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Peritonitis is a frequent complication of peritoneal dialysis (PD) in children as well in adults. Data on PD and peritonitis in pediatric patients are very scarce in developing countries. A retrospective cohort study was performed between 2000 and 2008 with the aim to evaluate PD treatment and peritonitis epidemiology in pediatric patients in South Africa and identify risk factors for peritonitis. Baseline characteristics and potential risk factors of peritonitis were recorded, including housing, socio-economic circumstances, distance to PD center, type of PD, mode of catheter placement, race, presence of gastrostomy tube, weight, and height. Outcome indices for peritonitis were peritonitis rate, time to first peritonitis, and number of peritonitis-free patients. The patient cohort comprised 67 patients who were on PD for a total of 544 months. The total number of peritonitis episodes was 129. Median peritonitis rate was one episode every 4.3 patient months (2.8 episodes/patient-year, range 0-21.2). Median time to first infection was 2.03 months (range 0.1-21.5 months), and 28.4% of patients remained free from peritonitis. Patients with good housing and good socio-economic circumstances had a significantly lower peritonitis rate and a longer time to first peritonitis episode. Peritonitis rate was high in this cohort, compared to numbers reported for the developed world; the characteristics of causative organisms are comparable. The most important risk factors for the development of peritonitis were poor housing and poor socio-economic circumstances. More intensive counseling may be beneficial, but improvement of general socio-economic circumstances will have the greatest influence on PD success.

Pathogenesis studies of SIV infection have not been performed to date in wild monkeys due to difficulty in collecting and storing samples on site and the lack of analytical reagents covering the extensive SIV diversity. We performed a large scale study of molecular epidemiology and natural history of SIVagm infection in 225 free-ranging AGMs from multiple locations in South Africa. SIV prevalence (established by sequencing pol, env, and gag) varied dramatically between infant/juvenile (7%) and adult animals (68%) (p, Author Summary We simultaneously assessed, for the first time in a natural host, the epidemiology, diversity and natural history of SIVagmVer infection in wild vervet populations from South Africa. We report that African green monkeys (AGMs) have likely been infected with SIVagm for a long period, ranging from the time of their speciation to Plio-Pleistocene migrations, refuting previous molecular clock calculations suggesting SIVagm to be of recent occurrence. As a result of virus-host coadaptation, SIVagmVer infection is characterized by a lack of disease progression in spite of robust viral replication. We show that very active SIVagm transmission in adult AGMs contrasts with a very limited transmission to their offspring, in spite of massive exposure to SIVagm both in utero and through breastfeeding. The observation that some AGMs remain uninfected in spite of life-long exposure to SIVagm identifies wild vervets as an acceptable animal model for the exposed uninfected individuals, which can be used to identify correlates of resistance to HIV/SIV infection.

Disorders of the nervous system represent a significant proportion of the global burden of non-communicable diseases, due to the trend towards ageing populations. The Department (now Division) of Human Genetics at the University of Cape Town (UCT) has been involved in pioneering research into these diseases since the appointment of Prof. Peter Beighton as Head of Department in 1972. Beighton's emphasis on understanding the genetic basis of disease laid the groundwork for investigations into several monogenic neurodegenerative conditions, including Huntington's disease and the polyglutamine spinocerebellar ataxias (SCAs). In particular, SCA7, which occurs at an unusually high frequency in the South African (SA) population, was identified as a target for further research and therapeutic development. Beginning with early epidemiological surveys, the SCA7 project progressed to molecular genetics-based investigations, leading to the identification of a founder effect in the SA SCA7 patient population in the mid-2000s. Capitalising on the founder haplotype shared by many SCA7 patients, UCT researchers went on to develop the first population-specific gene-silencing approach for the disease. More recently, efforts have shifted to the development of a more accurate model to decipher the precise mechanisms of neurodegeneration, using induced pluripotent stem cells derived from SA SCA7 patients. In many ways, the SA SCA7 journey reflects the legacy and vision of Prof. Peter Beighton, and his efforts to establish world-class, collaborative research into diseases affecting the African continent.

This review aims to summarize data published in the scientific literature and available on official websites on the epidemiology, policies and services for children and adults with intellectual disability in South Africa.There is a paucity of published literature on intellectual disability in South Africa. The lack of evidence-based publications within the prescribed review period of 12-18 months precludes an accurate description of the prevailing epidemiology and burden of disablement in this country. The few studies yielding epidemiological data were conducted prior to 2002. These suggest that the prevalence rate of intellectual disability is greater than in high-income countries. There is little data describing intellectual disability geographically and across population and age groups, further rendering it difficult to identify inequalities and differences in distribution. There is a high burden of preventable causes of intellectual disability.Despite the existence of policies and services for the population with intellectual disabilities in South Africa, recognition of and provision for their needs carries low priority. It is imperative that the information gap in epidemiology and the burden of disability be recognized in order to plan for and meet the needs of those with intellectual disability across the lifespan.

Morphometric and sex linked phenomena in male Bullia digitalis, from the Western Cape coast of South Africa, are related to infection with a digenean microphallid larva described here for the first time and named Cercaria hastata. Penis shedding in Bullia is not uncommon. Most of the stumps are found on infected whelks, and this is probably due to parasitic inhibition of an otherwise rapid regeneration. The infection also abolishes sperm production. Stumps were never seen on sperm producing males, all of which have large penes, and in non-infected males, shedding occurs only in non-producers. In large non-infected Bullia, those which have underdeveloped penes and are non-producers of sperm may be transient intersexes. This is supported by the exhibition of protandry indicators such as brooding, nonsize preferential mate selection and gregariousness. Infection prevalence is size dependent, large whelks being more commonly infected; but parasitic gigantism is thought unlikely as Bullia is iteroparous.

