TMT-Tracing Microbacteria Transimission - 2012

1 The HIV epidemic continues to present a major challenge to TB control. ART reduces TB risk at the individual level, but the risk remains well above that of HIV-negative individuals, even at high CD4 counts.1 With growing numbers of people on ART, with long survival and increased risk of smear-positive pulmonary disease, the expected population impacts are unclear. In Malawi TB notifications have stopped declining for the last two years.
The newly launched Stop TB 2011-2015 plan acknowledges that as well as stepping-up current control measures, more fundamental research is needed if the WHO target of “elimination of TB by 2050” is to be met.2 One area of research is to understand where transmission is occurring.
KPS has previously shown that recent infection is the predominant cause of TB in HIV-infected individuals,3-4 that HIV-infected cases play an important role in transmission,5 and that ART may be increasing TB rates at the population level in Karonga district. Interrupting ongoing transmission is key to control and will have more immediate impact than those interventions addressing latent infection which are required for long term control.
We know that most M.tb infection is due to casual contacts. Based on DNA fingerprinting, we have shown that about two thirds of the TB in adults is due to recent transmission, 6 but only about 12% of TB in the population is attributable to identifiable contacts, and even those with known household or close family contact with smear positive TB were likely to have acquired their TB elsewhere.7 This shows that contact tracing is unlikely to contribute much to TB control, with the exception is spouses of TB patients, about 40% of whom are HIV positive, have a high risk of TB, and can be easily identified.
Ongoing transmission in the population is measured by the rate of M.tb infection, most easily determined through age-specific skin test positivity in children. Since Mtb infection is a relatively rare event, if a child is infected with Mtb, the infection event should have happened recently. Considering the relative reduced mobility of children, the source of infection will also probably be local.
We intend to monitor children in our demographic surveillance area in the south of the District (total population ~35,000) to investigate the overall prevalence and distribution of skin test positivity, and the relationship to known smear positive cases of tuberculosis (62 smear positive cases in the past five years in the area), aiming to identify clusters of transmission events. We have previously found that although skin test positivity in the under fives is higher in those living in the household of a smear positive TB case, (34%, compared to 8% with no known household contact), 93% of infections occur in households without known cases.

2, Interrupting ongoing transmission of Mycobacterium tuberculosis is key to control and will have more immediate impact than those interventions addressing latent infection which are required for long term control.
In high burden countries, M.tuberculosis infection is due to casual contacts and only a small proportion of TB cases are attributable to identifiable contacts. Even in children under five years old, the majority of infections occur in households without known cases.
In the Karonga demographic survey area we propose to assess tuberculin skin test (TST) sensitivity in children and identify new infections to track transmission. Young children spend more time near their home and close family than do adults, and are less likely to be already infected, so increasing the chance of being able to pinpoint the source of infection. Staff will conduct TST on children <5 years, with follow-up a year. Prevalent TST “positivity” will be mapped to establish linkage to known cases within the last five years. All children <5 with evidence of incident infection will be investigated with a commercial interferon gamma release assay (IGRA). All household, neighbourhood and regular visitor contacts of these newly-infected children (~20 contacts/child) will be screened at the household. This will establish the contribution of known symptomatic cases, “silent” but detectable excretors, and unknown sources, to transmission of infection in the population. Children <5 with incident infection will be offered isoniazid preventive therapy.