulmonary oedema or
acidosis.
 Reduced urinary output (time patient last passed urine).
 Colour of urine: whether dark or coca-cola coloured (this may suggest
excessive breakdown of red blood cells or dehydration).
 Pregnancy: in adult females.

Ask history to exclude other severe diseases

 Drug History: Ask about antimalarial drugs, salicylates and herbal
concoctions that may influence treatment or cause some of the
symptoms.
 Previous illnesses: Ask about any history of recent febrile illness and
treatment which may suggest treatment failure or relapse (consider
typhoid, malaria and other infections).

7.5 Physical Examination:

In the physical examination you should aim at
 Assessing for the presence of signs of severe malaria.
 Identifying other possible causes of disease.

a. Central Nervous System

Assess the level of consciousness using an objective scale such as the

National Guidelines for Diagnosis and Treatment of Malaria 39

 AVPU scale, Glasgow coma scale or the Blantyre coma scale:
The AVPU scale is as show below
A = alertness (is the patient alert)
V = response to voice command (does the patient respond to his
name)
P = response to pain (does the patient feel pain or cry if a child)
U = unresponsive. (Patient does not respond at all)

b. Respiratory System
* Check for respiratory distress (fast, deep or laboured breathing)
* Listen to the chest for rales or other added sounds.

C. Cardiovascular
* Examine the rate, rhythm and volume of the pulse.
* Cold extremities or poor capillary refill at the tips of the
fingers (delay for >3 seconds).
* Check blood pressure
d. Abdomen
* Feel for the spleen and the liver

7.6 Differential Diagnosis:

 Meningitis- Patient may have a stiff neck.
 Encephalopathy- Repeated convulsions or deep coma.
 Diabetes Mellitus- Patient may be dehydrated, acidotic or in coma.
 Septicaemia- Usually very ill and toxic with warm extremities.
 Epilepsy- Usually no temperature and will have history of convulsions before.
 Acute renal failure from other causes- usually associated with reduced or no
urine output
 Viral hemorrhagic fevers- usually associated with jaundice and bleeding
tendency

7.7 Laboratory Investigations:

Laboratory investigation in aimed at confirming diagnosis, assess severity of

National Guidelines for Diagnosis and Treatment of Malaria 40

 disease and exclude other possible causes of severe disease.
Recommended tests include:
* Blood smear for malaria parasites
* Haematocrit (PCV)/Haemoglobin
* Blood sugar level
* Lumbar puncture in unconscious patients.
* Urinalysis for:-
Sugar (to exclude diabetes)
Proteins (exclude pregnancy-induced hypertension)

Notes about Diagnosis of Severe malaria:

 High index of suspicion in patients with fever and any of the

features discussed above.

 Absence of fever does not exclude a diagnosis of severe malaria.

 Microscopic diagnosis should not delay antimalarial treatment

if there is a clinical suspicion of severe malaria, with-holding
treatment may be fatal.

 Patients' progress should be monitored and management

changed as deemed necessary.

National Guidelines for Diagnosis and Treatment of Malaria 41

 7.8 Treatment
Severe malaria is a medical emergency requiring in-patient care. Deaths
from severe malaria can result either from direct effect of the disease or
the complications. The provider should attend to the immediate threats to
life first.

7.8.1 Life threatening emergencies

Coma or unconscious patient

 Ensure airway is patent; gentle suction of nostrils and the oro-
pharynx.
 Make sure the patient is breathing.
 Nurse the patient lying on the side or with the head sideways.
 Insert a naso-gastric tube (NGT).
 Establish an intravenous line. It will be necessary for giving drugs
and fluids.
 Correct hypoglycaemia:
Children: 0.5 ml/kg of 50% dextrose diluted to 10-15%.
Adults: 25 ml of 50%dextrose.
-Where intravenous access is not possible, give dextrose or
any sugar solution through the naso-gastric tube.

Convulsions
 Ensure patent airway and that the patient is breathing.
 Correct hypoglycaemia or control temperature.
 In children give rectal diazepam 0.5 mg/kg or IM paraldehyde 0.1
ml/kg. If convulsions continue, give IM phenobarbitone 10-15
mg/kg.
 In adults give 10 mg diazepam IV.

Severe dehydration or shock

 Give 20-30 ml/kg of normal saline and reassess the patient within
30 minutes to decide on the next fluid requirement according to

National Guidelines for Diagnosis and Treatment of Malaria 42

 the degree of dehydration.
 After correction of the fluid deficit it is important to reduce the
maintenance fluid to two thirds of the required volume when the
patient is well hydrated.

Severe Anaemia
 Give urgent blood transfusion to patients with severe
pallor/anaemia in heart failure. The blood must be screened to
ensure that it is HIV, Hepatitis B and C negative.
 Use packed cells (10 ml/kg in children) or whole blood (plus
frusemide).
 Where blood is not available, give pre-referral treatment and refer
urgently to a health facility with blood transfusion services.

7.8.2 Specific Antimalarial Treatment

Treatment Objectives
The primary objective of antimalarial treatment in severe malaria is to
prevent the patient from dying. The secondary objectives are
prevention of disabilities and recrudescence. The antimalaria

medicines recommended for the treatment of severe malaria in Nigeria

is Intravenous or intramuscular Artesunate. Where this is not readily
available, intravenous or intramuscular quinine, intramuscular
artemether can be used as alternative.

i. Artesunate
Recommended Dosages:
Give 2.4 mg/kg body weight IV or IM stat, repeat after 12 hours and 24
hours, then once daily for 6 days. However once patient regains
consciousness and can take orally, discontinue parenteral therapy and
commence full course of recommended ACT.
ii. Quinine

National Guidelines for Diagnosis and Treatment of Malaria 43

 It is administered by either IV or IM route, depending on the availability of
infusion facilities.
Recommended dosage:
Intravenous quinine

Children:
Give 20 mg/kg of Quinine dihydrochloride salt as loading dose diluted in
10 ml/kg of 4.3% dextrose in 0.18% saline or 5% dextrose over a period of 4
hours. Then 12 hours after the start of the loading dose, give 10 mg salt /kg
infusion over 4 hours every 8 hours until when patient is able to take orally.
Change to quinine tablets 10 mg/kg 8 hourly to complete a total of 7 days
treatment OR give a full course of recommended ACT.

