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1.  Diagnostic Accuracy and Cost-Effectiveness of Alternative Methods for Detection of Soil-Transmitted Helminths in a Post-Treatment Setting in Western Kenya 
Objectives
This study evaluates the diagnostic accuracy and cost-effectiveness of the Kato-Katz and Mini-FLOTAC methods for detection of soil-transmitted helminths (STH) in a post-treatment setting in western Kenya. A cost analysis also explores the cost implications of collecting samples during school surveys when compared to household surveys.
Methods
Stool samples were collected from children (n = 652) attending 18 schools in Bungoma County and diagnosed by the Kato-Katz and Mini-FLOTAC coprological methods. Sensitivity and additional diagnostic performance measures were analyzed using Bayesian latent class modeling. Financial and economic costs were calculated for all survey and diagnostic activities, and cost per child tested, cost per case detected and cost per STH infection correctly classified were estimated. A sensitivity analysis was conducted to assess the impact of various survey parameters on cost estimates.
Results
Both diagnostic methods exhibited comparable sensitivity for detection of any STH species over single and consecutive day sampling: 52.0% for single day Kato-Katz; 49.1% for single-day Mini-FLOTAC; 76.9% for consecutive day Kato-Katz; and 74.1% for consecutive day Mini-FLOTAC. Diagnostic performance did not differ significantly between methods for the different STH species. Use of Kato-Katz with school-based sampling was the lowest cost scenario for cost per child tested ($10.14) and cost per case correctly classified ($12.84). Cost per case detected was lowest for Kato-Katz used in community-based sampling ($128.24). Sensitivity analysis revealed the cost of case detection for any STH decreased non-linearly as prevalence rates increased and was influenced by the number of samples collected.
Conclusions
The Kato-Katz method was comparable in diagnostic sensitivity to the Mini-FLOTAC method, but afforded greater cost-effectiveness. Future work is required to evaluate the cost-effectiveness of STH surveillance in different settings.
Author Summary
Accurate methods of diagnosis and optimal strategies to sample the population are essential for the reliable mapping and surveillance of infectious diseases. The current standard for detection of soil-transmitted helminths (STH) entails use of the Kato-Katz diagnostic method. Alternative diagnostic methods, such as flotation techniques like the Mini-FLOTAC, have been developed with hopes of achieving greater sensitivity and ease of use. Here, we evaluate the diagnostic accuracy of the Kato-Katz method and the Mini-FLOTAC method for detecting STH infection. We use Bayesian latent class modeling to calculate the diagnostic accuracy in the absence of a gold-standard method for STH detection. Stool samples were collected from school-age children using school-based and community-based sampling. We present cost estimates for use of the Kato-Katz and Mini-FLOTAC diagnostic methods in combination with both sampling methods, providing cost data for the various survey scenarios. Sensitivity was comparable between the Kato-Katz and Mini-FLOTAC methods for detection of any STH species over a single day (Kato Katz: 52.0%, Mini-FLOTAC: 49.1%) and consecutive days (Kato-Katz: 76.9%, Mini-FLOTAC: 74.1%). Costs were lowest in scenarios using the Kato-Katz method; cost per child tested and cost per case correctly classified for school-based sampling with the Kato-Katz diagnostic were $10.14 and $12.84 respectively. The lowest cost per case detected was $128.24 with community-based sampling and use of Kato-Katz. Further work is required on the cost-effectiveness of diagnostic and sampling methods for STH surveys and surveillance of other neglected tropical diseases (NTDs) in various settings. To this end, we provide the model code used in the diagnostic analysis and a costing template for STH surveys.
doi:10.1371/journal.pntd.0002843
PMCID: PMC4014443  PMID: 24810593
2.  Geographical Inequalities in Use of Improved Drinking Water Supply and Sanitation across Sub-Saharan Africa: Mapping and Spatial Analysis of Cross-sectional Survey Data 
PLoS Medicine  2014;11(4):e1001626.
Using cross-sectional survey data, Rachel Pullan and colleagues map geographical inequalities in use of improved drinking water supply and sanitation across sub-Saharan Africa.
Please see later in the article for the Editors' Summary
Background
Understanding geographic inequalities in coverage of drinking-water supply and sanitation (WSS) will help track progress towards universal coverage of water and sanitation by identifying marginalized populations, thus helping to control a large number of infectious diseases. This paper uses household survey data to develop comprehensive maps of WSS coverage at high spatial resolution for sub-Saharan Africa (SSA). Analysis is extended to investigate geographic heterogeneity and relative geographic inequality within countries.
Methods and Findings
Cluster-level data on household reported use of improved drinking-water supply, sanitation, and open defecation were abstracted from 138 national surveys undertaken from 1991–2012 in 41 countries. Spatially explicit logistic regression models were developed and fitted within a Bayesian framework, and used to predict coverage at the second administrative level (admin2, e.g., district) across SSA for 2012. Results reveal substantial geographical inequalities in predicted use of water and sanitation that exceed urban-rural disparities. The average range in coverage seen between admin2 within countries was 55% for improved drinking water, 54% for use of improved sanitation, and 59% for dependence upon open defecation. There was also some evidence that countries with higher levels of inequality relative to coverage in use of an improved drinking-water source also experienced higher levels of inequality in use of improved sanitation (rural populations r = 0.47, p = 0.002; urban populations r = 0.39, p = 0.01). Results are limited by the quantity of WSS data available, which varies considerably by country, and by the reliability and utility of available indicators.
Conclusions
This study identifies important geographic inequalities in use of WSS previously hidden within national statistics, confirming the necessity for targeted policies and metrics that reach the most marginalized populations. The presented maps and analysis approach can provide a mechanism for monitoring future reductions in inequality within countries, reflecting priorities of the post-2015 development agenda.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Access to a safe drinking-water supply (a water source that is protected from contamination) and to adequate sanitation facilities (toilets, improved latrines, and other facilities that prevent people coming into contact with human urine and feces) is essential for good health. Unimproved drinking-water sources and sanitation are responsible for 85% of deaths from diarrhea and 1% of the global burden of disease. They also increase the transmission of parasitic worms and other neglected tropical diseases. In 2000, world leaders set a target of reducing the proportion of the global population without access to safe drinking water and basic sanitation to half of the 1990 level by 2015 as part of Millennium Development Goal (MDG) 7 (“Ensure environmental sustainability”; the MDGs are designed to improve the social, economic, and health conditions in the world's poorest countries). Between 1990 and 2010, more than 2 billion people gained access to improved drinking-water sources and 1.8 billion gained access to improved sanitation. In 2011, 89% of the world's population had access to an improved drinking-water supply, 1% above the MDG target, and 64% had access to improved sanitation (the MDG target is 75%).
