Long-lasting Insecticidal Bed Nets Research Articles

Physical durability and insecticidal activity of long-lasting insecticidal nets in Cruzeiro do Sul, Brazil

Vector control is one of the principal strategies used for reducing malaria transmission. Long-lasting insecticidal bed nets (LLINs) are a key tool used to protect populations at risk of malaria, since they provide both physical and chemical barriers to prevent human-vector contact. This study aimed to assess the physical durability and insecticidal efficacy of LLINs distributed in Cruzeiro do Sul (CZS), Brazil, after 4 years of use. A total of 3000 LLINs (PermaNet 2.0) were distributed in high malaria risk areas of CZS in 2007. After 4 years of use, 27 ‘rectangular’ LLINs and 28 ‘conical’ LLINs were randomly selected for analysis. The evaluation of physical integrity was based on counting the number of holes and measuring their size and location on the nets. Insecticidal efficacy was evaluated by cone bioassays, and the amount of residual insecticide remaining on the surface of the LLINs was estimated using a colorimetric method. After 4 years of use, physical damage was highly prevalent on the rectangular LLINs, with a total of 473 holes detected across the 27 nets. The upper portion of the side panels sustained the greatest damage in rectangular LLINs. The overall mosquito mortality by cone bioassay was < 80% in 25/27 rectangular LLINs, with panel A (at the end of the rectangular bednet) presenting the highest mortality (54%). The overall mean insecticide concentration was 0.5 µg/sample, with the bednet roof containing the highest average concentration (0.61 µg/sample). On the conical LLINs, 547 holes were detected, with the bottom areas sustaining the greatest damage. The cone bioassay mortality was < 80% in 26/28 of the conical LLINs. The mean insecticide concentration was 0.3 µg/sample. After 4 years of use, the insecticidal efficacy of the LLINs was diminished to below acceptable thresholds.

ROY Crystallization on Poly(ethylene) Fibers, a Model for Bed Net Crystallography.

Many long-lasting insecticidal bed nets for protection against disease vectors consist of poly(ethylene) fibers in which insecticide is incorporated during manufacture. Insecticide molecules diffuse from within the supersaturated polymers to surfaces where they become bioavailable to insects and often crystallize, a process known as blooming. Recent studies revealed that contact insecticides can be highly polymorphic. Moreover, insecticidal activity is polymorph-dependent, with forms having a higher crystal free energy yielding faster insect knockdown and mortality. Consequently, the crystallographic characterization of insecticide crystals that form on fibers is critical to understanding net function and improving net performance. Structural characterization of insecticide crystals on bed net fiber surfaces, let alone their polymorphs, has been elusive owing to the minute size of the crystals, however. Using the highly polymorphous compound ROY (5-methyl-2-[(2-nitrophenyl)-amino]thiophene-3-carbonitrile) as a proxy for insecticide crystallization, we investigated blooming and crystal formation on the surface of extruded poly(ethylene) fibers containing ROY. The blooming rates, tracked from the time of extrusion, were determined by UV-vis spectroscopy after successive washes. Six crystalline polymorphs (of the 13 known) were observed on poly(ethylene) fiber surfaces, and they were identified and characterized by Raman microscopy, scanning electron microscopy, and 3D electron diffraction. These observations reveal that the crystallization and phase behavior of polymorphs forming on poly(ethylene) fibers is complex and dynamic. The characterization of blooming and microcrystals underscores the importance of bed net crystallography for the optimization of bed net performance.

Ownership, coverage, utilisation and maintenance of long-lasting insecticidal bed nets in three Health Districts in Cameroon: a cross-sectional study.

the Bamenda, Santa and Tiko Health Districts are in the highest malaria transmission strata of Cameroon. The purpose of this study was to explore the indicators of ownership and utilisation as well as maintenance of Long-Lasting Insecticidal Nets (LLINs) in three health districts in Cameroon. a cross-sectional household survey involving 1,251 households was conducted in the Tiko Health District (THD) in June and July 2017 and in Bamenda and Santa Health Districts in March to May 2018. A structured questionnaire was used to collect data on LLIN ownership, utilisation, and maintenance as well as demographic characteristics. the average number of LLINs per household was higher in the Bamenda Health District (BHD) compared to the THD (2.5, range; 0-6 vs. 2.4, range; 0-6) as well as the household ownership of at least one LLIN (93.3% vs. 89.0%). The proportion of the defacto population with universal utilisation was higher in BHD compared to THD (13.1% vs 0.2%). In the multinomial regression analysis, households in the SHD (p = 5.5x10-4, OR; 0.3, 95% C.I; 0.1-0.6), were less likely to own at least one LLIN compared to those in THD. Eighty-seven point one percent (87.1%) of household heads admitted that LLINs could be washed, while 50.1% affirmed the correct washing frequency. ownership of LLINs was low in the THD in comparison to the goal of one for every two household members. Overall, LLINs coverage and accessibility was still low after the free mass distribution campaigns (MDCs), as only 14.6% of children 0-5 years and 16.1% of the entire population used LLIN the night before the survey.

