Depression: an individual-level early warning indicator of virologic failure in HIV patients in South Africa.

OBJECTIVE: To identify individual-level early warning indicators of virologic failure in HIV patients receiving antiretroviral therapy (ART) in South Africa. DESIGN: A matched case-control study of individuals with and without virologic failure (VF) (>5 months on ART and HIV-1 plasma viral load >1,000 copies/mL) was conducted between June 2014 and June 2018. Of the 1,000 participants enrolled in the parent cohort, 96 experienced VF, and 199 additional controls were identified from the parent cohort and matched 1:2 (some matched 1:3) for sex, age, ART duration, and site. Participants were interviewed while clinical, pharmacy refill, laboratory, and objective pharmacological data were obtained. Multivariate conditional logistic regression models were constructed using model selection to identify factors associated with VF. Significant determinants of VF were identified using an alpha level of 0.05. RESULTS: In a full conditional model, higher cumulative ART adherence, quantified using tenofovir-diphosphate concentrations in dried blood spots (OR 0.26) and medication possession ratio (OR 0.98) were protective against VF, whereas an increase in total depression score (OR 1.20) was predictive of VF. CONCLUSION: This analysis demonstrates the importance of depression as a key individual-level early warning indicator of VF. Efforts to address mental health concerns among patients with people living with HIV could improve virologic suppression.

OBJECTIF: Identifier les indicateurs d'alerte précoce au niveau individuel de l'échec virologique chez les patients séropositifs recevant un traitement antirétroviral (TAR) en Afrique du Sud. MÉTHODE: Une étude cas-témoins appariée de personnes avec et sans échec virologique (FV, pour l'anglais « virologic failure ¼) (>5 mois sous ART et charge virale plasmatique du VIH-1 >1 000 copies/ml) a été menée entre juin 2014 et juin 2018. Sur les 1 000 participants inscrits dans la cohorte parente, 96 ont présenté une FV et 199 témoins supplémentaires ont été identifiés dans la cohorte parentale et appariés 1:2 (certains appariés 1:3) pour le sexe, l'âge, la durée du TAR et le site. Les participants ont été interrogés pendant que des données cliniques, de renouvellement de pharmacie, de laboratoire et pharmacologiques objectives ont été obtenues. Des modèles de régression logistique conditionnelle multivariée ont été construits à l'aide d'une sélection de modèles pour identifier les facteurs associés à la FV. Les déterminants significatifs de la FV ont été identifiés à l'aide d'un niveau alpha de 0,05. RÉSULTATS: Dans un modèle conditionnel complet, une observance cumulative plus élevée du TAR, quantifiée à l'aide des concentrations de ténofovir-diphosphate dans les gouttes de sang séché (OR 0,26) et du ratio de possession de médicaments (OR 0,98) protégeait contre la FV, tandis qu'une augmentation du score de dépression totale (OR 1,20) était prédictive de la FV. CONCLUSION: Cette analyse démontre l'importance de la dépression en tant qu'indicateur précoce clé au niveau individuel de la FV. Les efforts visant à résoudre les problèmes de santé mentale chez les personnes vivant avec le VIH pourraient améliorer la suppression virologique.

Correction: Investigating risk factors for under-five mortality in an HIV hyper-endemic area of rural South Africa, from 2000-2014.

[This corrects the article DOI: 10.1371/journal.pone.0207294.].

Instrumental variable estimation of the marginal structural Cox model for time-varying treatments.

