A mycobacterial disease that is a major cause of disability and death in most of the world, especially developing countries. The initial infection usually goes unnoticed; tuberculin skin test sensitivity appears within 2-10 weeks. Early lung lesions commonly heal, leaving no residual changes except occasional pulmonary or tracheobronchial lymph node calcifications. About 10% of those initially infected will eventually develop active disease, half of them during the first 2 years following infection; 90% of untreated infected individuals will never develop active TB. Appropriate completion of treatment for latent TB infection (LTBI) can considerably reduce the lifetime risk of clinical tuberculosis (TB disease) and is effective in persons with HIV infection.
In some individuals, initial infection may progress rapidly to active tuberculosis. This is more common among infants, where the disease is often disseminated (e.g. miliary) or meningeal, and in the immunosuppressed, such as HIV-positive individuals.
Extrapulmonary TB occurs less commonly (30%) than pulmonary TB (70%). Children and persons with immunodeficiencies, such as HIV infection, have a higher risk of extrapulmonary TB, but pulmonary disease remains the most common type worldwide, even in these more susceptible groups. TB disease may affect any organ or tissue; in order of frequency: lymph nodes, pleura, pericardium, kidneys, bones and joints, larynx, middle ear, skin, intestines, peritoneum, eyes.
Pulmonary TB may arise from exogenous reinfection or endogenous reactivation of a latent focus originating from the initial sub-clinical infection. If untreated, about 65% of patients with sputum smear-positive pulmonary tuberculosis die within 5 years, most of these within 2 years. The classification of TB for treatment purposes is based mainly on the presence or absence of tubercle bacilli in the sputum. A smear positive for acid-fast bacilli (AFB) is indicative of high infectiousness. Fatigue, fever, night sweats and weight loss may occur early or late; localizing symptoms of cough, chest pain, hemoptysis and hoarseness become prominent in advanced stages. Radiography of the chest reveals pulmonary infiltrates, cavitations and, later, fibrotic changes with volume loss, all most commonly in the upper segments of the lobes.
| Table
of Contents 1. Identification 2. Infectious agents 3. Occurrence 4. Reservoir 5. Mode of transmission 6. Incubation period 7. Period of communicability 8. Susceptibility 9. Methods of control
A. Preventive measures: |
Immunocompetent people who are or have been infected with Mycobacterium tuberculosis, M. africanum or M. bovis usually react to an intermediate strength tuberculin skin test equivalent to 5 IUs of the International Standard of Purified Protein Derivative-Standard (PPD-S). A positive reaction is defined as a 5, 10, or 15 mm induration according to the risk of exposure or disease. Among persons with active TB disease 10%-20% may have no reaction to PPD--a negative skin test does not therefore rule out active TB disease. Interpreting the PPD skin test induration size is important to define positivity and the need to start treatment of latent TB infection (previously termed chemoprophylaxis or preventive chemotherapy). An induration of 5 mm or more is considered positive among HIV-infected persons, persons on highly potent immunosuppressive treatment, persons showing fibrotic lesions on chest X-rays, and recent close contacts of infectious TB patients. A diameter of 10 mm or more is considered positive among persons infected for less than 2 years and those with high-risk conditions (e.g. diabetes mellitus, hematological disorders, injection drug use, end-stage renal disease, rapid weight loss). Any reaction of 15 mm or more should be considered positive among low-risk persons.Skin tests for anergy are no longer recommended, even for high-risk patients. In many industrialized countries, including the USA, routine skin testing of all children is no longer recommended; children to be tested include those suspected of having active TB disease and those exposed to an infectious case; immigrants from an endemic country may also be tested. Incarcerated individuals and persons with HIV infection or children residing in a household with an HIV-infected person should be tested annually. Children should be tested every 2-3 years if exposed to persons at high risk of disease. Testing at 4-6 and 11-12 is indicated if the parents immigrated from a high-risk area or if the children reside in high-risk communities, as defined by local public health authorities.