Adults:
Quinine dihydrochloride 20 mg/kg of salt to a maximum of 1.2gm (loading
dose) diluted in 10 ml/kg isotonic fluid by intravenous infusion over 4
hours then, 8 hours after the start of the loading dose, give 10 mg/kg salt
to a maximum of 600 mg over 4 hours every 8hours patient is able to take
orally.
Then give a full dose of recommended ACT.

NOTE:
 If intravenous quinine is required for over 48 hours, reduce the dose to
5-7mg/kg to avoid toxicity. A practical way of doing this is to reduce the
dosing frequency to every 12 hours
 If there is a history of prior administration of quinine or mefloquine in
appropriate doses in the last 24 hours do not use loading dose.

Intramuscular Quinine:
Where intravenous access is not possible give quinine dihydrochloride
intramuscularly at a dosage of 20 mg/kg salt (loading dose), diluted to
60mg/ml, and continue with a maintenance dose of 10mg/kg 8hourly
until patient is able to take orally.

National Guidelines for Diagnosis and Treatment of Malaria 44

 Thereafter change to oral quinine at 10 mg/kg 8 hourly to complete a 7-
day treatment OR give a full dose of recommended ACT.
Quinine comes in highly concentrated salt (2ml ampoule containing
600mg quinine dihydrochloride). It is recommended that quinine be
diluted to 60 - 100mg/ml before administering intramuscularly.
To achieve 60mg/ml concentration, add 4mls of sterile water to 1ml of
quinine salt to make up to 5mls.

NOTE: Intramuscular injections should be given with sterile precautions

into the anterior or lateral thigh, NOT THE GLUTEAL REGION.

Quinine in pregnancy:
Quinine is administered as 10mg/kg body weight orally to a
maximum dose of 600mg 8 hourly, for 7 days.

Quinine is safe in pregnancy and it does not cause abortion or

premature delivery when given in normal therapeutic dose,
rather it is the malaria that causes these complications.

Treatment of severe malaria in pregnancy

First Trimester:
Current body of evidence is not conclusive on the safety of artemisinin
derivatives in the first trimester. However, the risk of death from severe
malaria far outweighs the potential risk of artesunate to the foetus,
therefore parenteral Artesunate can be used for treating severe malaria
during pregnancy. The use of Quinine is safe during the first trimester of
pregnancy.

National Guidelines for Diagnosis and Treatment of Malaria 45

 Second and Third trimesters:
The treatment of severe malaria in these periods of pregnancy is as
recommended for all adults.

7.8.3 Supportive Treatment

High temperature
 Give paracetamol (rectal) if temperature is >38.5 o C, in
children, also tepid sponge (wipe the body with towel soaked
in lukewarm water), avoid over -clothing.
Pulmonary oedema
 Prop up the patient at an angle of 45 degrees, give oxygen and
frusemide 2-4 mg/kg IV, stop intravenous fluids and exclude
other causes of pulmonary oedema. .
Renal failure
 Give fluids if patient is dehydrated 20 ml/kg of normal saline
and challenge with frusemide 1-2 mg/kg.
 Pass a urinary catheter to monitor urinary output.
 If patient does not pass urine within the next 24 hours refer for
peritoneal or haemodialysis.
 Exclude pre-renal causes
Profuse bleeding
 Transfuse with screened fresh whole blood, give pre-referral
treatment and refer urgently.
Other possible treatments:-
 1
 If meningitis is suspected, and cannot be immediately excluded by a
lumbar puncture, appropriate antibiotics should be given.
 Other severe diseases should be treated accordingly.

7.8.4 Treatments not recommended:

The following drugs have no role in the treatment of severe malaria.
 Corticosteroids and other anti-inflammatory agents
 Agents used for cerebral oedema e.g. Urea

National Guidelines for Diagnosis and Treatment of Malaria 46

  Adrenaline
 Heparin

8.0 NURSING AND QUALITY OF CARE

Severe malaria is a serious condition and the clinicians and nurses should
closely monitor patients. Therefore nursing care should include all the
following:-
1. Monitor vital signs
1. Pulse
2. Temperature
3. Respiratory rate
4. Blood pressure
These should be monitored at least every 6 hours but may be more
frequent at the initial stages.

2. Monitor input and output

A strict 24-hour input / output chart should be kept in all patients
with severe malaria. Examine regularly for signs of dehydration or
fluid overload.

3. Monitoring unconscious patient

Unconscious or comatose patients need close monitoring of all
vital signs more regularly to assess their progress. Monitor the
level of consciousness at least every 6 hours. Patients should be
turned in bed regularly to avoid bedsores.

4. Drug chart
A drug chart where all drugs given are recorded should be kept and
should include dose given, time given and number of times a day.

5. Pregnant women
They should be monitored closely ensuring the well being of the

National Guidelines for Diagnosis and Treatment of Malaria 47

 foetus and preventing the development of maternal
hypoglycaemia. Watch out for signs of severe anaemia and
pulmonary oedema.

Laboratory monitoring

5. Monitor the parasitaemia

Do blood smears daily. If high after 2-3 days, review adequacy of
the medicine dosages.

