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Tanzania is among the 22 countries with highest TB burden despite :-
implementing DOTS strategy since early 1980’s
Having national coverage of DOTS
Having a well functioning TB control programme
High Government and International commitment to TB control in the country
Notification rate total TB cases for 2002 was about 188/100,000
Underlying course is the HIV/AIDS epidemic in the country
TB is 3 rd leading cause of adult mortality
Estimated Global TB incidence rates, 2000 The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. Global Tuberculosis Control. WHO Report 2002 . WHO/CDS/TB/2002.295 25 - 49 50 - 99 100 - 300 0 - 9 10 - 24
Impact of HIV on the Epidemiology of Tuberculosis
Impact HIV in treatment outcomes High Mortality in HIV Co-infected patients van den Broek & Mfinanga, 1998 NTLP reports 2003
THE GENUS MYCOBACTERIUM CAN BE DIVIDED INTO FOUR BROAD GROUPS
THE TUBERCULOSIS COMPLEX
SLOW GROWING MYCOBACTERIA OTHER THAN TUBERCULOSIS (MOTT)
RAPIDLY GROWING MYCOBACTERIA
THE TUBERCULOSIS COMPLEX (Organisms that resemble M. tuberculosis; Causing a similar type of disease in humans)
THE RUNYON GROUPING: An older idea that Remains useful for differentiating mott
RUNYON GROUPS I,II,III: Slow growing mycobacterium Visible colonies on solid media After more than 5 days incubation GROUP I: PHOTOCHROMOGENS Produce pigment When grown in the light but not the dark EXAMPLES: M. kansasii ; M. marinum ; M. simiae GROUP II: SCOTOCHROMOGENS Pigment when grown in both light and dark EXAMPLES: M. scrofulaceum ; M. szulgai ; M. xenopi GROUP III: NONCHROMOGENS No pigment when grown in both light and dark EXAMPLES: M. avium-intracellulare ; M. genevense M. ulcerans and M. leprae do not fit in this scheme
RUNYON GROUP IV: Rapidly growing mycobacterium Visible colonies on solid medium In less than 5 days incubation EXAMPLES: M. fortuitum ; M. chelonae ; M. abscessus
MYCOBACTERIUM TUBERCULOSIS Prototypic facultative intracellular pathogen Primary human pathogen Transmitted from human to human Closely related to M. bovis It is an intracellular pathogen (typically inside alveolar macrophages). This organism does not secrete an identifiable exotoxin. Host immunity to M tuberculosis appears to be cell mediated (CMI).
CELL ASSOCIATED TOXINS MAY BE IMPORTANT VIRULENCE FACTORS FOR MANY MYCOBACTERIA The glycolipids, such as trehalose dimycolates, of Mycobacterium tuberculosis and related organisms appear to be related to their virulence .
Chest x-ray - hilar lymphadenopathy calcification of primary focus/LN
Delayed hypersensitivity response to purified protein derivative (PPD) MANTOUX /HEAF TEST
Evidence of active disease
Sputum for AFB positive
Evidence of active disease
Indirect evidence of infection (Mantoux)
Direct evidence of infection PCR / culture
Chest Radiograph Abnormalities often seen in apical or posterior segments of upper lobe or superior segments of lower lobe May have unusual appearance in HIV-positive persons Cannot confirm diagnosis of TB Arrow points to cavity in patient's right upper lobe.
Factors that affect the PPD Reaction Type of Reaction Possible Cause False-positive Nontuberculous mycobacteria BCG vaccination Anergy False-negative Recent TB infection Very young age (< 6 months old) Live-virus vaccination Overwhelming TB disease
Kinyon – uses a higher content of phenol (organic solvent) in the carbol fuchsin primary stain to allow penetration of the stain without the need to apply heat. Also uses acid alcohol to destain and methylene blue as the counterstain.
Auramine-rhodamine fluorochrome (a fluorescent stain) requires a fluorescent microscope, but allows one to scan the slide on high dry so that slides may be read much faster
Stain with auramine-rhodamine for 10 minutes (phenol in the solution allows for penetration)
Destain with acid alcohol
Counterstain with acridine orange
A positive result is a bright yellow fluorescence.
Ability of DNA strands from one organism to hybridize with the DNA strands of another organism
DNA fingerprinting Steps: 1. Digest DNA into smaller fragments 2. Separate fragments by size 3. Visualize bands 4. Each band corresponds to 1 fragment size 5. Unique pattern of bands identifies donor of DNA
‘ a paradoxical inflammatory reaction against a foreign antigen (alive or dead) in patients who have started antiretroviral therapy and who have undergone a reconstitution of their immune responses against this antigen’
Prevention and control of tuberculosis 1. Prompt and effective treatment of patients with active TB 2. Careful follow-up of contacts – tuberculin test, X-rays etc 3. Prophylaxis of asymptomatics, tuberculin positives 4. Correct underlying cause of immune suppression 5. Immunization with live-attenuated tubercle bacilli e.g. BCG 6. Eradication of TB in cattle and pasteurization of milk
HANSEN’S DISEASE (Leprosy) caused by M. leprae Hansen’s disease is a chronic, slowly progressive Granulomatous Disease involve ectodermally derived tissues e.g. skin and peripheral nerves. Usually limited to the cooler parts of the body e.g. skin, nose and upper respiratory tract. It rarely affects internal organs such as the brain, liver, spleen, kidneys, and bones. It has a specific predilection for peripheral nerves.
Mycobacterium leprae is an acid-fast rod that grows in macrophages, nerve cells, the foot pads of thymectimized mice, and the nine banded armadillo. It has never been grown in artificial medium, an obligate intracellular pathogen. has a generation time of 12 to 14 days, the incubation period for onset of disease is prolonged, therapy must also be prolonged (perhaps the lifetime of the individual).