Robins (1998) introduced marginal structural models, a general class of counterfactual models for the joint effects of time-varying treatments in complex longitudinal studies subject to time-varying confounding. Robins (1998) established the identification of marginal structural model parameters under a sequential randomization assumption, which rules out unmeasured confounding of treatment assignment over time. The marginal structural Cox model is one of the most popular marginal structural models for evaluating the causal effect of time-varying treatments on a censored failure time outcome. In this paper, we establish sufficient conditions for identification of marginal structural Cox model parameters with the aid of a time-varying instrumental variable, in the case where sequential randomization fails to hold due to unmeasured confounding. Our instrumental variable identification condition rules out any interaction between an unmeasured confounder and the instrumental variable in its additive effects on the treatment process, the longitudinal generalization of the identifying condition of Wang & Tchetgen Tchetgen (2018). We describe a large class of weighted estimating equations that give rise to consistent and asymptotically normal estimators of the marginal structural Cox model, thereby extending the standard inverse probability of treatment weighted estimation of marginal structural models to the instrumental variable setting. Our approach is illustrated via extensive simulation studies and an application to estimating the effect of community antiretroviral therapy coverage on HIV incidence.

Multi-drug-resistant tuberculosis clusters in Mpumalanga province, South Africa, 2013-2016: A spatial analysis.

OBJECTIVE: To identify spatial clusters with unusually high levels of MDR-TB, which are highly unlikely to have arisen by chance in Mpumalanga Province, South Africa. METHODS: Home addresses of all MDR-TB patients were collected from four MDR-TB facilities from 2013 to 2016. We mapped all addresses, linking them to the nearest ward with population estimates. A spatial analysis was conducted using kernel density in ArcGIS to estimate and map the distribution of the disease and used Gertis-Ord Gi to test for significant clustering. RESULTS: A total of 4065 MDR-TB patients were mapped. Ten significant clusters (p-value <0.05) were found across the province in six sub-districts: Mbombela, Nkomazi, Emalahleni, Govan Mbeki, Lekwa and Mkhondo. Mbombela has the highest number of significant clusters. The central region did not have any MDR-TB clusters. CONCLUSION: There is clear evidence of MDR-TB clustering in Mpumalanga. This calls for concentrated TB prevention efforts and proper allocation of resources. Further investigations are needed to identify MDR-TB predictors.

Findings from home-based HIV testing and facilitated linkage after scale-up of test and treat in rural South Africa: young people still missing.

OBJECTIVES: The aim of the study was to estimate rates of linkage to HIV care and antiretroviral treatment (ART) initiation after the introduction of home-based HIV counselling and testing (HBHCT) and telephone-facilitated support for linkage in rural South Africa. METHODS: A population-based prospective cohort study was carried out in KwaZulu Natal, South Africa. All residents aged ≥ 15 years were eligible for HBHCT. Those who tested positive and were not in care were referred for ART at one of 11 public-sector clinics. Individuals who did not attend the clinic within 2 weeks were sent a short message service (SMS) reminder; those who had not attended after a further 2 weeks were telephoned by a nurse counsellor, to discuss concerns and encourage linkage. Kaplan-Meier methods were used to estimate the proportion of newly diagnosed individuals linking to care and initiating ART. RESULTS: Among 38 827 individuals visited, 26% accepted HBHCT. Uptake was higher in women than in men (30% versus 20%, respectively), but similar in people aged < 30 years and ≥ 30 years (28% versus 26%, respectively). A total of 784 (8%) tested HIV positive, of whom 427 (54%) were newly diagnosed. Within 6 months, 31% of women and 18% of men < 30 years old had linked to care, and 29% and 16%, respectively, had started ART. Among those ≥ 30 years, 41% of women and 38% of men had linked to care within 6 months, and 41% and 35%, respectively, had started ART. CONCLUSIONS: Despite facilitated linkage, rates of timely linkage to care and ART initiation after HBHCT were very low, particularly among young men. Innovations are needed to provide effective HIV care and prevention interventions to young people, and thus maximize the benefits of universal test and treat.

Home-based intervention to test and start (HITS) protocol: a cluster-randomized controlled trial to reduce HIV-related mortality in men and HIV incidence in women through increased coverage of HIV treatment.

