Gut microbiome profiling of a rural and urban South African cohort reveals biomarkers of a population in lifestyle transition.

BACKGROUND: Comparisons of traditional hunter-gatherers and pre-agricultural communities in Africa with urban and suburban Western North American and European cohorts have clearly shown that diet, lifestyle and environment are associated with gut microbiome composition. Yet, little is known about the gut microbiome composition of most communities in the very diverse African continent. South Africa comprises a richly diverse ethnolinguistic population that is experiencing an ongoing epidemiological transition and concurrent spike in the prevalence of obesity, largely attributed to a shift towards more Westernized diets and increasingly inactive lifestyle practices. To characterize the microbiome of African adults living in more mainstream lifestyle settings and investigate associations between the microbiome and obesity, we conducted a pilot study, designed collaboratively with community leaders, in two South African cohorts representative of urban and transitioning rural populations. As the rate of overweight and obesity is particularly high in women, we collected single time-point stool samples from 170 HIV-negative women (51 at Soweto; 119 at Bushbuckridge), performed 16S rRNA gene sequencing on these samples and compared the data to concurrently collected anthropometric data. RESULTS: We found the overall gut microbiome of our cohorts to be reflective of their ongoing epidemiological transition. Specifically, we find that geographical location was more important for sample clustering than lean/obese status and observed a relatively higher abundance of the Melainabacteria, Vampirovibrio, a predatory bacterium, in Bushbuckridge. Also, Prevotella, despite its generally high prevalence in the cohorts, showed an association with obesity. In comparisons with benchmarked datasets representative of non-Western populations, relatively higher abundance values were observed in our dataset for Barnesiella (log2fold change (FC) = 4.5), Alistipes (log2FC = 3.9), Bacteroides (log2FC = 4.2), Parabacteroides (log2FC = 3.1) and Treponema (log2FC = 1.6), with the exception of Prevotella (log2FC = - 4.7). CONCLUSIONS: Altogether, this work identifies putative microbial features associated with host health in a historically understudied community undergoing an epidemiological transition. Furthermore, we note the crucial role of community engagement to the success of a study in an African setting, the importance of more population-specific studies to inform targeted interventions as well as present a basic foundation for future research.

The associations between interpersonal violence and psychological distress among rural and urban young women in South Africa.

BACKGROUND: Approximately 25% of the world's population consists of young people. The experience of violence peaks during adolescence and the early adult years. A link between personal experience of violence and mental health among young people has been demonstrated but rural-urban differences in these associations are less well known in low to middle income countries. The aim of this study was to investigate the associations between interpersonal violence and psychological distress among rural and urban young women. METHODS: Data on experiences of violence and psychological distress were collected from a total of 926 non-pregnant young women aged between 18 and 22 years of age in rural and urban sites in South Africa. The General Health Questionnaire-28 was used to assess psychological distress as an indicator of mental health. Generalised structural equation models were employed to assess potential pathways of association between interpersonal violence and psychological distress. RESULTS: Thirty-four percent of the urban young women (n = 161) reported psychological distress compared to 18% of rural young women (n = 81). In unadjusted analysis, exposure to interpersonal violence doubled the odds of psychological distress in the urban adolescents and increased the odds 1.6 times in the rural adolescents. In adjusted models, the relationship remained significant in the urban area only (OR 1.84, 95% CI 1.13-3.00). Rural residence seemed protective against psychological distress (OR 0.41, 95% CI 0.24-0.69). Structural equation modelling did not reveal any direct association between exposure to interpersonal violence and psychological distress among rural young women. Stressful household events were indirectly associated with psychological distress, mediated by violence among young women in the urban area. CONCLUSION: The relationship between violence and psychological distress differs between urban and rural-residing young women in South Africa, and is influenced by individual, household and community (contextual) factors.

The long road to elimination: malaria mortality in a South African population cohort over 21 years.

