Search

Summary Points * Partnerships between universities in high- and low-income countries have the potential to increase research capacity in both settings. * We describe a partnership between the Karolinska Institutet in Sweden and Makerere University in Uganda that includes a joint PhD degree program and sharing of scientific ideas and resources. * Ten years of financial support from the Swedish International Development Cooperation Agency has enabled 44 graduated PhD students and more than 500 peer-reviewed articles, the majority with a Ugandan as first author. * The collaborative research environment is addressing Ugandan health and health system priorities, in several cases resulting in policy and practice reforms. * Even though all Ugandan PhD graduates have remained in the country and 13 have embarked on postdoc training, remaining institutional challenges include developing functioning research groups, grant writing, network building at Makerere, and continued funding on both sides of the partnership., Background The Bamako Global Ministerial Forum on Research for Health emphasised the importance of developing national health research capacity in low- and middle-income countries (LMICs) as a key element in [...]

The commensal microbiota regulates susceptibility to enteric pathogens by fine-tuning mucosal innate immune responses, but how susceptibility to enteric viruses is shaped by the microbiota remains incompletely understood. Past reports have indicated that commensal bacteria may either promote or repress rotavirus replication in the small intestine of mice. We now report that rotavirus replicated more efficiently in the intestines of germ-free and antibiotic-treated mice compared to animals with an unmodified microbiota. Antibiotic treatment also facilitated rotavirus replication in type I and type III interferon (IFN) receptor-deficient mice, revealing IFN-independent proviral effects. Expression of interleukin-22 (IL-22) was strongly diminished in the intestine of antibiotic-treated mice. Treatment with exogenous IL-22 blocked rotavirus replication in microbiota-depleted wild-type and Stat1-/- mice, demonstrating that the antiviral effect of IL-22 in animals with altered microbiome is not dependent on IFN signaling. In antibiotic-treated animals, IL-22-induced a specific set of genes including Fut2, encoding fucosyl-transferase 2 that participates in the biosynthesis of fucosylated glycans which can mediate rotavirus binding. Interestingly, IL-22 also blocked rotavirus replication in antibiotic-treated Fut2-/- mice. Furthermore, IL-22 inhibited rotavirus replication in antibiotic-treated mice lacking key molecules of the necroptosis or pyroptosis pathways of programmed cell death. Taken together, our results demonstrate that IL-22 determines rotavirus susceptibility of antibiotic-treated mice, yet the IL-22-induced effector molecules conferring rotavirus resistance remain elusive. [ABSTRACT FROM AUTHOR]