Background: South Africa has endorsed a World Health Assembly (WHA) resolution calling for control of soil-transmitted helminths (STHs). In Cape Town, services and housing that exist in old-established suburbs should minimise the prevalence of intestinal parasitic infections, even when residents are poor. Where families live in shacks in densely-populated areas without effective sanitation, more than 90% of children can be infected by STHs. The humoral immune response to worms theoretically favours infection by Mycobacterium tuberculosis and HIV. Objectives: Obtain estimates of gender-, age-, school-related and overall prevalence of helminthiasis and giardiasis in a lowincome but well-serviced community. Assess possible sources of infection. Alert health services to the need for control measures and the threat from protozoal pathogens. Warn that the immune response to intestinal parasites may favour tuberculosis (TB) and HIV/ AIDS. Methods: A cross-sectional study of the prevalence of helminthiasis and giardiasis was carried out in a large, non-selective sample of children attending nine schools. Gender, school and age effects were related to non-medical preventive services, sewage disposal practices and possible sources of infection. Results: The overall STH infestation rate was 55.8%. Prevalence was in.uenced by school and age but not by gender. Eggs and cysts were seen at the following prevalence: Ascaris 24.8%; Trichuris 50.6%; Hymenolepis nana 2.2%; Enterobius 0.6%; Giardia 17.3%; hookworm 0.08%; and Trichostrongylus 0.1%. Approximately 60% of sewage sludge is used in a form that will contain viable eggs and cysts. Conclusions: Prevalence trends in this old community in Cape Town could indicate infection by swallowing eggs or cysts on food or in water, more than by exposure to polluted soil. Sewage sludge and effluent might be sources of infection. In adjacent, under serviced, newer communities, promiscuous defecation occurs. Probable vectors are discussed. The immune response to intestinal parasites might be a risk factor for HIV/AIDS and TB. Keywords: Ascaris; Enterobius; HIV/AIDS; hookworm; IgE; Trichuris; tuberculosis African Health Sciences Vol. 5 (3) 2005: pp. 276-280

BackgroundSince 1995, measles vaccination at nine and 18 months has been routine in South Africa; however, coverage seldom reached >95%. We describe the epidemiology of laboratory-confirmed measles case-patients and assess the impact of the nationwide mass vaccination campaign during the 2009 to 2011 measles outbreak in South Africa.MethodsSerum specimens collected from patients with suspected-measles were tested for measles-specific IgM antibodies using an enzyme-linked immunosorbent assay and genotypes of a subset were determined. To estimate the impact of the nationwide mass vaccination campaign, we compared incidence in the seven months pre- (1 September 2009-11 April 2010) and seven months post-vaccination campaign (24 May 2010-31 December 2010) periods in seven provinces of South Africa.ResultsA total of 18,431 laboratory-confirmed measles case-patients were reported from all nine provinces of South Africa (cumulative incidence 37 per 100,000 population). The highest cumulative incidence per 100,000 population was in children aged ConclusionWe observed a reduction in measles incidence following the nationwide mass vaccination campaign even though it was conducted approximately one year after the outbreak started. A booster dose at school entry may be of value given the high incidence in persons >5 years.

Globally, no person has been untouched by the COVID-19 pandemic. Yet, little attention has been given to children and adolescents in policy, provision and services. Moreover, there is a dearth of knowledge regarding the impact of COVID-19-associated orphanhood and caregiver loss on children. This study aims to provide early insights into the mental health and well-being of children and adolescents experiencing orphanhood or caregiver loss in South Africa. Data will be drawn from a quantitative longitudinal study in Cape Town, South Africa. A sample of children and adolescents between the ages of 9 and 18 years, experiencing parental or caregiver loss from COVID-19, will be recruited together with a comparison group of children in similar environments who did not experience loss. The study aims to recruit 500 children in both groups. Mental health and well-being among children will be explored through the use of validated and study-specific measures. Participants will be interviewed at two time points, with follow-up data being collected 12-18 months after baseline. A combination of analytical techniques (including descriptive statistics, regression modelling and structural equation modelling) will be used to understand the experience and inform future policy and service provision. This study received ethical approval from the Health Research Ethics Committee at Stellenbosch University (N 22/04/040). Results will be disseminated via academic and policy publications, as well as national and international presentations including high-level meetings with technical experts. Findings will also be disseminated at a community level via various platforms.

Background Engagement in protective behaviours relating to the COVID-19 pandemic has been proposed to be key to infection control. This is particularly the case for youths as key drivers of infections. A range of factors influencing adherence have been identified, including impulsivity and risk taking. We assessed the association between pre-COVID impulsivity levels and engagement in preventative measures during the COVID-19 pandemic in a longitudinal South African sample, in order to inform future pandemic planning. Methods Data were collected from N = 214 youths (mean age at baseline: M = 17.81 (SD = .71), 55.6% female) living in a South African peri-urban settlement characterised by high poverty and deprivation. Baseline assessments were taken in 2018/19 and the COVID follow-up was conducted in June–October 2020 via remote data collection. Impulsivity was assessed using the Balloon Analogue Task (BART), while hygiene and social distancing behaviours were captured through self-report. Stepwise hierarchical regression analyses were performed to estimate effects of impulsivity on measure adherence. Results Self-rated engagement in hygiene behaviours was high (67.1–86.1% “most of the time”, except for “coughing/sneezing into one’s elbow” at 33.3%), while engagement in social distancing behaviours varied (22.4–57.8% “most of the time”). Higher impulsivity predicted lower levels of hygiene (β = .14, p = .041) but not social distancing behaviours (β = −.02, p = .82). This association was retained when controlling for a range of demographic and COVID-related factors (β = .14, p = .047) and was slightly reduced when including the effects of a life-skills interventions on hygiene behaviour (β = −.13, p = .073). Conclusions Our data indicate that impulsivity may predict adolescent engagement in hygiene behaviours post COVID-19 pandemic onset in a high risk, sub-Saharan African setting, albeit with a small effect size. For future pandemics, it is important to understand predictors of engagement, particularly in the context of adversity, where adherence may be challenging. Limitations include a small sample size and potential measure shortcomings.

