Karonga Prevention Study

Karonga, Malawi

Karonga Prevention Study

Karonga, Malawi
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Crampin A.C.,London School of Hygiene and Tropical Medicine | Houben R.,London School of Hygiene and Tropical Medicine | Ndlovu R.,Karonga Prevention Study | Munthali L.,Karonga Prevention Study | And 3 more authors.
Journal of Clinical Microbiology | Year: 2010

The occurrence of mixed infections of Mycobacterium tuberculosis is no longer disputed. However, their frequency, and the impact they may have on our understanding of tuberculosis (TB) pathogenesis and epidemiology, remains undetermined. Most previous studies of frequency applied genotyping techniques to cultured M. tuberculosis isolates and found mixed infections to be rare. PCR-based techniques may be more sensitive for detecting multiple M. tuberculosis strains and can be applied to sputum. To date, one study in South Africa has used a PCR approach and suggested that mixed infection could be common. We investigated mixed infections in northern Malawi using two lineage-specific PCR assays targeting the Latin American-Mediterranean (LAM) and Beijing lineages. Compared with spoligotyping, the specificity and sensitivity of both assays was 100%. From 160 culture-positive sputa, mixed LAM and non-LAM strains were detected in 4 sputa belonging to 2 (2.8%) patients. Both patients were HIV positive, with no history of TB. Cultured isolates from both patients showed only LAM by PCR and spoligotyping. In a set of 377 cultured isolates, 4 were mixed LAM and non-LAM. Only one showed evidence of more than one M. tuberculosis strain using IS6110-based restriction fragment length polymorphism (IS6110-RFLP) and spoligotyping analyses. Corresponding sputa for the 4 isolates were unavailable. Mixed Beijing and non-Beijing strains were not detected in this study. Mixed infections appear to be rare in our setting and are unlikely to affect findings based on DNA finger-printing data. Molecular methods, which avoid the selective nature of culture and target distinct strains, are well suited to detection of mixed infections. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Ajdukiewicz K.M.B.,North Manchester General Hospital | Cartwright K.E.,Royal Infirmary | Scarborough M.,John Radcliffe Hospital | Zijlstra E.E.,Erasmus Medical Center | And 3 more authors.
The Lancet Infectious Diseases | Year: 2011

Background: Southern Africa has a high incidence of bacterial meningitis in adults, often associated with HIV co-infection. Mortality exceeds 50%, even with appropriate antibiotic therapy, and is not improved with corticosteroids. Glycerol adjuvant therapy reduces long-term morbidity in bacterial meningitis in children, and its use is being promoted. We aimed to assess the effectiveness of glycerol as an adjuvant therapy for adults with bacterial meningitis in Africa. Methods: The study was done in two phases. First, in an open-label dose-finding study, 45 adult patients with symptoms, signs, and cerebrospinal fluid findings consistent with bacterial meningitis received either 50 mL, 75 mL, or 100 mL of glycerol four times a day for 4 days. We then did a randomised, double-blind, placebo-controlled trial of oral glycerol in adults with bacterial meningitis. Patients with clinical and cerebrospinal fluid findings suggestive of bacterial meningitis were randomly assigned in blocks of 12 by use of a random number list produced by an independent statistician to receive either glycerol or an equivalent volume of sugar solution. Glycerol and placebo were indistinguishable by colour or taste. The primary outcome was mortality at 40 days, with secondary outcomes including disability and mortality restricted to pneumococcal disease. All patients were analysed for the primary outcome excluding those who were lost to follow-up. This trial is registered at controlled-trials.com, number ISRCTN70121840. Findings: 75 mL glycerol four times a day was the highest tolerated dose, and was used for the main study. 265 patients were assigned treatment: 137 glycerol and 128 placebo. The trial was stopped early on the advice of the data and safety monitoring board after a planned interim analysis. By day 40, 61 (49%) of 125 patients in the placebo group and 86 (63%) of 136 in the glycerol group had died (adjusted odds ratio 2·4, 95% CI 1·3-4·2, p=0·003). There was no benefit from glycerol for death and disability by day 40, and glycerol did not improve death and disability by day 40 or death at day 40 in patients with proven bacterial disease or pneumococcal disease. Two serious adverse events occurred that were possibly due to the study drug. Interpretation: Oral glycerol therapy cannot be recommended as an adjuvant therapy in adults with bacterial meningitis in resource-poor settings with a high HIV prevalence. Funding: Meningitis Research Foundation. © 2011 Elsevier Ltd.


