Window screening, ceilings and closed eaves as sustainable ways to control malaria in Dar es Salaam, Tanzania.

BACKGROUND\ud \ud Malaria transmission in Africa occurs predominantly inside houses where the primary vectors prefer to feed. Human preference and investment in blocking of specific entry points for mosquitoes into houses was evaluated and compared with known entry point preferences of the mosquitoes themselves.\ud \ud METHODS\ud \ud Cross-sectional household surveys were conducted in urban Dar es Salaam, Tanzania to estimate usage levels of available options for house proofing against mosquito entry, namely window screens, ceilings and blocking of eaves. These surveys also enabled evaluation of household expenditure on screens and ceilings and the motivation behind their installation.\ud \ud RESULTS\ud \ud Over three quarters (82.8%) of the 579 houses surveyed in Dar es Salaam had window screens, while almost half (48.9%) had ceilings. Prevention of mosquito entry was cited as a reason for installation of window screens and ceilings by 91.4% (394/431) and 55.7% (127/228) of respondents, respectively, but prevention of malaria was rarely cited (4.3%, 22/508). The median cost of window screens was between US $21-30 while that of ceilings was between US$301-400. The market value of insecticide-treated nets, window screening and ceilings currently in use in the city was estimated as 2, 5 and 42 million US$. More than three quarters of the respondents that lacked them said it was too expensive to install ceilings (82.2%) or window screens (75.5%).\ud \ud CONCLUSION\ud \ud High coverage and spending on screens and ceilings implies that these techniques are highly acceptable and excellent uptake can be achieved in urban settings like Dar es Salaam. Effective models for promotion and subsidization should be developed and evaluated, particularly for installation of ceilings that prevent entry via the eaves, which are the most important entry point for mosquitoes that cause malaria, a variety of neglected tropical diseases and the nuisance which motivates uptake

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

The Value of p-Value in Biomedical Research

Significance tests and the corresponding p-values play a crucial role in decision making. In this commentary the meaning, interpretation and misinterpretation of p-values is presented. Alternatives for evaluating the reported evidence are also discussed

Achieving high coverage of larval-stage mosquito surveillance: challenges for a community-based mosquito control programme in urban Dar es Salaam, Tanzania

BACKGROUND\ud \ud Preventing malaria by controlling mosquitoes in their larval stages requires regular sensitive monitoring of vector populations and intervention coverage. The study assessed the effectiveness of operational, community-based larval habitat surveillance systems within the Urban Malaria Control Programme (UMCP) in urban Dar es Salaam, Tanzania.\ud \ud METHODS\ud \ud Cross-sectional surveys were carried out to assess the ability of community-owned resource persons (CORPs) to detect mosquito breeding sites and larvae in areas with and without larviciding. Potential environmental and programmatic determinants of habitat detection coverage and detection sensitivity of mosquito larvae were recorded during guided walks with 64 different CORPs to assess the accuracy of data each had collected the previous day.\ud \ud RESULTS\ud \ud CORPs reported the presence of 66.2% of all aquatic habitats (1,963/2,965), but only detected Anopheles larvae in 12.6% (29/230) of habitats that contained them. Detection sensitivity was particularly low for late-stage Anopheles (2.7%, 3/111), the most direct programmatic indicator of malaria vector productivity. Whether a CORP found a wet habitat or not was associated with his/her unfamiliarity with the area (Odds Ratio (OR) [95% confidence interval (CI)] = 0.16 [0.130, 0.203], P < 0.001), the habitat type (P < 0.001) or a fence around the compound (OR [95%CI] = 0.50 [0.386, 0.646], P < 0.001). The majority of mosquito larvae (Anophelines 57.8% (133/230) and Culicines 55.9% (461/825) were not reported because their habitats were not found. The only factor affecting detection of Anopheline larvae in habitats that were reported by CORPs was larviciding, which reduced sensitivity (OR [95%CI] = 0.37 [0.142, 0.965], P = 0.042).\ud \ud CONCLUSIONS\ud \ud Accessibility of habitats in urban settings presents a major challenge because the majority of compounds are fenced for security reasons. Furthermore, CORPs under-reported larvae especially where larvicides were applied. This UMCP system for larval surveillance in cities must be urgently revised to improve access to enclosed compounds and the sensitivity with which habitats are searched for larvae

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

Ecology: a prerequisite for malaria elimination and eradication

* Existing front-line vector control measures, such as insecticide-treated nets and residual sprays, cannot break the transmission cycle of Plasmodium falciparum in the most intensely endemic parts of Africa and the Pacific * The goal of malaria eradication will require urgent strategic investment into understanding the ecology and evolution of the mosquito vectors that transmit malaria * Priority areas will include understanding aspects of the mosquito life cycle beyond the blood feeding processes which directly mediate malaria transmission * Global commitment to malaria eradication necessitates a corresponding long-term commitment to vector ecolog