COVID-19 has a substantial and unexpected impact on individuals’ daily life around the world. Unprecedented public health restrictions such as lockdowns have the potential to affect multiple dimensions of individuals’ well-being, while the severity of such restrictions varies across countries. However, a holistic perspective comparing differences in and drivers of the different dimensions of well-being across countries differentially affected by COVID-19 is missing to date. We address this gap in the literature by examining the mental, social, functional, and financial well-being of 2,100 individuals across Australia, France, Germany, and South Africa by means of a survey administered during May of 2021. Supporting our holistic approach, we find that the different dimensions of well-being are correlated, with survey respondents from France reporting the lowest and those from Australia reporting the highest overall level of well-being. Respondents’ subjective and objective evaluations of their living conditions during lockdowns as well as positive health and financial behaviors are positively associated with their well-being during the pandemic.

Three lineages (BA.1, BA.2 and BA.3) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern predominantly drove South Africa’s fourth Coronavirus Disease 2019 (COVID-19) wave. We have now identified two new lineages, BA.4 and BA.5, responsible for a fifth wave of infections. The spike proteins of BA.4 and BA.5 are identical, and similar to BA.2 except for the addition of 69–70 deletion (present in the Alpha variant and the BA.1 lineage), L452R (present in the Delta variant), F486V and the wild-type amino acid at Q493. The two lineages differ only outside of the spike region. The 69–70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure, on the background of variants not possessing this feature. BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50% of sequenced cases in South Africa by the first week of April 2022. Using a multinomial logistic regression model, we estimated growth advantages for BA.4 and BA.5 of 0.08 (95% confidence interval (CI): 0.08–0.09) and 0.10 (95% CI: 0.09–0.11) per day, respectively, over BA.2 in South Africa. The continued discovery of genetically diverse Omicron lineages points to the hypothesis that a discrete reservoir, such as human chronic infections and/or animal hosts, is potentially contributing to further evolution and dispersal of the virus.

Background Risk factors for coronavirus disease 2019 (COVID-19) death in sub-Saharan Africa and the effects of human immunodeficiency virus (HIV) and tuberculosis on COVID-19 outcomes are unknown. Methods We conducted a population cohort study using linked data from adults attending public-sector health facilities in the Western Cape, South Africa. We used Cox proportional hazards models, adjusted for age, sex, location, and comorbidities, to examine the associations between HIV, tuberculosis, and COVID-19 death from 1 March to 9 June 2020 among (1) public-sector “active patients” (≥1 visit in the 3 years before March 2020); (2) laboratory-diagnosed COVID-19 cases; and (3) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19, comparing adults living with and without HIV using modeled population estimates. Results Among 3 460 932 patients (16% living with HIV), 22 308 were diagnosed with COVID-19, of whom 625 died. COVID-19 death was associated with male sex, increasing age, diabetes, hypertension, and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.70–2.70), with similar risks across strata of viral loads and immunosuppression. Current and previous diagnoses of tuberculosis were associated with COVID-19 death (aHR, 2.70 [95% CI, 1.81–4.04] and 1.51 [95% CI, 1.18–1.93], respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95% CI, 1.96–2.86); population attributable fraction 8.5% (95% CI, 6.1–11.1). Conclusions While our findings may overestimate HIV- and tuberculosis-associated COVID-19 mortality risks due to residual confounding, both living with HIV and having current tuberculosis were independently associated with increased COVID-19 mortality. The associations between age, sex, and other comorbidities and COVID-19 mortality were similar to those in other settings.

Many new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been termed variants of concern/interest (VOC/I) because of the greater risk they pose due to possible enhanced transmissibility and/or severity, immune escape, diagnostic and/or treatment failure, and reduced vaccine efficacy.

BACKGROUND: Rugby carries a risk for serious injuries, including acute spinal cord injuries. The lifetime health consequences of these injuries may be far-reaching. PURPOSE: In this study, we aimed to describe barriers and facilitators to healthcare and rehabilitation, in individuals with rugby-related spinal cord injuries in South Africa. METHODS: This study adopted a pragmatic qualitative approach. Stratified purposive sampling was used to select interviews from players from a variety of socio-economic status and geographical areas for inclusion in this study. The final sample consisted of thirty-one (n = 31) participants. Thematic analysis was used to analyze the data. RESULTS: Participants described long-term, accessible, affordable, quality healthcare and rehabilitation as important contributors to their quality of life. Even though public healthcare is accessible from a cost point of view, quality of care, availability of rehabilitation services and factors such as affordability and availability of adequate transport remain a barrier for lower socio-economic groups. CONCLUSION: This population was unique, as the support from a dedicated organization enabled participants to overcome some barriers, highlighting the challenges of the healthcare system in maintaining the health of people with spinal cord injuries. Every effort should be made to create equitable access to healthcare and rehabilitation for persons with spinal cord injuries in South Africa.