7. Monitor blood glucose

Do blood glucose level or maintain with dextrose containing infusion

8. Monitor Haemoglobin/haematocrit

Assessment of recovery
When the patient recovers, assess for possible residual problems of the
disease or treatment.
 Assess the ability of the patient to do what he/she was able to do
before the illness.
 Assess vision and hearing by asking whether they can see or hear; for
children use objects or noisy rattles respectively.
 Organize for follow up of the patient.
 Management of residual disability might require a multi-disciplinary
approach.

9.0 PRE-REFERRAL TREATMENT

The risk of death for severe malaria is greatest in the first 24 hours. To
survive, a patient with severe illness must get access rapidly to a health
facility where parenteral treatment and other supportive care can be
given safely and as appropriate. The affected patient may die on the way
to hospital or be admitted with advanced disease and complications. It is

National Guidelines for Diagnosis and Treatment of Malaria 48

 recommended that the patients be treated with one of the following
recommended pre referral treatment. .
Intramuscular pre- referral treatment
 Artesunate 2.4mg/kg stat
 Quinine dihydrochloride at a dosage of 10 mg/kg salt diluted to
60mg/ml intramuscularly at the anterolateral aspect of the thigh
given at divided sites.

Artesunate suppositories
The appropriate single dose of Artesunate suppositories should be
administered rectally as soon as the presumptive diagnosis of malaria is
made. In the event that an Artesunate suppository is expelled from the
rectum within 30 minutes of insertion, a second suppository should be
inserted and, especially in young children, the buttocks should be held
together, or taped together, for 10 minutes to ensure retention of the
rectal dose of artesunate
Adults: One or more Artesunate Suppositories inserted in rectum as
indicated in Table below. Dose should be given once and followed as soon
as possible by definitive therapy for malaria.
Intra-rectal pre-referral treatment
Intra-rectal artemether at the dose of 10-40mg/kg body weight and intra-
rectal quinine at 12mg/kg body weight can also be used as alternative
based on availability. These should be administered with a syringe without
the needle

Dosage regimen for Artesunate suppositories in children

Weight (kg) Age Artesunate Dosage regimen (Single Dose)

<10 <12months 50mg One 50mg Suppository

10 - 19 1yr - 5yr months 100 mg One 100 mg Suppository
20 -29 6 - <10years 200 mg Two 100 mg Suppositoies
30 - 39 10 - 13 years 300 mg Three 100 mg Suppositories
> 40 >13 years 400 mg Four 100 mg Suppository

National Guidelines for Diagnosis and Treatment of Malaria 49

 Summary Box 3: Management of Severe Malaria

 Severe malaria is a medical emergency. Full doses of parenteral

antimalarial treatment should be commenced without delay with
an effective antimalaria first available after
rapid clinical assessment and confirmation of diagnosis.
 Artesunate 2.4mg/kg IV or IM given at time 0, 12 and 24 hours, then
once daily is the recommended treatment.
 Quinine is an acceptable alternative if parenteral artesunate is not
available. Quinine 20mg salt/kg IV or divided IM injection, then
10mg/kg every 8hrs, infusion rate should not exceed 5mg salt/kg per
hour.
 IM artemether 3.2mg/kg given on admission, then 1.6mg/kg per day
should be used if none of the alternatives are available as its
absorption may be erratic.
 Give parenteral antimalarial medicines in the treatment of severe
malaria for a minimum of 24hours, once started (irrespective of the
patient's ability to tolerate oral medications earlier) and thereafter
complete treatment by giving a complete course of ACT.

10.0 PREVENTIVE TREAMENTS AND CHEMOPROPHYLAXIS

10.1 Intermittent Preventive Treatment
Pregnant women have higher risk of malaria than same women before
pregnancy and other non-pregnant females and adults. The high
prevalence of malaria during pregnancy has been associated with
pregnancy-associated immune changes and the extensive proliferation of
the parasites within the placenta.

In high transmission areas such as Nigeria, malaria is usually

asymptomatic during pregnancy. The use of Intermittent Preventive

National Guidelines for Diagnosis and Treatment of Malaria 50

 Treatment (IPT) with Sulphadoxine-Pyrimethamine has been shown to be
effective in preventing several malaria related complications during
pregnancy. IPT is given as a one-dose of a full course treatment after
Quickening as Directly Observed Therapy (DOT) and the second dose is
given not earlier than one month after the first dose. A single dose is three
tablets of SP each containing Sulphadoxine (500 mg) + Pyrimethamine
(25 mg).

Pregnant women who are HIV positive and are on Co-trimoxazole

chemoprophylaxis, should not receive IPT. This is because of their
increased risk to the adverse effects of the Sulphonamides. Encourage
them to use other preventive measures such as regular use of Long Lasting
Insecticide Nets (LLINs).

10.2 Malaria Chemoprophylaxis

Malaria chemoprophylaxis is not recommended for individuals living in
areas of intense transmission, however, people with sickle cell anaemia
and non immune visitors are expected to be on regular chemoprophylaxis.
There is however no effective antimalarial presently available for long
term chemoprophylaxis. Until such becomes available, these risk group
should be targeted with other preventive interventions e.g. ITNs and also
ensuring that they have ready access to effective case management.

10.3 Non immune Visitors

The recommended chemoprophylaxis for non immune visitors will be as
available in the visitor's country of origin. The following options are
recommended for use in Nigeria; Mefloquine, and atovaquone-
proguanil. Doses should be taken prior to arrival in Nigeria and
continued during the stay and following departure from the country.

Mefloquine
5mg base per kg weekly, giving an adult dose of 250mg of base per week. It
should be started 2-3 weeks prior to arrival and two to three weeks after
departure.

