Entomological assessment of hessian fabric transfluthrin vapour emanators as a means to protect against outdoor-biting Aedes after providing them to households for routine use in Port-au-Prince, Haiti.

BACKGROUND: A simple treated fabric device for passively emanating the volatile pyrethroid transfluthrin was recently developed in Tanzania that protected against nocturnal Anopheles and Culex mosquitoes for several months. Here these transfluthrin emanators were assessed in Port-au-Prince, Haiti against outdoor-biting Aedes. METHODS: Transfluthrin emanators were distributed to participating households in poor-to-middle class urban neighbourhoods and evaluated once every two months in terms of their effects on human landing rates of wild Aedes populations. A series of three such entomological assessment experiments were conducted, to examine the influence of changing weather conditions, various transfluthrin formulations and emanator placement on protective efficacy measurements. Laboratory experiments assessed resistance of local Aedes aegypti to transfluthrin and deltamethrin, and the irritancy and repellency of the transfluthrin-treated fabric used in the field. RESULTS: Across all three entomological field assessments, little evidence of protection against wild Ae. aegypti was observed, regardless of weather conditions, transfluthrin formulation or emanator placement: A generalized linear mixed model fitted to the pooled data from all three assessment rounds (921 females caught over 5129 hours) estimated a relative landing rate [95% Confidence interval] of 0.87 [0.73, 1.04] for users of treated versus untreated emanators (P = 0.1241). Wild Ae. aegypti in this setting were clearly resistant to transfluthrin when compared to a fully susceptible colony. CONCLUSIONS: Transfluthrin emanators had little if any apparent effect upon Aedes landing rates by wild Ae. aegypti in urban Haiti, and similar results have been obtained by comparable studies in Tanzania, Brazil and Peru. In stark contrast, however, parallel sociological assessments of perspectives among these same end-users in urban Haitian communities indicate strong satisfaction in terms of perceived protection against mosquitoes. It remains unclear why the results obtained from these complementary entomological and sociological assessments in Haiti differ so much, as do those from a similar set of studies in Brazil. It is encouraging, however, that similar contrasts between the entomological and epidemiological results of a recent large-scale assessment of another transfluthrin emanator product in Peru, which indicate they provide useful protection against Aedes-borne arboviral infections, despite apparently providing only modest protection against Aedes mosquito bites.

Spatial Clustering and Risk Factors for Malaria Infections and Marker of Recent Exposure to Plasmodium falciparum from a Household Survey in Artibonite, Haiti.

Targeting malaria interventions in elimination settings where transmission is heterogeneous is essential to ensure the efficient use of resources. Identifying the most important risk factors among persons experiencing a range of exposure can facilitate such targeting. A cross-sectional household survey was conducted in Artibonite, Haiti, to identify and characterize spatial clustering of malaria infections. Household members (N = 21,813) from 6,962 households were surveyed and tested for malaria. An infection was defined as testing positive for Plasmodium falciparum by either a conventional or novel highly sensitive rapid diagnostic test. Seropositivity to the early transcribed membrane protein 5 antigen 1 represented recent exposure to P. falciparum. Clusters were identified using SaTScan. Associations among individual, household, and environmental risk factors for malaria, recent exposure, and living in spatial clusters of these outcomes were evaluated. Malaria infection was detected in 161 individuals (median age: 15 years). Weighted malaria prevalence was low (0.56%; 95% CI: 0.45-0.70%). Serological evidence of recent exposure was detected in 1,134 individuals. Bed net use, household wealth, and elevation were protective, whereas being febrile, over age 5 years, and living in either households with rudimentary wall material or farther from the road increased the odds of malaria. Two predominant overlapping spatial clusters of infection and recent exposure were identified. Individual, household, and environmental risk factors are associated with the odds of individual risk and recent exposure in Artibonite; spatial clusters are primarily associated with household-level risk factors. Findings from serology testing can further strengthen the targeting of interventions.

Acceptability, Feasibility, Drug Safety, and Effectiveness of a Pilot Mass Drug Administration with a Single Round of Sulfadoxine-Pyrimethamine Plus Primaquine and Indoor Residual Spraying in Communities with Malaria Transmission in Haiti, 2018.

