Anna Molesworth

Environmental Risk and Meningitis Epidemics in Africa

Epidemics of meningococcal meningitis occur in areas with particular environmental characteristics. We present evidence that the relationship between the environment and the location of these epidemics is quantifiable and propose a model based on environmental variables to identify regions at risk for meningitis epidemics. These findings, which have substantial implications for directing surveillance activities and health policy, provide a basis for monitoring the impact of climate variability and environmental change on epidemic occurrence in Africa.

Underestimation of HIV prevalence in surveys when some people already know their status, and ways to reduce the bias.

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 33u200a000 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.

Decreased morbidity and use of hospital services in English HIV-infected individuals with increased uptake of anti-retroviral therapy 1996-1997. National Prospective Monitoring System Steering Group.

OBJECTIVEnTo investigate the relationship between changing morbidity patterns, the use of hospital services by HIV-infected patients and the uptake of antiretroviral therapy (ART) in England.nnnDESIGNnProspective serial cross-sectional analyses based on data collected through the National Prospective Monitoring System (NPMS), a multi-centre prospective monitoring system.nnnSETTINGnHIV-infected patients seen in 10 clinics, five London and five non-London, during the three semesters, 1 January 1996 to 30 June 1997.nnnMAIN OUTCOME MEASURESnThe mean use of hospital services per patient-year, mean new HIV-related opportunistic illnesses per 1000 patient-years and percentage uptake of ART.nnnRESULTSnThe use of inpatient services changed particularly among AIDS patients. The mean number of inpatient days for AIDS patients decreased from 19.7 [95% confidence interval (CI) 13.7-25.7] in 1996 to 11.2 (95% CI 6.1-15.6) per patient-year in 1997. Concurrently the number of new AIDS-defining events decreased significantly from 567 (95% CI 529-607) to 203 (95% CI 183-225) per 1000 patient-years. The overall uptake of ART increased significantly from 33% (95% CI 31-35%) to 50% (95% CI 48-52%), and a switch from mono or dual to triple therapy or quadruple or more therapy was observed. However, by mid-1997 only 29% (95% CI 26-32%) of asymptomatic patients and 51% (95% CI 49-54%) of patients with symptomatic non-AIDS were on ART, compared with 69% (95% CI 66-71%) of AIDS patients.nnnCONCLUSIONnThe observed reduction in new AIDS-defining events has led to a reduction in the need for inpatient hospital care and has been associated with an increased uptake of ART, including a switch to triple therapy. All of these factors are likely to have contributed to the observed reduction in mortality among English AIDS patients. As the overall uptake of ART remained relatively low in English centres further improvements can be anticipated. However, the medium to long-term effects of these treatment regimens will need to be closely monitored.

High accuracy of home-based community rapid HIV testing in rural Malawi.

Objective:To assess the performance of rapid HIV antibody tests when used as part of a home-based community wide counseling and testing strategy in northern Malawi. Design:A cross-sectional population survey of HIV infection, 2007 to 2008. Methods:Adults aged 15 years or older in a demographic surveillance area were counseled and then offered an HIV test at their home by government-certified counselors. Two initial rapid tests (Determine and Uni-Gold) were performed on all samples and a third, tie-breaker test (SD Bioline) used to resolve discordant results. All people who wanted to know were posttest-counseled and informed of their results with referral to local clinical services if found to be HIV-positive. Laboratory quality control comprised retesting all positive and every tenth negative venous blood sample collected. Results:A total of 10,819 adults provided venous blood samples for HIV testing, of whom 7.5% (813) were HIV-positive. The accuracy of the parallel testing strategy used was high with 99.6% sensitivity, 100.0% specificity, 99.9% positive predictive value, and 99.9% negative predictive value. Conclusion:Face-to-face rapid testing by health personnel with minimum training at the clients home performs well when used on a wide scale in the community setting.

Measuring concurrency: an empirical study of different methods in a large population-based survey and evaluation of the UNAIDS guidelines

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. Conclusions: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.

Evaluation of the meningitis epidemics risk model in Africa

Meningitis epidemics have a strong environmental component in Africa with the most severe epidemics occurring in the Sahelian region known as the Meningitis Belt. The objective of this study is to evaluate an ecological model based on absolute humidity and land cover type to predict the location of these epidemics. The risk model is evaluated prospectively based on epidemics occurring in Africa from January 2000 to April 2004. Seventy-one epidemics occurred during this time period affecting 22% of continental African districts. The model predicted their location with a sensitivity of 88%. The evaluation also suggests that epidemics may be extending south of the Sahel, which is consistent with environmental changes in the region. This model could be used to select priority areas for the introduction of the newly developed conjugate meningococcal vaccines. Further studies are needed to enhance our understanding of the complex relationship between meningitis epidemics and the environment.

