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Background The World Health Organization recommends confirmatory diagnosis by microscopy or malaria rapid diagnostic test (RDT) in patients with suspected malaria. In recent years, mobile medical applications (MMAs), which can interpret RDT test results have entered the market. To evaluate the performance of commercially available MMAs, an evaluation was conducted by comparing RDT results read by MMAs to RDT results read by the human eye. Methods Five different MMAs were evaluated on six different RDT products using cultured Plasmodium falciparum blood samples at five dilutions ranging from 20 to 1000 parasites (p)/microlitre (µl) and malaria negative blood samples. The RDTs were performed in a controlled, laboratory setting by a trained operator who visually read the RDT results. A second trained operator then used the MMAs to read the RDT results. Sensitivity (Sn) and specificity (Sp) for the RDTs were calculated in a Bayesian framework using mixed models. Results The RDT Sn of the P. falciparum (Pf) test line, when read by the trained human eye was significantly higher compared to when read by MMAs (74% vs. average 47%) at samples of 20 p/µl. In higher density samples, the Sn was comparable to the human eye (97%) for three MMAs. The RDT Sn of test lines that detect all Plasmodium species (Pan line), when read by the trained human eye was significantly higher compared to when read by MMAs (79% vs. average 56%) across all densities. The RDT Sp, when read by the human eye or MMAs was 99% for both the Pf and Pan test lines across all densities. Conclusions The study results show that in a laboratory setting, most MMAs produced similar results interpreting the Pf test line of RDTs at parasite densities typically found in patients that experience malaria symptoms (> 100 p/µl) compared to the human eye. At low parasite densities for the Pf line and across all parasite densities for the Pan line, MMAs were less accurate than the human eye. Future efforts should focus on improving the band/line detection at lower band intensities and evaluating additional MMA functionalities like the ability to identify and classify RDT errors or anomalies.

In this work, we present a simple and flexible model for Plasmodium vivax dynamics which can be easily combined with routinely collected data on local and imported case counts to quantify transmission intensity and simulate control strategies. This model extends the model from White et al. (2016) by including case management interventions targeting liver-stage or blood-stage parasites, as well as imported infections. The endemic steady state of the model is used to derive a relationship between the observed incidence and the transmission rate in order to calculate reproduction numbers and simulate intervention scenarios. To illustrate its potential applications, the model is used to calculate local reproduction numbers in Panama and identify areas of sustained malaria transmission that should be targeted by control interventions., Highlights • A model for P. vivax including case management and imported infections is analysed. • The model is calibrated by linking its steady state to observed incidence data. • This method can be used to calculate reproduction numbers or simulate interventions. • Parameter sensitivity and coherence with an existing model are explored. • Practical applications of the model are illustrated in the Panama context.

The burden of malaria in Myanmar has declined rapidly in recent years; cases decreased from 333,871 in 2013 to 85,019 in 2017 (75% decrease). Decline of malaria in the Ayeyarwady Region of Myanmar reflects this trend with an 86% decrease in cases over this period. In this exploratory analysis, quantitative and qualitative information were assessed to explore potential factors responsible for the decline of malaria in Ayeyarwady. Data on malaria incidence, programmatic financing, surveillance, case management, vector control interventions, climate and ecological factors, and policies and guidelines spanning 2013 to 2017 were compiled. Poisson regression models that adjust for correlation were used to analyze the association between annual malaria case numbers with malaria intervention factors at the township level. Between 2013 and 2017, there was a decrease in mean township-level malaria incidence per 1000 from 3.03 (SD 4.59) to 0.34 (SD 0.79); this decline coincided with the implementation of the government’s multi-pronged malaria elimination strategy, an increase of approximately 50.8 million USD in malaria funding nationally, and a period of deforestation in the region. Increased funding in Ayeyarwady was invested in interventions associated with the decline in caseload, and the important roles of surveillance and case management should be maintained while Myanmar works towards malaria elimination.

