Successful malaria elimination strategies require interventions that target changing vector behaviours

BACKGROUND: The ultimate long-term goal of malaria eradication was recently placed back onto the global health agenda. When planning for this goal, it is important to remember why the original Global Malaria Eradication Programme (GMEP), conducted with DDT-based indoor residual spraying (IRS), did not achieve its goals. One of the technical reasons for the failure to eliminate malaria was over reliance on a single intervention and subsequently the mosquito vectors developed behavioural resistance so that they did not come into physical contact with the insecticide.Hypothesis and how to test it: Currently, there remains a monolithic reliance on indoor vector control. It is hypothesized that an outcome of long-term, widespread control is that vector populations will change over time, either in the form of physiological resistance, changes in the relative species composition or behavioural resistance. The potential for, and consequences of, behavioural resistance was explored by reviewing the literature regarding vector behaviour in the southwest Pacific. DISCUSSION: Here, two of the primary vectors that were highly endophagic, Anopheles punctulatus and Anopheles koliensis, virtually disappeared from large areas where DDT was sprayed. However, high levels of transmission have been maintained by Anopheles farauti, which altered its behaviour to blood-feed early in the evening and outdoors and, thereby, avoiding exposure to the insecticides used in IRS. This example indicates that the efficacy of programmes relying on indoor vector control (IRS and long-lasting, insecticide-treated nets [LLINs]) will be significantly reduced if the vectors change their behaviour to avoid entering houses. CONCLUSIONS: Behavioural resistance is less frequently seen compared with physiological resistance (where the mosquito contacts the insecticide but is not killed), but is potentially more challenging to control programmes because the intervention effectiveness cannot be restored by rotating the insecticide to one with a different mode of action. The scientific community needs to urgently develop systematic methods for monitoring behavioural resistance and then to work in collaboration with vector control programmes to implement monitoring in sentinel sites. In situations where behavioural resistance is detected, there will be a need to target other bionomic vulnerabilities that may exist in the larval stages, during mating, sugar feeding or another aspect of the life cycle of the vector to continue the drive towards elimination

Gene flow between island populations of the malaria mosquito, Anopheles hinesorum, may have contributed to the spread of divergent host preference phenotypes

Anopheles hinesorum is a mosquito species with variable host preference. Throughout New Guinea and northern Australia, An. hinesorum feeds on humans (it is opportunistically anthropophagic) while in the south-west Pacific's Solomon Archipelago, the species is abundant but has rarely been found biting humans (it is exclusively zoophagic in most populations). There are at least two divergent zoophagic (nonhuman biting) mitochondrial lineages of An. hinesorum in the Solomon Archipelago representing two independent dispersals. Since zoophagy is a derived (nonancestral) trait in this species, this leads to the question: has zoophagy evolved independently in these two populations? Or conversely: has nuclear gene flow or connectivity resulted in the transfer of zoophagy? Although we cannot conclusively answer this, we find close nuclear relationships between Solomon Archipelago populations indicating that recent nuclear gene flow has occurred between zoophagic populations from the divergent mitochondrial lineages. Recent work on isolated islands of the Western Province (Solomon Archipelago) has also revealed an anomalous, anthropophagic island population of An. hinesorum. We find a common shared mitochondrial haplotype between this Solomon Island population and another anthropophagic population from New Guinea. This finding suggests that there has been recent migration from New Guinea into the only known anthropophagic population from the Solomon Islands. Although currently localized to a few islands in the Western Province of the Solomon Archipelago, if anthropophagy presents a selective advantage, we may see An. hinesorum emerge as a new malaria vector in a region that is now working on malaria elimination

An extra-domiciliary method of delivering entomopathogenic fungus, Metharizium anisopliae IP 46 for controlling adult populations of the malaria vector, Anopheles arabiensis

Fungal biopesticides have the potential to significantly reduce densities of malaria vectors as well as associated malaria transmission. In previous field trials, entomopathogenic fungus was delivered from within human dwellings, where its efficacy was limited by low infection rates of target mosquitoes, high costs of spraying fungus inside houses, and potential public health concerns associated with introducing fungal conidia inside houses. Here we have demonstrated that Metarhizium anisopliae IP 46, delivered within an extra-domiciliary odor-baited station (OBS), can infect and slowly-kill a high proportion of the wild adult malaria vector, Anopheles arabiensis which entered and exited the OBS. This study, carried out in rural Tanzania, showed that by using a concentration of 3.9 × 1010 conidia/m2, more than 95% of mosquitoes that flew in and out of the OBS died within 14 days post-exposure. At least 86% infection of mosquito cadavers was recorded with a significant reduction in the probability of daily survival of exposed An. arabiensis in both treatments tested: low quantity of conidia (eave baffles plus one cotton panel; HR = 2.65, P < 0.0001) and high quantity of conidia (eave baffles plus two cotton panels; HR = 2.32, P < 0.0001). We conclude that high infection rates of entomopathogenic fungi on wild malaria vectors and possibly significant disruption of malaria transmission can be achieved if the fungus is delivered using optimally located outdoor odor-baited stations

