The fabric of life: What if mosquito nets were durable and widely available but insecticide-free?

Background: Bed nets are the commonest malaria prevention tool and arguably the most cost-effective. Their efficacy is because they prevent mosquito bites (a function of physical durability and integrity), and kill mosquitoes (a function of chemical content and mosquito susceptibility). This essay follows the story of bed nets, insecticides and malaria control, and asks whether the nets must always have insecticides. Methods: Key attributes of untreated or pyrethroid-treated nets are examined alongside observations of their entomological and epidemiological impacts. Arguments for and against adding insecticides to nets are analysed in contexts of pyrethroid resistance, personal-versus-communal protection, outdoor-biting, need for local production and global health policies. Findings: Widespread resistance in African malaria vectors has greatly weakened the historical mass mosquitocidal effects of insecticide-treated nets (ITNs), which previously contributed communal benefits to users and non-users. Yet ITNs still achieve substantial epidemiological impact, suggesting that physical integrity, consistent use and population-level coverage are increasingly more important than mosquitocidal properties. Pyrethroid-treatment remains desirable where vectors are sufficiently susceptible, but is no longer universally necessary and should be re-examined alongside other attributes, e.g. durability, coverage, acceptability and access. New ITNs with multiple actives or synergists could provide temporary relief in some settings, but their performance, higher costs, and drawn-out innovation timelines do not justify singular emphasis on insecticides. Similarly, sub-lethal insecticides may remain marginally-impactful by reducing survival of older mosquitoes and disrupting parasite development inside the mosquitoes, but such effects vanish under strong resistance. Conclusions: The public health value of nets is increasingly driven by bite prevention, and decreasingly by lethality to mosquitoes. For context-appropriate solutions, it is necessary to acknowledge and evaluate the potential and cost-effectiveness of durable untreated nets across different settings. Though ~ 90% of malaria burden occurs in Africa, most World Health Organization-prequalified nets are manufactured outside Africa, since many local manufacturers lack capacity to produce the recommended insecticidal nets at competitive scale and pricing. By relaxing conditions for insecticides on nets, it is conceivable that non-insecticidal but durable, and possibly bio-degradable nets, could be readily manufactured locally. This essay aims not to discredit ITNs, but to illustrate how singular focus on insecticides can hinder innovation and sustainability

Using Remotely Sensed Data to Explore Spatial and Temporal Relationships Between Photosynthetic Productivity of Vegetation and Malaria Transmission Intensities in Selected Parts of Africa

Spatial and temporal variations in malaria transmission are naturally associated with prevailing climatic and environmental factors, for example rainfall, humidity, temperature and human activities. These factors influence malaria transmission mainly in non-deterministic ways, making them less appropriate for accurate geographical mapping of malaria risk. One distinctive phenomenon, ‘photosynthetic productivity of vegetation’, is similarly affected by these factors, yet it can be easily estimated from remotely sensed data using standardized indices. In this study, multiple linear regression techniques are used to explore spatial and temporal associations between photosynthetic productivity of vegetation (measured as Normalized Difference Vegetation Index (NDVI)) and malaria transmission intensities (measured as Entomological Inoculation Rate (EIR)). The study shows significant relationships between NDVI and EIR both at continental level and at a number of the selected study sites. Moreover, in three of four sites where temporal analysis was conducted, a similarity of linear trends is observed between EIRs and means of current and previous month NDVIs. Both NDVI and EIR are significantly associated with altitude as well as to a rural/urban dummy variable. It is concluded that spatial and temporal variations in photosynthetic productivity of vegetation are strongly related to variations in malaria transmission at respective places and periods. Results of this basic exploration imply that vegetation production is a potential indicator of situations favourable for malaria transmission, and can therefore be used to improve mapping of geographical extents of risk of malaria, and perhaps several other vector borne diseases

The Paradigm of Eave Tubes: Scaling up House Improvement and Optimizing Insecticide Delivery against Disease-Transmitting Mosquitoes.

