A review of Musca sorbens (Diptera: Muscidae) and Musca domestica behavior and responses to chemical and visual cues.

Musca flies (Diptera: Muscidae) have been found culpable in the mechanical transmission of several infectious agents, including viruses, bacteria, protozoans, and helminths, particularly in low-income settings in tropical regions. In large numbers, these flies can negatively impact the health of communities and their livestock through the transmission of pathogens. In some parts of the world, Musca sorbens is of particular importance because it has been linked with the transmission of trachoma, a leading cause of preventable and irreversible blindness or visual impairment caused by Chlamydia trachomatis, but the contribution these flies make to trachoma transmission has not been quantified and even less is known for other pathogens. Current tools for control and monitoring of house flies remain fairly rudimentary and have focused on the use of environmental management, insecticides, traps, and sticky papers. Given that the behaviors of flies are triggered by chemical cues from their environment, monitoring approaches may be improved by focusing on those activities that are associated with nuisance behaviors or with potential pathogen transmission, and there are opportunities to improve fly control by exploiting behaviors toward semiochemicals that act as attractants or repellents. We review current knowledge on the odor and visual cues that affect the behavior of M. sorbens and Musca domestica, with the aim of better understanding how these can be exploited to support disease monitoring and guide the development of more effective control strategies.

A Qualitative Analysis of the Perceptions of Stakeholders Involved in Vector Control and Vector-Borne Disease Research and Surveillance in Orinoquia, Colombia.

Colombia has a tropical climate and environmental conditions that favour the circulation of most of the known vector-borne diseases (VBDs). Protocols have been established and implemented to address the threats of these diseases, but they are for country-wide use and do not take into consideration the nuances of the different environments of the country. Almost the entire population is vulnerable to infection with one or more VBD. This study aims to characterise the perceptions and experiences of stakeholders involved in vector control and VBDs in the Orinoquia region in Colombia. Two panel discussions, and 12 semi-structured interviews, were conducted. Experts from the Colombian National Health Institute (INS), health secretaries from Meta, Guaviare and Vichada Departments, academic researchers, and individuals from private vector control companies participated. All sessions were recorded, transcribed, and translated, and then subject to thematic analysis. Three major themes emerged: involvement, limitations, and recommendations. Results showed that participants are engaged in vector surveillance activities, education, and vector control research. Participants focused on problems of disjointed efforts towards VBD control between health secretaries and the health ministry, as well as societal issues, such as socioeconomic, cultural, and political issues, which became the rationale for the lack of vector control resources. Responses in the panel discussions and interviews overlapped in opinions, and suggested that vector control could be improved through better communication between vector control bodies, strengthened engagement with vulnerable communities, more collaborative actions, and a more balanced distribution of resources.

Validation of a method for the dry preservation and rehydration of Anopheles gambiae sensu lato for parity analysis to assess the impact of vector control measures in the field.

BACKGROUND: As the control of malaria remains heavily dependent on vector management interventions, it is important to understand the impact of these on mosquito populations. Age-grading is a valuable tool for this; however, logistical challenges in remote, resource-poor areas make current methodologies difficult to incorporate into clinical trials and routine surveillance. Our aim was to validate a methodology that could be easily implemented in such settings. Using dried mosquito specimens instead of freshly killed ones, we validated the commonly used ovarian tracheation technique for assessing population age structure. METHODS: Laboratory-reared Anopheles coluzzii mosquitoes with known parity status were dry preserved in silica gel for up to 12 weeks and rehydrated prior to parity assessment. The results were compared to parity results for freshly killed mosquitoes from the same colony. Preserved, field-caught Anopheles gambiae sensu lato (s.l.) from Guinea-Bissau were assessed by three different assessors blinded to each other's scores. An overall index of agreement was calculated using inter-rater reliability of all assessor pairings. The impact of preservation time was investigated using a one-way ANOVA to look for differences in assessor agreement over three time periods. RESULTS: The parity status was correctly identified for 90% of dry preserved and rehydrated insectary-reared An. coluzzii and for 98% of freshly killed insectary-reared An. coluzzii. The inter-rater reliability was highest (0.94) for freshly killed An. coluzzii. The results for all time points showed excellent strength of agreement between assessors. For field-caught An. gambiae s.l., the overall index of agreement between all three assessors was 0.86 (95% confidence interval 0.78-0.93), indicating almost perfect agreement. There was no significant difference between assessor agreement between time frames. CONCLUSIONS: Dry preserving and rehydrating Anopheles mosquitoes provides an alternative to using freshly killed mosquitoes to assess the efficacy of a control intervention in remote settings where it is logistically difficult to dissect fresh specimens. This method also provides the flexibility required for parity assessment to be done on larger scales over bigger areas.

