Baseline characterization of entomological drivers of malaria transmission in Namibia: a targeted operational entomological surveillance strategy.

BACKGROUND: Namibia's focus on the elimination of malaria requires an evidence-based strategy directed at understanding and targeting the entomological drivers of malaria transmission. In 2018 and 2019, the Namibia National Vector-borne Diseases Control Program (NVDCP) implemented baseline entomological surveillance based on a question-based approach outlined in the Entomological Surveillance Planning Tool (ESPT). In the present study, we report on the findings of the ESPT-based NVDCP on baseline vector species composition and bionomic traits in malaria endemic regions in northern Namibia, which has the aim of generating an evidence base for programmatic decision-making. METHODS: Nine representative sentinel sites were included in the 2018 entomological surveillance program (Kunene, Omusati, Oshana, Ohangwena, Oshikoto, Otjozondjupa, Kavango West, Kavango East and Zambezi); the number was reduced to four sites in 2019 due to limited funding (Ohangwena, Kavango West, Kavango East, and Zambezi). In the 2018 baseline collections, multiple sampling methods (human landing catches, pyrethroid spray catches, U.S. Centers for Disease Control and Prevention light traps [CDC-LTs], resting boxes [RBs] and larval sampling) were utilized to evaluate indoor/outdoor human biting rates, resting behaviors and insecticide resistance (IR). CDC-LTs and RBs were not used in 2019 due to low and non-representative sampling efficacies. RESULTS: Overall, molecular evidence demonstrated the presence of three primary mosquito vectors, namely Anopheles arabiensis, rediscovered Anopheles gambiae sensu stricto and Anopheles funestus sensu stricto, alongside Anopheles squamosus and members of the Anopheles coustani complex. Vectors were found to bite throughout the night (1800 hours 0600 hours) both indoors and outdoors, with An. arabiensis having the highest biting rates outdoors. Low numbers of indoor resting Anopheles point to possible low indoor residual spraying (IRS) efficacy-with An. arabiensis found to be the major vector species resting indoors. The IR tests demonstrated varying country-wide resistance levels to the insecticide deltamethrin, with the resistance levels confirmed to have increased in 2019, evidence that impacts national programmatic decision-making. Vectors demonstrated susceptibility to the insecticides dichlorodiphenyltrichloroethane, bendiocarb and Actellic 300CS in 2018, with mosquitoes from only one site (Kavango West) demonstrating possible resistance to DDT. Targeted and question-based entomological surveillance enabled a rapid and focused evidence base to be built, showing where and when humans were being bitten and providing entomological data on long-lasting insecticidal nets, IRS efficacy and insecticide resistance, which the Ministry of Health and Social Services-Namibia can use to further build a monitoring and evaluation framework for understanding the drivers of transmission. CONCLUSION: Identification and characterization of species-specific bionomic traits allows for an understanding of where and when vector human contact may occur as well as the potential impact of interventions. Low indoor resting rates as well as the presence of insecticide resistance (and the increase in its frequency) point to the need for mosquito-behavior-directed and appropriate interventions as well as the requirement for a resistance mitigation strategy. The ESPT-based question- and minimal essential indicator-based operational research strategy provides programs with directed and focused data for facilitating decision-making while requiring limited funding and capacity.

Demographic and environmental factors associated with the distribution of Aedes albopictus in Cameroon.

Aedes-transmitted arboviruses have spread globally due to the spread of Aedes aegypti and Aedes albopictus. Its distribution is associated with human and physical geography. However, these factors have not been quantified in Cameroon. Therefore, the aim was to develop an Ae. albopictus geo-referenced database to examine the risk factors associated with the vector distribution in Cameroon. Data on the Ae. albopictus presence and absence were collated and mapped from studies in published scientific literature between 2000 and 2020. Publicly available earth observation data were used to assess human geography, land use and climate risk factors related to the vector distribution. A logistic binomial regression was conducted to identify the significant risk factors associated with Ae. albopictus distribution. In total, 111 data points were collated (presence = 87; absence = 24). Different data collection methods and sites hindered the spatiotemporal analysis. An increase of one wet month in a year increased the odds of Ae. albopictus presence by 5.6 times. One unit of peri-urban area increased the odds by 1.3 times. Using publicly available demographic and environmental data to better understand the key determinants of mosquito distributions may facilitate appropriately targeted public health messages and vector control strategies.