Why Was This Study Done?
Despite these encouraging figures, the WHO/UNICEF Joint Monitoring Programme for Water Supply and Sanitation (JMP) estimates that, globally, 768 million people relied on unimproved drinking-water sources, 2.5 billion people did not use an improved sanitation facility, and more than 1 billion people (15% of the global population) were defecating in the open in 2011. The JMP estimates for 2011 also reveal national and sub-national inequalities in drinking-water supply and sanitation coverage but a better understanding of geographic inequalities is needed to track progress towards universal coverage of access to improved water and sanitation and to identify the populations that need the most help to achieve this goal. Here, the researchers use cross-sectional household survey data and modern statistical approaches to produce a comprehensive map of the coverage of improved drinking-water supply and improved sanitation at high spatial resolution for sub-Saharan Africa and to investigate geographic inequalities in coverage. Cross-sectional household surveys collect health and other information from households at a single time-point, including data on use of safe water and improved sanitation.
What Did the Researchers Do and Find?
The researchers extracted data on reported household use of an improved drinking-water supply (for example, a piped water supply), improved sanitation facilities (for example, a flushing toilet), and open defecation from 138 national household surveys undertaken between 1991 and 2012 in 41 countries in sub-Saharan Africa. They developed statistical models to fit these data and used the models to estimate coverage at the district (second administrative) level across sub-Saharan Africa for 2012. For ten countries, the estimated coverage of access to improved drinking water at the district level within individual countries ranged from less than 25% to more than 75%. Within-country ranges of a similar magnitude were estimated for coverage of access to improved sanitation (21 countries) and for open defecation (16 countries). Notably, rural households in the districts with the lowest coverage of access to improved water supply and sanitation within a country were 1.5–8 times less likely to access improved drinking water, 2–18 times less likely to access improved sanitation, and 2–80 times more likely to defecate in the open than rural households in districts with the best coverage. Finally, countries with high levels of inequality in improved drinking-water source coverage also experienced high levels of inequality in improved sanitation coverage.
What Do These Findings Mean?
These findings identify important geographic inequalities in the coverage of access to improved water sources and sanitation that were previously hidden within national statistics. The accuracy of these findings depends on the accuracy of the data on water supplies and sanitation provided by household surveys, on the researchers' definitions for improved water supplies and sanitation, and on their statistical methods. Nevertheless, these findings confirm that, to achieve universal coverage of access to improved drinking-water sources and sanitation, strategies that target the areas with the lowest coverage are essential. Moreover, the maps and the analytical approach presented here provide the means for monitoring future reductions in inequalities in the coverage of access to improved water sources and sanitation and thus reflect a major priority of the post-2015 development agenda.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001626.
A PLOS Medicine Collection on water and sanitation is available
The World Health Organization (WHO) provides information on water, sanitation, and health (in several languages)
The WHO/UNICEF Joint Monitoring Programme for Water Supply and Sanitation is the official United Nations mechanism tasked with monitoring progress toward MDG7, Target 7B; the JMP 2013 update report is available online (also available in French and Spanish through the JMP website)
The sub-national predictions resulting from this study and the final sub-national maps are available as a resource for researchers and planners
doi:10.1371/journal.pmed.1001626
PMCID: PMC3979660  PMID: 24714528
3.  Impact of Intermittent Preventive Treatment With Dihydroartemisinin-Piperaquine on Malaria in Ugandan Schoolchildren: A Randomized, Placebo-Controlled Trial 
Dihydroartemisinin-piperaquine administered at monthly intervals, but not that dosed once a school term, is a remarkably effective measure for the prevention of incidence of malaria, prevalence of parasitemia, and prevalence of anemia in schoolchildren living in a high-transmission setting.
Background. Intermittent preventive treatment (IPT) in schoolchildren offers a promising option for malaria control. However, the optimal drug and dosing regimens for IPT remain to be determined.
Methods. We conducted a randomized, double-blind, placebo-controlled trial in 740 schoolchildren aged 6–14 years living in a setting of high malaria transmission in Uganda. Enrolled children were randomized to dihydroartemisinin-piperaquine (DP) given once a month (IPTm), DP given once a school term (4 treatments over 12 months, IPTst), or placebo and followed for 12 months. The primary outcome was the incidence of malaria over 12 months. Secondary outcomes included parasite prevalence and anemia over 12 months. Analyses were conducted on an intention-to-treat basis.
Results. In the placebo arm, the incidence of malaria was 0.34 episodes per person-year and the prevalence of parasitemia and anemia was 38% and 20%, respectively. IPTm reduced the incidence of malaria by 96% (95% confidence interval [CI], 88%–99%, P < .0001), the prevalence of asymptomatic parasitemia by 94% (95% CI, 92%–96%, P < .0001), and the prevalence of anemia by 40% (95% CI, 19%–56%, P < .0001). IPTst had no significant effect on the incidence of symptomatic malaria or the prevalence of anemia, but reduced the prevalence of asymptomatic parasitemia by 54% (95% CI, 47%–60%, P < .0001).
Conclusions. Monthly IPT with DP offered remarkable protection against clinical malaria, parasitemia, and anemia in schoolchildren living in a high-malaria-transmission setting.
Clinical Trials Registration.  NCT01231880.
doi:10.1093/cid/ciu150
PMCID: PMC4001293  PMID: 24621953
malaria; intermittent preventive treatment; schoolchildren
4.  Impact of Intermittent Screening and Treatment for Malaria among School Children in Kenya: A Cluster Randomised Trial 
PLoS Medicine  2014;11(1):e1001594.
Katherine Halliday and colleagues conducted a cluster randomized controlled trial in Kenyan school children in an area of low to moderate malaria transmission to investigate the effect of intermittent screening and treatment of malaria on health and education.
Please see later in the article for the Editors' Summary
Background
Improving the health of school-aged children can yield substantial benefits for cognitive development and educational achievement. However, there is limited experimental evidence of the benefits of alternative school-based malaria interventions or how the impacts of interventions vary according to intensity of malaria transmission. We investigated the effect of intermittent screening and treatment (IST) for malaria on the health and education of school children in an area of low to moderate malaria transmission.
Methods and Findings
A cluster randomised trial was implemented with 5,233 children in 101 government primary schools on the south coast of Kenya in 2010–2012. The intervention was delivered to children randomly selected from classes 1 and 5 who were followed up for 24 months. Once a school term, children were screened by public health workers using malaria rapid diagnostic tests (RDTs), and children (with or without malaria symptoms) found to be RDT-positive were treated with a six dose regimen of artemether-lumefantrine (AL). Given the nature of the intervention, the trial was not blinded. The primary outcomes were anaemia and sustained attention. Secondary outcomes were malaria parasitaemia and educational achievement. Data were analysed on an intention-to-treat basis.
