A Systematic Review of Mosquito Coils and Passive Emanators: Defining Recommendations for Spatial Repellency Testing Methodologies.

Mosquito coils, vaporizer mats and emanators confer protection against mosquito bites through the spatial action of emanated vapor or airborne pyrethroid particles. These products dominate the pest control market; therefore, it is vital to characterize mosquito responses elicited by the chemical actives and their potential for disease prevention. The aim of this review was to determine effects of mosquito coils and emanators on mosquito responses that reduce human-vector contact and to propose scientific consensus on terminologies and methodologies used for evaluation of product formats that could contain spatial chemical actives, including indoor residual spraying (IRS), long lasting insecticide treated nets (LLINs) and insecticide treated materials (ITMs). PubMed, (National Centre for Biotechnology Information (NCBI), U.S. National Library of Medicine, NIH), MEDLINE, LILAC, Cochrane library, IBECS and Armed Forces Pest Management Board Literature Retrieval System search engines were used to identify studies of pyrethroid based coils and emanators with key-words "Mosquito coils" "Mosquito emanators" and "Spatial repellents". It was concluded that there is need to improve statistical reporting of studies, and reach consensus in the methodologies and terminologies used through standardized testing guidelines. Despite differing evaluation methodologies, data showed that coils and emanators induce mortality, deterrence, repellency as well as reduce the ability of mosquitoes to feed on humans. Available data on efficacy outdoors, dose-response relationships and effective distance of coils and emanators is inadequate for developing a target product profile (TPP), which will be required for such chemicals before optimized implementation can occur for maximum benefits in disease control

Experience and Challenges from Clinical Trials with Malaria Vaccines in Africa.

Malaria vaccines are considered amongst the most important modalities for potential elimination of malaria disease and transmission. Research and development in this field has been an area of intense effort by many groups over the last few decades. Despite this, there is currently no licensed malaria vaccine. Researchers, clinical trialists and vaccine developers have been working on many approached to make malaria vaccine available.African research institutions have developed and demonstrated a great capacity to undertake clinical trials in accordance to the International Conference on Harmonization-Good Clinical Practice (ICH-GCP) standards in the last decade; particularly in the field of malaria vaccines and anti-malarial drugs. This capacity is a result of networking among African scientists in collaboration with other partners; this has traversed both clinical trials and malaria control programmes as part of the Global Malaria Action Plan (GMAP). GMAP outlined and support global strategies toward the elimination and eradication of malaria in many areas, translating in reduction in public health burden, especially for African children. In the sub-Saharan region the capacity to undertake more clinical trials remains small in comparison to the actual need.However, sustainability of the already developed capacity is essential and crucial for the evaluation of different interventions and diagnostic tools/strategies for other diseases like TB, HIV, neglected tropical diseases and non-communicable diseases. There is urgent need for innovative mechanisms for the sustainability and expansion of the capacity in clinical trials in sub-Saharan Africa as the catalyst for health improvement and maintained

Comparative Field Evaluation of Combinations of Long-Lasting Insecticide Treated Nets and Indoor Residual Spraying, Relative to Either Method Alone, for Malaria Prevention in an Area where the main Vector is Anopheles Arabiensis.

Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are commonly used together in the same households to improve malaria control despite inconsistent evidence on whether such combinations actually offer better protection than nets alone or IRS alone. Comparative tests were conducted using experimental huts fitted with LLINs, untreated nets, IRS plus untreated nets, or combinations of LLINs and IRS, in an area where Anopheles arabiensis is the predominant malaria vector species. Three LLIN types, Olyset®, PermaNet 2.0® and Icon Life® nets and three IRS treatments, pirimiphos-methyl, DDT, and lambda cyhalothrin, were used singly or in combinations. We compared, number of mosquitoes entering huts, proportion and number killed, proportions prevented from blood-feeding, time when mosquitoes exited the huts, and proportions caught exiting. The tests were done for four months in dry season and another six months in wet season, each time using new intact nets. All the net types, used with or without IRS, prevented >99% of indoor mosquito bites. Adding PermaNet 2.0® and Icon Life®, but not Olyset® nets into huts with any IRS increased mortality of malaria vectors relative to IRS alone. However, of all IRS treatments, only pirimiphos-methyl significantly increased vector mortality relative to LLINs alone, though this increase was modest. Overall, median mortality of An. arabiensis caught in huts with any of the treatments did not exceed 29%. No treatment reduced entry of the vectors into huts, except for marginal reductions due to PermaNet 2.0® nets and DDT. More than 95% of all mosquitoes were caught in exit traps rather than inside huts. Where the main malaria vector is An. arabiensis, adding IRS into houses with intact pyrethroid LLINs does not enhance house-hold level protection except where the IRS employs non-pyrethroid insecticides such as pirimiphos-methyl, which can confer modest enhancements. In contrast, adding intact bednets onto IRS enhances protection by preventing mosquito blood-feeding (even if the nets are non-insecticidal) and by slightly increasing mosquito mortality (in case of LLINs). The primary mode of action of intact LLINs against An. arabiensis is clearly bite prevention rather than insecticidal activity. Therefore, where resources are limited, priority should be to ensure that everyone at risk consistently uses LLINs and that the nets are regularly replaced before being excessively torn. Measures that maximize bite prevention (e.g. proper net sizes to effectively cover sleeping spaces, stronger net fibres that resist tears and burns and net use practices that preserve net longevity), should be emphasized

