[Show abstract][Hide abstract] ABSTRACT: 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.
To investigate the relationship in the same area in 1997-2010.
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.
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.
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.
PLoS ONE 10/2013; 8(10):e77740. DOI:10.1371/journal.pone.0077740 · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We combined two tuberculosis genome-wide association studies from Ghana and The Gambia with subsequent replication in a combined 11,425 individuals. rs4331426, located in a gene-poor region on chromosome 18q11.2, was associated with disease (combined P = 6.8 x 10(-9), odds ratio = 1.19, 95% CI = 1.13-1.27). Our study demonstrates that genome-wide association studies can identify new susceptibility loci for infectious diseases, even in African populations, in which levels of linkage disequilibrium are particularly low.
[Show abstract][Hide abstract] ABSTRACT: Human immunodeficiency virus associated tuberculosis (TB) disease can follow reactivation of latent Mycobacterium tuberculosis infection or recent (re-)infection with M. tuberculosis. If contemporary TB cases share identical M. tuberculosis strains (i.e., are 'clustered'), the episode is likely to have followed recent (re-)infection, irrespective of evidence of previous latent infection.
Individuals experiencing a first TB episode between 1996 and 2008 in Karonga District, Northern Malawi, were included if information on M. tuberculosis infection status (from tuberculin tests) before 1990 and a DNA fingerprint from the TB episode were available. We explored differences in proportion clustered by prior M. tuberculosis infection status and HIV status, adjusting for age, sex, bacille Calmette-Guérin scar status and time since tuberculin testing.
Of 79 HIV-negative TB cases, those with previous M. tuberculosis infection were much less likely to be clustered than cases without prior infection (29% vs. 77%, adjusted OR = 0.15, 95%CI 0.04-0.59). Among 119 HIV-positive TB cases, clustering was similar in both groups (88% vs. 84%, adjusted OR = 1.85, 95%CI 0.41-8.29).
HIV infection appears to increase the risk of TB following recent re-infection in patients with latent M. tuberculosis infection. Our results add to the mounting evidence that HIV-associated TB mainly follows recent M. tuberculosis infection.
The International Journal of Tuberculosis and Lung Disease 07/2010; 14(7):909-15. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate individual, household and community factors associated with HIV test refusal in a counselling and testing programme offered at population level in rural Malawi.
HIV counselling and testing was offered to individuals aged 18-59 at their homes. Individual variables were collected by interviews and physical examinations. Household variables were determined as part of a previous census. Multivariate models allowing for household and community clustering were used to assess associations between HIV test refusal and explanatory variables.
Of 2303 eligible adults, 2129 were found and 1443 agreed to HIV testing. Test refusal was less likely by those who were never married [adjusted odds ratio (aOR) 0.50 for men (95% CI 0.32; 0.80) and 0.44 (0.21; 0.91) for women] and by farmers [aOR 0.70 (0.52; 0.96) for men and 0.59 (0.40; 0.87) for women]. A 10% increase in cluster refusal rates increased the odds of refusal by 1.48 (1.32; 1.66) in men and 1.68 (1.32; 2.12) in women. Women counsellors increased the odds of refusal by 1.39 (1.00; 1.92) in men. Predictors of HIV test refusal in women were refusal of the husband as head of household [aOR 15.08 (9.39; 24.21)] and living close to the main road [aOR 6.07 (1.76; 20.98)]. Common reasons for refusal were fear of testing positive, previous HIV test, knowledge of HIV serostatus and the need for more time to think.
Successful VCT strategies need to encourage couples counselling and should involve participation of men and communities.
Tropical Medicine & International Health 11/2008; 13(11):1341-50. DOI:10.1111/j.1365-3156.2008.02148.x · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Surveillance in the era of antiretroviral therapy (ART) requires estimates of HIV prevalence as well as the proportion eligible for ART. We estimated HIV prevalence and assessed field staging of individuals to estimate the burden of HIV disease needing treatment in rural Malawi.
Adults aged 18-59 years in a demographic surveillance system were interviewed, examined, and HIV counselled and tested. Staging that used a simplified version of the WHO criteria ('field checklist') was compared with staging by a medical assistant using a 'clinic checklist' and to CD4 cell results.
A total of 2129 of 2303 eligible adults (92.4%) were traced, and 2047 (96.1%) participated. Of the 1443 participants (70.5%) tested, 11.6% were HIV positive. ART eligibility classification by the field and clinic checklists were concordant in 122 of 133 HIV-positive individuals. Compared with the clinic checklist, the field checklist had a sensitivity of 50% and a specificity of 96%. Including those already known to be on ART, staging by the field and clinic checklists estimated ART eligibility at 16.3 and 17.7% of HIV-positive individuals, respectively. Using CD4 cell count under 250 cells/mul or WHO stage III/IV, the Malawi national programme criteria, 38% of HIV-positive individuals were eligible for ART, compared with 31% based on the 2006 WHO criteria of CD4 cell count under 200 cells/mul or WHO stage IV or CD4 cell count of 200-350 cells/mul and WHO stage III.