Interferons (IFNs) are key controllers of viral replication, with intact IFN responses suppressing virus growth and spread. Using the murine norovirus (MNoV) system, we show that IFNs exert selective pressure to limit the pathogenic evolutionary potential of this enteric virus. In animals lacking type I IFN signaling, the nonlethal MNoV strain CR6 rapidly acquired enhanced virulence via conversion of a single nucleotide. This nucleotide change resulted in amino acid substitution F514I in the viral capsid, which led to >10,000-fold higher replication in systemic organs including the brain. Pathogenicity was mediated by enhanced recruitment and infection of intestinal myeloid cells and increased extraintestinal dissemination of virus. Interestingly, the trade-off for this mutation was reduced fitness in an IFN-competent host, in which CR6 bearing F514I exhibited decreased intestinal replication and shedding. In an immunodeficient context, a spontaneous amino acid change can thus convert a relatively avirulent viral strain into a lethal pathogen. Author summary: The evolution of viruses both within a single host and during transmission between hosts often leads to novel characteristics as mutations develop, with increased lethality or transmissibility being particularly concerning potential outcomes. Here, using a novel in vivo experimental evolution strategy with intestinal pathogen murine norovirus (MNoV), we identified a single nucleotide mutation that consistently and exclusively arose when mice lacking interferon signaling, a key aspect of the early innate immune response, were infected intracranially with a nonlethal strain of MNoV. This mutation was both sufficient and necessary for viral virulence, conferring virulence by enhanced infection of immune cells to facilitate systemic spread, representing a shift in the cell types infected by the virus. Conversely, this mutation was also associated with more limited infection in the intestine, suggesting a fitness cost. Our work identifies key immunological constraints on the evolution of virulence and provides specific mechanistic insights into viral pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Studies from high-income countries reported reduced life expectancy in children with cerebral palsy (CP), while no population-based study has evaluated mortality of children with CP in sub-Saharan Africa. This study aimed to estimate the mortality rate (MR) of children with CP in a rural region of Uganda and identify risk factors and causes of death (CODs). Methods and findings: This population-based, longitudinal cohort study was based on data from Iganga-Mayuge Health and Demographic Surveillance System in eastern Uganda. We identified 97 children (aged 2–17 years) with CP in 2015, whom we followed to 2019. They were compared with an age-matched cohort from the general population (n = 41 319). MRs, MR ratios (MRRs), hazard ratios (HRs), and immediate CODs were determined. MR was 3952 per 100 000 person years (95% CI 2212–6519) in children with CP and 137 per 100 000 person years (95% CI 117–159) in the general population. Standardized MRR was 25·3 in the CP cohort, compared with the general population. In children with CP, risk of death was higher in those with severe gross motor impairments than in those with milder impairments (HR 6·8; p = 0·007) and in those with severe malnutrition than in those less malnourished (HR = 3·7; p = 0·052). MR was higher in females in the CP cohort, with a higher MRR in females (53·0; 95% CI 26·4–106·3) than in males (16·3; 95% CI 7·2–37·2). Age had no significant effect on MR in the CP cohort, but MRR was higher at 10–18 years (39·6; 95% CI 14·2–110·0) than at 2–6 years (21·0; 95% CI 10·2–43·2). Anaemia, malaria, and other infections were the most common CODs in the CP cohort. Conclusions: Risk of premature death was excessively high in children with CP in rural sub-Saharan Africa, especially in those with severe motor impairments or malnutrition. While global childhood mortality has significantly decreased during recent decades, this observed excessive mortality is a hidden humanitarian crisis that needs to be addressed. [ABSTRACT FROM AUTHOR]

The burden of type 2 diabetes is increasing rapidly, not least in Sub-Saharan Africa, and disadvantaged populations are disproportionally affected. Self-management is a key strategy for people at risk of or with type 2 diabetes, but implementation is a challenge. The objective of this study is to assess the determinants of self-management from an implementation perspective in three settings: two rural districts in Uganda, an urban township in South Africa, and socio-economically disadvantaged suburbs in Sweden. Data collection followed an exploratory multiple-case study design, integrating data from interviews, focus group discussions, and observations. Data collection and analysis were guided by a contextualized version of a transdisciplinary framework for self-management. Findings indicate that people at risk of or with type 2 diabetes are aware of major self-management strategies, but fail to integrate these into their daily lives. Depending on the setting, opportunities to facilitate implementation of self-management include: improving patient-provider interaction, improving health service delivery, and encouraging community initiatives supporting self-management. Modification of the physical environment (e.g. accessibility to healthy food) and the socio-cultural environment (i.e. norms, values, attitudes, and social support) may have an important influence on people’s lifestyle. Regarding the study methodology, we learned that this innovative approach can lead to a comprehensive analysis of self-management determinants across different settings. An important barrier was the difficult contextualization of concepts like perceived autonomy and self-efficacy. Intervention studies are needed to confirm whether the pathways suggested by this study are valid and to test the proposed opportunities for change. [ABSTRACT FROM AUTHOR]

Background: Quality Improvement (QI) approaches are increasingly used to bridge the quality gap in maternal and newborn care (MNC) in Sub Saharan Africa. Health workers typically serve as both recipients and implementers of QI activities; their understanding, motivation, and level of involvement largely determining the potential effect. In support of efforts to harmonise and integrate the various QI approaches implemented in parallel in Tanzanian health facilities, our objective was to investigate how different components of a collaborative QI intervention were understood and experienced by health workers, and therefore contributed positively to its mechanisms of effect. Materials and methods: A qualitative process evaluation of a collaborative QI intervention for MNC in rural Tanzania was carried out. Semi-structured interviews were conducted with 16 health workers in 13 purposively sampled health facilities. A deductive theory-driven qualitative content analysis was employed using the integrated Promoting Action on Research Implementation in Health services (i-PARIHS) framework as a lens with its four constructs innovation, recipients, facilitation, and context as guiding themes. Results: Health workers valued the high degree of fit between QI topics and their everyday practice and appreciated the intervention’s comprehensive approach. The use of run-charts to monitor progress was well understood and experienced as motivating. The importance and positive experience of on-site mentoring and coaching visits to individual health facilities was expressed by the majority of health workers. Many described the parallel implementation of various health programs as a challenge. Conclusion: Components of QI approaches that are well understood and experienced as supportive by health workers in everyday practice may enhance mechanisms of effect and result in more significant change. A focus on such components may also guide harmonisation, to avoid duplication and the implementation of parallel programs, and country ownership of QI approaches in resource limited settings. [ABSTRACT FROM AUTHOR]