Prospects for developing efficient targets for the xenomonitoring and control of Simulium damnosum s.l., the major vectors of onchocerciasis in Africa.

Despite the ethical issues concerning the continued use of Human Landing Catches (HLC) to monitor the Simulium damnosum complex for epidemiological monitoring of onchocericasis, few attempts to develop alternatives have been reported. In studies on a wild population of S. damnosum in Burkina Faso, we tested visual targets (different sizes and shapes) and olfactory stimuli (CO2 , and POCA and BG-lure® odour blends) for their ability to attract and collect host seeking blackflies. At each trap, blackflies were caught with appropriately sized electrocuting grids and results from Latin square design tests were compared. Throughout, HLCs captured more blackflies than the targets. Of the traps tested, small targets (0.0625 and 0.5 m2 ) were the most efficient visual lure in terms of the number of S. damnosum captured per unit area 1.7-5× more than larger targets. Overall, results suggested that sticky black targets of horizontal rectangular shape (0.125-0.5 m2 ) and baited with a POCA and/or CO2 mixture could provide a cheap practical field alternative to HLC for onchocerciasis xenomonitoring, subject to confirmation that the design has no inherent bias for certain members of the S. damnosum species complex.

Knowledge translation and evidence generation to increase the impact of vector control in Burkina Faso, Cameroon and Malawi.

Lack of context-specific evidence and inadequate evidence-use for decision-making contribute to poor health. This paper reports on our work aimed at addressing the knowledge translation (KT) gap between evidence generators and users. We present our experiences of strengthening KT via technical advisory groups (TAGs) in parallel with increasing evidence generation through research fellowships and operational research. Vectorborne diseases (VBDs) impose substantial health and economic burdens in sub-Saharan Africa despite being preventable with vector control. The Partnership for Increasing the Impact of Vector Control aimed to reduce the burden of VBDs in Burkina Faso, Cameroon, Malawi and at regional and global levels. TAGs can promote evidence-use in policy and practice by engaging relevant stakeholders in both research and policy processes. TAGs and related activities are best facilitated by a coordinator with skills in research and policy. Contextual factors should influence the design and governance of TAGs, which will likely evolve over time. Relevant national stakeholders should be included in TAGs and be actively involved in developing research agendas to increase the relevance and acceptability of research findings for decision-making. The countries present three differing contexts with longer-term research and evaluation necessary to draw lessons on impact.

Vector control and entomological capacity for onchocerciasis elimination.

Mass drug administration (MDA) of ivermectin is currently the main strategy to achieve elimination of transmission (EoT) of onchocerciasis. Modelling suggests that EoT may not be reached in all endemic foci using annual MDA alone. Onchocerciasis and loiasis are coendemic in forest areas of Central Africa where ivermectin treatment can lead to severe adverse events in individuals with heavy loiasis load, rendering MDA inappropriate. Vector control has been proposed as a complementary intervention strategy. Here, we discuss (i) achievements and pitfalls of previous interventions; (ii) epidemiological impact, feasibility, and combination with MDA to accelerate and/or protect EoT; (iii) role of modelling; (iv) opportunities for innovative methods of vector monitoring and control; and (v) strengthening entomological capacity in endemic countries.

Spatial targeting of Screening + Eave tubes (SET), a house-based malaria control intervention, in Côte d'Ivoire: A geostatistical modelling study.

New malaria control tools and tailoring interventions to local contexts are needed to reduce the malaria burden and meet global goals. The housing modification, screening plus a targeted house-based insecticide delivery system called the In2Care® Eave Tubes, has been shown to reduce clinical malaria in a large cluster randomised controlled trial. However, the widescale suitability of this approach is unknown. We aimed to predict household suitability and define the most appropriate locations for ground-truthing where Screening + Eave Tubes (SET) could be implemented across Côte d'Ivoire. We classified DHS sampled households into suitable for SET based on the walls and roof materials. We fitted a Bayesian beta-binomial logistic model using the integrated nested Laplace approximation (INLA) to predict suitability of SET and to define priority locations for ground-truthing and to calculate the potential population coverage and costs. Based on currently available data on house type and malaria infection rate, 31% of the total population and 17.5% of the population in areas of high malaria transmission live in areas suitable for SET. The estimated cost of implementing SET in suitable high malaria transmission areas would be $46m ($13m -$108m). Ground-truthing and more studies should be conducted to evaluate the efficacy and feasibility of SET in these settings. The study provides an example of implementing strategies to reflect local socio-economic and epidemiological factors, and move beyond blanket, one-size-fits-all strategies.