Protocol for a cluster randomised placebo-controlled trial of adjunctive ivermectin mass drug administration for malaria control on the Bijagós Archipelago of Guinea-Bissau: the MATAMAL trial.

INTRODUCTION: As malaria declines, innovative tools are required to further reduce transmission and achieve elimination. Mass drug administration (MDA) of artemisinin-based combination therapy (ACT) is capable of reducing malaria transmission where coverage of control interventions is already high, though the impact is short-lived. Combining ACT with ivermectin, an oral endectocide shown to reduce vector survival, may increase its impact, while also treating ivermectin-sensitive co-endemic diseases and minimising the potential impact of ACT resistance in this context. METHODS AND ANALYSIS: MATAMAL is a cluster-randomised placebo-controlled trial. The trial is being conducted in 24 clusters on the Bijagós Archipelago, Guinea-Bissau, where the peak prevalence of Plasmodium falciparum (Pf) parasitaemia is approximately 15%. Clusters have been randomly allocated to receive MDA with dihydroartemisinin-piperaquine and either ivermectin or placebo. The primary objective is to determine whether the addition of ivermectin MDA is more effective than dihydroartemisinin-piperaquine MDA alone in reducing the prevalence of P. falciparum parasitaemia, measured during peak transmission season after 2 years of seasonal MDA. Secondary objectives include assessing prevalence after 1 year of MDA; malaria incidence monitored through active and passive surveillance; age-adjusted prevalence of serological markers indicating exposure to P. falciparum and anopheline mosquitoes; vector parous rates, species composition, population density and sporozoite rates; prevalence of vector pyrethroid resistance; prevalence of artemisinin resistance in P. falciparum using genomic markers; ivermectin's impact on co-endemic diseases; coverage estimates; and the safety of combined MDA. ETHICS AND DISSEMINATION: The trial has been approved by the London School of Hygiene and Tropical Medicine's Ethics Committee (UK) (19156) and the Comite Nacional de Eticas de Saude (Guinea-Bissau) (084/CNES/INASA/2020). Results will be disseminated in peer-reviewed publications and in discussion with the Bissau-Guinean Ministry of Public Health and participating communities. TRIAL REGISTRATION NUMBER: NCT04844905.

The Threat of Vector-Borne Diseases in Sierra Leone.

Sierra Leone is vulnerable to a wide range of vector-borne diseases transmitted by mosquitoes, tsetse flies, black flies, and other vectors. Malaria, lymphatic filariasis, and onchocerciasis have posed the greatest threat and have received the most attention in terms of vector control and capacity for diagnosis. However, malaria infection rates remain high, and there is evidence of circulation of other vector-borne diseases, such as chikungunya and dengue, which may go undiagnosed and unreported. The limited understanding of the prevalence and transmission of these diseases restricts the capacity for predicting outbreaks, and impedes the planning of appropriate responses. We review the available literature and gather expert opinions from those working in the country to report on the status of vector-borne disease transmission and control in Sierra Leone, and present an assessment of the threats of these diseases. Our discussions highlight an absence of entomological testing for disease agents and the need for more investment in surveillance and capacity strengthening.

Repellent Screening of Selected Plant Essential Oils Against Dengue Fever Mosquitoes Using Behavior Bioassays.