Optimization of long-lasting insecticidal bed nets for resistance management: a modelling study and user-friendly app

BackgroundUp until the present, pyrethroid-treated bed nets have been a key tool for vector control in the fight against malaria. A global system that sets standards and facilitates procurement has successfully driven down the price of these bed nets to enable more of them to be distributed. As a result of their mass rollout, malaria cases have been significantly reduced, but pyrethroid resistance is now widespread. Going forward, new insecticides have been and continue to be developed for use on bed nets, but it is unclear how to best deploy them for maximum impact.MethodsHere, an app for the optimization of bed nets based on their insecticide loading concentration and deployment lifespan is presented. Underlying the app are simple models that incorporate the chemical and physical properties of bed nets, and the genetic and ecological properties of resistance evolution in mosquitoes. Where possible, default parameter values are fitted from experimental data. The app numerically searches across a massive number of these simple models with variable loading and lifespan to find their optima under different criteria that constrain the options for vector control.ResultsThe app is not intended to provide a definite answer about the best bed net design, but allows for the quantative exploration of trade-offs and constraints under different conditions. Here, results for the deployment of a new insecticide are explored under default parameter values across public health budgets for the purchase of bed nets. Optimization can lead to substantial gains in the average control of the mosquito population, and these gains are comparatively greater with lower budgets. Whilst optimizing a bed net within the constraints of the incentives of the existing system of standards and procurement leads to substantially greater control than not optimizing the bed net, optimizing the bed net without constraints leads to yet substantially greater control. The most important factor in this optimization is coverage, which depends on the price per bed net. With this in mind, it is unsurprising that the optimization for plausible budgets suggests that a pyrethroid would be the preferred partner for a new insecticide under current constraints because it is cost-effective in the balance of being less expensive than the new insecticide but also less effective due to pre-existing resistance. Surprisingly, a pyrethroid is shown to be an effective partner for a new insecticide in this model because of its contribution to resistance management in delaying the onset of resistance to the new insecticide.ConclusionsThis study highlights the importance of trade-offs in the design of bed nets for vector control. Further, it suggests that there are challenges in the roll-out of bed nets with new insecticides because of the constraints imposed by the global system of standards and procurement, which currently fails to adequately incentivize important considerations in bed net design like resistance management.

Evaluation of an accelerometer-based monitor for detecting bed net use and human entry/exit using a machine learning algorithm

BackgroundDistribution of long-lasting insecticidal bed nets (LLINs) is one of the main control strategies for malaria. Improving malaria prevention programmes requires understanding usage patterns in households receiving LLINs, but there are limits to what standard cross-sectional surveys of self-reported LLIN use can provide. This study was designed to assess the performance of an accelerometer-based approach for measuring a range of LLIN use behaviours as a proof of concept for more granular LLIN-use monitoring over longer time periods.MethodsThis study was carried out under controlled conditions from May to July 2018 in Liverpool, UK. A single accelerometer was affixed to the side panel of an LLIN and participants carried out five LLIN use behaviours: (1) unfurling a net; (2) entering an unfurled net; (3) lying still as if sleeping; (4) exiting from under a net; and, (5) folding up a net. The randomForest package in R, a supervised non-linear classification algorithm, was used to train models on 20-s epochs of tagged accelerometer data. Models were compared in a validation dataset using overall accuracy, sensitivity and specificity, receiver operating curves and the area under the curve (AUC).ResultsThe five-category model had overall accuracy of 82.9% in the validation dataset, a sensitivity of 0.681 for entering a net, 0.632 for exiting, 0.733 for net down, and 0.800 for net up. A simplified four-category model, combining entering/exiting a net into one category had accuracy of 94.8%, and increased sensitivity for net down (0.756) and net up (0.829). A further simplified three-category model, identifying sleeping, net up, and a combined net down/enter/exit category had accuracy of 96.2% (483/502), with an AUC of 0.997 for net down and 0.987 for net up. Models for detecting entering/exiting by adults were significantly more accurate than for children (87.8% vs 70.0%; p < 0.001) and had a higher AUC (p = 0.03).ConclusionsUnderstanding how LLINs are used is crucial for planning malaria prevention programmes. Accelerometer-based systems provide a promising new methodology for studying LLIN use. Further work exploring accelerometer placement, frequency of measurements and other machine learning approaches could make these methods even more accurate in the future.