BACKGROUND: To realize the full benefits of treatment as prevention in many hyperendemic African contexts, there is an urgent need to increase uptake of HIV testing and HIV treatment among men to reduce the rate of HIV transmission to (particularly young) women. This trial aims to evaluate the effect of two interventions - micro-incentives and a tablet-based male-targeted HIV decision support application - on increasing home-based HIV testing and linkage to HIV care among men with the ultimate aim of reducing HIV-related mortality in men and HIV incidence in young women. METHODS/DESIGN: This is a cluster randomized trial of 45 communities (clusters) in a rural area in the uMkhanyakude district of KwaZulu Natal, South Africa (2018-2021). The study is built upon the Africa Health Research Institute (AHRI)'s HIV testing platform, which offers annual home-based rapid HIV testing to individuals aged 15 years and above. In a 2 × 2 factorial design, individuals aged ≥15 years living in the 45 clusters are randomly assigned to one of four arms: i) a financial micro-incentive (food voucher) (n = 8); ii) male-targeted HIV specific decision support (EPIC-HIV) (n = 8); iii) both the micro incentives and male-targeted decision support (n = 8); and iv) standard of care (n = 21). The EPIC-HIV application is developed and delivered via a tablet to encourage HIV testing and linkage to care among men. A mixed method approach is adopted to supplement the randomized control trial and meet the study aims. DISCUSSION: The findings of this trial will provide evidence on the feasibility and causal impact of two interventions - micro-incentives and a male-targeted HIV specific decision support - on uptake of home-based HIV testing, linkage to care, as well as population health outcomes including population viral load, HIV related mortality in men, and HIV incidence in young women (15-30 years of age). TRIAL REGISTRATION: This trial was registered on 28 November 2018 on, identifier https://clinicaltrials.gov/ .

Investigating risk factors for under-five mortality in an HIV hyper-endemic area of rural South Africa, from 2000-2014.

INTRODUCTION: Despite global progress, there remains a disproportionate burden of under-five year old deaths in sub-Saharan Africa (SSA), where four out of five child deaths occur. Substantial progress has been made in improving sanitation, controlling communicable diseases and the spread of HIV in most parts of the world. However, significant strides to address some key risk factors related to under-five mortality are still needed in rural SSA if they are to attain relevant 2030 SDG targets. The aim of this study is to investigate the risk factors for under-five mortality in an HIV hyper-endemic area of rural South Africa, from 2000-2014. Some of the key risk factors investigated are, for example: household wealth, source of drinking water, distance to the national road and birth order. METHODS: We conducted a statistical analysis of 759 births from a population-based cohort in rural KwaZulu-Natal Province, South Africa, from 2000 to 2014. A Cox Proportional Hazards model was used to identify the risk factors and key socio-demographic correlates of under-five mortality leveraging the longitudinal structure of the population cohort. RESULTS: Child mortality rates declined by 80 per cent from 2000 to 2014, from >140 per 1,000 persons in years 2001-2003 to 20 per 1,000 persons in the year 2014. The highest under-five mortality rate was recorded in 2002/2003, which decreased following the start of antiretroviral therapy rollout in 2003/4. The results indicated that under-five and infant mortality are significantly associated with a low wealth index of 1.49 (1.007-2.48) for under-fives and 3.03 (1.72-5.34) for infants. Children and infants with a lower wealth index had a significantly increased risk of mortality as compared to those with a high wealth index. Other significant factors included: source of household drinking water (borehole) 3.03 (1.72-5.34) for under-fives and 2.98 (1.62-5.49) for infants; having an HIV positive mother 4.22 (2.68-6.65) for under-fives and 3.26 (1.93-5.51) for infants, and period of death 9.13 (5.70-14.6) for under-fives and 1.28 (0.75-2.20) for infants. Wealth index had the largest population attributable fraction of 25.4 per cent. CONCLUSIONS: The research findings show a substantial overall reduction in under-five mortality since 2003. Unsafe household water sources and having an HIV-positive mother were associated with an increased risk of under-five mortality in this rural setting. The significant risk factors identified align well with the SDG 2030 targets for reducing child mortality, which include improved nutrition, sanitation, hygiene and reduced HIV infections. Current trajectories suggest that there is some hope for meeting the 2030 SGD targets in rural South Africa and the region if the identified significant risk factors are adequately addressed.