During the intervention period, an average of 88.3% children in intervention schools were screened at each round, of whom 17.5% were RDT-positive. 80.3% of children in the control and 80.2% in the intervention group were followed-up at 24 months. No impact of the malaria IST intervention was observed for prevalence of anaemia at either 12 or 24 months (adjusted risk ratio [Adj.RR]: 1.03, 95% CI 0.93–1.13, p = 0.621 and Adj.RR: 1.00, 95% CI 0.90–1.11, p = 0.953) respectively, or on prevalence of P. falciparum infection or scores of classroom attention. No effect of IST was observed on educational achievement in the older class, but an apparent negative effect was seen on spelling scores in the younger class at 9 and 24 months and on arithmetic scores at 24 months.
Conclusion
In this setting in Kenya, IST as implemented in this study is not effective in improving the health or education of school children. Possible reasons for the absence of an impact are the marked geographical heterogeneity in transmission, the rapid rate of reinfection following AL treatment, the variable reliability of RDTs, and the relative contribution of malaria to the aetiology of anaemia in this setting.
Trial registration
www.ClinicalTrials.gov NCT00878007
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, more than 200 million cases of malaria occur worldwide and more than 600,000 people, mostly children living in sub-Saharan Africa, die from this mosquito-borne parasitic infection. Malaria can be prevented by controlling the night-biting mosquitoes that transmit Plasmodium parasites and by sleeping under insecticide-treated nets to avoid mosquito bites. Infection with malaria parasites causes recurring flu-like symptoms and needs to be treated promptly with antimalarial drugs to prevent the development of anaemia (a reduction in red blood cell numbers) and potentially fatal damage to the brain and other organs. Treatment also reduces malaria transmission. In 1998, the World Health Organization and several other international bodies established the Roll Back Malaria Partnership to provide a coordinated global approach to fighting malaria. In 2008, the Partnership launched its Global Malaria Action Plan, which aims to control malaria to reduce the current burden, to eliminate malaria over time country by country, and, ultimately, to eradicate malaria.
Why Was This Study Done?
In recent years, many malaria-endemic countries (countries where malaria is always present) have implemented successful malaria control programs and reduced malaria transmission levels. In these countries, immunity to malaria is now acquired more slowly than in the past, the burden of clinical malaria is shifting from very young children to older children, and infection rates with malaria parasites are now highest among school-aged children. Chronic untreated Plasmodium infection, even when it does not cause symptoms, can negatively affect children's health, cognitive development (the acquisition of thinking skills), and educational achievement. However, little is known about how school-based malaria interventions affect the health of children or their educational outcomes. In this cluster randomized trial, the researchers investigate the effect of intermittent screening and treatment (IST) of malaria on the health and education of school children in a rural area of southern Kenya with low-to-moderate malaria transmission. Cluster randomized trials compare the outcomes of groups (“clusters”) of people randomly assigned to receive alternative interventions. IST of malaria involves periodical screening of individuals for Plasmodium infection followed by treatment of everyone who is infected, including people without symptoms, with antimalarial drugs.
What Did the Researchers Do and Find?
The researchers enrolled more than 5,000 children aged between 5 and 20 years from 101 government primary schools in Kenya into their 24-month study. Half the schools were randomly selected to receive the IST intervention (screening once a school term for infection with a malaria parasite with a rapid diagnostic test [RDT] and treatment of all RDT-positive children, with or without malaria symptoms, with six doses of artemether-lumefantrine), which was delivered to randomly selected children from classes 1 and 5 (which contained younger and older children, respectively). During the study, 17.5% of the children in the intervention schools were RDT-positive at screening on average. The prevalences of anaemia and parasitemia (the proportion of children with anaemia and the proportion who were RDT-positive, respectively) were similar in the intervention and control groups at the 12-month and 24-month follow-up and there was no difference between the two groups in classroom attention scores at the 9-month and 24-month follow-up. The IST intervention also had no effect on educational achievement in the older class but, unexpectedly, appeared to have a negative effect on spelling and arithmetic scores in the younger class.
What Do These Findings Mean?
These findings indicate that, in this setting in Kenya, IST as implemented in this study provided no health or education benefits to school children. The finding that the educational achievement of younger children was lower in the intervention group than in the control group may be a chance finding or may indicate that apprehension about the finger prick needed to take blood for the RDT had a negative effect on the performance of younger children during educational tests. The researchers suggest that their failure to demonstrate that the school-based IST intervention they tested had any long-lasting health or education benefits may be because, in a low-to-moderate malaria transmission setting, most of the children screened did not require treatment and those who did lived in focal high transmission regions, where rapid re-infection occurred between screening rounds. Importantly, however, these findings suggest that school screening using RDT could be an efficient way to identify transmission hotspots in communities that should be targeted for malaria control interventions.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001594.
This study is further discussed in a PLOS Medicine Perspective by Lorenz von Seidlein
Information is available fro m the World Health Organization on malaria (in several languages); the 2012 World Malaria Report provides details of the current global malaria situation
The US Centers for Disease Control and Prevention provide information on malaria (in English and Spanish), including a selection of personal stories about children with malaria
Information is available from the Roll Back Malaria Partnership on the global control of malaria and on the Global Malaria Action Plan (in English and French); its website includes a fact sheet about malaria in Kenya
MedlinePlus provides links to additional information on malaria (in English and Spanish)
More information about this trial is available
More information about malaria control in schools is provided in the toolkit
doi:10.1371/journal.pmed.1001594
PMCID: PMC3904819  PMID: 24492859
5.  Global numbers of infection and disease burden of soil transmitted helminth infections in 2010 
Parasites & Vectors  2014;7:37.
Background
Quantifying the burden of parasitic diseases in relation to other diseases and injuries requires reliable estimates of prevalence for each disease and an analytic framework within which to estimate attributable morbidity and mortality. Here we use data included in the Global Atlas of Helminth Infection to derive new global estimates of numbers infected with intestinal nematodes (soil-transmitted helminths, STH: Ascaris lumbricoides, Trichuris trichiura and the hookworms) and use disability-adjusted life years (DALYs) to estimate disease burden.
Methods
Prevalence data for 6,091 locations in 118 countries were sourced and used to estimate age-stratified mean prevalence for sub-national administrative units via a combination of model-based geostatistics (for sub-Saharan Africa) and empirical approaches (for all other regions). Geographical variation in infection prevalence within these units was approximated using modelled logit-normal distributions, and numbers of individuals with infection intensities above given thresholds estimated for each species using negative binomial distributions and age-specific worm/egg burden thresholds. Finally, age-stratified prevalence estimates for each level of infection intensity were incorporated into the Global Burden of Disease Study 2010 analytic framework to estimate the global burden of morbidity and mortality associated with each STH infection.
