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[This corrects the article DOI: 10.1371/journal.pntd.0006845.].

BackgroundThe objective of mass antimalarial drug administration (MDA) is to eliminate malaria rapidly by eliminating the asymptomatic malaria parasite reservoirs and interrupting transmission. In the Greater Mekong Subregion, where artemisinin-resistant Plasmodium falciparum is now widespread, MDA has been proposed as an elimination accelerator, but the contribution of asymptomatic infections to malaria transmission has been questioned. The impact of MDA on entomological indices has not been characterized previously.MethodsMDA was conducted in 4 villages in Kayin State (Myanmar). Malaria mosquito vectors were captured 3 months before, during, and 3 months after MDA, and their Plasmodium infections were detected by polymerase chain reaction (PCR) analysis. The relationship between the entomological inoculation rate, the malaria prevalence in humans determined by ultrasensitive PCR, and MDA was characterized by generalized estimating equation regression.ResultsAsymptomatic P. falciparum and Plasmodium vivax infections were cleared by MDA. The P. vivax entomological inoculation rate was reduced by 12.5-fold (95% confidence interval [CI], 1.6-100-fold), but the reservoir of asymptomatic P. vivax infections was reconstituted within 3 months, presumably because of relapses. This was coincident with a 5.3-fold (95% CI, 4.8-6.0-fold) increase in the vector infection rate.ConclusionAsymptomatic infections are a major source of malaria transmission in Southeast Asia.

The global malaria burden has decreased over the last decade and many nations are attempting elimination. Asymptomatic malaria infections are not normally diagnosed or treated, posing a major hurdle for elimination efforts. One solution to this problem is mass drug administration (MDA), with success depending on adequate population participation. Here, we present a detailed spatial and temporal analysis of malaria episodes and asymptomatic infections in four villages undergoing MDA in Myanmar. In this study, individuals from neighborhoods with low MDA adherence had 2.85 times the odds of having a malaria episode post-MDA in comparison to those from high adherence neighborhoods, regardless of individual participation, suggesting a herd effect. High mosquito biting rates, living in a house with someone else with malaria, or having an asymptomatic malaria infection were also predictors of clinical episodes. Spatial clustering of non-adherence to MDA, even in villages with high overall participation, may frustrate elimination efforts.

BackgroundThe emergence and spread of multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion (GMS) threatens global malaria elimination efforts. Mass drug administration (MDA), the presumptive antimalarial treatment of an entire population to clear the subclinical parasite reservoir, is a strategy to accelerate malaria elimination. We report a cluster randomised trial to assess the effectiveness of dihydroartemisinin-piperaquine (DP) MDA in reducing falciparum malaria incidence and prevalence in 16 remote village populations in Myanmar, Vietnam, Cambodia, and the Lao People's Democratic Republic, where artemisinin resistance is prevalent.Methods and findingsAfter establishing vector control and community-based case management and following intensive community engagement, we used restricted randomisation within village pairs to select 8 villages to receive early DP MDA and 8 villages as controls for 12 months, after which the control villages received deferred DP MDA. The MDA comprised 3 monthly rounds of 3 daily doses of DP and, except in Cambodia, a single low dose of primaquine. We conducted exhaustive cross-sectional surveys of the entire population of each village at quarterly intervals using ultrasensitive quantitative PCR to detect Plasmodium infections. The study was conducted between May 2013 and July 2017. The investigators randomised 16 villages that had a total of 8,445 residents at the start of the study. Of these 8,445 residents, 4,135 (49%) residents living in 8 villages, plus an additional 288 newcomers to the villages, were randomised to receive early MDA; 3,790 out of the 4,423 (86%) participated in at least 1 MDA round, and 2,520 out of the 4,423 (57%) participated in all 3 rounds. The primary outcome, P. falciparum prevalence by month 3 (M3), fell by 92% (from 5.1% [171/3,340] to 0.4% [12/2,828]) in early MDA villages and by 29% (from 7.2% [246/3,405] to 5.1% [155/3,057]) in control villages. Over the following 9 months, the P. falciparum prevalence increased to 3.3% (96/2,881) in early MDA villages and to 6.1% (128/2,101) in control villages (adjusted incidence rate ratio 0.41 [95% CI 0.20 to 0.84]; p = 0.015). Individual protection was proportional to the number of completed MDA rounds. Of 221 participants with subclinical P. falciparum infections who participated in MDA and could be followed up, 207 (94%) cleared their infections, including 9 of 10 with artemisinin- and piperaquine-resistant infections. The DP MDAs were well tolerated; 6 severe adverse events were detected during the follow-up period, but none was attributable to the intervention.ConclusionsAdded to community-based basic malaria control measures, 3 monthly rounds of DP MDA reduced the incidence and prevalence of falciparum malaria over a 1-year period in areas affected by artemisinin resistance. P. falciparum infections returned during the follow-up period as the remaining infections spread and malaria was reintroduced from surrounding areas. Limitations of this study include a relatively small sample of villages, heterogeneity between villages, and mobility of villagers that may have limited the impact of the intervention. These results suggest that, if used as part of a comprehensive, well-organised, and well-resourced elimination programme, DP MDA can be a useful additional tool to accelerate malaria elimination.Trial registrationClinicalTrials.gov NCT01872702.

