15. MDR- AND XDR-TB CONTACTS
The opportunity to halt the spread of MDR- and XDR-TB in the communities, to diagnose and treat the disease early is often lost because close contacts of MDR- and XDR-TB patients are not investigated.
Close contacts are defined as persons living in the same household, or who spend many hours a day together with the patient in the same indoor space. While data is limited, studies have shown that close contacts of MDR- and XDR-TB patients often have MDR- and XDR-TB disease respectively and should be appropriately managed.
15.2. Evaluating the Risk of MDR-TB in Contacts
Factors that should be considered when investigating patient contacts include:
- The likelihood of infection in contacts thought to be newly infected.
- The likelihood that the contact, if infected, will develop active disease.
“Contacts before the initiation of treatment” that have had exposure to a patient with active disease and are likely to be newly infected should be evaluated to assess the likelihood of the actual infection being an MDR- or XDR-TB strain of M. tuberculosis. Factors that should be considered include:
- Infectiousness of the index patient: MDR-or XDR-TB patients who cough and are sputum smear-positive are substantially more infectious than those who do not cough or are sputum smear-negative.
- Closeness and intensity of the exposure: Persons who share air space with a patient with active disease for a prolonged time (e.g., a household member, hospital room mate) are at higher risk for infection than those who have a brief exposure. Exposure in a small, enclosed, poorly ventilated space is more likely to result in transmission of infection than exposure in a large, well-ventilated space. Exposure during cough-inducing procedures (e.g., sputum induction, bronchoscopy) may greatly increase the risk of transmission of infection.
- Likelihood of exposure to persons with drug-susceptible TB: In immuno-competent persons, the risk of developing TB is highest within the first two years following infection, after which this risk declines markedly. In general, 5%-10% of infected immuno-competent persons will develop active disease within the first two years. Child contacts of patients with MDR- or XDR-TB (especially those under two years of age) are at increased risk of getting infected and develop TB disease.
The most potent factor that increases the probability of developing active disease following infection is impaired immunity, such as that seen in HIV infection. It should be remembered, however, that there are many other medical causes of impaired immunity, including:
- Congenital syndromes.
- Certain haematological diseases.
- Endocrine diseases.
- Renal disease.
- Diabetes mellitus.
- Patients on immunosuppressive drugs (steroids, anti-cancer chemotherapy) or radiation therapy.
15.3. Managing Asymptomatic Contacts of MDR- and XDR-TB Patients
The use of second-line drugs for preventive therapy in MDR- or XDR-TB contacts is not recommended. To date, no controlled clinical trials have been conducted to assess the efficacy of treatment for latent MDR- or XDR-TB infection. Close monitoring of asymptomatic patients for development of symptoms is therefore more appropriate, particularly in high TB burden settings where many different tubercle strains (most often drug-susceptible) are circulating. Given the real possibility that contacts may have been infected by drug-susceptible strains, it is acceptable practice to manage asymptomatic contacts of DR-TB patients in the same way as contacts of drug-susceptible TB patients.
Asymptomatic contacts of smear-negative MDR- and XDR-TB patients should be managed according to the standard recommendations for contacts of drug-susceptible TB patients
Asymptomatic contacts of smear-positive MDR- and XDR-TB cases should be rapidly identified and screened. Child contacts aged five years and younger should be considered for isoniazid preventive therapy irrespective of health status and tuberculin response.
Asymptomatic child contacts aged five years and younger and HIV-infected children irrespective of age should be considered for isoniazid preventive therapy. All of these children should be examined clinically with Mantoux tuberculin skin test and a chest radiograph done. If there is any evidence of disease, specimens (from any appropriate source) should be obtained for culture and DST before commencement of anti-TB treatment according to the DST of the likely adult source case (that is MDR- or XDR-TB treatment if adult source case has MDR- or XDR-TB). If the children are well and chest radiographs are normal, all exposed and infected children (therefore irrespective of TST result) should receive preventive therapy (isoniazid 15 mg/kg/day for 6 months). However, isoniazid preventive therapy often fails in these children. Therefore regular two-monthly follow-up for symptoms (and CXR if indicated) should be done for first 6 months and 3-6 monthly thereafter for a minimum of two years.
In children older than five years and HIV negative adults, a strongly reactive tuberculin test indicates infection but not necessarily disease. The decision to start these persons on preventive (drug- susceptible) treatment depends on clinical history, examination and investigation.
Contacts of MDR/XDR-TB patients should report the first symptoms of possible TB and a careful risk assessment should be made. Sputum should be sent for smear, culture and DST. A chest X-ray should also be done.
Contacts that are HIV-positive should be followed up every six months for a period of two years and encouraged to report symptoms of TB as soon as they become evident.
15.4. Managing Symptomatic Contacts of MDR/XDR-TB Patients
15.4.1. Adult Contacts
All symptomatic close contacts of MDR- or XDR-TB cases should be examined immediately. If the contact appears to have active tuberculosis disease, culture and DST should be performed. While awaiting DST results, an empiric regimen based on either the resistance pattern of the index case or the most common resistance pattern in the community may be started.
If the work-up of a symptomatic adult is negative for TB, a trial of a broad-spectrum antibiotic that is not active against tuberculosis such as trimethoprim/sulfamethoxazole can be used. If the patient continues to be symptomatic, chest computed tomography, and/or directed bronchoscopy for smear and culture should be considered. If these diagnostic tools are not available or the results are not conclusive a diagnosis should be made with the clinical information at hand. If the initial work up is not suggestive of active tuberculosis, but the contact remains symptomatic, physical examinations should be repeated, together with monthly smears and cultures and repeat chest X-rays as needed.
15.4.2. Child Contacts
MDR- and XDR-TB should be suspected in the following situations with children:
- Who are contacts of a patient with confirmed MDR- or XDR-TB.
- Who are contacts of patients who died of tuberculosis while on treatment and there are reasons to suspect it was MDR- or XDR-TB.
- With bacteriologically proven TB that are not responding to first-line drugs despite treatment compliance.
In children, the diagnosis of TB is more difficult than in adults. Symptoms of TB in young children can be non-specific (e.g. chronic cough or wheeze, failure to thrive and recurrent fevers). Bacteriologic confirmation may be difficult to obtain due to the inability of children to produce sputum, the paucibacillary nature of paediatric TB, and the increased likelihood of extra-pulmonary TB in children. While every effort should be made to establish a bacteriologic diagnosis by DST in a child with suspected MDR/XDR-TB, it is not always possible.
Symptomatic child contacts of MDR/ XDR-TB patients should receive:
- A medical evaluation, including history and physical examination.
- Skin testing with tuberculin purified protein derivative (PPD).
- A chest X-ray. Computerised tomography is sometimes helpful, especially in documenting complications due to hilar adenopathy.
- Culture and DST: If the child is very young or cannot expectorate sputum, sputum induction with chest percussion or gastric aspiration should be performed.
If the tuberculin skin test is >5 mm, chest X-ray is negative and gastric aspirate or sputum culture is negative, the child can be treated with a broad spectrum antibiotic that is not active against tuberculosis, such as trimethoprim/sulfamethoxazole. The child should be followed up closely, with monthly evaluations that include sputum or gastric aspirate culture and chest X-rays, until three months of negative cultures or resolution of the symptoms occurs. If the patient’s clinical condition is highly suggestive of tuberculosis or progressively worsens, empiric treatment designed according to the DST pattern of the strain from the index case based may be started.