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.
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.
There has been rapid scale-up of malaria vector control in the last ten years. Both of the primary control strategies, long-lasting pyrethroid treated nets and indoor residual spraying, rely on the ...use of a limited number of insecticides. Insecticide resistance, as measured by bioassay, has rapidly increased in prevalence and has come to the forefront as an issue that needs to be addressed to maintain the sustainability of malaria control and the drive to elimination. Zambia's programme reported high levels of resistance to the insecticides it used in 2010, and, as a result, increased its investment in resistance monitoring to support informed resistance management decisions.
A country-wide survey on insecticide resistance in Zambian malaria vectors was performed using WHO bioassays to detect resistant phenotypes. Molecular techniques were used to detect target-site mutations and microarray to detect metabolic resistance mechanisms. Anopheles gambiae s.s. was resistant to pyrethroids, DDT and carbamates, with potential organophosphate resistance in one population. The resistant phenotypes were conferred by both target-site and metabolic mechanisms. Anopheles funestus s.s. was largely resistant to pyrethroids and carbamates, with potential resistance to DDT in two locations. The resistant phenotypes were conferred by elevated levels of cytochrome p450s.
Currently, the Zambia National Malaria Control Centre is using these results to inform their vector control strategy. The methods employed here can serve as a template to all malaria-endemic countries striving to create a sustainable insecticide resistance management plan.
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.
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.
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.
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.
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.
The implementation in Zambia, although a good example of how the DDMS can impact decision making, has not been without its challenges. Since November 2014, the DDMS has not been used, primarily ...because of a loss of momentum as the responsibility of maintaining the system shifted between malaria control partners. ...because of standardized data formats, the DDMS can facilitate cross-border collaboration and collective decision making. ...the DDMS uses open-source technology that can integrate with other widely-used HIS, such as District Health Information Software 2 (DHIS2).
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.
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.
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).
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.
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.
Global efforts to eliminate lymphatic filariasis are based on the annual mass administration of antifilarial drugs to reduce the microfilaria reservoir available to the mosquito vector. ...Insecticide-treated bed nets are being widely used in areas in which filariasis and malaria are coendemic.
We studied five villages in which five annual mass administrations of antifilarial drugs, which were completed in 1998, reduced the transmission of Wuchereria bancrofti, one of the nematodes that cause lymphatic filariasis. A total of 21,899 anopheles mosquitoes were collected for 26 months before and 11 to 36 months after bed nets treated with long-lasting insecticide were distributed in 2009. We evaluated the status of filarial infection and the presence of W. bancrofti DNA in anopheline mosquitoes before and after the introduction of insecticide-treated bed nets. We then used a model of population dynamics to estimate the probabilities of transmission cessation.
Village-specific rates of bites from anopheline mosquitoes ranged from 6.4 to 61.3 bites per person per day before the bed-net distribution and from 1.1 to 9.4 bites for 11 months after distribution (P<0.001). During the same period, the rate of detection of W. bancrofti in anopheline mosquitoes decreased from 1.8% to 0.4% (P=0.005), and the rate of detection of filarial DNA decreased from 19.4% to 14.9% (P=0.13). The annual transmission potential was 5 to 325 infective larvae inoculated per person per year before the bed-net distribution and 0 after the distribution. Among all five villages with a prevalence of microfilariae of 2 to 38%, the probability of transmission cessation increased from less than 1.0% before the bed-net distribution to a range of 4.9 to 95% in the 11 months after distribution.
Vector control with insecticide-treated bed nets is a valuable tool for W. bancrofti elimination in areas in which anopheline mosquitoes transmit the parasite. (Funded by the U.S. Public Health Service and the National Institutes of Health.).
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.
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