Outdoor biting and pyrethroid resistance as potential drivers of persistent malaria transmission in Zanzibar.

BACKGROUND: Low-level of malaria transmission persist in Zanzibar despite high coverage of core vector control interventions. This study was carried out in hot-spot sites to better understand entomological factors that may contribute to residual malaria transmission in Zanzibar. METHODS: A total of 135 households were randomly selected from six sites and consented to participate with 20-25 households per site. Mosquito vector surveillance was carried out indoors and outdoors from 6:00 pm-7:00 am using miniaturized double net trap (DN-Mini™). Additional collections were done indoors using mouth aspirators to retrieve resting mosquitoes from wall and ceiling surfaces, and outdoors using resting bucket and pit traps. All collected mosquitoes were morphologically and genetically (PCR) analysed in the laboratory. All collected anopheline and blood-fed mosquitoes were analysed for sporozoite infection and blood meal host preferences by Circumsporozoite Protein ELISA and blood meal ELISA, respectively. The differences between indoor and outdoor mosquito biting rates were analysed using generalized linear mixed models. Levels of resistance to commonly used insecticides were quantified by WHO susceptibility tests. RESULTS: Out of 704 malaria vectors collected across 135 households, PCR analysis shows that 98.60% were Anopheles arabiensis, 0.6% Anopheles merus and 0.6% Anopheles gambiae sensu stricto. Sporozoite ELISA analysis indicates that all mosquitoes were negative for the malaria parasite. The results show that more An. arabiensis were collected outdoor (~ 85%) compared to indoor (~ 15%). Furthermore, large numbers of An. arabiensis were caught in outdoor resting sites, where the pit trap (67.2%) collected more mosquitoes compared to the outdoor DN-Mini trap (32.8%). Nearly two-thirds (60.7%) of blood-fed mosquitoes had obtained blood meals from non-human hosts. Mosquitoes displayed non-uniform susceptibility status and resistance intensity among the tested insecticides across the study sites to all WHO recommended insecticides across the study sites. CONCLUSION: This study suggests that in contexts such as Zanzibar, testing of novel techniques to complement indoor protection and targeting outdoor biting and/or resting mosquitoes, may be warranted to complement existing interventions and contribute to malaria elimination efforts. The study highlights the need to implement novel interventions and/or adaptations of strategies that can target outdoors biting mosquitoes.

Key traveller groups of relevance to spatial malaria transmission: a survey of movement patterns in four sub-Saharan African countries.

BACKGROUND: As malaria prevalence declines in many parts of the world due to widescale control efforts and as drug-resistant parasites begin to emerge, a quantitative understanding of human movement is becoming increasingly relevant to malaria control. However, despite its importance, significant knowledge gaps remain regarding human movement, particularly in sub-Saharan Africa. METHODS: A quantitative survey of human movement patterns was conducted in four countries in sub-Saharan Africa: Mali, Burkina Faso, Zambia, and Tanzania, with three to five survey locations chosen in each country. Questions were included on demographic and trip details, malaria risk behaviour, children accompanying travellers, and mobile phone usage to enable phone signal data to be better correlated with movement. A total of 4352 individuals were interviewed and 6411 trips recorded. RESULTS: A cluster analysis of trips highlighted two distinct traveller groups of relevance to malaria transmission: women travelling with children (in all four countries) and youth workers (in Mali). Women travelling with children were more likely to travel to areas of relatively high malaria prevalence in Mali (OR = 4.46, 95% CI = 3.42-5.83), Burkina Faso (OR = 1.58, 95% CI = 1.23-1.58), Zambia (OR = 1.50, 95% CI = 1.20-1.89), and Tanzania (OR = 2.28, 95% CI = 1.71-3.05) compared to other travellers. They were also more likely to own bed nets in Burkina Faso (OR = 1.77, 95% CI = 1.25-2.53) and Zambia (OR = 1.74, 95% CI = 1.34 2.27), and less likely to own a mobile phone in Mali (OR = 0.50, 95% CI = 0.39-0.65), Burkina Faso (OR = 0.39, 95% CI = 0.30-0.52), and Zambia (OR = 0.60, 95% CI = 0.47-0.76). Malian youth workers were more likely to travel to areas of relatively high malaria prevalence (OR = 23, 95% CI = 17-31) and for longer durations (mean of 70 days cf 21 days, p < 0.001) compared to other travellers. CONCLUSIONS: Women travelling with children were a remarkably consistent traveller group across all four countries surveyed. They are expected to contribute greatly towards spatial malaria transmission because the children they travel with tend to have high parasite prevalence. Youth workers were a significant traveller group in Mali and are expected to contribute greatly to spatial malaria transmission because their movements correlate with seasonal rains and hence peak mosquito densities. Interventions aimed at interrupting spatial transmission of parasites should consider these traveller groups.