Background Ayeyarwady Region in Myanmar has made significant progress towards malaria elimination, with cases decreasing from 12,312 in 2015 to 122 in 2019. As transmission declines, malaria becomes increasingly focalized both in geographic hotspots and among population groups sharing certain risk factors. Developing a thorough profile of high-risk activities associated with malaria infections is critical to ensure intervention approaches are evidence-based. Methods A test-negative study was conducted from September 2017 to May 2018 in Ngaputaw, Pathein and Thabaung townships in Ayeyarwady Region. Patients that presented to selected public facilities or community health volunteers with fever answered survey questions on demographic and behavioural risk factors, including exposure to malaria interventions, and were assigned to case and control groups based on the result of a malaria rapid diagnostic test. A random-effects logistic regression model adjusted for clustering at the facility level, as well as any variables along the causal pathway described by a directed acyclic graph, was used to determine odds ratios and association with malaria infections. Results A total of 119 cases and 1744 controls were recruited from 41 public facilities, with a mean age of 31.3 and 63.7% male. Higher risk groups were identified as males (aOR 1.8, 95% CI 1.2–2.9) and those with a worksite located within the forest (aOR 2.8, 95% CI 1.4–5.3), specifically working in the logging (aOR 2.7, 95% CI 1.5–4.6) and rubber plantation (aOR 3.0, 95% CI 1.4–6.8) industries. Additionally, links between forest travel and malaria were observed, with risk factors identified to be sleeping in the forest within the past month (aOR 2.6, 95% CI 1.1–6.3), and extended forest travel with durations from 3 to 14 days (aOR 8.6, 95% CI 3.5–21.4) or longer periods (aOR 8.4, 95% CI 3.2–21.6). Conclusion Malaria transmission is highly focalized in Ayeyarwady, and results illustrate the need to target interventions to the most at-risk populations of working males and forest goers. It will become increasingly necessary to ensure full intervention coverage of at-risk populations active in forested areas as Myanmar moves closer to malaria elimination goals.

BackgroundSurveillance is a core component of an effective system to support malaria elimination. Poor surveillance data will prevent countries from monitoring progress towards elimination and targeting interventions to the last remaining at-risk places. An evaluation of the performance of surveillance systems in 16 countries was conducted to identify key gaps which could be addressed to build effective systems for malaria elimination.MethodsA standardized surveillance system landscaping was conducted between 2015 and 2017 in collaboration with governmental malaria programmes. Malaria surveillance guidelines from the World Health Organization and other technical bodies were used to identify the characteristics of an optimal surveillance system, against which systems of study countries were compared. Data collection was conducted through review of existing material and datasets, and interviews with key stakeholders, and the outcomes were summarized descriptively. Additionally, the cumulative fraction of incident infections reported through surveillance systems was estimated using surveillance data, government records, survey data, and other scientific sources.ResultsThe landscaping identified common gaps across countries related to the lack of surveillance coverage in remote communities or in the private sector, the lack of adequate health information architecture to capture high quality case-based data, poor integration of data from other sources such as intervention information, poor visualization of generated information, and its lack of availability for making programmatic decisions. The median percentage of symptomatic cases captured by the surveillance systems in the 16 countries was estimated to be 37%, mostly driven by the lack of treatment-seeking in the public health sector (64%) or, in countries with large private sectors, the lack of integration of this sector within the surveillance system.ConclusionsThe landscaping analysis undertaken provides a clear framework through which to identify multiple gaps in current malaria surveillance systems. While perfect systems are not required to eliminate malaria, closing the gaps identified will allow countries to deploy resources more efficiently, track progress, and accelerate towards malaria elimination. Since the landscaping undertaken here, several countries have addressed some of the identified gaps by improving coverage of surveillance, integrating case data with other information, and strengthening visualization and use of data.

Mosquitoes are important vectors for pathogens that infect humans and other vertebrate animals. Some aspects of adult mosquito behavior and mosquito ecology play an important role in determining the capacity of vector populations to transmit pathogens. Here, we re-examine factors affecting the transmission of pathogens by mosquitoes using a new approach. Unlike most previous models, this framework considers the behavioral states and state transitions of adult mosquitoes through a sequence of activity bouts. We developed a new framework for individual-based simulation models called MBITES (Mosquito Bout-based and Individual-based Transmission Ecology Simulator). In MBITES, it is possible to build models that simulate the behavior and ecology of adult mosquitoes in exquisite detail on complex resource landscapes generated by spatial point processes. We also developed an ordinary differential equation model which is the Kolmogorov forward equations for models developed in MBITES under a specific set of simplifying assumptions. While mosquito infection and pathogen development are one possible part of a mosquito’s state, that is not our main focus. Using extensive simulation using some models developed in MBITES, we show that vectorial capacity can be understood as an emergent property of simple behavioral algorithms interacting with complex resource landscapes, and that relative density or sparsity of resources and the need to search can have profound consequences for mosquito populations’ capacity to transmit pathogens., Author summary Mathematical modelling of pathogen transmission by mosquitoes began over a century ago with Ronald Ross and has produced a set of metrics that are the basis of measuring transmission. One crucial metric is vectorial capacity (VC), a simple equation describing the potential of mosquitoes to transmit pathogens. Despite its elegance, this formula lacks specificity to describe mosquitoes in a particular landscape. To study how these metrics arise in particular places, we built MBITES (Mosquito Bout-based and Individual-based Transmission Ecology Simulator), a complex stochastic individual-based model where mosquitoes fly from place to place to blood feed, sugar feed, lay eggs, mate, or rest. We also built a related model, MBDETES based on deterministic mathematics to show how the complex behaviors possible in MBITES can be summarized on average, and to provide a bridge to the simple equations describing VC. Through a series of computational experiments, we show a strong dependence VC and other metrics on fine details of the landscape mosquitoes inhabit which are not obvious from simple equations.

