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  • 1. Introduction 1 Tuberculosis Partners in Global Health Educationw to use this module Welcome to the tuberculosis (TB)arning outcomesat is TB? module.demiology robiologynsmission TB is a major cause of morbidityction 1 quizural history and mortality all over the world butction 2 quiz the greatest burden is borne bymptoms and signsction 3 quiz developing countries. Thegnosis bacterium Mycobacteriumatmentvention and control tuberculosis is responsible for mostction 4 quizormation sources TB cases.mmative assessment For more information about the authors and reviewers of this module, click here IUATLD; WHO/TBP/Falise
  • 2. Introduc tion 2 How should you study this module? Partners in Global Health Education • We suggest that you start with the learning objectives and try to keep these in mind as you go through the module slide by slide,w to use this module in order.arning outcomesat is TB? • Print-out the mark sheetdemiology • As you go along, write your answers to the questions on the robiology mark sheet as best you can before looking at the answers.nsmission • Award yourself marks as detailed on the mark sheet: one markction 1 quiz for each keyword (shown in red text) in the short answerural history questions and for every correct answer in the True/Falsection 2 quiz questions.mptoms and signsction 3 quiz • Repeat the module until you have achieved a mark of 28/35gnosis (≥80%).atment • Finish with the formative multiple choice questionnaire to assessvention and control how well you have covered the material as a whole.ction 4 quizormation sources • You should research any issues that you are unsure about. Lookmmative assessment in your textbooks, access the on-line resources indicated at the end of the module and discuss with your peers and teachers. • Finally, enjoy your learning! We hope that this module will be enjoyable to study and complement your learning about TB from other sources.
  • 3. Introduc tion 2 Learning Outcomes Partners in Global Health Educationw to use this module By the end of the module, you should be able to:arning outcomesat is TB? 1. Describe how TB can affect anyone, of any age, anywhere, but thatdemiology most cases occur in specific risk groups robiologynsmission 2. Describe how respiratory droplets are the main transmission agentction 1 quizural historyction 2 quiz 3. Describe how, following inhalation, M. tuberculosis causes infection in many people and disease in somemptoms and signsction 3 quizgnosis 4. Enumerate the general symptoms and signs of TB and the specific clinical features of pulmonary TBatmentvention and controlction 4 quiz 5. Discuss how CXR and sputum examination are used in diagnosisormation sourcesmmative assessment 6. Describe how TB is managed using combinations of antimicrobials 7. Describe how TB is prevented at the community level by immunisation, case finding and contact tracing
  • 4. What is tuberculosis (TB)? Partners in Global Health Education TB is a chronic bacterial infection. The great majority of infections inw to use this modulearning outcomes people are caused by Mycobacterium tuberculosis (M.at is TB? tuberculosis). A closely related bacteria, M. bovis, causes TB indemiology animals (especially cattle) and can infect people who drink robiology unpasteurised milk from infected cows.nsmissionction 1 quiz Although an ancient disease, TBural history remains a world wide problem:ction 2 quizmptoms and signs • about 1 in 3 of the world’sction 3 quiz population is infected with tuberclegnosis bacilli and someone is newlyatmentvention and control infected every secondction 4 quiz • although most infected peopleormation sourcesmmative assessment remain asymptomatic, there are about 9 million new cases and nearly 2 million TB deaths every year.
  • 5. Where does TB occur? Epidemiology 4 Partners in Global Health Education About 95% of the world’s cases of TB occur in South East Asia, sub-w to use this module Saharan Africa and the Western Pacific.arning outcomes The largest number of cases andat is TB? highest mortality occur in South Eastdemiology Asia and this region accounts for 33% robiology of incident cases globally.nsmission The annual incidence of TB isction 1 quiz increasing sub-Saharan Africa mainlyural history as a result of the increasedction 2 quiz susceptibility of people infected withmptoms and signs HIV.ction 3 quizgnosis Other factors which encourage TBatment transmission are:vention and control • the emergence of multidrug-resistant strains of M. tuberculosisction 4 quiz • poor national TB control programmes and worsening socio-economicormation sources conditions in many countriesmmative assessment In the UK, the annual incidence rate is increasing with >8,000 new cases/year. Most occur in the larger cities, especially London, and about 2/3 cases occur in people who were born abroad. TB causes or contributes to 300-400 deaths/year in the UK.
  • 6. pidemiology 2 Microbiology (1) Partners in Global Health Education M. tuberculosis is a non-motile, rod-shapedw to use this module bacterium measuring 2-4 x 0.2-0.5 μm. It isarning outcomes an obligate aerobe, which explains why it tends to be found in the well-aerated, upperat is TB? lobes of the lungs.demiology robiologynsmission It is a slow growing organism (dividing onlyction 1 quiz every 16-20 hours) that lives within tissue macrophages. Humans are the onlyural history reservoir of M. tuberculosis. Both animalsction 2 quiz and humans serve as reservoirs for M.mptoms and signs bovis.ction 3 quiz The Ziehl-Nielsen stain isgnosis used to demonstrate the The organism does not have the presence of the bacilli in aatment characteristics of either Gram positive or smear. Note the bright redvention and control negative bacteria. It has a peculiar cell wallction 4 quiz that consists of peptidoglycan and complex rods in this sputum smear.ormation sources lipids. Once stained (e.g. with carbolmmative assessment fuchsin), the organism will retain dyes when treated by acidified organic compounds. Therefore, it is classified as an “acid–fast” bacterium.
  • 7. demiology 3 Microbiology (2) Partners in Global Health Education The cell wall is a major factor in the virulence of the organism.w to use this modulearning outcomes It resists destruction by manyat is TB? antibiotics, acids, alkalis, osmoticdemiology lysis and oxidation and enables robiology the organism to survive andnsmission multiply within macrophages.ction 1 quizural historyction 2 quiz M. tuberculosis grows inmptoms and signs Lowenstein Jensen medium, anction 3 quiz egg-based medium, whichgnosis contains inhibitors to keepatment contaminants from outgrowing thevention and control organism. Because of its slowction 4 quiz growth, it takes 4-6 weeks before Typical small, buff coloured colonies of M. tuberculosis on Lowenstein Jensenormation sources small buff-coloured colonies are mediummmative assessment visible on the medium.
