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

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

Target product profiles for protecting against outdoor malaria transmission.

BACKGROUND\ud \ud Long-lasting insecticidal nets (LLINs) and indoor residual sprays (IRS) have decimated malaria transmission by killing indoor-feeding mosquitoes. However, complete elimination of malaria transmission with these proven methods is confounded by vectors that evade pesticide contact by feeding outdoors.\ud \ud METHODS\ud \ud For any assumed level of indoor coverage and personal protective efficacy with insecticidal products, process-explicit malaria transmission models suggest that insecticides that repel mosquitoes will achieve less impact upon transmission than those that kill them outright. Here such models are extended to explore how outdoor use of products containing either contact toxins or spatial repellents might augment or attenuate impact of high indoor coverage of LLINs relying primarily upon contact toxicity.\ud \ud RESULTS\ud \ud LLIN impact could be dramatically enhanced by high coverage with spatial repellents conferring near-complete personal protection, but only if combined indoor use of both measures can be avoided where vectors persist that prefer feeding indoors upon humans. While very high levels of coverage and efficacy will be required for spatial repellents to substantially augment the impact of LLINs or IRS, these ambitious targets may well be at least as practically achievable as the lower requirements for equivalent impact using contact insecticides.\ud \ud CONCLUSIONS\ud \ud Vapour-phase repellents may be more acceptable, practical and effective than contact insecticides for preventing outdoor malaria transmission because they need not be applied to skin or clothing and may protect multiple occupants of spaces outside of treatable structures such as nets or houses

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

Vortex nucleation as a case study of symmetry breaking in quantum systems

Mean-field methods are a very powerful tool for investigating weakly interacting many-body systems in many branches of physics. In particular, they describe with excellent accuracy trapped Bose-Einstein condensates. A generic, but difficult question concerns the relation between the symmetry properties of the true many-body state and its mean-field approximation. Here, we address this question by considering, theoretically, vortex nucleation in a rotating Bose-Einstein condensate. A slow sweep of the rotation frequency changes the state of the system from being at rest to the one containing one vortex. Within the mean-field framework, the jump in symmetry occurs through a turbulent phase around a certain critical frequency. The exact many-body ground state at the critical frequency exhibits strong correlations and entanglement. We believe that this constitutes a paradigm example of symmetry breaking in - or change of the order parameter of - quantum many-body systems in the course of adiabatic evolution.Comment: Minor change

The importance of considering community-level effects when selecting insecticidal malaria vector products

BACKGROUND\ud \ud Insecticide treatment of nets, curtains or walls and ceilings of houses represent the primary means for malaria prevention worldwide. Direct personal protection of individuals and households arises from deterrent and insecticidal activities which divert or kill mosquitoes before they can feed. However, at high coverage, community-level reductions of mosquito density and survival prevent more transmission exposure than the personal protection acquired by using a net or living in a sprayed house.\ud \ud METHODS\ud \ud A process-explicit simulation of malaria transmission was applied to results of 4 recent Phase II experimental hut trials comparing a new mosaic long-lasting insecticidal net (LLIN) which combines deltamethrin and piperonyl butoxide with another LLIN product by the same manufacturer relying on deltamethrin alone.\ud \ud RESULTS\ud \ud Direct estimates of mean personal protection against insecticide-resistant vectors in Vietnam, Cameroon, Burkina Faso and Benin revealed no clear advantage for combination LLINs over deltamethrin-only LLINs (P = 0.973) unless both types of nets were extensively washed (Relative mean entomologic inoculation rate (EIR) ± standard error of the mean (SEM) for users of combination nets compared to users of deltamethrin only nets = 0.853 ± 0.056, P = 0.008). However, simulations of impact at high coverage (80% use) predicted consistently better impact for the combination net across all four sites (Relative mean EIR ± SEM in communities with combination nets, compared with those using deltamethrin only nets = 0.613 ± 0.076, P < 0.001), regardless of whether the nets were washed or not (P = 0.467). Nevertheless, the degree of advantage obtained with the combination varied substantially between sites and their associated resistant vector populations.\ud \ud CONCLUSION\ud \ud Process-explicit simulations of community-level protection, parameterized using locally-relevant experimental hut studies, should be explicitly considered when choosing vector control products for large-scale epidemiological trials or public health programme procurement, particularly as growing insecticide resistance necessitates the use of multiple active ingredients

Advantages and Limitations of Commercially Available Electrocuting Grids for Studying Mosquito Behaviour.