Among the efforts to reduce mosquito-transmitted diseases, such as malaria and dengue fever, essential oils (EOs) have become increasingly popular as natural replacements for the repellant DEET. In this study, seven commercially available plant EOs against Aedes species mosquitoes were evaluated for their complete protection time (CPT, min) in vivo using human-hand in cage tests (GB2009/China and WHO2009). Among the EOs with the highest efficacy in repelling mosquitoes, Aedes albopictus (Skuse) were clove bud oil and patchouli oil. Both were further assessed according to the in vivo method recommended by the WHO, to determine their minimum effective dose and CPT. A comparison of the ED50 values (dose yielding a 50% repellent response) of these two EOs against Aedes aegypti(L.) showed that the ED50 (2.496 µg/cm2) of patchouli oil was 1248 times higher than that of clove bud oil (0.002 µg/cm2), thus demonstrating them greater efficacy of the latter in repelling Ae. aegypti mosquitoes. For the 2 EOs, eugenol was the major component with higher than 80% in relative amount of the clove bud oil. The patchouli oil had more than 30% of character chemical patchouli alcohol along with α-bulnesene (10.962%), α-guaiene (9.227%), and seychellene (7.566%). Clove bud oil was found to confer longer complete protection than patchouli oil against a common species of mosquito. These results suggest use of EOs as safe, highly potent repellents for use in daily life and against mosquito-transmitted diseases, such as malaria and dengue fever.

Evaluation of the efficacy of insecticide-treated scarves to protect children from the trachoma vector Musca sorbens (Diptera: Muscidae): A phase II randomised controlled trial in Oromia, Ethiopia.

Background: The eye-seeking fly Musca sorbens can act as a vector for ocular Chlamydia trachomatis, causing trachoma, yet there has been very little research on control measures. We investigated whether insect repellent products, specifically insecticide-treated clothing, could provide personal protection to the user from eye-seeking flies. Methods: We first conducted a series of phase I laboratory studies to inform our choice of field intervention. We then conducted a phase II randomised controlled trial testing the efficacy of permethrin-treated scarves (PTS) in reducing fly-face contact in Oromia, Ethiopia. Children aged 4-10 years in full health and with no known adverse reactions to permethrin or other insecticides were allocated to either arm using restricted randomisation. Intervention arm children wore Insect Shield® versatile wraps (as PTS) for 28 days. The primary outcomes, fly-eye, -nose and -mouth contact, were assessed on the first day (0/30/60/180 minutes), on day 7 and on day 28. All participants present per timepoint were included in analyses. This trial was registered with ClinicalTrials.gov (NCT03813069). Findings: Participants were recruited to the field trial between 29/10/2019 and 01/11/2019, 58 were randomised to test or control arm. More fly (-eye, -nose and -mouth) contacts were observed in the PTS arm at baseline. After adjusting for baseline contact rates, across all timepoints there was a 35% decrease in fly-eye contacts in the PTS relative to control arm (rate ratio [RR] 0.65, 95% CI 0.52-0.83). Similar cross-timepoint reductions were seen for fly-nose and fly-mouth contacts (RR 0.69, 95% CI 0.51-0.92 and RR 0.79, 95% CI 0.62-1.01, respectively). All children were included on day 0. Two in the control arm were absent on day 7, one left the study and four were excluded from analysis at day 28. No adverse events occurred in the trial. Interpretation: Musca sorbens flies are sufficiently repelled by PTS to reduce fly-eye contacts for the wearer, thus possibly reducing the risk of trachoma transmission. Permethrin-treated scarves may therefore an alternative to insecticide space spraying for protection from these flies. Funding: Wellcome Trust.

Increased Repellent Effect of DEET on Aedes aegypti (Diptera: Culicidae) Field Population.

