Glycated haemoglobin A1c (HbA1c) for detection of diabetes mellitus and impaired fasting glucose in Malawi: a diagnostic accuracy study.

OBJECTIVES: To examine the accuracy of glycated haemoglobin A1c (HbA1c) in detecting type 2 diabetes and impaired fasting glucose among adults living in Malawi. DESIGN: A diagnostic validation study of HbA1c. Fasting plasma glucose (FPG) ≥7.0 mmol/L was the reference standard for type 2 diabetes, and FPG between 6.1 and 6.9 mmol/L as impaired fasting glucose. PARTICIPANTS: 3645 adults (of whom 63% were women) recruited from two demographic surveillance study sites in urban and rural Malawi. This analysis excluded those who had a previous diagnosis of diabetes or had history of taking diabetes medication. RESULTS: HbA1c demonstrated excellent validity to detect FPG-defined diabetes, with an area under the receiver operating characteristic (AUROC) curve of 0.92 (95% CI 0.90 to 0.94). At HbA1c ≥6.5% (140 mg/dL), sensitivity was 78.7% and specificity was 94.0%. Subgroup AUROCs ranged from 0.86 for participants with anaemia to 0.94 for participants in urban Malawi. There were clinical and metabolic differences between participants with true diabetes versus false positives when HbA1c was ≥6.5% (140 mg/dL). CONCLUSIONS: The findings from this study provide justification to use HbA1c to detect type 2 diabetes. As HbA1c testing is substantially less burdensome to patients than either FPG testing or oral glucose tolerance testing, it represents a useful option for expanding access to diabetes care in sub-Saharan Africa.

Hypertension and diabetes in Africa: design and implementation of a large population-based study of burden and risk factors in rural and urban Malawi.

BACKGROUND: The emerging burden of cardiovascular disease and diabetes in sub-Saharan Africa threatens the gains made in health by the major international effort to combat infectious diseases. There are few data on distribution of risk factors and outcomes in the region to inform an effective public health response. A comprehensive research programme is being developed aimed at accurately documenting the burden and drivers of NCDs in urban and rural Malawi; to design and test intervention strategies. The programme includes population surveys of all people aged 18 years and above, linking individuals with newly diagnosed hypertension and diabetes to healthcare and supporting clinical services. The successes, challenges and lessons learnt from the programme to date are discussed. RESULTS: Over 20,000 adults have been recruited in rural Karonga and urban Lilongwe. The urban population is significantly younger and wealthier than the rural population. Employed urban individuals, particularly males, give particular recruitment challenges; male participation rates were 80.3 % in the rural population and 43.6 % in urban, whilst female rates were 93.6 and 75.6 %, respectively. The study is generating high quality data on hypertension, diabetes, lipid abnormalities and risk factors. CONCLUSIONS: It is feasible to develop large scale studies that can reliably inform the public health approach to diabetes, cardiovascular disease and other NCDs in Sub-Saharan Africa. It is essential for studies to capture both rural and urban populations to address disparities in risk factors, including age structure. Innovative approaches are needed to address the specific challenge of recruiting employed urban males.

Maternal HIV status associated with under-five mortality in rural Northern Malawi: a prospective cohort study.

BACKGROUND: Under-five mortality is decreasing but with little change in neonatal mortality rates. We examined the effect of maternal HIV status on under-five mortality and cause of death since widespread availability of antiretroviral therapy in rural Malawi. METHODS: Children born in 2006-2011 in the Karonga demographic surveillance area were included. Maternal HIV status was available from HIV serosurveys. Age-specific mortality rate ratios for children born to HIV-positive and HIV-negative mothers were obtained by fitting a Poisson model accounting for child clustering by mother and adjusting for potential confounders. Cause of death was ascertained by verbal autopsy. FINDINGS: There were 352 deaths among 6913 under-five singleton children followed for 20,754 person-years (py), giving a mortality rate of 17.0/1000 py overall, 218/1000 py (16.5/1000 live births) in neonates, 20/1000 py (17.4/1000 live births) in postneonatal infants, and 8/1000 py in 1-4 years old. Comparing those born to HIV-positive and HIV-negative mothers, the rate ratio adjusted for child age, sex, maternal age, parity, and drinking water source was 1.5 (95% confidence interval [CI]: 0.6 to 3.7) in neonates, 11.5 (95% CI: 7.2 to 18.5) in postneonatal infants, and 4.6 (95% CI: 2.7 to 7.9) in 1-4 years old. Birth injury/asphyxia, neonatal sepsis, and prematurity contributed >70% of neonatal deaths, whereas acute infections, malaria, diarrhea, and pneumonia accounted for most deaths in older children. CONCLUSIONS: Maternal HIV status had little effect on neonatal mortality but was associated with much higher mortality in the postneonatal period and among older children. Greater attention to HIV care in pregnant women and mothers should help improve child survival, but broader interventions are needed to reduce neonatal mortality.