Mosquito feeding behaviour plays a major role in determining malaria transmission intensity and the impact of specific prevention measures. Human Landing Catch (HLC) is currently the only method that can directly and consistently measure the biting rates of anthropophagic mosquitoes, both indoors and outdoors. However, this method exposes the participant to mosquito-borne pathogens, therefore new exposure-free methods are needed to replace it. Commercially available electrocuting grids (EGs) were evaluated as an alternative to HLC using a Latin Square experimental design in Dar es Salaam, Tanzania. Both HLC and EGs were used to estimate the proportion of human exposure to mosquitoes occurring indoors (πi), as well as its two underlying parameters: the proportion of mosquitoes caught indoors (Pi) and the proportion of mosquitoes caught between the first and last hour when most people are indoors (Pfl). HLC and EGs methods accounted for 69% and 31% of the total number of female mosquitoes caught respectively and both methods caught more mosquitoes outdoors than indoors. Results from the gold standard HLC suggest that An. gambiae s.s. in Dar es Salaam is neither exophagic nor endophagic (Pi ≈ 0.5), whereas An. arabiensis is exophagic (Pi < < 0.5). Both species prefer to feed after 10 pm when most people are indoors (Pfl > >0.5). EGs yielded estimates of Pi for An. gambiae s.s., An. arabiensis and An. coustani, that were approximately equivalent to those with HLC but significantly underestimated Pfl for An. gambiae s.s. and An. coustani. The relative sampling sensitivity of EGs declined over the course of the night (p ≤ 0.001) for all mosquito taxa except An. arabiensis. Commercial EGs sample human-seeking mosquitoes with high sensitivity both indoors and outdoors and accurately measure the propensity of Anopheles malaria vectors to bite indoors rather than outdoors. However, further modifications are needed to stabilize sampling sensitivity over a full nocturnal cycle so that they can be used to survey patterns of human exposure to mosquitoes

Impact of Community-Based Larviciding on the Prevalence of Malaria Infection in Dar es Salaam, Tanzania.

The use of larval source management is not prioritized by contemporary malaria control programs in sub-Saharan Africa despite historical success. Larviciding, in particular, could be effective in urban areas where transmission is focal and accessibility to Anopheles breeding habitats is generally easier than in rural settings. The objective of this study is to assess the effectiveness of a community-based microbial larviciding intervention to reduce the prevalence of malaria infection in Dar es Salaam, United Republic of Tanzania. Larviciding was implemented in 3 out of 15 targeted wards of Dar es Salaam in 2006 after two years of baseline data collection. This intervention was subsequently scaled up to 9 wards a year later, and to all 15 targeted wards in 2008. Continuous randomized cluster sampling of malaria prevalence and socio-demographic characteristics was carried out during 6 survey rounds (2004-2008), which included both cross-sectional and longitudinal data (N = 64,537). Bayesian random effects logistic regression models were used to quantify the effect of the intervention on malaria prevalence at the individual level. Effect size estimates suggest a significant protective effect of the larviciding intervention. After adjustment for confounders, the odds of individuals living in areas treated with larviciding being infected with malaria were 21% lower (Odds Ratio = 0.79; 95% Credible Intervals: 0.66-0.93) than those who lived in areas not treated. The larviciding intervention was most effective during dry seasons and had synergistic effects with other protective measures such as use of insecticide-treated bed nets and house proofing (i.e., complete ceiling or window screens). A large-scale community-based larviciding intervention significantly reduced the prevalence of malaria infection in urban Dar es Salaam

Target product profile choices for intra-domiciliary malaria vector control pesticide products: repel or kill?

BACKGROUND\ud \ud 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.\ud \ud METHODS\ud \ud 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.\ud \ud RESULTS\ud \ud 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.\ud \ud CONCLUSIONS\ud \ud 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

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