Results
Globally, an estimated 438.9 million people (95% Credible Interval (CI), 406.3 - 480.2 million) were infected with hookworm in 2010, 819.0 million (95% CI, 771.7 – 891.6 million) with A. lumbricoides and 464.6 million (95% CI, 429.6 – 508.0 million) with T. trichiura. Of the 4.98 million years lived with disability (YLDs) attributable to STH, 65% were attributable to hookworm, 22% to A. lumbricoides and the remaining 13% to T. trichiura. The vast majority of STH infections (67%) and YLDs (68%) occurred in Asia. When considering YLDs relative to total populations at risk however, the burden distribution varied more considerably within major global regions than between them.
Conclusion
Improvements in the cartography of helminth infection, combined with mathematical modelling approaches, have resulted in the most comprehensive contemporary estimates for the public health burden of STH. These numbers form an important benchmark upon which to evaluate future scale-up of major control efforts.
doi:10.1186/1756-3305-7-37
PMCID: PMC3905661  PMID: 24447578
Soil-transmitted helminths; Ascaris lumbricoides; Trichuris trichiura; Hookworm; Disease burden; Disability-adjusted life years
6.  Clinical Epidemiology, Diagnosis and Treatment of Visceral Leishmaniasis in the Pokot Endemic Area of Uganda and Kenya 
Between 2000 and 2010, Médecins Sans Frontières diagnosed and treated 4,831 patients with visceral leishmaniasis (VL) in the Pokot region straddling the border between Uganda and Kenya. A retrospective analysis of routinely collected clinical data showed no marked seasonal or annual fluctuations. Males between 5 and 14 years of age were the most affected group. Marked splenomegaly and anemia were striking features. An rK39 antigen-based rapid diagnostic test was evaluated and found sufficiently accurate to replace the direct agglutination test and spleen aspiration as the first-line diagnostic procedure. The case-fatality rate with sodium stibogluconate as first-line treatment was low. The VL relapses were rare and often diagnosed more than 6 months post-treatment. Post-kala-azar dermal leishmaniasis was rare but likely to be underdiagnosed. The epidemiological and clinical features of VL in the Pokot area differed markedly from VL in Sudan, the main endemic focus in Africa.
doi:10.4269/ajtmh.13-0150
PMCID: PMC3886423  PMID: 24218406
8.  Rates and intensity of re-infection with human helminths after treatment and the influence of individual, household, and environmental factors in a Brazilian community 
Parasitology  2011;138(11):10.1017/S0031182011001132.
SUMMARY
This study quantifies the rate and intensity of re-infection with human hookworm and Schistosoma mansoni infection 12 months following successful treatment, and investigates the influence of socio-economic, geographical and environmental factors. A longitudinal study of 642 individuals aged over 5 years was conducted in Minas Gerais State, Brazil from June 2004 to March 2006. Risk factors were assessed using interval censored regression for the rate and negative binomial regression for intensity. The crude rate and intensity of hookworm re-infection was 0·21 per year (95% confidence interval (CI) 0·15–0·29) and 70·9 epg (95% CI 47·2–106·6). For S. mansoni the rate was 0·06 per year (95% CI 0·03–0·10) and intensity 6·51 epg (95% CI 3·82–11·11). Rate and intensity of re-infection with hookworm were highest among males and positively associated with previous infection status, absence of a toilet and house structure. Rate and intensity of S. mansoni re-infection were associated with previous infection status as well as geographical, environmental and socio-economic factors. The implications of findings for the design of anti-helminth vaccine trials are discussed.
doi:10.1017/S0031182011001132
PMCID: PMC3827741  PMID: 21819640
Necator americanus; hookworm; Schistosoma mansoni; risk factors; re-infection; negative binomial
9.  Reliability of School Surveys in Estimating Geographic Variation in Malaria Transmission in the Western Kenyan Highlands 
PLoS ONE  2013;8(10):e77641.
Background
School surveys provide an operational approach to assess malaria transmission through parasite prevalence. There is limited evidence on the comparability of prevalence estimates obtained from school and community surveys carried out at the same locality.
Methods
Concurrent school and community cross-sectional surveys were conducted in 46 school/community clusters in the western Kenyan highlands and households of school children were geolocated. Malaria was assessed by rapid diagnostic test (RDT) and combined seroprevalence of antibodies to bloodstage Plasmodium falciparum antigens.
Results
RDT prevalence in school and community populations was 25.7% (95% CI: 24.4-26.8) and 15.5% (95% CI: 14.4-16.7), respectively. Seroprevalence in the school and community populations was 51.9% (95% CI: 50.5-53.3) and 51.5% (95% CI: 49.5-52.9), respectively. RDT prevalence in schools could differentiate between low (<7%, 95% CI: 0-19%) and high (>39%, 95% CI: 25-49%) transmission areas in the community and, after a simple adjustment, were concordant with the community estimates.
Conclusions
Estimates of malaria prevalence from school surveys were consistently higher than those from community surveys and were strongly correlated. School-based estimates can be used as a reliable indicator of malaria transmission intensity in the wider community and may provide a basis for identifying priority areas for malaria control.
doi:10.1371/journal.pone.0077641
PMCID: PMC3797060  PMID: 24143250
10.  Comparing the Performance of Cluster Random Sampling and Integrated Threshold Mapping for Targeting Trachoma Control, Using Computer Simulation 
Background
Implementation of trachoma control strategies requires reliable district-level estimates of trachomatous inflammation–follicular (TF), generally collected using the recommended gold-standard cluster randomized surveys (CRS). Integrated Threshold Mapping (ITM) has been proposed as an integrated and cost-effective means of rapidly surveying trachoma in order to classify districts according to treatment thresholds. ITM differs from CRS in a number of important ways, including the use of a school-based sampling platform for children aged 1–9 and a different age distribution of participants. This study uses computerised sampling simulations to compare the performance of these survey designs and evaluate the impact of varying key parameters.
Methodology/Principal Findings
Realistic pseudo gold standard data for 100 districts were generated that maintained the relative risk of disease between important sub-groups and incorporated empirical estimates of disease clustering at the household, village and district level. To simulate the different sampling approaches, 20 clusters were selected from each district, with individuals sampled according to the protocol for ITM and CRS. Results showed that ITM generally under-estimated the true prevalence of TF over a range of epidemiological settings and introduced more district misclassification according to treatment thresholds than did CRS. However, the extent of underestimation and resulting misclassification was found to be dependent on three main factors: (i) the district prevalence of TF; (ii) the relative risk of TF between enrolled and non-enrolled children within clusters; and (iii) the enrollment rate in schools.
