Birgit Nikolay

Sensitivity of diagnostic tests for human soil-transmitted helminth infections: a meta-analysis in the absence of a true gold standard

Reliable, sensitive and practical diagnostic tests are an essential tool in disease control programmes for mapping, impact evaluation and surveillance. To provide a robust global assessment of the relative performance of available diagnostic tools for the detection of soil-transmitted helminths, we conducted a meta-analysis comparing the sensitivities and the quantitative performance of the most commonly used copro-microscopic diagnostic methods for soil-transmitted helminths, namely Kato-Katz, direct microscopy, formol-ether concentration, McMaster, FLOTAC and Mini-FLOTAC. In the absence of a perfect reference standard, we employed a Bayesian latent class analysis to estimate the true, unobserved sensitivity of compared diagnostic tests for each of the soil-transmitted helminth species Ascaris lumbricoides, Trichuris trichiura and the hookworms. To investigate the influence of varying transmission settings we subsequently stratified the analysis by intensity of infection. Overall, sensitivity estimates varied between the different methods, ranging from 42.8% for direct microscopy to 92.7% for FLOTAC. The widely used double slide Kato-Katz method had a sensitivity of 74-95% for the three soil-transmitted helminth species at high infection intensity, however sensitivity dropped to 53-80% in low intensity settings, being lowest for hookworm and A. lumbricoides. The highest sensitivity, overall and in both intensity groups, was observed for the FLOTAC method, whereas the sensitivity of the Mini-FLOTAC method was comparable with the Kato-Katz method. FLOTAC average egg count estimates were significantly lower compared with Kato-Katz, while the compared McMaster counts varied. In conclusion, we demonstrate that the Kato-Katz and Mini-FLOTAC methods had comparable sensitivities. We further show that test sensitivity of the Kato-Katz method is reduced in low transmission settings.

Monitoring and evaluating the impact of national school-based deworming in Kenya : study design and baseline results

BackgroundAn increasing number of countries in Africa and elsewhere are developing national plans for the control of neglected tropical diseases. A key component of such plans is school-based deworming (SBD) for the control of soil-transmitted helminths (STHs) and schistosomiasis. Monitoring and evaluation (M&E) of national programmes is essential to ensure they are achieving their stated aims and to evaluate when to reduce the frequency of treatment or when to halt it altogether. The article describes the M&E design of the Kenya national SBD programme and presents results from the baseline survey conducted in early 2012.MethodsThe M&E design involves a stratified series of pre- and post-intervention, repeat cross-sectional surveys in a representative sample of 200 schools (over 20,000 children) across Kenya. Schools were sampled based on previous knowledge of STH endemicity and were proportional to population size. Stool (and where relevant urine) samples were obtained for microscopic examination and in a subset of schools; finger-prick blood samples were collected to estimate haemoglobin concentration. Descriptive and spatial analyses were conducted. The evaluation measured both prevalence and intensity of infection.ResultsOverall, 32.4% of children were infected with at least one STH species, with Ascaris lumbricoides as the most common species detected. The overall prevalence of Schistosoma mansoni was 2.1%, while in the Coast Province the prevalence of S. haematobium was 14.8%. There was marked geographical variation in the prevalence of species infection at school, district and province levels. The prevalence of hookworm infection was highest in Western Province (25.1%), while A. lumbricoides and T. trichiura prevalence was highest in the Rift Valley (27.1% and 11.9%). The lowest prevalence was observed in the Rift Valley for hookworm (3.5%), in the Coast for A. lumbricoides (1.0%), and in Nyanza for T. trichiura (3.6%). The prevalence of S. mansoni was most common in Western Province (4.1%).ConclusionsThe current findings are consistent with the known spatial ecology of STH and schistosome infections and provide an important empirical basis on which to evaluate the impact of regular mass treatment through the school system in Kenya.

A review of West Nile and Usutu virus co-circulation in Europe: how much do transmission cycles overlap?