National Guidelines for Diagnosis and Treatment of Malaria 51

 Atovaquone-Proguanil
Exist as a fixed dose combination. Commence 1-2 days before travel and
continue throughout the stay and 7 days after return.

Age Dosage

11 - 21kg Paediatric preparation (25mg/

62.5mg) daily

21 - 31kg 2 tablets daily

31 - 40kg 3 tablets daily

Adult and children over 40kg Adult preparation 1 tablet (100/

250mg) daily

11.0 ANTIMALARIAL DRUG RESISTANCE

Antimalarial drug resistance is defined as the ability of a parasite strain to

survive and/or multiply despite the proper administration and
absorption of an antimalarial medicines in the dose normally
recommended.

It has resulted in a global resurgence of malaria and it is a major threat to

malaria control. Widespread and indiscriminate use of antimalarial drugs
places a strong selective pressure on malaria parasites to evolve
mechanisms of resistance. Prevention of antimalarial drug resistance is
one of the main goals of these antimalarial treatment recommendations.
Resistance can be prevented by combining antimalarial medicines with
different mechanisms of action, and ensuring very high cure rates
through full adherence to correct dose regimens.

National Guidelines for Diagnosis and Treatment of Malaria 52

 11.1 Antimalarial drug resistance in Nigeria
Appreciable resistance of P. falciparum has developed against
monotherapeutic agents previously used in Nigeria, such as chloroquine
and Sulphadoxine Pyrimethamine. This is summarized below.

% Sensitivity
120

100

80

60

40

20

0
1980 1981 1984 1988 1989 1990 1991 1995 1997 2002
Year

Chloroquine efficacy estimated at various drug therapeutic testing sites in

Nigeria between 1980 and 2002 showing the decline in malaria parasite
sensitivity to chloroquine

{Source: National Drug therapeutic Efficacy Trials (DTET)}

It should be noted that anti-malarial medicines resistance is not

necessarily the same as malaria treatment failure, which is defined as the

National Guidelines for Diagnosis and Treatment of Malaria 53

 failure to clear malaria parasitemia and/or resolve clinical symptoms
despite the administration of antimalaria medicines. While drug resistance
may lead to treatment failure, not all treatment failures are caused by drug
resistance. Other causes of treatment failure are
 Incorrect dosing
 Problems of treatment compliance
 Poor drug quality
 Interactions with other drugs
 Compromised drug absorption
 Mis-diagnosis of the patient

11.2 Impact of resistance

The impact of antimalarial drug resistance is insidious initially. The initial
symptoms of the infection resolve and the patient is better for weeks.
When symptoms recur, usually more than two weeks later, anaemia has
worsened, and there is a greater probability of carrying gametocytes
(which in turn carry the resistance genes) and transmitting malaria. But
the patient and the doctor or dispenser may interpret this as a newly
acquired infection. At this stage unless drug trials are conducted,
resistance may be unrecognised.

As resistance worsens the interval between primary infection and

recrudescence shortens, until eventually the symptoms fail to resolve. At
this stage mortality begins to rise. Antimalarial medicine resistance
accounts for our failure to control malaria in many areas of the tropical
world and the consequent increasing global mortality. But resistance can
be prevented, or its onset slowed considerably with judicial use of the
limited number of effective drugs currently available to treat malaria.

12.0 BRIEFS ON PHARMACOLOGY OF ANTIMALARIAL

DRUGS
Chloroquine
Chloroquine resistance is now widespread globally. It is no longer

National Guidelines for Diagnosis and Treatment of Malaria 54

 recommended either alone or as a combination partner for the
treatment of uncomplicated falciparum malaria.

Amodiaquine
Amodiaquine is a Mannich base 4 amino-quinoline that interferes with
parasite heam detoxification. It is more effective than chloroquine in both
chloroquine sensitive and P.falciparum infections. However, there is
cross-resistance between chloroquine and amodiaquine.

It is available as tablets containing 200mg of amodiaquine base as the

hydrochloride and as 153.1 mg base as chlorohydrate. It is readily
absorbed in the GIT and rapidly converted in the liver to the active
metabolite, desethylamodiaquine. Desethylamodiaquine is responsible
for all the antimalaria effect. Adverse effect of amodiaquine includes
pruritis and when used for prophylaxis it causes agranulocytosis.
Amodiaquine is recommended as a partner drug in artemisinin based
combination therapy.

Sulphadoxine-Pyrimethamine
Sulphadoxine is a slowly eliminated Sulphonamide. It is used in a fixed
dose combination of 20 parts Sulphadoxine with 1 part Pyrimethamine
given orally or intramuscularly. It is available as tablet containing 500mg
Sulphadoxine and 25mg Pyrimethamine, and in ampoules containing
similar concentration of the 2 components for intramuscular use.

The medicine is no longer recommended for the treatment of malaria in

Nigeria. However, it has been proven to be effective for use for
Intermittent Preventive Treatment during pregnancy.

Sulphadoxine is readily absorbed from the GIT. It is widely distributed in

body tissues and fluids and crosses the placental into foetal circulation. It
is also readily detectable in breast milk. It is excreted predominantly as
the unchanged drug.