  • 8. Transmission 1 How is TB transmitted? Partners in Global Health Educationw to use this module Nearly all TB infection is acquired by inhalation of respiratoryarning outcomes droplets from people with TB in the lungs or throat.at is TB?demiology robiology Air droplets 3-5 μmnsmission diameter are coughed,ction 1 quiz sneezed or spat-out by anural historyction 2 quiz “open” case of TB. Themptoms and signs droplets are inhaled by action 3 quiz close contact. This isgnosisatment more likely to occur invention and control overcrowdedction 4 quiz environments.ormation sourcesmmative assessment NB. Abdominal TB can also result from drinking unpasteurised cow’s milk infected with M. bovis.
  • 9. End of Section 1 Partners in Global Health Educationw to use this modulearning outcomes Well done! You have come to the end of the first section.at is TB?demiology robiologynsmissionction 1 quizural historyction 2 quizmptoms and signsction 3 quizgnosisatmentvention and control We suggest that you answer questions 1 to assess yourction 4 quizormation sourcesmmative assessment learning so far. Please remember to write your answers on the mark sheet before looking at the correct answers!
  • 10. Question 1: Risk of exposure to TB Write “True” or “False” on the answer sheet. When you have completed all 5 questions, click on the boxes and mark your answers. Partners in Global Health Educationw to use this module Now that you know how TB is transmitted, are the followingarning outcomes people at increased risk of exposure? Click for the correctat is TB? answerdemiology robiologynsmission a) Close contacts of people with open TB (e.g. action 1 quiz family members)ural historyction 2 quiz b) People who drink unpasteurised milk bmptoms and signs c) People living in poor, overcrowdedction 3 quiz cgnosisatment environmentsvention and control d) People who work or are residents in long- dction 4 quizormation sources term facilitiesmmative assessment e) Infants and young children e
  • 11. Pathogenesis 1 What happens following inhalation of M. tuberculosis? Outcome 1: No infection Partners in Global Health Educationw to use this module Between 70-90% of individuals exposed to TB will notarning outcomesat is TB? develop the infection.demiology robiology The reasons for this are unclear. However, in view of thensmissionction 1 quiz known risk factors for infection, people who inhaleural history bacilli but do not develop an infection may:ction 2 quizmptoms and signs • inhale too few organisms to cause infectionction 3 quizgnosis • have sufficient immunity to prevent an infectionatment becoming establishedvention and controlction 4 quizormation sources Any factor associated with impaired immunity, such asmmative assessment extremes of age, malnutrition and HIV/AIDS will increase the risk of developing infection.
  • 12. Pathogenesis 2 What happens following inhalation of M. tuberculosis? Outcome 2: Infection with formation of a primary complex Partners in Global Health Education Following inhalation, tubercle bacilli settle in the alveoliw to use this module and result in local inflammation in the lungarning outcomes parenchyma. This “primary focus” usually occurs inat is TB? the upper lobes in adults but may occur in any of thedemiology lung lobes in children. More than one focus may occur robiology in the same patient.nsmissionction 1 quiz The organisms then spread via the local lymphatics to the nearest hilar lymph nodes, which may thenural history enlarge.ction 2 quizmptoms and signs The primary focus and the enlarged regional lymphction 3 quiz nodes form the “primary complex” or “Ghongnosis complex”. Primary focus successfullyatment contained by the host immunevention and control What happens next depends on the size of the systemction 4 quiz infecting dose and the resistance of the host. Mostormation sources commonly, the primary focus is “walled-off” by the The person is infected but does not immune system and lies dormant– “latent TB”. The have TB disease and cannotmmative assessment infection may be reactivated years later if the immune spread TB. However, an immune system of the host becomes weakened. response to M. tuberculosis will have developed – and can be demonstrated by a positive Mantoux test (see later).
  • 13. athogenesis 3 What happens following inhalation of M. tuberculosis? Outcome 3: Pulmonary disease Partners in Global Health Education If the primary focus is not contained, lung disease mayw to use this module develop in several ways:arning outcomes • The primary focus enlarges and undergoes centralat is TB? necrosis to form a cavitydemiology • The infection can spread locally and result in robiology tuberculous bronchopneumoniansmission • Marked swelling of the mediastinal lymph nodes mayction 1 quiz compress large bronchi and result in lobar collapseural historyction 2 quiz • The enlarged lymph node may act like a one-way valve causing hyperinflation of a lung or lobemptoms and signsction 3 quiz • The adjacent pleura can become infiltrated by M.gnosis tuberculosis resulting in a hypersensitivity reaction characterised by granulomas composed mainly ofatment lymphocytes Infection not contained byvention and control • Pleural infiltration may result in a pleural effusion the immune system.ction 4 quiz which is rich in lymphocytes – a useful pointer to the Person develops lungormation sources diagnosis when pleural fluid is aspirated and disease and becomes anmmative assessment analysed open case - capable of • Long term complications of the damage to lung infecting others via tissue include emphysema and bronchiectasis respiratory droplets.
  • 14. What happens following inhalation of M. tuberculosis? Pathogenesis 4 Outcome 4: Systemic disease Partners in Global Health Education Haematogenous dissemination of M.w to use this module tuberculosis leads to granuloma formation inarning outcomes many organs. Examples include:at is TB?demiology robiology • Diffuse infection of the lungs: “miliary” TBnsmission • Brain: TB brain abscessction 1 quiz • Meninges: TB meningitisural historyction 2 quiz • Bones: TB osteomyelitis – commonly affectsmptoms and signs the spine and is then called “Potts’ disease”ction 3 quiz • Pericardium: TB pericarditis and pericardialgnosisatment effusionvention and controlction 4 quiz As with acquiring infection after inhalation,ormation sources disseminated disease is most likely to occur inmmative assessment the immunocompromised person (e.g. HIV/AIDS, malnutrition) and at extremes of age.