The field checklist was not a suitable tool for individual staging. Criteria for ART eligibility based on clinical staging alone missed two-thirds of those eligible by clinical staging and CD4 cell count.
[Show abstract][Hide abstract] ABSTRACT: Total population surveys were carried out in 1980—84 (LEP-1) and 1986—89 (LEP-2) in Karonga District, northern Malawi, as part of a major cohort study of leprosy and tuberculosis. Retrospective information on fertility was collected from adult women in selected villages. Mortality estimates for the adult population were based on reported inter-survey deaths. This paper describes the demographic dynamics of the population in this time period, which coincided with the start of the HIV epidemic. A total of 112 886 individuals were interviewed in LEP-1, of whom 88 544 were also examined in LEP-2. Of this population, 46 per cent were under 15 years of age and about 20 per cent could not give a precise year of birth. Procedures for smoothing the age distribution and correcting the under-ascertainment of infants are explained. Total fertility in the interval between the two surveys was 6.4 children per woman and the crude birth rate was 48 per thousand. The crude death rate for the same interval was about 18 per thousand, and the growth rate was 4 per cent per year. Infant mortality was around 120 per thousand live births, under-5 mortality was around 190, the index of adult mortality (proportion of those who survived to age 15 dying before age 60) was 37 per cent, and life expectancy was around 50 years. Analyses adjusted for age, sex and socio-economic factors show higher mortality in north compared to south Karonga (rate ratio of 1.29, 95 per cent CI: 1.19, 1.38); and in those with estimated rather than precise years of birth (rate ratio of 1.14, 95 per cent CI: 1.03, 1.25). The similarities of the estimates of the age—sex distributions, and summary measures of mortality and fertility to the 1987 Malawi census and 1992 Malawi Demographic and Health Survey results mutually support the reliability of Karonga epidemiological survey data, and add details not available through the standard demographic survey and census methods, particularly with respect to adult mortality.
[Show abstract][Hide abstract] ABSTRACT: Twenty-seven polymorphisms from 12 genes have been investigated for association with tuberculosis (TB) in up to 514 cases and 913 controls from Karonga district, northern Malawi. Homozygosity for the complement receptor 1 (CR1) Q1022H polymorphism was associated with susceptibility to TB in this population (odds ratio [OR] = 3.12, 95% Confidence interval [CI] = 1.13-8.60, P = 0.028). This association was not observed among human immunodeficiency virus (HIV)-positive TB cases, suggesting either chance association or that HIV status may influence genetic associations with TB susceptibility. Heterozygosity for a newly studied CAAA insertion/deletion polymorphism in the 3'-untranslated region of solute carrier family 11, member 1 (SLC11A1, formerly NRAMP1) was associated with protection against TB in both HIV-positive (OR = 0.70, 95% CI = 0.49-0.99, P = 0.046) and HIV-negative (OR = 0.65, 95% CI = 0.46-0.92, P = 0.014) TB cases, suggesting that the SLC11A1 protein may have a role in innate TB immune responses that influence susceptibility even in immunocompromised individuals. However, associations of other variants of SCLA11A with TB reported from other populations were not replicated in Malawi. Furthermore, associations with vitamin D receptor, interferon-gamma, and mannose-binding lectin observed elsewhere were not observed in this Karonga study. Genetic susceptibility to TB in Africans appears polygenic. The relevant genes and variants may vary significantly between populations, and may be affected by HIV infection status.
The American journal of tropical medicine and hygiene 10/2004; 71(3):341-9. · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To estimate the impact of cotrimoxazole prophylaxis on the survival of human immunodeficiency virus (HIV)-positive tuberculosis (TB) patients.
A cohort study with a historical comparison group was conducted. End-of-treatment outcomes and 18-month survival were compared between TB patients registered in 1999 and patients registered in 2000 in Karonga District, Malawi. Case ascertainment, treatment and outpatient follow-up were identical in the two years except that in 2000 cotrimoxazole prophylaxis was offered to HIV-positive patients in addition to routine care. The prophylaxis was provided from the time a patient was identified as HIV-positive until 12 months after registration. Analyses were carried out on an intention-to-treat basis for all TB patients, and also separately by HIV status, TB type and certainty of diagnosis.
355 and 362 TB patients were registered in 1999 and 2000, respectively; 70% were HIV-positive. The overall case fatality rate fell from 37% to 29%, i.e. for every 12.5 TB patients treated, one death was averted. Case fatality rates were unchanged between the two years in HIV-negative patients, but fell in HIV-positive patients from 43% to 24%. The improved survival became apparent after the first 2 months and was maintained beyond the end of treatment. The improvement was most marked in patients with smear-positive TB and others with confirmed TB diagnoses.