National Guidelines for Diagnosis and Treatment of Malaria 55

 Adverse effect includes nausea vomiting and diarrhoea. Hypersensitivity
reaction may occur as well as photosensitivity and a variety of
dermatological adverse reaction. It may also cause a crystaluria and
interstitial nephritis. Pyrimethamine is a di-amino pyrimidine that is also
used in the treatment of toxoplasmosis and pneumocystic carini
pneumonia. Like sulphadoxine, it is rapidly absorbed from the GIT.
Prolonged administration may cause depression of haematopoiesis due
to interference with folate metabolism

Quinine
It is an alkaloid derived from the bark of cinchona tree. It is an isomer of
quinidine. Like other structurally related drugs, it is effective against
matured trophozoites of P.falciparum matured sexual forms of
P.falciparum, vivax and malariae. It is available as both tablets and
injectable solutions. It is rapidly and almost absorbed from the GIT and
also after IM in severe malaria. It is widely distributed throughout the
body tissues, and fluids including CSF and, breast milk. Toxicity includes
mild form of tinnitus, impaired high tuned hearing, headache, nausea,
dizziness, vomiting, abdominal pain, diarrhoea and vertigo.

Hypersensitivity reaction may also occur. Intravascular haemolysis that

may progress to life threatening haemolytic uremic syndrome can also
occur. Thrombocytopeania and haemolytic anaemia. Other adverse effect
includes cardiac rhythm disturbances, hypotension and hypoglycaemia

Artemisinin and its derivatives

Artemisinin and its derivatives, artemether, dihydro-artemisinin,
artesunate and artemotil are sesquiterpenelactones. These drugs are
potent and rapidly acting blood schizonticides active against all
plasmodium species. These medicines kill all stages of young rings to
schizonts and young gametocytes.

Artemisinin itself is now less frequently used compared to its derivatives;

dihydro-artemisinin, artemether, artesunate and artemotil. It is

National Guidelines for Diagnosis and Treatment of Malaria 56

 converted to dihydro-artemisinin.

Artesunate is a sodium salt of the hemisuccinate ester of artemisinin. It is

soluble in water but has poor stability in aqueous solution at neutral or
acidic pH. In the injectable form, artesuric acid is drawn up in sodium
bicarbonate to form sodium artesunate immediately before injection. It
is available as tablet, ampoules for IM or IV, rectal capsules, and as co-
formulation with amodiaquine. It is rapidly absorbed after oral, rectal and
IM administration and is almost entirely converted to dihydro-
artemisinin, the active metabolite. It is rapidly eliminated from the body.

Artemether is methyl ether of dihydro-artemisinin. It is more lipid soluble

than artemisinin or artesunate. It can be given as an oil based
intramuscular injection or orally, and as co-formulation with
lumefantrine. Absorption after oral administration is rapid. After IM
administration, absorption is variable particularly after administration in
children with poor peripheral perfusion. It is metabolized to dihydro-
artemisinin, the active metabolite.

In general, artemisinin and its related derivatives are well tolerated.

These drugs in general are less toxic than other currently available
antimalarial medicines. Mild GIT disturbances, dizziness, elevated liver
enzymes and minor ECG abnormalities and reticulo-cytopaenias have
been reported after the use of these drugs. Potentially, serious adverse
effects are related to Type I hypersensitivity reactions. Neurotoxicity has
been reported in experimental animals and largely has not been found in
humans. Currently, clinical resistance has not been reported to this class
of antimalaria.

Lumefantrine is an aryl amino alcohol. It is structurally related to

halofantrine. It is highly effective against P.falciparum. It is available as
oral preparation as co-formulation with artemether. Following oral
administration, bioavailability is variable but can be improved by co

National Guidelines for Diagnosis and Treatment of Malaria 57

 administration with fatty foods. Toxicity includes nausea, abdominal
discomfort, headache and dizziness. It does not significantly prolong the
ECG Q-T interval

National Guidelines for Diagnosis and Treatment of Malaria 58

 ANNEXURES

ANNEX 1

QUALITY ASSURANCE FOR MALARIA DIAGNOSIS WITH MICROSCOPY

The quality assurance (QA) of a malaria laboratory or diagnostic programme
is a system designed to continuously and systematically improve the
efficiency, cost-effectiveness and accuracy of test results. It is critical that QA
ensure:

 the clinical teams have full confidence in the laboratory results

 the diagnostic results are of benefit to the patient and the
community.

These demands can only be met through a commitment to QA that ensures

the microscopic services are staffed by competent and motivated staff
supported by both effective training and supervision and a logistics system
that provides an adequate and continual supply of quality reagents and
essential equipment which are maintained in working order.

The principles and concepts of QA for microscopic diagnosis of malaria are

similar to those for microscopic diagnosis of other communicable diseases,
such as other protozoan diseases, tuberculosis and helminth infections. This
provides a potential for the integration of laboratory services where it is
feasible and cost-effective.

National Guidelines for Diagnosis and Treatment of Malaria 59

 ANNEX 2 SUMMARY OF CHECK-LIST FOR INTERNAL QUALITY
ASSURANCE FOR MALARIA MICROSCOPY

Category Check List Questions Yes No

Laboratory There is sufficient working surface for

Design each member of the laboratory staff.
The electric microscope(s) are not located
directly in front of a window but face a
blank wall.
The laboratory has access to a clean
water supply.
There is hand washing facilities.
There is good ambient lighting at all
times (including cloudy weather).
There is an adequate electrical supply for
the microscope(s).

There is adequate storage space for

reagents, equipment, and storage of slides.
There is a safe waste management system.
Laboratory chairs and/or stools are
suitable for microscopy.
Quality of the The microscope(s) is binocular and
Microscope electrically powered.
The microscope lamp(s) has sufficient
power to provide good illumination at
small aperture settings.

The light source can be centred.

National Guidelines for Diagnosis and Treatment of Malaria 60

 Category Check List Questions Yes No

The microscope(s) have Plan C x 100

objectives.
Blood smears are able to be brought
into sharp focus x 100 oil immersion
magnification.
The stage movement mechanism is
precise and stable.
Microscope Microscope slides are clean.
Slides Microscope slides are not oily to the
touch.
Microscope slides do not have scratches
or surface aberrations.
Microscope slides do not give a blue
background colouration (microscopically
at x100) after staining.
Microscope slides do not have fungal
contamination.
Slides are protected against fungal
contamination (in high humidity settings).
Methanol Methanol is AR grade.
Methanol is supplied to the laboratory
is in the original sealed container as
supplied by the manufacturer, and is not
repackaged by the supplier.
Methanol is not oily (test place some
methanol on the fingers, it should not
be sticky).

