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Abstract Background The most common pesticide products for controlling malaria-transmitting mosquitoes combine two distinct modes of action: 1) conventional insecticidal activity which kills mosquitoes exposed to the pesticide and 2) deterrence of mosquitoes away from protected humans. While deterrence enhances personal or household protection of long-lasting insecticidal nets and indoor residual sprays, it may also attenuate or even reverse communal protection if it diverts mosquitoes to non-users rather than killing them outright. Methods A process-explicit model of malaria transmission is described which captures the sequential interaction between deterrent and toxic actions of vector control pesticides and accounts for the distinctive impacts of toxic activities which kill mosquitoes before or after they have fed upon the occupant of a covered house or sleeping space. Results Increasing deterrency increases personal protection but consistently reduces communal protection because deterrent sub-lethal exposure inevitably reduces the proportion subsequently exposed to higher lethal doses. If the high coverage targets of the World Health Organization are achieved, purely toxic products with no deterrence are predicted to generally provide superior protection to non-users and even users, especially where vectors feed exclusively on humans and a substantial amount of transmission occurs outdoors. Remarkably, this is even the case if that product confers no personal protection and only kills mosquitoes after they have fed. Conclusions Products with purely mosquito-toxic profiles may, therefore, be preferable for programmes with universal coverage targets, rather than those with equivalent toxicity but which also have higher deterrence. However, if purely mosquito-toxic products confer little personal protection because they do not deter mosquitoes and only kill them after they have fed, then they will require aggressive "catch up" campaigns, with behaviour change communication strategies that emphasize the communal nature of protection, to achieve high coverage rapidly.

Background: Gambiense human African trypanosomiasis ([gHAT] sleeping sickness) is a vector-borne disease that is typically fatal without treatment. Intensified, mainly medical-based, interventions in endemic areas have reduced the occurrence of gHAT to historically low levels. However, persistent regions, primarily in the Democratic Republic of Congo (DRC), remain a challenge to achieving the World Health Organization's goal of global elimination of transmission (EOT).Methods: We used stochastic models of gHAT transmission fitted to DRC case data and explored patterns of regional reporting and extinction. The time to EOT at a health zone scale (~100 000 people) and how an absence of reported cases informs about EOT was quantified.Results: Regional epidemiology and level of active screening (AS) both influenced the predicted time to EOT. Different AS cessation criteria had similar expected infection dynamics, and recrudescence of infection was unlikely. However, whether EOT has been achieved when AS ends is critically dependent on the stopping criteria. Two or three consecutive years of no detected cases provided greater confidence of EOT compared with a single year (~66%-75% and ~82%-84% probability of EOT, respectively, compared with 31%-51%).Conclusions: Multiple years of AS without case detections is a valuable measure to assess the likelihood that the EOT target has been met locally. [ABSTRACT FROM AUTHOR]

Background: The RTS,S malaria vaccine may soon be licensed. Models of impact of such vaccines have mainly considered deployment via the World Health Organization's Expanded Programme on Immunization (EPI) in areas of stable endemic transmission of Plasmodium falciparum, and have been calibrated for such settings. Their applicability to low transmission settings is unclear. Evaluations of the efficiency of different deployment strategies in diverse settings should consider uncertainties in model structure. Methods and Findings: An ensemble of 14 individual-based stochastic simulation models of P. falciparum dynamics, with differing assumptions about immune decay, transmission heterogeneity, and treatment access, was constructed. After fitting to an extensive library of field data, each model was used to predict the likely health benefits of RTS,S deployment, via EPI (with or without catch-up vaccinations), supplementary vaccination of school-age children, or mass vaccination every 5 y. Settings with seasonally varying transmission, with overall pre-intervention entomological inoculation rates (EIRs) of two, 11, and 20 infectious bites per person per annum, were considered. Predicted benefits of EPI vaccination programs over the simulated 14-y time horizon were dependent on duration of protection. Nevertheless, EPI strategies (with an initial catch-up phase) averted the most deaths per dose at the higher EIRs, although model uncertainty increased with EIR. At two infectious bites per person per annum, mass vaccination strategies substantially reduced transmission, leading to much greater health effects per dose, even at modest coverage. Conclusions: In higher transmission settings, EPI strategies will be most efficient, but vaccination additional to the EPI in targeted low transmission settings, even at modest coverage, might be more efficient than national-level vaccination of infants. The feasibility and economics of mass vaccination, and the circumstances under which vaccination will avert epidemics, remain unclear. The approach of using an ensemble of models provides more secure conclusions than a single-model approach, and suggests greater confidence in predictions of health effects for lower transmission settings than for higher ones. Please see later in the article for the Editors' Summary., Introduction Malaria vaccines have long been awaited by public health planners [1]. Promising results of recent phase II trials [2,3] and a current large-scale phase III trial of the RTS,S [...]