BACKGROUND: Malaria elimination is on global agendas following successful transmission reductions. Nevertheless moving from low to zero transmission is challenging. South Africa has an elimination target of 2018, which may or may not be realised in its hypoendemic areas. METHODS: The Agincourt Health and Demographic Surveillance System has monitored population health in north-eastern South Africa since 1992. Malaria deaths were analysed against individual factors, socioeconomic status, labour migration and weather over a 21-year period, eliciting trends over time and associations with covariates. RESULTS: Of 13 251 registered deaths over 1.58 million person-years, 1.2% were attributed to malaria. Malaria mortality rates increased from 1992 to 2013, while mean daily maximum temperature rose by 1.5 °C. Travel to endemic Mozambique became easier, and malaria mortality increased in higher socioeconomic groups. Overall, malaria mortality was significantly associated with age, socioeconomic status, labour migration and employment, yearly rainfall and higher rainfall/temperature shortly before death. CONCLUSIONS: Malaria persists as a small but important cause of death in this semi-rural South African population. Detailed longitudinal population data were crucial for these analyses. The findings highlight practical political, socioeconomic and environmental difficulties that may also be encountered elsewhere in moving from low-transmission scenarios to malaria elimination.

The need for an integrated approach for chronic disease research and care in Africa.

With the changing distribution of infectious diseases, and an increase in the burden of non-communicable diseases, low- and middle-income countries, including those in Africa, will need to expand their health care capacities to effectively respond to these epidemiological transitions. The interrelated risk factors for chronic infectious and non-communicable diseases and the need for long-term disease management, argue for combined strategies to understand their underlying causes and to design strategies for effective prevention and long-term care. Through multidisciplinary research and implementation partnerships, we advocate an integrated approach for research and healthcare for chronic diseases in Africa.

The development of a localised HIV epidemic and the associated excess mortality burden in a rural area of South Africa.

The human immunodeficiency virus (HIV) epidemic in South Africa rapidly developed into a major pandemic. Here we analyse the development of the epidemic in a rural area of the country. The data used were collected between 1992 and 2013 in a longitudinal population survey, the Agincourt Health and Demographic Surveillance Study, in the northeast of the country. Throughout the period of study mortality rates were similar in all villages, suggesting that there were multiple index cases evenly spread geographically. These were likely to have been returning migrant workers. For those aged below 39 years the HIV mortality rate was higher for women, above this age it was higher for men. This indicates the protective effect of greater access to HIV testing and treatment among older women. The recent convergence of mortality rates for Mozambicans and South Africans indicates that the former refugee population are being assimilated into the host community. More than 60% of the deaths occurring in this community between 1992 and 2013 could be attributed directly or indirectly to HIV. Recently there has been an increasing level of non-HIV mortality which has important implications for local healthcare provision. This study demonstrates how evidence from longitudinal analyses can support healthcare planning.

H3Africa AWI-Gen Collaborative Centre: a resource to study the interplay between genomic and environmental risk factors for cardiometabolic diseases in four sub-Saharan African countries.

Africa is experiencing a rapid increase in adult obesity and associated cardiometabolic diseases (CMDs). The H3Africa AWI-Gen Collaborative Centre was established to examine genomic and environmental factors that influence body composition, body fat distribution and CMD risk, with the aim to provide insights towards effective treatment and intervention strategies. It provides a research platform of over 10 500 participants, 40-60 years old, from Burkina Faso, Ghana, Kenya and South Africa. Following a process that involved community engagement, training of project staff and participant informed consent, participants were administered detailed questionnaires, anthropometric measurements were taken and biospecimens collected. This generated a wealth of demographic, health history, environmental, behavioural and biomarker data. The H3Africa SNP array will be used for genome-wide association studies. AWI-Gen is building capacity to perform large epidemiological, genomic and epigenomic studies across several African counties and strives to become a valuable resource for research collaborations in Africa.

Blood pressure-measuring devices in rural South Africa: an audit conducted by the SASPI team in the Agincourt field site.