National Guidelines for Diagnosis and Treatment of Malaria 61

 Category Check List Questions Yes No

There is no deformation or blistering of

red blood cells in the thin blood film
(this is caused by poor quality methanol).
The methanol used for slide fixing is
stored in moisture-proof containers.
Giemsa Stain Only stain prepared from high quality
Giemsa powder is used.
Commercial Giemsa stain is supplied to
the laboratory in the original sealed.
The stain is within the manufacturer's
expiry date.
The laboratory has a Stain QC Register
recording the batch number and expiry
date of supplies received the QC results
on each batch (staining time, staining
quality, and optimal pH of use) and any
problems encountered.
Stock stain is stored in a dark glass bottle
tightly sealed.
Stock stain is not stored in direct sunlight
or near a heat source.
The stock stain used by the laboratory
was prepared less than two years ago.
Stained blood films do not contain stain
precipitate.
Diluted Giemsa Stock stain is always diluted in buffer to
stain the correct pH.

National Guidelines for Diagnosis and Treatment of Malaria 62

 Category Check List Questions Yes No

The diluted stain contains no stain

precipitate.
The surface of the diluted stain does not
have an oily appearance. For horizontal
slide staining (using a staining rack) this
is best observed after the stain has been
added to the slides. This effect can be
caused by poor quality methanol used to
prepare Giemsa stain from powder.
Diluted stain is always discarded within
15 minutes of preparation.
Thick blood >95% of thick films have the correct
films thickness. It should be just possible to
read newsprint through the thick film
while it is still wet.
There is flaking in the centre of the
smear (a hole in the centre of the thick
film) in <2% of the thick films.
100% of the thick films are correctly stained.
None of the thick films contain stain
precipitate contamination.
There a protocol for the preparation of
thick films of the correct thickness from
patients with severe anaemia.
Slide warmers may be used with caution
in high humidity settings.
Thin blood >95% of the thin films have a smooth
films semi-circular tail.

National Guidelines for Diagnosis and Treatment of Malaria 63

 Category Check List Questions Yes No

In >95% of the thin films the red cells are

just touching and not overlapping in
approximately 20%30% of the film (the
reading area).
No thin films have water damage
(retractile artefacts inside the red cells).
Thin films are fixed immediately after
drying.
Staining The laboratory has a pH meter that
reads to 2 decimal places.
The pH meter is calibrated with
calibration buffers according to
manufacturer's directions.
pH adjusted buffer always used to
prepare diluted Giemsa.
The pH of the buffer is calibrated for
each batch of Giemsa.
Slides are always washed in water of the
same pH as the buffer used for Giemsa
dilution.
The diluted Giemsa is always prepared
in a clean measuring cylinder.
There is an absolute rule that the diluted
Giemsa stain is discarded in <15 minutes
after preparation.
The trophozoite chromatin stains red to
“rusty red”.
The trophozoite cytoplasm stains blue
to strong blue.

National Guidelines for Diagnosis and Treatment of Malaria 64

 Category Check List Questions Yes No
The thick film background is stained light
pink to grey.
The thick film background is stained light
pink to grey.
The red cells in the thin film are stained
pink.
The nuclear lobes of the polymorphs are
stained significantly darker than the
cytoplasm.
Slides are always washed from the thin
film end.
All slides are washed gently by a
technique that “floats”' the stain off with
minimal without disturbing the thick film.
Laboratory staff who perform staining
have protective clothing to protect their
personal clothing.
Counting The laboratory reports the actual number
of trophozoites when required against
500 (200) WBC.

Slide Reading All laboratory staff who report malaria

Times examination results read a minimum of
10 thick blood films each month.
Laboratory staff always read a minimum
of 100 fields before reporting a film as
negative.

National Guidelines for Diagnosis and Treatment of Malaria 65

 Category Check List Questions Yes No

There is no pressure on microscopists to

read slides more quickly than the
standard reading time (such as end of
day, “urgent cases”).

Is there a laboratory protocol that

ensures that microscopists do not
continuously read malaria slides for
more than 3 hours without a 30 minute
break?
Species Thin films are available for species
identification identification where a mixed infection
is suspected or species identification is
unclear on the thick film.

National Guidelines for Diagnosis and Treatment of Malaria 66

 ANNEX 3 QUALITY CONTROL IN LABORATORY DIAGNOSIS OF
MALARIA

The main focus of QC is on reproducibility (precision) of results. The

programme is used within the laboratory for checking its own
performance. Quality control (QC) is the responsibility of the laboratory
chief but all laboratory personnel must be involved.

Standard operating procedures (SOPs) need to be developed, depending

on the type of analyses carried out at each level of the health services so
that tests can be performed in an acceptable standard way. The SOPs
should state clearly the minimum QC for each method or test. By
standardizing test procedures, it allows easier clinical and epidemiological
interpretation of the results. Troubleshooting guides for equipment,
reagents and methods would be useful additions to the more isolate
laboratories where “instant” help is not available.

With such a multitude of steps involved in processing of a specimen, errors

can occur at any stage. Laboratory management needs to be aware where
errors can happen to reduce the possibility of their occurrence. Therefore,
all stages from the preparation through to the examination must be
monitored. Below quality controls issues will focus on microscopy and
rapid tests. The general points are equally pertinent for all techniques.