Evaluation of a game-based training course to build capacity for insecticide resistance management in vector control programmes.

Across Africa, malaria control programmes are increasingly challenged with the emergence of insecticide resistance among malaria vector populations. Confronted with this challenge, vector control staff must understand insecticide resistance management, think comprehensively and react positively when confronted with new problems. However, information on the subject is often only available through written guidelines that are difficult to put into practice. Based on the successes and strengths of educational games for health, we developed and evaluated a novel game-based course to fill the gap in training resources for insecticide resistance management. The training was evaluated by analysing results of pre- and post-course knowledge tests and self-efficacy surveys, as well as post-course interviews. At the start of the training, fundamental concepts of insecticide resistance were reviewed through Resistance101, a mobile app game. Subsequently, insecticide resistance management strategies were explored using the simulation game ResistanceSim, which was introduced by mini-lectures and complemented by class discussions and group work. The game-based training was conducted and evaluated in two African countries (Ethiopia and Zambia) using a mixed-methods approach. Quantitative outcome measures included knowledge acquisition and change in self-efficacy. We completed a qualitative inductive thematic analysis of participant interviews to explore the views and experiences of participants with the games and training, and the impact of the training on professional practices and attitudes. The game-based training increased knowledge in the short-term and improved self-efficacy scores. The training increased participants' knowledge base, stimulated knowledge sharing and changed work practices. The game-based training offers scalable training opportunities that could nurture and capacitate the next generation of professionals in vector control.

Efficacy of the In2Care® auto-dissemination device for reducing dengue transmission: study protocol for a parallel, two-armed cluster randomised trial in the Philippines.

BACKGROUND: Mosquito-borne viruses are imposing an ever increasing health burden worldwide. In addition to the recent Zika and chikungunya virus epidemics, dengue viruses have become the fastest growing problem with a 40-fold increase in the number of reported cases over the past five decades. Current mosquito control techniques involving larval source reduction, larviciding, and space spray of adulticides are costly, laborious, and of debatable efficacy. There remains an urgent need for the development of intervention methods that can be reasonably implemented in the context of modern day urbanisation. Auto-dissemination (AD) of insecticide by adult mosquitoes offers a potentially practical and useful tool in an integrated vector control programme. Recently, an immediately employable AD device, the In2Care® mosquito trap, has been commercialised and shows promise as an effective tool. However, there remains a lack of demonstration of epidemiological efficacy. METHODS/DESIGN: This trial aims to assess the extent to which implementation of In2Care® mosquito traps can reduce vector Aedes (Stegomyia) spp. adult mosquito densities and dengue virus transmission as measured by sequential sero-conversion rates in children 6-16 years of age in a dengue endemic location: Lipa City, Philippines. To achieve this, we will carry out a parallel, two-armed cluster randomised trial evaluating AD efficacy for reducing the incidence of dengue over a 2-year period with 4 consecutive months of vector control during peak dengue transmission each year. DISCUSSION: For decades, it has been commonly accepted that an integrated approach to mosquito control is required. The World Health Organization (WHO) Global Strategic Framework for Integrated Vector Management recommends a range of interventions, in combination, to increase control impact to reduce transmission. This efficacy trial of the first commercial product using the AD approach will be informative in assessing the general utility of AD in reducing not only adult vector densities but, more importantly, reducing the incidence of dengue. The AD technique may complement source reduction and larviciding campaigns by more efficiently targeting the most productive containers and those beyond human reach. If successful, this mosquito control strategy could prove an invaluable tool in the fight against urban mosquito vectors and a reduction in the burden of associated disease. TRIAL REGISTRATION: ISRCTN44272773 . Registered on 31 January 2019.

Species abundance, composition, and nocturnal activity of female Anopheles (Diptera: Culicidae) in malaria-endemic villages of Papua New Guinea: assessment with barrier screen sampling.