BACKGROUND: Cardiovascular disease is an important cause of morbidity and mortality in South Africa. The Southern Africa Stroke Prevention Initiative (SASPI) found a high prevalence of stroke in the rural Agincourt subdistrict, Limpopo province. Hypertension is the commonest vascular risk factor in our population and it is essential that primary care services be adequately equipped to detect and treat hypertension. The aim of this study was to assess the number, accuracy and working condition of blood pressure measuring devices (BMD) in the clinics that serve the field site, and to assess the clinic sisters' perceptions of the availability of antihypertensive medication and aspirin. METHODS: In each of the clinics serving the site we assessed the BMDs and cuffs using the following criteria: general condition, bladder size, state of rubber components, operation of the inlet valve and control of valve operation. The legibility of the gauge, level and condition of the mercury, and the condition of the glass tube were checked when relevant. The performance of the BMD was then assessed both with the cuff used in the clinic and with a new functioning cuff, against an accurate mercury sphygmomanometer. By interviewing the clinic sister we could assess the availability of antihypertensive medication and aspirin, as well as the state of the drug delivery system. RESULTS: All BMDs were mercury sphygmomanometers. Four clinics had one BMD each, one clinic had two, and one clinic had four. In one clinic the device was not functional at all until the study cuff was used. None of the clinics had spare cuffs and only one clinic had access to a large cuff. Nine out of 10 (90%) cuffs tested had unsatisfactory valve function, and none was of the size recommended by the guidelines. Although the condition of the mercury was only considered satisfactory in 40% of BMDs, once a new cuff had been fitted to the BMDs all of them were accurate to within 4 mmHg between 50 and 250 mmHg. Fifty per cent of clinic sisters felt they always had sufficient stock of hydrochlorothiazide and alpha-methyldopa, but the supply of more expensive medication was less reliable. Only one clinic always had sufficient aspirin. CONCLUSION: Although none of the primary care clinics had fully functioning BMDs, almost all the defects related to malfunctioning and inappropriately sized cuffs, which would be inexpensive to repair or replace. A procedure for routine servicing or replacement of both BMDs and cuffs is needed, as well as optimisation of medication delivery to remote areas.

Secondary prevention of stroke--results from the Southern Africa Stroke Prevention Initiative (SASPI) study.

OBJECTIVE: To describe the prevalence of risk factors and experience of preventive interventions in stroke survivors, and identilfy barriers to secondary prevention in rural South Africa. METHODS: A clinician visited individuals in the Agincourt field site (in South Africa's rural north east) who were identified in a census as possible stroke victims to confirm the diagnosis of stroke. We explored the impact of stroke on the individual's family, and health-seeking behaviour following stroke by conducting in-depth interviews in the households of 35 stroke survivors. We held two workshops to understand the knowledge, experience, and views of primary care nurses, who provide the bulk of professional health care. FINDINGS: We identified 103 stroke survivors (37 men), 73 (71%) of whom had hypertension, but only 8 (8%) were taking anti-hypertensive treatment. Smoking was uncommon; 8 men and 1 woman smoked a maximum of ten cigarettes daily. 94 (91%) stroke survivors had sought help, which involved allopathic health care for most of them (81; 79%). 42 had also sought help from traditional healers and churches, while another 13 people had sought help only from those sources. Of the 35 survivors who were interviewed, 29 reported having been prescribed anti-hypertensive pills after their stroke. Barriers to secondary prevention included cost of treatment, reluctance to use pills, difficulties with access to drugs, and lack of equipment to measure blood pressure. A negative attitude to allopathic care was not an important factor. CONCLUSION: In this rural area hypertension is the most important modifiable risk factor in stroke survivors. Effective secondary prevention may reduce the incidence of recurrent strokes, but there is no system to deliver such care. New strategies for care are needed involving both allopathic and non-allopathic-health care providers.

Undiagnosed pulmonary tuberculosis deaths in rural South Africa.

This research explores death from pulmonary tuberculosis (PTB) using a verbal autopsy (VA) tool within the established Agincourt Health and Demographic Surveillance System site in South Africa's rural northeast. Previous work on active case finding in the area highlighted a modest burden of undiagnosed PTB in the community. This VA research confirms the existence of undiagnosed PTB deaths, with 13 (46%) of 28 PTB deaths among the permanent adult population (n = 38,251) going undetected by the health service. There was a median duration of coughing in the community of 16 weeks among these undiagnosed PTB deaths. As most undiagnosed cases present to the health service at some point during their illness, intervention strategies to support early diagnosis at this level can only be re-emphasised by this work.

Active case finding: understanding the burden of tuberculosis in rural South Africa.

