Hugh J. W. Sturrock

The changing epidemiology of malaria elimination: new strategies for new challenges

Malaria-eliminating countries achieved remarkable success in reducing their malaria burdens between 2000 and 2010. As a result, the epidemiology of malaria in these settings has become more complex. Malaria is increasingly imported, caused by Plasmodium vivax in settings outside sub-Saharan Africa, and clustered in small geographical areas or clustered demographically into subpopulations, which are often predominantly adult men, with shared social, behavioural, and geographical risk characteristics. The shift in the populations most at risk of malaria raises important questions for malaria-eliminating countries, since traditional control interventions are likely to be less effective. Approaches to elimination need to be aligned with these changes through the development and adoption of novel strategies and methods. Knowledge of the changing epidemiological trends of malaria in the eliminating countries will ensure improved targeting of interventions to continue to shrink the malaria map.

Spatial Modelling of Soil-Transmitted Helminth Infections in Kenya: A Disease Control Planning Tool

Background Implementation of control of parasitic diseases requires accurate, contemporary maps that provide intervention recommendations at policy-relevant spatial scales. To guide control of soil transmitted helminths (STHs), maps are required of the combined prevalence of infection, indicating where this prevalence exceeds an intervention threshold of 20%. Here we present a new approach for mapping the observed prevalence of STHs, using the example of Kenya in 2009. Methods and Findings Observed prevalence data for hookworm, Ascaris lumbricoides and Trichuris trichiura were assembled for 106,370 individuals from 945 cross-sectional surveys undertaken between 1974 and 2009. Ecological and climatic covariates were extracted from high-resolution satellite data and matched to survey locations. Bayesian space-time geostatistical models were developed for each species, and were used to interpolate the probability that infection prevalence exceeded the 20% threshold across the country for both 1989 and 2009. Maps for each species were integrated to estimate combined STH prevalence using the law of total probability and incorporating a correction factor to adjust for associations between species. Population census data were combined with risk models and projected to estimate the population at risk and requiring treatment in 2009. In most areas for 2009, there was high certainty that endemicity was below the 20% threshold, with areas of endemicity ≥20% located around the shores of Lake Victoria and on the coast. Comparison of the predicted distributions for 1989 and 2009 show how observed STH prevalence has gradually decreased over time. The model estimated that a total of 2.8 million school-age children live in districts which warrant mass treatment. Conclusions Bayesian space-time geostatistical models can be used to reliably estimate the combined observed prevalence of STH and suggest that a quarter of Kenyas school-aged children live in areas of high prevalence and warrant mass treatment. As control is successful in reducing infection levels, updated models can be used to refine decision making in helminth control.

Epidemiology of subpatent Plasmodium falciparum infection: implications for detection of hotspots with imperfect diagnostics

BackgroundAt the local level, malaria transmission clusters in hotspots, which may be a group of households that experience higher than average exposure to infectious mosquitoes. Active case detection often relying on rapid diagnostic tests for mass screen and treat campaigns has been proposed as a method to detect and treat individuals in hotspots. Data from a cross-sectional survey conducted in north-western Tanzania were used to examine the spatial distribution of Plasmodium falciparum and the relationship between household exposure and parasite density.MethodsDried blood spots were collected from consenting individuals from four villages during a survey conducted in 2010. These were analysed by PCR for the presence of P. falciparum, with the parasite density of positive samples being estimated by quantitative PCR. Household exposure was estimated using the distance-weighted PCR prevalence of infection. Parasite density simulations were used to estimate the proportion of infections that would be treated using a screen and treat approach with rapid diagnostic tests (RDT) compared to targeted mass drug administration (tMDA) and Mass Drug Administration (MDA).ResultsPolymerase chain reaction PCR analysis revealed that of the 3,057 blood samples analysed, 1,078 were positive. Mean distance-weighted PCR prevalence per household was 34.5%. Parasite density was negatively associated with transmission intensity with the odds of an infection being subpatent increasing with household exposure (OR 1.09 per 1% increase in exposure). Parasite density was also related to age, being highest in children five to ten years old and lowest in those > 40 years. Simulations of different tMDA strategies showed that treating all individuals in households where RDT prevalence was above 20% increased the number of infections that would have been treated from 43 to 55%. However, even with this strategy, 45% of infections remained untreated.ConclusionThe negative relationship between household exposure and parasite density suggests that DNA-based detection of parasites is needed to provide adequate sensitivity in hotspots. Targeting MDA only to households with RDT-positive individuals may allow a larger fraction of infections to be treated. These results suggest that community-wide MDA, instead of screen and treat strategies, may be needed to successfully treat the asymptomatic, subpatent parasite reservoir and reduce transmission in similar settings.