Background Haiti and the Dominican Republic (DR) are targeting malaria elimination by 2022. The private health sector has been relatively unengaged in these efforts, even though most primary health care in Haiti is provided by non-state actors, and many people use traditional medicine. Data on private health sector participation in malaria elimination efforts are lacking, as are data on care-seeking behaviour of patients in the private health sector. This study sought to describe the role of private health sector providers, care-seeking behaviour of individuals at high risk of malaria, and possible means of engaging the private health sector in Hispaniola’s malaria elimination efforts. Methods In-depth interviews with 26 key informants (e.g. government officials), 62 private providers, and 63 patients of private providers, as well as 12 focus group discussions (FGDs) with community members, were conducted within seven study sites in Haiti and the DR. FGDs focused on local definitions of the private health sector and identified private providers for interview recruitment, while interviews focused on private health sector participation in malaria elimination activities and treatment-seeking behaviour of febrile individuals. Results Interviews revealed that self-medication is the most common first step in the trajectory of care for fevers in both Haiti and the DR. Traditional medicine is more commonly used in Haiti than in the DR, with many patients seeking care from traditional healers before, during, and/or after care in the formal health sector. Private providers were interested in participating in malaria elimination efforts but emphasized the need for ongoing support and training. Key informants agreed that the private health sector needs to be engaged, especially traditional healers in Haiti. The Haitian migrant population was reported to be one of the most at-risk groups by participants from both countries. Conclusion Malaria elimination efforts across Hispaniola could be enhanced by engaging traditional healers in Haiti and other private providers with ongoing support and trainings; directing educational messaging to encourage proper treatment-seeking behaviour; and refining cross-border strategies for surveillance of the high-risk migrant population. Increasing distribution of rapid diagnostic tests (RDTs) and bi-therapy to select private health sector facilities, accompanied by adopting regulatory policies, could help increase numbers of reported and correctly treated malaria cases.

Background The incidence of TB has doubled in the last 20 years in London. A better understanding of risk groups for recent transmission is required to effectively target interventions. We investigated the molecular epidemiological characteristics of TB cases to estimate the proportion of cases due to recent transmission, and identify predictors for belonging to a cluster. Methods The study population included all culture-positive TB cases in London residents, notified between January 2010 and December 2012, strain typed using 24-loci multiple interspersed repetitive units-variable number tandem repeats. Multivariable logistic regression analysis was performed to assess the risk factors for clustering using sociodemographic and clinical characteristics of cases and for cluster size based on the characteristics of the first two cases. Results There were 10 147 cases of which 5728 (57%) were culture confirmed and 4790 isolates (84%) were typed. 2194 (46%) were clustered in 570 clusters, and the estimated proportion attributable to recent transmission was 34%. Clustered cases were more likely to be UK born, have pulmonary TB, a previous diagnosis, a history of substance abuse or alcohol abuse and imprisonment, be of white, Indian, black-African or Caribbean ethnicity. The time between notification of the first two cases was more likely to be

Background Tanzania has seen a reduction in the fraction of fevers caused by malaria, likely due in part to scale-up of control measures. While national guidelines require parasite-based diagnosis prior to treatment, it is estimated that more than half of suspected malaria treatment-seeking in Tanzania initiates in the private retail sector, where diagnosis by malaria rapid diagnostic test (RDT) or microscopy is illegal. This pilot study investigated whether the introduction of RDTs into Accredited Drug Dispensing Outlets (ADDOs) under realistic market conditions would improve case management practices. Methods Dispensers from ADDOs in two intervention districts in Tanzania were trained to stock and perform RDTs and monitored quarterly. Each district was assigned a different recommended retail price to evaluate the need for a subsidy. Malaria RDT and artemisinin-based combination therapy (ACT) uptake and availability were measured pre-intervention and 1 year post-intervention through structured surveys of ADDO owners and exiting customers in both intervention districts and one contiguous control district. Descriptive analysis and logistic regression were used to compare the three districts and identify predictive variables for testing. Results and discussion A total of 310 dispensers from 262 ADDOs were trained to stock and perform RDTs. RDT availability in intervention ADDOs increased from 1% (n = 172) to 73% (n = 163) during the study; ACT medicines were available in 75% of 260 pre-intervention and 68% of 254 post-intervention ADDOs. Pre-treatment testing performed within the ADDO increased from 0 to 65% of suspected malaria patients who visited a shop (95% CI 60.8–69.6%) with no difference between intervention districts. Overall parasite-based diagnosis increased from 19 to 74% in intervention districts and from 3 to 18% in the control district. Prior knowledge of RDT availability (aOR = 1.9, p = 0.03) and RDT experience (aOR = 1.9, p = 0.01) were predictors for testing. Adherence data indicated that 75% of malaria positives received ACT, while 3% of negatives received ACT. Conclusions Trained and supervised ADDO dispensers in rural Tanzania performed and sold RDTs under real market conditions to two-thirds of suspected malaria patients during this one-year pilot. These results support the hypothesis that introducing RDTs into regulated private retail sector settings can improve malaria testing and treatment practices without an RDT subsidy. Trial registration ISRCTN ISRCTN14115509

