Accelerating Progress Towards the 2030 Neglected Tropical Diseases Targets: How Can Quantitative Modeling Support Programmatic Decisions?

Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Despite these advances, most NTD programs have recently experienced important setbacks; for example, NTD interventions were some of the most frequently and severely impacted by service disruptions due to the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021-2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets.

Spatio-temporal modelling of referrals to outpatient respiratory clinics in the integrated care system of the Morecambe Bay area, England.

BACKGROUND: Promoting integrated care is a key goal of the NHS Long Term Plan to improve population respiratory health, yet there is limited data-driven evidence of its effectiveness. The Morecambe Bay Respiratory Network is an integrated care initiative operating in the North-West of England since 2017. A key target area has been reducing referrals to outpatient respiratory clinics by upskilling primary care teams. This study aims to explore space-time patterns in referrals from general practice in the Morecambe Bay area to evaluate the impact of the initiative. METHODS: Data on referrals to outpatient clinics and chronic respiratory disease patient counts between 2012-2020 were obtained from the Morecambe Bay Community Data Warehouse, a large store of routinely collected healthcare data. For analysis, the data is aggregated by year and small area geography. The methodology comprises of two parts. The first explores the issues that can arise when using routinely collected primary care data for space-time analysis and applies spatio-temporal conditional autoregressive modelling to adjust for data complexities. The second part models the rate of outpatient referral via a Poisson generalised linear mixed model that adjusts for changes in demographic factors and number of respiratory disease patients. RESULTS: The first year of the Morecambe Bay Respiratory Network was not associated with a significant difference in referral rate. However, the second and third years saw significant reductions in areas that had received intervention, with full intervention associated with a 31.8% (95% CI 17.0-43.9) and 40.5% (95% CI 27.5-50.9) decrease in referral rate in 2018 and 2019, respectively. CONCLUSIONS: Routinely collected data can be used to robustly evaluate key outcome measures of integrated care. The results demonstrate that effective integrated care has real potential to ease the burden on respiratory outpatient services by reducing the need for an onward referral. This is of great relevance given the current pressure on outpatient services globally, particularly long waiting lists following the COVID-19 pandemic and the need for more innovative models of care.

Evaluation of eight lateral flow tests for the detection of anti-SARS-CoV-2 antibodies in a vaccinated population.

BACKGROUND: Rapid determination of an individual's antibody status can be beneficial in understanding an individual's immune response to SARS-CoV-2 and for initiation of therapies that are only deemed effective in sero-negative individuals. Antibody lateral flow tests (LFTs) have potential to address this need as a rapid, point of care test. METHODS: Here we present a proof-of-concept evaluation of eight LFT brands using sera from 95 vaccinated individuals to determine sensitivity for detecting vaccination generated antibodies. Samples were analysed on eight different brands of antibody LFT and an automated chemiluminescent microparticle immunoassay (CMIA) that identifies anti-spike antibodies which was used as our reference standard. RESULTS: All 95 (100%) participants tested positive for anti-spike antibodies by the chemiluminescent microparticle immunoassay (CMIA) reference standard post-dose two of their SARS-CoV-2 vaccine: BNT162b2 (Pfizer/BioNTech, n = 60), AZD1222 (AstraZeneca, n = 31), mRNA-1273 (Moderna, n = 2) and Undeclared Vaccine Brand (n = 2). Sensitivity increased from dose one to dose two in six out of eight LFTs with three tests achieving 100% sensitivity at dose two in detecting anti-spike antibodies. CONCLUSIONS: These tests are demonstrated to be highly sensitive to detect raised antibody levels in vaccinated individuals. RDTs are low cost and rapid alternatives to ELISA based systems.

Impact of population based indoor residual spraying with and without mass drug administration with dihydroartemisinin-piperaquine on malaria prevalence in a high transmission setting: a quasi-experimental controlled before-and-after trial in northeastern Uganda.