For a malaria elimination strategy, Haiti's National Malaria Control Program piloted a mass drug administration (MDA) with indoor residual spraying (IRS) in 12 high-transmission areas across five communes after implementing community case management and strengthened surveillance. The MDA distributed sulfadoxine-pyrimethamine and single low-dose primaquine to eligible residents during house visits. The IRS campaign applied pirimiphos-methyl insecticide on walls of eligible houses. Pre- and post-campaign cross-sectional surveys were conducted to assess acceptability, feasibility, drug safety, and effectiveness of the combined interventions. Stated acceptability for MDA before the campaign was 99.2%; MDA coverage estimated at 10 weeks post-campaign was 89.6%. Similarly, stated acceptability of IRS at baseline was 99.9%; however, household IRS coverage was 48.9% because of the high number of ineligible houses. Effectiveness measured by Plasmodium falciparum prevalence at baseline and 10 weeks post-campaign were similar: 1.31% versus 1.43%, respectively. Prevalence of serological markers were similar at 10 weeks post-campaign compared with baseline, and increased at 6 months. No severe adverse events associated with the MDA were identified in the pilot; there were severe adverse events in a separate, subsequent campaign. Both MDA and IRS are acceptable and feasible interventions in Haiti. Although a significant impact of a single round of MDA/IRS on malaria transmission was not found using a standard pre- and post-intervention comparison, it is possible there was blunting of the peak transmission. Seasonal malaria transmission patterns, suboptimal IRS coverage, and low baseline parasitemia may have limited the effectiveness or the ability to measure effectiveness.

How well do coverage surveys and programmatically reported mass drug administration coverage match? Results from 214 mass drug administration campaigns in 15 countries, 2008-2017.

INTRODUCTION: Delivering preventive chemotherapy through mass drug administration (MDA) is a central approach in controlling or eliminating several neglected tropical diseases (NTDs). Treatment coverage, a primary indicator of MDA performance, can be measured through routinely reported programmatic data or population-based coverage evaluation surveys. Reported coverage is often the easiest and least expensive way to estimate coverage; however, it is prone to inaccuracies due to errors in data compilation and imprecise denominators, and in some cases measures treatments offered as opposed to treatments swallowed. OBJECTIVE: Analyses presented here aimed to understand (1) how often coverage calculated using routinely reported data and survey data would lead programme managers to make the same programmatic decisions; (2) the magnitude and direction of the difference between these two estimates, and (3) whether there is meaningful variation by region, age group or country. METHODS: We analysed and compared reported and surveyed treatment coverage data from 214 MDAs implemented between 2008 and 2017 in 15 countries in Africa, Asia and the Caribbean. Routinely reported treatment coverage was compiled using data reported by national NTD programmes to donors, either directly or via NTD implementing partners, following the implementation of a district-level MDA campaign; coverage was calculated by dividing the number of individuals treated by a population value, which is typically based on national census projections and occasionally community registers. Surveyed treatment coverage came from post-MDA community-based coverage evaluation surveys, which were conducted as per standardised WHO recommended methodology. RESULTS: Coverage estimates using routine reporting and surveys gave the same result in terms of whether the minimum coverage threshold was reached in 72% of the MDAs surveyed in the Africa region and in 52% in the Asia region. The reported coverage value was within ±10 percentage points of the surveyed coverage value in 58/124 of the surveyed MDAs in the Africa region and 19/77 in the Asia region. Concordance between routinely reported and surveyed coverage estimates was 64% for the total population and 72% for school-age children. The study data showed variation across countries in the number of surveys conducted as well as the frequency with which there was concordance between the two coverage estimates. CONCLUSIONS: Programme managers must grapple with making decisions based on imperfect information, balancing needs for accuracy with cost and available capacity. The study shows that for many of the MDAs surveyed, based on the concordance with respect to reaching the minimum coverage thresholds, the routinely reported data were accurate enough to make programmatic decisions. Where coverage surveys do show a need to improve accuracy of routinely reported results, NTD programme managers should use various tools and approaches to strengthen data quality in order to use data for decision-making to achieve NTD control and elimination goals.

Factors Associated With Human IgG Antibody Response to Anopheles albimanus Salivary Gland Extract, Artibonite Department, Haiti, 2017.