Reactive case detection for malaria elimination: real-life experience from an ongoing program in Swaziland.

As countries move towards malaria elimination, methods to identify infections among populations who do not seek treatment are required. Reactive case detection, whereby individuals living in close proximity to passively detected cases are screened and treated, is one approach being used by a number of countries including Swaziland. An outstanding issue is establishing the epidemiologically and operationally optimal screening radius around each passively detected index case. Using data collected between December 2009 and June 2012 from reactive case detection (RACD) activities in Swaziland, we evaluated the effect of screening radius and other risk factors on the probability of detecting cases by reactive case detection. Using satellite imagery, we also evaluated the household coverage achieved during reactive case detection. Over the study period, 250 cases triggered RACD, which identified a further 74 cases, showing the value of RACD over passive surveillance alone. Results suggest that the odds of detecting a case within the household of the index case were significantly higher than in neighbouring households (odds ratio (OR) 13, 95% CI 3.1–54.4). Furthermore, cases were more likely to be detected when RACD was conducted within a week of the index presenting at a health facility (OR 8.7, 95% CI 1.1–66.4) and if the index household had not been sprayed with insecticide (OR sprayed vs not sprayed 0.11, 95% CI 0.03–0.46). The large number of households missed during RACD indicates that a 1 km screening radius may be impractical in such resource limited settings such as Swaziland. Future RACD in Swaziland could be made more effective by achieving high coverage amongst individuals located near to index cases and in areas where spraying has not been conducted. As well as allowing the programme to implement RACD more rapidly, this would help to more precisely define the optimal screening radius.

Communicating and Monitoring Surveillance and Response Activities for Malaria Elimination: China's “1-3-7” Strategy

Qi Gao and colleagues describe Chinas 1-3-7 strategy for eliminating malaria: reporting of malaria cases within one day, their confirmation and investigation within three days, and the appropriate public health response to prevent further transmission within seven days.

Spatial parasite ecology and epidemiology: a review of methods and applications.

SUMMARY The distributions of parasitic diseases are determined by complex factors, including many that are distributed in space. A variety of statistical methods are now readily accessible to researchers providing opportunities for describing and ultimately understanding and predicting spatial distributions. This review provides an overview of the spatial statistical methods available to parasitologists, ecologists and epidemiologists and discusses how such methods have yielded new insights into the ecology and epidemiology of infection and disease. The review is structured according to the three major branches of spatial statistics: continuous spatial variation; discrete spatial variation; and spatial point processes.

Integrated Mapping of Neglected Tropical Diseases: Epidemiological Findings and Control Implications for Northern Bahr-el-Ghazal State, Southern Sudan

