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Tuberculosis

Tuberculosis

Causative Agent

Mycobacterium tuberculosis (rarely M. bovis).

Incubation Period

Weeks to years

Initial infection usually goes unnoticed—latent TB infection (LTBI).  Approximately 10% of those with LTBI will eventually progress to active disease, and half will do so in the first 2 to 3 years following infection.  Immunocompromised patients (e.g. HIV infection, diabetes mellitus) are at higher risk for developing active TB.

Infectious Period

Sputum bacteriologically positive, drug-susceptible pulmonary TB is considered non-infectious after two weeks of effective therapy. (Multi-drug resistant TB may require a longer period of effective therapy before cases become non-infectious).

Non-pulmonary TB (except for laryngeal TB) is not infectious.

Transmission

Airborne. Rarely through unpasteurized milk (M. bovis).

Epidemiology

  • The TB incidence in the local Singapore population (i.e. citizens and permanent residents) rose for the first time in ten years to 40 per 100,000 in 2008 and 39 per 100,000 in 2009. Prior to this, the TB rate of the local population had declined steadily from 57 per 100,000 in 1998 to 35 per 100,000 in 2007. TB continued to be a disease of older males. The TB incidence rate among Malays remained the highest among the three main ethnic groups.
  • The majority (83.6%) had pulmonary TB. The two commonest extrapulmonary sites were the pleura and the lymphatic system.
  • The number of TB cases among foreigners in Singapore has increased since  2005. In 2009, long-term immigration pass holders comprised 20.8% and short- term pass holders 21.9% of all notified TB cases in the country.
  • In 2009, the proportion of primary drug resistance among new pulmonary TB cases in Singapore residents examined was 6.6%. Streptomycin resistance was the most commonly encountered. The proportion of multi-drug resistant (MDR) tuberculosis among new pulmonary TB cases in Singapore residents examined has remained very low, at 0.3%. The MDRTB rate is, however, 10 or more times higher among foreigners reported with TB in Singapore, i.e. 3% among Indonesians and those from the People’s Republic of China, 4% among Vietnamese and 6% among Burmese.
  • Pulmonary TB: Common symptoms  are prolonged cough (> 3 weeks), chest  pain and haemoptysis. Patients with miliary TB may have minimal respiratory symptoms and present with systemic complaints.
  • Extrapulmonary TB: Lymphadenitis (especially cervical), pleural effusion, osteomyelitis, meningitis or gastrointestinal involvement.
  • Patients often have associated fever, night sweats, loss of appetite,  loss  of weight and fatigue.
  • Risk factors for HIV and examination for physical signs of HIV (e.g. oral candidiasis) should be sought.

  • Chest X-Ray. All persons with chest X-ray findings suggestive of TB  should have sputum specimens submitted for microbiological examination.
  • Acid fast bacilli (AFB) smear and TB culture of sputum and other pathological specimens such as pleural fluid, CSF, urine and pus. All patients suspected of having pulmonary TB should have at least two, preferably three, sputum specimens obtained for microscopic examination and TB culture (with drug susceptibility testing), with at least one early morning specimen where possible.
  • Nucleic acid amplification tests (NAATs) do not obviate the  need  for  TB culture as these tests do not provide information on the drug susceptibility pattern of the organism. The NAATs are not sufficiently sensitive for a negative result to exclude TB in smear-negative sputum samples
  • HIV testing should be performed for all patients.
  • Screening for diabetes mellitus is strongly recommended.



  • Healthcare providers are required to notify suspected and confirmed cases to the Director, TB Control Unit, c/o STEP Registry (Form MD 532 or electronically via CD-LENS) within 72 hours.
  • Attending physicians should also submit Form MD 117, or via CD-LENS, to update treatment progress and changes at each visit, preferably monthly until a final outcome is reached.