Serological data can provide estimates of human exposure to both malaria vector and parasite based on antibody responses. A multiplex bead-based assay was developed to simultaneously detect IgG to Anopheles albimanus salivary gland extract (SGE) and 23 Plasmodium falciparum antigens among 4185 participants enrolled in Artibonite department, Haiti in 2017. Logistic regression adjusted for participant- and site-level covariates and found children under 5 years and 6-15 years old had 3.7- and 5.4-fold increase in odds, respectively, of high anti-SGE IgG compared to participants >15 years. Seropositivity to P. falciparum CSP, Rh2_2030, and SEA-1 antigens was significantly associated with high IgG response against SGE, and participant enrolment at elevations under 200 m was associated with higher anti-SGE IgG levels. The ability to approximate population exposure to malaria vectors through SGE serology data is very dependent by age categories, and SGE antigens can be easily integrated into a multiplex serological assay.

Country Reports on Practical Aspects of Conducting Large-Scale Community Studies of the Tolerability of Mass Drug Administration with Ivermectin/Diethylcarbamazine/Albendazole for Lymphatic Filariasis.

This article is a compilation of summaries prepared by lead investigators for large-scale safety and efficacy studies on mass drug administration of IDA (ivermectin, diethylcarbamazine, and albendazole) for lymphatic filariasis. The summaries highlight the experiences of study teams that assessed the safety and efficacy of IDA in five countries: India, Indonesia, Haiti, Papua New Guinea, and Fiji. They also highlight significant challenges encountered during these community studies and responses to those challenges that contributed to success.

Simulating the effect of evaluation unit size on eligibility to stop mass drug administration for lymphatic filariasis in Haiti.

BACKGROUND: The Transmission Assessment Survey (TAS) is a decision-making tool to determine when transmission of lymphatic filariasis is presumed to have reached a level low enough that it cannot be sustained even in the absence of mass drug administration. The survey is applied over geographic areas, called evaluation units (EUs); existing World Health Organization guidelines limit EU size to a population of no more than 2 million people. METHODOLOGY/PRINCIPAL FINDINGS: In 2015, TASs were conducted in 14 small EUs in Haiti. Simulations, using the observed TAS results, were performed to understand the potential programmatic impact had Haiti chosen to form larger EUs. Nine "combination-EUs" were formed by grouping adjacent EUs, and bootstrapping was used to simulate the expected TAS results. When the combination-EUs were comprised of at least one "passing" and one "failing" EU, the majority of these combination-EU would pass the TAS 79% - 100% of the time. Even in the case when both component EUs had failed, the combination-EU was expected to "pass" 11% of the time. Simulations of mini-TAS, a strategy with smaller power and hence smaller sample size than TAS, resulted in more conservative "passing" and "failing" when implemented in original EUs. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate the high potential for misclassification when the average prevalence of lymphatic filariasis in the combined areas differs with regards to the TAS threshold. Of particular concern is the risk of "passing" larger EUs that include focal areas where prevalence is high enough to be potentially self-sustaining. Our results reaffirm the approach that Haiti took in forming smaller EUs. Where baseline or monitoring data show a high or heterogeneous prevalence, programs should leverage alternative strategies like mini-TAS in smaller EUs, or consider gathering additional data through spot check sites to advise EU formation.

The Immediate Effects of a Combined Mass Drug Administration and Indoor Residual Spraying Campaign to Accelerate Progress Toward Malaria Elimination in Grande-Anse, Haiti.

BACKGROUND: Haiti is planning targeted interventions to accelerate progress toward malaria elimination. In the most affected department (Grande-Anse), a combined mass drug administration (MDA) and indoor residual spraying (IRS) campaign was launched in October 2018. This study assessed the intervention's effectiveness in reducing Plasmodium falciparum prevalence. METHODS: An ecological quasi-experimental study was designed, using a pretest and posttest with a nonrandomized control group. Surveys were conducted in November 2017 in a panel of easy access groups (25 schools and 16 clinics) and were repeated 2-6 weeks after the campaign, in November 2018. Single-dose sulfadoxine-pyrimethamine and primaquine was used for MDA, and pirimiphos-methyl as insecticide for IRS. RESULTS: A total of 10 006 participants were recruited. Fifty-two percent of the population in the intervention area reported having received MDA. Prevalence diminished between 2017 and 2018 in both areas, but the reduction was significantly larger in the intervention area (ratio of adjusted risk ratios, 0.32 [95% confidence interval, .104-.998]). CONCLUSIONS: Despite a moderate coverage, the campaign was effective in reducing P. falciparum prevalence immediately after 1 round. Targeted MDA plus IRS is useful in preelimination settings to rapidly decrease the parasite reservoir, an encouraging step to accelerate progress toward malaria elimination.