Matemba M.,Karonga Prevention Study | French N.,Karonga Prevention Study | French N.,London School of Hygiene and Tropical Medicine
Emerging Infectious Diseases | Year: 2011

To determine whether an association exists between group B streptococcus carriage and HIV infection, we recruited 1,857 pregnant women (21.7% HIV positive) from Queen Elizabeth Central Hospital, Blantyre, Malawi. Overall, group B streptococcus carriage was 21.2% and did not differ by HIV status. However, carriage was increased among HIV-positive women with higher CD4 counts.


Yeatman S.E.,University of Colorado at Denver | Hoffman R.M.,University of California at Los Angeles | Chilungo A.,Invest in Knowledge Initiative | Lungu S.R.,Invest in Knowledge Initiative | And 2 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2015

HIV transmission is most likely to occur during the first few months after infection, yet few cases are identified during this period. Using a population-based cohort of young Malawian women, we identify the distinct symptomology and health-seeking behavior marking early HIV infection by comparing it with periods of seronegativity and chronic infection. During early HIV infection, women are more likely to report malaria-like symptoms and visit clinics for malaria care. In malaria-endemic contexts, where acute HIV symptoms are commonly mistaken for malaria, early diagnostic HIV testing and counseling should be integrated into health care settings where people commonly seek treatment for malaria. Copyright © 2015 Wolters Kluwer Health, Inc.


Koole O.,London School of Hygiene and Tropical Medicine | Munthali L.,Karonga Prevention Study | Mhango B.,Ministry of Health | Mpunga J.,National TB Control Programme | And 2 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2014

We assessed the impact on measured burden and outcomes of the revised World Health Organization and Malawi guidelines reclassifying people with single (including 'scanty') positive smears as smear-positive pulmonary tuberculosis cases. In a retrospective cohort in rural Malawi, 567 (34%) of 1670 smear-positive episodes were based on single positive smears (including 176 with scanty smears). Mortality rates and the proportion starting treatment were similar in those with two positive smears or single, non-scanty smears. Those with single scanty smears had higher mortality and a lower proportion starting treatment. The reclassification will increase the reported burden substantially, but should improve treatment access. © 2014 The Union.


Guerra-Assuncao J.A.,London School of Hygiene and Tropical Medicine | Guerra-Assuncao J.A.,Wellcome Trust Sanger Institute | Crampin A.C.,London School of Hygiene and Tropical Medicine | Houben R.M.G.J.,London School of Hygiene and Tropical Medicine | And 12 more authors.
eLife | Year: 2015

To improve understanding of the factors influencing tuberculosis transmission and the role of pathogen variation, we sequenced all available specimens from patients diagnosed over 15 years in a whole district in Malawi. Mycobacterium tuberculosis lineages were assigned and transmission networks constructed, allowing ≤10 single nucleotide polymorphisms (SNPs) difference. We defined disease as due to recent infection if the network-determined source was within 5 years, and assessed transmissibility from forward transmissions resulting in disease. High-quality sequences were available for 1687 disease episodes (72% of all culture-positive episodes): 66% of patients linked to at least one other patient. The between-patient mutation rate was 0.26 SNPs/year (95% CI 0.21–0.31). We showed striking differences by lineage in the proportion of disease due to recent transmission and in transmissibility (highest for lineage-2 and lowest for lineage-1) that were not confounded by immigration, HIV status or drug resistance. Transmissions resulting in disease decreased markedly over time. © Copyright Guerra-Assunção et al..


Glynn J.R.,London School of Hygiene and Tropical Medicine | Dube A.,Karonga Prevention Study | Kayuni N.,Karonga Prevention Study | Floyd S.,London School of Hygiene and Tropical Medicine | And 4 more authors.
AIDS | Year: 2012