Background Following a measles outbreak in a vaccine-rejecting community between April and September 2011 in South-East England, local health agencies implemented a two-pronged measles–mumps–rubella (MMR) immunisation campaign from August to October offered at the local general practice where most cases were registered. The campaign included (a) accelerated vaccination of children earlier than scheduled (1st dose at 6–11 months, or 2nd dose at 18–39 months), (b) catch-up of those aged over 18 months who had had no MMR immunisations or were late for second MMR. We investigated the impact of the outbreak and campaign on the number of MMR doses given. Materials and methods In January 2012, we collected information on MMR vaccination for children registered at the practice aged 6 months–16 years on 1 August 2011, through the child health information system. We counted the number of MMR doses administered in 2011 and compared it to 2008–2010 data. We estimated the proportion vaccinated among the children eligible for the accelerated and catch-up campaign. Results The local practice administered 257 MMR doses in 2011, a 114% increase on the average for 2008–2010. Among children eligible for earlier MMR vaccination 5/26 (19%) received a first dose, and 34/57 (60%) a second dose. Among children eligible for catch-up, 20/329 (6%) received their first MMR and 39/121 (32%) their second. Of 1538 children, the proportion completely unimmunised for MMR declined by 3 percentage-points after the outbreak. Discussion Uptake of MMR vaccination significantly increased during the outbreak following the immunisation campaign. Those amenable to MMR vaccination seem to have benefited from the campaign more than those with no previous vaccinations. Future evaluations should address what made a few parents change their mind and have their children vaccinated for the first time during the outbreak.

Scientific Reports 6: Article number: 29628; published online: 13 July 2016; updated: 14 September 2016

Background Numerous countries around the world are approaching malaria elimination. Until global eradication is achieved, countries that successfully eliminate the disease will contend with parasite reintroduction through international movement of infected people. Human-mediated parasite mobility is also important within countries near elimination, as it drives parasite flows that affect disease transmission on a subnational scale. Methods Movement patterns exhibited in census-based migration data are compared with patterns exhibited in a mobile phone data set from Haiti to quantify how well migration data predict short-term movement patterns. Because short-term movement data were unavailable for Mesoamerica, a logistic regression model fit to migration data from three countries in Mesoamerica is used to predict flows of infected people between subnational administrative units throughout the region. Results Population flows predicted using census-based migration data correlated strongly with mobile phone-derived movements when used as a measure of relative connectivity. Relative population flows are therefore predicted using census data across Mesoamerica, informing the areas that are likely exporters and importers of infected people. Relative population flows are used to identify community structure, useful for coordinating interventions and elimination efforts to minimize importation risk. Finally, the ability of census microdata inform future intervention planning is discussed in a country-specific setting using Costa Rica as an example. Conclusions These results show long-term migration data can effectively predict the relative flows of infected people to direct malaria elimination policy, a particularly relevant result because migration data are generally easier to obtain than short-term movement data such as mobile phone records. Further, predicted relative flows highlight policy-relevant population dynamics, such as major exporters across the region, and Nicaragua and Costa Rica’s strong connection by movement of infected people, suggesting close coordination of their elimination efforts. Country-specific applications are discussed as well, such as predicting areas at relatively high risk of importation, which could inform surveillance and treatment strategies. Electronic supplementary material The online version of this article (doi:10.1186/s12936-016-1315-5) contains supplementary material, which is available to authorized users.

Temperature has played a critical role in the spatiotemporal dynamics of West Nile virus transmission throughout California from its introduction in 2003 through establishment by 2009. We compared two novel mechanistic measures of transmission risk, the temperature-dependent ratio of virus extrinsic incubation period to the mosquito gonotrophic period (BT), and the fundamental reproductive ratio (R(0)) based on a mathematical model, to analyze spatiotemporal patterns of receptivity to viral amplification. Maps of BT and R(0) were created at 20-km scale and compared throughout California to seroconversions in sentinel chicken flocks at half-month intervals. Overall, estimates of BT and R(0) agreed with intensity of transmission measured by the frequency of sentinel chicken seroconversions. Mechanistic measures such as these are important for understanding how temperature affects the spatiotemporal dynamics of West Nile virus transmission and for delineating risk estimates useful to inform vector control agency intervention decisions and communicate outbreak potential.