BACKGROUND: Declines in malaria burden in Uganda have slowed. Modelling predicts that indoor residual spraying (IRS) and mass drug administration (MDA), when co-timed, have synergistic impact. This study investigated additional protective impact of population-based MDA on malaria prevalence, if any, when added to IRS, as compared with IRS alone and with standard of care (SOC). METHODS: The 32-month quasi-experimental controlled before-and-after trial enrolled an open cohort of residents (46,765 individuals, 1st enumeration and 52,133, 4th enumeration) of Katakwi District in northeastern Uganda. Consented participants were assigned to three arms based on residential subcounty at study start: MDA+IRS, IRS, SOC. IRS with pirimiphos methyl and MDA with dihydroartemisinin- piperaquine were delivered in 4 co-timed campaign-style rounds 8 months apart. The primary endpoint was population prevalence of malaria, estimated by 6 cross-sectional surveys, starting at baseline and preceding each subsequent round. RESULTS: Comparing malaria prevalence in MDA+IRS and IRS only arms over all 6 surveys (intention-to-treat analysis), roughly every 6 months post-interventions, a geostatistical model found a significant additional 15.5% (95% confidence interval (CI): [13.7%, 17.5%], Z = 9.6, p = 5e-20) decrease in the adjusted odds ratio (aOR) due to MDA for all ages, a 13.3% reduction in under 5's (95% CI: [10.5%, 16.8%], Z = 4.02, p = 5e-5), and a 10.1% reduction in children 5-15 (95% CI: [8.5%, 11.8%], Z = 4.7, p = 2e-5). All ages residents of the MDA + IRS arm enjoyed an overall 80.1% reduction (95% CI: [80.0%, 83.0%], p = 0.0001) in odds of qPCR confirmed malaria compared with SOC residents. Secondary difference-in-difference analyses comparing surveys at different timepoints to baseline showed aOR (MDA + IRS vs IRS) of qPCR positivity between 0.28 and 0.66 (p < 0.001). Of three serious adverse events, one (nonfatal) was considered related to study medications. Limitations include the initial non-random assignment of study arms, the single large cluster per arm, and the lack of an MDA-only arm, considered to violate equipoise. CONCLUSIONS: Despite being assessed at long time points 5-7 months post-round, MDA plus IRS provided significant additional protection from malaria infection over IRS alone. Randomized trials of MDA in large areas undergoing IRS recommended as well as cohort studies of impact on incidence. TRIAL REGISTRATION: This trial was retrospectively registered 11/07/2018 with the Pan African Clinical Trials Registry (PACTR201807166695568).

A threshold-free approach with age-dependency for estimating malaria seroprevalence.

BACKGROUND: In malaria serology analysis, the standard approach to obtain seroprevalence, i.e the proportion of seropositive individuals in a population, is based on a threshold which is used to classify individuals as seropositive or seronegative. The choice of this threshold is often arbitrary and is based on methods that ignore the age-dependency of the antibody distribution. METHODS: Using cross-sectional antibody data from the Western Kenyan Highlands, this paper introduces a novel approach that has three main advantages over the current threshold-based approach: it avoids the use of thresholds; it accounts for the age dependency of malaria antibodies; and it allows us to propagate the uncertainty from the classification of individuals into seropositive and seronegative when estimating seroprevalence. The reversible catalytic model is used as an example for illustrating how to propagate this uncertainty into the parameter estimates of the model. RESULTS: This paper finds that accounting for age-dependency leads to a better fit to the data than the standard approach which uses a single threshold across all ages. Additionally, the paper also finds that the proposed threshold-free approach is more robust against the selection of different age-groups when estimating seroprevalence. CONCLUSION: The novel threshold-free approach presented in this paper provides a statistically principled and more objective approach to estimating malaria seroprevalence. The introduced statistical framework also provides a means to compare results across studies which may use different age ranges for the estimation of seroprevalence.

Neighbors' use of water and sanitation facilities can affect children's health: a cohort study in Mozambique using a spatial approach.

BACKGROUND: Impact evaluation of most water, sanitation and hygiene (WASH) interventions in health are user-centered. However, recent research discussed WASH herd protection - community WASH coverage could protect neighboring households. We evaluated the effect of water and sanitation used in the household and by household neighbors in children's morbidity and mortality using recorded health data. METHODS: We conducted a retrospective cohort including 61,333 children from a district in Mozambique during 2012-2015. We obtained water and sanitation household data and morbidity data from Manhiça Health Research Centre surveillance system. To evaluate herd protection, we estimated the density of household neighbors with improved facilities using a Kernel Density Estimator. We fitted negative binomial adjusted regression models to assess the minimum children-based incidence rates for every morbidity indicator, and Cox regression models for mortality. RESULTS: Household use of unimproved water and sanitation displayed a higher rate of outpatient visit, diarrhea, malaria, and anemia. Households with unimproved water and sanitation surrounded by neighbors with improved water and sanitation high coverage were associated with a lower rate of outpatient visit, malaria, anemia, and malnutrition. CONCLUSION: Household and neighbors' access to improve water and sanitation can affect children's health. Accounting for household WASH and herd protection in interventions' evaluation could foster stakeholders' investment and improve WASH related diseases control. Distribution of main water and sanitation facilities used during study period.