BackgroundDiseases caused by Aedes-borne viruses, such as dengue, Zika, chikungunya, and yellow fever, are emerging and reemerging globally. The causes are multifactorial and include global trade, international travel, urbanisation, water storage practices, lack of resources for intervention, and an inadequate evidence base for the public health impact of Aedes control tools. National authorities need comprehensive evidence-based guidance on how and when to implement Aedes control measures tailored to local entomological and epidemiological conditions.Methods and findingsThis review is one of a series being conducted by the Worldwide Insecticide resistance Network (WIN). It describes a framework for implementing Integrated Aedes Management (IAM) to improve control of diseases caused by Aedes-borne viruses based on available evidence. IAM consists of a portfolio of operational actions and priorities for the control of Aedes-borne viruses that are tailored to different epidemiological and entomological risk scenarios. The framework has 4 activity pillars: (i) integrated vector and disease surveillance, (ii) vector control, (iii) community mobilisation, and (iv) intra- and intersectoral collaboration as well as 4 supporting activities: (i) capacity building, (ii) research, (iii) advocacy, and (iv) policies and laws.ConclusionsIAM supports implementation of the World Health Organisation Global Vector Control Response (WHO GVCR) and provides a comprehensive framework for health authorities to devise and deliver sustainable, effective, integrated, community-based, locally adapted vector control strategies in order to reduce the burden of Aedes-transmitted arboviruses. The success of IAM requires strong commitment and leadership from governments to maintain proactive disease prevention programs and preparedness for rapid responses to outbreaks.

Aedes mosquito-borne diseases remain a significant global health threat, necessitating effective control strategies. This study introduces monoterpenes-based nanohydrogels for potential use as repellents against Aedes aegypti, the primary dengue vector worldwide. We formulated hydrogels using cymene- and myrcene-based nanoemulsions with different polymers: chitosan, carboxymethylcellulose (CMC), and carbopol®. Our evaluations of rheological, texture, and bioadhesive properties identified CMC hydrogel as the most promising gelling agent for topical application, exhibiting sustained monoterpene release over 12 h with low skin permeation and high retention in the stratum corneum. Myrcene-loaded CMC hydrogel achieved a 57% feeding deterrence compared to 47% with cymene hydrogel in the mosquito membrane-feeding model. Molecular docking studies revealed interactions between myrcene and an essential amino acid (Ile116) in the Ae. aegypti odorant-binding protein 22 (AeOBP22), corroborating its higher repellent efficacy. These findings suggest that myrcene-loaded CMC hydrogels offer a promising, minimally invasive strategy for personal protection against Ae. aegypti and warrant further investigation to optimize monoterpene concentrations for vector control. [ABSTRACT FROM AUTHOR]