Using a New Odour-Baited Device to Explore Options for Luring and Killing Outdoor-Biting Malaria Vectors: A Report on Design and Field Evaluation of the Mosquito Landing Box.

Mosquitoes that bite people outdoors can sustain malaria transmission even where effective indoor interventions such as bednets or indoor residual spraying are already widely used. Outdoor tools may therefore complement current indoor measures and improve control. We developed and evaluated a prototype mosquito control device, the 'Mosquito Landing Box' (MLB), which is baited with human odours and treated with mosquitocidal agents. The findings are used to explore technical options and challenges relevant to luring and killing outdoor-biting malaria vectors in endemic settings. Field experiments were conducted in Tanzania to assess if wild host-seeking mosquitoes 1) visited the MLBs, 2) stayed long or left shortly after arrival at the device, 3) visited the devices at times when humans were also outdoors, and 4) could be killed by contaminants applied on the devices. Odours suctioned from volunteer-occupied tents were also evaluated as a potential low-cost bait, by comparing baited and unbaited MLBs. There were significantly more Anopheles arabiensis, An. funestus, Culex and Mansonia mosquitoes visiting baited MLB than unbaited controls (P<=0.028). Increasing sampling frequency from every 120 min to 60 and 30 min led to an increase in vector catches of up to 3.6 fold (P<=0.002), indicating that many mosquitoes visited the device but left shortly afterwards. Outdoor host-seeking activity of malaria vectors peaked between 7:30 and 10:30pm, and between 4:30 and 6:00am, matching durations when locals were also outdoors. Maximum mortality of mosquitoes visiting MLBs sprayed or painted with formulations of candidate mosquitocidal agent (pirimiphos-methyl) was 51%. Odours from volunteer occupied tents attracted significantly more mosquitoes to MLBs than controls (P<0.001). While odour-baited devices such as the MLBs clearly have potential against outdoor-biting mosquitoes in communities where LLINs are used, candidate contaminants must be those that are effective at ultra-low doses even after short contact periods, since important vector species such as An. arabiensis make only brief visits to such devices. Natural human odours suctioned from occupied dwellings could constitute affordable sources of attractants to supplement odour baits for the devices. The killing agents used should be environmentally safe, long lasting, and have different modes of action (other than pyrethroids as used on LLINs), to curb the risk of physiological insecticide resistance

Mathematical Evaluation of Community Level Impact of Combining Bed Nets and Indoor Residual Spraying upon Malaria Transmission in Areas where the main Vectors are Anopheles Arabiensis Mosquitoes.

