The TIRS trial: Enrollment procedures and baseline characterization of a pediatric cohort to quantify the epidemiologic impact of targeted indoor residual spraying on Aedes-borne viruses in Merida, Mexico.

Aedes mosquito-borne viruses (ABVs) place a substantial strain on public health resources in the Americas. Vector control of Aedes mosquitoes is an important public health strategy to decrease or prevent spread of ABVs. The ongoing Targeted Indoor Residual Spraying (TIRS) trial is an NIH-sponsored clinical trial to study the efficacy of a novel, proactive vector control technique to prevent dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) infections in the endemic city of Merida, Yucatan, Mexico. The primary outcome of the trial is laboratory-confirmed ABV infections in neighborhood clusters. Despite the difficulties caused by the COVID-19 pandemic, by early 2021 the TIRS trial completed enrollment of 4,792 children aged 2-15 years in 50 neighborhood clusters which were allocated to control or intervention arms via a covariate-constrained randomization algorithm. Here, we describe the makeup and ABV seroprevalence of participants and mosquito population characteristics in both arms before TIRS administration. Baseline surveys showed similar distribution of age, sex, and socio-economic factors between the arms. Serum samples from 1,399 children were tested by commercially available ELISAs for presence of anti-ABV antibodies. We found that 45.1% of children were seropositive for one or more flaviviruses and 24.0% were seropositive for CHIKV. Of the flavivirus-positive participants, most were positive for ZIKV-neutralizing antibodies by focus reduction neutralization testing which indicated a higher proportion of participants with previous ZIKV than DENV infections within the cohort. Both study arms had statistically similar seroprevalence for all viruses tested, similar socio-demographic compositions, similar levels of Ae. aegypti infestation, and similar observed mosquito susceptibility to insecticides. These findings describe a population with a high rate of previous exposure to ZIKV and lower titers of neutralizing antibodies against DENV serotypes, suggesting susceptibility to future outbreaks of flaviviruses is possible, but proactive vector control may mitigate these risks.

Residual efficacy of the neonicotinoid insecticide clothianidin against pyrethroid-resistant Aedes aegypti.

BACKGROUND: Here we report the residual efficacy of the neonicotinoid insecticide clothianidin against pyrethroid-resistant Aedes aegypti. We first conducted a range-finding evaluation of clothianidin on three different substrates (wall, wood, cloth) using three doses (100, 300 and 600 mg a.i. m-2 ) and conducting World Health Organization (WHO) cone bioassays to assess acute (24 h) and delayed (up to 7 days) mortality. In experimental houses located in Merida (Mexico) and using free-flying pyrethroid-resistant Ae. aegypti females, we quantified the acute and delayed mortality after a 24-h exposure to the targeted indoor residual spraying (TIRS) of two clothianidin doses (100 and 300 mg a.i. m-2 ). RESULTS: Range-finding studies with WHO cones showed low (<50%) acute mortality for all surfaces, doses and times post spraying. Delayed mortality was higher, with average values above or close to the 60% mark (and 95% confidence interval estimates crossing 80% for the 600 mg a.i. m-2 dose). In experimental houses, a similar low acute mortality was quantified (range of mortality across 12 months was 2-44% for 100 mg a.i. m-2 and 8-61% for 300 mg a.i/m2 ). However, delayed mortality showed a strong effect of clothianidin on free-flying Ae. aegypti, with values above 80% up to 7 months post-TIRS. CONCLUSION: Novel residual insecticide molecules have a promising outlook for Ae. aegypti control and can contribute to the expansion and adoption of TIRS in urban areas. clothianidin can contribute to the control of resistant Ae. aegypti and provide residual control for up to 7 months after application. © 2022 Society of Chemical Industry.

Preventive residual insecticide applications successfully controlled Aedes aegypti in Yucatan, Mexico.