ANNEX 4 BLOOD SMEARS FOR MICROSCOPY

Blood smears-preparation and staining

Blood should be taken from a finger prick, when possible. Blood collected
in anticoagulant causes morphological changes to the parasite if left too
long before examination. Anticoagulant also causes thick smears not to
stick well onto the slide.

The specimen should be clearly labelled and be accompanied with

National Guidelines for Diagnosis and Treatment of Malaria 67

 correctly completed form (clinical request or field). A thick film exposed to
alcohol or placed in a hot oven to “quickly” dry the blood renders the film
unreadable as the erythrocytes cannot dehaemoglobinize. If blood films
in high temperature environments are not stained within a couple of days,
the films suffer auto fixation.

Smears stored in humid and hot conditions facilitate the growth of fungus
and bacteria. Similarly, dusty conditions cause the formation of deposits
making the smear unreadable or the deposits might be confused for
parasites leading to a false result. Smears, both stained and unstained
must be protected from the voracious appetites of cockroaches, flies and
ants and should where possible be stored in slide boxes.

The smears need to be well stained to facilitate the reading and if using
Giemsa, species determination and accurate parasite counts. A stain can
either be commercial or house made. It is imperative that each batch be
checked by comparing batches of new staining solution with the old on
the same group of thick and thin films. House made stain is not necessarily
reliable and requires high quality reagents. Standardized forms must be
draw up that indicate the stain, the lot number, the producer and the
dilutions used to determine concentration and staining time and the
result.
Dilution/buffer solutions also need to be controlled. With Giemsa stain
often used, well water is the normal choice of diluents as the supply of
reagents to the periphery is poor. Unfiltered stain and metallic scum of the
staining solution leaves as precipitate on the thick film which are often
confused with parasites. Working solution should be prepared daily to
avoid de-naturation and even changed during the day depending on the
workload.

Maintenance of a microscope is very important. It is an expensive piece of

equipment that in poor condition cannot aid the microscopist to read the
slide. Humid atmosphere can cause the growth of fungus especially on the

National Guidelines for Diagnosis and Treatment of Malaria 68

 lens. Other problems are the bad alignment of the microscope, immersion
oil not wiped from the objective and condenser leaving a coating.
Other materials to monitor are the slides and lancets, lancets should be
sterile and preferably single use and slide should be without oily residue.

Recommended procedure notes

 Make a thick and a thin film on a clean microscope slide
 Stain with Giemsa method (See box below)
 Examine under a high power objective starting with thick and then
thin films. The thick film is used to establish the presence of
malaria parasites, while the thin film is for parasite speciation
 Report type of parasite(s) seen, developmental stage and parasite
count as parasite/200WBCs or parasite/µl blood
 Ensure you always use relevant standard operating procedure
(SOPs) in all processes
 If blood slide is negative, it is recommended that further
investigations for the cause of disease including repeating blood
slide after 24 hours should be carried out. If the repeat slide is
positive, treat accordingly.

Rapid Staining Method

1. Fix the thin film by dabbing it with a pad of cotton wool

dampened with methanol or by briefly dipping the film into
methanol.
2. Avoid contact between the thick film and methanol, as
methanol and its vapours quickly fix the thick film, and make
it not to stain well.
3. Using a test tube or a small container to hold the prepared
stain, make up a 10% solution of Giemsa in the buffered water
by mixing three drops of Giemsa from the stock solution, using
the Pasteur pipette, with 1 ml of buffered water. Each slide
needs approximately 3 ml of stain to cover it.

National Guidelines for Diagnosis and Treatment of Malaria 69

 4. Depending on whether you are using a staining tray, plate or
rack, place the slides to be stained face down on the curved
staining tray or face upwards on the plate or rack tray until
each slide is covered with stain, or gently pour the stain onto
the slides lying face upwards on the plate or rack.
5. Stain the films for 810 min. Experience with the stain you are
using will help you to decide the exact time needed for good
staining.
6. Gently wash the stain from the slide by adding drops of clean
water. Do not pour the stain directly off the slides, or the
metallic-green surface scum will stick to the film, spoiling it for
microscopy.
7. When the stain has been washed away, place the slides in the
drying rack, film side downwards, to drain and dry. Ensure that
thick films do not scrape the edge of the rack.

Malaria Parasite Density Determination

This is a practical method of reasonable and acceptable accuracy. The
number of parasites per microlitre of blood in a thick film is counted in
relation to a standard number of leukocytes (8000). Although there are
variations in the number of leukocytes between healthy individuals and
even greater variations between individuals in ill health, this standard
allows for reasonable comparisons.

Step 1
(a) In routine practice, using a x100 oil immersion objective and an
eyepiece with a field number of 18, parasite quantitation is performed
against 200 or 500 WBCs.
(b) If, after counting 200 WBC, 100 or more parasites are found, record the
results in terms of number of parasites/200 WBC.
(c) If less than 100 parasites are found after counting 200 WBCs, parasite

National Guidelines for Diagnosis and Treatment of Malaria 70

 quantification should be continued until 500 WBCs are counted. All
parasites in the final field are counted even if the count exceeds 500 WBCs.

Step 2
To determine parasite density, the parasite count is adjusted against the
true WCC where available. If unavailable, the common practice is to
assume a WCC of 8000/µl. In each case, the number of parasites relative to
the leukocyte count can be converted to
parasites per microlitre of blood by the simple mathematical formula:
Number of parasites x 8,000 = parasites per microlitre
Number of leukocytes

In effect, this means that if 200 leukocytes are counted, the number of
parasites is multiplied by 40 and if 500 leukocytes are counted the number
of parasites is multiplied by 16.

