Thandi Kapwata

Transmission of Extensively Drug-Resistant Tuberculosis in South Africa.

BACKGROUND Drug‐resistant tuberculosis threatens recent gains in the treatment of tuberculosis and human immunodeficiency virus (HIV) infection worldwide. A widespread epidemic of extensively drug‐resistant (XDR) tuberculosis is occurring in South Africa, where cases have increased substantially since 2002. The factors driving this rapid increase have not been fully elucidated, but such knowledge is needed to guide public health interventions. METHODS We conducted a prospective study involving 404 participants in KwaZulu‐Natal Province, South Africa, with a diagnosis of XDR tuberculosis between 2011 and 2014. Interviews and medical‐record reviews were used to elicit information on the participants’ history of tuberculosis and HIV infection, hospitalizations, and social networks. Mycobacterium tuberculosis isolates underwent insertion sequence (IS)6110 restriction‐fragment–length polymorphism analysis, targeted gene sequencing, and whole‐genome sequencing. We used clinical and genotypic case definitions to calculate the proportion of cases of XDR tuberculosis that were due to inadequate treatment of multidrug‐resistant (MDR) tuberculosis (i.e., acquired resistance) versus those that were due to transmission (i.e., transmitted resistance). We used social‐network analysis to identify community and hospital locations of transmission. RESULTS Of the 404 participants, 311 (77%) had HIV infection; the median CD4+ count was 340 cells per cubic millimeter (interquartile range, 117 to 431). A total of 280 participants (69%) had never received treatment for MDR tuberculosis. Genotypic analysis in 386 participants revealed that 323 (84%) belonged to 1 of 31 clusters. Clusters ranged from 2 to 14 participants, except for 1 large cluster of 212 participants (55%) with a LAM4/KZN strain. Person‐to‐person or hospital‐based epidemiologic links were identified in 123 of 404 participants (30%). CONCLUSIONS The majority of cases of XDR tuberculosis in KwaZulu‐Natal, South Africa, an area with a high tuberculosis burden, were probably due to transmission rather than to inadequate treatment of MDR tuberculosis. These data suggest that control of the epidemic of drug‐resistant tuberculosis requires an increased focus on interrupting transmission. (Funded by the National Institute of Allergy and Infectious Diseases and others.)

Current and Potential Future Seasonal Trends of Indoor Dwelling Temperature and Likely Health Risks in Rural Southern Africa

Climate change has resulted in rising temperature trends which have been associated with changes in temperature extremes globally. Attendees of Conference of the Parties (COP) 21 agreed to strive to limit the rise in global average temperatures to below 2 °C compared to industrial conditions, the target being 1.5 °C. However, current research suggests that the African region will be subjected to more intense heat extremes over a shorter time period, with projections predicting increases of 4–6 °C for the period 2071–2100, in annual average maximum temperatures for southern Africa. Increased temperatures may exacerbate existing chronic ill health conditions such as cardiovascular disease, respiratory disease, cerebrovascular disease, and diabetes-related conditions. Exposure to extreme temperatures has also been associated with mortality. This study aimed to consider the relationship between temperatures in indoor and outdoor environments in a rural residential setting in a current climate and warmer predicted future climate. Temperature and humidity measurements were collected hourly in 406 homes in summer and spring and at two-hour intervals in 98 homes in winter. Ambient temperature, humidity and windspeed were obtained from the nearest weather station. Regression models were used to identify predictors of indoor apparent temperature (AT) and to estimate future indoor AT using projected ambient temperatures. Ambient temperatures will increase by a mean of 4.6 °C for the period 2088–2099. Warming in winter was projected to be greater than warming in summer and spring. The number of days during which indoor AT will be categorized as potentially harmful will increase in the future. Understanding current and future heat-related health effects is key in developing an effective surveillance system. The observations of this study can be used to inform the development and implementation of policies and practices around heat and health especially in rural areas of South Africa.