Background: Pneumonia is the major cause of death in children globally, with more than 900,000 deaths annually in children under five years of age. Streptococcus pneumoniae causes most deaths, most often in the form of community acquired pneumonia. Pneumococcal conjugate vaccines (PCVs) are currently being implemented in many low-income countries. PCVs decrease vaccine-type pneumococcal carriage, a prerequisite for invasive pneumococcal disease, and thereby affects pneumococcal disease and transmission. In Uganda, PCV was launched in 2014, but baseline data is lacking for pneumococcal serotypes in carriage. Objectives: To study pneumococcal nasopharyngeal carriage and serotype distribution in children under 5 years of age prior to PCV introduction in Uganda Methods: Three cross-sectional pneumococcal carriage surveys were conducted in 2008, 2009 and 2011, comprising respectively 150, 587 and 1024 randomly selected children aged less than five years from the Iganga/Mayuge Health and Demographic Surveillance Site. The caretakers were interviewed about illness history of the child and 1723 nasopharyngeal specimens were collected. From these, 927 isolates of S. pneumoniae were serotyped. Results: Overall, the carriage rate of S. pneumoniae was 56% (957/1723). Pneumococcal carriage was associated with illness on the day of the interview (OR = 1.50, p = 0.04). The most common pneumococcal serotypes were in descending order 19F (16%), 23F (9%), 6A (8%), 29 (7%) and 6B (7%). One percent of the strains were non-typeable. The potential serotype coverage rate for PCV10 was 42% and 54% for PCV13. Conclusion: About half of circulating pneumococcal serotypes in carriage in the Ugandan under-five population studied was covered by available PCVs. [ABSTRACT FROM AUTHOR]

Introduction: Drug shops are a major source of care for children in low income countries but they provide sub-standard care. We assessed the feasibility and effect on quality of care of introducing diagnostics and pre-packaged paediatric-dosage drugs for malaria, pneumonia and diarrhoea at drug shops in Uganda. Methods: We adopted and implemented the integrated community case management (iCCM) intervention within registered drug shops. Attendants were trained to perform malaria rapid diagnostic tests (RDTs) in each fever case and count respiratory rate in each case of cough with fast/difficult breathing, before dispensing recommended treatment. Using a quasi-experimental design in one intervention and one non-intervention district, we conducted before and after exit interviews for drug seller practices and household surveys for treatment-seeking practices in May–June 2011 and May–June 2012. Survey adjusted generalized linear models and difference-in-difference analysis was used. Results: 3759 (1604 before/2155 after) household interviews and 943 (163 before/780 after) exit interviews were conducted with caretakers of children under-5. At baseline, no child at a drug shop received any diagnostic testing before treatment in both districts. After the intervention, while no child in the non-intervention district received a diagnostic test, 87.7% (95% CI 79.0–96.4) of children with fever at the intervention district drug shops had a parasitological diagnosis of malaria, prior to treatment. The prevalence ratios of the effect of the intervention on treatment of cough and fast breathing with amoxicillin and diarrhoea with ORS/zinc at the drug shop were 2.8 (2.0–3.9), and 12.8 (4.2–38.6) respectively. From the household survey, the prevalence ratio of the intervention effect on use of RDTs was 3.2 (1.9–5.4); Artemisinin Combination Therapy for malaria was 0.74 (0.65–0.84), and ORS/zinc for diarrhoea was 2.3 (1.2–4.7). Conclusion: iCCM can be utilized to improve access and appropriateness of care for children at drug shops. [ABSTRACT FROM AUTHOR]