  • 15. Pathogenesis 5 Summary (1): natural history following TB exposure Partners in Global Health Educationw to use this module What are the likely outcomes following exposure to open TB?arning outcomesat is TB? Exposure to TBdemiology robiologynsmissionction 1 quizural history No infection Infectionction 2 quizmptoms and signs (70-90%) (10-30%)ction 3 quizgnosisatment Dormant TB (90%) Active TB (10%)vention and control • well • ill and likely to die ifction 4 quiz • no TB disease untreatedormation sources • not infectious to • infectiousmmative assessment others Activation of infection results in disease
  • 16. Pathogenesis 1 Summary (2): natural history following TB exposure Partners in Global Health Educationw to use this modulearning outcomesat is TB? There are 4 possible outcomes following inhalation of TB bacilli:demiology robiologynsmission Outcome Person Person Person developsction 1 quiz unwell? transmits an immuneural history disease? response to TB?ction 2 quiz 1: No infection No No Nomptoms and signsction 3 quiz 2. 1o lung complex No No Yesgnosisatment 3. Pulmonary disease Yes Yes Yesvention and controlction 4 quiz 4: Systemic disease Yes Yes Yesormation sourcesmmative assessment Note: outcomes 3 and 4 can develop many years after formation of the 1 o lung complex
  • 17. End of Section 2 Partners in Global Health Educationw to use this modulearning outcomes Well done! You have come to the end of the second section.at is TB?demiology robiologynsmissionction 1 quizural historyction 2 quizmptoms and signsction 3 quizgnosisatmentvention and control Answer questions 2 through 4 to assess your learning soction 4 quizormation sourcesmmative assessment far. Challenge yourself: complete the mark sheet before looking at the correct answers!
  • 18. Question 2: Groups of people at increased risk of TB disease and disseminated infection following exposure are: Write “True” or “False” on the answer sheet. Partners in Global Health Education Click for the correct answerw to use this modulearning outcomesat is TB? a) Infants and children <5 years ademiology robiologynsmission b) People with HIV/AIDS bction 1 quizural history c) People with diabetes mellitus, measles,ction 2 quizmptoms and signs cction 3 quiz pertussis or on prolonged corticosteroid therapy dgnosisatmentvention and control d) Young adultsction 4 quizormation sources e) Alcoholics and IV drug users emmative assessment
  • 19. Question 3: Factors underlying the resurgence of TB in the last 2 decades are: Write “True” or “False” on the answer sheet. Partners in Global Health Education Click for the correct answerw to use this modulearning outcomesat is TB? a) HIV pandemic ademiology robiologynsmission b) Poverty/worsening socioeconomic conditions bction 1 quizural historyction 2 quiz c) Poor hygiene cmptoms and signsction 3 quizgnosis d) Emergence of drug resistance strains datmentvention and controlction 4 quiz e) Poor national TB control programmes eormation sourcesmmative assessment
  • 20. Question 4: Following exposure to M. tuberculosis Write “True” or “False” on the answer sheet. Partners in Global Health Education Click for the correct answerw to use this modulearning outcomes a) The usual outcome is a primaryat is TB? infection ademiology robiologynsmission b) The primary complex consists of a bction 1 quiz cavity in the lung parenchyma andural history hilar lymphadenopathyction 2 quizmptoms and signsction 3 quiz c) A pleural aspirate rich in neutrophils cgnosis suggests TB as a causeatmentvention and control d) Miliary TB refers to disseminated dction 4 quiz infection spread via the bloodstreamormation sourcesmmative assessment
  • 21. inical features 1 What are the symptoms and signs of TB? 1. Primary infection with no spread of the disease Partners in Global Health Educationw to use this module Individuals with primary infection do notarning outcomes usually have any symptoms or signs of illat is TB? health although some people develop a Erythema nodosum:demiology robiology minor flu-like illness. ecchymotic papules foundnsmission along the shin or on thection 1 quiz Infection triggers an immune response flexural surfaces of the limbsural history and, in a minority of people, this mayction 2 quiz Phlyctenularmptoms and signs result in clinical signs of hypersensitivity keratoconjunctivitis: raised, yellowish nodule at thection 3 quiz to M. tuberculosis for example: corneoscleral junction. Smallgnosis blood vessels may be seenatment • erythema nodosum radiating from the nodule.vention and controlction 4 quiz • phlyctenular keratoconjunctivitisormation sourcesmmative assessment They will also have a positive Mantoux test (see below).
  • 22. cal features 2 What are the symptoms and signs of TB? 2. Active infection: symptoms Partners in Global Health Education Symptoms of TB can be divided General symptomsw to use this module into general symptoms and those • Feverarning outcomes specific to the organ infected. • Loss of weight in adults or growthat is TB? faltering in childrendemiology TB can result in a myriad of • Night sweats robiologynsmission symptoms depending on which • Malaise, tiredness and anorexiaction 1 quiz organs are involved and how their Organ specific - examples include:ural history function is affected.ction 2 quiz The lung is the predominant Lungsmptoms and signs • Cough – usually chronic (lasting >6ction 3 quiz organ affected, being involved in weeks)gnosis over 75% of cases. • Productive of whitish or mucoid sputumatment in adults but usually unproductive in childrenvention and control Commonly affected organs • Haemoptysis (coughing-up blood)ction 4 quiz following haematogenous spreadormation sources from the lung are the abdomen, Central Nervous Systemmmative assessment • TB meningitis lymph nodes, spine, meninges, • Tuberculoma, with the classical features kidneys, bone and reproductive of a space-occupying lesion simulating a organs. brain tumour
  • 23. cal features 3 What are the symptoms and signs of TB? 2. Active infection: signs Partners in Global Health Educationw to use this module General examination - look for:arning outcomesat is TB? • fever • signs of malnutrition signifying a chronic illnessdemiology • enlargement of the peripheral lymph nodes robiology • digital clubbing as a consequence of chronicnsmission infection/inflammation in the chest or abdomenction 1 quizural historyction 2 quiz TB lymphadenitis presents as painlessmptoms and signs enlargement of the superficial lymph nodes. Thection 3 quiz neck is the commonest site involving the cervical,gnosis submandibular, pre and post-auricular lymphatment nodes. The lymph nodes are non-tender, mattedvention and control together and rubbery in consistency. It is common for enlarged lymph nodes to ulceratection 4 quiz and discharge.ormation sourcesmmative assessment Look at this picture of a 4 year old boy from West Africa. Note that he is generally wasted and has marked enlargement of the cervical lymph nodes – especially on the right side.