The reach of human health risks associated with metals/metalloids in water and vegetables along a contaminated river catchment : South Africa and Mozambique

BACKGROUND Anthropogenic pollution was identified as an environmental problem of concern when, in 2008, dozens of crocodiles died in the Olifants River catchment near the border of South Africa and Mozambique. Given the close proximity of households to the river and their making use of river water, we aimed to determine to what extent water pollution has an impact on health of indigent communities in South Africa and Mozambique in the catchment area. METHODS Water and vegetable samples were collected from the study areas. Biota samples were washed with double de-ionized Milli-Q water and freeze-dried. Heavy metal analyses in water and vegetables were done by means of Inductively Coupled Plasma Optical Emission Spectroscopy. Metal concentrations were applied in a human health risk assessment to estimate health risks. RESULTS Mean concentrations of antimony, arsenic, cadmium, chromium, mercury, molybdenum, nickel and selenium in water samples from South Africa exceeded the World Health Organization guidelines for safe levels of intake. Only iron exceeded the recommended guidelines in water samples from Mozambique. Metals/metalloids were found in lower concentrations at Mozambique sites downstream of South African sites. In vegetables, uranium was between 10 and 20 times above safe guidelines in South Africa and between 3 and 6 times in Mozambique. Arsenic in water samples posed the highest cancer risk. CONCLUSIONS Even with a reduction in the metal concentrations in river water from South Africa to Mozambique, the potential to cause adverse human health impacts from direct use of polluted river water is evident in both countries.

Spatial distribution of extensively drug-resistant tuberculosis (XDR TB) patients in KwaZulu-Natal, South Africa.

Background KwaZulu-Natal province, South Africa, has among the highest burden of XDR TB worldwide with the majority of cases occurring due to transmission. Poor access to health facilities can be a barrier to timely diagnosis and treatment of TB, which can contribute to ongoing transmission. We sought to determine the geographic distribution of XDR TB patients and proximity to health facilities in KwaZulu-Natal. Methods We recruited adults and children with XDR TB diagnosed in KwaZulu-Natal. We calculated distance and time from participants’ home to the closest hospital or clinic, as well as to the actual facility that diagnosed XDR TB, using tools within ArcGIS Network analyst. Speed of travel was assigned to road classes based on Department of Transport regulations. Results were compared to guidelines for the provision of social facilities in South Africa: 5km to a clinic and 30km to a hospital. Results During 2011–2014, 1027 new XDR TB cases were diagnosed throughout all 11 districts of KwaZulu-Natal, of whom 404 (39%) were enrolled and had geospatial data collected. Participants would have had to travel a mean distance of 2.9 km (CI 95%: 1.8–4.1) to the nearest clinic and 17.6 km (CI 95%: 11.4–23.8) to the nearest hospital. Actual distances that participants travelled to the health facility that diagnosed XDR TB ranged from <10 km (n = 143, 36%) to >50 km (n = 109, 27%), with a mean of 69 km. The majority (77%) of participants travelled farther than the recommended distance to a clinic (5 km) and 39% travelled farther than the recommended distance to a hospital (30 km). Nearly half (46%) of participants were diagnosed at a health facility in eThekwini district, of whom, 36% resided outside the Durban metropolitan area. Conclusions XDR TB cases are widely distributed throughout KwaZulu-Natal province with a denser focus in eThekwini district. Patients travelled long distances to the health facility where they were diagnosed with XDR TB, suggesting a potential role for migration or transportation in the XDR TB epidemic.

Random forest variable selection in spatial malaria transmission modelling in Mpumalanga Province, South Africa

Malaria is an environmentally driven disease. In order to quantify the spatial variability of malaria transmission, it is imperative to understand the interactions between environmental variables and malaria epidemiology at a micro-geographic level using a novel statistical approach. The random forest (RF) statistical learning method, a relatively new variable-importance ranking method, measures the variable importance of potentially influential parameters through the percent increase of the mean squared error. As this value increases, so does the relative importance of the associated variable. The principal aim of this study was to create predictive malaria maps generated using the selected variables based on the RF algorithm in the Ehlanzeni District of Mpumalanga Province, South Africa. From the seven environmental variables used [temperature, lag temperature, rainfall, lag rainfall, humidity, altitude, and the normalized difference vegetation index (NDVI)], altitude was identified as the most influential predictor variable due its high selection frequency. It was selected as the top predictor for 4 out of 12 months of the year, followed by NDVI, temperature and lag rainfall, which were each selected twice. The combination of climatic variables that produced the highest prediction accuracy was altitude, NDVI, and temperature. This suggests that these three variables have high predictive capabilities in relation to malaria transmission. Furthermore, it is anticipated that the predictive maps generated from predictions made by the RF algorithm could be used to monitor the progression of malaria and assist in intervention and prevention efforts with respect to malaria.

Towards a reliable, non-invasive melanin assessment for pigmented skin

The South African Medical Research Council and the National Research Foundation of South Africa.