Effects of a new outdoor mosquito control device, the mosquito landing box, on densities and survival of the malaria vector, Anopheles arabiensis, inside controlled semi-field settings.

BACKGROUND: The significance of malaria transmission occurring outdoors has risen even in areas where indoor interventions such as long-lasting insecticidal nets and indoor residual spraying are common. The actual contamination rates and effectiveness of recently developed outdoor mosquito control device, the mosquito landing box (MLB), on densities and daily survival of host-seeking laboratory Anopheles arabiensis, which readily bites humans outdoors was demonstrated. METHODS: Experiments were conducted in large semi-field systems (SFS) with human volunteers inside, to mimic natural ecosystems, and using MLBs baited with natural or synthetic human odours and carbon dioxide. The MLBs were dusted with 10% pyriproxyfen (PPF) or entomopathogenic fungi (Metarhizium anisopliae) spores to mark mosquitoes physically contacting the devices. Each night, 400 laboratory-reared An. arabiensis females were released in one SFS chamber with two MLBs, and another chamber without MLBs (control). Mosquitoes were individually recaptured while attempting to bite volunteers inside SFS or by aspiration from SFS walls. Mosquitoes from chambers with PPF-treated MLBs and respective controls were individually dipped in water-filled cups containing ten conspecific third-instar larvae, whose subsequent development was monitored. Mosquitoes recaptured from chambers with fungi-treated MLBs were observed for fungal hyphal growth on their cadavers. Separately, effects on daily survival were determined by exposing An. arabiensis in chambers having MLBs treated with 5% pirimiphos methyl compared to chambers without MLBs (control), after which the mosquitoes were recaptured and monitored individually until they died. RESULTS: Up to 63% (152/240) and 43% (92/210) of mosquitoes recaptured inside treatment chambers were contaminated with pyriproxyfen and M. anisopliae, respectively, compared to 8% (19/240) and 0% (0/164) in controls. The mean number of larvae emerging from cups in which adults from chambers with PPF-treated MLBs were dipped was significantly lower [0.75 (0.50-1.01)], than in controls [28.79 (28.32-29.26)], P < 0.001). Daily survival of mosquitoes exposed to 5% pirimiphos methyl was nearly two-fold lower than controls [hazard ratio (HR) = 1.748 (1.551-1.920), P < 0.001]. CONCLUSION: High contamination rates in exposed mosquitoes even in presence of humans, demonstrates potential of MLBs for controlling outdoor-biting malaria vectors, either by reducing their survival or directly killing host-seeking mosquitoes. The MLBs also have potential for dispensing filial infanticides, such as PPF, which mosquitoes can transmit to their aquatic habitats for mosquito population control.

Increasing role of Anopheles funestus and Anopheles arabiensis in malaria transmission in the Kilombero Valley, Tanzania.