Due to the increasing global spread of arboviruses, the geographic extent of virus co-circulation is expanding. This complicates the diagnosis of febrile conditions and can have direct effects on the epidemiology. As previously demonstrated, subsequent infections by two closely related viruses, such as those belonging to the Japanese encephalitis virus (JEV) serocomplex, can lead to partial or complete cross-immunity, altering the risk of infections or the outcome of disease. Two flaviviruses that may interact at population level are West Nile virus (WNV) and Usutu virus (USUV). These pathogens have antigenic cross-reactivity and affect human and animal populations throughout Europe. This systematic review investigates the overlap of WNV and USUV transmission cycles, not only geographically but also in terms of host and vector ranges. Co-circulation of WNV and USUV was reported in 10 countries and the viruses were found to infect 34 common bird species belonging to 11 orders. Moreover, four mosquito species are potential vectors for both viruses. Taken together, these data suggest that WNV and USUV transmission overlaps substantially in Europe and highlight the importance of further studies investigating the interactions between the two viruses within host and vector populations.

Global feasibility assessment of interrupting the transmission of soil-transmitted helminths: a statistical modelling study

BACKGROUND Emphasis is being given to the control of neglected tropical diseases, including the possibility of interrupting the transmission of soil-transmitted helminths (STH). We evaluated the feasibility by country of achieving interruption of the transmission of STH. METHODS Based on a conceptual framework for the identification of the characteristics of a successful STH control programme, we assembled spatial data for a range of epidemiological, institutional, economic, and political factors. Using four different statistical methods, we developed a composite score of the feasibility of interrupting STH transmission and undertook a sensitivity analysis of the data and methods. FINDINGS The most important determining factors in the analysis were underlying intensity of STH transmission, current implementation of control programmes for neglected tropical diseases, and whether countries receive large-scale external funding and have strong health systems. The composite scores suggested that interrupting STH transmission is most feasible in countries in the Americas and parts of Asia (eg, Argentina [range of composite feasibility scores, depending on scoring method, 9·4-10·0], Brazil [8·7- 9·7], Chile [8·84-10·0], and Thailand [9·1-10·0]; there was perfect agreement between the four methods), and least feasible in countries in sub-Saharan Africa (eg, Congo [0·4-2·7] and Guinea [2·0-5·6]; there was full agreement between methods), but there were important exceptions to these trends (eg, Ghana [7·4-10·0]; there was agreement between three methods). Agreement was highest between the scores derived with the expert opinion and principal component analysis weighting schemes (Pearson correlation coefficient, r=0·98). The largest disagreement was between benefit-of-the-doubt-derived and principal-component-analysis-derived weighting schemes (r=0·74). INTERPRETATION The interruption of STH transmission is feasible, especially in countries with low intensity of transmission, supportive household environments, strong health systems, and the availability of suitable delivery platforms and in-country funds, but to achieve local elimination of STH an intersectoral approach to STH control will be needed. FUNDING Bill & Melinda Gates Foundation and Wellcome Trust.

Vector Competence of Culex neavei (Diptera: Culicidae) for Usutu Virus

Usutu virus (USUV), a flavivirus belonging to the Japanese encephalitis serocomplex, was isolated for the first time from a Culex neavei mosquito in 1959 in South Africa. Despite multiple isolations of USUV from Cx. neavei in Africa, its vector competence remains unproven. Therefore, we infected Cx. neavei orally with the USUV reference strain and used reverse transcription-polymerase chain reaction and an indirect immunofluorescence assay to detect virus in bodies, legs, wings, and saliva of mosquitoes. We demonstrated the susceptibility of Cx. neavei mosquitoes for the USUV reference strain, its potential to be transmitted, and infection, dissemination, and transmission rates of 90.9%, 40.0%, and 81.3%, respectively. Also, we showed that infection rates are dependent on the virus titer of the blood meal. Given the bionomics of Cx. neavei, its role as enzootic vector for USUV in Africa in a mosquito-bird transmission cycle or as bridge vector for USUV transmission to humans is discussed.

Interrupting transmission of soil-transmitted helminths: a study protocol for cluster randomised trials evaluating alternative treatment strategies and delivery systems in Kenya.

