Trends and measurement of HIV prevalence in northern Malawi.

BACKGROUND: Most data on HIV prevalence in Malawi come from antenatal clinic (ANC) surveillance and are, therefore, subject to bias. OBJECTIVES: HIV prevalence and risk factors were measured using population-based data to assess the accuracy of ANC surveillance and changes in prevalence and risk factors for HIV over time. METHODS: HIV prevalence was measured in 1988-1993 and 1998-2001 in community controls from case-control studies of mycobacterial disease in Karonga District, Malawi. ANC surveillance studies in the district began in 1999. RESULTS: Age and area-standardized HIV prevalence in women aged 15-49 years in the community was 3.9% in 1988-1990, 12.5% in 1991-1993 and 13.9% in 1998-2001. For men, HIV prevalence was 3.7%, 9.2% and 11.4% in the same periods. In 1988-1993, HIV positivity was associated with occupations other than farming, with increased schooling and being born outside Karonga District. In 1998-2001, non-farmers were still at higher risk but the other associations were not seen. The age- and area-adjusted HIV prevalence in the ANC in 1999-2001 was 9.2%. The underestimate can be explained largely by marriage and mobility. Reduced fertility in HIV-positive individuals was demonstrated in both ANC and community populations. A previously recommended parity-based adjustment gave an estimated female HIV prevalence of 15.0%. CONCLUSIONS: HIV prevalence has increased and continues to be higher in non-farmers. The increase is particularly marked in those with no education. ANC surveillance underestimated HIV prevalence in the female population in all but the youngest age group. Although there were differences in sociodemographic factors, a parity-based adjustment gave a reasonable estimate of female HIV prevalence

The impact of HIV on morbidity and mortality from tuberculosis in sub-Saharan Africa: a study of rural Malawi and review of the literature

Since the mid-1980s tuberculosis (TB) case numbers and HIV seroprevalence have both risen sharply in sub-Saharan Africa. Estimates for the relative risk of TB in those infected with HIV have ranged from less than five to more than 20. The proportion of TB cases attributable to HIV (the population attributable fraction) has been calculated for several populations but is difficult to interpret if no account is taken of the age and sex distribution of the cases. In a rural area of Malawi we have studied the proportion of TB attributable to HIV over time. Nearly 40 per cent of smear-positive TB cases in this rural area of Malawi can now be attributed directly to HIV. The actual effect of HIV on TB is even greater than this because increased case numbers increase transmission of tuberculosis infection to both HIV-infected and non-infected sections of the population. We compare our findings with others from sub-Saharan Africa and discuss reasons for the differences, and methodological issues in interpretatio

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

BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies.

BACKGROUND: The efficacy of BCG vaccines against pulmonary tuberculosis varies between populations, showing no protection in Malawi but 50-80% protection in the UK. To investigate the mechanism underlying these differences, randomised controlled studies were set up to measure vaccine-induced immune responsiveness to mycobacterial antigens in both populations. METHODS: 483 adolescents and young adults in Malawi and 180 adolescents in the UK were tested for interferon-gamma (IFN-gamma) response to M tuberculosis purified protein derivative (PPD) in a whole blood assay, and for delayed type hypersensitivity (DTH) skin test response to tuberculin PPD, before and 1 year after receiving BCG (Glaxo 1077) vaccination or placebo or no vaccine. FINDINGS: The percentages of the randomised individuals who showed IFN-gamma and DTH responses were higher in Malawi than in the UK pre-vaccination-ie, 61% (331/546) versus 22% (47/213) for IFN-gamma and 46% (236/517) versus 13% (27/211) for DTH. IFN-gamma responses increased more in the UK than in Malawi, with 83% (101/122) and 78% (251/321) respectively of the vaccinated groups responding, with similar distributions in the two populations 1 year post-vaccination. The DTH response increased following vaccination in both locations, but to a greater extent in the UK than Malawi. The IFN-gamma and DTH responses were strongly associated, except among vaccinees in Malawi. INTERPRETATION: The magnitude of the BCG-attributable increase in IFN-gamma responsiveness to M tuberculosis PPD, from before to 1 year post-vaccination, correlates better with the known levels of protection induced by immunisation with BCG than does the absolute value of the IFN-gamma or DTH response after vaccination. It is likely that differential sensitisation due to exposure to environmental mycobacteria is the most important determinant of the observed differences in protection by BCG between populations

Measurement and determinants of tuberculosis outcome in Karonga District, Malawi.