Conclusions/Significance
Although in some contexts the two methodologies may be equivalent, ITM can introduce a bias-dependent shift as prevalence of TF increases, resulting in a greater risk of misclassification around treatment thresholds. In addition to strengthening the evidence base around choice of trachoma survey methodologies, this study illustrates the use of a simulated approach in addressing operational research questions for trachoma but also other NTDs.
Author Summary
Reliable district-level prevalence estimates of active trachoma are essential to targeting control interventions. While cluster randomised surveys (CRS) remain the recommended strategy for obtaining these estimates, more rapid and cost-effective methods that can be integrated with other diseases are under investigation. One proposed method is Integrated Threshold Mapping (ITM), which incorporates a school-based platform into the sampling protocol. This study uses a computerised sampling approach to evaluate whether ITM and CRS are equivalent, and explore the impact of varying key parameters on the performance of these sampling methodologies. The results from these simulations reflect a known limitation of school-based sampling: that resulting prevalence estimates are unreliable when the enrollment is low and/or the risk of disease in schools differs from communities. However, quantification of the performance of ITM at the district level highlights the variation in performance in different contexts and provides important information for national control programmes. The results from this study strengthen the evidence base around trachoma sampling methodologies and demonstrate the advantages of using a simulated approach to evaluate different sampling scenarios.
doi:10.1371/journal.pntd.0002389
PMCID: PMC3749968  PMID: 23991238
11.  The Geographical Distribution and Burden of Trachoma in Africa 
Background
There remains a lack of epidemiological data on the geographical distribution of trachoma to support global mapping and scale up of interventions for the elimination of trachoma. The Global Atlas of Trachoma (GAT) was launched in 2011 to address these needs and provide standardised, updated and accessible maps. This paper uses data included in the GAT to describe the geographical distribution and burden of trachoma in Africa.
Methods
Data assembly used structured searches of published and unpublished literature to identify cross-sectional epidemiological data on the burden of trachoma since 1980. Survey data were abstracted into a standardised database and mapped using geographical information systems (GIS) software. The characteristics of all surveys were summarized by country according to data source, time period, and survey methodology. Estimates of the current population at risk were calculated for each country and stratified by endemicity class.
Results
At the time of writing, 1342 records are included in the database representing surveys conducted between 1985 and 2012. These data were provided by direct contact with national control programmes and academic researchers (67%), peer-reviewed publications (17%) and unpublished reports or theses (16%). Prevalence data on active trachoma are available in 29 of the 33 countries in Africa classified as endemic for trachoma, and 1095 (20.6%) districts have representative data collected through population-based prevalence surveys. The highest prevalence of active trachoma and trichiasis remains in the Sahel area of West Africa and Savannah areas of East and Central Africa and an estimated 129.4 million people live in areas of Africa confirmed to be trachoma endemic.
Conclusion
The Global Atlas of Trachoma provides the most contemporary and comprehensive summary of the burden of trachoma within Africa. The GAT highlights where future mapping is required and provides an important planning tool for scale-up and surveillance of trachoma control.
Author Summary
In order to target resources and drugs to reach trachoma elimination targets by the year 2020, data on the burden of disease are required. Using prevalence data in African countries derived from the Global Atlas of Trachoma (GAT), the distribution of trachoma continues to be focused in East and West Sub-Saharan Africa, North Africa and a few endemic countries in Central Sub-Saharan Africa. Currently, 129.4 million people are estimated to live in areas that are confirmed to be trachoma endemic and 98 million are known to require access to the SAFE strategy. The maps and information presented in this work highlight the GAT as important open-access planning and advocacy tool for efforts to finalize trachoma mapping and assist national programmes in planning interventions.
doi:10.1371/journal.pntd.0002359
PMCID: PMC3738464  PMID: 23951378
12.  Spatial Distribution of Podoconiosis in Relation to Environmental Factors in Ethiopia: A Historical Review 
PLoS ONE  2013;8(7):e68330.
Background
An up-to-date and reliable map of podoconiosis is needed to design geographically targeted and cost-effective intervention in Ethiopia. Identifying the ecological correlates of the distribution of podoconiosis is the first step for distribution and risk maps. The objective of this study was to investigate the spatial distribution and ecological correlates of podoconiosis using historical and contemporary survey data.
Methods
Data on the observed prevalence of podoconiosis were abstracted from published and unpublished literature into a standardized database, according to strict inclusion and exclusion criteria. In total, 10 studies conducted between 1969 and 2012 were included, and data were available for 401,674 individuals older than 15 years of age from 229 locations. A range of high resolution environmental factors were investigated to determine their association with podoconiosis prevalence, using logistic regression.
Results
The prevalence of podoconiosis in Ethiopia was estimated at 3.4% (95% CI 3.3%–3.4%) with marked regional variation. We identified significant associations between mean annual Land Surface Temperature (LST), mean annual precipitation, topography of the land and fine soil texture and high prevalence of podoconiosis. The derived maps indicate both widespread occurrence of podoconiosis and a marked variability in prevalence of podoconiosis, with prevalence typically highest at altitudes >1500 m above sea level (masl), with >1500 mm annual rainfall and mean annual LST of 19–21°C. No (or very little) podoconiosis occurred at altitudes <1225 masl, with annual rainfall <900 mm, and mean annual LST of >24°C.
Conclusion
Podoconiosis remains a public health problem in Ethiopia over considerable areas of the country, but exhibits marked geographical variation associated in part with key environmental factors. This is work in progress and the results presented here will be refined in future work.
doi:10.1371/journal.pone.0068330
PMCID: PMC3706425  PMID: 23874587
13.  Monitoring and evaluating the impact of national school-based deworming in Kenya: study design and baseline results 
Parasites & Vectors  2013;6:198.
Background
An 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.
Methods
The 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.
Results
Overall, 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%).
Conclusions
The 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.
doi:10.1186/1756-3305-6-198
PMCID: PMC3723516  PMID: 23829767
Soil-transmitted helminths; Schistosomiasis; School-based deworming; Monitoring and evaluation; Kenya
14.  Asymptomatic Plasmodium Infection and Cognition among Primary Schoolchildren in a High Malaria Transmission Setting in Uganda 
Asymptomatic parasitemia is common among schoolchildren living in areas of high malaria transmission, yet little is known about its effect on cognitive function in these settings. To investigate associations between asymptomatic parasitemia, anemia, and cognition among primary schoolchildren living in a high malaria transmission setting, we studied 740 children enrolled in a clinical trial in Tororo, Uganda. Parasitemia, measured by thick blood smears, was present in 30% of the children. Infected children had lower test scores for abstract reasoning (adjusted mean difference [AMD] −0.6, 95% confidence interval [CI] −1.01 to −0.21) and sustained attention (AMD −1.6 95% CI −2.40 to −0.81) compared with uninfected children. There was also evidence for a dose–response relationship between parasite density and scores for sustained attention. No associations were observed between anemia and either test of cognition. Schoolchildren in high transmission settings may experience cognitive benefits, from interventions aimed at reducing the prevalence of asymptomatic parasitemia.
doi:10.4269/ajtmh.12-0633
PMCID: PMC3752809  PMID: 23589533
15.  Challenges for consent and community engagement in the conduct of cluster randomized trial among school children in low income settings: experiences from Kenya 
Trials  2013;14:142.