In some persons with TB infection, delayed type hypersensitivity to tuberculin may wane with time. When skin-tested many years after initial infection, they may show a negative reaction, but the skin test may boost their ability to react to tuberculin and cause a positive reaction to subsequent tests. This “boosted” reaction may be mistaken for a new infection; it can persist for 1 to 2 years. Boosting has also been reported in persons who have received BCG. A 2-step testing procedure distinguishes boosted reactions and reactions due to new infection. If the reaction to the first test is classified as negative, a positive reaction to a second test 1-3 weeks later probably represents a boosted reaction. On the basis of this second result, the person should be classified as previously infected and managed accordingly. If the second test is also negative, the person should be classified as uninfected. Two-step testing should be used for initial skin testing of adults who will be retested periodically (e.g. health care workers), who are not known to have a prior positive skin test and have not had a tuberculin test during the previous year or so.
Demonstration of acid-fast bacilli in stained smears from sputum or other body fluids in a clinical and epidemiological situation suggestive of TB is a presumptive diagnosis of active TB disease and usually justifies initiation of antituberculosis treatment. Where resources permit, isolation of organisms of the Mycobacterium tuberculosis complex on culture confirms the diagnosis and also permits determination of drug susceptibility for the infecting organism. In the absence of bacteriological confirmation, active disease can be presumed if clinical, histological or radiological evidence is suggestive of TB and other likely disease processes can be ruled out.
 This photomicrograph reveals Mycobacterium tuberculosis bacteria using acid-fast Ziehl-Neelsen stain; Magnified 1000X. The acid-fast stains depend on the ability of mycobacteria to retain dye when treated with mineral acid or an acid-alcohol solution, such as the Ziehl-Neelsen or the Kinyoun stains that are carbolfuchsin methods specific for M. tuberculosis. |
Mycobacterium tuberculosis complex. This includes M. tuberculosis, M. africanum, M. canettii (the latter two responsible for a small number of cases in Africa), all primarily from humans, and M. bovis primarily from cattle. Other mycobacteria occasionally produce disease clinically indistinguishable from tuberculosis; the causal agents can be identified only through culture. Genetic sequence analyses using PCR offers potential for noncultural identification.
Worldwide; industrialized countries showed downward trends of mortality and morbidity for many years, but in the mid-1980s reported cases reached a plateau; areas and population groups with a high prevalence of HIV infection or with large numbers of persons from areas with a high prevalence of tuberculosis have since increased. In regions with declining TB incidence, TB mortality and morbidity rates increase with age, and in older people rates are higher in males than in females. In regions and groups with high rates of new transmission and rising incidence, morbidity is highest among working-age adults. TB morbidity rates are higher among disadvantaged populations, and usually higher in cities than in rural areas.
In the low incidence areas of USA and many other industrialized countries, most TB disease in adults results from reactivation of latent foci remaining from an initial infection. In some large urban areas about one-third of TB disease cases may result from recent infection. Long exposure of some contacts, notably household associates, may lead to a 30% lifetime risk of becoming infected. For infected children, the lifetime risk of developing disease may approach 10%. For people infected with HIV, the annual risk has been estimated at 2%-13%, depending upon he CD4 cell count, and the cumulative risk at up to 50%. Epidemics have been reported in enclosed spaces, such as nursing homes, shelters for the homeless, hospitals, schools, prisons, and during long-haul-flights. From 1989 to the early 1990s, extensive outbreaks of multidrug-resistant TB (MDR-TB), defined as resistance to at least isoniazid and rifampicin, have been recognized in US settings where many HIV-infected persons are congregated (hospitals, prisons, drug treatment clinics and HIV residences). These outbreaks are associated with high fatality rates and transmission of M. tuberculosis to health care workers. Strict enforcement of infection control guidelines, pro-active case-finding, contact investigations, and measures to ensure completion of appropriate treatment regimens have been effective in combating and preventing these outbreaks. Worldwide, 1%-2% of all TB cases at most are due to multidrug resistant strains; in some countries; e.g. parts of China, India, the former USSR, MDR-TB is a major problem.
The prevalence of TB infection detected by tuberculin testing increases with age. The incidence of infection in industrialized countries has declined rapidly in recent decades; in the USA, the annual risk of new infection is estimated to average about 10/100 000 people at most, although there probably are areas in the USA with a relatively high annual risk of new infection. In areas where human infection with mycobacteria other than tubercle bacilli is prevalent, cross-reactions complicate interpretation of the tuberculin reaction.