Eliminating malaria from a defined region involves draining the endemic parasite reservoir and minimizing local malaria transmission around imported malaria infections. In the last phases of malaria elimination, as universal interventions reap diminishing marginal returns, national resources must become increasingly devoted to identifying where residual transmission is occurring. The needs for accurate measures of progress and practical advice about how to allocate scarce resources require new analytical methods to quantify fine-grained heterogeneity in malaria risk. Using routine national surveillance data from Swaziland (a sub-Saharan country on the verge of elimination), we estimated individual reproductive numbers. Fine-grained maps of reproductive numbers and local malaria importation rates were combined to show ‘malariogenic potential’, a first for malaria elimination. As countries approach elimination, these individual-based measures of transmission risk provide meaningful metrics for planning programmatic responses and prioritizing areas where interventions will contribute most to malaria elimination. DOI: http://dx.doi.org/10.7554/eLife.09520.001, eLife digest Swaziland has set a national goal of eliminating malaria transmission in the very short term, which would make it the first country in sub-Saharan Africa to do so. More than half of the cases of malaria that are observed in Swaziland are caused by infections picked up by travelers while they were in other countries where the disease is much more prevalent. The other cases – people who became infected in Swaziland – are the cases that the government of Swaziland is trying to prevent. If Swaziland is going to eliminate malaria, it will need to identify any places where the malaria parasites are still spreading throughout the population so it can target those communities with effective prevention measures. It will also need to manage the risk that infections imported from abroad may re-start transmission in places where it has been stopped. To work out how likely it is that a malaria infection will be transmitted by mosquitoes in a particular place, researchers can look at past malaria data and calculate how many new infections are caused by each case. Reiner et al. have now produced a computer model that estimates how this number varies across Swaziland, highlighting places where the government is going to need to focus efforts to eliminate malaria. The model shows that in some rural areas near Mozambique, each individual infected with malaria is causing more than one other person to become infected. This confirms that the disease has not yet been eliminated from these areas. However, in other regions of the country, malaria rarely spreads between individuals. The detailed regional information from the model may help public health authorities in Swaziland better target their anti-malaria resources. In large cities where most cases are imported, Reiner et al. suggest focusing resources on providing preventive treatment to travelers who plan on visiting places where malaria is spreading. However, in rural areas where malaria continues to spread, preventively treating the whole population or providing them with tools to protect them from mosquitoes might be more appropriate. Similar considerations of regional differences in the spread of malaria could also help other countries to more effectively combat the disease. DOI: http://dx.doi.org/10.7554/eLife.09520.002

Background Mapping malaria risk is an integral component of efficient resource allocation. Routine health facility data are convenient to collect, but without information on the locations at which transmission occurred, their utility for predicting variation in risk at a sub-catchment level is presently unclear. Methods Using routinely collected health facility level case data in Swaziland between 2011–2013, and fine scale environmental and ecological variables, this study explores the use of a hierarchical Bayesian modelling framework for downscaling risk maps from health facility catchment level to a fine scale (1 km x 1 km). Fine scale predictions were validated using known household locations of cases and a random sample of points to act as pseudo-controls. Results Results show that fine-scale predictions were able to discriminate between cases and pseudo-controls with an AUC value of 0.84. When scaled up to catchment level, predicted numbers of cases per health facility showed broad correspondence with observed numbers of cases with little bias, with 84 of the 101 health facilities with zero cases correctly predicted as having zero cases. Conclusions This method holds promise for helping countries in pre-elimination and elimination stages use health facility level data to produce accurate risk maps at finer scales. Further validation in other transmission settings and an evaluation of the operational value of the approach is necessary. Electronic supplementary material The online version of this article (doi:10.1186/1475-2875-13-421) contains supplementary material, which is available to authorized users.

Mathematical models of mosquito-borne pathogen transmission originated in the early twentieth century to provide insights into how to most effectively combat malaria. The foundations of the Ross-Macdonald theory were established by 1970. Since then, there has been a growing interest in reducing the public health burden of mosquito-borne pathogens and an expanding use of models to guide their control. To assess how theory has changed to confront evolving public health challenges, we compiled a bibliography of 325 publications from 1970 through 2010 that included at least one mathematical model of mosquito-borne pathogen transmission and then used a 79-part questionnaire to classify each of 388 associated models according to its biological assumptions. As a composite measure to interpret the multidimensional results of our survey, we assigned a numerical value to each model that measured its similarity to 15 core assumptions of the Ross-Macdonald model. Although the analysis illustrated a growing acknowledgement of geographical, ecological and epidemiological complexities in modelling transmission, most models during the past 40 years closely resemble the Ross-Macdonald model. Modern theory would benefit from an expansion around the concepts of heterogeneous mosquito biting, poorly mixed mosquito-host encounters, spatial heterogeneity and temporal variation in the transmission process., Journal of The Royal Society Interface, 10(81), 20120921; 2013