Mapping the endemicity and seasonality of clinical malaria for intervention targeting in Haiti using routine case data.

Towards the goal of malaria elimination on Hispaniola, the National Malaria Control Program of Haiti and its international partner organisations are conducting a campaign of interventions targeted to high-risk communities prioritised through evidence-based planning. Here we present a key piece of this planning: an up-to-date, fine-scale endemicity map and seasonality profile for Haiti informed by monthly case counts from 771 health facilities reporting from across the country throughout the 6-year period from January 2014 to December 2019. To this end, a novel hierarchical Bayesian modelling framework was developed in which a latent, pixel-level incidence surface with spatio-temporal innovations is linked to the observed case data via a flexible catchment sub-model designed to account for the absence of data on case household locations. These maps have focussed the delivery of indoor residual spraying and focal mass drug administration in the Grand'Anse Department in South-Western Haiti.

Detecting Malaria Hotspots in Haiti, a Low-Transmission Setting.

In 2006, Haiti committed to malaria elimination when the transmission was thought to be low, but before robust national parasite prevalence estimates were available. In 2011, the first national population-based survey confirmed the national malaria parasite prevalence was < 1%. In both 2014 and 2015, Haiti reported approximately 17,000 malaria cases identified passively at health facilities. To detect malaria transmission hotspots for targeting interventions, the National Malaria Control Program (NMCP) piloted an enhanced geographic information surveillance system in three departments with relatively high-, medium-, and low-transmission areas. From October 2014-September 2015, NMCP staff abstracted health facility records of confirmed malaria cases from 59 health facilities and geo-located patients' households. Household locations were aggregated to 1-km2 grid cells to calculate cumulative incidence rates (CIRs) per 1,000 persons. Spatial clustering of CIRs were tested using Getis-Ord Gi* analysis. Space-time permutation models searched for clusters up to 6 km in distance using a 1-month malaria transmission window. Of the 2,462 confirmed cases identified from health facility records, 58% were geo-located. Getis-Ord Gi* analysis identified 43 1-km2 hotspots in coastal and inland areas that overlapped primarily with 13 space-time clusters (size: 0.26-2.97 km). This pilot describes the feasibility of detecting malaria hotspots in resource-poor settings. More data from multiple years and serological household surveys are needed to assess completeness and hotspot stability. The NMCP can use these pilot methods and results to target foci investigations and malaria interventions more accurately.

A multicenter, community-based, mixed methods assessment of the acceptability of a triple drug regimen for elimination of lymphatic filariasis.

BACKGROUND: Many countries will not reach elimination targets for lymphatic filariasis in 2020 using the two-drug treatment regimen (diethylcarbamazine citrate [DEC] and albendazole [DA]). A cluster-randomized, community-based safety study performed in Fiji, Haiti, India, Indonesia and Papua New Guinea tested the safety and efficacy of a new regimen of ivermectin, DEC and albendazole (IDA). METHODOLOGY/PRINCIPAL FINDINGS: To assess acceptability of IDA and DA, a mixed methods study was embedded within this community-based safety study. The study objective was to assess the acceptability of IDA versus DA. Community surveys were performed in each country with randomly selected participants (>14 years) from the safety study participant list in both DA and IDA arms. In depth interviews (IDI) and focus group discussions (FGD) assessed acceptability-related themes. In 1919 individuals, distribution of sex, microfilariae (Mf) presence and circulating filarial antigenemia (CFA), adverse events (AE) and age were similar across arms. A composite acceptability score summed the values from nine indicators (range 9-36). The median (22.5) score indicated threshold of acceptability. There was no difference in scores for IDA and DA regimens. Mean acceptability scores across both treatment arms were: Fiji 33.7 (95% CI: 33.1-34.3); Papua New Guinea 32.9 (95% CI: 31.9-33.8); Indonesia 30.6 (95% CI: 29.8-31.3); Haiti 28.6 (95% CI: 27.8-29.4); India 26.8 (95% CI: 25.6-28) (P<0.001). AE, Mf or CFA were not associated with acceptability. Qualitative research (27 FGD; 42 IDI) highlighted professionalism and appreciation for AE support. No major concerns were detected about number of tablets. Increased uptake of LF treatment by individuals who had never complied with MDA was observed. CONCLUSIONS/SIGNIFICANCE: IDA and DA regimens for LF elimination were highly and equally acceptable in individuals participating in the community-based safety study in Fiji, Haiti, India, Indonesia, and Papua New Guinea. Country variation in acceptability was significant. Acceptability of the professionalism of the treatment delivery was highlighted.

