MBChB student JKUAT

1. TUBERCULOSIS
FAITH CHELANG’AT
MBChB Level 4 jkuat

2. Tuberculosis is a communicable chronic
granulomatous disease caused by
Mycobacteria tuberculosis.
Usually involves the lungs but also affect
any other tissue in the body.

3. EPIDEMIOLOGY.
Most common cause of death resulting
from a single infectious agent according to
WHO.
About 1.7 billion individuals are affected
worldwide.
8-10 million new cases annually.
About 1.5 million deaths per year.

4. EPIDEMIOLOGY
 Tuberculosis flourishes under conditions of poverty,
crowding and chronic debilitating illness.
 High-prevalence populations include:
Immigrant from high-prevalence area
Homeless or medically underserved
Resident or worker in jail or long-term facility
Health care worker at facility with TB
Close contact to patient with active TB

5. EPIDEMIOLOGY
 High-risk populations include;
HIV and other immunosuppressing conditions
Chronic renal failure
DM
Malnourishment
Malignancy
Gastrectomy
Biologics e.g. TNF inhibitors

6. ETIOLOGY
 Mycobacteria; Family – Mycobacteriaceae, Order - Actinomycetales.
 Slender rods that are acid-fast that stubbornly resist decolourization.
 They contain a waxy coating on the cell surface due to presence of mycolic
acid.
 M. tuberculosis hominis - responsible for most cases of tuberculosis, the
reservoir of infection found in individuals with active pulmonary disease.
 Transmission - direct inhalation of airborne organisms in aerosols generated
by expectoration or by contaminated secretions of infected individuals.
 Oropharyngeal and intestinal tuberculosis acquired by drinking milk
contaminated with Mycobacterium bovis.
 Other mycobacteria, particularly Mycobacterium avium complex, are much
less virulent than M. tuberculosis and rarely cause disease in
immunocompetent individuals.

7. PATHOGENESIS.
Results in development of cell mediated
immunity in a previously immunocompetent
individual.
This confers resistance to the organism
resulting in development of tissue
hypersensitivity to the tubercular antigens.
The sequence of events from inhalation of the
infectious inoculum is as follows;

8. ENTRY OF MACROPHAGES
 A virulent strain of mycobacterium gains entry to
macrophage endosomes.
 This process mediated by several macrophage
receptors including the macrophage mannose
receptor and complement receptors that recognize
several components of the bacterial cell wall.

9. REPLICATION IN MACROPHAGES.
Once internalized the organisms inhibit
normal microbicidal responses by preventing
the fusion of lysosomes with the phagocytic
vacuole, allowing the mycobacterium to
persist and proliferate.

10. DEVELOPMENT OF CELL MEDIATED
IMMUNITY.
 Occurs approximately three weeks after exposure.
 Processed mycobacterial antigens reach the
draining lymph nodes and are presented to CD4 T
cells by dendritic cells and macrophages.
 Under the influence of macrophage secreted IL-12
, CD4+ T cells of the Th1 subset are generated that
are capable of secreting IFN- gamma.

11. T- CELL MEDIATED MACROPHAGE
ACTIVATED AND KILLING OF
BACTERIA.
 IFN-gamma released by the CD4+ cells is crucial for activating macrophages.
 Activated macrophages in turn release a variety of mediators and up-regulate
expression of genes important with downstream events including;
 TNF-α - responsible for recruitment of monocytes, which in turn undergo
activation and differentiation into epithelioid histocytes that characterize the
granulomatous response.
 Inducible NO synthase - raises NO levels, which creates a reactive nitrogen
intermediates that appear to be particularly important in killing mycobacteria
and;
 Antimicrobial peptides (defensins) that are toxic to mycobacterial organisms.

12. GRANULOMATOUS INFLAMMATION
AND TISSUE DAMAGE.
In addition to stimulating macrophages to kill
mycobacteria, the Th1 response leads the
formation of granulomas and caseous
necrosis.

14. PRIMARY TUBERCULOSIS
 Develops in a previously unexposed and therefore unsensitized patient.
 In a large majority of otherwise healthy individuals the only consequence of
primary tuberculosis are the foci of scarring.
 Uncommonly new infection may result to progressive primary tuberculosis.
 This complication may happen in patients that are overly
immunocompromised or who may have more subtle defects in there immune
system.
 A clear example is in HIV-positive patients with significant
immunosuppression. This is because immunosuppression results in an
inability to mount a CD4+ cell mediated response that would contain the
primary focus.

15. SECONDARY
TUBERCULOSIS
This arises from a previously infected
individual, particularly when the host
immunity is weakened.
It is classically localized to the apex of one or
both of the upper lobes.
Usually manifests as cavitary lesions in the
apices.