BACKGROUND: Community composition of Anopheles mosquitoes, and their host-seeking and peridomestic behaviour, are important factors affecting malaria transmission. In this study, barrier screen sampling was used to investigate species composition, abundance, and nocturnal activity of Anopheles populations in villages of Papua New Guinea. METHODS: Mosquitoes were sampled from 6 pm to 6 am in five villages from 2012 to 2016. The barrier screens were positioned between the village houses and the perimeter of villages where cultivated and wild vegetation ("the bush") grew thickly. Female Anopheles that rested on either village or bush side of the barrier screens, as they commuted into and out of the villages, were captured. Similarity in species composition among villages was assessed. Mosquitoes captured on village and bush sides of the barrier screens were sorted by feeding status and by hour of collection, and their numbers were compared using negative binomial generalized linear models. RESULTS: Females of seven Anopheles species were present in the sample. Species richness ranged from four to six species per village, but relative abundance was highly uneven within and between villages, and community composition was similar for two pairs of villages and highly dissimilar in a fifth. For most Anopheles populations, more unfed than blood-fed mosquitoes were collected from the barrier screens. More blood-fed mosquitoes were found on the side of the barrier screens facing the village and relatively more unfed ones on the bush side, suggesting commuting behaviour of unfed host-seeking females into the villages from nearby bush and commuting of blood-fed females away from villages towards the bush. For most populations, the majority of host-seeking mosquitoes arrived in the village before midnight when people were active and unprotected from the mosquitoes by bed nets. CONCLUSION: The uneven distribution of Anopheles species among villages, with each site dominated by different species, even among nearby villages, emphasizes the importance of vector heterogeneity in local malaria transmission and control. Yet, for most species, nocturnal activity patterns of village entry and host seeking predominantly occurred before midnight indicating common behaviours across species and populations relative to human risk of exposure to Anopheles bites.

ResistanceSim: development and acceptability study of a serious game to improve understanding of insecticide resistance management in vector control programmes.

The use of insecticides is the cornerstone of effective malaria vector control. However, the last two decades has seen the ubiquitous use of insecticides, predominantly pyrethroids, causing widespread insecticide resistance and compromising the effectiveness of vector control. Considerable efforts to develop new active ingredients and interventions are underway. However, it is essential to deploy strategies to mitigate the impact of insecticide resistance now, both to maintain the efficacy of currently available tools as well as to ensure the sustainability of new tools as they come to market. Although the World Health Organization disseminated best practice guidelines for insecticide resistance management (IRM), Rollback Malaria's Vector Control Working Group identified the lack of practical knowledge of IRM as the primary gap in the translation of evidence into policy. ResistanceSim is a capacity strengthening tool designed to address this gap. The development process involved frequent stakeholder consultation, including two separate workshops. These workshops defined the learning objectives, target audience, and the role of mathematical models in the game. Software development phases were interspersed with frequent user testing, resulting in an iterative design process. User feedback was evaluated via questionnaires with Likert-scale and open-ended questions. The game was regularly evaluated by subject-area experts through meetings of an external advisory panel. Through these processes, a series of learning domains were identified and a set of specific learning objectives for each domain were defined to be communicated to vector control programme personnel. A simple "game model" was proposed that produces realistic outputs based on player strategy and also runs in real-time. Early testing sessions revealed numerous usability issues that prevented adequate player engagement. After extensive revisions, later testing sessions indicated that the tool would be a valuable addition to IRM training.

Converging Human and Malaria Vector Diagnostics with Data Management towards an Integrated Holistic One Health Approach.

Monitoring malaria prevalence in humans, as well as vector populations, for the presence of Plasmodium, is an integral component of effective malaria control, and eventually, elimination. In the field of human diagnostics, a major challenge is the ability to define, precisely, the causative agent of fever, thereby differentiating among several candidate (also non-malaria) febrile diseases. This requires genetic-based pathogen identification and multiplexed analysis, which, in combination, are hardly provided by the current gold standard diagnostic tools. In the field of vectors, an essential component of control programs is the detection of Plasmodium species within its mosquito vectors, particularly in the salivary glands, where the infective sporozoites reside. In addition, the identification of species composition and insecticide resistance alleles within vector populations is a primary task in routine monitoring activities, aiming to support control efforts. In this context, the use of converging diagnostics is highly desirable for providing comprehensive information, including differential fever diagnosis in humans, and mosquito species composition, infection status, and resistance to insecticides of vectors. Nevertheless, the two fields of human diagnostics and vector control are rarely combined, both at the diagnostic and at the data management end, resulting in fragmented data and mis- or non-communication between various stakeholders. To this direction, molecular technologies, their integration in automated platforms, and the co-assessment of data from multiple diagnostic sources through information and communication technologies are possible pathways towards a unified human vector approach.

