Determinants of cluster size in large, population-based molecular epidemiology study of tuberculosis, northern Malawi.

Tuberculosis patients with identical strains of Mycobacterium tuberculosis are described as clustered. Cluster size may depend on patient or strain characteristics. In a 7-year population-based study of tuberculosis in Karonga District, Malawi, clusters were defined by using IS6110 restriction fragment length polymorphism, excluding patterns with <5 bands. Spoligotyping was used to compare strains with an international database. Among 682 clustered patients, cluster size ranged from 2 to 37. Male patients, young adults, and town residents were over-represented in large clusters. Cluster size was not associated with HIV status or death from tuberculosis. Spoligotypes from 9 (90%) of 10 large cluster strains were identical or very similar (1 spacer different) to common spoligotypes found elsewhere, compared with 37 (66%) of 56 of those from nonclustered patients (p = 0.3). Large clusters were associated with factors likely to be related to social mixing, but spoligotypes of common strains in this setting were also common types elsewhere, consistent with strain differences in transmissibility.

Mycobacterium tuberculosis Beijing genotype, northern Malawi.

In a 7-year population-based study in Malawi, we showed that Beijing genotype tuberculosis (TB) increased as a proportion of TB cases. All the Beijing genotype strains were fully drug sensitive. Contact histories, TB type, and case-fatality rates were similar for Beijing and non-Beijing genotype TB.

DNA fingerprint changes in tuberculosis: reinfection, evolution, or laboratory error?

BACKGROUND: DNA fingerprint patterns of Mycobacterium tuberculosis strains vary within individuals and between epidemiologically linked individuals because of pattern evolution, new infections, and laboratory error. We explored the importance of these factors. METHODS: Cultures from individuals in northern Malawi who had been diagnosed with tuberculosis (TB) during 1996-2001 were fingerprinted with restriction fragment-length polymorphism (RFLP). Probable laboratory error was inferred by use of dates or isolated positive cultures. Pattern evolution was explored within and between individuals, and the relative importance of relapse and reinfection was estimated in individuals with recurrent TB. RESULTS: RFLP results were available for 930 isolates from 806 individuals. The maximum laboratory-error rate was 3.9%. Pattern evolution was more common in linked individuals (17%) than on relapse (11%) or during treatment (3%). Twenty individuals had recurrent TB after completing treatment: in human immunodeficiency virus (HIV)-positive individuals, 7 of 12 recurrences were due to reinfection, compared with 0 of 8 in HIV-negative individuals (P=.01). CONCLUSIONS: The rate of DNA fingerprint-pattern evolution is not linear, and rates of change calculated from repeat cultures within individuals may not be applicable to transmission between individuals. The high proportion of recurrence due to reinfection found in HIV-positive individuals suggests that secondary prophylaxis and/or antiretroviral treatments are needed for such individuals.

Trends in tuberculosis and the influence of HIV infection in northern Malawi, 1988-2001.

OBJECTIVE: To document the changing incidence and patterns of tuberculosis (TB) in rural Africa and the extent to which they are influenced by HIV. METHODS: As part of longstanding epidemiological studies in Karonga District, Malawi, a series of case control studies of TB and HIV were conducted from 1988 onwards. Data from these studies, from a total population survey, and from the Malawi national census have been used to reconstruct the changes in the TB epidemic in the area from 1988 to 2001, examining the role of HIV. RESULTS: The incidence of all confirmed TB, and of new smear-positive TB, in adults increased to peak in the late 1990s but appears to have decreased since. Two-thirds of cases are now HIV positive. The rise in incidence was greatest in the 30-44-year-old age group and was particularly marked for women, leading to a decrease in the male : female ratio for TB incidence from 1.3 to 0.8. The proportion of new smear-positive TB cases attributable to HIV increased from 17% in 1988-1990 to 57% in 2000-2001, but the estimated rate of smear-positive TB in the absence of HIV decreased from 0.78/1000 to 0.45/1000. CONCLUSIONS: Without HIV the incidence of smear-positive TB would have fallen in this population. Instead it has risen and is predominantly affecting young adults and women. There is some evidence that the HIV-associated TB epidemic may have passed its peak.