Model-Based Geostatistical Methods Enable Efficient Design and Analysis of Prevalence Surveys for Soil-Transmitted Helminth Infection and Other Neglected Tropical Diseases.

Maps of the geographical variation in prevalence play an important role in large-scale programs for the control of neglected tropical diseases. Precontrol mapping is needed to establish the appropriate control intervention in each area of the country in question. Mapping is also needed postintervention to measure the success of control efforts. In the absence of comprehensive disease registries, mapping efforts can be informed by 2 kinds of data: empirical estimates of local prevalence obtained by testing individuals from a sample of communities within the geographical region of interest, and digital images of environmental factors that are predictive of local prevalence. In this article, we focus on the design and analysis of impact surveys, that is, prevalence surveys that are conducted postintervention with the aim of informing decisions on what further intervention, if any, is needed to achieve elimination of the disease as a public health problem. We show that geospatial statistical methods enable prevalence surveys to be designed and analyzed as efficiently as possible so as to make best use of hard-won field data. We use 3 case studies based on data from soil-transmitted helminth impact surveys in Kenya, Sierra Leone, and Zimbabwe to compare the predictive performance of model-based geostatistics with methods described in current World Health Organization (WHO) guidelines. In all 3 cases, we find that model-based geostatistics substantially outperforms the current WHO guidelines, delivering improved precision for reduced field-sampling effort. We argue from experience that similar improvements will hold for prevalence mapping of other neglected tropical diseases.

Predicted Impact of COVID-19 on Neglected Tropical Disease Programs and the Opportunity for Innovation.

Due to the COVID-19 pandemic, many key neglected tropical disease (NTD) activities have been postponed. This hindrance comes at a time when the NTDs are progressing towards their ambitious goals for 2030. Mathematical modelling on several NTDs, namely gambiense sleeping sickness, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiases (STH), trachoma, and visceral leishmaniasis, shows that the impact of this disruption will vary across the diseases. Programs face a risk of resurgence, which will be fastest in high-transmission areas. Furthermore, of the mass drug administration diseases, schistosomiasis, STH, and trachoma are likely to encounter faster resurgence. The case-finding diseases (gambiense sleeping sickness and visceral leishmaniasis) are likely to have fewer cases being detected but may face an increasing underlying rate of new infections. However, once programs are able to resume, there are ways to mitigate the impact and accelerate progress towards the 2030 goals.

Maplaria: a user friendly web-application for spatio-temporal malaria prevalence mapping.

BACKGROUND: Model-based geostatistical (MBG) methods have been extensively used to map malaria risk using community survey data in low-resource settings where disease registries are incomplete or non-existent. However, the wider adoption of MBG methods by national control programmes to inform health policy decisions is hindered by the lack of advanced statistical expertise and suitable computational equipment. Here, Maplaria, an interactive, user-friendly web-application that allows users to upload their own malaria prevalence data and carry out geostatistical prediction of annual malaria prevalence at any desired spatial scale, is introduced. METHODS: In the design of the Maplaria web application, two main criteria were considered: the application should be able to classify subnational divisions into the most likely endemicity levels; the web application should allow only minimal input from the user in the set-up of the geostatistical inference process. To achieve this, the process of fitting and validating the geostatistical models is carried out by statistical experts using publicly available malaria survey data from the Harvard database. The stage of geostatistical prediction is entirely user-driven and allows the user to upload malaria data, as well as vector data that define the administrative boundaries for the generation of spatially aggregated inferences. RESULTS: The process of data uploading and processing is split into a series of steps spread across screens through the progressive disclosure technique that prevents the user being immediately overwhelmed by the length of the form. Each of these is illustrated using a data set from the Malaria Indicator carried out in Tanzania in 2017 as an example. CONCLUSIONS: Maplaria application provides a user-friendly solution to the problem making geostatistical methods more accessible to users that have not undertaken formal training in statistics. The application is a useful tool that can be used to foster ownership, among policy makers, of disease risk maps and promote better use of data for decision-making in low resource settings.

