Ryan G. Wagner

Profile: Agincourt Health and Socio-demographic Surveillance System

The Agincourt health and socio-demographic surveillance system (HDSS), located in rural northeast South Africa close to the Mozambique border, was established in 1992 to support district health systems development led by the post-apartheid ministry of health. The HDSS (90 000 people), based on an annual update of resident status and vital events, now supports multiple investigations into the causes and consequences of complex health, population and social transitions. Observational work includes cohorts focusing on different stages along the life course, evaluation of national policy at population, household and individual levels and examination of household responses to shocks and stresses and the resulting pathways influencing health and well-being. Trials target children and adolescents, including promoting psycho-social well-being, preventing HIV transmission and reducing metabolic disease risk. Efforts to enhance the research platform include using automated measurement techniques to estimate cause of death by verbal autopsy, full ‘reconciliation’ of in- and out-migrations, follow-up of migrants departing the study area, recording of extra-household social connections and linkage of individual HDSS records with those from sub-district clinics. Fostering effective collaborations (including INDEPTH multi-centre work in adult health and ageing and migration and urbanization), ensuring cross-site compatibility of common variables and optimizing public access to HDSS data are priorities.

Prevalence of active convulsive epilepsy in sub-Saharan Africa and associated risk factors: Cross-sectional and case-control studies

Summary Background The prevalence of epilepsy in sub-Saharan Africa seems to be higher than in other parts of the world, but estimates vary substantially for unknown reasons. We assessed the prevalence and risk factors of active convulsive epilepsy across five centres in this region. Methods We did large population-based cross-sectional and case-control studies in five Health and Demographic Surveillance System centres: Kilifi, Kenya (Dec 3, 2007–July 31, 2008); Agincourt, South Africa (Aug 4, 2008–Feb 27, 2009); Iganga-Mayuge, Uganda (Feb 2, 2009–Oct 30, 2009); Ifakara, Tanzania (May 4, 2009–Dec 31, 2009); and Kintampo, Ghana (Aug 2, 2010–April 29, 2011). We used a three-stage screening process to identify people with active convulsive epilepsy. Prevalence was estimated as the ratio of confirmed cases to the population screened and was adjusted for sensitivity and attrition between stages. For each case, an age-matched control individual was randomly selected from the relevant centres census database. Fieldworkers masked to the status of the person they were interviewing administered questionnaires to individuals with active convulsive epilepsy and control individuals to assess sociodemographic variables and historical risk factors (perinatal events, head injuries, and diet). Blood samples were taken from a randomly selected subgroup of 300 participants with epilepsy and 300 control individuals from each centre and were screened for antibodies to Toxocara canis, Toxoplasma gondii, Onchocerca volvulus, Plasmodium falciparum, Taenia solium, and HIV. We estimated odds ratios (ORs) with logistic regression, adjusted for age, sex, education, employment, and marital status. Results 586 607 residents in the study areas were screened in stage one, of whom 1711 were diagnosed as having active convulsive epilepsy. Prevalence adjusted for attrition and sensitivity varied between sites: 7·8 per 1000 people (95% CI 7·5–8·2) in Kilifi, 7·0 (6·2–7·4) in Agincourt, 10·3 (9·5–11·1) in Iganga-Mayuge, 14·8 (13·8–15·4) in Ifakara, and 10·1 (9·5–10·7) in Kintampo. The 1711 individuals with the disorder and 2032 control individuals were given questionnaires. In children (aged <18 years), the greatest relative increases in prevalence were associated with difficulties feeding, crying, or breathing after birth (OR 10·23, 95% CI 5·85–17·88; p<0·0001); abnormal antenatal periods (2·15, 1·53–3·02; p<0·0001); and head injury (1·97, 1·28–3·03; p=0·002). In adults (aged ≥18 years), the disorder was significantly associated with admission to hospital with malaria or fever (2·28, 1·06–4·92; p=0·036), exposure to T canis (1·74, 1·27–2·40; p=0·0006), exposure to T gondii (1·39, 1·05–1·84; p=0·021), and exposure to O volvulus (2·23, 1·56–3·19; p<0·0001). Hypertension (2·13, 1·08–4·20; p=0·029) and exposure to T solium (7·03, 2·06–24·00; p=0·002) were risk factors for adult-onset disease. Interpretation The prevalence of active convulsive epilepsy varies in sub-Saharan Africa and that the variation is probably a result of differences in risk factors. Programmes to control parasitic diseases and interventions to improve antenatal and perinatal care could substantially reduce the prevalence of epilepsy in this region. Funding Wellcome Trust, University of the Witwatersrand, and South African Medical Research Council.