Genetic analysis reveals unique characteristics of Plasmodium falciparum parasite populations in Haiti.

BACKGROUND: With increasing interest in eliminating malaria from the Caribbean region, Haiti is one of the two countries on the island of Hispaniola with continued malaria transmission. While the Haitian population remains at risk for malaria, there are a limited number of cases annually, making conventional epidemiological measures such as case incidence and prevalence of potentially limited value for fine-scale resolution of transmission patterns and trends. In this context, genetic signatures may be useful for the identification and characterization of the Plasmodium falciparum parasite population in order to identify foci of transmission, detect outbreaks, and track parasite movement to potentially inform malaria control and elimination strategies. METHODS: This study evaluated the genetic signals based on analysis of 21 single-nucleotide polymorphisms (SNPs) from 462 monogenomic (single-genome) P. falciparum DNA samples extracted from dried blood spots collected from malaria-positive patients reporting to health facilities in three southwestern Haitian departments (Nippes, Grand'Anse, and Sud) in 2016. RESULTS: Assessment of the parasite genetic relatedness revealed evidence of clonal expansion within Nippes and the exchange of parasite lineages between Nippes, Sud, and Grand'Anse. Furthermore, 437 of the 462 samples shared high levels of genetic similarity-at least 20 of 21 SNPS-with at least one other sample in the dataset. CONCLUSIONS: These results revealed patterns of relatedness suggestive of the repeated recombination of a limited number of founding parasite types without significant outcrossing. These genetic signals offer clues to the underlying relatedness of parasite populations and may be useful for the identification of the foci of transmission and tracking of parasite movement in Haiti for malaria elimination.

Establishing a National Molecular Surveillance Program for the Detection of Plasmodium falciparum Markers of Resistance to Antimalarial Drugs in Haiti.

Chloroquine remains the first-line treatment for uncomplicated malaria in Haiti, and until recently, sulfadoxine-pyrimethamine was the second-line treatment. A few studies have reported the presence of molecular markers for resistance in Plasmodium falciparum parasites, and in vivo therapeutic efficacy studies (TESs) have been limited. Recognizing the history of antimalarial resistance around the globe and the challenges of implementing TESs in low-endemic areas, the Ministry of Health established a surveillance program to detect molecular markers of antimalarial resistance in Haiti. Sentinel sites were purposefully selected in each of Haiti's 10 administrative departments; an 11th site was selected in Grand'Anse, the department with the highest number of reported cases. Factors considered for site selection included the number of malaria cases identified, observed skills of laboratory technicians conducting rapid diagnostic tests (RDTs), stock and storage conditions of RDTs, accuracy of data reporting to the national surveillance system, and motivation to participate. Epidemiologic data from 2,437 patients who tested positive for malaria from March 2016 to December 2018 and consented to provide samples for molecular sequencing are presented here. Of these, 936 (38.4%) patients reported self-treatment with any medication since the onset of their illness before diagnosis; overall, 69 (2.8%) patients reported taking an antimalarial. Ten patients (0.4%) reported travel away from their home for at least one night in the month before diagnosis. Establishing a molecular surveillance program for antimalarial drug resistance proved practical and feasible in a resource-limited setting and will provide the evidence needed to make informed treatment policy decisions at the national level.