Insecticides and repellents are routinely used in Brazil because of the high rates of arbovirus transmission and the nuisance caused by mosquitoes. However, few studies have assessed the effectiveness of repellents against mosquito populations that have been under exposure to xenobiotics, mainly insecticides and repellents. This study investigated the sensitivity of a field population of Aedes aegypti (Linnaeus, 1762) from a dengue-endemic area under high insecticide pressure to N,N-diethylmethylbenzamide (DEET), the active ingredient in common repellent products. The field (Laranjeiras, Sergipe, Brazil) and laboratory (Rockefeller) populations were characterized for the presence of the Val1016Ile kdr mutation, associated with pyrethroid resistance, and locomotor activity. Repellency bioassays were performed to assess the response of the mosquitoes to human odor by exposing them to 10% DEET applied to the skin in ethanol. Samples from the field population showed higher frequency of the kdr mutation, 21.9% homozygous and 21.9% heterozygous, greater locomotor activity and greater sensitivity to DEET than the laboratory population. These results suggest increased sensitivity to DEET in field populations and a possible interaction between insecticide exposure and sensitivity to DEET.

Skin microbiome alters attractiveness to Anopheles mosquitoes.

BACKGROUND: Some people produce specific body odours that make them more attractive than others to mosquitoes, and consequently are at higher risk of contracting vector-borne diseases. The skin microbiome can break down carbohydrates, fatty acids and peptides on the skin into volatiles that mosquitoes can differentiate. RESULTS: Here, we examined how skin microbiome composition of women differs in relation to level of attractiveness to Anopheles coluzzii mosquitoes, to identify volatiles in body odour and metabolic pathways associated with individuals that tend to be poorly-attractive to mosquitoes. We used behavioural assays to measure attractiveness of participants to An. coluzzii mosquitoes, 16S rRNA amplicon sequencing of the bacteria sampled from the skin and gas chromatography of volatiles in body odour. We found differences in skin microbiome composition between the poorly- and highly-attractive groups, particularly eight Amplicon Sequence Variants (ASVs) belonging to the Proteobacteria, Actinobacteria and Firmicutes phyla. Staphylococcus 2 ASVs are four times as abundant in the highly-attractive compared to poorly-attractive group. Associations were found between these ASVs and volatiles known to be attractive to Anopheles mosquitoes. Propanoic pathways are enriched in the poorly-attractive participants compared to those found to be highly-attractive. CONCLUSIONS: Our findings suggest that variation in attractiveness of people to mosquitoes is related to the composition of the skin microbiota, knowledge that could improve odour-baited traps or other next generation vector control tools.

Using trained dogs and organic semi-conducting sensors to identify asymptomatic and mild SARS-CoV-2 infections: an observational study.

BACKGROUND: A rapid, accurate, non-invasive diagnostic screen is needed to identify people with SARS-CoV-2 infection. We investigated whether organic semi-conducting (OSC) sensors and trained dogs could distinguish between people infected with asymptomatic or mild symptoms, and uninfected individuals, and the impact of screening at ports-of-entry. METHODS: Odour samples were collected from adults, and SARS-CoV-2 infection status confirmed using RT-PCR. OSC sensors captured the volatile organic compound (VOC) profile of odour samples. Trained dogs were tested in a double-blind trial to determine their ability to detect differences in VOCs between infected and uninfected individuals, with sensitivity and specificity as the primary outcome. Mathematical modelling was used to investigate the impact of bio-detection dogs for screening. RESULTS: About, 3921 adults were enrolled in the study and odour samples collected from 1097 SARS-CoV-2 infected and 2031 uninfected individuals. OSC sensors were able to distinguish between SARS-CoV-2 infected individuals and uninfected, with sensitivity from 98% (95% CI 95-100) to 100% and specificity from 99% (95% CI 97-100) to 100%. Six dogs were able to distinguish between samples with sensitivity ranging from 82% (95% CI 76-87) to 94% (95% CI 89-98) and specificity ranging from 76% (95% CI 70-82) to 92% (95% CI 88-96). Mathematical modelling suggests that dog screening plus a confirmatory PCR test could detect up to 89% of SARS-CoV-2 infections, averting up to 2.2 times as much transmission compared to isolation of symptomatic individuals only. CONCLUSIONS: People infected with SARS-CoV-2, with asymptomatic or mild symptoms, have a distinct odour that can be identified by sensors and trained dogs with a high degree of accuracy. Odour-based diagnostics using sensors and/or dogs may prove a rapid and effective tool for screening large numbers of people.Trial Registration NCT04509713 (clinicaltrials.gov).