Vector composition, abundance, biting patterns and malaria transmission intensity in Madang, Papua New Guinea: assessment after 7\xa0years of an LLIN-based malaria control programme

BackgroundA malaria control programme based on distribution of long-lasting insecticidal bed nets (LLINs) and artemisinin combination therapy began in Papua New Guinea in 2009. After implementation of the programme, substantial reductions in vector abundance and malaria transmission intensity occurred. The research reported here investigated whether these reductions remained after seven years of sustained effort.MethodsAll-night (18:00 to 06:00) mosquito collections were conducted using human landing catches and barrier screen methods in four villages of Madang Province between September 2016 and March 2017. Anopheles species identification and sporozoite infection with Plasmodium vivax and Plasmodium falciparum were determined with molecular methods. Vector composition was expressed as the relative proportion of different species in villages, and vector abundance was quantified as the number of mosquitoes per barrier screen-night and per person-night. Transmission intensity was quantified as the number of sporozoite-infective vector bites per person-night.ResultsFive Anopheles species were present, but vector composition varied greatly among villages. Anopheles koliensis, a strongly anthropophilic species was the most prevalent in Bulal, Matukar and Wasab villages, constituting 63.7–73.8% of all Anopheles, but in Megiar Anopheles farauti was the most prevalent species (97.6%). Vector abundance varied among villages (ranging from 2.8 to 72.3 Anopheles per screen-night and 2.2–31.1 Anopheles per person-night), and spatially within villages. Malaria transmission intensity varied among the villages, with values ranging from 0.03 to 0.5 infective Anopheles bites per person-night. Most (54.1–75.1%) of the Anopheles bites occurred outdoors, with a substantial proportion (25.5–50.8%) occurring before 22:00.ConclusionThe estimates of vector abundance and transmission intensity in the current study were comparable to or higher than estimates in the same villages in 2010–2012, indicating impeded programme effectiveness. Outdoor and early biting behaviours of vectors are some of the likely explanatory factors. Heterogeneity in vector composition, abundance and distribution among and within villages challenge malaria control programmes and must be considered when planning them.

The application of digital holography for accurate three-dimensional localisation of mosquito-bednet interaction

Understanding mosquito interaction with long-lasting insecticidal bednets is crucial in the development of more effective intervention methods to protect humans from malaria transmission. As such, a 240 × 240 × 1000 mm laboratory setup for the in-line recording of digital holograms and subsequent in-focus reconstruction and 3D localisation of mosquitoes is presented. Simple bednet background removal methods are used to accurately localise a mosquito obscured by a bednet in 3D coordinates. Simulations and physical data demonstrate that this method is suitable for mosquitoes positioned 3−1000 mm behind a bednet. A novel post-processing technique, involving a cascade-correlation of a Tamura of Intensity focus metric extracted from digitally reconstructed scenes, accurately localises mosquitoes positioned 35−100 mm behind a bednet from a single digital hologram. The result of this study is a scalable digital holographic methodology to examine mosquito-bednet interaction in 3D at a level of accuracy previously only seen in 2D imaging of mosquitoes in a much smaller volume.

Mass drug administration for the acceleration of malaria elimination in a region of Myanmar with artemisinin-resistant falciparum malaria: a cluster-randomised trial