Control of mosquito-borne diseases is greatly compromised by spread of insecticide resistance, high implementation costs and sub-optimal compliance among users. Improved housing has potential to reduce malaria transmission nearly as much as long-lasting insecticide-treated nets (LLINs), while also preventing other arthropod-borne diseases and improving overall well-being. Yet, it is hardly promoted as mainstream intervention, partly because of high costs, minimal communal benefits to people in non-improved houses, and low scalability. By exploiting biological observations of mosquito behaviours around dwellings, scientists have developed a new approach that integrates effective vector control into housing developments. The technique involves blocking eave spaces in local houses, leaving a few cylindrical holes into which plastic tubes with insecticide-laden electrostatic nettings are inserted. Where houses already have blocked eaves, these cylindrical holes are drilled and the tubes inserted. The eave tube technology, as it is called, is an innovative new approach for implementing housing improvements, by creating a new scalable product that can be integrated in houses during or after construction. It takes away insecticides from proximity of users, and instead puts them where mosquitoes are most likely to enter houses, thereby reducing insecticidal exposure among household occupants, while maximizing exposure of mosquitoes. This way, lower quantities of insecticides are used, better house ventilation achieved, intervention costs reduced, and mass communal benefits achieved even were vectors are resistant to similar insecticides when delivered conventionally. There are however still some critical pieces missing, notably epidemiological, social and economic evidence that the above assertions are true and sustainable. Besides, there also some technical limitations to be considered, namely: (1) need for extensive house modifications before eave tubes are inserted, (2) ineligibility of poorest and highest-risk households living in housing structures not amenable to eave tubes, and (3) poor synergies when eave tubes are combined with LLINs or IRS in same households. Overall, this paradigm significantly improves delivery of insecticides against disease-transmitting mosquitoes, and provides opportunities for scaling-up the long-neglected concept of house improvement as a malaria intervention

PMI Activity TZ-1,2: IRS and LLIN: Integration of Methods and Insecticide Mode of Actions for Control of African Malaria Vector Mosquitoes