Spatial clustering of drug-resistant tuberculosis in Hlabisa subdistrict, KwaZulu-Natal, 2011-2015.

SETTING: Incidencerates of tuberculosis (TB) in South Africa are among the highest in the world, and drug resistance is a major concern. Understanding geographic variations in disease may guide targeted interventions. OBJECTIVE: To characterise the spatial distribution of drug-resistant TB (DR-TB) in a rural area of KwaZulu-Natal, South Africa, and to test for clustering. DESIGN: This was a cross-sectional analysis of DR-TB patients managed at a rural district hospital from 2011 to 2015. We mapped all patients in hospital data to local areas, and then linked to a population-based demographic surveillance system to map the patients to individual homesteads. We used kernel density estimation to visualise the distribution of disease and tested for clustering using spatial scan statistics. RESULTS: There were 489 patients with DR-TB in the subdistrict; 111 lived in the smaller demographic surveillance area. Spatial clustering analysis identified a high-risk cluster (relative risk of DR-TB inside vs. outside cluster 3.0, P < 0.001) in the south-east, a region characterised by high population density and a high prevalence of human immunodeficiency virus infection. CONCLUSION: We have demonstrated evidence of a geographic high-risk cluster of DR-TB. This suggests that targeting interventions to spatial areas of highest risk, where transmission may be ongoing, could be effective.

Space-time patterns in maternal and mother mortality in a rural South African population with high HIV prevalence (2000-2014): results from a population-based cohort.

BACKGROUND: International organs such as, the African Union and the South African Government view maternal health as a dominant health prerogative. Even though most countries are making progress, maternal mortality in South Africa (SA) significantly increased between 1990 and 2015, and prevented the country from achieving Millennium Development Goal 5. Elucidating the space-time patterns and risk factors of maternal mortality in a rural South African population could help target limited resources and policy guidelines to high-risk areas for the greatest impact, as more generalized interventions are costly and often less effective. METHODS: Population-based mortality data from 2000 to 2014 for women aged 15-49 years from the Africa Centre Demographic Information System located in the Umkhanyakude district of KwaZulu-Natal Province, South Africa were analysed. Our outcome was classified into two definitions: Maternal mortality; the death of a woman while pregnant or within 42 days of cessation of pregnancy, regardless of the duration and site of the pregnancy, from any cause related to or exacerbated by the pregnancy or its management but not from unexpected or incidental causes; and 'Mother death'; death of a mother whilst child is less than 5 years of age. Both the Kulldorff and Tango spatial scan statistics for regular and irregular shaped cluster detection respectively were used to identify clusters of maternal mortality events in both space and time. RESULTS: The overall maternal mortality ratio was 650 per 100,000 live births, and 1204 mothers died while their child was less than or equal to 5 years of age, of a mortality rate of 370 per 100,000 children. Maternal mortality declined over the study period from approximately 600 per 100,000 live births in 2000 to 400 per 100,000 live births in 2014. There was no strong evidence of spatial clustering for maternal mortality in this rural population. However, the study identified a significant spatial cluster of mother deaths in childhood (p = 0.022) in a peri-urban community near the national road. Based on our multivariable logistic regression model, HIV positive status (Adjusted odds ratio [aOR] = 2.5, CI 95%: [1.5-4.2]; primary education or less (aOR = 1.97, CI 95%: [1.04-3.74]) and parity (aOR = 1.42, CI 95%: [1.24-1.63]) were significant predictors of maternal mortality. CONCLUSIONS: There has been an overall decrease in maternal and mother death between 2000 and 2014. The identification of a clear cluster of mother deaths shows the possibility of targeting intervention programs in vulnerable communities, as population-wide interventions may be ineffective and too costly to implement.

Measuring ventilation and modelling M. tuberculosis transmission in indoor congregate settings, rural KwaZulu-Natal.