Rickettsia spp. can be found across the globe and cause disease of varying clinical severity, ranging from life-threatening infections with widespread vasculitis to milder, more localized presentations. Vector and, to some degree, reservoir are hematophagous arthropods, with most species harboured by ticks. In Denmark, rickettsiae are known as a cause of imported travel-related infections, but are also found endemically in ticks across the country. Data are, however, lacking on the geographical origin and clinical features of diagnosed cases. In this study, we have examined the travel history and clinical features of two groups of patients; 1) hospital-patients diagnosed with rickettsioses in the years 2010–2015 and 2) patients from primary health care (PHC) centers in Denmark having demonstrated anti-rickettsia antibodies in the years 2012–2015. The patients were identified using the Danish National Patient Registry (DNPR) and through the serological database at the State Serum Institute, where the laboratory diagnosis of rickettsioses is currently centralized. Data were collected for 86 hospital patients and 26 PHC center patients by reviewing hospital medical records and performing telephone interviews with PHC centers. Of the hospital patients, 91% (78/86) had a history of international travel 14 days prior to symptom start, with most having imported their infection from southern Africa, South Africa in particular (65%), and presenting with a clinical picture most compatible with African tick-bite fever caused by R. africae. Only two patients presented with a CRP > 100 mg/L and no mortalities were reported. At the PHC centers, most patients presented with mild flu-like symptoms and had an unknown (50%) or no history (19%) of international travel, raising the possibility of endemic rickettsioses. In view of our findings, rickettsioses do not appear to constitute a major public health problem in Denmark, with most cases being imported infections and potential endemic cases presenting as mild infections.

Background:Reducing doses of antiretroviral drugs, including stavudine (d4T), may lower toxicity, while preserving efficacy. There are substantial concerns about renal and bone toxicities of tenofovir disoproxil fumarate (TDF).Setting:HIV-1-infected treatment-naive adults in India, South Africa, and Uganda.Methods:A phase-4, 96-week, randomized, double-blind, noninferiority trial compared d4T 20 mg twice daily and TDF, taken in combination with lamivudine (3TC) and efavirenz (EFV). The primary endpoint was the proportion of participants with HIV-1 RNA

Oral and fecal microbial biomarkers have previously been associated with cardiometabolic (CM) risk, however, no comprehensive attempt has been made to explore this association in minority populations or across different geographic regions. We characterized gut- and oral-associated microbiota and CM risk in 655 participants of African-origin, aged 25-45, from Ghana, South Africa, Jamaica, and the United States (US). CM risk was classified using the CM risk cut-points for elevated waist circumference, elevated blood pressure and elevated fasted blood glucose, low high-density lipoprotein (HDL), and elevated triglycerides. Gut-associated bacterial alpha diversity negatively correlated with elevated blood pressure and elevated fasted blood glucose. Similarly, gut bacterial beta diversity was also significantly differentiated by waist circumference, blood pressure, triglyceridemia and HDL-cholesterolemia. Notably, differences in inter- and intra-personal gut microbial diversity were geographic-region specific. Participants meeting the cut-points for 3 out of the 5 CM risk factors were significantly more enriched with Lachnospiraceae, and were significantly depleted of Clostridiaceae, Peptostreptococcaceae, andPrevotella. The predicted relative proportions of the genes involved in the pathways for lipopolysaccharides (LPS) and butyrate synthesis were also significantly differentiated by the CM risk phenotype, whereby genes involved in the butyrate synthesis via lysine, glutarate and 4-aminobutyrate/succinate pathways and LPS synthesis pathway were enriched in participants with greater CM risk. Furthermore, inter-individual oral microbiota diversity was also significantly associated with the CM risk factors, and oral-associatedStreptococcus, Prevotella, andVeillonellawere enriched in participants with 3 out of the 5 CM risk factors. We demonstrate that in a diverse cohort of African-origin adults, CM risk is significantly associated with reduced microbial diversity, and the enrichment of specific bacterial taxa and predicted functional traits in both gut and oral environments. As well as providing new insights into the associations between the gut and oral microbiota and CM risk, this study also highlights the potential for novel therapeutic discoveries which target the oral and gut microbiota in CM risk.

Background Research on reproductive health effects on children from low-level, long-term exposure to pesticides currently used in the agricultural industry is limited and those on neurobehavioral effects have produced conflicting evidence. We aim at investigating the association between pesticide exposure on the reproductive health and neurobehavior of children in South Africa, by including potential relevant co-exposures from the use of electronic media and maternal alcohol consumption. Methods The design entails a prospective cohort study with a follow-up duration of 2 years starting in 2017, including 1000 school going children between the ages of 9 to 16 years old. Children are enrolled with equal distribution in sex and residence on farms and non-farms in three different agricultural areas (mainly apple, table grapes and wheat farming systems) in the Western Cape, South Africa. The neurobehavior primary health outcome of cognitive functioning was measured through the iPad-based CAmbridge Neuropsychological Test Automated Battery (CANTAB) including domains for attention, memory, and processing speed. The reproductive health outcomes include testicular size in boys and breast size in girls assessed in a physical examination, and blood samples to detect hormone levels and anthropometric measurements. Information on pesticide exposure, co-exposures and relevant confounders are obtained through structured questionnaire interviews with the children and their guardians. Environmental occurrence of pesticides will be determined while using a structured interview with farm owners and review of spraying records and collection of passive water and air samples in all three areas. Pesticide metabolites will be analysed in urine and hair samples collected from the study subjects every 4 months starting at baseline. Discussion The inclusion of three different agricultural areas will yield a wide range of pesticide exposure situations. The prospective longitudinal design is a further strength of this study to evaluate the reproductive and neurobehavioural effects of different pesticides on children. This research will inform relevant policies and regulatory bodies to improve the health, safety and learning environments for children and families in agricultural settings.