  • Any physician treating a patient for TB is assuming an important public health responsibility; he must not only prescribe an appropriate regimen but also becapable of assessing adherence of the patient to the regimen, and addressing poor adherence when it occurs.
  • Initial drug therapy for new cases should consist of 4 first-line drugs: isoniazid (INH), rifampicin, pyrazinamide and ethambutol or streptomycin. Initiating treatment using a quinolone as a first-line drug is not a standard practice. In uncomplicated, drug-susceptible TB cases, 6 months of drug therapy is sufficient. Monotherapy should never be given as this will generate drug- resistant TB. A single drug should never be added to a failing regimen.
  • The treating physician should be alert to the TB culture and drug susceptibility results which may take several weeks to be available. There should be an index of suspicion for the possibility of drug-resistant TB in patients who were previously treated, who fail treatment, who are known contacts of MDRTB cases, or who come from countries with high prevalence of TB drug resistance.
  • Non-adherence because of adverse reactions and prolonged therapy is a major problem. Non-adherence leads to possible treatment failure and acquired drug resistance.
  • Directly observed therapy (DOT) is recommended for all TB patients,  as  it allows for closer monitoring, thus ensuring adherence to treatment, preventing the development of drug resistance. DOT is available at the TB Control Unit (TBCU) and polyclinics.
  • All patients should be issued with medical leave for at least two weeks, after which they may be considered non-infectious.
  • Follow-up appointments should be at no longer than monthly intervals  for patients on TB treatment. Patients should be asked about clinical response to treatment, adherence to therapy and any adverse drug effects, particularly hepatitis. Patients with signs or symptoms suggestive of hepatitis such as jaundice, nausea, loss of appetite, abdominal discomfort, tea coloured urine and easy fatiguability should be further evaluated with liver function studies.
  • Response to treatment is best monitored bacteriologically with repeat sputum examination at the very least at two months (end of intensive phase) and at the end of treatment. Those who do not convert their sputum cultures at two months may require extension of treatment duration beyond six months.
  • A record of all medications given, bacteriological response, and  adverse  reactions should be maintained for all patients.
  • Sputum smear-positive cases, relapsed cases and those with risk factors for drug-resistant TB should be referred to the TBCU.
  • Non-compliance to TB treatment should be detected promptly, and these cases should be referred to TBCU.

In an endemic area, BCG vaccination at birth helps to reduce the incidence of miliary TB and TB meningitis in childhood.

  • Early recognition and early appropriate treatment of TB cases. Suspect TB in any person with unexplained cough for three or more weeks.
  • In hospitals and other institutions, isolation of smear-positive patients for at least 2 weeks after initiation of appropriate drug therapy will help reduce transmission.
  • Screening of close contacts of infectious (i.e. sputum bacteriologically positive) TB cases for latent TB infection (LTBI) and preventive therapy. This is performed by the TBCU Contact Clinic.
  • The tuberculin skin (Mantoux) test is the standard method of LTBI screening. Criteria for a positive reaction depend on the patient’s health status and TB risk.
  • All screened close contacts found to have LTBI should be offered treatment, regardless of age and BCG vaccination status. Before initiating treatment, active TB must be ruled out by patient history, physical examination, and chest X-ray.
  • Isoniazid (INH) is the treatment of choice for LTBI. For adults,  the recommended duration of treatment is at least six, and preferably, nine months.


  • According to WHO guidelines, people with infectious or potentially infectious TB should not travel by commercial air transportation on a flight of any duration, until there is no longer a risk of transmitting infection to others.
  • Physicians should inform all patients with infectious or potentially infectious TB that they pose a risk of infection to others, and advise them that they must not travel by any public air transportation as long as they are considered infectious or potentially infectious.








References

  1. Ministry of Health. Communicable Diseases Surveillance in Singapore 2009.
  2. US Centers for Disease Control and Prevention. Treatment of tuberculosis. MMWR Recomm Rep 2003; 52RR(11): 1-77.
  3. Small PM, Fujiwara PI. Management of tuberculosis in the United States. N Engl J Med 2001; 345: 189-200.
  4. Tuberculosis Coalition for Technical Assistance. International Standards of Tuberculosis Care (ISTC), second edition.. The Hague, Tuberculosis Coalitions for Technical Assistance, 2009.
  5. Ministry of Health. Multidrug-resistant pulmonary tuberculosis in Singapore, 2000 to 2006. Epidemiological News Bulletin 2007; 33:50-5.
  6. Fern RH, Brian HN, Amiesha SP. Identification and management of latent tuberculosis infection. American Family Physician, May 15 2009. Available at: http://www.aafp.org/afp/2009/0515/p879.html#afp20090515p879-b14. Accessed Dec 2010.
  7. World Health Organization. Tuberculosis and air travel–Guidelines for prevention and Control, 3rd edition 2008.





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