The Ross-Macdonald model has dominated theory for mosquito-borne pathogen transmission dynamics and control for over a century. The model, like many other basic population models, makes the mathematically convenient assumption that populations are well mixed; i.e., that each mosquito is equally likely to bite any vertebrate host. This assumption raises questions about the validity and utility of current theory because it is in conflict with preponderant empirical evidence that transmission is heterogeneous. Here, we propose a new dynamic framework that is realistic enough to describe biological causes of heterogeneous transmission of mosquito-borne pathogens of humans, yet tractable enough to provide a basis for developing and improving general theory. The framework is based on the ecological context of mosquito blood meals and the fine-scale movements of individual mosquitoes and human hosts that give rise to heterogeneous transmission. Using this framework, we describe pathogen dispersion in terms of individual-level analogues of two classical quantities: vectorial capacity and the basic reproductive number, . Importantly, this framework explicitly accounts for three key components of overall heterogeneity in transmission: heterogeneous exposure, poor mixing, and finite host numbers. Using these tools, we propose two ways of characterizing the spatial scales of transmission—pathogen dispersion kernels and the evenness of mixing across scales of aggregation—and demonstrate the consequences of a model's choice of spatial scale for epidemic dynamics and for estimation of , both by a priori model formulas and by inference of the force of infection from time-series data., Author Summary Pathogens transmitted by mosquitoes, such as malaria and dengue, are notorious for the biological complexity associated with how they are transmitted within local communities. Yet mathematical models for these pathogens, which are critical tools for making recommendations for control policy, are based around concepts originally designed to describe how molecules interact in chemical systems. To provide those interested in mosquito-borne diseases a more appropriate tool for modeling their transmission, we introduce a mathematical framework that is based on the spatial locations where mosquitoes lay eggs and feed on blood and how mosquitoes and hosts move about those locations. Analysis of this framework shows that the transmission contributions of different hosts and locations can be calculated, and that overall potential for transmission in a community depends on three concepts: heterogeneous exposure (some people bitten by mosquitoes more than others), poor mixing (non-random contacts between hosts and mosquitoes), and finite population sizes (each host can contribute at most one new infection towards the population total). Together, these factors determine critical levels of vaccination coverage to eliminate a pathogen and the spatial areas over which transmission should be modeled and studied in the field.

The prevalence of Plasmodium falciparum malaria in Zanzibar has reached historic lows. Improving control requires quantifying malaria importation rates, identifying high-risk travelers and assessing onwards transmission. Estimates of Zanzibar's importation rate were calculated through two independent methodologies. First, mobile phone usage data and ferry traffic between Zanzibar and mainland Tanzania were re-analyzed using a model of heterogeneous travel risk. Second, a dynamic mathematical model of importation and transmission rates was used. Zanzibar residents traveling to malaria endemic regions were estimated to contribute 1–15 times more imported cases than infected visitors. The malaria importation rate was estimated to be 1.6 incoming infections per 1,000 inhabitants per year. Local transmission was estimated too low to sustain transmission in most places. Malaria infections in Zanzibar largely result from imported malaria and subsequent transmission. Plasmodium falciparum malaria elimination appears feasible by implementing control measures based on detecting imported malaria cases and controlling onward transmission.

On November 4, 2010, the Republic of the Congo declared a poliomyelitis outbreak. A cross-sectional survey in Pointe-Noire showed poor sanitary conditions and low vaccination coverage (55.5%), particularly among young adults. Supplementary vaccination should focus on older age groups in countries with evidence of immunity gaps.

It has been reported that Escherichia coli B2 phylogenetic group strains are more susceptible to antibiotics, especially to quinolones, and tend to carry less integrons than other phylogenetic groups in commensal environments. To gain a better understanding of the relationships between antibiotic resistance, integrons, and phylogenetic groups in an environment with high antibiotic selective pressure, we compared these characteristics in three selected groups of urinary tract infection E. coli isolated in a university hospital (G1, G2, and G3). The isolates were fully susceptible to antibiotics, resistant to amoxicillin and cotrimoxazol, or resistant to amoxicillin, cotrimoxazol, and nalidixic acid in the G1, G2, and G3 group, respectively. The prevalence of B2 isolates was significantly lower in the most resistant G3 group (22.6%) than in susceptible G1 (57.8%, p0.001) and G2 groups (50%, p0.01). In contrast, the prevalence of B2 isolates was not significantly different between G1 and G2 groups. The prevalence of integrons was nil in G1 isolates but very high in G2 (94.3%) and G3 (87.5%) isolates, and integrons were equally distributed among the phylogenetic groups. We propose a step-by-step mechanism for the emergence of antibiotic resistance in E. coli. Under very low selective pressure, resistance emerges without integrons. When the antibiotic pressure increases, quinolone and integron-mediated resistance occurs outside phylogenetic group B2. With strong antibiotic selective pressure, integrons are highly prevalent and widespread regardless of the phylogenetic group.