The effect of a conditional cash transfer on HIV incidence in young women in rural South Africa (HPTN 068): a phase 3, randomised controlled trial

BACKGROUND Cash transfers have been proposed as an intervention to reduce HIV-infection risk for young women in sub-Saharan Africa. However, scarce evidence is available about their effect on reducing HIV acquisition. We aimed to assess the effect of a conditional cash transfer on HIV incidence among young women in rural South Africa. METHODS We did a phase 3, randomised controlled trial (HPTN 068) in the rural Bushbuckridge subdistrict in Mpumalanga province, South Africa. We included girls aged 13-20 years if they were enrolled in school grades 8-11, not married or pregnant, able to read, they and their parent or guardian both had the necessary documentation necessary to open a bank account, and were residing in the study area and intending to remain until trial completion. Young women (and their parents or guardians) were randomly assigned (1:1), by use of numbered sealed envelopes containing a randomisation assignment card which were numerically ordered with block randomisation, to receive a monthly cash transfer conditional on school attendance (≥80% of school days per month) versus no cash transfer. Participants completed an Audio Computer-Assisted Self-Interview (ACASI), before test HIV counselling, HIV and herpes simplex virus (HSV)-2 testing, and post-test counselling at baseline, then at annual follow-up visits at 12, 24, and 36 months. Parents or guardians completed a Computer-Assisted Personal Interview at baseline and each follow-up visit. A stratified proportional hazards model was used in an intention-to-treat analysis of the primary outcome, HIV incidence, to compare the intervention and control groups. This study is registered at ClinicalTrials.gov (NCT01233531). FINDINGS Between March 5, 2011, and Dec 17, 2012, we recruited 10 134 young women and enrolled 2537 and their parents or guardians to receive a cash transfer programme (n=1225) or not (control group; n=1223). At baseline, the median age of girls was 15 years (IQR 14-17) and 672 (27%) had reported to have ever had sex. 107 incident HIV infections were recorded during the study: 59 cases in 3048 person-years in the intervention group and 48 cases in 2830 person-years in the control group. HIV incidence was not significantly different between those who received a cash transfer (1·94% per person-years) and those who did not (1·70% per person-years; hazard ratio 1·17, 95% CI 0·80-1·72, p=0·42). INTERPRETATION Cash transfers conditional on school attendance did not reduce HIV incidence in young women. School attendance significantly reduced risk of HIV acquisition, irrespective of study group. Keeping girls in school is important to reduce their HIV-infection risk. FUNDING National Institute of Allergy and Infectious Diseases, National Institute of Mental Health of the National Institutes of Health.