SETTING: Molecular epidemiology suggests that most Mycobacterium tuberculosis transmission in high-burden settings occurs outside the home. OBJECTIVE: To estimate the risk of M. tuberculosis transmission inside public buildings in a high TB burden community in KwaZulu-Natal, South Africa. DESIGN: Carbon dioxide (CO2) sensors were placed inside eight public buildings. Measurements were used with observations of occupancy to estimate infection risk using an adaptation of the Wells-Riley equation. Ventilation modelling using CONTAM was used to examine the impact of low-cost retrofits on transmission in a health clinic. RESULTS: Measurements indicate that infection risk in the church, classroom and clinic waiting room would be high with typical ventilation, occupancy levels and visit durations. For example, we estimated that health care workers in a clinic waiting room had a 16.9-24.5% annual risk of M. tuberculosis infection. Modelling results indicate that the simple addition of two new windows allowing for cross-ventilation, at a cost of US$330, would reduce the annual risk to health care workers by 57%. CONCLUSIONS: Results indicate that public buildings in this community have a range of ventilation and occupancy characteristics that may influence transmission risks. Simple retrofits may result in dramatic reductions in M. tuberculosis transmission, and intervention studies should therefore be considered.

Spatial-temporal dynamics and structural determinants of child and maternal mortality in a rural, high HIV burdened South African population, 2000-2014: a study protocol.

INTRODUCTION: Child (infant and under-5) and maternal mortality rates are key indicators for assessing the health status of populations. South Africa's maternal and child mortality rates are high, and the country mirrors the continental trend of slow progress towards its Millennium Development Goals. Rural areas are often more affected regarding child and maternal mortalities, specifically in areas with a high HIV burden. This study aims to understand the factors affecting child and maternal mortality in the Africa Centre Demographic Surveillance Area (DSA) from 2003 to 2014 towards developing tailored interventions to reduce the deaths in resource poor settings. This will be done by identifying child and maternal mortality 'hotspots' and their associated risk factors. METHODS AND ANALYSIS: This retrospective study will use data for 2003-2014 from the Africa Centre Demographic Information System (ACDIS) in rural KwaZulu-Natal Province, South Africa. All homesteads in the study area have been mapped to an accuracy of <2 m, all deaths recorded and the assigned cause of death established using a verbal autopsy interview. Advanced spatial-temporal clustering techniques (both regular (Kulldorff) and irregular (FleXScan)) will be used to identify mortality 'hotspots'. Various advanced statistical modelling approaches will be tested and used to identify significant risk factors for child and maternal mortality. Differences in attributability and risk factors profiles in identified 'hotspots' will be assessed to enable tailored intervention guidance/development. This multicomponent study will enable a refined intervention model to be developed for typical rural populations with a high HIV burden. ETHICS: Ethical approval was received from the Biomedical Research Ethics Committee (BREC) of the University of KwaZulu-Natal (BE 169/15).

Plan Beta for tuberculosis: it's time to think seriously about poorly ventilated congregate settings.

Globally, the rates of decline in tuberculosis (TB) incidence are disappointing, but in line with model predictions regarding the likely impact of the DOTS strategy. Here, we review evidence from basic epidemiology, molecular epidemiology and modelling, all of which suggest that, in high-burden settings, the majority of Mycobacterium tuberculosis transmission may occur in indoor congregate settings. We argue that mass environmental modifications in these places might have a significant impact on TB control and suggest a research agenda that might inform interventions of this nature. The necessary technology exists and, critically, implementation would not be dependent on health care workers who are in short supply in the communities worst affected by TB.

HIV status and participation in HIV surveillance in the era of antiretroviral treatment: a study of linked population-based and clinical data in rural South Africa.