Vector control strategies in Brazil: a qualitative investigation into community knowledge, attitudes and perceptions following the 2015-2016 Zika virus epidemic.

OBJECTIVE: The World Health Organization declared a Public Health Emergency of International Concern following the rapid emergence of neonatal microcephaly in Brazil during the 2015-2016 Zika virus (ZIKV) epidemic. In response, a national campaign sought to control Aedes mosquito populations and reduce ZIKV transmission. Achieving adherence to vector control or mosquito-bite reduction behaviours, including the use of topical mosquito repellents, is challenging. Coproduction of research at the community level is needed to understand and mitigate social determinants of lower engagement with Aedes preventive measures, particularly within disempowered groups. DESIGN: In 2017, the Zika Preparedness Latin America Network (ZikaPLAN) conducted a qualitative study to understand individual and community level experiences of ZIKV and other mosquito-borne disease outbreaks. Presented here is a thematic analysis of 33 transcripts from community focus groups and semistructured interviews, applying the Health Belief Model (HBM) to elaborate knowledge, attitudes and perceptions of ZIKV and vector control strategies. PARTICIPANTS: 120 purposively sampled adults of approximate reproductive age (18-45); 103 women participated in focus groups and 17 men in semistructured interviews. SETTING: Two sociopolitically and epidemiologically distinct cities in Brazil: Jundiaí (57 km north of São Paolo) and Salvador (Bahia state capital). RESULTS: Four key and 12 major themes emerged from the analysis: (1) knowledge and cues to action; (2) attitudes and normative beliefs (perceived threat, barriers, benefits and self-efficacy); (3) behaviour change (household prevention and community participation); and (4) community preferences for novel repellent tools, vector control strategies and ZIKV messaging. CONCLUSIONS: Common barriers to repellent adherence were accessibility, appearance and effectiveness. A strong case is made for the transferability of the HBM to inform epidemic preparedness for mosquito-borne disease outbreaks at the community level. Nationally, a health campaign targeting men is recommended, in addition to local mobilisation of funding to strengthen surveillance, risk communication and community engagement.

Public health messages on arboviruses transmitted by Aedes aegypti in Brazil.

BACKGROUND: The outbreak of Zika virus in Brazil in 2015 followed the arrival of chikungunya in 2014 and a long history of dengue circulation. Vital to the response to these outbreaks of mosquito-borne pathogens has been the dissemination of public health messages, including those promoted through risk communication posters. This study explores the content of a sample of posters circulated in Brazil towards the end of the Zika epidemic in 2017 and analyses their potential effectiveness in inducing behaviour change. METHODS: A content analysis was performed on 37 posters produced in Brazil to address outbreaks of mosquito-borne pathogens. The six variables of the Health Belief Model were used to assess the potential effectiveness of the posters to induce behaviour change. RESULTS: Three overarching key messages emerged from the posters. These included (i) the arboviruses and their outcomes, (ii) a battle against the mosquito, and (iii) a responsibility to protect and prevent. Among the six variables utilised through the Health Belief Model, cues to action were most commonly featured, whilst the perceived benefits of engaging in behaviours to prevent arbovirus transmission were the least commonly featured. CONCLUSIONS: The posters largely focused on mosquito-borne transmission and the need to eliminate breeding sites, and neglected the risk of the sexual and congenital transmission of Zika and the importance of alternative preventive actions. This, we argue, may have limited the potential effectiveness of these posters to induce behaviour change.

Towards an odour-baited trap to control Musca sorbens, the putative vector of trachoma.

