Considerations for first field trials of low-threshold gene drive for malaria vector control.

Sustainable reductions in African malaria transmission require innovative tools for mosquito control. One proposal involves the use of low-threshold gene drive in Anopheles vector species, where a 'causal pathway' would be initiated by (i) the release of a gene drive system in target mosquito vector species, leading to (ii) its transmission to subsequent generations, (iii) its increase in frequency and spread in target mosquito populations, (iv) its simultaneous propagation of a linked genetic trait aimed at reducing vectorial capacity for Plasmodium, and (v) reduced vectorial capacity for parasites in target mosquito populations as the gene drive system reaches fixation in target mosquito populations, causing (vi) decreased malaria incidence and prevalence. Here the scope, objectives, trial design elements, and approaches to monitoring for initial field releases of such gene dive systems are considered, informed by the successful implementation of field trials of biological control agents, as well as other vector control tools, including insecticides, Wolbachia, larvicides, and attractive-toxic sugar bait systems. Specific research questions to be addressed in initial gene drive field trials are identified, and adaptive trial design is explored as a potentially constructive and flexible approach to facilitate testing of the causal pathway. A fundamental question for decision-makers for the first field trials will be whether there should be a selective focus on earlier points of the pathway, such as genetic efficacy via measurement of the increase in frequency and spread of the gene drive system in target populations, or on wider interrogation of the entire pathway including entomological and epidemiological efficacy. How and when epidemiological efficacy will eventually be assessed will be an essential consideration before decisions on any field trial protocols are finalized and implemented, regardless of whether initial field trials focus exclusively on the measurement of genetic efficacy, or on broader aspects of the causal pathway. Statistical and modelling tools are currently under active development and will inform such decisions on initial trial design, locations, and endpoints. Collectively, the considerations here advance the realization of developer ambitions for the first field trials of low-threshold gene drive for malaria vector control within the next 5 years.

Current and future opportunities of autodissemination of pyriproxyfen approach for malaria vector control in urban and rural Africa.

Despite the progress made in reducing malaria burden, new ways to address the increasing challenges of insecticide resistance and the invasion and spread of exotic malaria vectors such as Anopheles stephensi in Africa are urgently needed. While African countries are adopting larviciding as a complementary intervention for malaria vector control, the autodissemination technology has the potential to overcome barriers associated with the identification and treatment of prolific habitats that impede conventional larviciding approaches in rural settings. The autodissemination technology as a "lure and release" strategy works by exploiting the resting behavior of gravid mosquitoes to transfer lethal concentration of biological or chemical insecticide such as pyriproxyfen (PPF), an insect growth regulator (IGRs) to their oviposition sites and result in adult emergence inhibition. Despite the evidence of the autodissemination approach to control other mosquito-borne diseases, there is growing and promising evidence for its use in controlling malaria vectors in Africa, which highlights the momentous research that needs to be sustained. This article reviews the evidence for efficacy of the autodissemination approach using PPF and discusses its potential as efficient and affordable complementary malaria vector control intervention in Africa. In the previous studies that were done in controlled semi-field environments, autodissemination with PPF demonstrated its potential in reducing densities of captive population of malaria vectors such as Anopheles gambiae and Anopheles arabiensis. Of importance, empirical evidence and biology-informed mathematical models to demonstrate the utility of the autodissemination approach to control wild populations of malaria vectors under field environment either alone or in combination with other tools are underway. Among others, the key determining factors for future introduction of this approach at scale is having scalable autodissemination devices, optimized PPF formulations, assess its integration/complementarity to existing conventional larviciding, and community perception and acceptance of the autodissemination approach.

Susceptibility status of major malaria vectors to novaluron, an insect growth regulator South-Eastern Tanzania.

Introduction: application of Insect Growth Regulator (IGR) such as pyriproxyfen has shown a promising result in controlling malaria transmitting mosquitoes through autodissemination technique. Novaluron that inhibits the chitin development at mosquito larval stage present a promising candidate IGR for rotation with pyriproxyfen to prevent a chance of resistance development. This study assessed the susceptibility of immature stages of Anopheles arabiensis, Anopheles gambiae and Anopheles funestus to novaluron. Methods: susceptibility bioassays using technical grade novaluron (98% active ingredient) were performed inside the semi-field system using first instar larvae of Anopheles species. For each tested species, a total of 1500 larvae were used in the bioassay. Concentration range of 0.01 mg/l to 2 mg/l of novaluron were tested to establish Lethal Concentration (LC) sufficient to kills 50%, 90% and 99% of the exposed larvae by using log-dose response analysis. Results: of the tested mosquitoes, Anopheles gambiae were highly susceptible to novaluron followed by An. Arabiensis and then An. funestus. Lethal concentrations, LC50, LC90 and LC99 (95%CI) in mg/l for An. gambiae were 0.018, 0.332 and 2.001 respectively. For An. arabiensis were 0.026, 0.546 and 2.013; and for An. funestus were 0.032, 1.00 and 5.580. High larval mortality was recorded at high concentration (2mg/L), with 80% mortality within 3 days post exposure. Conclusion: the study demonstrates the efficacy of novaluron in controlling Anopheles mosquito species at immature stages via larval mortality. These findings warrant further testing of novaluron for autodissemination by different vector species for its inclusion in rotation to prevent development of resistance.