Survival of HIV-positive TB patients improved dramatically with the addition of cotrimoxazole prophylaxis to the treatment regimen. The improvement can be attributed to cotrimoxazole because other factors were unchanged and the survival of HIV-negative patients was not improved. Cotrimoxazole prophylaxis should therefore be added to the routine care of HIV-positive TB patients.
Bulletin of the World Health Organisation 06/2004; 82(5):354-63. DOI:10.1590/S0042-96862004000500009 · 5.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In many populations there is an excess of tuberculosis in young women and older men. We explored possible explanations for these patterns, concentrating on human immunodeficiency virus (HIV) status, pregnancy, smoking, cooking smoke exposure, contact with tuberculosis cases within the household or outside, and gender differences in health service usage and diagnostic delay.
Case control study in Karonga District, Malawi.
Cases were new tuberculosis patients with bacteriological or histological evidence of tuberculosis. Controls were selected in the community using field-based random sampling.
The study included 598 tuberculosis cases and 992 controls, with an excess of tuberculosis in young females and older males. This was more marked in HIV-positive individuals. HIV infection was a similarly strong risk factor for tuberculosis in both men and women. Tuberculosis was associated with having a family or household contact with tuberculosis for both men and women. For women, but not men, contacts outside the close family and household were also a risk factor for tuberculosis. Tuberculosis was not associated with current or recent pregnancy, or with smoking or smoke exposure. There were no differences between men and women in health service usage or delay.
In this population, HIV infection and contacts with known tuberculosis patients are important determinants of the gender distribution of cases.
The International Journal of Tuberculosis and Lung Disease 03/2004; 8(2):194-203. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: As part of an epidemiological study of leprosy and tuberculosis, a total of 112 026 individuals belonging to 17 889 households in Karonga District, northern Malawi, were interviewed and examined in the early 1980s and followed up over five years. The mean and median household size (6.4 and 5 respectively in the first survey) were similar in the two surveys. Males headed 85 per cent of all households. The proportion of females who were household heads increased with age, from less than 10 per cent among females under 45 years of age to more than 30 per cent of those over age 60. The implications of household definition for studies of household change over time is discussed. More than 84 per cent of the households were considered to have maintained their identity over the five years, and an appreciable proportion did so despite changes in location (21 per cent) or headship (8 per cent), or even both (1 per cent). The rate at which individuals changed households was strongly dependent upon age, sex and membership status, being low (c. 20 per cent) for children under 5 years, very high for females 15–19 years of age (63 per cent) and males 20–24 years of age (50 per cent), then lower for older adults though increasing gradually with age for females over age 50. The probability of survival of a household over time was strongly correlated with household size. These analyses reveal the complexities of household dynamics, and provide a basis for detailed studies of leprosy, tuberculosis and HIV transmission and impact in this population.
[Show abstract][Hide abstract] ABSTRACT: Selection bias, particularly of controls, is common in case-control studies and may materially affect the results. Methods of control selection should be tailored both for the risk factors and disease under investigation and for the population being studied. We present here a control selection method devised for a case-control study of tuberculosis in rural Africa (Karonga, northern Malawi) that selects an age/sex frequency-matched random sample of the population, with a geographical distribution in proportion to the population density. We also present an audit of the selection process, and discuss the potential of this method in other settings.
Transactions of the Royal Society of Tropical Medicine and Hygiene 09/2001; 95(5):481-3. DOI:10.1016/S0035-9203(01)90009-4 · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Transactions of the Royal Society of Tropical Medicine and Hygiene 09/2000; 94(5):500-3. DOI:10.1016/S0035-9203(00)90065-8 · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background Repeat BCG vaccination is standard practice in many countries for prevention of tuberculosis and leprosy, but its effectiveness has not been evaluated. The addition of Mycobacterium leprae antigens to BCG might improve its effectiveness against leprosy. A double-blind, randomised, controlled trial to evaluate both these procedures was carried out in Karonga District, northern Malawi, where a single BCG vaccine administered by routine health services had previously been found to afford greater than 50% protection against leprosy, but no protection against tuberculosis. Methods Between 1986 and 1989, individuals lacking a BCG scar were randomly assigned BCG alone (27 904) or BCG plus killed M leprae (38 251). Individuals with a BCG scar were randomly allocated placebo (23 307), a second BCG (23 456), or BCG plus killed M leprae (8102). Incident cases of leprosy and tuberculosis were ascertained over the subsequent 5-9 years. Findings 139 cases of leprosy were identified by May, 1995; 93 of these were diagnostically certain, definitely postvaccination cases. Among scar-positive individuals, a second BCG vaccination gave further protection against leprosy (about 50%) over a first BCG vaccination. The rate ratio for all diagnostically certain, definitely postvaccination cases, all ages, was 0.51 (95% CI 0.25-1.03, p=0.05) for BCG versus placebo. This benefit was apparent in all subgroups, although the greatest effect was among individuals vaccinated below 15 years of age (RR=0.40 [95% CI 0.15-1.01], p=0.05). The addition of killed M leprae did not improve the protection afforded by a primary BCG vaccination. The rate ratio for BCG plus killed M leprae versus BCG alone among scar-negative individuals was 1.06 (0.62-1.82, p=0.82) for all ages, though 0.37 (0.11-1.24, p=0 09) for individuals vaccinated below 15 years of age. 376 cases of postvaccination pulmonary tuberculosis and 31 of glandular tuberculosis were ascertained by May, 1995. The rate of diagnostically certain tuberculosis was higher among scar-positive individuals who had received a second BCG (1.43 [0.88-2.35], p=0.15) than among those who had received placebo and there was no evidence that any of the trial vaccines contributed to protection against pulmonary tuberculosis. Interpretation In a population in which a single BCG vaccination affords 50% or more protection against leprosy, but none against tuberculosis, a second vaccination can add appreciably to the protection against leprosy, without providing any protection against tuberculosis.