Human infection with M. bovis, the bovine tubercle bacillus, is still a problem in areas where the disease in cattle has not been controlled and milk and milk products are consumed raw.
Primarily humans, rarely primates; in some areas, diseased cattle, badgers, swine and other mammals are infected.
Exposure to tubercle bacilli in airborne droplet nuclei, 1 to 5 microns in diameter, produced by people with pulmonary or respiratory tract tuberculosis during expiratory efforts (coughing, singing or sneezing), and inhaled by a vulnerable contact into the pulmonary alveolae, where they are taken up by alveolar macrophages, initiating a new infection. Health care workers are exposed during procedures such as bronchoscopy or intubation and at autopsy. Laryngeal tuberculosis is highly contagious but rare. Prolonged or repeated close exposure to an infectious case may lead to infection of contacts. Direct invasion through mucous membranes or breaks in the skin may occur but is rare. Bovine tuberculosis, a rare event, results from exposure to tuberculous cattle, usually through ingestion of unpasteurized milk or dairy products, and sometimes through airborne spread to farmers and animal handlers. Except for rare situations where there is a draining sinus, extrapulmonary tuberculosis (other than laryngeal) is generally not communicable.
From infection to demonstrable primary lesion or significant tuberculin reaction, about 2-10 weeks. While the subsequent risk of progressive pulmonary or extrapulmonary TB is greatest within the first year or two after infection, latent infection may persist for a lifetime. Tuberculin reactivity also persists regardless of treatment. HIV infection increases the risk and shortens the interval for the development of TB disease following infection.
Theoretically, as long as viable tubercle bacilli are discharged in the sputum. Some untreated or inadequately treated patients may be intermittently sputum-positive for years. The degree of communicability depends on number of bacilli discharged, virulence of the bacilli, adequacy of ventilation, exposure of bacilli to sun or UV light, and opportunities for aerosolization through coughing, sneezing, talking or singing, or during procedures such as intubations or bronchoscopies and at autopsies. Effective antimicrobial chemotherapy usually eliminates communicability within 2-4 weeks, at least in household settings, even though TB bacteria may still grow from expectorated sputum. Children with primary tuberculosis are generally not infectious.
The risk of infection with the tubercle bacillus is directly related to the degree of exposure and does not appear related to genetic or other host factors. The first 12-24 months after infection constitute the most hazardous period for the development of clinical disease. The risk of developing disease is highest in children under 3, lowest in later childhood, and high again among young adults, the very old and the immunosuppressed. Population groups not previously touched by tuberculosis appear to have greater susceptibility to new infection and disease. Reactivation of long-latent infections accounts for a large proportion of TB disease cases in older people. For infected persons, susceptibility to TB disease is markedly increased by HIV infection and other forms of immunosuppression, and among the underweight or undernourished, people with a debilitating disorder (e.g. chronic renal failure, some forms of cancer, silicosis, diabetes or gastrectomy), or substance users. For adults with latent TB infection also infected with HIV, the lifetime risk of developing TB disease rises from an estimated 10% to up to 50%. This has resulted in a parallel pandemic of TB disease: in some urban sub-Saharan African areas, where 10-15% of the adult population are co-infected with both HIV and TB; annual TB disease rates have increased 5- to 10-fold between the 1980s and today. Under such conditions, the risk of multi-drug-resistant (MDR) TB is high where TB control is inadequate.
A. Preventive measures:
1. Promptly identify, diagnose and treat potentially infectious patients with TB disease. Establish case-finding and treatment facilities for infectious cases to reduce transmission.
2. Ensure medical, laboratory and X-ray facilities for
prompt
examination of patients, contacts and suspects; ensure
provision of drugs and facilities for early and complete
treatment of cases and people at high risk of infection; and
of beds for those needing hospitalization.
In high incidence areas, direct microscopy examination of
sputum for those presenting because of chest symptoms
(with culture confirmation when possible) may give a high
yield of infectious tuberculosis. In most situations, direct
microscopy is the most cost-effective method of casefinding
and is the first priority in developing countries.
Because of serious outbreaks of MDR-TB in the 1990s, all
initial isolates in the USA and many other countries must be
submitted to drug susceptibility testing. In countries with
limited resources/laboratory capacity, drug susceptibility
testing may be restricted to re-treatment cases, such as
treatment failures and defaulters of previous treatment.