Background: Recent UNAIDS guidelines recommend measuring concurrency 6 months before the interview date, based on overlapping partnership dates. This has theoretical advantages, but little is known about how well it can be measured in practice. Methods: The assumptions underlying the UNAIDS measure were tested using data from a sexual behaviour survey conducted in rural northern Malawi. All resident adults aged 15-59 were eligible. Questions included self-reported concurrency and dates for all marital and nonmarital partnerships in the past 12 months. Results: A total of 6796 women and 5253 men were interviewed, 83 and 72% of those eligible, respectively. Since few women reported multiple partners, detailed analysis was restricted to men. Overall 19.2% [95% confidence interval (CI) 18.1-20.2] of men self-reported concurrent relationships in the past year (almost all of those with more than one partner). Using overlapping dates the estimate was 16.7% (15.7-17.7). Excluding partnerships which tied on dates (making overlap uncertain) or restricting the analysis to the three most recent partners gave similar results. The UNAIDS 6-month measure was 12.0% (11.1-12.9), and current concurrency was 11.5% (10.6-12.4). The difference between dates-based and self-reported 12-month measures was much larger for unmarried men: 11.1% (9.7-12.4) self-reported; 7.1% (6.9-8.2) on dates. Polygyny (15% of married men) and the longer duration of relationships stabilized the estimates for married men. Nonmarital partnerships were under-reported, particularly those starting longer ago. Conclusion: The difficulties of recall of dates for relationships, and under-reporting of partners lead to underestimation of concurrency using date-based measures. Self-reported concurrency is much easier to measure and appears more complete. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Crampin A.C.,Karonga Prevention Study | Crampin A.C.,London School of Hygiene and Tropical Medicine | Mwaungulu J.N.,Karonga Prevention Study | Mwaungulu F.D.,Karonga Prevention Study | And 5 more authors.
AIDS | Year: 2010

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. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Glynn J.R.,London School of Hygiene and Tropical Medicine | Kayuni N.,Karonga Prevention Study | Gondwe L.,Karonga Prevention Study | Price A.J.,London School of Hygiene and Tropical Medicine | Crampin A.C.,London School of Hygiene and Tropical Medicine
eLife | Year: 2014

Remarkably little is known about associations between age at menarche and sexually transmitted infections, although girls with earlier menarche tend to have earlier sexual debut and school drop-out, so an association might be expected. In a population-based survey of >3000 women aged 15-30 in northern Malawi we show that those with earlier menarche had earlier sexual debut, earlier marriage and were more often Herpes simplex type-2 (HSV-2) positive. Compared to those with menarche aged <14, the age-adjusted odds ratios for HSV-2 were 0.89 (95%CI 0.71-1.1), 0.71 (0.57-0.89) and 0.69 (0.54-0.89) for menarche aged 14, 15 and 16+ respectively. This association persisted after adjusting for socio-economic factors, including schooling, and for sexual behaviour. No such association was seen with HIV infection, which is much less common and less uniformly distributed than HSV-2 in this population. The extra vulnerability of girls with earlier menarche needs to be recognised. © Glynn et al.


Floyd S.,London School of Hygiene and Tropical Medicine | Molesworth A.,London School of Hygiene and Tropical Medicine | Dube A.,Karonga Prevention Study | Crampin A.C.,London School of Hygiene and Tropical Medicine | And 7 more authors.
AIDS | Year: 2013

OBJECTIVE: To quantify refusal bias due to prior HIV testing, and its effect on HIV prevalence estimates, in general-population surveys. DESIGN: Four annual, cross-sectional, house-to-house HIV serosurveys conducted during 2006-2010 within a demographic surveillance population of 33000 in northern Malawi. METHODS: The effect of prior knowledge of HIV status on test acceptance in subsequent surveys was analysed. HIV prevalence was then estimated using ten adjustment methods, including age-standardization; multiple imputation of missing data; a conditional probability equations approach incorporating refusal bias; using longitudinal data on previous and subsequent HIV results; including self-reported HIV status; and including linked antiretroviral therapy clinic data. RESULTS: HIV test acceptance was 55-65% in each serosurvey. By 2009/2010 79% of men and 85% of women had tested at least once. Known HIV-positive individuals were more likely to be absent, and refuse interviewing and testing. Using longitudinal data, and adjusting for refusal bias, the best estimate of HIV prevalence was 7% in men and 9% in women in 2008/2009. Estimates using multiple imputations were 4.8 and 6.4%, respectively. Using the conditional probability approach gave good estimates using the refusal risk ratio of HIV-positive to HIV-negative individuals observed in this study, but not when using the only previously published estimate of this ratio, even though this was also from Malawi. CONCLUSION: As the proportion of the population who know their HIV-status increases, survey-based prevalence estimates become increasingly biased. As an adjustment method for cross-sectional data remains elusive, sources of data with high coverage, such as antenatal clinics surveillance, remain important. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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