A unified and flexible modelling framework for the analysis of malaria serology data.

Serology data are an increasingly important tool in malaria surveillance, especially in low transmission settings where the estimation of parasite-based indicators is often problematic. Existing methods rely on the use of thresholds to identify seropositive individuals and estimate transmission intensity, while making assumptions about the temporal dynamics of malaria transmission that are rarely questioned. Here, we present a novel threshold-free approach for the analysis of malaria serology data which avoids dichotomization of continuous antibody measurements and allows us to model changes in the antibody distribution across age in a more flexible way. The proposed unified mechanistic model combines the properties of reversible catalytic and antibody acquisition models, and allows for temporally varying boosting and seroconversion rates. Additionally, as an alternative to the unified mechanistic model, we also propose an empirical approach to analysis where modelling of the age-dependency is informed by the data rather than biological assumptions. Using serology data from Western Kenya, we demonstrate both the usefulness and limitations of the novel modelling framework.

Design and Analysis of Elimination Surveys for Neglected Tropical Diseases.

As neglected tropical diseases approach elimination status, there is a need to develop efficient sampling strategies for confirmation (or not) that elimination criteria have been met. This is an inherently difficult task because the relative precision of a prevalence estimate deteriorates as prevalence decreases, and classic survey sampling strategies based on random sampling therefore require increasingly large sample sizes. More efficient strategies for survey design and analysis can be obtained by exploiting any spatial correlation in prevalence within a model-based geostatistics framework. This framework can be used for constructing predictive probability maps that can inform in-country decision makers of the likelihood that their elimination target has been met, and where to invest in additional sampling. We evaluated our methodology using a case study of lymphatic filariasis in Ghana, demonstrating that a geostatistical approach outperforms approaches currently used to determine an evaluation unit's elimination status.

The global prevalence of hepatitis D virus infection: Systematic review and meta-analysis.

BACKGROUND AND AIMS: There are uncertainties about the epidemic patterns of HDV infection and its contribution to the burden of liver disease. We estimated the global prevalence of HDV infection and explored its contribution to the development of cirrhosis and hepatocellular carcinoma (HCC) among HBsAg-positive people. METHODS: We searched Pubmed, EMBASE and Scopus for studies reporting on total or IgG anti-HDV among HBsAg-positive people. Anti-HDV prevalence was estimated using a binomial mixed model, weighting for study quality and population size. The population attributable fraction (PAF) of HDV to cirrhosis and HCC among HBsAg-positive people was estimated using random effects models. RESULTS: We included 282 studies, comprising 376 population samples from 95 countries, which together tested 120,293 HBsAg-positive people for anti-HDV. The estimated anti-HDV prevalence was 4.5% (95% CI 3.6-5.7) among all HBsAg-positive people and 16.4% (14.6-18.6) among those attending hepatology clinics. Worldwide, 0.16% (0.11-0.25) of the general population, totalling 12.0 (8.7-18.7) million people, were estimated to be anti-HDV positive. Prevalence among HBsAg-positive people was highest in Mongolia, the Republic of Moldova and countries in Western and Middle Africa, and was higher in injecting drug users, haemodialysis recipients, men who have sex with men, commercial sex workers, and those with HCV or HIV. Among HBsAg-positive people, preliminary PAF estimates of HDV were 18% (10-26) for cirrhosis and 20% (8-33) for HCC. CONCLUSIONS: An estimated 12 million people worldwide have experienced HDV infection, with higher prevalence in certain geographic areas and populations. HDV is a significant contributor to HBV-associated liver disease. More quality data are needed to improve the precision of burden estimates. LAY SUMMARY: We combined all available studies to estimate how many people with hepatitis B also have hepatitis D, a viral infection that only affects people with hepatitis B. About 1 in 22 people with hepatitis B also have hepatitis D, increasing to 1 in 6 when considering people with liver disease. Hepatitis D may cause about 1 in 6 of the cases of cirrhosis and 1 in 5 of the cases of liver cancer that occur in people with hepatitis B. Hepatitis D is an important contributor to the global burden of liver disease.