  • 24. cal features 3 What are the symptoms and signs of TB? 3. Pulmonary and abdominal TB Partners in Global Health Education Pulmonary TB (PTB)w to use this module The apical region is the mostarning outcomes commonly affected in adults.at is TB? Pulmonary lesions may involve anydemiology part of the lung in infancy and robiology childhood.nsmissionction 1 quiz Abnormalities detected clinicallyural history include consolidation, collapse, pleural effusion and fibrosis. Butction 2 quiz beware: examination of themptoms and signs respiratory system may bection 3 quiz completely normal even in activegnosis disease! Upper lobe changes on CXRatment Source: WHO/TBP/Pierre Virotvention and control Abdominal TBction 4 quizormation sources Pathology affects the mesenteric and the retroperitoneal glands, the omentum andmmative assessment the gastrointestinal tract. Patients may present with weight loss, diarrhoea or constipation, abdominal distension (from ascites) or chronic intestinal obstruction. Enlarged mesenteric lymph nodes may be palpable as multiple intra-abdominal masses.
  • 25. Tuberculosis of the spine – “Pott’s disease” Partners in Global Health Educationw to use this module TB commonly affects the spine,arning outcomes especially in young children, andat is TB? usually presents as a swelling on thedemiology back. robiologynsmission The lower thoracic and the upper lumbar vertebrae are the usual sites,ction 1 quiz however any vertebra can beural history affected.ction 2 quizmptoms and signs The patient may also present withction 3 quiz kyphosis, scoliosis, kyphoscoliosis, or features of spastic paraparesis.gnosis There may be a sharp angulation ofatment the spine caused by collapse of avention and control vertebra – referred to as a “gibbus”ction 4 quizormation sourcesmmative assessment A young child from West Africa. Note the swelling over the lower thoracic vertebrae.
  • 26. End of Section 3 Partners in Global Health Education Well done!w to use this modulearning outcomesat is TB? This is the end of the second section.demiology robiologynsmissionction 1 quizural historyction 2 quizmptoms and signsction 3 quizgnosisatmentvention and control We suggest that you proceed to answer question 5 toction 4 quiz assess your learning further. Do remember to write yourormation sources answers on the mark sheet before looking at the rightmmative assessment answer!
  • 27. Clinical features Quiz 1 Question 5: What 2 features are consistent with pulmonary TB in this man? Partners in Global Health Educationw to use this modulearning outcomesat is TB?demiology robiologynsmissionction 1 quizural history Write Down Yourction 2 quiz Answers on yourmptoms and signs mark sheet, thenction 3 quiz click below to revealgnosis the answersatmentvention and controlction 4 quizormation sourcesmmative assessment Man with advanced TB in Bangladesh source: WHO/TBP/England Click to Reveal Answers
  • 28. Investigation 1 Diagnosis Partners in Global Health Education In developing countries, the diagnosisw to use this module of TB is based on the combination ofarning outcomes clinical assessment and simpleat is TB? laboratory methods:demiology robiology 1. History of chronic cough with thensmission general symptoms of fever, malaisection 1 quiz and weight lossural history 2. Presence of general and specific clinical signsction 2 quiz 3. Positive findings on relevantmptoms and signs investigations – usually CXR andction 3 quiz sputum smear stained for acid-fastgnosis bacilliatment Examining a CXR in Chinavention and control It is important to note that specific Source: WHO/TBP/Pierre Virotction 4 quiz symptoms and signs may be absent.ormation sourcesmmative assessment TB should be suspected in any chronically ill person!
  • 29. Investigation 4 Bacteriological diagnosis Partners in Global Health Education • Sputum microscopy is most useful in adults with a productive cough. A sputumw to use this module smear is stained with the Ziehl-Nielsenarning outcomes stain to demonstrate the presence of theat is TB? acid and alcohol fast bacilli (AFB). Whendemiology positive, the patient is “smear-positive” or “open TB” and the risk of transmission of robiology infection to others is very high. However,nsmission the test is often falsely negative in patientsction 1 quiz with TB. The yield of the test is higher inural history patients with lung cavities.ction 2 quizmptoms and signs • Gastric washings examined for AFB:ction 3 quiz Carried out in children as they swallow rather than cough-up sputum. The testgnosis aims to recover the swallowed AFB fromatment the stomach using a naso-gastric tube. Thevention and control test is positive in only about one third ofction 4 quiz children with TB. Sputum samples collected in aormation sources health facility in Ethiopiammative assessment • Bacterial culture: This takes about 6-8 source: WHO/TBP/Jan Van den weeks and so is of limited use in clinical Hombergh diagnosis. M. tuberculosis grows on a special medium called the Lowenstein Jensen medium.
