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 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 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.

Reversal in mortality trends: evidence from the Agincourt field site, South Africa, 1992-1995.

OBJECTIVE: To examine changes in mortality in rural South Africa over the period 1992-1995 by age, sex and cause of death. DESIGN: As with much of sub-Saharan Africa, South Africa lacks effective vital registration and information on mortality is lacking. The Agincourt demographic and health surveillance system was established to inform health policy and practice with regard to rural subdistrict populations. METHODS: Prospective community-based study involving annual update of a household census with enquiry into all birth, death and migration events. All reported deaths (n = 1001) are the subject of a verbal autopsy. RESULTS: An increasing trend in overall mortality relative to general population growth in the study area is apparent. There is evidence for a reversal in the previously declining trend in mortality among women 20-44 years. A comparison of 1992-1993 with 1994-1995 shows that most of the increase in mortality is concentrated in the younger adult (20-49 year) age group. AIDS and related diseases, particularly tuberculosis, appear primarily responsible. Injuries and violence (especially homicide) and circulatory disease are important, under-recognized causes of death, although their levels have remained constant over the period. CONCLUSIONS: Mortality from AIDS and related diseases appears responsible for the probable reversal in mortality emerging in South Africa's rural northeast. Findings carry implications for the emerging system of decentralized health care.

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.

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.

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.

The Pholela Health Centre--the origins of community-oriented primary health care (COPC). An appreciation of the work of Sidney and Emily Kark.

The health centre practice pioneered by Sidney and Emily Kark and their colleagues at Pholela during the 1940s was a forerunner of and direct contributor to what later emerged as 'the primary health care approach'. This article gives a detailed account of the context, work and methodologies used at the Pholela Health Centre, emphasising the development of concepts that are now well recognised and described as community-oriented primary health care (COPC). COPC remains highly relevant to health service development in South Africa today.

The Agincourt field site--evolution and current status.

OBJECTIVE: To describe the evolution and current status of the Agincourt field site, Bushbuckridge, in South Africa's rural north-east. SETTING: A defined subdistrict, with a population of some 60,000 people including Mozambican refugees, in a former 'homeland' area with substantial labour migration. APPROACH: Three phases are described: origins and establishment of the field site; a programme of health systems research underpinned by multi-round (prospective) demographic and health surveillance; and contributions to the University of the North's Dikgale field site. COMMENT: Knowledge of trends in population health (e.g. mortality) is important when shaping the skill base and organisational framework of a district health system. There are valuable opportunities for collaborative research with field sites elsewhere in sub-Saharan Africa, and within South Africa itself. This will be facilitated by a common data model. A country-wide network of field sites, with surveillance capability, would complement the occasional national census and demographic and health survey, and strengthen South Africa's embryonic health information system.

Public health initiatives in South Africa in the 1940s and 1950s: lessons for a post-apartheid era.

Inspiration drawn from South African public health initiatives in the 1940s played an important role in the development of the network of community and migrant health centers in the United States. The first such center at Pholela in Natal emphasized the need for a comprehensive (preventive and curative) service that based its practices on empirical data derived from epidemiological and anthropological research. In addition, community consultation preceded the introduction of new service or research initiatives. The Institute of Family and Community Health in Durban pioneered community-based multidisciplinary training and developed Pholela and other sites as centers for service, teaching, and research. Several important lessons for South African health professionals emerge from the Pholela experience. First, public health models of the past need to be reintroduced locally; second, the training of public health professionals needs to be upgraded and reoriented; third, appropriate research programs need to respond to community needs and address service demands; fourth, community involvement strategies need to be implemented early on; and fifth, funding sources for innovation in health service provision should be sought.

Planning professional education at schools of public health.