Smallest Anopheles farauti occur during the peak transmission season in the Solomon Islands

Background: Malaria transmission varies in intensity amongst Solomon Island villages where Anopheles farauti is the only vector. This variation in transmission intensity might be explained by density-dependent processes during An. farauti larval development, as density dependence can impact adult size with associated fitness costs and daily survivorship. Methods: Adult anophelines were sampled from six villages in Western and Central Provinces, Solomon Islands between March 2014 and February 2017. The size of females was estimated by measuring wing lengths, and then analysed for associations with biting densities and rainfall. Results: In the Solomon Islands, three anopheline species, An. farauti, Anopheles hinesorum and Anopheles lungae, differed in size. The primary malaria vector, An. farauti, varied significantly in size among villages. Greater rainfall was directly associated with higher densities of An. farauti biting rates, but inversely associated with body size with the smallest mean sized mosquitoes present during the peak transmission period. A measurable association between body size and survivorship was not found. Conclusions: Density dependent effects are likely impacting the size of adult An. farauti emerging from a range of larval habitats. The data suggest that rainfall increases An. farauti numbers and that these more abundant mosquitoes are significantly smaller in size, but without any reduced survivorship being associated with smaller size. The higher malaria transmission rate in a high malaria focus village appears to be determined more by vector numbers than size or survivorship of the vectors

Influence of environmental factors on the abundance of Anopheles farauti larvae in large brackish water streams in Northern Guadalcanal, Solomon Islands

Background: The main vector of malaria in Solomon Islands is Anopheles farauti, which has a mainly coastal distribution. In Northern Guadalcanal, Solomon Islands, high densities of An. farauti are supported by large brackish streams, which in the dry season are dammed by localized sand migration. The factors controlling the high larval productivity of these breeding sites have not been identified. Accordingly the influence of environmental factors on the presence and density of An. farauti larvae was assessed in three large naturally dammed streams. Methods. Larval sites were mapped and anopheline larvae were collected monthly for 12 months (July 2007 to June 2008) from three streams using standard dippers. Larval collections were made from 10 locations spaced at 50 m intervals along the edge of each stream starting from the coast. At each collection point, floating filamentous algae, aquatic emergent plants, sun exposure, and salinity were measured. These environmental parameters along with rainfall were correlated with larval presence and density. Results: The presence and abundance of An. farauti larvae varied between streams and was influenced by the month of collection, and distance from the ocean (p < 0.001). Larvae were more frequently present and more abundant within 50 m of the ocean during the dry season when the streams were dammed. The presence and density of larvae were positively associated with aquatic emergent plants (presence: p = 0.049; density: p = 0.001). Although filamentous algae did not influence the presence of larvae, this factor did significantly influence the density of larvae (p < 0.001). Rainfall for the month prior to sampling was negatively associated with both larval presence and abundance (p < 0.001), as high rainfall flushed larvae from the streams. Salinity significantly influenced both the presence (p = 0.002) and density (p = 0.014) of larvae, with larvae being most present and abundant in brackish water at < 10 seawater. Conclusion: This study has demonstrated that the presence and abundance An. farauti larvae are influenced by environmental factors within the large streams. Understanding these parameters will allow for targeted cost effective implementation of source reduction and larviciding to support the frontline malaria control measures i.e. indoor residual spraying (IRS) and distribution of long-lasting insecticidal nets (LLINs)

Changes in vector species composition and current vector biology and behaviour will favour malaria elimination in Santa Isabel Province, Solomon Islands

Background: In 2009, Santa Isabel Province in the Solomon Islands embarked on a malaria elimination programme. However, very little is known in the Province about the anopheline fauna, which species are vectors, their bionomics and how they may respond to intensified intervention measures. The purpose of this study was to provide baseline data on the malaria vectors and to ascertain the possibility of successfully eliminating malaria using the existing conventional vector control measures, such as indoor residual spraying (IRS) and long-lasting insecticidal nets (LLIN). Methods. Entomological surveys were undertaken during October 2009. To determine species composition and distribution larval surveys were conducted across on the whole island. For malaria transmission studies, adult anophelines were sampled using human landing catches from two villages - one coastal and one inland. Results: Five Anopheles species were found on Santa Isabel: Anopheles farauti, Anopheles hinesorum, Anopheles lungae, Anopheles solomonis, and Anopheles nataliae. Anopheles hinesorum was the most widespread species. Anopheles farauti was abundant, but found only on the coast. Anopheles punctulatus and Anopheles koliensis were not found. Anopheles farauti was the only species found biting in the coastal village, it was incriminated as a vector in this study; it fed early in the night but equally so indoors and outdoors, and had a low survival rate. Anopheles solomonis was the main species biting humans in the inland village, it was extremely exophagic, with low survival rates, and readily fed on pigs. Conclusion: The disappearance of the two major vectors, An. punctulatus and An. koliensis, from Santa Isabel and the predominance of An. hinesorum, a non-vector species may facilitate malaria elimination measures. Anopheles farauti was identified as the main coastal vector with An. solomonis as a possible inland vector. The behaviour of An. solomonis is novel as it has not been previously found biting humans in any numbers. Both species appear to be short-lived, a characteristic that will limit their transmission potential. The early night feeding behaviour and a degree of outdoor biting seen in An. farauti and particularly in An. solomonis will require that their response to IRS and LLIN be closely monitored. In coastal villages, where large, favourable breeding sites allow for high numbers of An. farauti may require the addition of larval control to achieve elimination