  • 30. Investigation 5 Mantoux or tuberculin skin test Partners in Global Health Education This test detects a delayed hypersensitivity, cutaneous reaction to a purified protein derivative (PPD) of M. tuberculosis – also called “tuberculoprotein”:w to use this modulearning outcomesat is TB? 1. PPD is injected intradermallydemiology 2. the injection site is inspected 48-72 hours later robiology 3. erythema and induration at the site signify an immune response and,nsmission therefore, previous exposure to mycobacteriaction 1 quizural history The limitations of this test are well-known:ction 2 quiz  False positive: a skin reaction in people who do not have TB because ofmptoms and signs exposure to non-pathogenic mycobacteria and also due to the immune response following BCG immunisation (see later).ction 3 quiz  False negative: a negative result in a person with TB in early primarygnosis infection or because they are immunocompromised – for example, due toatment HIV/AIDS, malnutrition or people who develop disseminated TB.vention and controlction 4 quiz In general, the greater the degree of erythema and induration, the more likelyormation sources the patient has TB disease. Several detailed criteria are available to guidemmative assessment the interpretation of Mantoux results, e.g. from the American Thoracic Society and Centers for Disease Control & Prevention
  • 31. nvestigation 7 Diagnosis: Other investigations Partners in Global Health Education Other investigations are indicated depending on the organs/ systemsw to use this module affected by the diseasearning outcomesat is TB?  Spinal radiographs in Pott’s diseasedemiology  Lymph node aspirate (microscopy, culture and cytology) or biopsy robiology (histology and culture) in TB lymphadenitisnsmissionction 1 quiz  Lumbar puncture for cerebrospinal fluid analysis in TB meningitisural history (microscopy, biochemical analysis and culture)ction 2 quizmptoms and signs A recent development is the detection of the growth of TB in liquidction 3 quiz culture by microscopy. Diagnosis can be made within 10 days andgnosis addition of drugs to the cultures allows the detection of drugatment resistance.*vention and controlction 4 quiz Also, a number of new diagnostic tests have been developed basedormation sources on molecular methods such as the amplification of nucleic-acid.mmative assessment However, these assays have not been fully evaluated and are expensive. * Moore DA et al. Microscopic-observation drug-susceptibility assay for the diagnosis of TB. N Engl J Med 2006; 355:1539-50
  • 32. Treatment Partners in Global Health Education Resistance of M. tuberculosis to antimicrobials is a majorw to use this modulearning outcomes problem in TB treatment. Because it is a slow growingat is TB? organism, treatment courses are long - at least 6 months.demiology robiologynsmission • Treatment requires action 1 quiz combination of drugs to whichural history the organisms are sensitive.ction 2 quizmptoms and signs • Treatment courses must bection 3 quiz completed for effective curegnosis and to prevent the emergenceatment of drug-resistant strains.vention and controlction 4 quiz • Longer treatment courses areormation sourcesmmative assessment needed for TB meningitis or if Combination antibiotic therapy the bacteria are resistant and in India Source: IUTBLD WHO/TBP/Gary additional drugs are required. Hampton
  • 33. Management Treatment: DOTS Partners in Global Health Education DOTS is the acronym for Directly Observed Treatment Short Course.w to use this modulearning outcomes It involves the daily administration of a combination of antituberculous drugs toat is TB? a TB patient under the supervision of a healthcare personnel. DOTS helps todemiology ensure compliance, reduce transmission by shortening the period of infectivity, robiology improve the cure rate and reduce the risk of drug resistance.nsmissionction 1 quiz There are many regimens for treating TB. The most frequently recommendedural history regimen that is also effective in people with HIV infection is:ction 2 quizmptoms and signs Drug 0-2 months 3-6 monthsction 3 quizgnosis Isoniazid + +atment Rifampicin + +vention and control Pyrazinamide + -ction 4 quizormation sources Ethambutol* + -mmative assessment *IM streptomycin is often substituted for oral ethambutol for children < 6 years
  • 34. Drug-resistant TB Partners in Global Health Education There are 2 classes of drug resistant TB:w to use this modulearning outcomesat is TB? 1. Multidrug-resistant (MDR)demiology • defined as resistance to rifampicin and isoniazid, +/- other robiology drug resistancensmission • worldwide, >4% of TB patients are MDR, with the highestction 1 quiz prevalence in Eastern Europeural history • treatment requires longer drug regimens, is less effective,ction 2 quiz more costly and poorly toleratedmptoms and signsction 3 quizgnosis 2. Extensively drug-resistant (XDR)atment • defined as resistance to rifampicin and isoniazid and, invention and control addition, resistance to any quinolone and at least onction 4 quiz injectable second-line drugormation sources • XDR TB is essentially untreatable and has a very highmmative assessment mortality
  • 35. ention Prevention and Control Partners in Global Health Education TB control strategies include –w to use this module • Case finding: aims to identify TB cases promptly, treat themarning outcomes with an effective combination of drugs and ensure that theat is TB? course is completed.demiology robiology • Contact tracing: Close contacts of TB cases are screened fornsmission evidence of infection. Mantoux positive cases are treated withction 1 quiz oral isoniazid for 6-12 months to prevent them from developingural history the disease. This regimen is also used in HIV-positive people.ction 2 quizmptoms and signsction 3 quiz • Bacillus Calmette-Guérin (BCG) vaccinegnosis • contains an attenuated strain of M. bovisatment • is administered as a single intradermal injectionvention and control • Has limited efficacy against pulmonary TB (and, therefore,ction 4 quiz TB transmission) but does appear to prevent disseminatedormation sources disease and death – especially in childrenmmative assessment • is given routinely to infants in developing countries and to people at increased risk of TB infection in developed countries
  • 36. TB: the future Partners in Global Health Education WHO declared TB a global health emergency in 1993 and aims tow to use this module eliminate TB as a public health problem by 2050.arning outcomes • Other organisations involved in TBat is TB? control include the International Uniondemiology Against TB and Lung Disease, the robiology Center for Disease Control (USA) andnsmission the Global Plan to Stop TB.ction 1 quiz • TB remains a worldwide challenge.ural history There is a need to improve DOTSction 2 quiz coverage and meet the emergingmptoms and signs challenges of TB in people withction 3 quiz HIV/AIDS and multidrug resistant TB.gnosis • Improved techniques for diagnosis areatment required especially in people withvention and control compromised immunity where diagnosisction 4 quiz is difficult such as HIV/AIDS andormation sources malnourished children.mmative assessment • A more effective vaccine and improved treatment strategies that would decrease the duration of treatment are also high IUATLD; WHO/TBP/Falise priorities.
  • 37. End of Section 4 Partners in Global Health Education You have come a long way!w to use this modulearning outcomesat is TB? This is the last of the sections.demiology robiologynsmissionction 1 quizural historyction 2 quizmptoms and signsction 3 quizgnosisatmentvention and controlction 4 quiz For the section just ended, you should be able to answerormation sources Questions 6 - 8 to assess what you have learnt. It is stillmmative assessment required that you put down your answers on the mark sheet before looking at the right answer!