OBJECTIVES: Professional education in public health should equip graduates with adequate knowledge and skills to manage diverse and complex problems. How best to address this challenge is widely debated. We describe the Harvard School of Public Health's self-evaluation and development of a practice-oriented program. METHODS: As part of Harvard's schoolwide review of the master of public health (MPH), self-administered questionnaires were distributed to all MPH students, 1987 to 1989, and international and US alumni, 1979 to 1986. Extensive discussions were conducted with relevant student and faculty groups. RESULTS: Survey results provided a basis for educational policy and curricular changes that culminated in a revised MPH that targets key areas of public health practice. Examples from the Harvard experience are provided. CONCLUSIONS: Information derived from student and alumni surveys can be highly effective in the process of guiding curricular change at schools of public health. This should be coupled with a strategic approach to gain faculty support for proposed innovations. Ongoing monitoring and modification of the new curriculum is essential.

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.

Stroke in rural South Africa--contributing to the little known about a big problem.

OBJECTIVES: To describe the extent of mortality from cerebrovascular accident (CVA) in a rural South African population. DESIGN: Annual demographic and health surveillance with verbal autopsy of all deaths, 1992-1995. OUTCOME MEASURES: Stroke mortality rate by age and sex. RESULTS: Stroke mortality increased with age and is higher in men than women over age 35. Proportionate mortality ratio from CVA: 10.3% of deaths in the 35-64-year age group. CONCLUSION: Cerebrovascular disease is an important cause of death in South Africa's rural north-east. Community-based research is needed to inform policy and practice.

Developing district health systems in the rural Transvaal. Issues arising from the Tintswalo/Bushbuckridge experience.

District health systems are increasingly acknowledged as a foundation for national health services based on primary health care. Initial efforts to institute a demonstration district health system in the Bushbuckridge area of the eastern Transvaal are described. These include efforts to overcome the organisational and administrative fragmentation caused by homeland and provincial boundaries. Close attention needs to be given to district-level health management, the complementary roles of district and regional health authorities, working relationships and accountability among professional staff from different disciplines, involvement of the community in a district health authority and the district health system as an element of local government.

Vaccination coverage in Mhala and Elim in 1990--a health systems approach.

This paper assesses the implementation of the 1986 Gazankulu policy on immunisation in 2 of the homeland's 6 health wards, Mhala and Elim. Vaccination coverage was estimated using the cluster sampling technique recommended by the Expanded Programme on Immunisation of the World Health Organisation. Vaccination coverage of children aged 12-23 months who have received eight valid doses (as stipulated in the programme) is estimated at 25% in Mhala and 53% in Elim (P < 0.001). While both figures can be substantially improved, the analysis concentrates on factors that help explain the differences between 2 districts that fall under the same central administration. As well as demographic differences, key factors include the presence of community-based health facilities and availability of staff (including programme leaders). The need for regional planners to have detailed and comprehensive knowledge of the health system at district level, and to make allowance for this, is put forward as vital to effective health planning. The failure of the Gazankulu policy to attain its objectives also reflects the often unrecognised consequences of the fragmentation of health services.

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.

Who dies from what? Determining cause of death in South Africa's rural north-east.

Information on cause of death is essential for rational public health planning, yet mortality data in South Africa is limited. In the Agincourt subdistrict, verbal autopsies (VA) have been used to determine cause of death. A VA is conducted on all deaths recorded during annual demographic and health surveillance. Trained lay fieldworkers interview a close caregiver to elicit signs and symptoms of the terminal illness. Each questionnaire is reviewed by three medical practitioners blind to each other's assessment, who assign a 'probable cause of death' where possible. Of 1001 deaths of adults and children identified between 1992 and 1995, 932 VAs were completed. The profile of deaths reflects a mixed picture: the 'unfinished agenda' of communicable disease and malnutrition (diarrhoea and kwashiorkor predominantly) are responsible for over half of deaths in under-fives, accidents are prominent in the 5-14 age-group, while the 'emerging agenda' of violence and chronic degenerative disease (particularly circulatory disease) is pronounced among the middle-aged and elderly. This profile shows the social and demographic transition to be well underway within a rural, underdeveloped population. Validation of VA findings demonstrate that the cause of death profile derived from VA can be used with confidence for planning purposes. Findings of note include the high death rates from kwashiorkor and violence, emerging AIDS and pulmonary tuberculosis, and circulatory deaths in the middle-aged and young elderly. A deeper understanding of the causal factors underlying these critical health problems is needed to strengthen policy and better target interventions.