Mycobacterium tuberculosis Responds to Chloride and pH as Synergistic Cues to the Immune Status of its Host Cell

PubMed ID: 23592993This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

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

The Oregon Promise Barley Population: A tool for understanding the genetic basis of traits fundamental for barley production, malting, brewing, and distilling

The simultaneous availability of unique germplasm resources and cost-effective high-throughput genotyping allows for accelerated genome exploration and gene discovery. Our germplasm -the Oregon Promise population- is an array of 200 barley doubled haploids developed from the cross of Full Pint x Golden Promise. The spring 2-row parents have contrasting alleles at two of the dwarfing genes deployed in current varieties. The four homozygous combinations of these plant height alleles lead to contrasting phenotypes and each allele has pleiotropic effects on a range of other traits. Golden Promise is an iconic variety for malting, brewing, and distilling; Full Pint is a contributor to the craft brew Renaissance. Accordingly, the Oregon Promise will provide a valuable resource for extending current knowledge of malting and brewing genes to the frontiers of sensory assessment. The population shows transgressive segregation for adult plant resistance to stripe rust. As this disease is likely to become increasingly prevalent as a consequence of climate change, expanding the catalog of genes conferring durable resistance to this pathogen is an essential defensive breeding step. The availability of a quick-turnaround and cost effective SNP genotyping service (400+ markers) at Eureka Genomics (developed in collaboration with the James Hutton Institute) allows accelerated linkage map construction, QTL detection, and unraveling of gene interactions and pleiotropic effects based on the multi-environment, multi-trait phenotyping of the Oregon Promise population. This project is possible thanks to the tools and knowledge generated by the USDA-NIFA T-CAP project.Peer Reviewe

An affordable, quality-assured community-based system for high-resolution entomological surveillance of vector mosquitoes that reflects human malaria infection risk patterns.

ABSTRACT: BACKGROUND: More sensitive and scalable entomological surveillance tools are required to monitor low levels of transmission that are increasingly common across the tropics, particularly where vector control has been successful. A large-scale larviciding programme in urban Dar es Salaam, Tanzania is supported by a community-based (CB) system for trapping adult mosquito densities to monitor programme performance. Methodology An intensive and extensive CB system for routine, longitudinal, programmatic surveillance of malaria vectors and other mosquitoes using the Ifakara Tent Trap (ITT-C) was developed in Urban Dar es Salaam, Tanzania, and validated by comparison with quality assurance (QA) surveys using either ITT-C or human landing catches (HLC), as well as a cross-sectional survey of malaria parasite prevalence in the same housing compounds. RESULTS: Community-based ITT-C had much lower sensitivity per person-night of sampling than HLC (Relative Rate (RR) [95% Confidence Interval (CI)] = 0.079 [0.051, 0.121], P < 0.001 for Anopheles gambiae s.l. and 0.153 [0.137, 0.171], P < 0.001 for Culicines) but only moderately differed from QA surveys with the same trap (0.536 [0.406,0.617], P = 0.001 and 0.747 [0.677,0.824], P < 0.001, for An. gambiae or Culex respectively). Despite the poor sensitivity of the ITT per night of sampling, when CB-ITT was compared with QA-HLC, it proved at least comparably sensitive in absolute terms (171 versus 169 primary vectors caught) and cost-effective (153US$versus 187US$ per An. gambiae caught) because it allowed more spatially extensive and temporally intensive sampling (4284 versus 335 trap nights distributed over 615 versus 240 locations with a mean number of samples per year of 143 versus 141). Despite the very low vectors densities (Annual estimate of about 170 An gambiae s.l bites per person per year), CB-ITT was the only entomological predictor of parasite infection risk (Odds Ratio [95% CI] = 4.43[3.027,7. 454] per An. gambiae or Anopheles funestus caught per night, P =0.0373). Discussion and conclusion CB trapping approaches could be improved with more sensitive traps, but already offer a practical, safe and affordable system for routine programmatic mosquito surveillance and clusters could be distributed across entire countries by adapting the sample submission and quality assurance procedures accordingly