BACKGROUND: In order to sustain the gains achieved by current malaria control strategies, robust surveillance systems that monitor dynamics of vectors and their roles in malaria transmission over time are essential. This longitudinal study demonstrates the trends in malaria vector dynamics and their relative contribution to malaria transmission in hyperendemic transmission settings in Tanzania. METHODS: The study was conducted in two villages within the Kilombero Valley, in rural Tanzania for five consecutive years (2008-2012). Seventy-two houses were selected per village and each house was sampled for mosquitoes monthly using a CDC light trap. Collected mosquitoes were assessed for species identity and sporozoite infection status using PCR and ELISA, respectively. Anopheles funestus and Anopheles arabiensis susceptibility to insecticides was assessed using WHO guidelines. RESULTS: A total of 100,810 malaria vectors were collected, of which 76% were Anopheles gambiae s. l. and 24% were An. funestus. Of all An. funestus samples that amplified with PCR (n = 2,737), 97% were An. funestus s.s., 2% were Anopheles rivorulum and 1% Anopheles leesoni. Whereas for An. gambiae s.l. (n = 8,117), 93% were An. arabiensis and 7% were Anopheles gambiae s.s. The proportion of An. gambiae s.s. identified by PCR (2,924) declined from 0.2% in the year 2008 to undetectable levels in 2012. Malaria transmission intensity significantly decreased from an EIR of 78.14 infectious bites/person/year in 2008 to 35 ib/p/yr in 2011 but rebounded to 226 ib/p/yr in 2012 coinciding with an increased role of An. funestus in malaria transmission. Insecticide susceptibility tests indicated high levels of resistance in An. funestus against deltamethrin (87%), permethrin (65%), lambda cyhalothrin (74%), bendiocarb (65%), and DDT (66%). Similarly, An. arabiensis showed insecticide resistance to deltamethrin (64%), permethrin (77%) and lambda cyhalothrin (42%) in 2014. CONCLUSION: The results indicate the continuing role of An. arabiensis and the increasing importance of An. funestus in malaria transmission, and pyrethroid resistance development in both species. Complementary vector control and surveillance tools are needed that target the ecology, behaviour and insecticide resistance management of these vector species, in order to preserve the efficacy of LLINs.

Comparative assessment of diverse strategies for malaria vector population control based on measured rates at which mosquitoes utilize targeted resource subsets.

BACKGROUND: Eliminating malaria requires vector control interventions that dramatically reduce adult mosquito population densities and survival rates. Indoor applications of insecticidal nets and sprays are effective against an important minority of mosquito species that rely heavily upon human blood and habitations for survival. However, complementary approaches are needed to tackle a broader diversity of less human-specialized vectors by killing them at other resource targets. METHODS: Impacts of strategies that target insecticides to humans or animals can be rationalized in terms of biological coverage of blood resources, quantified as proportional coverage of all blood resources mosquito vectors utilize. Here, this concept is adapted to enable impact prediction for diverse vector control strategies based on measurements of utilization rates for any definable, targetable resource subset, even if that overall resource is not quantifiable. RESULTS: The usefulness of this approach is illustrated by deriving utilization rate estimates for various blood, resting site, and sugar resource subsets from existing entomological survey data. Reported impacts of insecticidal nets upon human-feeding vectors, and insecticide-treated livestock upon animal-feeding vectors, are approximately consistent with model predictions based on measured utilization rates for those human and animal blood resource subsets. Utilization rates for artificial sugar baits compare well with blood resources, and are consistent with observed impact when insecticide is added. While existing data was used to indirectly measure utilization rates for a variety of resting site subsets, by comparison with measured rates of blood resource utilization in the same settings, current techniques for capturing resting mosquitoes underestimate this quantity, and reliance upon complex models with numerous input parameters may limit the applicability of this approach. CONCLUSIONS: While blood and sugar consumption can be readily quantified using existing methods for detecting natural markers or artificial tracers, improved techniques for labelling mosquitoes, or other arthropod pathogen vectors, will be required to assess vector control measures which target them when they utilize non-nutritional resources such as resting, oviposition, and mating sites.

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

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.

Biologically meaningful coverage indicators for eliminating malaria transmission.

