Presentation on theme: "Unit 3 – Overview of TB Disease"— Presentation transcript:
1 Unit 3 – Overview of TB Disease Botswana National Tuberculosis Programme Manual Training for Medical Officers
2 Learning ObjectivesAt the end of this unit, participants will be able to:Describe the causes of TBDescribe how TB is transmittedDescribe the difference between TB infection and TB diseaseIdentify high risk populations and high risk behavioursDescribe the pathogenesis of TBReview objectives of the unit
3 What is Tuberculosis?TB is an illness caused by one of four (4) types of bacteria:Mycobacterium tuberculosis (M. tuberculosis)Mycobacterium bovis (M. bovis)Mycobacterium africanum (M. africanum)Mycobacterium microti (M. microti)The majority of TB cases are caused by Mycobacterium tuberculosisM. tuberculosis complex consists of all four bacteriaHuman TB is caused by MTB or rarely other organisms that all share several characteristics: they are acid fast, slow growing, aerobic (require oxygen) and can become dormantMycobacteria other than TB (MOTT) or non-tuberculous mycobacteria (NTM) can cause a positive smear at times but do not cause disease in humans as often as M. tuberculosis complex. The MOTT are found in the environment and can cause disease in a person whose immune system is suppressed but they are not transmitted person to person through the air like tuberculosis and are therefore not considered a public health riskTB more common in than MOTT in Africa/Asia, but the opposite is true in Europe/N America. In addition to immunosuppression, lung damage (scarring, bronchiectasis) from prior infections (including TB) is a major risk factor for pulmonary MOTT. MOTT is “treatable” but is less often cured than is TB.
4 Characteristics of M. tuberculosis (1) TB bacilli as seen under the microscopeSlightly curved, rod shaped bacillimicrons in diameter and microns in lengthAcid fast - resists decolourisation with acid/alcoholM.TB is not the only AFB+ micro-organism.Acid fast is when the high lipid content of the cell wall of MTB resists decolourization with acid/alcoholThe differential diagnosis of AFB+ smeal include MOTT (Mycobacterial Other than Tuberculosis), such as MAC, and false positives due to stain contamination or the presence of dead organisms after treatment has begun.Source: Kubica GP. Public Health Image Library [database on the Internet]. Atlanta, GA: Centers for Disease Control and Prevention; 1979 [site updated 2005 Mar 18, cited 2008 Jan 22]. Available from:Source: Kubica GP, CDC, 1979
5 Characteristics of M. tuberculosis (2) Thick lipid cell wallMultiplies every hoursCan remain dormant for decadesAerobicNon-motileNon-motile means it can not move around by itself; it needs a transport systemAerobic means it likes an oxygen-rich environmentDuring primary infection, the germs go where the air goes, and any part of the lung can be affected. Upper lobe predominance in reactivation reflects the oxygen-rich environment of the upper lung zone airspaces, where the ventilation-to-perfusion ratio is greater than in lower zones. Upper lobe predominance does not occur by “spread” from elsewhere; the reactivating organisms were there from the time of primary infection.
6 Pathogenesis of TB Infection (implantation) Multiplication Dissemination (spread to other parts of the body)Cell-mediated immune response (healing)Reactivation
7 Definitions Alveoli Macrophage Granuloma The small air sac at the end of the airways in the lungsMacrophageA type of white blood cell that eats bacteria or foreign organisms, found in the alveoli of the lungsGranulomaNodular inflammatory lesions that contain compactly grouped mononuclear phagocytes (macrophages)Tuberculous granulomas are often caseating (necrotic at their center) and contain Langerhans giant cellsAFB can often be seen on stainingNote the difference in pathology of TB between normal immunity and immunosuppressed personsPathology in persons with normal immunity:GranulomasGiant cellsCaseous degenerationPathology in immunosuppressed personsPoorly formed or no granulomasNo caseous degenerationMay be larger numbers of organisms
8 Infection (Implantation Stage) HIV+ persons with TB infection have a very high risk of developing active TB diseaseThe implantation stage involves:The TB bacteria is inhaled and travels through the airway to the alveoli of the lungs. When the TB bacteria reaches the alveolous, it is ingested by alveolar macrophagesHowever, the macrophage, before activation, cannot kill the TB bacteria. Once the TB bacteria is inside of the macrophage it multipliesOrganism prefers environment with high oxygen contentLives within macrophages (intracellular pathogen)Also grows outside cells in cavities and abscessesThe organism is primarily an intracellular pathogen, so we rely on our cell mediated immunity to control it. Antibodies play little or no roleOxygen content of lungs: the upper lobes have comparatively lesser blood flow and ventilation which leads to an increase in alveolar oxygen pressure, and the disease tends to spread towards these regions from the post-primary seeding sitesSource: Centers for Disease Control and Prevention. Self-Study Modules on Tuberculosis, Atlanta, GA. Mod 1, Fig 1.4. Accessed from:Source: CDC, 2001
9 Primary Infection A person with primary infection may have: No symptomsLimited symptomsProgressive symptomsWhen TB is first acquired, it causes primary infectionIt may be asymptomatic and not recognisedIt may cause symptoms but be self-limiting, healing without therapyRarely it may be symptomatic and progressive causing a serious diseaseThis primary disease may be limited to the lung and intrathoracic lymph nodes, or it may spread to other organs causing disseminated diseaseProgressive Primary TB on chest x-ray is not necessarily in the upper lobesTypical findings are hilar/paratracheal adenopathy, plueral effusion and/or a periperhal infiltrate in any lobeA person with a calcified peripheral nodule and calcified adjacent hilar node is said to have a “Ghon complex”