3. Educate the public in mode of spread and methods of control and regarding the importance of early diagnosis and continued adherence to treatment.
4. Reduce or eliminate those social conditions that increase the risk of infection.
5. Set up TB prevention and control programs in institutional settings where health care is provided and/or where immunocompromised patients such as HIV-infected persons congregate (e.g. hospitals, drug treatment programs, prisons, nursing homes and homeless shelters).
6. Preventive chemotherapy with isoniazid for
6-12 months
has been effective in preventing the progression of latent
TB infection to TB disease in up to 90% of compliant
individuals. Studies in adults with HIV infection have shown
the effectiveness of alternative regimens including shorter
courses (2 months) of rifampicin and pyrazinamide. Since
this regimen has been associated with severe hepatotoxicity
it is not currently recommended for general use. It is
important to rule out active TB disease before starting
treatment for latent TB infection, especially in immunocompromised
persons such as HIV-infected individuals, in order
to avoid inadvertently treating active disease with a 1- or
2-drug regimen that would encourage the development of
drug resistance. Because of the risk of isoniazid-associated
hepatitis, isoniazid is not routinely advised for persons with
active liver disease.
Persons started on treatment for latent TB infection must be
informed of possible adverse effects (e.g. hepatitis, drug
fever or severe rash), reminded of these possibilities and
checked for symptoms monthly, prior to prescription refills;
they should be advised to discontinue treatment and seek
medical advice if suggestive symptoms develop. Baseline
liver function tests are important in patients with signs,
symptoms or history of liver disease and in those who abuse
alcohol. Avoiding or discontinuing isoniazid generally is
advised for persons with transaminase levels more than 5
times the upper limit of normal values (3 times if symptoms
suggest hepatic dysfunction). Directly observed supervised
treatment should be used when possible (e.g. prisons, drug
treatment programs, schools) and can be administered
twice weekly, adjusting dosage upwards to compensate for
the reduction in frequency. Not more than 1 month’s
supply of medication should be given at any one time, and
patients should be queried at least monthly about adverse
effects. Routine biochemical monitoring for hepatitis is not
necessary but monitoring is mandatory if symptoms or signs
of hepatitis occur.
During pregnancy, it may be wise to postpone treatment for
latent TB infection until after delivery except in high-risk
individuals, and then it should be administered with caution.
Mass treatment for latent TB infection is unrealistic and
unsuitable in most communities unless there is a wellorganized
program to supervise and encourage adherence
to treatment and unless a high rate of cure can be achieved
among patients with active TB disease. Persons with HIV
infection and a positive PPD who do not have active TB
disease should receive treatment for latent TB infection.
7. Provide public health nursing and outreach services for support to patients; ensure supervision of treatment and arrange for examination and treatment for latent TB infection among contacts.
8. Persons infected with HIV should be skin-tested with intermediate strength PPD at the time their HIV infection is identified; they should start treatment for latent TB infection if they are PPD-positive (5 mm or more induration) and if active TB disease has been ruled out. Conversely, all people with evidence of TB disease should be considered for counselling and tested for HIV infection if appropriate counselling is available.
9. In industrialized countries where BCG immunization is not routinely carried out, selective tuberculin-testing and treatment for latent TB infection may be considered for groups at high risk of TB infection and/or HIV infection, including health care workers and groups such as prison inmates and injecting drug users; this may also be considered for foreignborn persons from areas of high tuberculosis prevalence, and possibly for travellers to and from high-prevalence areas. In population groups where disease still occurs, systematic tuberculin test surveys may help monitor the incidence of infection. Prior BCG immunization may complicate interpretation of a positive skin test in a child or recently immunized adult. Since skin test reactions from BCG wane over time, strongly positive reactions or significant increases in reactivity should be considered indicative of TB infection. In the USA, targeted testing, standard interpretation of tuberculin skin tests, and treatment for latent TB infection are recommended regardless of prior history of BCG vaccination.