OBJECTIVE: To examine whether HIV status affects participation in a population-based longitudinal HIV surveillance in the context of an expanding HIV treatment and care programme in rural South Africa. METHOD: We regressed consent to participate in the HIV surveillance during the most recent fieldworker visit on HIV status (based on previous surveillance participation or enrollment in pre-antiretroviral treatment (pre-ART) care or ART in the local HIV treatment and care programme), controlling for sex, age and year of the visit (N = 25,940). We then repeated the regression using the same sample but, in one model, stratifying HIV-infected persons into three groups (neither enrolled in pre-ART care nor receiving ART; enrolled in pre-ART care but not receiving ART; receiving ART) and, in another model, additionally stratifying the group enrolled in pre-ART and the group receiving ART into those with CD4 count ≤ 200/µl (i.e. the ART eligibility threshold at the time) vs. those with CD4 count >200/µl. RESULTS: HIV-infected individuals were significantly less likely to consent to participate in the surveillance than HIV-uninfected individuals [adjusted odds ratio (aOR), 0.74; 95% confidence interval, 0.70-0.79, P < 0.001], controlling for other factors. Persons who were receiving ART were less likely to consent to participate (aOR, 0.75, 0.68-0.84, P < 0.001) than those who had never sought HIV treatment or care (aOR, 0.82, 0.75-0.89, P < 0.001), but more likely to consent than persons enrolled in pre-ART care (aOR 0.62, 0.56-0.69, P < 0.001). Those with CD4 count ≤ 200/µl were significantly less likely to consent to participate than those with CD4 count >200/µl in both the group enrolled in pre-ART and the group receiving ART. CONCLUSION: As HIV test results are not made available to participants in the HIV surveillance, our findings agree with the hypothesis that HIV-infected persons are less likely than HIV-uninfected persons to participate in HIV surveillance because they fear the negative consequences of others learning about their HIV infection. Our results further suggest that the increased knowledge of HIV status that accompanies improved ART access can reduce surveillance participation of HIV-infected persons, but that this effect decreases after ART initiation, in particular in successfully treated patients.

The application of GIS technology to equitably distribute fieldworker workload in a large, rural South African health survey.

A method is presented that has numerous applications to health systems provision in developing countries where limited physical access to primary health care is a major factor contributing to the poor health of populations. An accessibility model within a geographical information system (GIS) is used to predict average inter-homestead walking times and subdivide the study area into units of equal completion time. The method could be used to ergonomically design home-based care and tuberculosis directly observed treatment programmes and inform the siting of health facilities. The paper highlights the use of GIS technology as a powerful tool in developing countries.

New approaches to spatially analyse primary health care usage patterns in rural South Africa.

OBJECTIVE: To develop indices to quantitatively assess and understand the spatial usage patterns of health facilities in the Hlabisa district of South Africa. METHODOLOGY: We mapped and interviewed more than 23 000 homesteads (approximately 200 000 people) in Hlabisa district, South Africa and spatially analysed their modal primary health usage patterns using a geographical information system. We generated contour maps of health service use and quantified the relationship between clinic catchments and distance-defined catchments using inclusion and exclusion error. We propose the distance usage index (DUI) as an overall spatial measure of clinic usage. This index is the sum of the distances from clinic to all client homesteads divided by the sum of the distances from clinic to all homesteads within its distance-defined catchment. The index encompasses inclusion, exclusion, and strength of patient attraction for each clinic. RESULTS: Eighty-seven per cent of homesteads use the nearest clinic. Residents of homesteads travel an average Euclidean distance of 4.72 km to attend clinics. There is a significant logarithmic relationship between distance from clinic and their use by homesteads (r(2)=0.774, P < 0.0001). The DUI values range between 31 and 198% (mean=110%, SD=43.7) for 12 clinics and highlight clinic usage patterns across the district. CONCLUSIONS: The DUI is a powerful and informative composite measure of clinic usage. The results of the study have important implications for health care provision in developing countries.