Mosquitoes, which evade contact with long-lasting insecticidal nets and indoor residual sprays, by feeding outdoors or upon animals, are primary malaria vectors in many tropical countries. They can also dominate residual transmission where high coverage of these front-line vector control measures is achieved. Complementary strategies, which extend insecticide coverage beyond houses and humans, are required to eliminate malaria transmission in most settings. The overwhelming diversity of the world's malaria transmission systems and optimal strategies for controlling them can be simply conceptualized and mapped across two-dimensional scenario space defined by the proportion of blood meals that vectors obtain from humans and the proportion of human exposure to them which occurs indoors.

Why lockdown? Why national unity? Why global solidarity? Simplified arithmetic tools for decision-makers, health professionals, journalists and the general public to explore containment options for the 2019 novel coronavirus.

As every country in the world struggles with the ongoing COVID-19 pandemic, it is essential that as many people as possible understand the epidemic containment, elimination and exclusion strategies required to tackle it. Simplified arithmetic models of COVID-19 transmission, control and elimination are presented in user-friendly Shiny and Excel formats that allow non-specialists to explore, query, critique and understand the containment decisions facing their country and the world at large. Although the predictive model is broadly applicable, the simulations presented are based on parameter values representative of the United Republic of Tanzania, which is still early enough in its epidemic cycle and response to avert a national catastrophe. The predictions of these models illustrate (1) why ambitious lock-down interventions to crush the curve represent the only realistic way for individual countries to contain their national-level epidemics before they turn into outright catastrophes, (2) why these need to be implemented so early, so stringently and for such extended periods, (3) why high prevalence of other pathogens causing similar symptoms to mild COVID-19 precludes the use of contact tracing as a substitute for lock down interventions to contain and eliminate epidemics, (4) why partial containment strategies intended to merely flatten the curve, by maintaining epidemics at manageably low levels, are grossly unrealistic, and (5) why local elimination may only be sustained after lock down ends if imported cases are comprehensively excluded, so international co-operation to conditionally re-open trade and travel between countries certified as free of COVID-19 represents the best strategy for motivating progress towards pandemic eradication at global level. The three sequential goals that every country needs to emphatically embrace are contain, eliminate and exclude. As recently emphasized by the World Health Organization, success will require widespread genuine national unity and unprecedented global solidarity.

An autoencoder and artificial neural network-based method to estimate parity status of wild mosquitoes from near-infrared spectra.

After mating, female mosquitoes need animal blood to develop their eggs. In the process of acquiring blood, they may acquire pathogens, which may cause different diseases in humans such as malaria, zika, dengue, and chikungunya. Therefore, knowing the parity status of mosquitoes is useful in control and evaluation of infectious diseases transmitted by mosquitoes, where parous mosquitoes are assumed to be potentially infectious. Ovary dissections, which are currently used to determine the parity status of mosquitoes, are very tedious and limited to few experts. An alternative to ovary dissections is near-infrared spectroscopy (NIRS), which can estimate the age in days and the infectious state of laboratory and semi-field reared mosquitoes with accuracies between 80 and 99%. No study has tested the accuracy of NIRS for estimating the parity status of wild mosquitoes. In this study, we train an artificial neural network (ANN) models on NIR spectra to estimate the parity status of wild mosquitoes. We use four different datasets: An. arabiensis collected from Minepa, Tanzania (Minepa-ARA); An. gambiae s.s collected from Muleba, Tanzania (Muleba-GA); An. gambiae s.s collected from Burkina Faso (Burkina-GA); and An.gambiae s.s from Muleba and Burkina Faso combined (Muleba-Burkina-GA). We train ANN models on datasets with spectra preprocessed according to previous protocols. We then use autoencoders to reduce the spectra feature dimensions from 1851 to 10 and re-train the ANN models. Before the autoencoder was applied, ANN models estimated parity status of mosquitoes in Minepa-ARA, Muleba-GA, Burkina-GA and Muleba-Burkina-GA with out-of-sample accuracies of 81.9±2.8 (N = 274), 68.7±4.8 (N = 43), 80.3±2.0 (N = 48), and 75.7±2.5 (N = 91), respectively. With the autoencoder, ANN models tested on out-of-sample data achieved 97.1±2.2% (N = 274), 89.8 ± 1.7% (N = 43), 93.3±1.2% (N = 48), and 92.7±1.8% (N = 91) accuracies for Minepa-ARA, Muleba-GA, Burkina-GA, and Muleba-Burkina-GA, respectively. These results show that a combination of an autoencoder and an ANN trained on NIR spectra to estimate the parity status of wild mosquitoes yields models that can be used as an alternative tool to estimate parity status of wild mosquitoes, especially since NIRS is a high-throughput, reagent-free, and simple-to-use technique compared to ovary dissections.