  • 38. Question 6: A person with latent TB Write “True” or “False” on the answer sheet. Partners in Global Health Education Click for the correct answerw to use this modulearning outcomesat is TB? a) Is infectious to other people ademiology robiologynsmission b) Feels well bction 1 quizural historyction 2 quiz c) Tuberculin skin test is positive cmptoms and signsction 3 quizgnosis d) Can not develop TB later in life datmentvention and controlction 4 quizormation sourcesmmative assessment
  • 39. Question 7: The following are recognised manifestations of TB Partners in Global Health Education Click for the correct answerw to use this modulearning outcomesat is TB? a) Pericarditis ademiology robiologynsmission bction 1 quizural history b) Meningitisction 2 quizmptoms and signs cction 3 quizgnosis c) Erythema nodosumatmentvention and control dction 4 quizormation sources d) Osteomyelitismmative assessment e) Phlyctenular conjunctivitis e
  • 40. Question 8: The following are indicated in the management of miliary TB Partners in Global Health Education Click for the correct answerw to use this modulearning outcomesat is TB?demiology a) High protein diet a robiologynsmissionction 1 quiz b) BCG Vaccination bural historyction 2 quizmptoms and signsction 3 quiz c) Contact tracing cgnosisatmentvention and controlction 4 quiz d) Isoniazid prophylaxis for 6-12 dormation sources monthsmmative assessment e e) Lumbar puncture
  • 41. Sources of information / bibliography Partners in Global Health Education You can copy and paste the links below into your browser to accessw to use this module the resources:arning outcomesat is TB? • Maartens G, Wilkinson RJ. Tuberculosis. The Lancet 2007; 370:2030-demiology 43 robiology • Diagnostic atlas of intra-thoracic tuberculosis in children; A guide fornsmission Low Income Countries. Dr. Robert Gie, International Union againstction 1 quiz Tuberculosis and Lung Disease (IUATLD) 2003. Available at:ural history http://www.iuatld.orgction 2 quiz • The Division for Tuberculosis Elimination, Centre for Disease Controlmptoms and signs (CDC), Atlanta, USA http://www.cdc.gov/nchstp/tb/faqs/qa.htmction 3 quiz • Stop TB Partnership; http://www.stoptb.org/gnosisatment • WHO – several information resources available at http://www.who.int/tb/en/vention and controlction 4 quiz • Treatment guidelines: http://www.Nice.ac.ukormation sources • TB in the UK: http://www.Hpa.org.ukmmative assessment
  • 42. Partners in Global Health Educationw to use this module Summative assessmentarning outcomesat is TB?demiology robiologynsmission • Well done! We hope that you enjoyedction 1 quiz completing this module.ural historyction 2 quizmptoms and signs • Now try the summative assessment (available fromction 3 quizgnosisatment http://www.medicine.swansea.ac.uk/inthealth.html)vention and controlction 4 quizormation sources • … and good luck!mmative assessment
  • 43. Authors and reviewers Partners in Global Health Education Authors: Expert reviewers:w to use this modulearning outcomes Dr. Ike Lagunju, Consultant We would like to thank the followingat is TB? Paediatrician and Lecturer, College people for reviewing this module:demiology of Medicine, University of Ibadan, Ibadan, Nigeria. robiology At the College of Medicine, University ofnsmission Ibadan, Ibadan, Nigeriaction 1 quiz Dr. David Lewis, Learning Technologist, The School of • Professor Olugbemiro Sodeindeural history Medicine, Swansea University, • Professor Kikelomo Osinusiction 2 quiz Swansea, UKmptoms and signs • Professor Adegoke Faladection 3 quiz Dr. Stephen Allen, Professor ofgnosis Paediatrics and International At the School of Medicine, Swanseaatment Health; The School of Medicine, University, Swansea, UK Swansea University, Swansea, UKvention and control • Professor Julian Hopkinction 4 quiz • Dr Gwyneth Daviesormation sourcesmmative assessment We would like to acknowledge the of the Association of Commonwealth Universities, London for awarding the Fulton Fellowship which supported Dr. Lagunju in developing this module Back
  • 44. Partners in Global Health Educationw to use this modulearning outcomes Answer to question 1aat is TB?demiology This statement is True. robiology nsmissionction 1 quizural history People with open TB produce TB bacilli inction 2 quizmptoms and signs their respiratory droplets. This exposesction 3 quizgnosis their close contacts to the organism.atmentvention and controlction 4 quizormation sourcesmmative assessment Back
  • 45. Partners in Global Health Educationw to use this modulearning outcomesat is TB? Answer to question 1bdemiology robiologynsmissionction 1 quizural history This statement is True.ction 2 quiz mptoms and signs Tubercle bacilli are not only acquired byction 3 quizgnosis respiratory droplets. M. bovis may be acquired byatmentvention and control ingestion of infected unpasteurised cow’s milk.ction 4 quizormation sourcesmmative assessment Back
  • 46. Partners in Global Health Educationw to use this modulearning outcomesat is TB? Answer to question 1cdemiology robiologynsmissionction 1 quizural history This statement is True.ction 2 quiz  In overcrowded and poorly ventilatedmptoms and signsction 3 quizgnosis environments, all diseases that are transmittedatmentvention and control by respiratory droplets are easily spread.ction 4 quizormation sourcesmmative assessment Back
  • 47. Partners in Global Health Educationw to use this modulearning outcomesat is TB? Answer to question 1ddemiology robiologynsmissionction 1 quizural history This statement is True.ction 2 quiz  Prolonged contact and exposure inmptoms and signsction 3 quizgnosis overcrowded, low resource institutions (e.g.atmentvention and control some hospitals and prisons) increases the riskction 4 quizormation sources of acquiring TB.mmative assessment Back
  • 48. Partners in Global Health Educationw to use this modulearning outcomesat is TB? Answer to question 1edemiology robiologynsmission This statement is False.ction 1 quizural historyction 2 quiz Tuberculosis affects all age groups. Infants  and young children not residing in overcrowdedmptoms and signsction 3 quizgnosis environments will not have an increased risk ofatmentvention and control exposure. You will learn about factors whichction 4 quizormation sources favour disease progression after exposuremmative assessment shortly. Back
  • 49. Partners in Global Health Educationw to use this modulearning outcomesat is TB? Answer to question 2ademiology robiologynsmissionction 1 quiz This statement is True.ural historyction 2 quiz Infants and young children, and also the mptoms and signsction 3 quiz elderly, are more likely than young and middle-gnosisatment aged adults to develop an infection andvention and controlction 4 quiz progress to disseminated disease whenormation sourcesmmative assessment exposed to the bacillus. This is thought to be due to an immature or weakened immune system. Back