To contain multidrug-resistant Plasmodium falciparum, malaria elimination in the Greater Mekong subregion needs to be accelerated while current antimalarials remain effective. We evaluated the safety, effectiveness, and potential resistance selection of dihydroartemisinin-piperaquine mass drug administration (MDA) in a region with artemisinin resistance in Myanmar. We did a cluster-randomised controlled trial in rural community clusters in Kayin (Karen) state in southeast Myanmar. Malaria prevalence was assessed using ultrasensitive quantitative PCR (uPCR) in villages that were operationally suitable for MDA (villages with community willingness, no other malaria control campaigns, and a population of 50-1200). Villages were eligible to participate if the prevalence of malaria (all species) in adults was greater than 30% or P falciparum prevalence was greater than 10% (or both). Contiguous villages were combined into clusters. Eligible clusters were paired based on P falciparum prevalence (estimates within 10%) and proximity. Community health workers provided routine malaria case management and distributed long-lasting insecticidal bed-nets (LLINs) in all clusters. Randomisation of clusters (1:1) to the MDA intervention group or control group was by public coin-flip. Group allocations were not concealed. Three MDA rounds (3 days of supervised dihydroartemisinin-piperaquine [target total dose 7 mg/kg dihydroartemisinin and 55 mg/kg piperaquine] and single low-dose primaquine [target dose 0·25 mg base per kg]) were delivered to intervention clusters. Parasitaemia prevalence was assessed at 3, 5, 10, 15, 21, 27, and 33 months. The primary outcomes were P falciparum prevalence at months 3 and 10. All clusters were included in the primary analysis. Adverse events were monitored from the first MDA dose until 1 month after the final dose, or until resolution of any adverse event occurring during follow-up. This trial is registered with ClinicalTrials.gov, NCT01872702. Baseline uPCR malaria surveys were done in January, 2015, in 43 villages that were operationally suitable for MDA (2671 individuals). 18 villages met the eligibility criteria. Three villages in close proximity were combined into one cluster because a border between them could not be defined. This gave a total of 16 clusters in eight pairs. In the intervention clusters, MDA was delivered from March 4 to March 17, from March 30 to April 10, and from April 27 to May 10, 2015. The weighted mean absolute difference in P falciparum prevalence in the MDA group relative to the control group was -10·6% (95% CI -15·1 to -6·1; p=0·0008) at month 3 and -4·5% (-10·9 to 1·9; p=0·14) at month 10. At month 3, the weighted P falciparum prevalence was 1·4% (0·6 to 3·6; 12 of 747) in the MDA group and 10·6% (7·0 to 15·6; 56 of 485) in the control group. Corresponding prevalences at month 10 were 3·2% (1·5 to 6·8; 34 of 1013) and 5·8% (2·5 to 12·9; 33 of 515). Adverse events were reported for 151 (3·6%) of 4173 treated individuals. The most common adverse events were dizziness (n=109) and rash or itching (n=20). No treatment-related deaths occurred. In this low-transmission setting, the substantial reduction in P falciparum prevalence resulting from support of community case management was accelerated by MDA. In addition to supporting community health worker case management and LLIN distribution, malaria elimination programmes should consider using MDA to reduce P falciparum prevalence rapidly in foci of higher transmission. The Global Fund to Fight AIDS, Tuberculosis and Malaria.

Community knowledge, attitude and practices regarding malaria and long-lasting insecticidal nets in Churachandpur, Manipur

Background: The disease is endemic in many parts of India, especially in the North- Eastern region. A study was done on head of the family’s knowledge, attitude and practice regarding malaria and long-lasting insecticidal bed nets and to determine the association between socio-demographic profile and knowledge and attitude.Methods: A cross-sectional study was conducted in the communities from 3 subcentres namely Pearsonmun, Thingkhangpai and Soipum under Saikot PHC, Churachandpur district of Manipur. House to house survey was carried out and only those who are eligible were interviewed using structured questionnaire. Random sampling and PPS was carried out to select the households head. SPSS was used for analysis.Results: Total of 289 heads of the family was interviewed. The total adequate knowledge score was 30.6% and only 26.3% had favourable attitude towards malaria and long-lasting insecticidal bed nets. There was significant association between marital status, educational qualification, occupation and monthly income with adequacy of knowledge. There was significant association between religion and attitude.Conclusions: Majority of the participants still lacks knowledge and attitude towards the malaria and long-lasting insecticidal nets (LLIN). IEC and awareness campaign should be carried out intensively and further study to be done to see the improvement of knowledge.

Evaluation of malaria preventive measures among adult patients attending the Bamendjou and Foumbot district hospitals of the West Region of Cameroon

BackgroundAlthough a significant decrease in entomological and epidemiological indicators was reported in Cameroon since the introduction of insecticide-treated bed nets, malaria prevalence remains high also in some parts of the West Region of Cameroon. This study was designed to evaluate malaria preventive measures among patients attending the Bamendjou and Foumbot District hospitals of the West Region of Cameroon.MethodsThis was a cross-sectional study carried out within a period of 3 months, from January to March 2020. Data was obtained using a structured questionnaire and laboratory analysis. The CareStart™ Pf Malaria HRP2 qualitative rapid diagnostic test was used for malaria diagnosis. The questionnaire was designed to collect information on respondent’s socio-demographic characteristics, and the use of malaria preventive measures. Data were analysed using descriptive statistics, regression analysis, and Chi-square (and Fisher’s exact) test.ResultsA total of 170 study participants were recruited in Foumbot and 197 in Bamendjou. Malaria was significantly (P < 0.0001) more prevalent in Foumbot (47.06%) than in Bamendjou (19.8%). In Foumbot, non-use of insect repellent spray (P = 0.0214), insect repellent body cream (P = 0.0009), mosquito spray (P = 0.0001) and not draining stagnant water (P = 0.0004) predisposed to higher risk of malaria. In Bamendjou, non-use of insect repellent spray (P = 0.0012), long-lasting insecticidal bed nets (P = 0.0001), window and door nets (P = 0.0286), predisposed to a higher risk of malaria.ConclusionsMalaria prevalence was high among the study participants especially in Foumbot. An adequate follow-up to ensure effective execution of the recently launched third phase of LLINs distribution campaign in Cameroon is recommended. Additionally, integrated vector management is required to ensure effective control of malaria transmission in Foumbot and Bamendjou.