Background
There are a number of practical and ethical issues raised in school-based health research, particularly those related to obtaining consent from parents and assent from children. One approach to developing, strengthening, and supporting appropriate consent and assent processes is through community engagement. To date, much of the literature on community engagement in biomedical research has concentrated on community- or hospital-based research, with little documentation, if any, of community engagement in school-based health research. In this paper we discuss our experiences of consent, assent and community engagement in implementing a large school-based cluster randomized trial in rural Kenya.
Methods
Data collected as part of a qualitative study investigating the acceptability of the main trial, focus group discussions with field staff, observations of practice and authors’ experiences are used to: 1) highlight the challenges faced in obtaining assent/consent; and 2) strategies taken to try to both protect participant rights (including to refuse and to withdraw) and ensure the success of the trial.
Results
Early meetings with national, district and local level stakeholders were important in establishing their co-operation and support for the project. Despite this support, both practical and ethical challenges were encountered during consenting and assenting procedures. Our strategy for addressing these challenges focused on improving communication and understanding of the trial, and maintaining dialogue with all the relevant stakeholders throughout the study period.
Conclusions
A range of stakeholders within and beyond schools play a key role in school based health trials. Community entry and information dissemination strategies need careful planning from the outset, and with on-going consultation and feedback mechanisms established in order to identify and address concerns as they arise. We believe our experiences, and the ethical and practical issues and dilemmas encountered, will be of interest for others planning to conduct school-based research in Africa.
Trial registration
National Institute of Health NCT00878007
doi:10.1186/1745-6215-14-142
PMCID: PMC3661351  PMID: 23680181
Malaria; Cluster-randomized trial; Consent; Community engagement; School-based research; Kenya
16.  The Human Hookworm Vaccine 
Vaccine  2013;31(Suppl 2):B227-B232.
Highlights
► Human hookworm infection is a leading cause of iron deficiency anemia. ► An estimated 700 million people in developing countries are affected. ► The Sabin Vaccine Institute PDP is developing the vaccine in collaboration with FIOCRUZ. ► The vaccine comprises two recombinant protein antigens on alum and a TLR4 agonist. ► The partnership's plan is that the vaccine will be licensed by 2020.
Hookworm infection is one of the world's most common neglected tropical diseases and a leading cause of iron deficiency anemia in low- and middle-income countries. A Human Hookworm Vaccine is currently being developed by the Sabin Vaccine Institute and is in phase 1 clinical testing. The candidate vaccine is comprised of two recombinant antigens known as Na-GST-1 and Na-APR-1, each of which is an important parasite enzyme required for hookworms to successfully utilize host blood as a source of energy. The recombinant proteins are formulated on Alhydrogel® and are being tested in combination with a synthetic Toll-like receptor 4 agonist. The aim of the vaccine is to induce anti-enzyme antibodies that will reduce both host blood loss and the number of hookworms attached to the gut. Transfer of the manufacturing technology to the Oswaldo Cruz Foundation (FIOCRUZ)/Bio-Manguinhos (a Brazilian public sector developing country vaccine manufacturer) is planned, with a clinical development plan that could lead to registration of the vaccine in Brazil. The vaccine would also need to be introduced in the poorest regions of Africa and Asia, where hookworm infection is highly endemic. Ultimately, the vaccine could become an essential tool for achieving hookworm control and elimination, a key target in the 2012 London Declaration on Neglected Tropical Diseases.
doi:10.1016/j.vaccine.2012.11.034
PMCID: PMC3988917  PMID: 23598487
Hookworm; Helminth; Na-GST-1; Na-APR-1; Anemia
17.  How Effective Is School-Based Deworming for the Community-Wide Control of Soil-Transmitted Helminths? 
Background
The London Declaration on neglected tropical diseases was based in part on a new World Health Organization roadmap to “sustain, expand and extend drug access programmes to ensure the necessary supply of drugs and other interventions to help control by 2020”. Large drug donations from the pharmaceutical industry form the backbone to this aim, especially for soil-transmitted helminths (STHs) raising the question of how best to use these resources. Deworming for STHs is often targeted at school children because they are at greatest risk of morbidity and because it is remarkably cost-effective. However, the impact of school-based deworming on transmission in the wider community remains unclear.
Methods
We first estimate the proportion of parasites targeted by school-based deworming using demography, school enrolment, and data from a small number of example settings where age-specific intensity of infection (either worms or eggs) has been measured for all ages. We also use transmission models to investigate the potential impact of this coverage on transmission for different mixing scenarios.
Principal Findings
In the example settings <30% of the population are 5 to <15 years old. Combining this demography with the infection age-intensity profile we estimate that in one setting school children output as little as 15% of hookworm eggs, whereas in another setting they harbour up to 50% of Ascaris lumbricoides worms (the highest proportion of parasites for our examples). In addition, it is estimated that from 40–70% of these children are enrolled at school.
Conclusions
These estimates suggest that, whilst school-based programmes have many important benefits, the proportion of infective stages targeted by school-based deworming may be limited, particularly where hookworm predominates. We discuss the consequences for transmission for a range of scenarios, including when infective stages deposited by children are more likely to contribute to transmission than those from adults.
Author Summary
Large donations of drugs to treat soil-transmitted helminths (STHs, intestinal worms) means that many more school-aged children will be treated, improving their well-being and development. These children will have to be repeatedly treated since reinfection will occur due to contaminated environments in the absence of improvements in hygiene and sanitation. Repeated treatment of school-aged children may have the added benefit of reductions in levels of infection for the whole community. This will in part be determined by the proportion of the total worms harboured or eggs output by school-aged children, a product of how heavily infected school-aged children are and how many school-aged children there are in the community. In one setting school-aged children output as little as 15% of hookworm eggs whereas in another setting they harbour up to 50% of roundworms. Thus, whilst school-based programmes may have important health benefits, the community-level impact on transmission could be limited unless school-aged children over-contribute to infection. We use mathematical models to show that if children contribute more infective stages to the environment which adults are exposed to than adults do, the reductions in transmission resulting from treating children will be larger, but may still be limited.
doi:10.1371/journal.pntd.0002027
PMCID: PMC3585037  PMID: 23469293
18.  Estimating the relative contribution of parasitic infections and nutrition for anaemia among school-aged children in Kenya: a subnational geostatistical analysis 
BMJ Open  2013;3(2):e001936.