The ability of Anopheles funestus and A. arabiensis to penetrate LLINs and its effect on their mortality.

Background: Variation in mosquito body size and the ability to penetrate long-lasting insecticide-treated nets (LLINs) remains unknown. This study evaluated the ability of Anopheles funestus and A. arabiensis to penetrate commercially available treated and untreated bednets and how this behaviour affects mosquito mortality. Methods: Three types of LLINs; DawaPlus 2.0, PermaNet 2.0, Olyset 2.0, and untreated (Safi Net) were tested inside a semi-field system. One hundred 3-5-day-old and non-starved female A. funestus and A. arabiensis were released in a chamber with a sleeping adult volunteer under a treated or untreated bednet. Mosquitoes that penetrated inside the nets were collected every two hours using a mouth aspirator. Live mosquitoes were put in paper cups, fed on glucose ad libitum and their mortality rate was monitored for 48 h. Results: The ability of A. funestus to penetrate treated and untreated bednets was significantly higher than for A. arabiensis for all three LLIN net types ( P<0.001). For both species the penetration rate was higher for untreated bednets than treated ones except for the Olyset net. Regardless of the assessed mosquito species, all the mosquitoes that penetrated the net, successfully blood-fed on the sleeping volunteer. Compared to A. arabiensis, significant mortality was recorded for A. funestus that were caught inside Olyset nets within 48 hrs of monitoring ( P<0.001). Conclusions: These findings demonstrate the ability of A. funestus and A. arabiensis mosquitoes to penetrate the human-occupied treated and untreated bednets. Despite this ability, mosquitoes that penetrated the bednet succumbed to death within two days.

Infrastructure alone cannot ensure resilience to weather events in drinking water supplies.

Climate resilient water supplies are those that provide access to drinking water that is sustained through seasons and through extreme events, and where good water quality is also sustained. While surface and groundwater quality are widely understood to vary with rainfall, there is a gap in the evidence on the impact of weather and extremes in rainfall and temperature on drinking water quality, and the role of changes in water system management. A three-country (Bangladesh, Nepal and Tanzania) observational field study tracked 2353 households clustered around 685 water sources across seven different geographies over 14 months. Water quality (E. coli) data was modelled using GEE to account for clustering effects and repeated measures at households. All types of infrastructure were vulnerable to changes in weather, with differences varying between geographies; protected boreholes provided the greatest protection at the point of collection (PoC). Water quality at the point of use (PoU) was vulnerable to changes in weather, through changes in PoC water quality as well as changes in management behaviours, such as safe storage, treatment and cleaning. This is the first study to demonstrate the impact of rainfall and temperature extremes on water quality at the PoC, and the role that weather has on PoU water quality via management behaviours. Climate resilience for water supplies needs to consider the infrastructure as well as the management decisions that are taking place at a community and household level.

A retrospective study on the epidemiology and trends of road traffic accidents, fatalities and injuries in three Municipalities of Dar es Salaam Region, Tanzania between 2014-2018.

INTRODUCTION: Over 90% of injuries and deaths still occur in low and middle-income countries like Tanzania due to Road traffic accidents. Available literature indicates that Tanzania suffers massive human and economic losses every year from RTAs despite several interventions that have been made to curb this scourge. To gain an insight into the current state of RTAs we examined the pre- historical case fatality rates from RTAs in Ilala and two other municipalities (Kinondoni and Temeke) in Dar es Salaam Region, Tanzania. METHODS: We conducted a retrospective study using the secondary data on road accidents from Road Accident Information System (RAIS) for the period 2014 to 2018. RESULTS: A total of 6,772 road traffic injuries were reported between 2014 and 2018 and the study recorded the highest RTAs in the year 2014 as compared to the other years within the study period. The death rate from RTAs in Ilala Municipality alone was 36.4 per 100,000 population. About 28% of the total fatalities were recorded among the pedestrians, and there was a significant difference (P < 0.05) in the RTAs among the other road users. CONCLUSION: The study recommends the improvement of road transport infrastructure to ensure safety for all the road users by implementing the existing policies, strengthening the enforcement of existing legislation and introducing express penalties on a real-time basis. We encourage the use of this data to develop strategies in Tanzania that protect pedestrians and other vulnerable road users from RTAs.