Background Insecticide Treated Nets (ITNs) are an important tool for malaria control. ITNs are effective because they work on several parts of the mosquito feeding cycle, including both adult killing and repelling effects. Methods Using an elaborated description of the classic feeding cycle model, simple formulas have been derived to describe how ITNs change mosquito behaviour and the intensity of malaria transmission, as summarized by vectorial capacity and EIR. The predicted changes are illustrated as a function of the frequency of ITN use for four different vector populations using parameter estimates from the literature. Results The model demonstrates that ITNs simultaneously reduce mosquitoes' lifespans, lengthen the feeding cycle, and by discouraging human biting divert more bites onto non-human hosts. ITNs can substantially reduce vectorial capacity through small changes to all of these quantities. The total reductions in vectorial capacity differ, moreover, depending on baseline behavior in the absence of ITNs. Reductions in lifespan and vectorial capacity are strongest for vector species with high baseline survival. Anthropophilic and zoophilic species are affected differently by ITNs; the feeding cycle is lengthened more for anthrophilic species, and the proportion of bites that are diverted onto non-human hosts is higher for zoophilic species. Conclusion This model suggests that the efficacy of ITNs should be measured as a total reduction in transmission intensity, and that the quantitative effects will differ by species and by transmission intensity. At very high rates of ITN use, ITNs can generate large reductions in transmission intensity that could provide very large reductions in transmission intensity, and effective malaria control in some areas, especially when used in combination with other control measures. At high EIR, ITNs will probably not substantially reduce the parasite rate, but when transmission intensity is low, reductions in vectorial capacity combine with reductions in the parasite rate to generate very large reductions in EIR.

International audience; Recent avian flu epidemics (A/H5N1) in Southeast Asia and case reports from around the world have led to fears of a human pandemic. Control of these outbreaks in birds would probably lead to reduced transmission of the avian virus to humans. This study presents a mathematical model based on stochastic farm-to-farm transmission that incorporates flock size and spatial contacts to evaluate the impact of control strategies. Fit to data from the recent epidemic in the Netherlands, we evaluate the efficacy of control strategies and forecast avian influenza dynamics. Our results identify high-risk areas of spread by mapping of the farm level reproductive number. Results suggest that an immediate depopulation of infected flocks following an accurate and quick diagnosis would have a greater impact than simply depopulating surrounding flocks. Understanding the relative importance of different control measures is essential for response planning

International audience; Foot-and-mouth disease is one of the most contagious diseases of animal livestock. We used statistical tools to explore the dynamics of epidemics and to evaluate the consequences of virus reintroduction in France. We developed a stochastic farm-based model adapted to the French farm structure from previous modeling works following the 2001 epidemic in the United Kingdom. This model depends upon the distance between the 280 000 French farms and on species type (e.g. cows and sheep) and it tracks each animal's farm status at any given day. Since data were only available at the town scale, the farm location and the number of animals in each farm were simulated over the surface area of each French town, as well as the number of mixed farms. Based on 200 simulations of the model, our results allowed for the study of local disease transmission, since it begins simulations once limitation of movement is put into place. On average, the same 50 randomly chosen initially infected farms would lead to 1 110 infected farms (610; 1 590) when two control strategies (culling within 0.5 km from an infected farm and vaccination within 3 km) are put into place. Regions with high densities of cows and sheep (e.g. Pays-de-la-Loire) are high-risk zones, confirming that the epidemic process depends upon the location and the type of initially infected farms (size, species type). The results of this model highlight the importance of Geographical Information Systems (GIS) to obtain more precise data concerning herds.

The study of integrons in 181 Escherichia coli isolates from three groups of healthy subjects who lived in communities and had not taken antibiotics for at least 1 month showed that the presence of integrons was associated with antibiotic resistance and phylogenetic grouping of the bacterial host and dependent on a subject's living environment.