Background There are few detailed data on the geographic distribution of most neglected tropical diseases (NTDs) in post-conflict Southern Sudan. To guide intervention by the recently established national programme for integrated NTD control, we conducted an integrated prevalence survey for schistosomiasis, soil-transmitted helminth (STH) infection, lymphatic filariasis (LF), and loiasis in Northern Bahr-el-Ghazal State. Our aim was to establish which communities require mass drug administration (MDA) with preventive chemotherapy (PCT), rather than to provide precise estimates of infection prevalence. Methods and Findings The integrated survey design used anecdotal reports of LF and proximity to water bodies (for schistosomiasis) to guide selection of survey sites. In total, 86 communities were surveyed for schistosomiasis and STH; 43 of these were also surveyed for LF and loiasis. From these, 4834 urine samples were tested for blood in urine using Hemastix reagent strips, 4438 stool samples were analyzed using the Kato-Katz technique, and 5254 blood samples were tested for circulating Wuchereria bancrofti antigen using immunochromatographic card tests (ICT). 4461 individuals were interviewed regarding a history of ‘eye worm’ (a proxy measure for loiasis) and 31 village chiefs were interviewed regarding the presence of clinical manifestations of LF in their community. At the village level, prevalence of Schistosoma haematobium and S. mansoni ranged from 0 to 65.6% and from 0 to 9.3%, respectively. The main STH species was hookworm, ranging from 0 to 70% by village. Infection with LF and loiasis was extremely rare, with only four individuals testing positive or reporting symptoms, respectively. Questionnaire data on clinical signs of LF did not provide a reliable indication of endemicity. MDA intervention thresholds recommended by the World Health Organization were only exceeded for urinary schistosomiasis and hookworm in a few, yet distinct, communities. Conclusion This was the first attempt to use an integrated survey design for this group of infections and to generate detailed results to guide their control over a large area of Southern Sudan. The approach proved practical, but could be further simplified to reduce field work and costs. The results show that only a few areas need to be targeted with MDA of PCT, thus confirming the importance of detailed mapping for cost-effective control.

Optimal Survey Designs for Targeting Chemotherapy Against Soil-Transmitted Helminths: Effect of Spatial Heterogeneity and Cost-Efficiency of Sampling

Implementation of helminth control programs requires information on the distribution and prevalence of infection to target mass treatment to areas of greatest need. In the absence of data, the question of how many schools/communities should be surveyed depends on the spatial heterogeneity of infection and the cost efficiency of surveys. We used geostatistical techniques to quantify the spatial heterogeneity of soil-transmitted helminths in multiple settings in eastern Africa, and using the example of Kenya, conducted conditional simulation to explore the implications of alternative sampling strategies in identifying districts requiring mass treatment. Cost analysis is included in the simulations using data from actual field surveys and control programs. The analysis suggests that sampling four or five schools in each district provides a cost-efficient strategy in identifying districts requiring mass treatment, and that efficiency of sampling was relatively insensitive to the number of children sampled per school.

The performance of haematuria reagent strips for the rapid mapping of urinary schistosomiasis: field experience from Southern Sudan.

The implementation of programmes to control neglected tropical diseases (NTDs) requires up‐to‐date information on the prevalence and distribution of each NTD. This study evaluated the performance of reagent strip testing for haematuria to diagnose Schistosoma haematobium infection among school‐aged children in the context of a rapid mapping survey in Southern Sudan. The reagent strips were highly sensitive (97.8%) but only moderately specific (58.8%). The proportion of false positive diagnoses was significantly higher among girls than boys, especially among girls aged 5–10 years. These findings suggest that reagent strips alone are not sufficient for rapid mapping surveys. A two‐step approach is thus recommended whereby haematuria‐positive urine samples are subsequently examined using urine filtration.

Predicting malaria vector distribution under climate change scenarios in China: Challenges for malaria elimination

Projecting the distribution of malaria vectors under climate change is essential for planning integrated vector control activities for sustaining elimination and preventing reintroduction of malaria. In China, however, little knowledge exists on the possible effects of climate change on malaria vectors. Here we assess the potential impact of climate change on four dominant malaria vectors (An. dirus, An. minimus, An. lesteri and An. sinensis) using species distribution models for two future decades: the 2030 s and the 2050 s. Simulation-based estimates suggest that the environmentally suitable area (ESA) for An. dirus and An. minimus would increase by an average of 49% and 16%, respectively, under all three scenarios for the 2030 s, but decrease by 11% and 16%, respectively in the 2050 s. By contrast, an increase of 36% and 11%, respectively, in ESA of An. lesteri and An. sinensis, was estimated under medium stabilizing (RCP4.5) and very heavy (RCP8.5) emission scenarios. in the 2050 s. In total, we predict a substantial net increase in the population exposed to the four dominant malaria vectors in the decades of the 2030 s and 2050 s, considering land use changes and urbanization simultaneously. Strategies to achieve and sustain malaria elimination in China will need to account for these potential changes in vector distributions and receptivity.