HIV heterogeneity and proximity of homestead to roads in rural South Africa: an exploration using a geographical information system.

objective To describe heterogeneity of HIV prevalence among pregnant women in Hlabisa health district, South Africa and to correlate this with proximity of homestead to roads. methods HIV prevalence measured through anonymous surveillance among pregnant women and stratified by local village clinic. Polygons were created around each clinic, assuming women attend the clinic nearest their home. A geographical information system (GIS) calculated the mean distance from homesteads in each clinic catchment to nearest primary (1 degrees ) and to nearest primary or secondary (2 degrees ) road. results We found marked HIV heterogeneity by clinic catchment (range 19-31% (P < 0.001). A polygon plot demonstrated lower HIV prevalence in catchments remote from 1 degrees roads. Mean distance from homesteads to nearest 1 degrees or 2 degrees road varied by clinic catchment from 1623 to 7569 m. The mean distance from homesteads to a 1 degrees or 2 degrees road for each clinic catchment was strongly correlated with HIV prevalence (r = 0.66; P = 0.002). conclusions The substantial HIV heterogeneity in this district is closely correlated with proximity to a 1 degrees or 2 degrees road. GIS is a powerful tool to demonstrate and to start to analyse this observation. Further research is needed to better understand this relationship both at ecological and individual levels, and to develop interventions to reduce the spread of HIV infection.

Spatial implications of the tuberculosis DOTS strategy in rural South Africa: a novel application of geographical information system and global positioning system technologies.

We used GIS/GPS technology to document and quantify improved access to tuberculosis treatment through a community-based programme in Hlabisa, South Africa. We plotted tuberculosis supervision points used by the district health system in 1991 (programme's first year) and 1996 (programme fully established), and quantified access by using GIS to measure the mean distance from each homestead in the district to hospital, clinics, community health workers (CHW) and volunteer supervisors. While the tuberculosis caseload tripled, the number of community supervision points used increased from 37 in 1991 to 147 in 1996. Adding clinics and then CHWs to the hospital as treatment points reduced the mean distance from homestead to treatment point from 29.6 km to 4.2 km and to 1.9 km, respectively. Adding volunteers further decreased the distance to 800 m. GIS/GPS effectively documents and quantifies the impact of community-based tuberculosis treatment on access to treatment.

GIS/GPS to document increased access to community-based treatment for tuberculosis in Africa. Geographic information system/global positioning system.

Application of geographic information system (GIS) and global positioning system (GPS) technology in the Hlabisa community-based tuberculosis treatment programme documents the increase in accessibility to treatment after the expansion of the service from health facilities to include community workers and volunteers.

Models to predict the intensity of Plasmodium falciparum transmission: applications to the burden of disease in Kenya.

There is an increasing need to provide spatial distribution maps of the clinical burden of Plasmodium falciparum malaria in Africa. Recent evidence suggests that risk groups and the clinical spectrum of severe malaria are related to the intensity of P. falciparum transmission. Climate operates to affect the vectorial capacity of P. falciparum transmission and this is particularly important in the Horn of Africa and parts of East Africa. We have used a fuzzy logic climate suitability model to define areas of Kenya unsuitable for stable transmission. Kenya's unstable transmission areas can be divided into areas where transmission potential is limited by low rainfall or low temperature and, combined, encompass over 8 million people. Among areas of stable transmission we have used empirical data on P. falciparum infection rates among 124 childhood populations in Kenya to develop a climate-based statistical model of transmission intensity. This model correctly identified 75% (95% confidence interval CI 70-85) of 3 endemicity classes (low, < 20%; high, > or = 70%; and intermediate parasite prevalences). The model was applied to meteorological and remote sensed data using a geographical information system to provide estimates of endemicity for all of the 1080 populated fourth level administrative regions in Kenya. National census data for 1989 on the childhood populations within each administrative region were projected to provide 1997 estimates. Endemicity-specific estimates of morbidity and mortality were derived from published and unpublished sources and applied to their corresponding exposed-to-risk childhood populations. This combined transmission, population and disease-risk model suggested that every day in Kenya approximately 72 and 400 children below the age of 5 years either die or develop clinical malaria warranting in-patient care, respectively. Despite several limitations, such an approach goes beyond 'best guesses' to provide informed estimates of the geographical burden of malaria and its fatal consequences in Kenya.