Long lasting Insecticidal nets (LLINs) and indoor residual spraying (IRS) are the preferred techniques for malaria vector control in Africa, where their application has a proven contribution to the recent significant reductions in the burden of the disease. Even though both methods are commonly used together in the same households, evidence of improved malaria control due to the use of combinations as opposed to use of either method alone has been minimal and inconclusive.To measure the mode of action of three classes of insecticides used for IRS at the WHO recommended dose: the organochlorine DDT 70 wettable powder (AVIMA, South Africa) at 2g/m2; the pyrethroid lambda-cyhalothrin capsule suspension ICON CS, (Syngenta, Switzerland), at 0.03g/m2; and the organophosphate pirimiphos-methyl (PM) emulsified concentrate, also known as actellic (Syngenta, Switzerland), at 2g/m2 used alone or in combination with three leading LLIN brands: PermaNet 2.0® nets (Vastergaard, Switzerland), Olyset® nets (manufactured by A-Z, Tanzania), and Icon Life® nets (Bestnet Europe ltd, Denmark). All LLINS were used intact and were not subjected to repeated washing to reflect their optimum performance. The control was untreated polyester net. Data were collected from experimental huts developed during the project to measure both behavioral and toxic modes of actions of insecticides in Southern Tanzania. The primary malaria vector is Anopheles arabiensis with >90% susceptibility to insecticides of all classes at diagnostic doses in WHO susceptibility assays. Two rounds of data collection were performed: 1) 4 months during the dry season 2) six months during the wet season. Data generated from the experimental hut studies were analysed with Poisson-lognormal generalized linear mixed effects models (GLMM). Data was also simulated using deterministic mathematical model to measure potential impacts of each IRS, LLIN and combination thereof on malaria at a community level. Bite prevention (feeding inhibition): During both rounds, all the IRS treatments, LLINs and the controls (which consisted of intact untreated mosquito nets), provided greater than 99% protection from potentially infectious bites by the malaria vector, An. arabiensis, for the entire duration of the study. Most of the mosquitoes were caught inside the exit traps as opposed to inside the experimental huts, regardless of whether the huts were had LLINs, IRS or non-insecticidal nets. More than 95% of An. arabiensis, Culex pipiens quinquefasciatus and Mansonia africana / uniformis mosquitoes were caught inside the exit traps while exiting the huts. Toxicity: All IRS treatments, all the LLINs and the majority of LLIN/IRS combinations significantly increased proportions of dead An. arabiensis mosquitoes, relative to the control huts. The most toxic IRS relative to the controls was PM (RR = 2.21 (1.82 – 2.68), P < 0.001), followed by ICON CS (RR = 1.55 (1.27 – 1.89), P < 0.001) and then DDT (RR = 1.44 (1.18 – 1.77), P < 0.001). The most toxic LLIN relative to the controls was PermaNet 2.0® nets (RR = 1.65 (1.58 – 1.74), P < 0.001), followed by Icon Life® nets (RR = 1.55 (1.42 – 1.69), P < 0.001) and then Olyset® nets (RR = 1.33 (1.12 – 1.47), P < 0.001). Combinations of IRS and LLINs relative to LLINs alone: In most cases, there was no significant increase in An. arabiensis mortality in huts combining LLINs plus IRS, relative to huts having LLINs only, except in cases where the specific IRS treatment was PM. Addition of PM significantly increased proportional mortality of An. arabiensis when combined with Olyset® nets (RR = 1.38 (1.14 – 1.65), P = 0.001), PermaNet 2.0® nets (RR = 1.42 (1.18 – 1.71), P <0.001) and Icon Life® (RR = 1.24 (1.03 – 1.49), P = 0.023). Combinations of LLINs and DDT or lambda cyhalothrin resulted in marginal increases in An. arabiensis mortality relative to huts with LLINs alone although none of these combinations resulted in a statistically significant increase. Combinations of IRS and LLINs relative to IRS alone: There was a trend of significant increases in An. arabiensis mortality in huts having IRS plus LLINs, relative to huts having just the IRS alone, except for the combinations of 1) Olyset® with ICON CS, 2) DDT with Olyset® or 3) DDT with Icon Life® nets. In the huts that had been sprayed with PM, there was a significant increase in An. arabiensis mortality whenever Icon Life® nets (RR = 1.39 (1.18 – 1.63), P < 0.001), Olyset® nets (RR = 1.32 (1.13 – 1.55), P = 0.001) or PermaNet 2.0® nets (RR = 1.26 (1.08 – 1.48), P = 0.004) were added, relative to the huts where PM IRS was used alone. Similarly, in the huts that had been sprayed with ICON CS, there was a significant increase in An. arabiensis mortality in combination with Icon Life® nets (RR = 1.43 (1.19 – 1.73), P < 0.001) or PermaNet 2.0® nets (RR = 1.70 (1.35 – 2.13), P < 0.001), but not Olyset® nets (RR = 1.16 (0.92 – 1.45), P = 0.210), relative to the IRS alone. In huts sprayed with DDT, none of the LLINs significantly improved proportional mortality of the An. Arabiensis mosquitoes, except PermaNet 2.0® nets (RR = 1.18 (1.06 – 1.32), P = 0.003). Residual efficacy bioassays of IRS: All IRS formulations were highly effective during the first month after spraying and rapidly decayed losing most activity within 1-3 months. In month 1, all An. arabiensis exposed to palm ceilings sprayed with either PM or ICON CS died, and 85% were killed by DDT (despite full susceptibility most likely because it flaked away). On mud walls sprayed with the same chemicals, 100%, 90.0% and 97.5% mortality was observed, respectively, during the first month. Activity of the IRS declined significantly so that by the third month, PM on palm and mud killed 42.5% and 55.0% of exposed An. arabiensis, respectively. ICON CS killed only 46.3% on palm and 52.5% on mud walls. By month 6, PM had nearly entirely decayed, killing only 7.5% of An. arabiensis exposed to sprayed palm ceilings and 27.5% of those exposed to sprayed mud walls; ICON CS killed 30.0% on ceilings and 27.5% on walls. DDT had a longer residual action, killing 42.5% of An. arabiensis exposed to sprayed ceilings, and 36.3% of those exposed to sprayed walls after 6 months. Residual efficacy bioassays of LLINs: While all the LLINs generally performed better (i.e. killed more mosquitoes) on wire frame assays than on the cone assays, their activity rapidly deteriorated by the second month of use relative to new nets. Only PermaNet® nets retained mosquitocidal efficacy of >80% by the sixth month of net use (killing 92.7% on wire ball tests and 84% on cone assays). All the LLINs however retained very high knock-down rates (> 90% in wire ball tests and >80% in cone tests) on the exposed mosquitoes, except Olyset® nets whose knock-down activity reduced to 72.7% on wire ball tests and 62% on cone tests by the sixth month. Both the field studies and the model simulations showed that any synergies or redundancies resulting from LLIN/IRS combinations are primarily a function of modes of action of active ingredients used in the two interventions. None of the IRS or LLINs tested was deterrent so they do not protect by keeping mosquitoes from houses in this setting. Very few mosquitoes were able to obtain a blood meal due to the use of intact LLINs and untreated control nets. Therefore, where households are correctly using and maintaining LLINs there is no added value in the additional application of IRS unless the IRS chemical is highly toxic and non-irritant, as is PM. This compound consistently increased mosquito mortality in combination with any LLIN even though mosquitoes did not rest indoors as they were unable to obtain a blood meal. The average duration of effect of insecticides in this setting was 3 months, far lower than that stated by the manufacturers, so IRS should be carefully timed. Where IRS is the pre-existing intervention, providing households with additional LLINs confers additional protection. Therefore, IRS households should always be supplemented with nets, preferably LLINs, which not only protect house occupants against mosquito bites, but also kill additional mosquitoes. Finally, where resources are limited, priority should be given to providing everybody with LLINs and ensuring that these nets are consistently and appropriately used, rather than trying to implement both LLINs and IRS in the same community at the same time.\ud \u