Adaptation of a malaria surveillance system for use in a visceral leishmaniasis elimination programme.

Background: Successful public practice relies on generation and use of high-quality data. A data surveillance system (the Disease Data Management System [DDMS]) in use for malaria was adapted for use in the Indian visceral leishmaniasis elimination programme. Methods: A situational analysis identified the data flows in current use. Taxonomic trees for the vector of visceral leishmaniasis in India, Phlebotomus argentipes, were incorporated into the DDMS to allow entry of quality assurance and insecticide susceptibility data. A new quality assurance module was created to collate the concentration of DDT that was applied to walls during the indoor residual spraying (IRS) vector control programme. Results: The DDMS was implemented in Bihar State and used to collate and manage data from sentinel sites in eight districts. Quality assurance data showed that DDT was under-applied to walls during IRS; this, combined with insecticide susceptibility data showing widespread vector resistance to DDT prompted a national policy change to using compression pumps and alpha-cypermethrin insecticide for IRS. Conclusions: The adapted DDMS centralises programmatic data and enhances evidence-based decision making and active policy change. Moving forward, further modules of the system will be implemented, allowing extended data capture and streamlined transmission of key information to decision makers.

Plasticity of host selection by malaria vectors of Papua New Guinea.

BACKGROUND: Host selection is an important determinant of vectorial capacity because malaria transmission increases when mosquitoes feed more on humans than non-humans. Host selection also affects the outcome of long-lasting insecticidal nets (LLIN). Despite the recent nationwide implementation of LLIN-based malaria control program in Papua New Guinea (PNG), little is known about the host selection of the local Anopheles vectors. This study investigated the host selection of Anopheles vectors in PNG. METHODS: Blood-engorged mosquitoes were sampled using the barrier screen method and blood meals analyzed for vertebrate host source with PCR-amplification of the mitochondrial cytochrome b gene. Abundance of common hosts was estimated in surveys. The test of homogeneity of proportions and the Manly resource selection ratio were used to determine if hosts were selected in proportion to their abundance. RESULTS: Two thousand four hundred and forty blood fed Anopheles females of seven species were sampled from five villages in Madang, PNG. Of 2,142 samples tested, 2,061 (96.2%) yielded a definitive host source; all were human, pig, or dog. Hosts were not selected in proportion to their abundance, but rather were under-selected or over-selected by the mosquitoes. Four species, Anopheles farauti (sensu stricto) (s.s.), Anopheles punctulatus (s.s.), Anopheles farauti no. 4 and Anopheles longirostris, over-selected humans in villages with low LLIN usage, but over-selected pigs in villages with high LLIN usage. Anopheles koliensis consistently over-selected humans despite high LLIN usage, and Anopheles bancroftii over-selected pigs. CONCLUSIONS: The plasticity of host selection of an Anopheles species depends on its opportunistic, anthropophilic or zoophilic behavior, and on the extent of host availability and LLIN usage where the mosquitoes forage for hosts. The high anthropophily of An. koliensis increases the likelihood of contacting the LLIN inside houses. This allows its population size to be reduced to levels insufficient to support transmission. In contrast, by feeding on alternative hosts the likelihood of the opportunistic species to contact LLIN is lower, making them difficult to control. By maintaining high population size, the proportion that feed on humans outdoors can sustain residual transmission despite high LLIN usage in the village.

Mosquito Behavior Change After Distribution of Bednets Results in Decreased Protection Against Malaria Exposure.