Background: A treated fabric device for emanating the volatile pyrethroid transfluthrin was recently developed in Tanzania that protected against night-biting Anopheles and Culex mosquitoes for several months. Here perceptions of community end users provided with such transfluthrin emanators, primarily intended to protect them against day-active Aedes vectors of human arboviruses that often attack people outdoors, were assessed in Port-au-Prince, Haiti. Methods: Following the distribution of transfluthrin emanators to participating households in poor-to-middle class urban neighbourhoods, questionnaire surveys and in-depth interviews of end-user households were supplemented with conventional and Photovoice-based focus group discussions. Observations were assessed synthetically to evaluate user perceptions of protection and acceptability, and to solicit advice for improving and promoting them in the future. Results: Many participants viewed emanators positively and several outlined various advantages over current alternatives, although some expressed concerns about smell, health hazards, bulkiness, unattractiveness and future cost. Most participants expressed moderate to high satisfaction with protection against mosquitoes, especially indoors. Protection against other arthropod pests was also commonly reported, although satisfaction levels were highly variable. Diverse use practices were reported, some of which probably targeted nocturnal Culex resting indoors, rather than Aedes attacking them outdoors during daylight hours. Perceived durability of protection varied: While many participants noted some slow loss over months, others noted rapid decline within days. A few participants specifically attributed efficacy loss to outdoor use and exposure to wind or moisture. Many expressed stringent expectations of satisfactory protection levels, with even a single mosquito bite considered unsatisfactory. Some participants considered emanators superior to fans, bedsheets, sprays and coils, but it is concerning that several preferred them to bed nets and consequently stopped using the latter. Conclusions: The perspectives shared by Haitian end-users are consistent with those from similar studies in Brazil and recent epidemiological evidence from Peru that other transfluthrin emanator products can protect against arbovirus infection. While these encouraging sociological observations contrast starkly with evidence of essentially negligible effects upon Aedes landing rates from parallel entomological assessments across Haiti, Tanzania, Brazil and Peru, no other reason to doubt the generally encouraging views expressed herein by Haitian end users could be identified. [ABSTRACT FROM AUTHOR]

ABSTRACT The global malaria burden has decreased over the last decade and many nations are attempting elimination. Asymptomatic infections aren’t normally diagnosed or treated, posing a major hurdle for elimination efforts. One solution to this problem is mass drug administration (MDA), which is dependent on adequate population participation to disrupt transmission. There is little empirical evidence regarding the necessary threshold level of participation. Here we present a detailed spatiotemporal analysis of malaria episodes and asymptomatic infections in four villages undergoing MDA in Myanmar. Individuals from neighborhoods with high MDA adherence had 90% decreased odds of having a malaria episode post-MDA, regardless of individual participation, suggesting a strong herd effect. High mosquito biting rates, living in a house with someone else with malaria, or having an asymptomatic malaria infection were also predictors of clinical episodes. Spatial clustering of non-adherence to MDA, even in villages with high overall participation, can frustrate elimination efforts.

Timely identification and treatment of malaria transmission "hot spots" is essential to achieve malaria elimination. Here we investigate the relevance of using an Anopheles salivary biomarker to estimate Plasmodium falciparum malaria exposure risk along the Thailand-Myanmar border to guide malaria control. Between May 2013 and December 2014, > 9,000 blood samples collected in a cluster randomized control trial were screened with serological assays to measure the antibody responses to Anopheles salivary antigen (gSG6-P1) and P. falciparum malaria antigens (circumsporozoite protein, merozoite surface protein 119 [MSP-119]). Plasmodium falciparum infections were monitored through passive and active case detection. Seroprevalence to gSG6-P1, MSP-119, and CSP were 71.8% (95% Confidence interval [CI]: 70.9, 72.7), 68.6% (95% CI: 67.7, 69.5), and 8.6% (95% CI: 8.0, 9.2), respectively. Multivariate analysis showed that individuals with the highest Ab response to gSG6-P1 had six times the odds of being positive to CSP antigens (P < 0.001) and two times the odds of P. falciparum infection compared with low gSG6-P1 responders (P = 0.004). Spatial scan statistics revealed the presence of clusters of gSG6-P1 that partially overlapped P. falciparum infections. The gSG6-P1 salivary biomarker represents a good proxy for estimating P. falciparum malaria risk and could serve to implement hot spot-targeted vector control interventions to achieve malaria elimination.