Effect of A Sun Protection Intervention on the Immune Response to Measles Booster Vaccination in Infants in Rural South Africa

The incidence of many serious childhood infections can be reduced by vaccination. High sun exposure at the time of vaccination has been associated with a reduced antigen‐specific immune response. We hypothesized that providing sun protection advice and equipment to mothers of children who were waiting to be vaccinated would result in a more robust immunization response. We conducted a pilot study in 2015/2016 (data analyzed in 2017–2018) among 98 Black African children (~18 months of age) receiving the booster measles vaccination at two clinics in South Africa. Clinics were randomized to receive (or not) sun protection advice and equipment. We recorded demographic information on children and mothers and data on the childs usual sun exposure. At approximately 4 weeks’ postmeasles vaccination, we measured measles immunoglobulin G levels in children. All children with blood results (n = 87, 89%) across both groups had antibody titers higher than 200 mIU mL−1 which was considered the protective antibody concentration. There was no statistically significant difference in titers between groups: geometric difference in mean titers 1.13 mIU mL−1 (95% CI 0.85, 1.51; P = 0.39) and 1.38 mIU mL−1 (95% CI 0.90, 2.11, P = 0.14) for unadjusted and adjusted analyses, respectively. This study demonstrated that a sun protection intervention study could be performed in a developing‐world pediatric vaccination setting. Although the sun protection intervention around the time of vaccination was not associated with a higher antibody level, given the potential importance of such an effect, a larger study should be considered.

Diarrhoeal Disease in Relation to Possible Household Risk Factors in South African Villages

Diarrhoeal disease is a significant contributor to child morbidity and mortality, particularly in the developing world. Poor sanitation, a lack of personal hygiene and inadequate water supplies are known risk factors for diarrhoeal disease. Since risk factors may vary by population or setting, we evaluated the prevalence of diarrhoeal disease at the household level using a questionnaire to better understand household-level risk factors for diarrhoea in selected rural areas in South Africa. In a sub-sample of dwellings, we measured the microbial quality of drinking water. One in five households had at least one case of diarrhoea during the previous summer. The most widespread source of drinking water was a stand-pipe (inside yard) (45%) followed by an indoor tap inside the dwelling (29%). Storage of water was common (97%) with around half of households storing water in plastic containers with an opening large enough to fit a hand through. After adjusting for confounders, the occurrence of diarrhoea was statistically significantly associated with sourcing water from an indoor tap (Adjusted Odds Ratio (AOR): 2.73, 95% CI: 2.73, 1.14–6.56) and storing cooked/perishable food in non-refrigerated conditions (AOR: 2.17, 95% CI: 2.17, 1.44–3.26). The highest total coliform counts were found in water samples from kitchen containers followed by stand-pipes. Escherichia coli were most often detected in samples from stand-pipes and kitchen containers. One in four households were at risk of exposure to contaminated drinking water, increasing the susceptibility of the study participants to episodes of diarrhoea. It is imperative that water quality meets guideline values and routine monitoring of quality of drinking water is done to minimise diarrhoea risk in relevant rural communities. The security of water supply in rural areas should be addressed as a matter of public health urgency to avoid the need for water storage.

0050 Working towards assessing occupational carcinogenic exposures in an african lower and middle income country

Aim We aim to use the Canadian CAREX (CARcinogen EXposure) tool, adapted for local context, as a method to assess prevalence and level of exposure to priority occupational carcinogens in South Africa. Methods The work entails first understanding the CAREX tool, and adapting it as well as reviewing its use in other countries (phase 1). Once the tool and database are prepared, we will gather publicly available data (i.e. Census data, information on chemical use, trade data, published and grey literature, expert consultation, etc.) on occupational exposure to carcinogens as well as exposure monitoring data (phase 2). We will consider all occupational health and safety legislation and its regulations regarding occupational exposure limits, and those carcinogens prioritised locally and internationally, for example by the International Agency for Research on Cancer. All data will be used to estimate the number of South African workers occupationally exposed to carcinogens (and where possible, their level of exposure) (phase 3). Ultimately, this will help guide the development of appropriate health promotion and worker protection programmes, among other resources aimed at cancer prevention (phase 4). Results Here we will present the experience of the team during phase 1 of the project, including challenges and opportunities encountered. Expected outcomes Key future outcomes include prevalence of exposure to occupational environmental carcinogens in the South African workplace; also proportions of the workforce in various occupational groups exposed to specific carcinogens; key occupational groups in need of protection; data and information that can be used to guide prevention programs.