Indoor residual insecticide spraying (IRS) and long-lasting insecticide treated nets (LLINs) are commonly used together even though evidence that such combinations confer greater protection against malaria than either method alone is inconsistent. A deterministic model of mosquito life cycle processes was adapted to allow parameterization with results from experimental hut trials of various combinations of untreated nets or LLINs (Olyset, PermaNet 2.0, Icon Life nets) with IRS (pirimiphos methyl, lambda cyhalothrin, DDT), in a setting where vector populations are dominated by Anopheles arabiensis, so that community level impact upon malaria transmission at high coverage could be predicted. Intact untreated nets alone provide equivalent personal protection to all three LLINs. Relative to IRS plus untreated nets, community level protection is slightly higher when Olyset or PermaNet 2.0 nets are added onto IRS with pirimiphos methyl or lambda cyhalothrin but not DDT, and when Icon Life nets supplement any of the IRS insecticides. Adding IRS onto any net modestly enhances communal protection when pirimiphos methyl is sprayed, while spraying lambda cyhalothrin enhances protection for untreated nets but not LLINs. Addition of DDT reduces communal protection when added to LLINs. Where transmission is mediated primarily by An. arabiensis, adding IRS to high LLIN coverage provides only modest incremental benefit (e.g. when an organophosphate like pirimiphos methyl is used), but can be redundant (e.g. when a pyrethroid like lambda cyhalothin is used) or even regressive (e.g. when DDT is used for the IRS). Relative to IRS plus untreated nets, supplementing IRS with LLINs will only modestly improve community protection. Beyond the physical protection that intact nets provide, additional protection against transmission by An. arabiensis conferred by insecticides will be remarkably small, regardless of whether they are delivered as LLINs or IRS. The insecticidal action of LLINs and IRS probably already approaches their absolute limit of potential impact upon this persistent vector so personal protection of nets should be enhanced by improving the physical integrity and durability. Combining LLINs and non-pyrethroid IRS in residual transmission systems may nevertheless be justified as a means to manage insecticide resistance and prevent potential rebound of not only An. arabiensis, but also more potent, vulnerable and historically important species such as Anopheles gambiae and Anopheles funestus

Geographic Coincidence of Increased Malaria Transmission Hazard and Vulnerability Occurring at the Periphery of two Tanzanian Villages.

The goal of malaria elimination necessitates an improved understanding of any fine-scale geographic variations in transmission risk so that complementary vector control tools can be integrated into current vector control programmes as supplementary measures that are spatially targeted to maximize impact upon residual transmission. This study examines the distribution of host-seeking malaria vectors at households within two villages in rural Tanzania. Host-seeking mosquitoes were sampled from 72 randomly selected households in two villages on a monthly basis throughout 2008 using CDC light-traps placed beside occupied nets. Spatial autocorrelation in the dataset was examined using the Moran's I statistic and the location of any clusters was identified using the Getis-Ord Gi* statistic. Statistical associations between the household characteristics and clusters of mosquitoes were assessed using a generalized linear model for each species. For both Anopheles gambiae sensu lato and Anopheles funestus, the density of host-seeking females was spatially autocorrelated, or clustered. For both species, houses with low densities were clustered in the semi-urban village centre while houses with high densities were clustered in the periphery of the villages. Clusters of houses with low or high densities of An. gambiae s.l. were influenced by the number of residents in nearby houses. The occurrence of high-density clusters of An. gambiae s.l. was associated with lower elevations while An. funestus was also associated with higher elevations. Distance from the village centre was also positively correlated with the number of household occupants and having houses constructed with open eaves. The results of the current study highlight that complementary vector control tools could be most effectively targeted to the periphery of villages where the households potentially have a higher hazard (mosquito densities) and vulnerability (open eaves and larger households) to malaria infection

A genetically attenuated malaria vaccine candidate based on P. falciparum b9/slarp gene-deficient sporozoites

A highly efficacious pre-erythrocytic stage vaccine would be an important tool for the control and elimination of malaria but is currently unavailable. High-level protection in humans can be achieved by experimental immunization with Plasmodium falciparum sporozoites attenuated by radiation or under anti-malarial drug coverage. Immunization with genetically attenuated parasites (GAP) would be an attractive alternative approach. Here we present data on safety and protective efficacy using sporozoites with deletions of two genes i.e. the newly identified b9 and slarp, which govern independent and critical processes for successful liver-stage development. In the rodent malaria model, Pb Delta b9 Delta slarpGAP was completely attenuated showing no breakthrough infections while efficiently inducing high level protection. The human Pf Delta b9 Delta slarpGAP generated without drug-resistance markers were infective to human hepatocytes in vitro and to humanized mice engrafted with human hepatocytes in vivo but completely aborted development after infection. These findings support the clinical development of a Pf Delta b9 Delta slarpSPZ vaccine

Eliminating Malaria Vectors.