10. BCG immunization of uninfected (tuberculin-negative) people induces tuberculin reactivity in approximately half of vaccinees. Tuberculin reactivity and protection vary markedly in different field trials, and are perhaps related to immunological characteristics of population, quality of vaccine, or BCG strain. Some controlled trials indicate that protection may persist for as long as 20 years in highincidence situations; others have shown no protection at all. Meta-analyses on BCG effectiveness provide conflicting results. Ongoing efforts to develop a vaccine more effective than BCG have identified candidate vaccines that are currently undergoing testing in humans for safety and immunogenicity. Case-control and contact studies consistently show protection against TB meningitis and disseminated disease in children under 5. Because the risk of infection is low in many industrialized countries, BCG may not be used routinely; it may be considered for children with a negative PPD skin test who cannot be placed on preventive therapy but have continuous exposure to people with untreated or ineffectively treated active disease, or are continuously and irremovably exposed to patients infected by organisms resistant to isoniazid and rifampicin. BCG is contraindicated for people with immunodeficiency diseases including symptomatic HIV infection; WHO recommends BCG for routine immunization programs in developing countries, including asymptomatic HIV-infected children and those at high risk of acquiring HIV infection.
11. Eliminate bovine tuberculosis among dairy cattle through tuberculin testing and slaughtering of reactors; pasteurize or boil milk.
12. Take measures to prevent silicosis among those working in industrial plants and mines.
Report to local health authority when diagnosis is suspected: Obligatory case report in most countries, Class 2 (see Reporting). Case report must state if the case is bacteriologically positive or based on clinical and/or X-ray findings. Health departments must maintain a register of cases requiring treatment and be actively involved with planning and monitoring the course of treatment.
Isolation: For pulmonary tuberculosis, control of infectivity is best achieved through prompt specific drug treatment, usually leading to sputum conversion within 4-8 weeks. Hospitalization is necessary only for patients with severe illness requiring hospital-level care and for those whose medical or social circumstances make home-treatment impossible. If practicable and possible, consider placing adult patients who reside in a congregate setting with sputum-positive pulmonary tuberculosis in a private room with negative pressure ventilation. Patients should be taught to cover both mouth and nose when coughing or sneezing. Persons entering the room should preferably wear personal respiratory protective devices capable of filtering submicron particles. Patients whose sputum is bacteriologically negative, who do not cough and who are known to be on adequate chemotherapy (known or probable drug susceptibility and clear clinical response to treatment) do not require isolation, nor do children with active TB disease with negative sputum smears and no cough--they are not contagious. Adolescents should be managed as adults. The need to adhere to the prescribed chemotherapeutic regimen must be emphasized repeatedly to all patients. Proper patient support ensuring that drugs are taken as prescribed, including DOTS (the internationally recommended strategy for TB control), is essential, especially for persons with suspected drug resistance, a previous history of poor compliance to treatment, or who live in conditions where relapse would result in exposure of many other persons.
Concurrent disinfection: Handwashing and good housekeeping practices must be maintained according to policy. No special precautions necessary for handling fomites. Decontamination of air may be achieved by ventilation; this may be supplemented by ultraviolet light.
Quarantine: Not applicable.
Management of contacts: In countries where BCG vaccination is not routinely undertaken, preventive chemotherapy (also referred to as chemoprophylaxis or treatment of latent TB infection--TLTBI) is usually recommended for persons who are or have been in contact with TB infection and in whom TB disease has been ruled out. Treatment is also recommended for highest-risk persons--HIV-infected and those younger than 5 years old--even though a skin test is negative, once TB disease has been ruled out. Persons with an initial negative skin test are also offered a repeat skin test about 3 months after the contact has been “broken” (which may mean the day the source case starts treatment). Small children with negative skin tests at 3 months can be taken off TLTBI at that time. HIV-infected contacts usually are advised to complete a course of TLTBI whatever the 3-month skin test result. BCG immunization of tuberculin-negative household contacts may be warranted under special circumstances (see above).