Background: In 2010, the World Health Organization revised guidelines to recommend diagnosis of all suspected malaria cases prior to treatment. There has been no systematic assessment of malaria test uptake for pediatric fevers at the population level as countries start implementing guidelines. We examined test use for pediatric fevers in relation to malaria endemicity and treatment-seeking behavior in multiple sub-Saharan African countries in initial years of implementation. Methods and Findings: We compiled data from national population-based surveys reporting fever prevalence, care-seeking and diagnostic use for children under five years in 13 sub-Saharan African countries in 2009–2011/12 (n = 105,791). Mixed-effects logistic regression models quantified the influence of source of care and malaria endemicity on test use after adjusting for socioeconomic covariates. Results were stratified by malaria endemicity categories: low (PfPR2–10<5%), moderate (PfPR2–10 5–40%), high (PfPR2–10>40%). Among febrile under-fives surveyed, 16.9% (95% CI: 11.8%–21.9%) were tested. Compared to hospitals, febrile children attending non-hospital sources (OR: 0.62, 95% CI: 0.56–0.69) and community health workers (OR: 0.31, 95% CI: 0.23–0.43) were less often tested. Febrile children in high-risk areas had reduced odds of testing compared to low-risk settings (OR: 0.51, 95% CI: 0.42–0.62). Febrile children in least poor households were more often tested than in poorest (OR: 1.63, 95% CI: 1.39–1.91), as were children with better-educated mothers compared to least educated (OR: 1.33, 95% CI: 1.16–1.54). Conclusions: Diagnostic testing of pediatric fevers was low and inequitable at the outset of new guidelines. Greater testing is needed at lower or less formal sources where pediatric fevers are commonly managed, particularly to reach the poorest. Lower test uptake in high-risk settings merits further investigation given potential implications for diagnostic scale-up in these areas. Findings could inform continued implementation of new guidelines to improve access to and equity in point-of-care diagnostics use for pediatric fevers. [ABSTRACT FROM AUTHOR]

Background: Development of resistance to first line antimalarials led to recommendation of artemisinin based combination therapies (ACTs). High adherence to ACTs provided by community health workers (CHWs) gave reassurance that community based interventions did not increase the risk of drug resistance. Integrated community case management of illnesses (ICCM) is now recommended through which children will access both antibiotics and antimalarials from CHWs. Increased number of medicines has been shown to lower adherence. Objective: To compare adherence to antimalarials alone versus antimalarials combined with antibiotics under ICCM in children less than five years. Methods: A cohort study was nested within a cluster randomized trial that had CHWs treating children less than five years with antimalarials and antibiotics (intervention areas) and CHWs treating children with antimalarials only (control areas). Children were consecutively sampled from the CHWs' registers in the control areas (667 children); and intervention areas (323 taking antimalarials only and 266 taking antimalarials plus antibiotics). The sampled children were visited at home on day one and four of treatment seeking. Adherence was assessed using self reports and pill counts. Results: Adherence in the intervention arm to antimalarials alone and antimalarials plus antibiotics arm was similar (mean 99% in both groups) but higher than adherence in the control arm (antimalarials only) (mean 96%). Forgetfulness (38%) was the most cited reason for non-adherence. At adjusted analysis: absence of fever (OR = 3.3, 95%CI = 1.6–6.9), seeking care after two or more days (OR = 2.2, 95%CI = 1.3–3.7), not understanding instructions given (OR = 24.5, 95%CI = 2.7–224.5), vomiting (OR = 2.6, 95%CI = 1.2–5.5), and caregivers' perception that the child's illness was not severe (OR = 2.0, 95%CI = 1.1–3.8) were associated with non-adherence. Conclusions: Addition of antibiotics to antimalarials did not lower adherence. However, caregivers should be adequately counseled to understand the dosing regimens; continue with medicines even when the child seems to improve; and re-administer doses that have been vomited. [ABSTRACT FROM AUTHOR]