Objectives
To quantify geographical variation in the relative contribution of parasitic infections, socioeconomic factors and malnutrition in the aetiology of anaemia among schoolchildren across Kenya, thereby providing a rational basis for the targeting of an integrated school health package.
Design
Nationally representative cross-sectional survey data were collected using standard protocols. For all included children, data were recorded on haemoglobin (Hb) concentration and common parasitic infections (Plasmodium falciparum, hookworm and schistosomes) and socioeconomic indicators. Ecological proxies of malnutrition and food security were generated using Demographic and Health Survey and UN Food and Agriculture Organization food security data, respectively. Spatially explicit, multilevel models were used to quantify impact upon child Hb concentration.
Setting
Randomly selected schools in ecologically diverse settings across Kenya.
Main outcome measures
Mean Hb concentration adjusted for infection, nutritional and socioeconomic risk factors; associated risk ratios and adjusted Population Attributable Fractions (PAFs) for anaemia, by region.
Results
Data were available for 16 941 children in 167 schools; mean Hb was 122.1 g/l and 35.3% of children were anaemic. In multivariate analysis, mean Hb was significantly lower in boys and younger children. Severe malnutrition and interactions between P falciparum and hookworm infections were significantly associated with lower Hb, with greater impacts seen for coinfected children. The contribution of risk factors to anaemia risk varied by province: in 14-year-old girls, PAFs ranged between 0% and 27.6% for P falciparum, 0% and 29% for hookworm and 0% and 18.4% for severe malnutrition.
Conclusions
The observed geographical heterogeneity in the burden of anaemia attributable to different aetiological factors has important implications for the rational targeting of antianaemia interventions that can be included in an integrated school health programme.
doi:10.1136/bmjopen-2012-001936
PMCID: PMC3586185  PMID: 23435794
Nutrition & Dietetics
19.  The Use of Bivariate Spatial Modeling of Questionnaire and Parasitology Data to Predict the Distribution of Schistosoma haematobium in Coastal Kenya 
Background
Questionnaires of reported blood in urine (BIU) distributed through the existing school system provide a rapid and reliable method to classify schools according to the prevalence of Schistosoma haematobium, thereby helping in the targeting of schistosomiasis control. However, not all schools return questionnaires and it is unclear whether treatment is warranted in such schools. This study investigates the use of bivariate spatial modelling of available and multiple data sources to predict the prevalence of S. haematobium at every school along the Kenyan coast.
Methodology
Data from a questionnaire survey conducted by the Kenya Ministry of Education in Coast Province in 2009 were combined with available parasitological and environmental data in a Bayesian bivariate spatial model. This modeled the relationship between BIU data and environmental covariates, as well as the relationship between BIU and S. haematobium infection prevalence, to predict S. haematobium infection prevalence at all schools in the study region. Validation procedures were implemented to assess the predictive accuracy of endemicity classification.
Principal Findings
The prevalence of BIU was negatively correlated with distance to nearest river and there was considerable residual spatial correlation at small (∼15 km) spatial scales. There was a predictable relationship between the prevalence of reported BIU and S. haematobium infection. The final model exhibited excellent sensitivity (0.94) but moderate specificity (0.69) in identifying low (<10%) prevalence schools, and had poor performance in differentiating between moderate and high prevalence schools (sensitivity 0.5, specificity 1).
Conclusions
Schistosomiasis is highly focal and there is a need to target treatment on a school-by-school basis. The use of bivariate spatial modelling can supplement questionnaire data to identify schools requiring mass treatment, but is unable to distinguish between moderate and high prevalence schools.
Author Summary
The highly focal nature of schistosomiasis means that treatment is most cost-effective when delivered on a school-by-school basis. Questionnaires of reported blood in urine (BIU) distributed through the existing school system are a rapid, valid method to classify schools according to WHO treatment thresholds. Their usefulness, however, can be hampered by incomplete return rates that impede treatment decisions in schools with missing questionnaire data. Using data from coastal Kenya, this study describes the use of Bayesian spatial modeling that combines questionnaire data with available parasitological data to make predictions of S. haematobium infection prevalence at all schools. Results showed that reported BIU was highly focal and was negatively associated with the distance to the nearest river. The final model was able to discriminate between schools that require treatment or not, but was less reliable at distinguishing between medium and high prevalence schools. Similar Bayesian spatial models may prove useful for modeling and predicting other diseases where multiple diagnostic techniques are employed.
doi:10.1371/journal.pntd.0002016
PMCID: PMC3554572  PMID: 23359829
20.  Understanding the Impact of Subsidizing Artemisinin-Based Combination Therapies (ACTs) in the Retail Sector – Results from Focus Group Discussions in Rural Kenya 
PLoS ONE  2013;8(1):e54371.
Background
There is considerable interest in the potential of private sector subsidies to increase availability and affordability of artemisinin-based combination therapies (ACTs) for malaria treatment. A cluster randomized trial of such subsidies was conducted in 3 districts in Kenya, comprising provision of subsidized packs of paediatric ACT to retail outlets, training of retail staff, and community awareness activities. The results demonstrated a substantial increase in ACT availability and coverage, though patient counselling and adherence were suboptimal. We conducted a qualitative study in order to understand why these successes and limitations occurred.
Methodology/Principal Findings
Eighteen focus group discussions were conducted, 9 with retailers and 9 with caregivers, to document experiences with the intervention. Respondents were positive about intervention components, praising the focused retailer training, affordable pricing, strong promotional activities, dispensing job aids, and consumer friendly packaging, which are likely to have contributed to the positive access and coverage outcomes observed. However, many retailers still did not stock ACT, due to insufficient supplies, lack of capital and staff turnover. Advice to caregivers was poor due to insufficient time, and poor recall of instructions. Adherence by caregivers to dosing guidelines was sub-optimal, because of a wish to save tablets for other episodes, doses being required at night, stopping treatment when the child felt better, and the number and bitter taste of the tablets. Caregivers used a number of strategies to obtain paediatric ACT for older age groups.
Conclusions/Significance
This study has highlighted that important components of a successful ACT subsidy intervention are regular retailer training, affordable pricing, a reliable supply chain and community mobilization emphasizing patient adherence and when to seek further care.
doi:10.1371/journal.pone.0054371
PMCID: PMC3544761  PMID: 23342143
22.  Integrated Rapid Mapping of Neglected Tropical Diseases in Three States of South Sudan: Survey Findings and Treatment Needs 
PLoS ONE  2012;7(12):e52789.