Age grading An. gambiae and An. arabiensis using near infrared spectra and artificial neural networks.

BACKGROUND: Near infrared spectroscopy (NIRS) is currently complementing techniques to age-grade mosquitoes. NIRS classifies lab-reared and semi-field raised mosquitoes into < or ≥ 7 days old with an average accuracy of 80%, achieved by training a regression model using partial least squares (PLS) and interpreted as a binary classifier. METHODS AND FINDINGS: We explore whether using an artificial neural network (ANN) analysis instead of PLS regression improves the current accuracy of NIRS models for age-grading malaria transmitting mosquitoes. We also explore if directly training a binary classifier instead of training a regression model and interpreting it as a binary classifier improves the accuracy. A total of 786 and 870 NIR spectra collected from laboratory reared An. gambiae and An. arabiensis, respectively, were used and pre-processed according to previously published protocols. The ANN regression model scored root mean squared error (RMSE) of 1.6 ± 0.2 for An. gambiae and 2.8 ± 0.2 for An. arabiensis; whereas the PLS regression model scored RMSE of 3.7 ± 0.2 for An. gambiae, and 4.5 ± 0.1 for An. arabiensis. When we interpreted regression models as binary classifiers, the accuracy of the ANN regression model was 93.7 ± 1.0% for An. gambiae, and 90.2 ± 1.7% for An. arabiensis; while PLS regression model scored the accuracy of 83.9 ± 2.3% for An. gambiae, and 80.3 ± 2.1% for An. arabiensis. We also find that a directly trained binary classifier yields higher age estimation accuracy than a regression model interpreted as a binary classifier. A directly trained ANN binary classifier scored an accuracy of 99.4 ± 1.0 for An. gambiae and 99.0 ± 0.6% for An. arabiensis; while a directly trained PLS binary classifier scored 93.6 ± 1.2% for An. gambiae and 88.7 ± 1.1% for An. arabiensis. We further tested the reproducibility of these results on different independent mosquito datasets. ANNs scored higher estimation accuracies than when the same age models are trained using PLS. Regardless of the model architecture, directly trained binary classifiers scored higher accuracies on classifying age of mosquitoes than regression models translated as binary classifiers. CONCLUSION: We recommend training models to estimate age of An. arabiensis and An. gambiae using ANN model architectures (especially for datasets with at least 70 mosquitoes per age group) and direct training of binary classifier instead of training a regression model and interpreting it as a binary classifier.

Do NIR spectra collected from laboratory-reared mosquitoes differ from those collected from wild mosquitoes?