Malaria vectors which predominantly feed indoors upon humans have been locally eliminated from several settings with insecticide treated nets (ITNs), indoor residual spraying or larval source management. Recent dramatic declines of An. gambiae in east Africa with imperfect ITN coverage suggest mosquito populations can rapidly collapse when forced below realistically achievable, non-zero thresholds of density and supporting resource availability. Here we explain why insecticide-based mosquito elimination strategies are feasible, desirable and can be extended to a wider variety of species by expanding the vector control arsenal to cover a broader spectrum of the resources they need to survive. The greatest advantage of eliminating mosquitoes, rather than merely controlling them, is that this precludes local selection for behavioural or physiological resistance traits. The greatest challenges are therefore to achieve high biological coverage of targeted resources rapidly enough to prevent local emergence of resistance and to then continually exclude, monitor for and respond to re-invasion from external populations

Evaluation De La Qualité Physico-Chimique et Microbiologique Des Eaux De Puits Consommées Dans Le Quartier Kombé À Brazzaville

La présente étude vise à évaluer la qualité physico-chimique et microbiologique des eaux de puits consommées dans le quartier Kombé à Brazzaville. Quatre puits ont été identifiés et caractérisés. La caractérisation a montré trois puits équipés des mêmes systèmes de protection et de remontée d'eau et, un seul point de prélèvement diffère des autres par le système de remontée d'eau. Trente-trois paramètres physico-chimiques et neuf paramètres microbiologiques ont été évalués par des méthodes normées et référencées. Les résultats obtenus révèlent du point de vue physico-chimique que, les eaux de puits étudiées sont faiblement minéralisées et tous les paramètres physico-chimiques répondent aux normes de l'OMS, excepté le pH, la concentration des ions cadmium, chrome, phosphate ainsi que de la silice dans certains cas. La projection des points d’eau sur le diagramme de Piper montre deux familles chimiques&nbsp;: les eaux chlorurées sodique et potassique et les eaux bicarbonatées sodique et potassique. Par contre, les eaux consommées par la population de quartier Kombé sont fortement chargées en E.coli, salmonella et shigella, coliformes totaux, pseudomonas aeruginosa, germes totaux, staphylocoques et, levures et moisissures et sont impropres à la consommation humaine. Avant leur consommation ces eaux doivent subir quelques traitements préliminaires comme la correction du pH à la chaux et la désinfection à l’hypochlorite de sodium. &nbsp; This study aims to assess the physico-chemical and microbiological quality of well water consumed in the Kombé district in Brazzaville. Four wells have been identified and characterized. The characterization showed three wells equipped with the same protection and upwelling systems and only one sampling point differs from the others by the upwelling system. Thirty-three physico-chemical parameters and nine microbiological parameters were evaluated by standardized and referenced methods. The results obtained reveal from the physico-chemical point of view that the waters of the wells studied are weakly mineralized and all the physico-chemical parameters meet WHO standards, except the pH, the concentration of cadmium, chromium and phosphate ions as well as than silica in some cases. The projection of the water points on the Piper diagram shows two chemical families: sodium and potassium chlorinated waters and sodium and potassium bicarbonate waters. On the other hand, the water consumed by the population of the Kombé district is heavily loaded with E.coli, salmonella and shigella, total coliforms, pseudomonas aeruginosa, total germs, staphylococci and yeasts and molds and is unfit for human consumption. Before being consumed, this water must undergo some preliminary treatments such as pH correction with lime and disinfection with sodium hypochlorite

malERA: an updated research agenda for health systems and policy research in malaria elimination and eradication

Health systems underpin disease elimination and eradication programmes. In an elimination and eradication context, innovative research approaches are needed across health systems to assess readiness for programme reorientation, mitigate any decreases in effectiveness of interventions ('effectiveness decay'), and respond to dynamic and changing needs. The malaria eradication research agenda (malERA) Refresh consultative process for the Panel on Health Systems and Policy Research identifies opportunities to build health systems evidence and the tools needed to eliminate malaria from different zones, countries, and regions and to eradicate it globally. The research questions are organised as a portfolio that global health practitioners, researchers, and funders can identify with and support. This supports the promotion of an actionable and more cohesive approach to building the evidence base for scaled-up implementation of findings. Gaps and opportunities discussed in the paper include delivery strategies to meet the changing dynamics of needs of individuals, environments, and malaria programme successes; mechanisms and approaches to best support accelerated policy and financial responsiveness at national and global level to ensure timely response to evidence and needs, including in crisis situations; and systems' readiness tools and decision-support systems