10 How TB is Spread (1) Person-to-person Through the air by a person with TB disease of the lungsLess frequently transmitted by ingestion of Mycobacterium bovis found in unpasteurised milk productsRarely transmitted by inhalation of aerosolized infected fluids (e.g., TB abscess)For last bullet: It is important to recognize that it is not just the site or abscess but the aerosolizing of the germs within the site
12 Probability of Transmission Environment in which exposure occurredInfectiousness of person with TBImmunologic status of exposed personDuration of exposureVirulence of the organismThe probability that TB will be transmitted from one person to another depends on four factors:EnvironmentChance of infection increases when with an infectious person in areas where the bacteria can easily survive such as: Indoors, in areas with poor ventilation, in areas with no sunlightThe bacteria can survive in the air for long periods of time but can be killed by sunlight or spread about by the wind.Transmission is more likely to occur in a closed environment and less likely to occur outside where there is excellent ventilationInfectiousnessDirectly related to the number of TB bacteria that he or she expels into the air when he/she coughs, sneezes, etc. A person with TB disease who is coughing is putting more bacteria into the air than a person with TB disease who is simply breathing. An uninfected person who breathes in a lot of bacteria is more likely to become infected than someone who breathes in fewer bacteria.A study by Kenyon, et al. showed that the risk of transmission of infected children increased with the degree of sputum smear positivity for acid-fast bacilli among female index cases – 10.8% if smear 0, 9.3% if smear 1+, 29.4% if smear 2+, 44% if smear 3+ (p<0.001)Source: Kenyon T, Creek T, Laserson K, Makhoa M, Chimidza N, Mwasekaga M, Tappero J, Lockman S, Moeti T, Binkin N. Risk factors for transmission of Mycobacterium tuberculosis from HIV-infected tuberculosis patients, Botswana. Int J Tuberc Lung Dis. 2002; 6(10):Immunologic status of exposed personThe stronger/healthier one’s immune system is, the less likely TB is to be transmittedDuration of exposureThe longer an uninfected person is around someone with pulmonary TB disease the greater the chance that person will breathe in the bacteria. People who spend a lot of time around a person with TB disease, such as family members, roommates, friends, and coworkers, are at high risk of becoming infected with the TB bacteria.Virulence of the organismThe ability of any agent of infection to produce disease. The virulence of a microorganism (such as a bacterium or virus) is a measure of the severity of the disease it is capable of causing.Source: Medicinenet.com [Homepage on the Internet]. Definition of Virulence. c [reviewed 2001 Oct 20, cited 2008 Jan 23].
15 Latent InfectionPeriod of time during which the person experiences no symptoms but is still infected with the bacteriaThe bacteria lives inside macrophages or within a granuloma where the bacteria remains dormantA person with latent TB infection cannot spread the bacteria to other people
16 Reactivation of TB (1) Dormant bacteria can become active again Escape granuloma and enter the airwayThe dormant TB bacteria inside of the granuloma can become active again later in a person’s life: this typically occurs when the immune system becomes weak allowing the TB bacteria to multiply out of the control of the immune systemDuring the reactivation stage, a person will generally experience symptoms and can spread the TB bacteria to othersSource: Centers for Disease Control and Prevention. Self-Study Modules on Tuberculosis, Atlanta, GA. Mod 1, Fig 1.4. Accessed from:Source: CDC, 2001
17 Reactivation of TB (2)Latent infection can reactivate, causing active TB diseaseReactivation occurs when the immune system weakens and the TB bacteria multipliesTB bacteria and dead cells in the airway will cause a person to coughHigher proportion of smear-negative PTB in PLWHADuring the reactivation stage, a person will generally experience symptoms and can spread the TB bacteria to othersThis is the usual mechanism of development of active TB among adults. The disease may be pulmonary alone, extra-pulmonary alone, or both“Most of the increasing TB burden in Botswana may be attributable to reactivation of latent infection.”Source: Lockman S, Sheppard J, Braden C, Mwasekaga M, Woodley C, Kenyon T, Binkin N, Steinman M, Montsho F, Kesupile-Reed M, Hirschfeldt C, Notha M, Moeti T, Tappero J. Molecular and Conventional Epidemiology of Mycobacterium tuberculosis in Botswana: A Population-Based Prospective Study of 301 Pulmonary Tuberculosis Patients. Journal of Clinical Microbiology. March 2001; 39(3):On account of the impact of HIV in decreasing the sensitivity of sputum smear-microscopy and the specificity of chest X-ray in the diagnosis of pulmonary TB in adults, it is important to follow recommended diagnostic guidelines (WHO 2003b) as closely as possible and to ensure good quality control of sputum smear-microscopy (Harries et al. 1998). NTPs should also consider the costs and benefits of expanding the use of fluorescence microscopy (Crampin et al. 2001; Kivihya-Ndugga et al. 2003) and the bleach (sodium hypochlorite) method to improve the AFB smear microscopy (Angeby et al. 2004)Source: Maher D, Harries A, Getahun H. Tuberculosis and HIV interaction in Sub-Saharan Africa: impact on patients and programs; implication for policies. Tropical Medicine and International Health Aug; 10(8):HIV is the most powerful known risk factor for reactivation of latent M. Tuberculosis infection to active disease
18 Question What is the difference between TB infection and disease? Ask participants the question before reviewing the next slides.Allow participants a few minutes to answer the question aloud.Ensure that at the end of this step, participants are very comfortable with explaining the difference between infection and disease.