The Lancet 07/1996; 348(9019):17-24. DOI:10.1016/S0140-6736(96)02166-6 · 45.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Geographical differences in leprosy risk are not understood, but may provide clues about the natural history of the disease. We report an analysis of the geographical distribution of leprosy in Karonga District, a rural area of Northern Malawi, between 1979 and 1989.
Cohort study of the incidence of leprosy based on two total population surveys. Area of residence was determined using aerial photographs, which allowed identification of households, as well as location of roads, rivers and the lake shore.
Incidence rates were between two and three times higher in the north compared to the south of the district, and lowest in the semi-urban district capital. The most obvious environmental difference between these regions is the north's higher rainfall and more fertile soil. There was no overall association between leprosy incidence and population density, although highest rates were observed in the least densely populated areas. Looking at the entire district, incidence rates increased with increasing distance from a main road, but declined with increasing distance from a river or from the shore of Lake Malawi. The negative association with proximity to rivers may reflect the larger number of rivers in the north of the district. Apparent differences in incidence rates between groups speaking different languages reflected confounding by area of residence.
There is a marked variation, not explained by socioeconomic or cultural factors, in the incidence of leprosy within Karonga District. Our results are consistent with a theme in the literature associating the environment, particularly proximity to water, with leprosy.
International Journal of Epidemiology 01/1996; 24(6):1211-22. DOI:10.1093/ije/24.6.1211 · 9.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Incidence rates of leprosy in Karonga District, northern Malawi, are analyzed by duration of schooling and housing conditions, controlling for age, sex, BCG scar and geographical zone of the household. There is a strong inverse relationship between the number of completed years of schooling and leprosy risk. Good housing conditions are also associated with a decreased risk of developing leprosy in this population. The effect of housing is seen most strongly in young people. It is hypothesized that schooling changes behavior and housing determines environment in ways which are relevant for the transmission of Mycobacterium leprae or for the appropriate priming of the immune system.
International Journal of Leprosy and Other Mycobacterial Diseases 10/1994; 62(3):345-52. · 0.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This paper describes incidence rates by age, sex, prior BCG status and classification in Karonga District, northern Malawi. New cases (489) were identified among 83,500 individuals followed for an average of 5 years (1.12 cases per 1000 person years). Only 29 (6%) of the incident cases were multibacillary. Incidence rates generally were higher among females than males, and increased steadily with age. Although the highest incidence rates of disease were recorded among young adults without BCG scars (males 15-19; females 20-24), these peaks were less dramatic than those reported among young adults in The Philippines and Norway. In the absence of historical data and data on infection status, it is not possible to assess to what extent these peaks may reflect either greater exposure or greater susceptibility to disease among adolescents or young adults. The incidence rates of leprosy among individuals with a prior recorded BCG scar were approximately half those of individuals lacking a scar, at all ages. Since BCG had been introduced into this population only during the 1970s, this provides strong evidence for the effectiveness of BCG when given to adults. It was estimated that past vaccination of approximately 40% of the district population had reduced the overall incidence rate of leprosy by 18%, and that this impact would increase with aging of the vaccinated cohorts. A retrospective examination of the detailed records of initial examinations revealed that 62 (13%) of the incidence cases were recorded as having skin hypopigmentation or blemishes, at the site of subsequent confirmed leprosy lesions, several months or years before they were suspected of having leprosy. The nonspecificity of these lesions, some of which were probably attributable to Mycobacterium leprae infection, highlights the difficulty of diagnosing leprosy in its earliest forms.
International Journal of Leprosy and Other Mycobacterial Diseases 04/1994; 62(1):10-23. · 0.22 Impact Factor