Biomarkers that predict who among recently Mycobacterium tuberculosis (MTB)-exposed individuals will progress to active tuberculosis are urgently needed. Intracellular microRNAs (miRNAs) regulate the host response to MTB and circulating miRNAs (c-miRNAs) have been developed as biomarkers for other diseases. We performed machine-learning analysis of c-miRNA measurements in the serum of adult household contacts (HHCs) of TB index cases from South Africa and Uganda and developed a c-miRNA-based signature of risk for progression to active TB. This c-miRNA-based signature significantly discriminated HHCs within 6 months of progression to active disease from HHCs that remained healthy in an independent test set [ROC area under the ROC curve (AUC) 0.74, progressors

Rickettsia spp. can be found across the globe and cause disease of varying clinical severity, ranging from life-threatening infections with widespread vasculitis to milder, more localized presentations. Vector and, to some degree, reservoir are hematophagous arthropods, with most species harboured by ticks. In Denmark, rickettsiae are known as a cause of imported travel-related infections, but are also found endemically in ticks across the country. Data are, however, lacking on the geographical origin and clinical features of diagnosed cases. In this study, we have examined the travel history and clinical features of two groups of patients; 1) hospital-patients diagnosed with rickettsioses in the years 2010-2015 and 2) patients from primary health care (PHC) centers in Denmark having demonstrated anti-rickettsia antibodies in the years 2012-2015. The patients were identified using the Danish National Patient Registry (DNPR) and through the serological database at the State Serum Institute, where the laboratory diagnosis of rickettsioses is currently centralized. Data were collected for 86 hospital patients and 26 PHC center patients by reviewing hospital medical records and performing telephone interviews with PHC centers. Of the hospital patients, 91% (78/86) had a history of international travel 14 days prior to symptom start, with most having imported their infection from southern Africa, South Africa in particular (65%), and presenting with a clinical picture most compatible with African tick-bite fever caused by R. africae. Only two patients presented with a CRP > 100 mg/L and no mortalities were reported. At the PHC centers, most patients presented with mild flu-like symptoms and had an unknown (50%) or no history (19%) of international travel, raising the possibility of endemic rickettsioses. In view of our findings, rickettsioses do not appear to constitute a major public health problem in Denmark, with most cases being imported infections and potential endemic cases presenting as mild infections.

BackgroundThe Programme for Improving Mental Health Care (PRIME) sought to implement mental health care plans (MHCP) for four priority mental disorders (depression, alcohol use disorder, psychosis and epilepsy) into routine primary care in five low- and middle-income country districts. The impact of the MHCPs on disability was evaluated through establishment of priority disorder treatment cohorts. This paper describes the methodology of these PRIME cohorts.MethodsOne cohort for each disorder was recruited across some or all five districts: Sodo (Ethiopia), Sehore (India), Chitwan (Nepal), Dr. Kenneth Kaunda (South Africa) and Kamuli (Uganda), comprising 17 treatment cohorts in total (N = 2182). Participants were adults residing in the districts who were eligible to receive mental health treatment according to primary health care staff, trained by PRIME facilitators as per the district MHCP. Patients who screened positive for depression or AUD and who were not given a diagnosis by their clinicians (N = 709) were also recruited into comparison cohorts in Ethiopia, India, Nepal and South Africa. Caregivers of patients with epilepsy or psychosis were also recruited (N = 953), together with or on behalf of the person with a mental disorder, depending on the district. The target sample size was 200 (depression and AUD), or 150 (psychosis and epilepsy) patients initiating treatment in each recruiting district. Data collection activities were conducted by PRIME research teams. Participants completed follow-up assessments after 3 months (AUD and depression) or 6 months (psychosis and epilepsy), and after 12 months. Primary outcomes were impaired functioning, using the 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS), and symptom severity, assessed using the Patient Health Questionnaire (depression), the Alcohol Use Disorder Identification Test (AUD), and number of seizures (epilepsy).DiscussionCohort recruitment was a function of the clinical detection rate by primary health care staff, and did not meet all planned targets. The cross-country methodology reflected the pragmatic nature of the PRIME cohorts: while the heterogeneity in methods of recruitment was a consequence of differences in health systems and MHCPs, the use of the WHODAS as primary outcome measure will allow for comparison of functioning recovery across sites and disorders.

Background Obesity is a major risk factor for hypertension, however, the physiologic mechanisms linking increased adiposity to elevations in blood pressure are not well described. An increase in resting energy expenditure (REE) is an obligatory consequence of obesity. Previous survey research has demonstrated that REE is an independent predictor of blood pressure, and eliminates the co-linear association of body mass index. This observation has received little attention and there have been no attempts to provide a causal explanation. Methods At baseline in an international comparative study on obesity, 289 participants aged 25–44 were recruited from communities in the US, the Seychelles, Ghana and South Africa and had REE measured with indirect calorimetry. All participants were thought to be free of major illness. Results In multivariate regression models, both systolic and diastolic blood pressure were positively associated with REE (p