Safety and efficacy of co-administered diethylcarbamazine, albendazole and ivermectin during mass drug administration for lymphatic filariasis in Haiti: Results from a two-armed, open-label, cluster-randomized, community study.

In Haiti, 22 communes still require mass drug administration (MDA) to eliminate lymphatic filariasis (LF) as a public health problem. Several clinical trials have shown that a single oral dose of ivermectin (IVM), diethylcarbamazine (DEC) and albendazole (ALB) (IDA) is more effective than DEC plus ALB (DA) for clearing Wuchereria bancrofti microfilariae (Mf). We performed a cluster-randomized community study to compare the safety and efficacy of IDA and DA in an LF-endemic area in northern Haiti. Ten localities were randomized to receive either DA or IDA. Participants were monitored for adverse events (AE), parasite antigenemia, and microfilaremia. Antigen-positive participants were retested one year after MDA to assess treatment efficacy. Fewer participants (11.0%, 321/2917) experienced at least one AE after IDA compared to DA (17.3%, 491/2844, P<0.001). Most AEs were mild, and the three most common AEs reported were headaches, dizziness and abdominal pain. Serious AEs developed in three participants who received DA. Baseline prevalence for filarial antigenemia was 8.0% (239/3004) in IDA localities and 11.5% (344/2994) in DA localities (<0.001). Of those with positive antigenemia, 17.6% (42/239) in IDA localities and 20.9% (72/344, P = 0.25) in DA localities were microfilaremic. One year after treatment, 84% percent of persons with positive filarial antigen tests at baseline could be retested. Clearance rates for filarial antigenemia were 20.5% (41/200) after IDA versus 25.4% (74/289) after DA (P = 0.3). However, 94.4% (34/36) of IDA recipients and 75.9% (44/58) of DA recipients with baseline microfilaremia were Mf negative at the time of retest (P = 0.02). Thus, MDA with IDA was at least as well tolerated and significantly more effective for clearing Mf compared to the standard DA regimen in this study. Effective MDA coverage with IDA could accelerate the elimination of LF as a public health problem in the 22 communes that still require MDA in Haiti.

Risk factors associated with failing pre-transmission assessment surveys (pre-TAS) in lymphatic filariasis elimination programs: Results of a multi-country analysis.

Achieving elimination of lymphatic filariasis (LF) as a public health problem requires a minimum of five effective rounds of mass drug administration (MDA) and demonstrating low prevalence in subsequent assessments. The first assessments recommended by the World Health Organization (WHO) are sentinel and spot-check sites-referred to as pre-transmission assessment surveys (pre-TAS)-in each implementation unit after MDA. If pre-TAS shows that prevalence in each site has been lowered to less than 1% microfilaremia or less than 2% antigenemia, the implementation unit conducts a TAS to determine whether MDA can be stopped. Failure to pass pre-TAS means that further rounds of MDA are required. This study aims to understand factors influencing pre-TAS results using existing programmatic data from 554 implementation units, of which 74 (13%) failed, in 13 countries. Secondary data analysis was completed using existing data from Bangladesh, Benin, Burkina Faso, Cameroon, Ghana, Haiti, Indonesia, Mali, Nepal, Niger, Sierra Leone, Tanzania, and Uganda. Additional covariate data were obtained from spatial raster data sets. Bivariate analysis and multilinear regression were performed to establish potential relationships between variables and the pre-TAS result. Higher baseline prevalence and lower elevation were significant in the regression model. Variables statistically significantly associated with failure (p-value ≤0.05) in the bivariate analyses included baseline prevalence at or above 5% or 10%, use of Filariasis Test Strips (FTS), primary vector of Culex, treatment with diethylcarbamazine-albendazole, higher elevation, higher population density, higher enhanced vegetation index (EVI), higher annual rainfall, and 6 or more rounds of MDA. This paper reports for the first time factors associated with pre-TAS results from a multi-country analysis. This information can help countries more effectively forecast program activities, such as the potential need for more rounds of MDA, and prioritize resources to ensure adequate coverage of all persons in areas at highest risk of failing pre-TAS.

Risk Factors for Malaria Infection and Seropositivity in the Elimination Area of Grand'Anse, Haiti: A Case-Control Study among Febrile Individuals Seeking Treatment at Public Health Facilities.