Cost-Effectiveness of PBO versus Conventional Long-Lasting Insecticidal Bed Nets in Preventing Symptomatic Malaria in Nigeria: Results of a Pragmatic Randomized Trial.

ABSTRACTInsecticide treated nets (ITNs) have been the major tool in halving malaria’s burden since 2000, but pyrethroid insecticide resistance threatens their ongoing effectiveness. In 2017, the WHO concluded that long-lasting ITNs (LLINs) with a synergist, piperonyl butoxide (PBO), provided additional public health benefit over conventional (pyrethroid-only) LLINs alone in areas of moderate insecticide resistance and endorsed them as a new class of vector control products. We performed an economic appraisal of PBO nets compared with conventional LLINs in 2019 US$ from prevention and health systems perspectives (including treatment cost offsets). We used data from a pragmatic randomized 2012–2014 trial in Nigeria with epidemiological outcomes in an area with confirmed pyrethroid resistance. Each village had 50 months of epidemiologic data, analyzed by village by month, using negative binomial regression. Compared with LLINs, although adding $0.90 per net delivered, PBO nets reduced symptomatic malaria cases by 33.4% (95% CI 10.2–50.6%). From a prevention perspective, the incremental cost-effectiveness ratio was $11 (95% CI $8–$37) per disability-adjusted life year averted. From the health systems perspective, PBO nets were significantly cost-saving relative to conventional LLINs. The benefit–cost analysis found that the added economic benefits of PBO nets over LLINs were $201 (95% CI $61–$304) for every $1 in incremental costs. Growing pyrethroid resistance is likely to strengthen the economic value of PBO nets over LLINs. Beyond their contribution to reducing malaria, PBO nets deliver outstanding economic returns for a small additional cost above conventional LLINs in locations with insecticide resistance.

Anopheline and human drivers of malaria risk in northern coastal, Ecuador: a pilot study

BackgroundUnderstanding local anopheline vector species and their bionomic traits, as well as related human factors, can help combat gaps in protection.MethodsIn San José de Chamanga, Esmeraldas, at the Ecuadorian Pacific coast, anopheline mosquitoes were sampled by both human landing collections (HLCs) and indoor-resting aspirations (IAs) and identified using both morphological and molecular methods. Human behaviour observations (HBOs) (including temporal location and bed net use) were documented during HLCs as well as through community surveys to determine exposure to mosquito bites. A cross-sectional evaluation of Plasmodium falciparum and Plasmodium vivax infections was conducted alongside a malaria questionnaire.ResultsAmong 222 anopheline specimens captured, based on molecular analysis, 218 were Nyssorhynchus albimanus, 3 Anopheles calderoni (n = 3), and one remains unidentified. Anopheline mean human-biting rate (HBR) outdoors was (13.69), and indoors (3.38) (p = 0.006). No anophelines were documented resting on walls during IAs. HBO-adjusted human landing rates suggested that the highest risk of being bitten was outdoors between 18.00 and 20.00 h. Human behaviour-adjusted biting rates suggest that overall, long-lasting insecticidal bed nets (LLINs) only protected against 13.2% of exposure to bites, with 86.8% of exposure during the night spent outside of bed net protection. The malaria survey found 2/398 individuals positive for asymptomatic P. falciparum infections. The questionnaire reported high (73.4%) bed net use, with low knowledge of malaria.ConclusionThe exophagic feeding of anopheline vectors in San Jose de Chamanga, when analysed in conjunction with human behaviour, indicates a clear gap in protection even with high LLIN coverage. The lack of indoor-resting anophelines suggests that indoor residual spraying (IRS) may have limited effect. The presence of asymptomatic infections implies the presence of a human reservoir that may maintain transmission.

Insecticides and Insecticide Resistance.

Vector control has significantly reduced malaria morbidity in many regions of the world where the disease was endemic and is now moving toward malaria elimination. Among the tools available for vector control, the use of long-lasting insecticidal bed nets (LLINs) and indoor residual spraying (IRS) has proved most effective. However, Anopheles mosquitoes are becoming increasingly resistant to insecticides. In this chapter, we describe the main aspects of vector control-with a particular focus on insecticidal products commonly used in vector control as well as on mechanisms of insecticide resistance. We also discuss the impact of insecticide resistance on malaria transmission.