Note: It is normal practice to count all the species present and to count
and record separately the gametocytes of P. falciparum and the asexual
parasites. This is particularly important when monitoring the response to
schizontocidal drugs, which would not be expected to have any effects on
the gametocytes.

Re-examination of Blood Slides

Cross- checking in malaria diagnosis is part of supervision activities and
involves the re examination of a proportion of positive and negatives
slides from each laboratory. Cross checking of slides provides the
supervisor with information about the accuracy of the examination by
scientist and criteria for improvement if required. An idea about the
quality of the preparation can also be ascertained.

Measurement of quality

Assessment can be made on three different areas.

National Guidelines for Diagnosis and Treatment of Malaria 71

 These areas are;
 Positive and negative readings
 Intensity of infection
 Species identification

Intensity of infection
Before now, only positive and negative results have been discussed. The
results from the majority of routine malaria diagnosis tests have been
given in a semi-quantitative fashion (plus system) but in epidemiological
studies, parasite density is always applied. The frequency of agreement
and disagreement between laboratories can be calculated by using kappa
statistics.

For semi-quantitative results, which are subjective, a two- step grading of

positive could suffice those slides that have parasites in every field and
those that have less than one parasite per field. This would certainly be
sufficient to determine those failing to detect low parasitaemia from
those failing to detect parasites at all.

Species identification
Misdiagnosis of the species can be addressed. This is particularly
important where there is high degree of chloroquine resistance of both P.
falciparum and P. vivax. The type of species determined the treatment
that is given. In Nigeria, where over 90% of single infections are due to P.
falciparum, non- recognition of the other species would cause mis-
readings of about 10% of the slides, which is a considerable proportion of
error.

ANNEX 5: ISSUES WITH RDTS IN THE FIELD

• Detects antigen, not parasites
• Parasite load is not quantified
• HRP-2 RDTs could remain positive even after the patient has taken
ACTs and the antigen could remain in the blood for over 2 weeks

National Guidelines for Diagnosis and Treatment of Malaria 72

 • Occasionally, test could be negative in the presence of parasites
• Degraded by excessive heat and may not function properly
• Limited shelf life (18 24 months)

Accuracy is dependent on following the prescribed procedures:

Appropriate Storage of RDTs

• Determine a cool place in your facility for RDTs storage. Storage
temperature must never go beyond 35oC
• Keep RDTs in a cool place where drugs are stored
• Do not expose RDTs to direct sunlight
• Do not keep RDTs in a car parked in the sun (temperature may
sometimes rise beyond what RDTs can tolerate)
• Open a pack only when you are ready to use them
Just before and RDT is done
• Be ready to use the results to inform treatment
• Check that the RDT has not expired
• Read the instructions in order to do it well
• Put on latex gloves

Materials required before doing an RDT

An RDT kit contains the following:
• alcohol swab
• sterile lancet
• a blood transfer device
• Buffer solution
The following items must also be available:
• Watch or clock to use as a timer
• Marker to write patients' data on RDT
• Sharp container(s) for used lancets & blood transfer device
• Waste bin for used alcohol swabs, cotton wool, gloves etc

National Guidelines for Diagnosis and Treatment of Malaria 73

 Recommended Procedure notes

Note: It is pertinent to follow specific instructions on various RDT types

before use.

1. Wear your latex gloves

2. Open an RDT cassette and write the name of the patient and
date.
3. Swab patient's fourth finger (the left hand of a right handed
person) with methylated spirit and allow to dry (this will
ensure that the patient's blood collects and not spread
around the finger).
4. Take an unused lancet and prick the tip of the swabbed finger
and discard lancet in the sharps quickly (do not re-cap the
lancet).
5. Get the blood transfer device and collect the recommended
volume of blood
6. Dispense the blood in the well (allow the transfer device to
touch the pad in the well before releasing the content so that
the blood collected is deposited fully insufficient blood can
give a false result).
7. Dispose transfer immediately (do not leave on your table)
8. Put the recommended drops of buffer in the buffer well
(ensure that the buffer container faces the well vertically, a
little above the RDT cassette do not allow buffer to spill on
the side of the well)
9. Note the time immediately by writing the start time on the
cassette. Also indicate the stop time by adding the
recommended time for the test. For
example, if you were to read the test result after 15 minutes,
add 15 minutes to the start time to get the stop time.
10. Interpret the result at the recommended time and not after
as this could give you a false result.

National Guidelines for Diagnosis and Treatment of Malaria 74

 ANNEX 6: PHARMACOVIGILANCE

Pharmacovigilance is the science and activities relating to the detection,

assessment, understanding and prevention of adverse drug reactions or
any other drug related problems such as drug abuse and misuse,
medication errors, lack of efficacy and counterfeits.

An Adverse Drug Reaction (ADR) is a response to a medicine which is

noxious (harmful) and unintended, and occurs at doses normally used in
man for prophylaxis (prevention), diagnosis or therapy (treatment) of
disease or the modification of physiological function

The recent medicine mishap in Nigeria has increased the need to ensure
the quality, safety and efficacy and the rational use of deployed medicines
hence it is mandatory for all levels of care to be involved in
Pharmacovigilance.

In all suspected cases of an adverse drug reaction, the Pharmacovigilance

form from NAFDAC should be completed at all levels of care. It is necessary
to complete all section of the adverse drug reaction form.

Completed ADR forms should be sent to the following:

- The National Pharmacovigilance Centre (NPC) NAFDAC

- Plot 2032 Olusegun Obansanjo Way, Wuse Zone 7, Abuja
- Through NAFDAC offices in the 36 states & FCT
- Reports can also be scanned & emailed to [email protected]
- By Telephone: 08086899571 or 07098211221

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National Guidelines for Diagnosis and Treatment of Malaria 76