Background: Women live on average five years longer than men, and the sex difference in longevity is typically lower in populations with high mortality. South Africa – a high mortality population with a large sex disparity – is an exception, but the causes of death that contribute to this difference are not well understood. Methods: Using data from a demographic surveillance system in rural KwaZulu-Natal (2000-2014), we estimate differences between male and female adult life expectancy by HIV status. The contribution of causes of death to these life expectancy differences are computed with demographic decomposition techniques. Cause of death information comes from verbal autopsy interviews that are interpreted with the InSilicoVA tool.Results: Adult women lived an average of 10.4 years (95% confidence Interval 9.0-11.6) longer than men. Sex differences in adult life expectancy were even larger when disaggregated by HIV status: 13.1 (95% confidence interval 10.7-15.3) and 11.2 (95% confidence interval 7.5-14.8) years among known HIV negatives and positives, respectively. Elevated male mortality from pulmonary tuberculosis (TB) and external injuries were responsible for 43% and 31% of the sex difference in life expectancy among the HIV negative population, and 81% and 16% of the difference among people living with HIV.Conclusions: The sex differences in adult life expectancy in rural KwaZulu-Natal are exceptionally large, atypical for an African population, and largely driven by high male mortality from pulmonary TB and injuries. This is the case for both HIV positive and HIV negative men and women, signalling a need to improve the engagement of men with health services, irrespective of their HIV status.

Item does not contain fulltext Objectives: Cardiovascular disease (CVD) risk calculators developed for the general population do not accurately predict CVD events in patients with RA. We sought to externally validate risk calculators recommended for use in patients with RA including the EULAR 1.5 multiplier, the Expanded Cardiovascular Risk Prediction Score for RA (ERS-RA) and QRISK2. Methods: Seven RA cohorts from UK, Norway, Netherlands, USA, South Africa, Canada and Mexico were combined. Data on baseline CVD risk factors, RA characteristics and CVD outcomes (including myocardial infarction, ischaemic stroke and cardiovascular death) were collected using standardized definitions. Performance of QRISK2, EULAR multiplier and ERS-RA was compared with other risk calculators [American College of Cardiology/American Heart Association (ACC/AHA), Framingham Adult Treatment Panel III Framingham risk score-Adult Treatment Panel (FRS-ATP) and Reynolds Risk Score] using c-statistics and net reclassification index. Results: Among 1796 RA patients without prior CVD [mean ( s . d .) age: 54.0 (14.0) years, 74% female], 100 developed CVD events during a mean follow-up of 6.9 years (12430 person-years). Estimated CVD risk by ERS-RA [mean ( s . d .) 8.8% (9.8%)] was comparable to FRS-ATP [mean ( s . d .) 9.1% (8.3%)] and Reynolds [mean ( s . d .) 9.2% (12.2%)], but lower than ACC/AHA [mean ( s . d .) 9.8% (12.1%)]. QRISK2 substantially overestimated risk [mean ( s . d .) 15.5% (13.9%)]. Discrimination was not improved for ERS-RA (c-statistic = 0.69), QRISK2 or EULAR multiplier applied to ACC/AHA compared with ACC/AHA (c-statistic = 0.72 for all) or for FRS-ATP (c-statistic = 0.75). The net reclassification index for ERS-RA was low (-0.8% vs ACC/AHA and 2.3% vs FRS-ATP). Conclusion: The QRISK2, EULAR multiplier and ERS-RA algorithms did not predict CVD risk more accurately in patients with RA than CVD risk calculators developed for the general population.

Background:Reducing doses of antiretroviral drugs, including stavudine (d4T), may lower toxicity, while preserving efficacy. There are substantial concerns about renal and bone toxicities of tenofovir disoproxil fumarate (TDF).Setting:HIV-1-infected treatment-naive adults in India, South Africa, and Uganda.Methods:A phase-4, 96-week, randomized, double-blind, noninferiority trial compared d4T 20 mg twice daily and TDF, taken in combination with lamivudine (3TC) and efavirenz (EFV). The primary endpoint was the proportion of participants with HIV-1 RNA

Background and aims Apelin-APJ signaling reduces cardiovascular disease (CVD) risk. In rheumatoid arthritis (RA), the atherosclerosis burden and plaque vulnerability to rupture are increased. We explored relationships between apelin concentrations and subclinical CVD in RA. Methods Apelin levels were measured in 235 (114 black, 121 white) RA patients. Associations between apelin concentrations and ultrasound determined carotid artery intima-media thickness (cIMT) and plaque, and levels of matrix metalloproteinase (MMP)-2 and -9 that mediate plaque stability and vulnerability respectively, were identified in confounder adjusted multivariate regression analysis. Results In all patients, apelin concentrations were directly associated with those of MMP-2 (β (SE) = 0.324 (0.112), p = 0.004) and inversely with those of MMP-9 (β (SE) = -0.239 (0.060), p = 0.000). Apelin concentration-subclinical CVD relations were influenced by population origin, RA disease activity, erythrocyte sedimentation rate (ESR) and interleukin (IL)-6 concentrations (interaction p = 0.001 to 0.04). Accordingly, the apelin-MMP-2 concentration relationship was reproduced in white (β (SE) = 0.367 (0.146), p = 0.01) but not black RA patients (β (SE) = 0.197 (0.220), p = 0.4), and only in those without (but not with) large erythrocyte sedimentation rates (β (SE) = 0.428 (0.143), p = 0.003) or interleukin-6 levels (β (SE) = 0.485 (0.288), p = 0.04). By contrast, the apelin-MMP-9 concentration relation was reproduced more consistently. Apelin levels were inversely related to cIMT in patients with RA remission or mild (β (SE) = -0.068 (0.033), p = 0.04) but not moderate or high disease activity (β (SE) = 0.015 (0.112), p = 0.7). Conclusions Apelin concentrations are associated with altered plaque stability mediator levels and atherosclerosis in patients with RA. These relations are partially dependent on population origin and systemic inflammatory status.