Evaluation of disease outcome is central to the assessment of tuberculosis (TB) control programmes. In the study reported in this article we examined the factors influencing the measurement of outcome, survival rates during and after treatment, smear conversion rates, and relapse rates for patients diagnosed with TB in a rural area of Malawi between 1986 and mid-1994. Patients with less certain diagnoses of TB were more likely to die than those with confirmed TB, both among those who were seropositive and those who were seronegative to human immunodeficiency virus (HIV). The mortality rate among smear-positive patients with a separate culture-positive specimen was half that of patients with no such diagnostic confirmation. Patients not registered by the Ministry of Health had much higher mortality and default rates than did registered patients. Among smear-positive patients, HIV serostatus was the most important influence on mortality both during and after treatment (crude hazard ratios (95% confidence intervals) = 5.6 (3.0-10) and 7.7 (3.4-17), resp.), but HIV serostatus did not influence smear conversion rates. The initial degree of smear positivity influenced smear conversion rates, but not mortality rates. No significant predictors of relapse were identified. Unless considerable care is taken to include all TB patients, and to exclude nontuberculous patients, recorded TB outcome statistics are difficult to interpret and may be misleading. In populations with high rates of HIV infection, TB target cure rates of 85% are unrealistic. When new interventions are assessed it cannot be assumed that factors which influence the smear conversion rate will also influence the mortality rate

BCG scars in northern Malawi: sensitivity and repeatability of scar reading, and factors affecting scar size.

Karonga district, northern Malawi. To assess the sensitivity and repeatability of BCG scar reading, and factors affecting scar size. Follow-up of individuals aged > 3 months who were recruited into a BCG vaccine trial (1986-1989), and of infants vaccinated in health centres (1989-1991), who were examined for presence and size of BCG scars in subsequent years. All examinations were carried out blind of information on true vaccination status or the results of previous examinations. For trial individuals who were considered scar negative at recruitment and received BCG, the sensitivity of scar reading was > or = 93%, repeatability was > or = 94% for those 1 BCG scar post-vaccination. For infants vaccinated when < 1 month old in health centres, the proportion who still had recognisable scars 4 years later was < 80%. Scars were larger in individuals with a prior BCG vaccination, and for those aged 15-59 at vaccination the scars were approximately 1 mm larger for males than for females. A BCG scar is a highly sensitive and repeatable indicator of vaccination status when the vaccine is properly handled, delivered appropriately, and given at over 3 months of age, but not for vaccinations given within 1 month of birth. Given that most vaccinations in the world are given soon after birth, this low sensitivity will lead to both vaccine coverage and vaccine efficacy being underestimated in studies in which vaccination status is inferred from the presence/absence of a distinctive BCG scar. Age-sex patterns identified for scar size show important similarities to those found with skin test responses to tuberculin

Tuberculosis: associations with HIV and socioeconomic status in rural Malawi.

Tuberculosis (TB) is associated with human immunodeficiency virus (HIV) infection, increasing age and male sex, but less is known about other risk factors in developing countries. As part of the Karonga Prevention Study in northern Malawi, we conducted a retrospective cohort study in the general population to assess risk factors for the development of TB. Individuals were identified in 1986-89 and TB cases diagnosed up to 1996 were included. TB was confirmed in 62/11,059 (0.56%) HIV negative individuals and 7/182 (3.9%) HIV positive individuals (relative risk 7.1, 95% confidence interval 3.2-15.7). This association was little altered by adjustment for age, sex or socioeconomic factors. The risk of TB was higher in those aged over 30 years than in younger individuals, in men than in women, in those engaged in occupations other than farming than in subsistence farmers, in those living in households with burnt brick dwellings than in those with less well built dwellings, and in those with some schooling than in those with none. These associations persisted after adjusting for age, sex, HIV status and population density. The absolute risks of TB were low in this study due to the passive follow-up and strict diagnostic criteria. The relative risk with HIV was of a similar magnitude to that measured elsewhere. Increased risks of TB with age and in men are expected. Associations with measures of higher socioeconomic status were unexpected. They may reflect a greater likelihood of diagnosis in this group