Background: Few studies have examined the behavioural correlates of non-communicable, chronic disease risk in low-income countries. The objective of this study was to identify socio-behavioural characteristics associated with being overweight or being hypertensive in a low-income setting, so as to highlight possible interventions and target groups. Methods: A population based survey was conducted in a Health and Demographic Surveillance Site (HDSS) in eastern Uganda. 1656 individuals aged 35 to 60 years had their Body Mass Index (BMI) and blood pressure (BP) assessed. Seven lifestyle factors were also assessed, using a validated questionnaire. Logistic regression was used to identify socio-behavioural factors associated with being overweight or being hypertensive. Results: Prevalence of overweight was found to be 18% (25.2% of women; 9.7% of men; p,0.001) while prevalence of obesity was 5.3% (8.3% of women; 2.2% of men). The prevalence of hypertension was 20.5%. Factors associated with being overweight included being female (OR 3.7; 95% CI 2.69-5.08), peri-urban residence (OR 2.5; 95% CI 1.46-3.01), higher socio-economic status (OR 4.1; 95% CI 2.40-6.98), and increasing age (OR 1.8; 95% CI 1.12-2.79). Those who met the recommended minimum physical activity level, and those with moderate dietary diversity were less likely to be overweight (OR 0.5; 95% CI 0.35-0.65 and OR 0.7; 95% CI 0.49-3.01). Factors associated with being hypertensive included peri-urban residence (OR 2.4; 95%CI 1.60-3.66), increasing age (OR 4.5; 95% CI 2.94-6.96) and being over-weight (OR 2.8; 95% CI 1.98-3.98). Overweight persons in rural areas were significantly more likely to be hypertensive than those in peri-urban areas (p = 0.013). Conclusions: Being overweight in low-income settings is associated with sex, physical activity and dietary diversity and being hypertensive is associated with being overweight; these factors are modifiable. There is need for context-specific health education addressing disparities in lifestyles at community levels in rural Africa. [ABSTRACT FROM AUTHOR]

Background:Seventy-five percent of newborn deaths happen in the first-week of life, with the highest risk of death in the first 24-hours after birth.WHO and UNICEF recommend home-visits for babies in the first-week of life to assess for danger-signs and counsel caretakers for immediate referral of sick newborns. We assessed timely compliance with newborn referrals made by community-health workers (CHWs), and its determinants in Iganga and Mayuge Districts in rural eastern Uganda. Methods:A historical cohort study design was used to retrospectively follow up newborns referred to health facilities between September 2009 and August 2011. Timely compliance was defined as caretakers of newborns complying with CHWs’ referral advice within 24-hours. Results:A total of 724 newborns were referred by CHWs of whom 700 were successfully traced. Of the 700 newborns, 373 (53%) were referred for immunization and postnatal-care, and 327 (47%) because of a danger-sign. Overall, 439 (63%) complied, and of the 327 sick newborns, 243 (74%) caretakers complied with the referrals. Predictors of referral compliance were; the newborn being sick at the time of referral- Adjusted Odds Ratio (AOR) = 2.3, and 95% Confidence-Interval (CI) of [1.6 - 3.5]), the CHW making a reminder visit to the referred newborn shortly after referral (AOR =1.7; 95% CI: [1.2 -2.7]); and age of mother (25-29) and (30-34) years, (AOR =0.4; 95% CI: [0.2 - 0.8]) and (AOR = 0.4; 95% CI: [0.2 - 0.8]) respectively. Conclusion:Caretakers’ newborn referral compliance was high in this setting. The newborn being sick, being born to a younger mother and a reminder visit by the CHW to a referred newborn were predictors of newborn referral compliance. Integration of CHWs into maternal and newborn care programs has the potential to increase care seeking for newborns, which may contribute to reduction of newborn mortality. [ABSTRACT FROM AUTHOR]

Background:Our aim was to estimate the prevalence of abnormal glucose regulation (AGR) (i.e. diabetes and pre-diabetes) and its associated factors among people aged 35-60 years so as to clarify the relevance of targeted screening in rural Africa. Methods:A population-based survey of 1,497 people (786 women and 711 men) aged 35-60 years was conducted in a predominantly rural Demographic Surveillance Site in eastern Uganda. Participants responded to a lifestyle questionnaire, following which their Body Mass Index (BMI) and Blood Pressure (BP) were measured. Fasting plasma glucose (FPG) was measured from capillary blood using On-Call® Plus (Acon) rapid glucose meters, following overnight fasting. AGR was defined as FPG ≥6.1mmol L-1 (World Health Organization (WHO) criteria or ≥5.6mmol L-1 (American Diabetes Association (ADA) criteria. Diabetes was defined as FPG >6.9mmol L-1, or being on diabetes treatment. Results:The mean age of participants was 45 years for men and 44 for women. Prevalence of diabetes was 7.4% (95%CI 6.1-8.8), while prevalence of pre-diabetes was 8.6% (95%CI 7.3-10.2) using WHO criteria and 20.2% (95%CI 17.5-22.9) with ADA criteria. Using WHO cut-offs, the prevalence of AGR was 2 times higher among obese persons compared with normal BMI persons (Adjusted Prevalence Rate Ratio (APRR) 1.9, 95%CI 1.3-2.8). Occupation as a mechanic, achieving the WHO recommended physical activity threshold, and higher dietary diversity were associated with lower likelihood of AGR (APRR 0.6, 95%CI 0.4-0.9; APRR 0.6, 95%CI 0.4-0.8; APRR 0.5, 95%CI 0.3-0.9 respectively). The direct medical cost of detecting one person with AGR was two US dollars with ADA and three point seven dollars with WHO cut-offs. Conclusions:There is a high prevalence of AGR among people aged 35-60 years in this setting. Screening for high risk persons and targeted health education to address obesity, insufficient physical activity and non-diverse diets are necessary. [ABSTRACT FROM AUTHOR]