The island of Hispaniola aims to eliminate malaria by 2025; however, there are limited data to describe epidemiologic risk factors for malaria in this setting. A prospective case-control study was conducted at four health facilities in southwest Haiti, aiming to describe factors influencing the risk of current and past malaria infection. Cases were defined as individuals attending facilities with current or recent fever and positive malaria rapid diagnostic test (RDT), while controls were those with current or recent fever and RDT negative. Serological markers of recent and cumulative exposure to Plasmodium were assessed using the multiplex bead assay from dried blood spots and used for alternate case definitions. Kuldorff's spatial scan statistic was used to identify local clusters of infection or exposure. Logistic regression models were used to assess potential risk factors for RDT positivity and recent exposure markers, including age-group, gender, and recruiting health facility as group-matching variables. A total of 192 cases (RDT positive) and 915 controls (RDT negative) were recruited. Consistent spatial clusters were identified for all three infection and exposure metrics, indicating temporal stability of malaria transmission at these sites. Risk factors included remoteness from health facilities and household construction, furthermore, insecticide-treated net ownership or use was associated with reduced odds of RDT positivity. These findings indicate the malaria risk in Grand'Anse is driven primarily by location. Travel, occupation, and other behavioral factors were not associated with malaria. These data can support the National Malaria Program to refine and target their intervention approaches, and to move toward elimination.

The roles of stakeholder experience and organizational learning in declining mass drug administration coverage for lymphatic filariasis in Port-au-Prince, Haiti: A case study.

The World Health Organization (WHO) defines an effective round of mass drug administration (MDA) for lymphatic filariasis (LF) as one that reaches at least 65% of the target population. In its first round of MDA in 2011-2012, the National Program to Eliminate LF in Haiti achieved a 79% epidemiological coverage in urban Port-au-Prince. In 2013, coverage dropped below the WHO threshold and has declined year-over-year to a low of 41% in 2017. We conducted a retrospective qualitative case study to identify key factors behind the decline in coverage in Port-au-Prince and ways to address them. Our findings suggest that the main contributors to the decline in MDA coverage appear to be the absence of effective documentation of practices, reporting, analysis, and program quality improvement-i.e., learning mechanisms-within the program's MDA design and implementation strategy. In addition to their contribution to the program's failure to meet its coverage targets, these deficits have resulted in a high cost for the MDA campaign in both lost momentum and depleted morale. Through a proposed operating logic model, we explore how the pathway from program inputs to outcomes is influenced by a wide array of mediating factors, which shape potential participants' experience of MDA and, in turn, influence their reasoning and decisions to take, or not take, the pills. Our model suggests that the decisions and behavior of individuals are a reflection of their overall experience of the program itself, mediated through a host of contextual factors, and not simply the expression of a fixed choice or preference. This holistic approach offers a novel and potentially valuable framing for the planning and evaluation of MDA strategies for LF and other diseases, and may be applicable in a variety of global health programs.

Association between the proportion of Plasmodium falciparum and Plasmodium vivax infections detected by passive surveillance and the magnitude of the asymptomatic reservoir in the community: a pooled analysis of paired health facility and community data.

BACKGROUND: Passively collected malaria case data are the foundation for public health decision making. However, because of population-level immunity, infections might not always be sufficiently symptomatic to prompt individuals to seek care. Understanding the proportion of all Plasmodium spp infections expected to be detected by the health system becomes particularly paramount in elimination settings. The aim of this study was to determine the association between the proportion of infections detected and transmission intensity for Plasmodium falciparum and Plasmodium vivax in several global endemic settings. METHODS: The proportion of infections detected in routine malaria data, P(Detect), was derived from paired household cross-sectional survey and routinely collected malaria data within health facilities. P(Detect) was estimated using a Bayesian model in 431 clusters spanning the Americas, Africa, and Asia. The association between P(Detect) and malaria prevalence was assessed using log-linear regression models. Changes in P(Detect) over time were evaluated using data from 13 timepoints over 2 years from The Gambia. FINDINGS: The median estimated P(Detect) across all clusters was 12·5% (IQR 5·3-25·0) for P falciparum and 10·1% (5·0-18·3) for P vivax and decreased as the estimated log-PCR community prevalence increased (adjusted odds ratio [OR] for P falciparum 0·63, 95% CI 0·57-0·69; adjusted OR for P vivax 0·52, 0·47-0·57). Factors associated with increasing P(Detect) included smaller catchment population size, high transmission season, improved care-seeking behaviour by infected individuals, and recent increases (within the previous year) in transmission intensity. INTERPRETATION: The proportion of all infections detected within health systems increases once transmission intensity is sufficiently low. The likely explanation for P falciparum is that reduced exposure to infection leads to lower levels of protective immunity in the population, increasing the likelihood that infected individuals will become symptomatic and seek care. These factors might also be true for P vivax but a better understanding of the transmission biology is needed to attribute likely reasons for the observed trend. In low transmission and pre-elimination settings, enhancing access to care and improvements in care-seeking behaviour of infected individuals will lead to an increased proportion of infections detected in the community and might contribute to accelerating the interruption of transmission. FUNDING: Wellcome Trust.