Uptake of prevention of mother-to-child-transmission using Option B+ in northern rural Malawi: a retrospective cohort study.

To identify points of dropout on the pathway from offering HIV testing to maintenance on antiretroviral therapy (ART), following the introduction of the Option B+ policy for pregnant women in Malawi (lifelong ART for HIV-positive mothers and 6 weeks nevirapine for the infants), a retrospective cohort study within a demographic surveillance system in northern Malawi. Women living in the demographic surveillance system who initiated antenatal care (ANC) between July 2011 (date of policy change) and January 2013, were eligible for inclusion. Women who consented were interviewed at home about their health facility attendance and care since pregnancy, including antenatal clinic (ANC) visits, delivery and postpartum care. Women's reports, patient-held health records and clinic health records were manually linked to ascertain service use. Among 395 women, 86% had tested for HIV before the pregnancy, 90% tested or re-tested at the ANC visit, and <1% had never tested. Among 53 mothers known to be HIV-positive before attending ANC, 15 (28%) were already on ART prior to pregnancy. Ten women tested HIV-positive for the first time during pregnancy. Of the 47 HIV-positive mothers not already on ART, 26/47 (55%) started treatment during pregnancy. All but five women who started ART were still on treatment at the time of study interview. HIV testing was almost universal and most women who initiated ART were retained in care. However, nearly half of eligible pregnant women not on ART at the start of ANC had not taken up the invitation to initiate (lifelong) ART by the time of delivery, leaving their infants potentially HIV-exposed.

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 33 000 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.

Very early anthropometric changes after antiretroviral therapy predict subsequent survival, in karonga, Malawi.

BACKGROUND: Antiretroviral (ART) scale-up in Malawi has been achieved on a large scale based mainly on clinical criteria. Simple markers of prognosis are useful, and we investigated the value of very early anthropometric changes in predicting mortality. PRINCIPAL FINDINGS: Adult patients who initiated ART in Karonga District, northern Malawi, between September 2005 and August 2006 were included in a prospective cohort study, and followed for up to one year. We used Cox regression to examine the association between anthropometric changes at 2 and 6 weeks and deaths within the first year. 573 patients were included, of whom 59% were women; the median age at initiation was 37 and 64% were in WHO stage 4. Both body mass index (BMI) and mid-upper arm circumference (MUAC) increased linearly with increased time on ART, and were closely correlated with each other. There were 118 deaths. After 2 weeks on ART, a BMI increase of <0.5 kg/m(2) (HR 2.47, 95%CI 1.24-4.94, p=0.005) or a MUAC increase of <0.5cm (HR 2.79, 95%CI 1.19-6.55, p=0.008) were strong predictors of death, and these associations were stronger after adjusting for baseline charactertistics. Similar results were found after 6 weeks on ART. CONCLUSIONS: Very early anthropometric changes, after 2 and 6 weeks on ART, are strong predictors of survival, independent of baseline characteristics. This should help identify patients requiring more detailed assessment where facilities are limited. MUAC is particularly valuable, requiring the simplest equipment and being appropriate for patients who have problems standing.

What happens to ART-eligible patients who do not start ART? Dropout between screening and ART initiation: a cohort study in Karonga, Malawi.

BACKGROUND: Routine ART programme statistics generally only provide information about individuals who start treatment. We aimed to investigate the outcome of those who are eligible but do not start ART in the Malawi programme, factors associated with this dropout, and reasons for not starting treatment, in a prospective cohort study. METHODS: Individuals having a first screening visit at the ART clinic at Karonga District Hospital, northern Malawi, between September 2005 and July 2006 were interviewed. Study follow-up to identify treatment outcomes was conducted at the clinic and in the community. Logistic regression models were used to identify factors associated with dropout before ART initiation among participants identified as clinically eligible for ART. RESULTS: 88 participants eligible for ART at their first screening visit (out of 633, 13.9%) defaulted before starting ART. Participants with less education, difficulties in dressing, a more delayed ART initiation appointment, and mid-upper arm circumference (MUAC) < 22 cm were significantly less likely to have visited the clinic subsequently. Thirty-five (58%) of the 60 participants who defaulted and were tracked at home had died, 21 before their ART initiation appointment. CONCLUSIONS: MUAC and reported difficulties in dressing may provide useful screening indicators to identify sicker ART-eligible individuals at high risk of dropping out of the programme who might benefit from being brought back quickly or admitted to hospital for observation. Individuals with less education may need adapted health information at screening. Deaths of ART-eligible individuals occurring prior to ART initiation are not included in routine programme statistics. Considering all those who are eligible for ART as a denominator for programme indicators would help to highlight this vulnerable group, in order to identify new opportunities for further improving ART programmes.

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 client's home performs well when used on a wide scale in the community setting.

Estimating the need for antiretroviral treatment and an assessment of a simplified HIV/AIDS case definition in rural Malawi.

BACKGROUND: 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. METHODS: 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. 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. CONCLUSION: 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.