BACKGROUND: Near infrared spectroscopy (NIRS) is a high throughput technique that measures absorbance of specific wavelengths of light by biological samples and uses this information to classify the age of lab-reared mosquitoes as younger or older than seven days with an average accuracy greater than 80%. For NIRS to estimate ages of wild mosquitoes, a sample of wild mosquitoes with known age in days would be required to train and test the model. Mark-release-recapture is the most reliable method to produce wild-caught mosquitoes of known age in days. However, it is logistically demanding, time inefficient, subject to low recapture rates, and raises ethical issues due to the release of mosquitoes. Using labels from Detinova dissection results in a mathematical model with poor accuracy. Alternatively, a model trained on spectra from laboratory-reared mosquitoes where age in days is known can be applied to estimate the age of wild mosquitoes, but this would be appropriate only if spectra collected from laboratory-reared and wild mosquitoes are similar. METHODS AND FINDINGS: We performed k-means (k = 2) cluster analysis on a mixture of spectra collected from lab-reared and wild Anopheles arabiensis to determine if there is any significant difference between these two groups. While controlling the numbers of mosquitoes included in the model at each age, we found two clusters with no significant difference in distribution of spectra collected from lab-reared and wild mosquitoes (p = 0.25). We repeated the analysis using hierarchical clustering, and similarly, no significant difference was observed (p = 0.13). CONCLUSION: We find no difference between spectra collected from laboratory-reared and wild mosquitoes of the same age and species. The results strengthen and support the on-going practice of applying the model trained on spectra collected from laboratory-reared mosquitoes, especially first-generation laboratory-reared mosquitoes.

Mathematical models of human mobility of relevance to malaria transmission in Africa.

As Africa-wide malaria prevalence declines, an understanding of human movement patterns is essential to inform how best to target interventions. We fitted movement models to trip data from surveys conducted at 3-5 sites throughout each of Mali, Burkina Faso, Zambia and Tanzania. Two models were compared in terms of their ability to predict the observed movement patterns - a gravity model, in which movement rates between pairs of locations increase with population size and decrease with distance, and a radiation model, in which travelers are cumulatively "absorbed" as they move outwards from their origin of travel. The gravity model provided a better fit to the data overall and for travel to large populations, while the radiation model provided a better fit for nearby populations. One strength of the data set was that trips could be categorized according to traveler group - namely, women traveling with children in all survey countries and youth workers in Mali. For gravity models fitted to data specific to these groups, youth workers were found to have a higher travel frequency to large population centers, and women traveling with children a lower frequency. These models may help predict the spatial transmission of malaria parasites and inform strategies to control their spread.

Attacking the mosquito on multiple fronts: Insights from the Vector Control Optimization Model (VCOM) for malaria elimination.

BACKGROUND: Despite great achievements by insecticide-treated nets (ITNs) and indoor residual spraying (IRS) in reducing malaria transmission, it is unlikely these tools will be sufficient to eliminate malaria transmission on their own in many settings today. Fortunately, field experiments indicate that there are many promising vector control interventions that can be used to complement ITNs and/or IRS by targeting a wide range of biological and environmental mosquito resources. The majority of these experiments were performed to test a single vector control intervention in isolation; however, there is growing evidence and consensus that effective vector control with the goal of malaria elimination will require a combination of interventions. METHOD AND FINDINGS: We have developed a model of mosquito population dynamic to describe the mosquito life and feeding cycles and to optimize the impact of vector control intervention combinations at suppressing mosquito populations. The model simulations were performed for the main three malaria vectors in sub-Saharan Africa, Anopheles gambiae s.s, An. arabiensis and An. funestus. We considered areas having low, moderate and high malaria transmission, corresponding to entomological inoculation rates of 10, 50 and 100 infective bites per person per year, respectively. In all settings, we considered baseline ITN coverage of 50% or 80% in addition to a range of other vector control tools to interrupt malaria transmission. The model was used to sweep through parameters space to select the best optimal intervention packages. Sample model simulations indicate that, starting with ITNs at a coverage of 50% (An. gambiae s.s. and An. funestus) or 80% (An. arabiensis) and adding interventions that do not require human participation (e.g. larviciding at 80% coverage, endectocide treated cattle at 50% coverage and attractive toxic sugar baits at 50% coverage) may be sufficient to suppress all the three species to an extent required to achieve local malaria elimination. CONCLUSION: The Vector Control Optimization Model (VCOM) is a computational tool to predict the impact of combined vector control interventions at the mosquito population level in a range of eco-epidemiological settings. The model predicts specific combinations of vector control tools to achieve local malaria elimination in a range of eco-epidemiological settings and can assist researchers and program decision-makers on the design of experimental or operational research to test vector control interventions. A corresponding graphical user interface is available for national malaria control programs and other end users.