Larvicidal effects of a neem (Azadirachta indica) oil formulation on the malaria vector Anopheles gambiae

Larviciding is a key strategy used in many vector control programmes around the world. Costs could be reduced if larvicides could be manufactured locally. The potential of natural products as larvicides against the main African malaria vector, Anopheles gambiae s.s was evaluated. To assess the larvicidal efficacy of a neem (Azadirachta indica) oil formulation (azadirachtin content of 0.03% w/v) on An. gambiae s.s., larvae were exposed as third and fourth instars to a normal diet supplemented with the neem oil formulations in different concentrations. A control group of larvae was exposed to a corn oil formulation in similar concentrations. Neem oil had an LC50 value of 11 ppm after 8 days, which was nearly five times more toxic than the corn oil formulation. Adult emergence was inhibited by 50% at a concentration of 6 ppm. Significant reductions on growth indices and pupation, besides prolonged larval periods, were observed at neem oil concentrations above 8 ppm. The corn oil formulation, in contrast, produced no growth disruption within the tested range of concentrations. Neem oil has good larvicidal properties for An. gambiae s.s. and suppresses successful adult emergence at very low concentrations. Considering the wide distribution and availability of this tree and its products along the East African coast, this may prove a readily available and cheap alternative to conventional larvicides

A Geographical Location Model for Targeted Implementation of Lure-and-Kill Strategies Against Disease-Transmitting Mosquitoes in Rural Areas

Outdoor devices for luring and killing disease-transmitting mosquitoes have been proposed as potential com- plementary interventions alongside existing intra-domiciliary methods namely insecticide treated nets and house spraying with residual insecticides. To enhance effectiveness of such outdoor interventions, it is essential to optimally locate them in such a way that they target most of the outdoor mosquitoes. Using odour-baited lure and kill stations (OBS) as an example, we describe a map model derived from: 1) com-munity participatory mapping conducted to identify mosquito breeding habitats, 2) entomological field studies conducted to estimate outdoor mosquito densities and to determine safe distances of the OBS from human dwellings, and 3) field surveys conducted to map households, roads, outdoor human aggregations and landmarks. The resulting data were combined in a Ge- ographical Information Systems (GIS) environment and analysed to determine optimal locations for the OBS. Separately, a GIS-interpolated map produced by asking community members to rank different zones of the study area and show where they expected to find most mosquitoes, was visually compared to another map interpolated from the entomological survey of outdoor mosquito densities. An easy-to-interpret suitability map showing optimal sites for placing OBS was produced, which clearly depicted areas least suitable and areas most suitable for locating the devices. Comparative visual interpretation of maps derived from interpolating the community knowledge and entomological data revealed major similarities between the two maps. Using distribution patterns of human and mosquito populations as well as characteristics of candidate outdoor interventions, it is possible to readily determine suitable areas for targeted positioning of the interventions, thus improve effectiveness. This study also highlights possibilities of relying on community knowledge to approximate areas where mosquitoes are most abundant and where to locate outdoor complementary interventions such as odour-baited lure and kill stations for controlling disease-transmitting mosquitoes.\u