REPRODUCTIVE PREFERENCES AND CONTRACEPTIVE USE: A COMPARISON OF MONOGAMOUS AND POLYGAMOUS COUPLES IN NORTHERN MALAWI

Summary There is now widespread agreement on the importance of mens role in reproductive decision-making. Several studies have argued that fertility preferences and their translation into behaviour differ between polygamous and monogamous unions. Studies investigating the dominance of mens preferences over womens preferences, in cases of couple disagreement, found mixed evidence of the effect of polygamy. However, an often cited limitation of these studies has been the inability to link husbands intention with each of his wives in a polygamous union. By adding fertility-intention questions to an on-going Demographic Surveillance Site in Karonga District in northern Malawi the fertility preferences and contraceptive use of husbands and wives were investigated. An analysis of the relationship between the level of agreement and disagreement between husbands and wives fertility preferences was then performed to gain insight into the reproductive decision-making process of polygamous couples.

Sporadic Creutzfeldt-Jakob disease and risk of blood transfusion in the United Kingdom.

An article in TRANSFUSION has recently implicated blood transfusion as a possible risk factor for sporadic Creutzfeldt-Jakob disease (sCJD) in Italy. In this study of patients notified to the Italian National Registry for CJD, Puopolo and colleagues compared blood transfusion histories in patients with a final diagnosis of sCJD with those of noncases, concluding that patients exposed to blood transfusion more than 10 years before clinical onset had a significantly greater risk of subsequently developing sCJD than patients who had been exposed earlier or not at all. In contrast, analysis of similar data from the UK National CJD Surveillance system provides no evidence that blood transfusion is a risk factor for sCJD. In the UK study, we considered all patients referred to the UK national surveillance program with suspected CJD from May 1990 until December 2010 and included in our analysis cases with a final diagnosis of definite or probable sCJD and noncases (patients who definitely did not have CJD or in whom a CJD diagnosis was considered unlikely), in which the history of blood transfusion before clinical onset of symptoms was known, based on information provided by the patients’ families at interview. Patients with sCJD were compared to noncases with respect to 1) having ever received a blood transfusion before onset and 2) the interval between the year of first transfusion and year of clinical onset. Patients transfused in the same year or after onset of illness were considered as not having been transfused before onset. The risks of sCJD by blood transfusion history and interval were evaluated by calculating the odds ratios (ORs, with 95% confidence interval [CI]) for sCJD in exposed compared to unexposed patients, adjusted for potential confounders such as age at onset, sex, year of notification (which might mask changes in transfusion rates and referral practice over time), and history of surgery (which may be associated with blood transfusion as well as a potential risk factor for sCJD), using a multivariable logistic regression model. All analyses were conducted with computer software (STATA/IC 11.1, StataCorp LP, College Station, TX). Between 1990 and 2010, a total of 1206 patients with a final diagnosis of sCJD and 585 noncases were notified in the United Kingdom. Of these, the preonset blood transfusion history was known for 987 (81.8%) patients with sCJD and 159 (27.2%) of noncases. The characteristics of patients with sCJD and noncases are presented in terms of their preonset blood transfusion history and interval and associated adjusted ORs in Table 1. Having received a blood transfusion before onset was not identified as a risk factor for sCJD, either overall or accounting for the interval between first transfusion and clinical onset. There are of course limitations to analyses such as this, including the quality of information on blood transfusion history for both sCJD cases and noncases, which may be recalled inaccurately by family members, and the potential bias that might arise if a noncomparable control group was selected. Preonset hospital medical records, where one might expect blood transfusions to be accurately recorded, are not routinely examined in CJD suspects or cases in the United Kingdom. As in the Italian study we have tried to minimize recall and other bias, by selecting a control group (noncases) that is comparable to patients with sCJD in terms of demographic and referral characteristics, all of whom had been notified and interviewed as CJD suspects before a more definitive later diagnosis. While data are more complete for patients with sCJD than for noncases, the age and sex distribution of both sCJD cases and noncases with known blood transfusion histories was no different from those with unknown histories who were excluded from

Drug Resistance Mutations in Drug-Naive HIV Type 1 Subtype C-Infected Individuals from Rural Malawi

In this preliminary study we show that in 2008, 3 years after antiretroviral therapy was introduced into the Karonga District, Malawi, a greater than expected number of drug-naive individuals have been infected with HIV-1 subtype C virus harboring major and minor drug resistance mutations (DRMs). From a sample size of 40 reverse transcriptase (RT) consensus sequences from drug-naive individuals we found five showing NRTI and four showing NNRTI mutations with one individual showing both. From 29 protease consensus sequences, again from drug-naive individuals, we found evidence of minor DRMs in three. Additional major and minor DRMs were found in clonal sequences from a number of individuals that were not present in the original consensus sequences. This clearly illustrates the importance of sequencing multiple HIV-1 variants from individuals to fully assess drug resistance.

Sporadic Creutzfeldt-Jakob Disease in 2 Plasma Product Recipients, United Kingdom

Two cases of sporadic CJD with clotting disorders have been identified, but this may represent a chance event.