A geostatistical framework for combining spatially referenced disease prevalence data from multiple diagnostics.

Multiple diagnostic tests are often used due to limited resources or because they provide complementary information on the epidemiology of a disease under investigation. Existing statistical methods to combine prevalence data from multiple diagnostics ignore the potential overdispersion induced by the spatial correlations in the data. To address this issue, we develop a geostatistical framework that allows for joint modelling of data from multiple diagnostics by considering two main classes of inferential problems: (a) to predict prevalence for a gold-standard diagnostic using low-cost and potentially biased alternative tests; (b) to carry out joint prediction of prevalence from multiple tests. We apply the proposed framework to two case studies: mapping Loa loa prevalence in Central and West Africa, using miscroscopy, and a questionnaire-based test called RAPLOA; mapping Plasmodium falciparum malaria prevalence in the highlands of Western Kenya using polymerase chain reaction and a rapid diagnostic test. We also develop a Monte Carlo procedure based on the variogram in order to identify parsimonious geostatistical models that are compatible with the data. Our study highlights (a) the importance of accounting for diagnostic-specific residual spatial variation and (b) the benefits accrued from joint geostatistical modelling so as to deliver more reliable and precise inferences on disease prevalence.

Dealing with spatial misalignment to model the relationship between deprivation and life expectancy: a model-based geostatistical approach.

BACKGROUND : Life expectancy at birth (LEB), one of the main indicators of human longevity, has often been used to characterise the health status of a population. Understanding its relationships with the deprivation is key to develop policies and evaluate interventions that are aimed at reducing health inequalities. However, methodological challenges in the analysis of LEB data arise from the fact that different Government agencies often provide spatially aggregated information on LEB and the index of multiple deprivation (IMD) at different spatial scales. Our objective is to develop a geostatistical framework that, unlike existing methods of inference, allows to carry out spatially continuous prediction while dealing with spatial misalignment of the areal-level data. METHODS : We developed a model-based geostatistical approach for the joint analysis of LEB and IMD, when these are available over different partitions of the study region. We model the spatial correlation in LEB and IMD across the areal units using inter-point distances based on a regular grid covering the whole of the study area. The advantages and strengths of the new methodology are illustrated through an analysis of LEB and IMD data from the Liverpool district council. RESULTS : We found that the effect of IMD on LEB is stronger in males than in females, explaining about 63.35% of the spatial variation in LEB in the former group and 38.92% in the latter. We also estimate that LEB is about 8.5 years lower between the most and least deprived area of Liverpool for men, and 7.1 years for women. Finally, we find that LEB, both in males and females, is at least 80% likely to be above the England wide average only in some areas falling in the electoral wards of Childwall, Woolton and Church. CONCLUSION : The novel model-based geostatistical framework provides a feasible solution to the spatial misalignment problem. More importantly, the proposed methodology has the following advantages over existing methods used model LEB: (1) it can deliver spatially continuous inferences using spatially aggregated data; (2) it can be applied to any form of misalignment with information provided at a range of spatial scales, from areal-level to pixel-level.

A spatially discrete approximation to log-Gaussian Cox processes for modelling aggregated disease count data.

In this paper, we develop a computationally efficient discrete approximation to log-Gaussian Cox process (LGCP) models for the analysis of spatially aggregated disease count data. Our approach overcomes an inherent limitation of spatial models based on Markov structures, namely, that each such model is tied to a specific partition of the study area, and allows for spatially continuous prediction. We compare the predictive performance of our modelling approach with LGCP through a simulation study and an application to primary biliary cirrhosis incidence data in Newcastle upon Tyne, UK. Our results suggest that, when disease risk is assumed to be a spatially continuous process, the proposed approximation to LGCP provides reliable estimates of disease risk both on spatially continuous and aggregated scales. The proposed methodology is implemented in the open-source R package SDALGCP.

Understanding the spatial distribution of trichiasis and its association with trachomatous inflammation-follicular.