  • 50. Partners in Global Health Educationw to use this modulearning outcomesat is TB? Answer to question 2bdemiology robiologynsmissionction 1 quizural history This statement is True.ction 2 quiz  People with HIV/AIDS have depressedmptoms and signsction 3 quizgnosis immunity. Therefore, they are more likely toatmentvention and control acquire TB when exposed and also to developction 4 quizormation sources disseminated infection. An annual incidence ofmmative assessment TB as high as 30% has been reported in clinically advanced HIV. Back
  • 51. Partners in Global Health Educationw to use this modulearning outcomesat is TB? Answer to question 2cdemiology robiologynsmissionction 1 quizural history This statement is True.ction 2 quiz mptoms and signs People with these conditions are likely to bection 3 quizgnosis immunocompromised putting them at increasedatmentvention and control risk. Also, those with silicosis and otherction 4 quizormation sources conditions that compromise lung function aremmative assessment also at increased risk if exposed. Back
  • 52. Partners in Global Health Educationw to use this modulearning outcomesat is TB? Answer to question 2ddemiology robiology This statement is False.nsmissionction 1 quizural historyction 2 quiz 70% - 90% of individuals will not develop any mptoms and signsction 3 quiz infection following exposure. In healthy young adultsgnosisatment who do develop a primary TB focus, a competentvention and controlction 4 quiz immune system “walls-off” the lesion and prevents itormation sourcesmmative assessment from spreading. Such people do not develop disease and do not spread TB. Back
  • 53. Partners in Global Health Educationw to use this modulearning outcomesat is TB? Answer to question 2edemiology robiologynsmissionction 1 quizural history This statement is True. ction 2 quizmptoms and signs Many factors present in alcoholics and IV drugction 3 quizgnosis users, such as poor nutritional status andatmentvention and control frequent other infections, tend to impairction 4 quizormation sources immunity and increase the risk of TB disease.mmative assessment Back
  • 54. Partners in Global Health Educationw to use this modulearning outcomesat is TB? Answer to question 3ademiology robiologynsmissionction 1 quiz The correct answer is True: The HIV ural historyction 2 quizmptoms and signs pandemic has caused an increase in the number ofction 3 quizgnosis people susceptible to disseminated TB. The highatmentvention and control number of HIV-infected people in sub-Saharanction 4 quizormation sources Africa is a major factor that underlies the increasingmmative assessment annual incidence of TB in this region. Back
  • 55. Partners in Global Health Educationw to use this modulearning outcomesat is TB? Answer to question 3bdemiology robiologynsmissionction 1 quizural history The correct answer is True: Poverty and ction 2 quizmptoms and signsction 3 quiz poor socioeconomic conditions are associated withgnosisatment factors such as overcrowding and poor nutrition thatvention and controlction 4 quiz increase transmission and susceptibility to TB.ormation sourcesmmative assessment Back
  • 56. Partners in Global Health Educationw to use this modulearning outcomesat is TB? Answer to question 3cdemiology robiologynsmissionction 1 quizural history The correct answer is False: Hygiene ction 2 quizmptoms and signsction 3 quiz has no direct bearing on the transmission of TB.gnosisatmentvention and controlction 4 quizormation sourcesmmative assessment Back
  • 57. Partners in Global Health Educationw to use this modulearning outcomesat is TB? Answer to question 3ddemiology robiologynsmissionction 1 quizural history The correct answer is True: The ction 2 quizmptoms and signs emergence of strains of TB that are resistant to thection 3 quizgnosis commonly-available drugs means that open casesatmentvention and control are more difficult to treat. Therefore, these peoplection 4 quizormation sources continue to spread infection through respiratorymmative assessment droplets. More information about drug-resistant TB is provided later in this module. Back
  • 58. Partners in Global Health Educationw to use this modulearning outcomesat is TB? Answer to question 3edemiology robiologynsmissionction 1 quizural history The correct answer is True: Factors ction 2 quizmptoms and signs such as conflict and inadequate resources andction 3 quizgnosis political will weaken control programmes. TBatmentvention and control transmission increases in these circumstances.ction 4 quizormation sourcesmmative assessment Back
  • 59. Partners in Global Health Educationw to use this modulearning outcomesat is TB? Answer to question 4ademiology robiologynsmissionction 1 quizural historyction 2 quiz The answer is False: the majority of mptoms and signsction 3 quiz people exposed to TB do NOT develop symptomsgnosisatment or show any signs of infectionvention and controlction 4 quizormation sourcesmmative assessment Back
  • 60. Partners in Global Health Educationw to use this modulearning outcomesat is TB? Answer to question 4bdemiology robiology The correct answer is False: thensmissionction 1 quizural historyction 2 quiz primary complex consists of the primary focus and mptoms and signsction 3 quiz hilar lymphadenopathy. This occurs when agnosisatment competent immune system contains the infection.vention and controlction 4 quiz A cavity results from local spread of the primaryormation sourcesmmative assessment focus with central necrosis. Back
  • 61. Partners in Global Health Educationw to use this modulearning outcomesat is TB? Answer to question 4cdemiology robiologynsmissionction 1 quizural historyction 2 quiz The correct answer is False: both the mptoms and signsction 3 quiz pleural inflammation and the resultant effusion aregnosisatment characterised by lymphocyte infiltrationvention and controlction 4 quizormation sourcesmmative assessment Back
  • 62. Partners in Global Health Educationw to use this modulearning outcomesat is TB? Answer to question 4ddemiology robiologynsmissionction 1 quizural history The correct answer is True: miliary TB ction 2 quizmptoms and signsction 3 quiz refers to the characteristic features on CXRgnosisatment signifying dissemination of infection.vention and controlction 4 quizormation sourcesmmative assessment Back
  • 63. Partners in Global Health Educationw to use this modulearning outcomesat is TB? Answer to question 5demiology robiologynsmissionction 1 quiz 1. He is markedly wasted suggesting a chronicural history illnessction 2 quizmptoms and signs 2. There is clear evidence of poverty – even fromction 3 quiz this limited view of the health facilitygnosisatmentvention and controlction 4 quizormation sourcesmmative assessment Back