In the USA and many other countries, investigation of contacts and source of infection: PPD testing of all members of the household and other close contacts is recommended. If negative, a repeat skin test should be performed 2-3 months after exposure has ended. Chest X-rays should be obtained for positive reactors (at least 5 mm induration) when identified. TLTBI is indicated (see 9A6) for contacts who are positive reactors and for some initially negative reactors at high risk of developing active disease, especially young (5 or younger) and HIV-infected close contacts, at least until the repeat skin test is shown to remain negative. In many developing countries, investigation of household contacts is limited to sputum microscopy of those contacts who have symptoms suggestive of TB disease.Specific treatment: Adequate patient support ensuring that drugs are taken as prescribed, including directly observed treatment, is highly effective in achieving cure and is recommended for treatment of TB disease worldwide. Patients with TB disease must be given prompt treatment with an appropriate combination of antimicrobial drugs and sputum smears must be monitored at regular intervals. For most cases of drug-susceptible disease, a 6-month regimen is recommended, including isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA) and ethambutol (EMB) for the first 2 months, followed by INH and RIF for 4 months. After drug susceptibility results become available, a specific drug regimen can be selected if drug resistant strains are present (e.g. to isoniazid and rifampicin).
As regards HIV-associated TB, interactions between drugs must be borne in mind. Rifampicin lowers serum levels of many protease inhibitors and some nucleoside reverse transcriptase inhibitors and its replacement by rifabutin can be considered when antiretrovirals are started simultaneously with anti-TB drugs, although with some loss of effectiveness for the latter. Patients on rifampicin with advanced immunosuppression must receive TB treatment at least thrice weekly or even daily. Co-trimoxazole prophylaxis against opportunistic infections may reduce mortality and mortality in HIVinfected TB patients; post-treatment isoniazid prophylaxis can decrease the risk of TB recurrence but does not affect overall survival.If sputum fails to become negative after 2 months of regular treatment or reverts to positive after a series of negative results, or if clinical response is poor, examination for drug compliance and for bacterial drug resistance is indicated. Treatment failure (sputum smear positivity at 5 months from start of treatment) can be due to irregular drug-taking or to the presence of drug-resistant bacilli. A change in supervision practices may be required if a favorable clinical response is not observed. If drug susceptibility testing is available, at least 2 drugs to which the organisms are susceptible should be included in the regimen; a single new drug should never be added to a failing regimen. If INH or RIF cannot be included, treatment should continue for at least 18 months after cultures have become negative.
For newly diagnosed smear-positive patients in developing countries, WHO recommends that treatment include 2 months of daily doses of INH, RIF, PZA and EMB, followed by 4 months of daily or intermittent INH and RIF. All treatment should be supervised or directly observed; if treatment cannot be directly observed in the subsequent phase, 6 months of INH and EMB may be substituted.
Children receive the same regimens as adults with some modifications; susceptibility of the causal organism can often be inferred from testing isolates of the adult source case. Children with pulmonary or extrapulmonary TB can be treated with INH, RIF, PZA for 2 months followed by INH and RIF for 4 months. EMB generally is not used until the child is old enough for color vision to be checked (usually 5 years or older), although it is usually added to the regimen of children with severe disease. Children with meningitis, miliary disease, bone/joint disease or HIV infection should be treated for 9 to 12 months.
All drugs occasionally cause adverse reactions. Thoracic surgery is rarely indicated, usually in multidrug resistant cases. For details of case management (including MDR- and HIV-associated TB) see Treatment of tuberculosis: Guidelines for national programmes (WHO/CDS/TB/2003.313 http://whqlibdoc.who.int/hq/2003/WHO_CDS_TB_2003.313.pdf)
Monitoring of treatment response calls for symptom evaluation and sputum smear microscopy and culture monthly, or at least after 1, 2, 5 and 6 months, as in most developing countries where only smear microscopy is readily available. Radiological abnormalities may persist for months after a bacteriological response, often with permanent scarring, and monitoring by serial chest radiographs is thus not recommended. An end-oftreatment chest X-ray in patients with pulmonary or pleural TB may help show new baseline anatomy.
WHO strongly recommends that cohort analysis of treatment outcomes include all patients registered for treatment. The 6 mutually exclusive categories of treatment results are: bacteriologically proven cure; treatment completion (without bacteriological evidence of cure); failure (smear positive at month 5); default; death; and transfer to other administrative units. Cohort analysis allows proper evaluation of treatment program performance and prompts corrective measures in case of unacceptable levels of treatment failures, deaths, and defaulting.