Bio-efficacy of DuraNet\xae long-lasting insecticidal nets against wild populations of Anopheles arabiensis in experimental huts

BackgroundMosquitoes have developed resistance to multiple classes of insecticides for malaria vector control. A new generation of long-lasting insecticidal bed nets (LLINs) has been developed with increased efficacy against these resistant mosquitoes. The present study therefore evaluated the efficacy of the pyrethroid-based LLINs, DuraNet versus PermaNet 3.0, in an Eastern Africa hut design in Magugu in northern Tanzania where mosquitoes’ population higher proportion (69.3%) has been identified as Anopheles gambiae s.l.MethodsStandard World Health Organization bioefficacy evaluations were conducted in both laboratory and experimental huts. Experimental hut evaluations were conducted in an area with high populations of Anopheles arabiensis. All nets used were subjected to laboratory cone bioassays and then to experimental hut trials. Mosquito mortality, blood-feeding inhibition, and personal protection rate were compared between untreated nets, unwashed LN, and LN that were washed 20 times.ResultsStandard WHO laboratory bioefficacy evaluations of DuraNet and PermaNet® 3.0 which were untreated, washed, or 20 times washed showed optimal knockdown and mortality for both net types against a susceptible strain of An. arabiensis. In standard experimental hut evaluations, the blood feeding inhibition for PermaNet® 3.0 unwashed and washed was 82.4% (76.3–88.6%) to 91.5% (84.1–98.8%) while for DuraNet was 98.3% (97.0–99.5%) to 96.0% (94.1–88.2%) respectively. The DuraNet LLINs showed a significantly higher killing effect than the other treatment of 90.0% (86.1–94.2%) and 94.0% (90.2–97.9%) for unwashed and washed nets respectively. No significant difference in deterrence or induced exophily was detected between the treatment arms. There were no adverse effects reported among sleepers in the experimental huts.ConclusionThe findings of this study indicate that the pyrethroid-based net DuraNet LLINs attained required efficacy when evaluated against wild population of An. arabiensis from Northern Tanzania. This adds value to the existing vector control tool box which gives community wider choice for vector control.

Empirical and theoretical investigation into the potential impacts of insecticide resistance on the effectiveness of insecticide-treated bed nets.

In spite of widespread insecticide resistance in vector mosquitoes throughout Africa, there is limited evidence that long‐lasting insecticidal bed nets (LLINs) are failing to protect against malaria. Here, we showed that LLIN contact in the course of host‐seeking resulted in higher mortality of resistant Anopheles spp. mosquitoes than predicted from standard laboratory exposures with the same net. We also found that sublethal contact with an LLIN caused a reduction in blood feeding and subsequent host‐seeking success in multiple lines of resistant mosquitoes from the laboratory and the field. Using a transmission model, we showed that when these LLIN‐related lethal and sublethal effects were accrued over mosquito lifetimes, they greatly reduced the impact of resistance on malaria transmission potential under conditions of high net coverage. If coverage falls, the epidemiological impact is far more pronounced. Similarly, if the intensity of resistance intensifies, the loss of malaria control increases nonlinearly. Our findings help explain why insecticide resistance has not yet led to wide‐scale failure of LLINs, but reinforce the call for alternative control tools and informed resistance management strategies.

Safety and effectiveness of mass drug administration to accelerate elimination of artemisinin-resistant falciparum malaria: A pilot trial in four villages of Eastern Myanmar

Background: Artemisinin and partner drug-resistant falciparum malaria is expanding over the Greater Mekong Sub-region (GMS). Eliminating falciparum malaria in the GMS while drugs still retain enough efficacy could prevent global spread of antimalarial resistance. Eliminating malaria rapidly requires targeting the reservoir of asymptomatic parasite carriers. This pilot trial aimed to evaluate the acceptability, safety, feasibility and effectiveness of mass-drug administration (MDA) in reducing malaria in four villages in Eastern Myanmar. Methods: Villages with ≥30% malaria prevalence were selected. Long-lasting insecticidal bednets (LLINs) and access to malaria early diagnosis and treatment (EDT) were provided. Two villages received MDA immediately and two were followed for nine months pre-MDA. MDA consisted of a 3-day supervised course of dihydroartemisinin-piperaquine and single low-dose primaquine administered monthly for three months. Adverse events (AE) were monitored by interviews and consultations. Malaria prevalence was assessed by ultrasensitive PCR quarterly for 24 months. Symptomatic malaria incidence,entomological indices, and antimalarial resistance markers were monitored. Results: MDA was well tolerated. There were no serious AE and mild to moderate AE were reported in 5.6%(212/3931) interviews. In the smaller villages, participation to three MDA courses was 61% and 57%, compared to 28% and 29% in the larger villages. Baseline prevalence was higher in intervention than in control villages (18.7% (95%CI=16.1-21.6) versus 6.8%(5.2-8.7), p<0.0001) whereas three months after starting MDA, prevalence was lower in intervention villages (0.4%(0.04-1.3) versus 2.7%(1.7-4.1), p=0.0014). After nine months the difference was no longer significant (2.0%(1.0-3.5) versus 0.9%(0.04-1.8), p=0.10). M0-M9 symptomatic falciparum incidence was similar between intervention and control. Before/after MDA comparisons showed that asymptomatic P. falciparum carriage and anopheline vector positivity decreased significantly whereas prevalence of the artemisinin-resistance molecular marker remained stable. Conclusions: This MDA was safe and feasible, and, could accelerate elimination of P. falciparum in addition to EDT and LLINs when community participation was sufficient.