Insecticide-based approaches remain a key pillar for Aedes-borne virus (ABV, dengue, chikungunya, Zika) control, yet they are challenged by the limited effect of traditional outdoor insecticide campaigns responding to reported arboviral cases and by the emergence of insecticide resistance in mosquitoes. A three-arm Phase II unblinded entomological cluster randomized trial was conducted in Merida, Yucatan State, Mexico, to quantify the entomological impact of targeted indoor residual spraying (TIRS, application of residual insecticides in Ae. aegypti indoor resting sites) applied preventively 2 months before the beginning of the arbovirus transmission season. Trial arms involved the use of two insecticides with unrelated modes of action (Actellic 300CS, pirimiphos-methyl, and SumiShield 50WG, clothianidin) and a control arm where TIRS was not applied. Entomological impact was quantified by Prokopack adult collections performed indoors during 10 min per house. Regardless of the insecticide, conducting a preventive TIRS application led to significant reductions in indoor Ae. aegypti densities, which were maintained at the same levels as in the low arbovirus transmission period (Actellic 300CS reduced Ae. aegypti density up to 8 months, whereas SumiShield 50WG up to 6 months). The proportional reduction in Ae. aegypti abundance in treatment houses compared to control houses was 50-70% for Actellic 300CS and 43-63% for SumiShield 50WG. Total operational costs including insecticide ranged from US$4.2 to US$10.5 per house, depending on the insecticide cost. Conducting preventive residual insecticide applications can maintain Ae. aegypti densities at low levels year-round with important implications for preventing ABVs in the Americas and beyond.

Mosquito species (Diptera: culicidae) collected after tropical storm cristobal in Merida, Yucatan, South-east Mexico.

After the tropical storm Cristobal, we performed special adult entomological collections in the peri-domicile of 35 houses from 25 neighborhoods of Mérida, Yucatan, Mexico in response to complaints from the community about an increased nuisance due to an abundance of mosquitoes. A total of 1,275 specimens from four genera and 13 species were collected: Aedes taeniorhynchus (92%), Culex quinquefasciatus (72%), Aedes aegypti (72%), Psorophora mexicana (36%), Psorophora cyanescens (32%), Aedes scapularis (24%), Culex nigripalpus (24%), Aedes albopictus (8%), Psorophora ferox (4%), Haemagogus equinus (4%), Aedes trivittatus (4%), Culex coronator (4%), Culex iolambdis (4%). From these collections, the increased mosquito nuisance was mainly the result of invasive species such as Aedes taeniorhynchus and Psorophora. City wide, vehicle mounted ULV spraying was performed by the MoH and the municipality of Merida to control adult mosquito populations. We report Culex iolambdis for the first time in Merida and Psorophora mexicana for the state of Yucatan.

Efficacy of targeted indoor residual spraying with the pyrrole insecticide chlorfenapyr against pyrethroid-resistant Aedes aegypti.

BACKGROUND: There is an increased need to mitigate the emergence of insecticide resistance and incorporate new formulations and modes of application to control the urban vector Aedes aegypti. Most research and development of insecticide formulations for the control of Ae. aegypti has focused on their peridomestic use as truck-mounted ULV-sprays or thermal fogs despite the widespread knowledge that most resting Ae. aegypti are found indoors. A recent modification of indoor residual spraying (IRS), termed targeted IRS (TIRS) works by restricting applications to 1.5 m down to the floor and on key Ae. aegypti resting sites (under furniture). TIRS also opens the possibility of evaluating novel residual insecticide formulations currently being developed for malaria IRS. METHODS: We evaluated the residual efficacy of chlorfenapyr, formulated as Sylando 240SC, for 12 months on free-flying field-derived pyrethroid-resistant Ae. aegypti using a novel experimental house design in Merida, Mexico. On a monthly basis, 600 female Ae. aegypti were released into the houses and left indoors with access to sugar solution for 24 hours. After the exposure period, dead and alive mosquitoes were counted in houses treated with chlorfenapyr as well as untreated control houses to calculate 24-h mortality. An evaluation for these exposed cohorts of surviving mosquitoes was extended up to seven days under laboratory conditions to quantify "delayed mortality". RESULTS: Mean acute (24-h) mortality of pyrethroid-resistant Ae. aegypti ranged 80-97% over 5 months, dropping below 30% after 7 months post-TIRS. If delayed mortality was considered (quantifying mosquito mortality up to 7 days after exposure), residual efficacy was above 90% for up to 7 months post-TIRS application. Generalized Additive Mixed Models quantified a residual efficacy of chlorfenapyr of 225 days (ca. 7.5 months). CONCLUSIONS: Chlorfenapyr represents a new option for TIRS control of Ae. aegypti in urban areas, providing a highly-effective time of protection against indoor Ae. aegypti females of up to 7 months.