Recognition and treatment of aggregates of new infections and secondary cases of disease resulting from contact with an unrecognized infectious case; intensive search for and treatment of the source of infection.
In industrialized countries, a high proportion of new disease cases arises among foreign-born persons, especially those from high prevalence areas. In the USA the annual proportion of new cases born abroad has been growing steadily and exceeded 50% for the first time in 2002. Surveillance allows the identification of those at excess risk and, among that population, screening allows individuals to benefit from curative and preventive interventions. These include: i) adequate notification systems (physician and laboratory reports) to identify populations at risk; ii) chest radiograph, PPD, smears and culture with curative/preventive interventions for symptomatic persons among the entering foreign-born population; iii) provision of comprehensive curative and preventive services against tuberculosis; iv) provision of culturally and socially sensitive services and follow-up of interventions; v) ongoing evaluation of interventions (efficiency/efficacy).
Mycobacteria other than M. tuberculosis, M. africanum, M. bovis and M. leprae are ubiquitous and may produce disease in humans. These acid-fast bacilli have in the past been variously termed atypical, unclassified mycobacteria, nontuberculous mycobacteria (NTM), or mycobacteria other than tuberculosis (MOTT). Of the identified species only about 15 are recognized as pathogenic to people.
Clinical syndromes associated with the pathogenic species of mycobacteria can be classified broadly as follows:
1. Disseminated disease--(in the presence of severe immunodeficiency as in AIDS)--M. avium complex, M. kansasii, M. haemophilum, M. chelonae;
2. Pulmonary disease resembling tuberculosis--M. kansasii, M. avium complex, M. absessus, M. xenopi, M. simiae;
3. Lymphadenitis (primarily cervical)--M. avium complex, M. scrofulaceum, M. kansasii;
4. Skin ulcers--M. ulcerans (see Buruli ulcer), M. marinum;
5. Post-traumatic wound infections--M. fortuitum, M. chelonae, M. absessus, M. marinum, M. avium complex;
6. Nosocomial disease: surgical wound infections (following cardiac surgery, mammoplasty wounds), catheter-related infections (bacteraemia, peritonitis, post-injection abscesses)--M. fortuitum, M. chelonae, M. absessus;
7. Crohn disease--M. paratuberculosis has been suggested as the causative agent in some cases of regional enteritis; incorrect diagnosis of inflammatory bowel disease may delay diagnosis and treatment of TB disease of the bowel, and worsening of disease if immunosuppressive drugs are used inadvertently.
The epidemiology of the diseases attributable to these organisms has not been well delineated, but the organisms have been found in soil, milk and water; other factors, such as host tissue damage and immunodeficiency, may predispose to infection. With the exception of organisms causing skin lesions, there is no evidence of person-to-person transmission. A single isolation from sputum or gastric washings can occur in the absence of signs or symptoms of clinical disease. Multiple isolations of MOTT from respiratory specimens, in the absence of illness or other specific pathology, may be evidence of commensal colonization, with no clinical significance. A single positive culture from a wound or tissue is generally considered diagnostic.
In general, the diagnosis of disease requiring treatment is based on repeated isolations of many colonies from symptomatic patients with progressive illness. Where human infections with nontuberculous mycobacteria are prevalent, cross-reactions may interfere with the interpretation of skin tests for M. tuberculosis infection. Chemotherapy is relatively effective against M. kansasii and M. marinum disease, but traditional antituberculosis drugs (especially PZA) may not be effective for other mycobacterioses. Some cases of failure of TB treatment, in settings with limited facilities for culture and sensitivity testing, may in fact be cases of disease with MOTT, which commonly are resistant to standard TB drugs. Drug susceptibility tests on the isolated organism will help select an efficient drug combination. Surgery should be given more consideration than in TB disease, especially when the disease is limited, as in localized pulmonary disease, cervical lymphadenitis or subcutaneous abscess. Disseminated Mycobacterium avium complex (MAC) infection is a major problem in HIV-infected persons; until recently it was considered poorly amenable to treatment. Drug regimens containing rifabutin and clarithromycin have shown therapeutic potential. Rifabutin has been approved for MAC prophylaxis in HIV-infected patients with CD4+ counts below 100.
Further information on http://www.who.int/tdr/disease/tb/default.htm
[M. Raviglione]