Safety and effectiveness of mass drug administration to accelerate elimination of artemisinin-resistant falciparum malaria: A pilot trial in four villages of Eastern Myanmar.

Background: Artemisinin and partner drug-resistant falciparum malaria is expanding over the Greater Mekong Sub-region (GMS). Eliminating falciparum malaria in the GMS while drugs still retain enough efficacy could prevent global spread of antimalarial resistance. Eliminating malaria rapidly requires targeting the reservoir of asymptomatic parasite carriers. This pilot trial aimed to evaluate the acceptability, safety, feasibility and effectiveness of mass-drug administration (MDA) in reducing malaria in four villages in Eastern Myanmar. Methods: Villages with ≥30% malaria prevalence were selected. Long-lasting insecticidal bednets (LLINs) and access to malaria early diagnosis and treatment (EDT) were provided. Two villages received MDA immediately and two were followed for nine months pre-MDA. MDA consisted of a 3-day supervised course of dihydroartemisinin-piperaquine and single low-dose primaquine administered monthly for three months. Adverse events (AE) were monitored by interviews and consultations. Malaria prevalence was assessed by ultrasensitive PCR quarterly for 24 months. Symptomatic malaria incidence,entomological indices, and antimalarial resistance markers were monitored. Results: MDA was well tolerated. There were no serious AE and mild to moderate AE were reported in 5.6%(212/3931) interviews. In the smaller villages, participation to three MDA courses was 61% and 57%, compared to 28% and 29% in the larger villages. Baseline prevalence was higher in intervention than in control villages (18.7% (95%CI=16.1-21.6) versus 6.8%(5.2-8.7), p<0.0001) whereas three months after starting MDA, prevalence was lower in intervention villages (0.4%(0.04-1.3) versus 2.7%(1.7-4.1), p=0.0014). After nine months the difference was no longer significant (2.0%(1.0-3.5) versus 0.9%(0.04-1.8), p=0.10). M0-M9 symptomatic falciparum incidence was similar between intervention and control. Before/after MDA comparisons showed that asymptomatic P. falciparum carriage and anopheline vector positivity decreased significantly whereas prevalence of the artemisinin-resistance molecular marker remained stable. Conclusions: This MDA was safe and feasible, and, could accelerate elimination of P. falciparumin addition to EDT and LLINs when community participation was sufficient.

The implementation of long-lasting insecticidal bed nets has differential effects on the genetic structure of the African malaria vectors in the Anopheles gambiae complex in Dielmo, Senegal

BackgroundMosquitoes belonging to the Anopheles gambiae complex are the main vectors of malaria in sub-Saharan Africa. Among these, An. gambiae, Anopheles coluzzii and Anopheles arabiensis are the most efficient vectors and are largely distributed in sympatric locations. However, these species present ecological and behavioural differences that impact their vectorial capacity and complicate vector-control efforts, mainly based on long-lasting insecticidal bed nets (LLINs) and indoor residual spraying (IRS). In this study, the genetic structure of these three species in a Senegalese village (Dielmo) was investigated using microsatellite data in samples collected in 2006 before implementation of LLINs, in 2008, when they were introduced, and in 2010, 2 years after the use of LLINs.ResultsIn this study 611 individuals were included, namely 136 An. coluzzii, 101 An. gambiae, 6 An. coluzzii/An. gambiae hybrids and 368 An. arabiensis. According to the species, the effect of the implementation of LLINs in Dielmo is differentiated. Populations of the sister species An. coluzzii and An. gambiae regularly experienced bottleneck events, but without significant inbreeding. The Fst values suggested in 2006 a breakdown of assortative mating resulting in hybrids, but the introduction of LLINs was followed by a decrease in the number of hybrids. This suggests a decrease in mating success of hybrids, ecological maladaptation, or a lesser probability of mating between species due to a decrease in An. coluzzii population size. By contrast, the introduction of LLINs has favoured the sibling species An. arabiensis. In this study, some spatial and temporal structuration between An. arabiensis populations were detected, especially in 2008, and the higher genetic diversity observed could result from a diversifying selection.ConclusionsThis work demonstrates the complexity of the malaria context and shows the need to study the genetic structure of Anopheles populations to evaluate the effectiveness of vector-control tools and successful management of malaria vector control.