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation

FUNDING AND DISCLOSURE The research was funded by Wellcome Trust (WT098012) to LKH; and National Institute of Health (DK056731) and the Marilyn H. Vincent Foundation to MGM. The University of Michigan Transgenic Core facility is partially supported by the NIH-funded University of Michigan Center for Gastrointestinal Research (DK034933). The remaining authors declare no conflict of interest. ACKNOWLEDGMENTS We thank Dr Celine Cansell, Ms Raffaella Chianese and the staff of the Medical Research Facility for technical assistance. We thank Dr Vladimir Orduña for the scientific advice and technical assistance.Peer reviewedPublisher PD

Empirical correlation of triggered activity and spatial and temporal re-entrant substrates with arrhythmogenicity in a murine model for Jervell and Lange-Nielsen syndrome

KCNE1 encodes the β-subunit of the slow component of the delayed rectifier K+ current. The Jervell and Lange-Nielsen syndrome is characterized by sensorineural deafness, prolonged QT intervals, and ventricular arrhythmogenicity. Loss-of-function mutations in KCNE1 are implicated in the JLN2 subtype. We recorded left ventricular epicardial and endocardial monophasic action potentials (MAPs) in intact, Langendorff-perfused mouse hearts. KCNE1−/− but not wild-type (WT) hearts showed not only triggered activity and spontaneous ventricular tachycardia (VT), but also VT provoked by programmed electrical stimulation. The presence or absence of VT was related to the following set of criteria for re-entrant excitation for the first time in KCNE1−/− hearts: Quantification of APD90, the MAP duration at 90% repolarization, demonstrated alterations in (1) the difference, ∆APD90, between endocardial and epicardial APD90 and (2) critical intervals for local re-excitation, given by differences between APD90 and ventricular effective refractory period, reflecting spatial re-entrant substrate. Temporal re-entrant substrate was reflected in (3) increased APD90 alternans, through a range of pacing rates, and (4) steeper epicardial and endocardial APD90 restitution curves determined with a dynamic pacing protocol. (5) Nicorandil (20 µM) rescued spontaneous and provoked arrhythmogenic phenomena in KCNE1−/− hearts. WTs remained nonarrhythmogenic. Nicorandil correspondingly restored parameters representing re-entrant criteria in KCNE1−/− hearts toward values found in untreated WTs. It shifted such values in WT hearts in similar directions. Together, these findings directly implicate triggered electrical activity and spatial and temporal re-entrant mechanisms in the arrhythmogenesis observed in KCNE1−/− hearts

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 fitness of African malaria vectors in the presence and limitation of host behaviour

&lt;p&gt;Background Host responses are important sources of selection upon the host species range of ectoparasites and phytophagous insects. However little is known about the role of host responses in defining the host species range of malaria vectors. This study aimed to estimate the relative importance of host behaviour to the feeding success and fitness of African malaria vectors, and assess its ability to predict their known host species preferences in nature.&lt;/p&gt; &lt;p&gt;Methods Paired evaluations of the feeding success and fitness of African vectors Anopheles arabiensis and Anopheles gambiae s.s in the presence and limitation of host behaviour were conducted in a semi-field system (SFS) at Ifakara Health Institute, Tanzania. In one set of trials, mosquitoes were released within the SFS and allowed to forage overnight on a host that was free to exhibit natural behaviour in response to insect biting. In the other, mosquitoes were allowed to feed directly on from the skin surface of immobile hosts. The feeding success and subsequent fitness of vectors under these conditions were investigated on 6 host types (humans, calves, chickens, cows, dogs and goats) to assess whether physical movements of preferred host species (cattle for An. arabiensis, humans for An. gambiae s.s.) were less effective at preventing mosquito bites than those of common alternatives.&lt;/p&gt; &lt;p&gt;Results Anopheles arabiensis generally had greater feeding success when applied directly to host skin than when foraging on unrestricted hosts (in five of six host species). However, An. gambiae s.s obtained blood meals from free and restrained hosts with similar success from most host types (four out of six). Overall, the blood meal size, oviposition rate, fecundity and post-feeding survival of mosquito vectors were significantly higher after feeding on hosts free to exhibit behaviour, than those who were immobilized during feeding trials.&lt;/p&gt; &lt;p&gt;Conclusions Allowing hosts to move freely during exposure to mosquitoes was associated with moderate reductions in mosquito feeding success, but no detrimental impact to the subsequent fitness of mosquitoes that were able to feed upon them. This suggests that physical defensive behaviours exhibited by common host species including humans do not impose substantial fitness costs on African malaria vectors.&lt;/p&gt