BACKGROUND: Unexpected death of a loved one (UD) is the most commonly reported traumatic experience in cross-national surveys. However, much remains to be learned about posttraumatic stress disorder (PTSD) after this experience. The WHO World Mental Health (WMH) survey initiative provides a unique opportunity to address these issues. METHODS: Data from 19 WMH surveys (n = 78,023; 70.1% weighted response rate) were collated. Potential predictors of PTSD (respondent sociodemographics, characteristics of the death, history of prior trauma exposure, history of prior mental disorders) after a representative sample of UDs were examined using logistic regression. Simulation was used to estimate overall model strength in targeting individuals at highest PTSD risk. RESULTS: PTSD prevalence after UD averaged 5.2% across surveys and did not differ significantly between high-income and low-middle income countries. Significant multivariate predictors included the deceased being a spouse or child, the respondent being female and believing they could have done something to prevent the death, prior trauma exposure, and history of prior mental disorders. The final model was strongly predictive of PTSD, with the 5% of respondents having highest estimated risk including 30.6% of all cases of PTSD. Positive predictive value (i.e., the proportion of high-risk individuals who actually developed PTSD) among the 5% of respondents with highest predicted risk was 25.3%. CONCLUSIONS: The high prevalence and meaningful risk of PTSD make UD a major public health issue. This study provides novel insights into predictors of PTSD after this experience and suggests that screening assessments might be useful in identifying high-risk individuals for preventive interventions. The World Health Organization World Mental Health (WMH) Survey Initiative is supported by the National Institute of Mental Health (NIMH; R01 MH070884 and R01 MH093612-01), the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the US Public Health Service (R13-MH066849, R01-MH069864, and R01 DA016558) and the Fogarty International Center (FIRCA R03- TW006481). The São Paulo Megacity Mental Health Survey is supported by the State of São Paulo Research Foundation (FAPESP) Thematic Project grant 03/00204-3. The ESEMeD project is funded by the European Commission (contracts QLG5-1999-01042; SANCO 2004123, and EAHC 20081308; the Piedmont Region [Italy]), Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spain (FIS 00/0028), Ministerio de Ciencia y Tecnología, Spain (SAF 2000-158-CE), Departament de Salut, Generalitat de Catalunya, Spain and Instituto de Salud Carlos III (CIBER CB06/02/0046, RETICS RD06/0011 REM-TAP) . The World Mental Health Japan (WMHJ) survey is supported by the Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H13-SHOGAI-023, H14-TOKUBETSU026, H16-KOKORO-013) from the Japan Ministry of Health, Labour and Welfare. The Lebanese Evaluation of the Burden of Ailments and Needs of the Nation (L.E.B.A.N.O.N.) is supported by the Lebanese Ministry of Public Health and the WHO (Lebanon), National Institute of Health/Fogarty International Center (R03 TW006481-01). The South Africa Stress and Health Study (SASH) is supported by the US National Institute of Mental Health (R01-MH059575). The Ukraine Comorbid Mental Disorders during Periods of Social Disruption (CMDPSD) study is funded by the US National Institute of Mental Health (RO1-MH61905). The US National Comorbidity Survey Replication (NCS-R) is supported by the National Institute of Mental Health (NIMH; U01-MH60220) with supplemental support from the National Institute of Drug Abuse (NIDA), the Substance Abuse and Mental Health Services Administration (SAMHSA), the Robert Wood Johnson Foundation (RWJF; grant 044708), and the John W. Alden Trust

Background The implications of rising obesity for cardiovascular health in middle-income countries has generated interest, in part because associations between obesity and cardiovascular health seem to vary across ethnic groups. Objective We assessed general and central obesity in Africa, East Asia, South America, and South Asia. We further investigated whether body mass index (BMI) and waist circumference differentially relate to cardiovascular health; and associations between obesity metrics and adverse cardiovascular health vary by region. Methods Using baseline anthropometric data collected between 2008 and 2012 from 7 cohorts in 9 countries, we estimated the proportion of participants with general and central obesity using BMI and waist circumference classifications, respectively, by study site. We used Poisson regression to examine the associations (prevalence ratios) of continuously measured BMI and waist circumference with prevalent diabetes and hypertension by sex. Pooled estimates across studies were computed by sex and age. Results This study analyzed data from 31,118 participants aged 20 to 79 years. General obesity was highest in South Asian cities and central obesity was highest in South America. The proportion classified with general obesity (range 11% to 50%) tended to be lower than the proportion classified as centrally obese (range 19% to 79%). Every standard deviation higher of BMI was associated with 1.65 and 1.60 times higher probability of diabetes and 1.42 and 1.28 times higher probability of hypertension, for men and women, respectively, aged 40 to 69 years. Every standard deviation higher of waist circumference was associated with 1.48 and 1.74 times higher probability of diabetes and 1.34 and 1.31 times higher probability of hypertension, for men and women, respectively, aged 40 to 69 years. Associations of obesity measures with diabetes were strongest in South Africa among men and in South America among women. Associations with hypertension were weakest in South Africa among both sexes. Conclusions BMI and waist circumference were both reasonable predictors of prevalent diabetes and hypertension. Across diverse ethnicities and settings, BMI and waist circumference remain salient metrics of obesity that can identify those with increased cardiovascular risk. Fil: Patel, Shivani A.. University of Emory; Estados Unidos. Centre For Control Of Chronic Conditions; India Fil: Ali, Mohammed K.. University of Emory; Estados Unidos. Centre For Control Of Chronic Conditions; India Fil: Alam, Dewan. University of York; Reino Unido. Li Ka Shing Knowledge Institute; Canadá Fil: Yan, Lijing L.. Peking University; China. Duke Kunshan University; China Fil: Levitt, Naomi S.. University Of Cape Town; Sudáfrica Fil: Bernabe Ortiz, Antonio. Cronicas Centro de Excelencia En Enfermedades Crónicas; Perú Fil: Checkley, William. University Johns Hopkins; Estados Unidos Fil: Wu, Yangfeng. Peking University; China Fil: Irazola, Vilma. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Gutierrez, Laura. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Rubinstein, Adolfo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Shivashankar, Roopa. Public Health Foundation of India; India Fil: Li, Xian. Peking University; China Fil: Miranda, J. Jaime. Cronicas Centro de Excelencia En Enfermedades Crónicas; Perú. Universidad Peruana Cayetano Heredia; Perú Fil: Chowdhury, Muhammad Ashique Haider. International Centre For Diarrhoeal Disease Research Bangladesh; Bangladesh Fil: Siddiquee, Ali Tanweer. International Centre For Diarrhoeal Disease Research Bangladesh; Bangladesh Fil: Gaziano, Thomas A.. Harvard University. Harvard School of Public Health; Estados Unidos. Brigham And Women's Hospital; Estados Unidos Fil: Kadir, M. Masood. The Aga Khan University; Pakistán Fil: Prabhakaran, Dorairaj. Public Health Foundation of India; India