BackgroundPotentially untreatable Plasmodium falciparum malaria threatens the Greater Mekong subregion. A previous series of pilot projects in Myanmar, Laos, Cambodia, and Vietnam suggested that mass drug administration was safe, and when added to provision of early diagnosis and treatment, could reduce the reservoir of P falciparum and interrupts transmission. We examined the effects of a scaled-up programme of this strategy in four townships of eastern Myanmar on the incidence of P falciparum malaria.MethodsThe programme was implemented in the four townships of Myawaddy, Kawkareik, Hlaingbwe, and Hpapun in Kayin state, Myanmar. Increased access to early diagnosis and treatment of malaria was provided to all villages through community-based malaria posts equipped with rapid diagnostic tests, and treatment with artemether-lumefantrine plus single low-dose primaquine. Villages were identified as malarial hotspots (operationally defined as >40% malaria, of which 20% was P falciparum) with surveys using ultrasensitive quantitative PCR either randomly or targeted at villages where the incidence of clinical cases of P falciparum malaria remained high (ie, >100 cases per 1000 individuals per year) despite a functioning malaria post. During each survey, a 2 mL sample of venous blood was obtained from randomly selected adults. Hotspots received targeted mass drug administration with dihydroartemisinin-piperaquine plus single-dose primaquine once per month for 3 consecutive months in addition to the malaria posts. The main outcome was the change in village incidence of clinical P falciparum malaria, quantified using a multivariate, generalised, additive multilevel model. Malaria prevalence was measured in the hotspots 12 months after mass drug administration.FindingsBetween May 1, 2014, and April 30, 2017, 1222 malarial posts were opened, providing early diagnosis and treatment to an estimated 365 000 individuals. Incidence of P falciparum malaria decreased by 60 to 98% in the four townships. 272 prevalence surveys were undertaken and 69 hotspot villages were identified. By April 2017, 50 hotspots were treated with mass drug administration. Hotspot villages had a three times higher incidence of P falciparum at malarial posts than neighbouring villages (adjusted incidence rate ratio [IRR] 2·7, 95% CI 1·8-4·4). Early diagnosis and treatment was associated with a significant decrease in P falciparum incidence in hotspots (IRR 0·82, 95% CI 0·76-0·88 per quarter) and in other villages (0·75, 0·73-0·78 per quarter). Mass drug administration was associated with a five-times decrease in P falciparum incidence within hotspot villages (IRR 0·19, 95% CI 0·13-0·26). By April, 2017, 965 villages (79%) of 1222 corresponding to 104 village tracts were free from P falciparum malaria for at least 6 months. The prevalence of wild-type genotype for K13 molecular markers of artemisinin resistance was stable over the three years (39%; 249/631).InterpretationProviding early diagnosis and effective treatment substantially decreased village-level incidence of artemisinin-resistant P falciparum malaria in hard-to-reach, politically sensitive regions of eastern Myanmar. Targeted mass drug administration significantly reduced malaria incidence in hotspots. If these activities could proceed in all contiguous endemic areas in addition to standard control programmes already implemented, there is a possibility of subnational elimination of P falciparum.FundingThe Bill & Melinda Gates Foundation, the Regional Artemisinin Initiative (Global Fund against AIDS, Tuberculosis and Malaria), and the Wellcome Trust.

ABSTRACT The global malaria burden has decreased over the last decade and many nations are attempting elimination. Asymptomatic infections aren’t normally diagnosed or treated, posing a major hurdle for elimination efforts. One solution to this problem is mass drug administration (MDA), which is dependent on adequate population participation to disrupt transmission. There is little empirical evidence regarding the necessary threshold level of participation. Here we present a detailed spatiotemporal analysis of malaria episodes and asymptomatic infections in four villages undergoing MDA in Myanmar. Individuals from neighborhoods with high MDA adherence had 90% decreased odds of having a malaria episode post-MDA, regardless of individual participation, suggesting a strong herd effect. High mosquito biting rates, living in a house with someone else with malaria, or having an asymptomatic malaria infection were also predictors of clinical episodes. Spatial clustering of non-adherence to MDA, even in villages with high overall participation, can frustrate elimination efforts.

BackgroundThe modalities of malaria transmission along the Thailand-Myanmar border are poorly understood. Here we address the relevance of using a specific Anopheles salivary biomarker to measure the risk among humans of exposure to Anopheles bites.MethodsSerologic surveys were conducted from May 2013 to December 2014 in 4 sentinel villages. More than 9400 blood specimens were collected in filter papers from all inhabitants at baseline and then every 3 months thereafter, for up to 18 months, for analysis by enzyme-linked immunosorbent assay. The relationship between the intensity of the human antibody response and entomological indicators of transmission (human biting rates and entomological inoculation rates [EIRs]) was studied using a multivariate 3-level mixed model analysis. Heat maps for human immunoglobulin G (IgG) responses for each village and survey time point were created using QGIS 2.4.ResultsThe levels of IgG response among participants varied significantly according to village, season, and age (P

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