Introduction In recent years, an unprecedented emphasis has been given to the control of neglected tropical diseases, including soil-transmitted helminths (STHs). The mainstay of STH control is school-based deworming (SBD), but mathematical modelling has shown that in all but very low transmission settings, SBD is unlikely to interrupt transmission, and that new treatment strategies are required. This study seeks to answer the question: is it possible to interrupt the transmission of STH, and, if so, what is the most cost-effective treatment strategy and delivery system to achieve this goal? Methods and analysis Two cluster randomised trials are being implemented in contrasting settings in Kenya. The interventions are annual mass anthelmintic treatment delivered to preschool- and school-aged children, as part of a national SBD programme, or to entire communities, delivered by community health workers. Allocation to study group is by cluster, using predefined units used in public health provision—termed community units (CUs). CUs are randomised to one of three groups: receiving either (1) annual SBD; (2) annual community-based deworming (CBD); or (3) biannual CBD. The primary outcome measure is the prevalence of hookworm infection, assessed by four cross-sectional surveys. Secondary outcomes are prevalence of Ascaris lumbricoides and Trichuris trichiura, intensity of species infections and treatment coverage. Costs and cost-effectiveness will be evaluated. Among a random subsample of participants, worm burden and proportion of unfertilised eggs will be assessed longitudinally. A nested process evaluation, using semistructured interviews, focus group discussions and a stakeholder analysis, will investigate the community acceptability, feasibility and scale-up of each delivery system. Ethics and dissemination Study protocols have been reviewed and approved by the ethics committees of the Kenya Medical Research Institute and National Ethics Review Committee, and London School of Hygiene and Tropical Medicine. The study has a dedicated web site. Trial registration number NCT02397772.

Associations between school- and household-level water, sanitation and hygiene conditions and soil-transmitted helminth infection among Kenyan school children

BackgroundSoil-transmitted helminths, a class of parasitic intestinal worms, are pervasive in many low-income settings. Infection among children can lead to poor nutritional outcomes, anaemia, and reduced cognition. Mass treatment, typically administered through schools, with yearly or biannual drugs is inexpensive and can reduce worm burden, but reinfection can occur rapidly. Access to and use of sanitation facilities and proper hygiene can reduce infection, but rigorous data are scarce. Among school-age children, infection can occur at home or at school, but little is known about the relative importance of WASH in transmission in these two settings.MethodsWe explored the relationships between school and household water, sanitation, and hygiene conditions and behaviours during the baseline of a large-scale mass drug administration programme in Kenya. We assessed several WASH measures to quantify the exposure of school children, and developed theory and empirically-based parsimonious models.ResultsResults suggest mixed impacts of household and school WASH on prevalence and intensity of infection. WASH risk factors differed across individual worm species, which is expected given the different mechanisms of infection.ConclusionsNo trend of the relative importance of school versus household-level WASH emerged, though some factors, like water supply were more strongly related to lower infection, which suggests it is important in supporting other school practices, such as hand-washing and keeping school toilets clean.

Modelling the distribution and transmission intensity of lymphatic filariasis in sub-Saharan Africa prior to scaling up interventions: integrated use of geostatistical and mathematical modelling

BackgroundLymphatic filariasis (LF) is one of the neglected tropical diseases targeted for global elimination. The ability to interrupt transmission is, partly, influenced by the underlying intensity of transmission and its geographical variation. This information can also help guide the design of targeted surveillance activities. The present study uses a combination of geostatistical and mathematical modelling to predict the prevalence and transmission intensity of LF prior to the implementation of large-scale control in sub-Saharan Africa.MethodsA systematic search of the literature was undertaken to identify surveys on the prevalence of Wuchereria bancrofti microfilaraemia (mf), based on blood smears, and on the prevalence of antigenaemia, based on the use of an immuno-chromatographic card test (ICT). Using a suite of environmental and demographic data, spatiotemporal multivariate models were fitted separately for mf prevalence and ICT-based prevalence within a Bayesian framework and used to make predictions for non-sampled areas. Maps of the dominant vector species of LF were also developed. The maps of predicted prevalence and vector distribution were linked to mathematical models of the transmission dynamics of LF to infer the intensity of transmission, quantified by the basic reproductive number (R0).ResultsThe literature search identified 1267 surveys that provide suitable data on the prevalence of mf and 2817 surveys that report the prevalence of antigenaemia. Distinct spatial predictions arose from the models for mf prevalence and ICT-based prevalence, with a wider geographical distribution when using ICT-based data. The vector distribution maps demonstrated the spatial variation of LF vector species. Mathematical modelling showed that the reproduction number (R0) estimates vary from 2.7 to 30, with large variations between and within regions.ConclusionsLF transmission is highly heterogeneous, and the developed maps can help guide intervention, monitoring and surveillance strategies as countries progress towards LF elimination.