Musca sorbens is a synanthropic filth fly that aggressively attacks people to feed from mucous membranes of the eyes, nose or mouth, from open sores, or from sweat. It has long been suspected that this fly contributes to the transmission of eye infections, particularly trachoma, and recent work has added to the evidence base that M. sorbens is a trachoma vector in Ethiopia. There are few options to control M. sorbens, largely due to a lack of evidence. Space spraying with insecticides is effective, but an environmentally sound and long-term sustainable solution would be better, for example, mass trapping. We tested commercially available and homemade trap types in a pilot (laboratory) study and three field studies. A homemade design, built from a bucket and two empty water bottles, baited with a commercially available lure, The Buzz, was found to be most effective. This trap caught 3848 M. sorbens over 26 trap 'events' (3- or 4-day periods); mean/median per 24 h 43.6 (standard deviation 137.10)/2.25 (IQR 0.25-12.67). The Buzz lure is cheap and effective for 4 weeks, and trap components cheap and locally available. Further studies are needed to understand the impact of this trap on local fly populations and the local transmission of trachoma.

The use of islands and cluster-randomized trials to investigate vector control interventions: a case study on the Bijagós archipelago, Guinea-Bissau.

Vector-borne diseases threaten the health of populations around the world. While key interventions continue to provide protection from vectors, there remains a need to develop and test new vector control tools. Cluster-randomized trials, in which the intervention or control is randomly allocated to clusters, are commonly selected for such evaluations, but their design must carefully consider cluster size and cluster separation, as well as the movement of people and vectors, to ensure sufficient statistical power and avoid contamination of results. Island settings present an opportunity to conduct these studies. Here, we explore the benefits and challenges of conducting intervention studies on islands and introduce the Bijagós archipelago of Guinea-Bissau as a potential study site for interventions intended to control vector-borne diseases. This article is part of the theme issue 'Novel control strategies for mosquito-borne diseases'.

Novel control strategies for mosquito-borne diseases.

Mosquito-borne diseases are an increasing global health challenge, threatening over 40% of the world's population. Despite major advances in malaria control since 2000, recent progress has stalled. Additionally, the risk of Aedes-borne arboviruses is rapidly growing, with the unprecedented spread of dengue and chikungunya viruses, outbreaks of yellow fever and the 2015 epidemic of Zika virus in Latin America. To counteract this growing problem, diverse and innovative mosquito control technologies are currently under development. Conceptually, these span an impressive spectrum of approaches, from invasive transgene cassettes with the potential to crash mosquito populations or reduce the vectorial capacity of a population, to low-cost alterations in housing design that restrict mosquito entry. This themed issue will present articles providing insight into the breadth of mosquito control research, while demonstrating the requirement for an interdisciplinary approach. The issue will highlight mosquito control technologies at varying stages of development and includes both opinion pieces and research articles with laboratory and field-based data on control strategy development. This article is part of the theme issue 'Novel control strategies for mosquito-borne diseases'.

Differential attraction in mosquito-human interactions and implications for disease control.

Mosquito-borne diseases are a major burden on human health worldwide and their eradication through vector control methods remains challenging. In particular, the success of vector control interventions for targeting diseases such as malaria is under threat, in part due to the evolution of insecticide resistance, while for other diseases effective control solutions are still lacking. The rate at which mosquitoes encounter and bite humans is a key determinant of their capacity for disease transmission. Future progress is strongly reliant on improving our understanding of the mechanisms leading to a mosquito bite. Here, we review the biological factors known to influence the attractiveness of mosquitoes to humans, such as body odour, the skin microbiome, genetics and infection by parasites. We identify the knowledge gaps around the relative contribution of each factor, and the potential links between them, as well as the role of natural selection in shaping vector-host-parasite interactions. Finally, we argue that addressing these questions will contribute to improving current tools and the development of novel interventions for the future. This article is part of the theme issue 'Novel control strategies for mosquito-borne diseases'.

The Role of the Private Sector in Supporting Malaria Control in Resource Development Settings.

Industrial operations of the private sector, such as extraction, agriculture, and construction, can bring large numbers of people into new settlement areas and cause environmental change that promotes the transmission of vector-borne diseases. Industry-related workers and communities unduly exposed to infection risk typically lack the knowledge and means to protect themselves. However, there is a strong business rationale for protecting local resident employees through integrated vector control programs, as well as an ethical responsibility to care for these individuals and the affected communities. We discuss the role and challenges of the private sector in developing malaria control programs, which can include extensive collaborations with the public sector that go on to form the basis of national vector control programs or more broadly support local healthcare systems.