19 InfectionThe bacteria lives inside a person without that person having any symptoms because the immune system is able to control the infectionNot all infected people develop TB diseaseIn HIV negative individuals, 10% lifetime risk of developing disease if TB infectedIn HIV positive individuals, 10% ANNUAL risk of developing disease if TB infected
20 DiseaseIf the immune system cannot control the infection the bacteria multiply and cause diseaseTB disease can develop soon after infection, many years after infection or it may never developWhat is one factor, besides HIV, that might increase the chance that TB infection progresses to disease?Review slideAsk participants to write down one risk factor, besides HIV, that might increase a person’s chance of infection progressing to TB diseaseThey can record this anywhereIt is important that you allow participants enough time to brainstorm and record something before moving on to the next slide, as the next two slides contain risk factors for progression from infection to diseaseParticipants will share their responses on the next slide
21 Risk Factors for Progression from TB Infection to TB Disease (1) HIV/AIDSMalnutritionRecent TB infectionExtremes of age (children under 5 years of age and the very old)Alcoholism and other substance abuseAsk volunteers to share the responses they wrote down during the previous slide and say why they think it is a factorExplain the greatest risk of active TB disease occurs in the first 2 years after infectionReview the slides and add factors that were not mentionedRisk of reactivation is 10% over life-time for normal immune systems, risk of reactivation is 5-10% per year in the HIV infected populationImmune status – TB is more likely to progress from infection to disease in persons with a weak immune system. The very young (children under 5 years of age) and the very old have weak immune systems. Young children have weak immune systems because they are not yet fully developed. The elderly have weak immune systems because the immune system naturally weakens with age. Also, a person with HIV has a weak immune system and is at high risk for latent TB infection progressing to TB disease. It’s very important to identify TB infection in persons living with HIV as they have a 10% annual risk (50% lifetime risk) of their TB infection progressing to TB disease.Many factors can increase the progression from latent TB infection to disease, although in the current time HIV/AIDS is the most frequent and most importantLymphatic Malignancies – that cause decreased immunity and where the treatment is often immunosupressiveImmunosuppressive medications and treatmentsExtremes of age – very old/very young
22 Risk Factors for Progression from TB Infection to TB Disease (2) Silicosis of lungRenal failureDiabetes MellitusLymphatic malignanciesImmunosuppressive medications and treatments including prolonged corticosteroid therapyGastrectomyGastrectomy - associated with high tuberculosis morbidity possibly due to other factors such as loss of weightRenal failure - end stage renal failure patients often at risk of tuberculosisThe strength of a person’s immune system is also influenced by the food that a person eats. A person must eat enough and have a balanced diet to have a strong immune system. Someone who does not get enough vitamins in their diet or does not get enough food to eat has a weak immune systemSilicosis is permanent scarring of the lungs caused by inhaling silica (quartz) dust. Silica is the main constituent of sand, so exposure is common among metal miners, sandstone and granite cutters, foundry workers, and potters. Usually symptoms appear after years, and it is dependent upon the occupational exposureSource: Merck Manuals Online Medical Library [database on the Internet]. Merck & Co., Inc. c2005 [cited 2008 Feb 4, content modified 2005 Nov]. Entry: Tuberculosis. Available from:Source: Merck, 2005
23 Key Points (1)Evidence of TB has been seen to be affecting humans for centuriesTB transmission occurs from persons with active pulmonary TBTB droplets remain suspended in the air for hoursThe bacteria can be killed by direct sunlightVentilation is importantReview the Key Points and summarise the unit
24 Key Points (2) When TB is first acquired, it causes primary infection Persons with poor immunity, especially very young children and persons with AIDS, are more likely to have primary progressive diseaseLatent infection-- period of time when person experiences no symptoms but is still infected with the bacteria