Background Diabetes mellitus is one of the leading causes of death and disability worldwide. Approximately three-quarters of people with diabetes live in low- and middle-income countries, and these countries are projected to experience the greatest increase in diabetes burden. Objectives We sought to compare the prevalence, awareness, treatment, and control of diabetes in 3 urban and periurban regions: the Southern Cone of Latin America and Peru, South Asia, and South Africa. In addition, we examined the relationship between diabetes and pre-diabetes with known cardiovascular and metabolic risk factors. Methods A total of 26,680 participants (mean age, 47.7 ± 14.0 years; 45.9% male) were enrolled in 4 sites (Southern Cone of Latin America = 7,524; Peru = 3,601; South Asia = 11,907; South Africa = 1,099). Detailed demographic, anthropometric, and biochemical data were collected. Diabetes and pre-diabetes were defined as a fasting plasma glucose ≥126 mg/dl and 100 to 125 mg/dl, respectively. Diabetes control was defined as fasting plasma glucose

BACKGROUND: Cardiovascular diseases (CVD) mortality has been shown to follow a seasonal pattern. Several studies suggested several possible determinants of this pattern, including misclassification of causes of deaths. We aimed at assessing seasonality in overall, CVD, cancer and non-CVD/non-cancer mortality using data from 19 countries from different latitudes. METHODS AND FINDINGS: Monthly mortality data were compiled from 19 countries, amounting to over 54 million deaths. We calculated ratios of the observed to the expected numbers of deaths in the absence of a seasonal pattern. Seasonal variation (peak to nadir difference) for overall and cause-specific (CVD, cancer or non-CVD/non-cancer) mortality was analyzed using the cosinor function model. Mortality from overall, CVD and non-CVD/non-cancer showed a consistent seasonal pattern. In both hemispheres, the number of deaths was higher than expected in winter. In countries close to the Equator the seasonal pattern was considerably lower for mortality from any cause. For CVD mortality, the peak to nadir differences ranged from 0.185 to 0.466 in the Northern Hemisphere, from 0.087 to 0.108 near the Equator, and from 0.219 to 0.409 in the Southern Hemisphere. For cancer mortality, the seasonal variation was nonexistent in most countries. CONCLUSIONS: In countries with seasonal variation, mortality from overall, CVD and non-CVD/non-cancer show a seasonal pattern with mortality being higher in winter than in summer. Conversely, cancer mortality shows no substantial seasonality.

Mycobacterium bovis is the causal agent of bovine tuberculosis (BTB), with a diverse host range, extending from livestock to domestic and captive wild animals as well as free-ranging wildlife species. In South Africa, BTB is endemic in the Kruger National Park (KNP) and the Hluluwe iMfolozi National Park (HiP), where the high prevalence of M. bovis infections in buffalo herds has led to infection of a number of wildlife species. This has raised concerns about the spillover into the rhinoceros population, a species known to be susceptible to both M. bovis and Mycobacterium tuberculosis, jeopardizing breeding and relocation projects that serve to conserve and protect this species. In view of the advantages of the interferon-gamma (IFN-γ) assay in the diagnosis of BTB in a variety of species worldwide, such an assay has been developed for rhinoceroses by Morar and co-workers in 2007. In this study, this assay was optimized using recombinant eukaryotic rhinoceros IFN-γ and the lower detection limit was calculated to be 0.5 ng/ml. Subsequently, assessing the detection of native rhinoceros IFN-γ protein in whole-blood samples revealed stimulation with each of the mitogens: pokeweed (PWM), phytohaemagglutinin (PHA) & phorbol 12-myristate 13-acetate and calcium ionophore (PMA/CaI), though most prominently with the latter two. In addition, samples collected from 52 clinically healthy rhinoceroses, of presumed negative BTB status, from two different areas in South Africa were used to determine the cut-off value for a negative test result. This was calculated to be 0.10 (OD490 nm ) and as determined in this study is a preliminary recommendation based on IFN-γ responses observed in samples from BTB-free rhinoceroses only.