BACKGROUND: Whilst previous work has identified clustering of the active trachoma sign "trachomatous inflammation-follicular" (TF), there is limited understanding of the spatial structure of trachomatous trichiasis (TT), the rarer, end-stage, blinding form of disease. Here we use community-level TF prevalence, information on access to water and sanitation, and large-scale environmental and socio-economic indicators to model the spatial variation in community-level TT prevalence in Benin, Cote d'Ivoire, DRC, Guinea, Ethiopia, Malawi, Mozambique, Nigeria, Sudan and Uganda. METHODS: We fit binomial mixed models, with community-level random effects, separately for each country. In countries where spatial correlation was detected through a semi-variogram diagnostic check we then fitted a geostatistical model to the TT prevalence data including TF prevalence as an explanatory variable. RESULTS: The estimated regression relationship between community-level TF and TT was significant in eight countries. We estimate that a 10% increase in community-level TF prevalence leads to an increase in the odds for TT ranging from 20 to 86% when accounting for additional covariates. CONCLUSION: We find evidence of an association between TF and TT in some parts of Africa. However, our results also suggest the presence of additional, country-specific, spatial risk factors which modulate the variation in TT risk.

Sub national variation and inequalities in under-five mortality in Kenya since 1965.

BACKGROUND: Despite significant declines in under five mortality (U5M) over the last 3 decades, Kenya did not achieve Millennium Development Goal 4 (MDG 4) by 2015. To better understand trends and inequalities in child mortality, analysis of U5M variation at subnational decision making units is required. Here the comprehensive compilation and analysis of birth history data was used to understand spatio-temporal variation, inequalities and progress towards achieving the reductions targets of U5M between 1965 and 2013 and projected to 2015 at decentralized health planning units (counties) in Kenya. METHODS: Ten household surveys and three censuses with data on birth histories undertaken between 1989 and 2014 were assembled. The birth histories were allocated to the respective counties and demographic methods applied to estimate U5M per county by survey. To generate a single U5M estimate for year and county, a Bayesian spatio-temporal Gaussian process regression was fitted accounting for variation in sample size, surveys and demographic methods. Inequalities and the progress in meeting the goals set to reduce U5M were evaluated subnationally. RESULTS: Nationally, U5M reduced by 61·6%, from 141·7 (121·6-164·0) in 1965 to 54·5 (44·6-65·5) in 2013. The declining U5M was uneven ranging between 19 and 80% across the counties with some years when rates increased. By 2000, 25 counties had achieved the World Summit for Children goals. However, as of 2015, no county had achieved MDG 4. There was a striking decline in the levels of inequality between counties over time, however, disparities persist. By 2013 there persists a 3·8 times difference between predicted U5M rates when comparing counties with the highest U5M rates against those with the lowest U5M rates. CONCLUSION: Kenya has made huge progress in child survival since independence. However, U5M remains high and heterogeneous with substantial differences between counties. Better use of the current resources through focused allocation is required to achieve further reductions, reduce inequalities and increase the likelihood of achieving Sustainable Development Goal 3·2 on U5M by 2030.

Do hotspots fuel malaria transmission: a village-scale spatio-temporal analysis of a 2-year cohort study in The Gambia.

BACKGROUND: Despite the biological plausibility of hotspots fueling malaria transmission, the evidence to support this concept has been mixed. If transmission spreads from high burden to low burden households in a consistent manner, then this could have important implications for control and elimination program development. METHODS: Data from a longitudinal cohort in The Gambia was analyzed. All consenting individuals residing in 12 villages across the country were sampled monthly from June (dry season) to December 2013 (wet season), in April 2014 (mid dry season), and monthly from June to December 2014. A study nurse stationed within each village recorded passively detected malaria episodes between visits. Plasmodium falciparum infections were determined by polymerase chain reaction and analyzed using a geostatistical model. RESULTS: Household-level observed monthly incidence ranged from 0 to 0.50 infection per person (interquartile range = 0.02-0.10) across the sampling months, and high burden households exist across all study villages. There was limited evidence of a spatio-temporal pattern at the monthly timescale irrespective of transmission intensity. Within-household transmission was the most plausible hypothesis examined to explain the observed heterogeneity in infections. CONCLUSIONS: Within-village malaria transmission patterns are concentrated in a small proportion of high burden households, but patterns are stochastic regardless of endemicity. Our findings support the notion of transmission occurring at the household and village scales but not the use of a targeted approach to interrupt spreading of infections from high to low burden areas within villages in this setting.