Background: Behavioral resilience in mosquitoes poses a significant challenge to mosquito control. Although behavior changes in anopheline vectors have been reported over the last decade, there are no empirical data to suggest they compromise the efficacy of vector control in reducing malaria transmission. Methods: In this study, we quantified human exposure to both bites and infective bites of a major malaria vector in Papua New Guinea over the course of 4 years surrounding nationwide bednet distribution. We also quantified malaria infection prevalence in the human population during the same time period. Results: We observed a shift in mosquito biting to earlier hours of the evening, before individuals are indoors and protected by bednets, followed by a return to preintervention biting rates. As a result, net users and non-net users experienced higher levels of transmission than before the intervention. The personal protection provided by a bednet decreased over the study period and was lowest in the adult population, who may be an important reservoir for transmission. Malaria prevalence decreased in only 1 of 3 study villages after the distribution. Discussion: This study highlights the necessity of validating and deploying vector control measures targeting outdoor exposure to control and eliminate malaria.

Spatial and Temporal Trends in Insecticide Resistance among Malaria Vectors in Chad Highlight the Importance of Continual Monitoring.

BACKGROUND: A longitudinal Anopheles gambiae s.l. insecticide resistance monitoring programme was established in four sentinel sites in Chad 2008-2010. When this programme ended, only sporadic bioassays were performed in a small number of sites. METHODS: WHO diagnostic dose assays were used to measure the prevalence of insecticide resistance to 0.1% bendiocarb, 4% DDT, 0.05% deltamethrin, 1% fenitrothion, and 0.75% permethrin in the main malaria vectors at the beginning and end of the malaria transmission season for three years 2008-2010, with subsequent collections in 2011 and 2014. Species and molecular identification of An. gambiae M and S forms and kdr genotyping was performed using PCR-RLFP; circumsporozoite status was assessed using ELISA. RESULTS: Between 2008 and 2010, significant changes in insecticide resistance profiles to deltamethrin and permethrin were seen in 2 of the sites. No significant changes were seen in resistance to DDT in any site during the study period. Testing performed after the period of routine monitoring had ended showed dramatic increases to DDT and pyrethroid resistance in 3 sites. No resistance to organophosphate or carbamate insecticides was detected. An. arabiensis was the predominate member of the An. gambiae complex in all 4 sites; adult collections showed temporal variation in species composition in only 1 site. Kdr analysis identified both 1014F and 1014S alleles in An. gambiae S only. Circumsporozoite analysis showed the highest vector infection rates were present in Donia, a site with extensive use of agricultural insecticides. CONCLUSIONS: During the monitoring gap of four years, significant changes occurred in resistance prevalence in 3 of the 4 sites (p = <0.001), endangering the efficacy of currently implemented malaria control interventions. Significant changes in insecticide resistance profiles and a lack of kdr resistance alleles in adult populations highlight the urgent need for comprehensive entomological monitoring to be implemented and sustained in country.

An Operational Framework for Insecticide Resistance Management Planning.

Arthropod vectors transmit organisms that cause many emerging and reemerging diseases, and their control is reliant mainly on the use of chemical insecticides. Only a few classes of insecticides are available for public health use, and the increased spread of insecticide resistance is a major threat to sustainable disease control. The primary strategy for mitigating the detrimental effects of insecticide resistance is the development of an insecticide resistance management plan. However, few examples exist to show how to implement such plans programmatically. We describe the formulation and implementation of a resistance management plan for mosquito vectors of human disease in Zambia. We also discuss challenges, steps taken to address the challenges, and directions for the future.

Malaria transmission dynamics surrounding the first nationwide long-lasting insecticidal net distribution in Papua New Guinea.