Conventional and High-Sensitivity Malaria Rapid Diagnostic Test Performance in 2 Transmission Settings: Haiti 2017.

Accurate malaria diagnosis is foundational for control and elimination, and Haiti relies on histidine-rich protein 2 (HRP2)-based rapid diagnostic tests (RDTs) identifying Plasmodium falciparum in clinical and community settings. In 2017, 1 household and 2 easy-access group surveys tested all participants (N = 32 506) by conventional and high-sensitivity RDTs. A subset of blood samples (n = 1154) was laboratory tested for HRP2 by bead-based immunoassay and for P. falciparum 18S rDNA by photo-induced electron transfer polymerase chain reaction. Both RDT types detected low concentrations of HRP2 with sensitivity estimates between 2.6 ng/mL and 14.6 ng/mL. Compared to the predicate HRP2 laboratory assay, RDT sensitivity ranged from 86.3% to 96.0% between tests and settings, and specificity from 90.0% to 99.6%. In the household survey, the high-sensitivity RDT provided a significantly higher number of positive tests, but this represented a very small proportion (<0.2%) of all participants. These data show that a high-sensitivity RDT may have limited utility in a malaria elimination setting like Haiti.

Assessing the role of the private sector in surveillance for malaria elimination in Haiti and the Dominican Republic: a qualitative study.

BACKGROUND: Haiti and the Dominican Republic (DR) are targeting malaria elimination by 2022. The private health sector has been relatively unengaged in these efforts, even though most primary health care in Haiti is provided by non-state actors, and many people use traditional medicine. Data on private health sector participation in malaria elimination efforts are lacking, as are data on care-seeking behaviour of patients in the private health sector. This study sought to describe the role of private health sector providers, care-seeking behaviour of individuals at high risk of malaria, and possible means of engaging the private health sector in Hispaniola's malaria elimination efforts. METHODS: In-depth interviews with 26 key informants (e.g. government officials), 62 private providers, and 63 patients of private providers, as well as 12 focus group discussions (FGDs) with community members, were conducted within seven study sites in Haiti and the DR. FGDs focused on local definitions of the private health sector and identified private providers for interview recruitment, while interviews focused on private health sector participation in malaria elimination activities and treatment-seeking behaviour of febrile individuals. RESULTS: Interviews revealed that self-medication is the most common first step in the trajectory of care for fevers in both Haiti and the DR. Traditional medicine is more commonly used in Haiti than in the DR, with many patients seeking care from traditional healers before, during, and/or after care in the formal health sector. Private providers were interested in participating in malaria elimination efforts but emphasized the need for ongoing support and training. Key informants agreed that the private health sector needs to be engaged, especially traditional healers in Haiti. The Haitian migrant population was reported to be one of the most at-risk groups by participants from both countries. CONCLUSION: Malaria elimination efforts across Hispaniola could be enhanced by engaging traditional healers in Haiti and other private providers with ongoing support and trainings; directing educational messaging to encourage proper treatment-seeking behaviour; and refining cross-border strategies for surveillance of the high-risk migrant population. Increasing distribution of rapid diagnostic tests (RDTs) and bi-therapy to select private health sector facilities, accompanied by adopting regulatory policies, could help increase numbers of reported and correctly treated malaria cases.