  • 64. Partners in Global Health Educationw to use this modulearning outcomes Answer to question 6aat is TB?demiology robiologynsmission The answer is False: A person withction 1 quizural history latent TB has TB infection. However,ction 2 quiz  the infection is walled-off in the lungmptoms and signsction 3 quizgnosisatmentvention and control and they are not producing infectedction 4 quizormation sourcesmmative assessment respiratory droplets. They are not an “open case”. Back
  • 65. Partners in Global Health Educationw to use this modulearning outcomesat is TB? Answer to question 6bdemiology robiologynsmission This statement is True. People with latentction 1 quizural history TB usually have no symptoms.ction 2 quiz  Occasionally, they have manifestations ofmptoms and signsction 3 quizgnosisatment an immune response to M. tuberculosisvention and controlction 4 quiz such as erythema nodosum or phlyctenularormation sourcesmmative assessment keratoconjunctivitis. Back
  • 66. Partners in Global Health Educationw to use this modulearning outcomesat is TB? Answer to question 6cdemiology robiologynsmission This statement is True. As in the lastction 1 quizural history question, people with latent TB will havection 2 quiz  developed an immune response to M.mptoms and signsction 3 quizgnosisatment tuberculosis. Therefore, they will developvention and controlction 4 quiz redness and induration at the site of PPDormation sourcesmmative assessment injection. Back
  • 67. Partners in Global Health Educationw to use this modulearning outcomes Answer to question 6dat is TB?demiology robiology The answer is False: The dormant primarynsmissionction 1 quizural history complex in latent TB can become activated.ction 2 quiz This may occur many years after TB mptoms and signsction 3 quizgnosis infection occurred. It occurs when theatmentvention and controlction 4 quiz person’s immune system is compromised,ormation sourcesmmative assessment for example, by malnutrition or steroid treatment. Back
  • 68. Partners in Global Health Educationw to use this modulearning outcomes Answer to question 7aat is TB?demiology This statement is True. robiology nsmissionction 1 quizural history Correct, this statement is True. Tuberculousction 2 quizmptoms and signs pericarditis is a recognised form of the disease.ction 3 quizgnosisatmentvention and controlction 4 quizormation sourcesmmative assessment Back
  • 69. Partners in Global Health Educationw to use this modulearning outcomes Answer to question 7bat is TB?demiology This statement is True. robiology nsmissionction 1 quizural history The organisms can invade the meningesction 2 quizmptoms and signs following haematogenous dissemination, therebyction 3 quizgnosis leading to tuberculous meningitis.atmentvention and controlction 4 quizormation sourcesmmative assessment Back
  • 70. Partners in Global Health Educationw to use this modulearning outcomes Answer to question 7cat is TB?demiology This statement is False. robiologynsmission ction 1 quizural history Erythema nodosum is not a manifestation ofction 2 quizmptoms and signs tuberculous disease. It is seen in patients withction 3 quizgnosis tuberculous infection and occurs as a result ofatmentvention and control hypersensitivity to the tuberculoprotein.ction 4 quizormation sourcesmmative assessment Back
  • 71. Partners in Global Health Educationw to use this modulearning outcomes Answer to question 7dat is TB?demiology This statement is True. robiology nsmissionction 1 quizural history Tuberculous osteomyelitis is a recognised form ofction 2 quizmptoms and signs the disease. The spine is the commonest sitection 3 quizgnosis involved in TB osteomyelitis.atmentvention and controlction 4 quizormation sourcesmmative assessment Back
  • 72. Partners in Global Health Educationw to use this modulearning outcomes Answer to question 7eat is TB?demiology This statement is False. robiologynsmission ction 1 quizural history Phlyctenular conjunctivitis is not a manifestation ofction 2 quizmptoms and signs TB disease. Just as it is explained in (c), it is a signction 3 quizgnosis of TB infection and an allergic reaction to theatmentvention and control tuberculoprotein. It does not signify the presence ofction 4 quizormation sources the disease.mmative assessment Back
  • 73. Partners in Global Health Educationw to use this modulearning outcomes Answer to question 8aat is TB?demiology This statement is True. robiology nsmissionction 1 quizural history Most patients with miliary TB are malnourishedction 2 quizmptoms and signs and so nutritional rehabilitation is an essentialction 3 quizgnosis aspect of their management.atmentvention and controlction 4 quizormation sourcesmmative assessment Back
  • 74. Partners in Global Health Educationw to use this modulearning outcomes Answer to question 8bat is TB?demiology This statement is False. robiologynsmission ction 1 quizural history There is no indication for BCG vaccination after action 2 quizmptoms and signs patient has developed the disease! BCG is givenction 3 quizgnosis as part of routine childhood immunisation in someatmentvention and control countries and helps to prevent life-threateningction 4 quizormation sources forms of TB.mmative assessment Back
  • 75. Partners in Global Health Educationw to use this modulearning outcomes Answer to question 8cat is TB?demiology This statement is True. robiology nsmissionction 1 quizural history This is very important. Close contacts of thection 2 quizmptoms and signs patient should be tested for evidence ofction 3 quizgnosis tuberculous infection or disease and managedatmentvention and control appropriately. This is an important public healthction 4 quizormation sources measure in the control of TB.mmative assessment Back
  • 76. Partners in Global Health Educationw to use this modulearning outcomes Answer to question 8dat is TB?demiology robiologynsmission This statement is False. ction 1 quiz This patient requires treatment with combinationural historyction 2 quiz chemotherapy of anti-TB drugs because he has themptoms and signsction 3 quiz disease. INH prophylaxis is only given to people who havegnosisatment been infected with the tubercle bacilli but do not have thevention and control disease. The drug helps to prevent progression to disease.ction 4 quizormation sourcesmmative assessment Back
  • 77. Partners in Global Health Educationw to use this modulearning outcomes Answer to question 8eat is TB?demiology This statement is True. robiology nsmissionction 1 quizural history Lumbar puncture is indicated in all patients withction 2 quizmptoms and signs miliary TB, as this condition signifiesction 3 quizgnosis haematogenous dissemination and meningealatmentvention and control involvement must be excluded.ction 4 quizormation sourcesmmative assessment Back

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