Whole Genome Sequencing Shows a Low Proportion of Tuberculosis Disease Is Attributable to Known Close Contacts in Rural Malawi.

BACKGROUND: The proportion of tuberculosis attributable to transmission from close contacts is not well known. Comparison of the genome of strains from index patients and prior contacts allows transmission to be confirmed or excluded. METHODS: In Karonga District, Malawi, all tuberculosis patients are asked about prior contact with others with tuberculosis. All available strains from culture-positive patients were sequenced. Up to 10 single nucleotide polymorphisms between index patients and their prior contacts were allowed for confirmation, and ≥ 100 for exclusion. The population attributable fraction was estimated from the proportion of confirmed transmissions and the proportion of patients with contacts. RESULTS: From 1997-2010 there were 1907 new culture-confirmed tuberculosis patients, of whom 32% reported at least one family contact and an additional 11% had at least one other contact; 60% of contacts had smear-positive disease. Among case-contact pairs with sequences available, transmission was confirmed from 38% (62/163) smear-positive prior contacts and 0/17 smear-negative prior contacts. Confirmed transmission was more common in those related to the prior contact (42.4%, 56/132) than in non-relatives (19.4%, 6/31, p = 0.02), and in those with more intense contact, to younger index cases, and in more recent years. The proportion of tuberculosis attributable to known contacts was estimated to be 9.4% overall. CONCLUSIONS: In this population known contacts only explained a small proportion of tuberculosis cases. Even those with a prior family contact with smear positive tuberculosis were more likely to have acquired their infection elsewhere.

Association between socioeconomic position and tuberculosis in a large population-based study in rural Malawi.

SETTING: There is increasing interest in social structural interventions for tuberculosis. The association between poverty and tuberculosis is well established in many settings, but less clear in rural Africa. In Karonga District, Malawi, we found an association between higher socioeconomic status and tuberculosis from 1986-1996, independent of HIV status and other factors. OBJECTIVE: To investigate the relationship in the same area in 1997-2010. DESIGN: All adults in the district with new laboratory-confirmed tuberculosis were included. They were compared with community controls, selected concurrently and frequency-matched for age, sex and area. RESULTS: 1707 cases and 2678 controls were interviewed (response rates >95%). The odds of TB were increased in those working in the cash compared to subsistence economy (p<0.001), and with better housing (p-trend=0.006), but decreased with increased asset ownership (p-trend=0.003). The associations with occupation and housing were partly mediated by HIV status, but remained significant. CONCLUSION: Different socioeconomic measures capture different pathways of the association between socioeconomic status and tuberculosis. Subsistence farmers may be relatively unexposed whereas those in the cash economy travel more, and may be more likely to come forward for diagnosis. In this setting "better houses" may be less well ventilated and residents may spend more time indoors.

Recurrent TB: relapse or reinfection? The effect of HIV in a general population cohort in Malawi.

OBJECTIVE: To estimate rates of recurrent tuberculosis due to reinfection and relapse, by HIV status, in a general population. DESIGN: Long-term cohort study in Karonga district, rural Malawi. METHODS: All tuberculosis patients with culture-proven disease in Karonga district were followed up after treatment. HIV testing was offered and all Mycobacterium tuberculosis isolates were fingerprinted using IS6110 RFLP. Fingerprints from initial and recurrent disease episodes were compared to distinguish relapse and reinfection: a second episode was considered a relapse if the fingerprint was identical or differed by only 1-4 bands and was the first occurrence of that pattern in the population. Rates of and risk factors for recurrence, reinfection disease, and relapse were estimated using survival analysis and Poisson regression. RESULTS: Five hundred and eighty-four culture-positive episodes of tuberculosis were diagnosed and treatment was completed during 1995-2003 in patients with known HIV status; 53 culture-positive recurrences occurred by May 2005. Paired fingerprints were available for 39 of these. Reinfections accounted for 1/16 recurrences in HIV-negative and 12/23 in HIV-positive individuals. Rates of relapse were similar in HIV-positive and HIV-negative individuals. Using multiple imputation to allow for missing fingerprint information, the rate of reinfection disease in HIV-positive individuals was 2.2/100 person-years, and in HIV-negative individuals 0.4/100 person-years. CONCLUSIONS: HIV increases the rate of recurrent tuberculosis in this setting by increasing the rate of reinfection disease, not relapse.

HIV and the risk of tuberculosis due to recent transmission over 12 years in Karonga District, Malawi.

Tuberculosis (TB) patients with strains common to other recent cases ('clustering') suggest recent transmission. HIV status and age may affect proportions clustered. We investigated TB clustering by HIV and age in a population-based study in Malawi. Among 746 patients, HIV infection increased the proportion clustered. Sex-period-adjusted odds ratios for the association of HIV and clustering were 1.26 (95% CI 0.4-4.1) for ages 15-25 years, 1.40 (0.9-2.3) for 25-50 years and 10.44 (2.3-47.9) for >50 years and remained stable over two periods examined. These results suggest that HIV increases the proportion of TB due to recent transmission in the elderly.