Measuring, manipulating and exploiting behaviours of adult mosquitoes to optimise malaria vector control impact.

Residual malaria transmission can persist despite high coverage with effective long-lasting insecticidal nets (LLINs) and/or indoor residual spraying (IRS), because many vector mosquitoes evade them by feeding on animals, feeding outdoors, resting outdoors or rapidly exiting from houses after entering them. However, many of these behaviours that render vectors resilient to control with IRS and LLINs also make them vulnerable to some emerging new alternative interventions. Furthermore, vector control measures targeting preferred behaviours of mosquitoes often force them to express previously rare alternative behaviours, which can then be targeted with these complementary new interventions. For example, deployment of LLINs against vectors that historically fed predominantly indoors on humans typically results in persisting transmission by residual populations that survive by feeding outdoors on humans and animals, where they may then be targeted with vapour-phase insecticides and veterinary insecticides, respectively. So while the ability of mosquitoes to express alternative behaviours limits the impact of LLINs and IRS, it also creates measurable and unprecedented opportunities for deploying complementary additional approaches that would otherwise be ineffective. Now that more diverse vector control methods are finally becoming available, well-established entomological field techniques for surveying adult mosquito behaviours should be fully exploited by national malaria control programmes, to rationally and adaptively map out new opportunities for their effective deployment.

Going beyond personal protection against mosquito bites to eliminate malaria transmission: population suppression of malaria vectors that exploit both human and animal blood.

Protecting individuals and households against mosquito bites with long-lasting insecticidal nets (LLINs) or indoor residual spraying (IRS) can suppress entire populations of unusually efficient malaria vector species that predominantly feed indoors on humans. Mosquitoes which usually feed on animals are less reliant on human blood, so they are far less vulnerable to population suppression effects of such human-targeted insecticidal measures. Fortunately, the dozens of mosquito species which primarily feed on animals are also relatively inefficient vectors of malaria, so personal protection against mosquito bites may be sufficient to eliminate transmission. However, a handful of mosquito species are particularly problematic vectors of residual malaria transmission, because they feed readily on both humans and animals. These unusual vectors feed often enough on humans to be potent malaria vectors, but also often enough on animals to evade population control with LLINs, IRS or any other insecticidal personal protection measure targeted only to humans. Anopheles arabiensis and A. coluzzii in Africa, A. darlingi in South America and A. farauti in Oceania, as well as A. culicifacies species E, A. fluviatilis species S, A. lesteri and A. minimus in Asia, all feed readily on either humans or animals and collectively mediate residual malaria transmission across most of the tropics. Eliminating malaria transmission by vectors exhibiting such dual host preferences will require aggressive mosquito population abatement, rather than just personal protection of humans. Population suppression of even these particularly troublesome vectors is achievable with a variety of existing vector control technologies that remain underdeveloped or underexploited.

The Hitchhiking Parasite: Why Human Movement Matters to Malaria Transmission and What We Can Do About It.

The failure of the Global Malaria Eradication Program (GMEP) during the 1960s highlighted the relevance of human movement to both re-introducing parasites in elimination settings and spreading drug-resistant parasites widely. Today, given the sophisticated surveillance of human movement patterns and key traveler groups, it is hoped that interventions can be implemented to protect and treat travelers, prevent onward transmission in low transmission settings, and eliminate sources of transmission, including sources of drug-resistant parasites.

A generic schema and data collection forms applicable to diverse entomological studies of mosquitoes.