Spatio-temporal analysis of Plasmodium falciparum prevalence to understand the past and chart the future of malaria control in Kenya.

BACKGROUND: Spatial and temporal malaria risk maps are essential tools to monitor the impact of control, evaluate priority areas to reorient intervention approaches and investments in malaria endemic countries. Here, the analysis of 36 years data on Plasmodium falciparum prevalence is used to understand the past and chart a future for malaria control in Kenya by confidently highlighting areas within important policy relevant thresholds to allow either the revision of malaria strategies to those that support pre-elimination or those that require additional control efforts. METHODS: Plasmodium falciparum parasite prevalence (PfPR) surveys undertaken in Kenya between 1980 and 2015 were assembled. A spatio-temporal geostatistical model was fitted to predict annual malaria risk for children aged 2-10 years (PfPR2-10) at 1 × 1 km spatial resolution from 1990 to 2015. Changing PfPR2-10 was compared against plausible explanatory variables. The fitted model was used to categorize areas with varying degrees of prediction probability for two important policy thresholds PfPR2-10 < 1% (non-exceedance probability) or ≥ 30% (exceedance probability). RESULTS: 5020 surveys at 3701 communities were assembled. Nationally, there was an 88% reduction in the mean modelled PfPR2-10 from 21.2% (ICR: 13.8-32.1%) in 1990 to 2.6% (ICR: 1.8-3.9%) in 2015. The most significant decline began in 2003. Declining prevalence was not equal across the country and did not directly coincide with scaled vector control coverage or changing therapeutics. Over the period 2013-2015, of Kenya's 47 counties, 23 had an average PfPR2-10 of < 1%; four counties remained ≥ 30%. Using a metric of 80% probability, 8.5% of Kenya's 2015 population live in areas with PfPR2-10 ≥ 30%; while 61% live in areas where PfPR2-10 is < 1%. CONCLUSIONS: Kenya has made substantial progress in reducing the prevalence of malaria over the last 26 years. Areas today confidently and consistently with < 1% prevalence require a revised approach to control and a possible consideration of strategies that support pre-elimination. Conversely, there remains several intractable areas where current levels and approaches to control might be inadequate. The modelling approaches presented here allow the Ministry of Health opportunities to consider data-driven model certainty in defining their future spatial targeting of resources.

Using non-exceedance probabilities of policy-relevant malaria prevalence thresholds to identify areas of low transmission in Somalia.

BACKGROUND: Countries planning malaria elimination must adapt from sustaining universal control to targeted intervention and surveillance. Decisions to make this transition require interpretable information, including malaria parasite survey data. As transmission declines, observed parasite prevalence becomes highly heterogeneous with most communities reporting estimates close to zero. Absolute estimates of prevalence become hard to interpret as a measure of transmission intensity and suitable statistical methods are required to handle uncertainty of area-wide predictions that are programmatically relevant. METHODS: A spatio-temporal geostatistical binomial model for Plasmodium falciparum prevalence (PfPR) was developed using data from cross-sectional surveys conducted in Somalia in 2005, 2007-2011 and 2014. The fitted model was then used to generate maps of non-exceedance probabilities, i.e. the predictive probability that the region-wide population-weighted average PfPR for children between 2 and 10 years (PfPR2-10) lies below 1 and 5%. A comparison was carried out with the decision-making outcomes from those of standard approaches that ignore uncertainty in prevalence estimates. RESULTS: By 2010, most regions in Somalia were at least 70% likely to be below 5% PfPR2-10 and, by 2014, 17 regions were below 5% PfPR2-10 with a probability greater than 90%. Larger uncertainty is observed using a threshold of 1%. By 2011, only two regions were more than 90% likely of being < 1% PfPR2-10 and, by 2014, only three regions showed such low level of uncertainty. The use of non-exceedance probabilities indicated that there was weak evidence to classify 10 out of the 18 regions as < 1% in 2014, when a greater than 90% non-exceedance probability was required. CONCLUSION: Unlike standard approaches, non-exceedance probabilities of spatially modelled PfPR2-10 allow to quantify uncertainty of prevalence estimates in relation to policy relevant intervention thresholds, providing programmatically relevant metrics to make decisions on transitioning from sustained malaria control to strategies that encompass methods of malaria elimination.