Malaria persists at low levels on Zanzibar despite the use of vector control and case management. We use a metapopulation model to investigate the role of human mobility in malaria persistence on Zanzibar, and the impact of reactive case detection. The model was parameterized using survey data on malaria prevalence, reactive case detection, and travel history. We find that in the absence of imported cases from mainland Tanzania, malaria would likely cease to persist on Zanzibar. We also investigate potential intervention scenarios that may lead to elimination, especially through changes to reactive case detection. While we find that some additional cases are removed by reactive case detection, a large proportion of cases are missed due to many infections having a low parasite density that go undetected by rapid diagnostic tests, a low rate of those infected with malaria seeking treatment, and a low rate of follow up at the household level of malaria cases detected at health facilities. While improvements in reactive case detection would lead to a reduction in malaria prevalence, none of the intervention scenarios tested here were sufficient to reach elimination. Imported cases need to be treated to have a substantial impact on prevalence. • Imported infections are a key driver in the persistence of malaria in Zanzibar. • Elimination will be difficult to reach without targeting ongoing imported cases. • Presumptively treating household members of malaria cases reduces transmission. • Testing and treating neighbours of malaria cases has minimal impact on transmission. [ABSTRACT FROM AUTHOR]

Background: Mosquito survival, oviposition interval and gonotrophic concordance are important determinants of vectorial capacity. These may vary between species or within a single species depending on the environment. They may be estimated by examination of the ovaries of host-seeking mosquitoes. Methods: Landing collections, Furvela tent-trap and CDC light-trap collections were undertaken sequentially in four locations in Cambodia between February 2012 and December 2013 and samples from the collected mosquitoes were dissected to determine parity, sac stage (indicative of time spent prior to returning to feed) and egg stage. Results: A total of 27,876 Anopheles from 15 species or species groups were collected in the four locations and 2883 specimens were dissected. Both the density and predominant species collected varied according to location and trapping method. Five species were dissected in sufficient numbers to allow comparisons between locations. Estimated oviposition interval differed markedly between species but less within species among different locations. Anopheles aconitus had the shortest cycle, which was 3.17 days (95 % CI 3-3.64), and Anopheles barbirostris had the longest cycle, which took four days (95 % CI 3.29-4). Anopheles minimus had a higher sac rate in weeks leading up to a full moon but there was apparently little effect of moon phase on Anopheles dirus. Despite the fact that many of the species occurred at very low densities, there was no evidence of gonotrophic dissociation in any of them, even during sustained hot, dry periods. The principal Cambodian malaria vector, An. dirus, was only common in one location where it was collected in miniature light-traps inside houses. It did not appear to have an exceptional survival rate (as judged by the low average parous rate) or oviposition cycle. Conclusions: Differences in the oviposition interval were more pronounced among species within locations than within species among ecologically diverse locations. A nationwide survey using CDC light-traps for the collection of An. dirus inside houses may help in determining patterns of malaria transmission in Cambodia. [ABSTRACT FROM AUTHOR]