Understanding Heterogeneity in the Impact of National Neglected Tropical Disease Control Programmes: Evidence from School-Based Deworming in Kenya

Background The implementation of soil-transmitted helminth (STH) treatment programmes occurs in varied environmental, social and economic contexts. Programme impact will be influenced by factors that affect the reduction in the prevalence and intensity of infections following treatment, as well as the subsequent rate of reinfection. To better understand the heterogeneity of programme impact and its underlying reasons, we investigated the influence of contextual factors on reduction in STH infection as part of the national school based deworming (SBD) programme in Kenya. Materials and Methods Data on the prevalence and intensity of infection were collected within the monitoring and evaluation component of the SBD programme at baseline and after delivery of two annual treatment rounds in 153 schools in western Kenya. Using a framework that considers STH epidemiology and transmission dynamics, capacity to deliver treatment, operational feasibility and financial capacity, data were assembled at both school and district (county) levels. Geographic heterogeneity of programme impact was assessed by descriptive and spatial analyses. Factors associated with absolute reductions of Ascaris lumbricoides and hookworm infection prevalence and intensity were identified using mixed effects linear regression modelling adjusting for baseline infection levels. Principal Findings The reduction in prevalence and intensity of A. lumbricoides and hookworms varied significantly by county and within counties by school. Multivariable analysis of factors associated with programme impact showed that absolute A. lumbricoides reductions varied by environmental conditions and access to improved sanitation at schools or within the community. Larger reduction in prevalence and intensity of hookworms were found in schools located within areas with higher community level access to improved sanitation and within counties with higher economic and health service delivery indicator scores. Conclusions The study identifies factors associated with the impact of school-based deworming and in particular highlights how access to water, sanitation and hygiene and environmental conditions influence the impact of deworming programmes.

Socioeconomic and environmental determinants of dengue transmission in an urban setting: An ecological study in Nouméa, New Caledonia

Background Dengue is a mosquito-borne virus that causes extensive morbidity and economic loss in many tropical and subtropical regions of the world. Often present in cities, dengue virus is rapidly spreading due to urbanization, climate change and increased human movements. Dengue cases are often heterogeneously distributed throughout cities, suggesting that small-scale determinants influence dengue urban transmission. A better understanding of these determinants is crucial to efficiently target prevention measures such as vector control and education. The aim of this study was to determine which socioeconomic and environmental determinants were associated with dengue incidence in an urban setting in the Pacific. Methodology An ecological study was performed using data summarized by neighborhood (i.e. the neighborhood is the unit of analysis) from two dengue epidemics (2008–2009 and 2012–2013) in the city of Nouméa, the capital of New Caledonia. Spatial patterns and hotspots of dengue transmission were assessed using global and local Moran’s I statistics. Multivariable negative binomial regression models were used to investigate the association between dengue incidence and various socioeconomic and environmental factors throughout the city. Principal findings The 2008–2009 epidemic was spatially structured, with clusters of high and low incidence neighborhoods. In 2012–2013, dengue incidence rates were more homogeneous throughout the city. In all models tested, higher dengue incidence rates were consistently associated with lower socioeconomic status (higher unemployment, lower revenue or higher percentage of population born in the Pacific, which are interrelated). A higher percentage of apartments was associated with lower dengue incidence rates during both epidemics in all models but one. A link between vegetation coverage and dengue incidence rates was also detected, but the link varied depending on the model used. Conclusions This study demonstrates a robust spatial association between dengue incidence rates and socioeconomic status across the different neighborhoods of the city of Nouméa. Our findings provide useful information to guide policy and help target dengue prevention efforts where they are needed most.