Background
Integrated rapid mapping to target interventions for schistosomiasis, soil-transmitted helminthiasis (STH) and lymphatic filariasis (LF) is ongoing in South Sudan. From May to September 2010, three states – Unity, Eastern Equatoria and Central Equatoria – were surveyed with the aim of identifying which administrative areas are eligible for mass drug administration (MDA) of preventive chemotherapy (PCT).
Methods and Principal Findings
Payams (third administrative tier) were surveyed for Schistosoma mansoni, S. haematobium and STH infections while counties (second administrative tier) were surveyed for LF. Overall, 12,742 children from 193 sites were tested for schistosome and STH infection and, at a subset of 50 sites, 3,980 adults were tested for LF. Either S. mansoni or S. haematobium or both species were endemic throughout Unity State and occurred in foci in Central and Eastern Equatoria. STH infection was endemic throughout Central Equatoria and the western counties of Eastern Equatoria, while LF was endemic over most of Central- and Eastern Equatoria, but only in selected foci in Unity. All areas identified as STH endemic were co-endemic for schistosomiasis and/or LF.
Conclusions
The distribution and prevalence of major NTDs, particularly schistosomiasis, varies considerably throughout South Sudan. Rapid mapping is therefore important in identifying (co)-endemic areas. The present survey established that across the three surveyed states between 1.2 and 1.4 million individuals are estimated to be eligible for regular MDA with PCT to treat STH and schistosomiasis, respectively, while approximately 1.3 million individuals residing in Central- and Eastern Equatoria are estimated to require MDA for LF.
doi:10.1371/journal.pone.0052789
PMCID: PMC3527617  PMID: 23285184
23.  Use of Rapid Diagnostic Tests in Malaria School Surveys in Kenya: Does their Under-performance Matter for Planning Malaria Control? 
Malaria rapid diagnostic tests (RDTs) are known to yield false-positive results, and their use in epidemiologic surveys will overestimate infection prevalence and potentially hinder efficient targeting of interventions. To examine the consequences of using RDTs in school surveys, we compared three RDT brands used during a nationwide school survey in Kenya with expert microscopy and investigated the cost implications of using alternative diagnostic approaches in identifying localities with differing levels of infection. Overall, RDT sensitivity was 96.1% and specificity was 70.8%. In terms of classifying districts and schools according to prevalence categories, RDTs were most reliable for the < 1% and > 40% categories and least reliable in the 1–4.9% category. In low-prevalence settings, microscopy was the most expensive approach, and RDT results corrected by either microscopy or polymerase chain reaction were the cheapest. Use of polymerase chain reaction-corrected RDT results is recommended in school malaria surveys, especially in settings with low-to-moderate malaria transmission.
doi:10.4269/ajtmh.2012.12-0215
PMCID: PMC3516067  PMID: 23091194
24.  Use of Rapid Diagnostic Tests in Malaria School Surveys in Kenya: Does their Under-performance Matter for Planning Malaria Control? 
Malaria rapid diagnostic tests (RDTs) are known to yield false-positive results, and their use in epidemiologic surveys will overestimate infection prevalence and potentially hinder efficient targeting of interventions. To examine the consequences of using RDTs in school surveys, we compared three RDT brands used during a nationwide school survey in Kenya with expert microscopy and investigated the cost implications of using alternative diagnostic approaches in identifying localities with differing levels of infection. Overall, RDT sensitivity was 96.1% and specificity was 70.8%. In terms of classifying districts and schools according to prevalence categories, RDTs were most reliable for the < 1% and > 40% categories and least reliable in the 1–4.9% category. In low-prevalence settings, microscopy was the most expensive approach, and RDT results corrected by either microscopy or polymerase chain reaction were the cheapest. Use of polymerase chain reaction–corrected RDT results is recommended in school malaria surveys, especially in settings with low-to-moderate malaria transmission.
doi:10.4269/ajtmh.2012.12-0215
PMCID: PMC3516067  PMID: 23091194
25.  Multiple Category-Lot Quality Assurance Sampling: A New Classification System with Application to Schistosomiasis Control 
Background
Originally a binary classifier, Lot Quality Assurance Sampling (LQAS) has proven to be a useful tool for classification of the prevalence of Schistosoma mansoni into multiple categories (≤10%, >10 and <50%, ≥50%), and semi-curtailed sampling has been shown to effectively reduce the number of observations needed to reach a decision. To date the statistical underpinnings for Multiple Category-LQAS (MC-LQAS) have not received full treatment. We explore the analytical properties of MC-LQAS, and validate its use for the classification of S. mansoni prevalence in multiple settings in East Africa.
Methodology
We outline MC-LQAS design principles and formulae for operating characteristic curves. In addition, we derive the average sample number for MC-LQAS when utilizing semi-curtailed sampling and introduce curtailed sampling in this setting. We also assess the performance of MC-LQAS designs with maximum sample sizes of n = 15 and n = 25 via a weighted kappa-statistic using S. mansoni data collected in 388 schools from four studies in East Africa.
Principle Findings
Overall performance of MC-LQAS classification was high (kappa-statistic of 0.87). In three of the studies, the kappa-statistic for a design with n = 15 was greater than 0.75. In the fourth study, where these designs performed poorly (kappa-statistic less than 0.50), the majority of observations fell in regions where potential error is known to be high. Employment of semi-curtailed and curtailed sampling further reduced the sample size by as many as 0.5 and 3.5 observations per school, respectively, without increasing classification error.
Conclusion/Significance
This work provides the needed analytics to understand the properties of MC-LQAS for assessing the prevalance of S. mansoni and shows that in most settings a sample size of 15 children provides a reliable classification of schools.
Author Summary
The control of schistosomiasis calls for rapid and reliable classification tools. This study evaluates the performance of one such tool, Lot Quality Assurance Sampling (LQAS) for assessing the prevalence of S. mansoni in African schoolchildren. We outline the design considerations and introduce novel sequential sampling plans for Multiple Category-LQAS. We use data from 388 schools in Uganda, Kenya, and Tanzania to assess the performance of LQAS as a tool for classification of S. mansoni infection into one of three classes: ≤10% >10 and <50%, ≥50%. Our findings suggest that an LQAS-based multiple classification system performs as well as the World Health Organization recommended methods at a fraction of the sampling effort. Our work validates LQAS as a rapid assessment tool and extends it to allow investigators to apply the method to control other infectious diseases.
doi:10.1371/journal.pntd.0001806
PMCID: PMC3435238  PMID: 22970333

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