1.
TUBERCULOSIS
2. TUBERCULOUS MENINGITIS
3. TUBERCULOMA
MD 3
Dr. Nyasatu
OUTLINE
● Introduction
● Pathophysiology
● Signs and symptoms
● Diagnosis
● Treatment
● Prevention
Definition
● Tuberculosis (TB) is an infectious disease primarily
affecting lung parenchyma caused by Mycobacterium
Tuberculosis.
● Pulmonary TB ( lungs affected) 80% of all cases.
● It may spread to any part of the body including meninges,
kidneys, bones and lymphnodes (Extrapulmonary TB)
SPREAD
● TB is spread from person to person through the air.
● Through small Mycobacterium tuberculosis-containing
aerosol droplets (typically, 1 to 5μm in diameter), which
are expectorated by coughing, sneezing, or
talking/singing.
Types
1. Pulmonary Tuberculosis
2. Avian Tuberculosis ( Mycobacterium avium of birds)
3. Bovine Tuberculosis (Mycobacterium bovis of cattle)
4. Miliary Tuberculosis / Disseminated Tuberculosis (Invade
the blood stream and spread to all body organs).
INCIDENCE OF TUBERCULOSIS
● By the end of 2019, approximately 10 million
people were affected with tuberculosis
worldwide. 5.6 million men, 3.2 million
women and 1.2 million children (WHO,
2020).
● Most TB cases South-East Asia (44%),
Africa (25%) and the Western Pacific (18%),
with smaller shares in the Eastern
Mediterranean (8.2%), the Americas (2.9%)
and Europe (2.5%).
● TB is the world’s second most common
cause of death from infectious disease after
HIV/AIDS. Source: WHO, Global Tuberculosis Report 2020.
Risk Factors
● Close contact with someone who has active TB
● Immuno compromised status
● Drug abuse and alcoholism
● Pre existing medical conditions (DM, CKD)
● Immigrants from countries with higher incidence of TB
● Occupation (Health care workers)
● Living in sub-standard conditions
Pathophysiology
● Initial infection or Primary infection
● Entry of micro-organism through droplet nuclei
● Bacteria is transmitted to aveoli through airways
● Deposition and multiplication of bacteria
● Bacilli are also transported to other parts of the body via blood
stream and phagocytosis by neutrophils and macrophages
Pathophysiology
● Mycobacterium
● Pulmonary alveoli
● Immune system had lodged in (Alveolar Macrophages)
● Detects presence of pathogen and engulph the bacteria
● Mycobacterium bacteria inhibits the macrophages
(phagosome+lysosome) to form phagolysosme and remains
protected inside the macrophages.
Pathophysiology
● Starts replication inside macrophages
● Primary infection occurs
● Cell mediated immunity gets activated, surrounds the cell to form
granuloma (3 weeks)
● Leads to necrosis of tissues at infection site (Terminus Gone Focus)
● Involve nearby lymph nodes (Cone Complex)
● Calcification of cone complex (Latent TB)
Clinical Manifestation
• Anorexia
• Fever
• Night sweats
• Fatigue
• Weight loss
• Cough for 2 weeks or more
• Hemoptysis Clinical features for Extra pulmonary
• Chest pain tuberculosis depends on the organ
affected.
• Pain and Inflammation.
Assessment and Diagnosis
• History Collection
• Physical Examination
DIAGNOSIS OF TUBERCULOSIS
1. MICROSCOPY.
AFB (Acid Fast Bacilli) microscopic examination of a diagnostic specimen, such as a
smear of expectorated sputum or of tissue (e.g., a lymph node biopsy).
Different types of microscopic examination include:
● Ziehl-Neelsen basic fuchsin dyes
● Auramine–rhodamine staining
● light-emitting diode (LED) fluorescence microscopes
2. NUCLEIC ACID AMPLIFICATION.
● Gene Xpert MTB/RIF assay- rapid confirmation of TB in persons with AFB positive
specimens.
● Also have utility for the diagnosis of AFB-negative pulmonary and extrapulmonary
TB.
● Has high specificity and sensitivity (approaching that of culture) is fully automated,
real-time nucleic acid amplification technology.
● simultaneously detect TB and rifampin resistance in <2 hrs.
3. MYCOBACTERIAL CULTURE.
It includes:
● Solid culture (4-8weeks).
Specimens may be inoculated onto egg- or agar-based medium (e.g., Löwenstein-
Jensen or Middlebrook 7H10) and incubated at 37°C (under 5% CO2 for Middlebrook
medium).
Because most species of mycobacteria, including M. tuberculosis, grow slowly, 4–8
weeks may be required before growth is detected.
• Liquid culture (2- 3 weeks).
4. IMAGING MODALITIES
● CHEST X-RAY.
The “classic” picture is that of upper-lobe disease with infiltrates and cavities.
Immunosuppressed patients, including those with HIV infection, may have “atypical”
findings on chest radiography—e.g., lower-zone infiltrates without cavity formation.
● CT - Better resolution
and helps in diagnosing
some forms of
extrapulmonary TB
(e.g., Pott’s disease)
● MRI is useful in the
diagnosis of intracranial
TB
Figure:CT scan showing a large cavity in the right lung of a TB patient
5. HISTOLOGY
• characteristically will
reveal caseating
granulomatous
inflammation in the
presence of TB
TREATMENT
● PTB is treated primarily with anti-TB agents for 6 months
● PTB treatment regimes are divided into two phases:
○ intensive and continuation phase.
● In intensive phase the majority of TB bacilli are rapidly killed and the infectious
patients become non-infectious with one to two weeks.