SETTING: The Agincourt demographic and health surveillance site in South Africa's rural Northern Province. OBJECTIVES: To accurately assess the true burden of tuberculosis in a rural sub-district with a known high prevalence of human immunodeficiency virus. DESIGN: Data on hospital registrations of tuberculosis were combined with data from an ongoing demographic health and surveillance system to accurately describe the burden of tuberculosis in a well-defined community. Undiagnosed active cases of sputum-positive disease in the community were detected among chronic coughers identified by heads of household during a single-pass census interview. RESULTS: The incidence of hospitalised tuberculosis among the permanently resident population (n = 56 566) was 212/100,000 person-years during 1999. The average point prevalence of detected tuberculosis (all forms) among patients aged over 10 years was 133/100,000, and 81/100,000 for sputum-positive pulmonary disease. This compares with a point prevalence of 16/100,000 cases of sputum-positive disease detected through active case finding. CONCLUSION: For every nine cases of sputum positive pulmonary tuberculosis being treated at any one time, there are two cases of undiagnosed disease in the community. This study demonstrates a modest burden of undiagnosed tuberculosis among residents in a rural sub-district in South Africa.

Assessing health seeking behaviour among tuberculosis patients in rural South Africa.

SETTING: South Africa's rural Northern Province. OBJECTIVES: To examine patterns of health seeking behaviour among hospitalised tuberculosis patients. DESIGN: Information on personal characteristics, health seeking behaviour and delays to presentation and hospitalisation was collected from hospitalised TB patients. Analysis of rates was used to investigate factors associated with delay. RESULTS: Among 298 patients, median total delay to hospitalisation was 10 weeks, with patient delay contributing a greater proportion than service provider delay. Patients more often presented initially to public hospitals (41%) or clinics (31 %) than to spiritual/traditional healers (15%) or private GPs (13%). Total delay was shorter amongst those presenting to hospitals than those presenting to clinics (rate ratio 1.33, 95%CI 1.13-1.85), with a significantly smaller proportion of the total delay attributable to the health service provider (18% vs. 42%). Those exhibiting a conventional risk profile for TB (migrants, alcohol drinkers, history of TB) were diagnosed most quickly by health services, while women remained undiagnosed for longer. CONCLUSION: Considerable delay exists between symptom onset and treatment initiation among pulmonary tuberculosis patients. While a substantial delay was attributable to late patient presentation, an important, preventable period of infectiousness was caused by the failure of recognised clinical services to diagnose tuberculosis among symptomatic individuals.

Validation and application of verbal autopsies in a rural area of South Africa.

OBJECTIVE: To validate the causes of death determined with a single verbal autopsy instrument covering all age groups in the Agincourt subdistrict of rural South Africa. METHODS: Verbal autopsies (VAs) were conducted on all deaths recorded during annual demographic and health surveillance over a 3-year period (1992-95) in a population of about 63 000 people. Trained fieldworkers elicited signs and symptoms of the terminal illness from a close caregiver, using a comprehensive questionnaire written in the local language. Questionnaires were assessed blind by three clinicians who assigned a probable cause of death using a stepwise consensus process. Validation involved comparison of VA diagnoses with hospital reference diagnoses obtained for those who died in a district hospital; and calculation of sensitivity, specificity and positive predictive value (PPV) for children under 5 years, and adults 15 years and older. RESULTS: A total of 127 hospital diagnoses satisfied the criteria for inclusion as reference diagnoses. For communicable diseases, sensitivity of VA diagnoses among children was 69%, specificity 96%, and PPV 90%; among adults the values were 89, 93 and 76%. Lower values were found for non-communicable diseases: 75, 91 and 86% among children; and 64, 50 and 80% among adults. Most misclassification occurred within the category itself. For deaths due to accidents or violence, sensitivity was 100%, specificity 97%, and PPV 80% among children; and 75, 98 and 60% among adults. Since causes of death were largely age-specific, few differences in sensitivity, specificity and PPV were found for adults and children. The frequency distribution of causes of death based on VAs closely approximated that of the hospital records used for validation. CONCLUSION: VA findings need to be validated before they can be applied to district health planning. In Agincourt, a single verbal autopsy instrument provided a reasonable estimate of the frequency of causes of death among adults and children. Findings can be reliably used to inform local health planning and evaluation.

Causes of death in a rural area of South Africa: an international perspective.