BACKGROUND: Standardized schemas, databases, and public data repositories are needed for the studies of malaria vectors that encompass a remarkably diverse array of designs and rapidly generate large data volumes, often in resource-limited tropical settings lacking specialized software or informatics support. RESULTS: Data from the majority of mosquito studies conformed to a generic schema, with data collection forms recording the experimental design, sorting of collections, details of sample pooling or subdivision, and additional observations. Generically applicable forms with standardized attribute definitions enabled rigorous, consistent data and sample management with generic software and minimal expertise. Forms use now includes 20 experiments, 8 projects, and 15 users at 3 research and control institutes in 3 African countries, resulting in 11 peer-reviewed publications. CONCLUSION: We have designed generic data schema that can be used to develop paper or electronic based data collection forms depending on the availability of resources. We have developed paper-based data collection forms that can be used to collect data from majority of entomological studies across multiple study areas using standardized data formats. Data recorded on these forms with standardized formats can be entered and linked with any relational database software. These informatics tools are recommended because they ensure that medical entomologists save time, improve data quality, and data collected and shared across multiple studies is in standardized formats hence increasing research outputs.

Predicting Scenarios for Successful Autodissemination of Pyriproxyfen by Malaria Vectors from Their Resting Sites to Aquatic Habitats; Description and Simulation Analysis of a Field-Parameterizable Model.

BACKGROUND: Large-cage experiments indicate pyriproxifen (PPF) can be transferred from resting sites to aquatic habitats by Anopheles arabiensis--malaria vector mosquitoes to inhibit emergence of their own offspring. PPF coverage is amplified twice: (1) partial coverage of resting sites with PPF contamination results in far higher contamination coverage of adult mosquitoes because they are mobile and use numerous resting sites per gonotrophic cycle, and (2) even greater contamination coverage of aquatic habitats results from accumulation of PPF from multiple oviposition events. METHODS AND FINDINGS: Deterministic mathematical models are described that use only field-measurable input parameters and capture the biological processes that mediate PPF autodissemination. Recent successes in large cages can be rationalized, and the plausibility of success under full field conditions can be evaluated a priori. The model also defines measurable properties of PPF delivery prototypes that may be optimized under controlled experimental conditions to maximize chances of success in full field trials. The most obvious flaw in this model is the endogenous relationship that inevitably occurs between the larval habitat coverage and the measured rate of oviposition into those habitats if the target mosquito species is used to mediate PPF transfer. However, this inconsistency also illustrates the potential advantages of using a different, non-target mosquito species for contamination at selected resting sites that shares the same aquatic habitats as the primary target. For autodissemination interventions to eliminate malaria transmission or vector populations during the dry season window of opportunity will require comprehensive contamination of the most challenging subset of aquatic habitats [Formula: see text] that persist or retain PPF activity (Ux) for only one week [Formula: see text], where Ux = 7 days). To achieve >99% contamination coverage of these habitats will necessitate values for the product of the proportional coverage of the ovipositing mosquito population with PPF contamination (CM) by the ovitrap-detectable rates of oviposition by wild mosquitoes into this subset of habitats [Formula: see text], divided by the titre of contaminated mosquitoes required to render them unproductive [Formula: see text], that approximately approach unity [Formula: see text]. CONCLUSIONS: The simple multiplicative relationship between CM and [Formula: see text], and the simple exponential decay effect they have upon uncontaminated aquatic habitats, allows application of this model by theoreticians and field biologists alike.

Comprehensive sterilization of malaria vectors using pyriproxyfen: a step closer to malaria elimination.

One of the main challenges to malaria elimination is the resilience of vectors, such as Anopheles arabiensis, that evade lethal exposure to insecticidal control measures or express resistance to their active ingredients. This study investigated a novel technology for population control that sterilizes mosquitoes using pyriproxyfen, a juvenile hormone analogue. Females of An. arabiensis were released in a semifield system divided into four equal sections, and each section had a mud hut sheltering a tethered cow providing a blood source for mosquitoes. In all sections, the inner mud hut walls and roofs were lined with black cotton cloth. In one-half of the sections, the cloth was dusted with pyriproxyfen. An overwhelming 96% reduction in adult production was achieved in pyriproxyfen-treated sections compared with control sections. This unprecedented level of control can be exploited to design new vector control strategies that particularly target existing behaviorally resilient and insecticide-resistant populations.

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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.