BACKGROUND: The major malaria vectors of Papua New Guinea exhibit heterogeneities in distribution, biting behaviour and malaria infection levels. Long-lasting, insecticide-treated nets (LLINs), distributed as part of the National Malaria Control Programme, are the primary intervention targeting malaria transmission. This study evaluated the impact of LLINs on anopheline density, species composition, feeding behaviour, and malaria transmission. METHODS: Mosquitoes were collected by human landing catch in 11 villages from East Sepik Province and Madang Province. Mosquitoes were collected for 3 years (1 year before distribution and 2 years after), and assayed to determine mosquito species and Plasmodium spp. infection prevalence. The influence of weather conditions and the presence of people and animals on biting density was determined. Determinants of biting density and sporozoite prevalence were analysed by generalized estimating equations (GEE). RESULTS: Mosquito biting rates and entomological inoculation rates decreased significantly after the distribution. Plasmodium falciparum and P. vivax sporozoite prevalence decreased in year 2, but increased in year 3, suggesting the likelihood of resurgence in transmission if low biting rates are not maintained. An earlier shift in the median biting time of Anopheles punctulatus and An. farauti s.s. was observed. However, this was not accompanied by an increase in the proportion of infective bites occurring before 2200 hours. A change in species composition was observed, which resulted in dominance of An. punctulatus in Dreikikir region, but a decrease in An. punctulatus in the Madang region. When controlling for village and study year, An. farauti s.s., An. koliensis and An. punctulatus were equally likely to carry P. vivax sporozoites. However, An. punctulatus was significantly more likely than An. farauti s.s. (OR 0.14; p = 0.007) or An. koliensis (OR 0.27; p < 0.001) to carry P. falciparum sporozoites. CONCLUSIONS: LLINs had a significant impact on malaria transmission, despite exophagic and crepuscular feeding behaviours of dominant vectors. Changes in species composition and feeding behaviour were observed, but their epidemiological significance will depend on their durability over time.

Efficacy, Safety, and Pharmacokinetics of Coadministered Diethylcarbamazine, Albendazole, and Ivermectin for Treatment of Bancroftian Filariasis.

BACKGROUND: Available treatments for lymphatic filariasis (LF) are limited in their longterm clearance of microfilaria from the blood. The safety and efficacy of a single-dose triple-drug therapy of the antifilarial drugs diethylcarbamazine (DEC), ivermectin (IVM), and albendazole (ALB) for LF are unknown. METHODS: We performed a pilot study to test the efficacy, safety, and pharmacokinetics of single-dose DEC, IVM, and ALB in Wuchereria bancrofti-infected Papua New Guineans. Adults were randomized into 2 treatment arms, DEC 6 mg/kg + ALB 400 mg (N = 12) or DEC 6 mg/kg + ALB 400 mg + IVM 200 µg/kg (N = 12), and monitored for microfilaria, parasite antigenemia, adverse events (AEs), and serum drug levels. RESULTS: Triple-drug therapy induced >2-log reductions in microfilaria levels at 36 and 168 hours after treatment compared with approximately 1-log reduction with 2 drugs. All 12 individuals who received 3 drugs were microfilaria negative 1 year after treatment, whereas 11 of 12 individuals in the 2-drug regimen were microfilaria positive. In 6 participants followed 2 years after treatment, those who received 3 drugs remained microfilaria negative. AEs, particularly fever, myalgias, pruritus, and proteinuria/hematuria, occurred in 83% vs 50% of those receiving triple-drug compared to 2-drug treatment respectively (P = .021); all resolved within 7 days after treatment. No serious AEs were observed in either group. There was no significant effect of IVM on DEC or ALB drug levels. CONCLUSIONS: Triple-drug therapy is safe and more effective than DEC + ALB for Bancroftian filariasis and has the potential to accelerate elimination of lymphatic filariasis. CLINICAL TRIALS REGISTRATION: NCT01975441.

Fit for purpose: do we have the right tools to sustain NTD elimination?

Priorities for NTD control programmes will shift over the next 10-20 years as the elimination phase reaches the 'end game' for some NTDs, and the recognition that the control of other NTDs is much more problematic. The current goal of scaling up programmes based on preventive chemotherapy (PCT) will alter to sustaining NTD prevention, through sensitive surveillance and rapid response to resurgence. A new suite of tools and approaches will be required for both PCT and Intensive Disease Management (IDM) diseases in this timeframe to enable disease endemic countries to: 1. Sensitively and sustainably survey NTD transmission and prevalence in order to identify and respond quickly to resurgence. 2. Set relevant control targets based not only on epidemiological indicators but also entomological and ecological metrics and use decision support technology to help meet those targets. 3. Implement verified and cost-effective tools to prevent transmission throughout the elimination phase. Liverpool School of Tropical Medicine (LSTM) and partners propose to evaluate and implement existing tools from other disease systems as well as new tools in the pipeline in order to support endemic country ownership in NTD decision-making during the elimination phase and beyond.