16. CLINICAL FEATURES
 Clinical manifestations take the form of ;
Acute (primary)pulmonary infection
Chronic(granulomatous) pulmonary disease or
Disseminated miliary disease.

17. Pulmonary TB
 Productive cough,
 Fever
 Unexplained weight loss.
 Blood streaking of the sputum is frequently documented.
 May occasionally present with hemoptysis or chest pain.
 Other systemic symptoms include anorexia, fatigue, and night
sweats

18. Miliary TB
Characterized by 2-3 weeks of;
Fever
Night sweats
Anorexia
Weight loss
Dry cough.

19. Extra pulmonary TB
 May present with the following depending on the organ involved
 Lymphadenitis – usually unilateral and painless. Most commonly at posterior
cervical and supraclavicular sites (a condition historically referred to as scrofula).
Lymph nodes are usually discrete in early disease but develop into a matted
nontender mass over time and may result in a fistulous tract draining caseous
material.
 Meningitis - present with intermittent headache or persistent for 2 to 3 weeks, may
progress to coma
 Bony TB - The spine is the most common site for bony TB (Pott’s disease), which
usually presents with chronic back pain and typically involves the lower thoracic
and lumbar spine. The infection starts as a discitis and then spreads along the spinal
ligaments to involve the adjacent anterior vertebral bodies, causing angulation of
the vertebrae with subsequent kyphosis. Paravertebral and psoas abscess formation
is common and the disease may present with a large (cold) abscess in the inguinal
region.

20. Cutaneous TB –ulcer or wart like lesion at the site of
inoculation.
Genitourinary TB- include flank pain, dysuria, and frequency,
epididymitis or a scrotal mass in male and may mimic pelvic
inflammatory disease in women
Pericarditis - Disease occurs in two forms; pericardial
effusion and constrictive pericarditis. Fever and night sweats
are rarely prominent and the presentation is usually insidious,
with breathlessness and abdominal swelling.
Peritonitis

22. INVESTIGATIONS
 Microbiology – sputum, bronchoscopy alveolar lavage and other
clinical smear for acid-fast smear and culture
 Radiological – chest x-ray may show consolidation or patchy or
nodular infiltrate or appearance of numerous small nodular
lesions that resemble millet seeds in miliary TB
 Tuberculin skin testing (Mantoux test)- induration of more than
10mm in 48 to 72 hours
 Newer technologies, including ribosomal RNA probes or DNA
polymerase chain reaction, allow identification within 24 hour.

23. TREATMENT OF TB
 For initial empiric treatment of tuberculosis (TB), start patients on a 4-
drug regimen:
Isoniazid,
Rifampin,
Pyrazinamide, and
Either Ethambutol or Streptomycin.
 Standard treatment involves 6 months’ treatment with isoniazid and
rifampicin, supplemented in the first 2 months with pyrazinamide and
ethambutol.
 Fixed-dose tablets combining two or three drugs are preferred.

26.  Indications for immediate treatment:
any patient who is smear-positive, or
smear-negative but with typical chest X-ray changes and no response
to standard antibiotics.
 New-onset pulmonary TB and most cases of extra pulmonary TB – 6
months of therapy.
 Meningeal & spinal TB – 12 months of therapy; in these cases,
ethambutol may be replaced by streptomycin.
 Pregnant women and malnourished patients – prescribed with
pyridoxine to reduce risk of peripheral neuropathy associated with
isoniazid.
 Patients can be assumed to be non-infectious after 2 weeks of
appropriate therapy when drug resistance is not anticipated.

27.  Baseline liver function and regular monitoring are important for patients
treated with standard therapy.
 In the event of hepatotoxicity is appropriate to stop treatment and allow any
symptoms to subside and the liver function tests (LFTs) to recover before
commencing a stepwise re-introduction of the individual drugs.
 Indications of hospital admission:
Uncertainty about the diagnosis, intolerance of medication, questionable
treatment adherence, adverse social conditions or a significant risk of MDR-
TB (culture-positive after 2 months on treatment, or contact with known
MDR-TB).
 Corticosteroids and are currently recommended when treating pericardial or
meningeal disease, and in children with endobronchial disease. They may
confer benefit in TB of the ureter, pleural effusions and extensive pulmonary
disease, and can suppress hypersensitivity drug reactions.

28. The effectiveness of therapy for pulmonary TB
is assessed by further sputum smear at 2
months and at 5 months.
Extra pulmonary TB must be assessed
clinically or radiographically, as appropriate
Treatment failure is defined as a positive
sputum smear or culture at 5 months or any
patient with a multidrug resistant strain,
regardless of whether they are smear-positive
or negative