Background Mosquitoes commute between blood-meal hosts and water. Thus, heterogeneity in human biting reflects underlying spatial heterogeneity in the distribution and suitability of larval habitat as well as inherent differences in the attractiveness, suitability and distribution of blood-meal hosts. One of the possible strategies of malaria control is to identify local vector species and then attack water bodies that contain their larvae. Methods Biting and host seeking, not oviposition, have been the focus of most previous studies of mosquitoes and malaria transmission. This study presents a mathematical model that incorporates mosquito oviposition behaviour. Results The model demonstrates that oviposition is one potential factor explaining heterogeneous biting and vector distribution in a landscape with a heterogeneous distribution of larval habitat. Adult female mosquitoes tend to aggregate around places where they oviposit, thereby increasing the risk of malaria, regardless of the suitability of the habitat for larval development. Thus, a water body may be unsuitable for adult mosquito emergence, but simultaneously, be a source for human malaria. Conclusion Larval density may be a misleading indicator of a habitat's importance for malaria control. Even if mosquitoes could be lured to oviposit in sprayed larval habitats, this would not necessarily mitigate – and might aggravate – the risk of malaria transmission. Forcing mosquitoes to fly away from humans in search of larval habitat may be a more efficient way to reduce the risk of malaria than killing larvae. Thus, draining, fouling, or filling standing water where mosquitoes oviposit can be more effective than applying larvicide.

International audience; Ticks are known vectors for a wide range of pathogenic microorganisms. Their role in the transmission of some others is so far only suspected. Ticks can transmit multiple pathogens, however, little is known about the co-existence of these pathogens within questing ticks. We looked for the presence of DNA from three micro-organisms, Bartonella sp., Borrelia burgdorferi sensu lato and Babesia sp. which are known or suspected tick-borne pathogens, using a cohort of 92 questing Ixodes ricinus ticks collected from pastures in northern France. DNA was extracted from each individual tick and the presence of the three pathogens was investigated using Polymerase Chain Reaction (PCR) amplification. Nine among 92 samples (9.8%) demonstrated PCR products using Bartonella specific primers, 3 among 92 (3.3%) using Borrelia burgdorferi sensu lato specific primers and 19 among 92 (20.6%) using Babesia specific primers. Seven among 92 samples (7.6%) were PCR positive for at least two of the pathogens and one sample was positive for all three. Adult ticks (12/18; 67%) showed significantly higher infection rates compared to nymphs (11/74; 15%) for all three pathogens (P < 0.001). This study is the demonstration of the simultaneous presence of Bartonella sp., Borrelia burgdorferi sensu lato and Babesia sp. in questing Ixodes ricinus ticks.

International audience; Molecular detection of pathogenic microorganisms in ticks is based on DNA amplification of the target pathogen; therefore, extraction of DNA from the tick is a major step. In this study, we compared three different tick DNA extraction protocols based on an enzymatic digestion by proteinase K followed by DNA extraction by a commercial kit (method 1), or on mortar crushing, proteinase K digestion and phenol/chloroform DNA extraction (method 2) and fine crushing with a beads beater, proteinase K digestion and DNA extraction using a commercial kit (method 3). The absence of PCR inhibitors and the DNA quality were evaluated by PCR amplification of the tick mitochondrial 16S rRNA gene using tick-specific primers. With method 1, 23/30 (77%) of the samples were extracted; with method 2, 30/31 (97%) of the samples were extracted and with method 3, 30/30 (100%) of the samples were extracted. DNA extraction efficiency using method 3 is significantly higher than DNA extraction efficiency using method 1 (100% versus 77%, P < 0.05). There was no significant difference between methods 2 and 3. Method 3 was however more adapted to cohort studies than method 2. This technique was validated for cohort tick DNA extraction and applicable to the treatment of small samples such as nymphs and soft ticks with 100% efficiency.

Background Haiti has a set a target of eliminating malaria by 2020. However, information on malaria vector research in Haiti is not well known. This paper presents results from a systematic review of the literature on malaria vector research, bionomics and control in Haiti. Methods A systematic search of literature published in French, Spanish and English languages was conducted in 2015 using Pubmed (MEDLINE), Google Scholar, EMBASE, JSTOR WHOLIS and Web of Science databases as well other grey literature sources such as USAID, and PAHO. The following search terms were used: malaria, Haiti, Anopheles, and vector control. Results A total of 132 references were identified with 40 high quality references deemed relevant and included in this review. Six references dealt with mosquito distribution, seven with larval mosquito ecology, 16 with adult mosquito ecology, three with entomological indicators of malaria transmission, eight with insecticide resistance, one with sero-epidemiology and 16 with vector control. In the last 15 years (2000–2015), there have only been four published papers and three-scientific meeting abstracts on entomology for malaria in Haiti. Overall, the general literature on malaria vector research in Haiti is limited and dated. Discussion Entomological information generated from past studies in Haiti will contribute to the development of strategies to achieve malaria elimination on Hispaniola. However it is of paramount importance that malaria vector research in Haiti is updated to inform decision-making for vector control strategies in support of malaria elimination.