Exposure to Multiple Parasites Is Associated with the Prevalence of Active Convulsive Epilepsy in Sub-Saharan Africa

Background Epilepsy is common in developing countries, and it is often associated with parasitic infections. We investigated the relationship between exposure to parasitic infections, particularly multiple infections and active convulsive epilepsy (ACE), in five sites across sub-Saharan Africa. Methods and Findings A case-control design that matched on age and location was used. Blood samples were collected from 986 prevalent cases and 1,313 age-matched community controls and tested for presence of antibodies to Onchocerca volvulus, Toxocara canis, Toxoplasma gondii, Plasmodium falciparum, Taenia solium and HIV. Exposure (seropositivity) to Onchocerca volvulus (OR = 1.98; 95%CI: 1.52–2.58, p<0.001), Toxocara canis (OR = 1.52; 95%CI: 1.23–1.87, p<0.001), Toxoplasma gondii (OR = 1.28; 95%CI: 1.04–1.56, p = 0.018) and higher antibody levels (top tertile) to Toxocara canis (OR = 1.70; 95%CI: 1.30–2.24, p<0.001) were associated with an increased prevalence of ACE. Exposure to multiple infections was common (73.8% of cases and 65.5% of controls had been exposed to two or more infections), and for T. gondii and O. volvulus co-infection, their combined effect on the prevalence of ACE, as determined by the relative excess risk due to interaction (RERI), was more than additive (T. gondii and O. volvulus, RERI = 1.19). The prevalence of T. solium antibodies was low (2.8% of cases and 2.2% of controls) and was not associated with ACE in the study areas. Conclusion This study investigates how the degree of exposure to parasites and multiple parasitic infections are associated with ACE and may explain conflicting results obtained when only seropositivity is considered. The findings from this study should be further validated.

Clinical features, proximate causes, and consequences of active convulsive epilepsy in Africa.

Epilepsy is common in sub‐Saharan Africa (SSA), but the clinical features and consequences are poorly characterized. Most studies are hospital‐based, and few studies have compared different ecological sites in SSA. We described active convulsive epilepsy (ACE) identified in cross‐sectional community‐based surveys in SSA, to understand the proximate causes, features, and consequences.

Do Helminths cause Epilepsy

Both helminthiases and epilepsy occur globally, and are particularly prevalent in developing regions of the world. Studies have suggested an association between epilepsy and helminth infection, but a causal relationship is not established in many helminths, except perhaps with neurocysticercosis. We review the available literature on the global burden of helminths, and the epidemiological evidence linking helminths to epilepsy. We discuss possible routes that helminths affect the central nervous system (CNS) of humans and the immunological response to helminth infection in the CNS, looking at possible mechanisms of epileptogenesis. Finally, we discuss the current gaps in knowledge about the interaction between helminths and epilepsy.

Prevalence and risk factors for active convulsive epilepsy in rural northeast South Africa

Highlights • Epilepsy is prevalent in rural South Africa, but less than other parts of Africa.• Most epilepsy starts in childhood.• Poor obstetric history and snoring were associated with active convulsive epilepsy.• HIV and parasitic infection were not associated with active convulsive epilepsy.

A comparative analysis of national HIV policies in six African countries with generalized epidemics

Abstract Objective To compare national human immunodeficiency virus (HIV) policies influencing access to HIV testing and treatment services in six sub-Saharan African countries. Methods We reviewed HIV policies as part of a multi-country study on adult mortality in sub-Saharan Africa. A policy extraction tool was developed and used to review national HIV policy documents and guidelines published in Kenya, Malawi, South Africa, Uganda, the United Republic of Tanzania and Zimbabwe between 2003 and 2013. Key informant interviews helped to fill gaps in findings. National policies were categorized according to whether they explicitly or implicitly adhered to 54 policy indicators, identified through literature and expert reviews. We also compared the national policies with World Health Organization (WHO) guidance. Findings There was wide variation in policies between countries; each country was progressive in some areas and not in others. Malawi was particularly advanced in promoting rapid initiation of antiretroviral therapy. However, no country had a consistently enabling policy context expected to increase access to care and prevent attrition. Countries went beyond WHO guidance in certain areas and key informants reported that practice often surpassed policy. Conclusion Evaluating the impact of policy differences on access to care and health outcomes among people living with HIV is challenging. Certain policies will exert more influence than others and official policies are not always implemented. Future research should assess the extent of policy implementation and link these findings with HIV outcomes.