The study compares the cause of death profile in a rural area of South Africa (Agincourt), with that in a rural area of West Africa (Niakhar), and in a developed country with the same life expectancy (France, 1951) in order to determine causes with high and low mortality and priorities for future health interventions. In the two African sites, causes of death were assessed by verbal autopsies, whereas they were derived from regular cause of death registration in France. Age-standardized death rates were used to compare cause-specific mortality in the three studies. Life expectancy in Agincourt was estimated at 66 years, similar to that of France in 1951, and much higher than that of Niakhar. Causes of death with outstandingly high mortality in Agincourt were violent deaths (homicide and suicide), accidents (road traffic accidents and household accidents), certain infectious diseases (HIV/AIDS, tuberculosis, diarrhea and dysentery), certain chronic diseases (cancer of genital organs, liver cirrhosis, gastrointestinal hemorrhage, maternal mortality, epilepsy, acute rheumatic fever, and pneumoconiosis) and malnutrition of young children (kwashiorkor). Causes of death with lower mortality than expected were primarily respiratory diseases (pneumonia, bronchitis, influenza, lung cancer), other cancers, vaccine preventable diseases (measles, whooping cough, tetanus), and marasmus. Verbal autopsies could be used in a rural area of a developing country without formal cause of death registration to identify the most salient health problems of the population, and could be compared with a formal cause of death registration system of a developed country.

Premarital fertility in rural South Africa: a challenge to existing population policy.

The age pattern of fertility in a rural area of South Africa under demographic surveillance (Agincourt subdistrict) was investigated over the 1992-97 period. The total fertility rate (TFR) averaged 3.3 births per woman of reproductive age over the period, a major drop from earlier estimates in the same area (6.0 births in 1970-74). Age-specific fertility rates showed an atypical bimodal pattern. They were decomposed into two components of similar magnitude: premarital fertility (among women aged 12-26) and marital fertility (among women aged 15-49). The decomposition revealed the two underlying modes: a mode of premarital fertility (among women aged 18-20) and a mode of marital fertility (among women aged 28-30). Premarital fertility accounted for 21 percent of all births and for 47 percent of births among women aged 12-26. This pattern of high premarital fertility appears to reflect a low incidence of contraceptive use before the first birth, especially among adolescents, a low prevalence of abortion, and a high contraceptive prevalence thereafter. This finding calls for a reorientation of the family planning policy, which until now has targeted married women and women who have been pregnant once, but has failed to address the contraceptive needs of young women before their first pregnancy, especially adolescents.

Health system reform and the role of field sites based upon demographic and health surveillance.

Field sites for demographic and health surveillance have made well-recognized contributions to the evaluation of new or untested interventions, largely through efficacy trials involving new technologies or the delivery of selected services, e.g. vaccines, oral rehydration therapy and alternative contraceptive methods. Their role in health system reform, whether national or international, has, however, proved considerably more limited. The present article explores the characteristics and defining features of such field sites in low-income and middle-income countries and argues that many currently active sites have a largely untapped potential for contributing substantially to national and subnational health development. Since the populations covered by these sites often correspond with the boundaries of districts or subdistricts, the strategic use of information generated by demographic surveillance can inform the decentralization efforts of national and provincial health authorities. Among the areas of particular importance are the following: making population-based information available and providing an information resource; evaluating programmes and interventions; and developing applications to policy and practice. The question is posed as to whether their potential contribution to health system reform justifies arguing for adaptations to these field sites and expanded investment in them.

PIP: This article explores the characteristics and defining features of demographic and health surveillance (DHS) field sites in low-income and middle-income countries, considers their value, and examines their advantages and limitations on issues of health sector reforms. It further argues that the field sites have untapped potential for contributing substantially to national and subnational health development. Field sites for DHS have made well-recognized contributions to the evaluation of new or untested interventions, largely through efficacy trials involving new technologies or the delivery of selected services such as vaccines, oral rehydration therapy, and alternative contraceptive methods. However, despite the contributions, their role in the national and international health system have been limited. DHS field sites, whether they were originally efficacy-oriented or effectiveness-oriented share a number of core features. The populations covered by DHS field sites often correspond with the boundaries of districts or subdistricts, the strategic use of information generated by demographic surveillance can inform the decentralization efforts of national and provincial health authorities. Among the areas of particular importance are the following: 1) making population-based information and providing information resource; 2) evaluating programs and interventions; and 3) developing applications to policy. Recommendations for the improvement of DHS role in the national and subnational levels are outlined.