There is a need to understand the growth and burden of malnutrition in children with cerebral palsy (CP) in order to design appropriate inclusive nutrition strategies. We compared the nutritional status and four-year longitudinal growth of a population-based cohort of children and adolescents (C&A) with CP (n = 97; 2-17 years; 55/42 M/F), and an age and sex matched group without CP (n = 91; 2-17y; 50/41 M/F) in rural Uganda. The cohorts were assessed in 2015 and 2019 for weight, height, social demographic characteristics, and feeding related factors. Nutritional status was determined using the World Health Organization (WHO) Z-scores. Wilcoxon sign rank and Mann-Whitney tests were used to test within and between group differences. Multivariable linear regression was used to determine predictors of the change in growth. Approximately two thirds (62/97 (64%)) of C&A with CP were malnourished (with <-2SD in any of the WHO Z-scores), especially those with feeding difficulties (OR = 2.65; P = 0.032), and those who needed to be fed (OR = 3.8; P = 0.019). Both the CP and non-CP groups deviated negatively from the WHO reference growth curve for height, with a significantly slower growth in the CP group (median change score of height-for-age Z score (HAZ) between assessments = -0.80(-1.56, 0.31), p<0.01), than the non-CP group (median HAZ change score = -0.27(-0.92,0.34, p = 0.034). There was a statistically significant group difference in the median HAZ change score between the CP and non-CP groups (z = -2.21, p = 0.026). Severity of motor impairment measured by the Gross Motor Function Classification System (GMFCS-level) correlated negatively (r = -1.37,95%CI -2.67, -0.08) with the change in HAZ scores among the CP group. Children and adolescents with severe motor impairments exhibit an increased risk of malnutrition and growth retardation compared to their age matched peers without CP, which underscores the need to develop inclusive community-based nutrition strategies for children with cerebral palsy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hamid Namaganda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Epilepsy is one of the most common neurological conditions globally, estimated to constitute 0.75% of the global burden of disease, with the majority of this burden found in low- and middle- income countries (LMICs). Few studies from LMICs, including much of sub-Saharan Africa, have described the incidence, remission or mortality rates due to epilepsy, which are needed to quantify the burden and inform policy. This study investigates the epidemiological parameters of convulsive epilepsy within a context of high HIV prevalence and an emerging burden of cardiovascular disease., Methods: A cross-sectional population survey of 82,818 individuals, in the Agincourt Health and Socio-demographic Surveillance Site (HDSS) in rural northeast South Africa was conducted in 2008, from which 296 people were identified with active convulsive epilepsy. A follow-up survey was conducted in 2012. Incidence and mortality rates were estimated, with duration and remission rates calculated using the DISMOD II software package., Results: The crude incidence for convulsive epilepsy was 17.4/100,000 per year (95%CI: 13.1-23.0). Remission was 4.6% and 3.9% per year for males and females, respectively. The standardized mortality ratio was 2.6 (95%CI: 1.7-3.5), with 33.3% of deaths directly related to epilepsy. Mortality was higher in men than women (adjusted rate ratio (aRR) 2.6 (95%CI: 1.2-5.4)), and was significantly associated with older ages (50+ years versus those 0-5 years old (RR 4.8 (95%CI: 0.6-36.4))., Conclusions: The crude incidence was lower whilst mortality rates were similar to other African studies; however, this study found higher mortality amongst older males. Efforts aimed at further understanding what causes epilepsy in older people and developing interventions to reduce prolonged seizures are likely to reduce the overall burden of ACE in rural South Africa.