Comparing ownership and use of bed nets at two sites with differential malaria transmission in western Kenya.

BackgroundChallenges persist in ensuring access to and optimal use of long-lasting, insecticidal bed nets (LLINs). Factors associated with ownership and use may differ depending on the history of malaria and prevention control efforts in a specific region. Understanding how the cultural and social-environmental context of bed net use may differ between high- and low-risk regions is important when identifying solutions to improve uptake and appropriate use.MethodsCommunity forums and a household, cross-sectional survey were used to collect information on factors related to bed net ownership and use in western Kenya. Sites with disparate levels of transmission were selected, including an endemic lowland area, Miwani, and a highland epidemic-prone area, Kapkangani. Analysis of ownership was stratified by site. A combined site analysis was conducted to examine factors associated with use of all available bed nets. Logistic regression modelling was used to determine factors associated with ownership and use of owned bed nets.ResultsAccess to bed nets as the leading barrier to their use was identified in community forums and cross-sectional surveys. While disuse of available bed nets was discussed in the forums, it was a relatively rare occurrence in both sites. Factors associated with ownership varied by site. Education, perceived risk of malaria and knowledge of individuals who had died of malaria were associated with higher bed net ownership in the highlands, while in the lowlands individuals reporting it was easy to get a bed net were more likely to own one. A combined site analysis indicated that not using an available bed net was associated with the attitudes that taking malaria drugs is easier than using a bed net and that use of a bed net will not prevent malaria. In addition, individuals with an unused bed net in the household were more likely to indicate that bed nets are difficult to use, that purchased bed nets are better than freely distributed ones, and that bed nets should only be used during the rainy season.ConclusionVariations in factors associated with ownership should be acknowledged when constructing messaging and distribution campaigns. Despite reports of bed nets being used for other purposes, those in the home were rarely unused in these communities. Disuse seemed to be related to beliefs that can be addressed through education programmes. As mass distributions continue to take place, additional research is needed to determine if factors associated with LLIN ownership and use change with increasing availability of LLIN.

Spatially variable risk factors for malaria in a geographically heterogeneous landscape, western Kenya: an explorative study

BackgroundLarge reductions in malaria transmission and mortality have been achieved over the last decade, and this has mainly been attributed to the scale-up of long-lasting insecticidal bed nets and indoor residual spraying with insecticides. Despite these gains considerable residual, spatially heterogeneous, transmission remains. To reduce transmission in these foci, researchers need to consider the local demographical, environmental and social context, and design an appropriate set of interventions. Exploring spatially variable risk factors for malaria can give insight into which human and environmental characteristics play important roles in sustaining malaria transmission.MethodsOn Rusinga Island, western Kenya, malaria infection was tested by rapid diagnostic tests during two cross-sectional surveys conducted 3 months apart in 3632 individuals from 790 households. For all households demographic data were collected by means of questionnaires. Environmental variables were derived using Quickbird satellite images. Analyses were performed on 81 project clusters constructed by a traveling salesman algorithm, each containing 50–51 households. A standard linear regression model was fitted containing multiple variables to determine how much of the spatial variation in malaria prevalence could be explained by the demographic and environmental data. Subsequently, a geographically-weighted regression (GWR) was performed assuming non-stationarity of risk factors. Special attention was taken to investigate the effect of residual spatial autocorrelation and local multicollinearity.ResultsCombining the data from both surveys, overall malaria prevalence was 24 %. Scan statistics revealed two clusters which had significantly elevated numbers of malaria cases compared to the background prevalence across the rest of the study area. A multivariable linear model including environmental and household factors revealed that higher socioeconomic status, outdoor occupation and population density were associated with increased malaria risk. The local GWR model improved the model fit considerably and the relationship of malaria with risk factors was found to vary spatially over the island; in different areas of the island socio-economic status, outdoor occupation and population density were found to be positively or negatively associated with malaria prevalence.DiscussionIdentification of risk factors for malaria that vary geographically can provide insight into the local epidemiology of malaria. Examining spatially variable relationships can be a helpful tool in exploring which set of targeted interventions could locally be implemented. Supplementary malaria control may be directed at areas, which are identified as at risk. For instance, areas with many people that work outdoors at night may need more focus in terms of vector control.Trial registration: Trialregister.nl NTR3496—SolarMal, registered on 20 June 2012