WHO fixed drug combination are RHZE, rifampicin 150mg,
isoniazid 75mg, pyrazinamide 400mg and ethambutol 275mg.
● Isoniazid(H).
● Rifampicin ®.
● Pyrazinamide (z)
● Ethambutol (E)
DURATION OF TREATMENT:
Duration of treatment in a patient of PTB.
2 Months intensive phase; RHZE (150/75/400/275)
4 Months Continuation Phase RH (150/75).
Extrapulmonary TB treatment duration will depend on the
type.
DOTS
Directly observed treatment Short-course (DOTS)
● Standardized treatment regimen directly observed by a
health care worker or community health worker for at least
the first 2 months.
● A regular drug supply
● A standardized recording and reporting system that allows
assessment of treatment results.
PREVENTION
Primary prevention:- include
(vaccination-BCG, environmental control, use of PPE, tracing & investigating
contacts, health education)
Secondary prevention:- include
(early diagnosis of TB and correct treatment, screening of TB-Tuberculin skin
test/Interferon-gamma Release Assays)
Tertiary prevention:- include
(Proper treatment duration & completion to improve quality of life and prevent
disability)
TUBERCULOUS
MENINGITIS
Tuberculous Meningitis (TBM)
• Most common form of CNS tuberculosis
• High frequency of neurologic sequelae and mortality if not
treated
• TBM complicates 0.3% of untreated TB infections in
children.
• Clinical progression of TBM may be rapid or gradual
• Rapid progression more often in infants and young
children
• Occasionally TBM occurs many years after the infection.
Classification of Neurotuberculosis
Intracranial TB
1. Tubercular meningitis and meningoencephalitis
2. Space Occupying lesions (Tuberculomas, tubercular abscess)
3. Tubercular encephalopathy
4. Tubercular vasculopathy
Spinal TB
5. Potts Spine
6. Tubercular arachnoiditis
7. Spinal Tuberculoma
8. Spinal meningitis and radiculomyelitis
Pathogenesis of TB Meningitis
Summary-Pathogenesis
• Primary infection
• Lymphohematogenous dissemination
• Metastatic caseous lesion in the cerebral cortex or meninges
• Discharges few tubercle bacilli into the subarachnoid space
• Forms gelatinous exudate
• Infiltrates the corticomeningeal blood vessels
• Inflammation, obstruction and infarction of cerebral cortex
• Brainstem (commonest site) Interferes CSF flow
• Dysfunction of CNIII, VI and VII Hydrocephalus
Clinical features
First Stage:
• Lasts for 1-2 weeks Nonspecific symptoms
• Fever
• Headache
• Irritability
• Drowsiness
• Malaise
• Stagnation or loss of developmental milestones
• Focal neurologic signs are absent
Second stage
• Begins more abruptly
• Lethargy
• Neck rigidity/ Hypertonia
• Seizures
• Positive Kernig and Brudzinski signs
• Cranial nerve palsies /Focal neurological signs
• Hydrocephalus/ Vasculitis
• Some with encephalitis
• Disorientation
• Movement disorders
• Speech impairment
Third stage
• Signs of brain stem compression (Opisthotonic posture, neck
retractions, decorticate and decerebrate posture, hyperpyrexia,
monoplegia, hemiplegia, paraplegia)
• Deterioration of vital signs
• Deep Coma and Death
Diagnosis
• Chest Xray
• HIV serology
• Lumbar CSF study
• CSF cells – Leukocyte 10-500cells/ul
• CSF Protein – markedly high (400-5,000mg/dl)
• CSF glucose - <40mg/dl
• Aid-fast stain positive in up to 30%of cases
• Culture is positive in 50-70%of cases
• TST – Nonreactive in up to 50% of cases
• Polymerase chain reaction (PCR)
• CT scan / MRI
• Basilar enhancement
• Communicating hydrcephalus
• Signs of cerebral edema
Management of TB Meningitis
• Should be hospitalized - at least the first 2 months
• Four anti-TB drugs are recommended for intensive phase
RHZE ( 2 months)
• Isoniazid and rifampicin are used for continuation phase
• Continuation phase is longer – for 10 months instead of 4
months
• Corticosteroids (usually Prednisolone) 2mg/kg/day daily for 4
weeks and then gradually taper over 1-2 weeks.
• Alternatively Dexamethasone 0.4mg/kg/day followed by
prednisolone.
Differential Diagnosis
• Partially treated bacterial Meningitis
• Cryptococcal Meningitis
• Viral meningoencephalitis
• Carcinomatous Meningitis
• Neurosarcoiditis
• Neurosyphilis
TUBERCULOMA
• Another manifestation of CNS tuberculosis
• Tumor-like mass
• Formed by aggregation of caseous tubercles
• Singular / Multiple
• Clinically manifests as a brain tumor
• Account for up to 30% of brain tumors
Clinical Features
• Intracranial tuberculomas usually present with seizures
without meningeal signs
• Raised ICP due to mass effect
• Various brain stem syndromes depending on location
Diagnosis
• TST – Reactive
• Chest xray – normal
• CT or MRI Brain
• Discrete lesions with surrounding edema
• Contrast medium enhancement shows ring-like lesion
• Surgical excision
• To distinguish tuberculoma from other causes of brain tumour
Treatment
• Intensive phase
• 4 drugs (RHZE) are recommended for 2 months
• Continuation phase
• Isoniazide and rifampicin are recommended for 10months
• Corticosteroids (usually prednisolone)
• HIV Negative and Positive patients
THANK YOU