Prevalence and factors associated with convulsive status epilepticus in Africans with epilepsy

Objective: We conducted a community survey to estimate the prevalence and describe the features, risk factors, and consequences of convulsive status epilepticus (CSE) among people with active convulsive epilepsy (ACE) identified in a multisite survey in Africa. Methods: We obtained clinical histories of CSE and neurologic examination data among 1,196 people with ACE identified from a population of 379,166 people in 3 sites: Agincourt, South Africa; Iganga-Mayuge, Uganda; and Kilifi, Kenya. We performed serologic assessment for the presence of antibodies to parasitic infections and HIV and determined adherence to antiepileptic drugs. Consequences of CSE were assessed using a questionnaire. Logistic regression was used to identify risk factors. Results: The adjusted prevalence of CSE in ACE among the general population across the 3 sites was 2.3 per 1,000, and differed with site (p < 0.0001). Over half (55%) of CSE occurred in febrile illnesses and focal seizures were present in 61%. Risk factors for CSE in ACE were neurologic impairments, acute encephalopathy, previous hospitalization, and presence of antibody titers to falciparum malaria and HIV; these differed across sites. Burns (15%), lack of education (49%), being single (77%), and unemployment (78%) were common in CSE; these differed across the 3 sites. Nine percent with and 10% without CSE died. Conclusions: CSE is common in people with ACE in Africa; most occurs with febrile illnesses, is untreated, and has focal features suggesting preventable risk factors. Effective prevention and the management of infections and neurologic impairments may reduce the burden of CSE in ACE.

Closing the mental health treatment gap in South Africa: a review of costs and cost-effectiveness

Background Nearly one in three South Africans will suffer from a mental disorder in his or her lifetime, a higher prevalence than many low- and middle-income countries. Understanding the economic costs and consequences of prevention and packages of care is essential, particularly as South Africa considers scaling-up mental health services and works towards universal health coverage. Economic evaluations can inform how priorities are set in system or spending changes. Objective To identify and review research from South Africa and sub-Saharan Africa on the direct and indirect costs of mental, neurological, and substance use (MNS) disorders and the cost-effectiveness of treatment interventions. Design Narrative overview methodology. Results and conclusions Reviewed studies indicate that integrating mental health care into existing health systems may be the most effective and cost-efficient approach to increase access to mental health services in South Africa. Integration would also direct treatment, prevention, and screening to people with HIV and other chronic health conditions who are at high risk for mental disorders. We identify four major knowledge gaps: 1) accurate and thorough assessment of the health burdens of MNS disorders, 2) design and assessment of interventions that integrate mental health screening and treatment into existing health systems, 3) information on the use and costs of traditional medicines, and 4) cost-effectiveness evaluation of a range of specific interventions or packages of interventions that are tailored to the national context.Background Nearly one in three South Africans will suffer from a mental disorder in his or her lifetime, a higher prevalence than many low- and middle-income countries. Understanding the economic costs and consequences of prevention and packages of care is essential, particularly as South Africa considers scaling-up mental health services and works towards universal health coverage. Economic evaluations can inform how priorities are set in system or spending changes. Objective To identify and review research from South Africa and sub-Saharan Africa on the direct and indirect costs of mental, neurological, and substance use (MNS) disorders and the cost-effectiveness of treatment interventions. Design Narrative overview methodology. Results and conclusions Reviewed studies indicate that integrating mental health care into existing health systems may be the most effective and cost-efficient approach to increase access to mental health services in South Africa. Integration would also direct treatment, prevention, and screening to people with HIV and other chronic health conditions who are at high risk for mental disorders. We identify four major knowledge gaps: 1) accurate and thorough assessment of the health burdens of MNS disorders, 2) design and assessment of interventions that integrate mental health screening and treatment into existing health systems, 3) information on the use and costs of traditional medicines, and 4) cost-effectiveness evaluation of a range of specific interventions or packages of interventions that are tailored to the national context.