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This paper reports the prevalence and intensity of soil-transmitted helminth (STH) infections measured in Zimbabwe before and after a control intervention based on annual deworming of school-age children (SAC) conducted from 2012 to 2018. In 2010, epidemiological data were collected from 13 195 SAC in 255 randomly selected schools in all districts nationwide using, as diagnostic methods, the Kato–Katz and the formal ether stool concentration technique. At follow up, conducted in 2017, only Kato–Katz was performed; specimens were collected from 13 352 children in 336 schools. The data were evaluated using a geospatial approach. The national prevalence of STH infection in SAC was estimated at 5.8% at baseline, with 0.8% of infections of moderate and heavy intensity. Preventive chemotherapy (PC) targeted all 2.5 million children of school age enrolled in Zimbabwe, with coverage ranging from 49% to 85%. At follow up, national prevalence of STH in SAC was estimated at 0.8%; infections of moderate and heavy intensity almost disappeared (0.1% prevalence). As a result, Zimbabwe can suspend deworming activities in 54 districts and reduce the frequency of PC in the remaining six districts. The total amount of albendazole tablets needed will be approximately 100 000 a year., Author summary We analysed the impact of 6 years of preventive chemotherapy intervention by the Ministry of Health and Child Care of Zimbabwe (MoHCC) to control STH infections in Zimbabwe. We applied a geostatistical method to analyse the epidemiological data before and after the intervention. The results are interesting because they demonstrate a complete elimination of infection of moderate heavy intensity (that are considered the ones causing most of STH morbidity and a drastic reduction in prevalence that entails an estimated reduction of 90% in the need for anthelminthic medicines to maintain the situation and a consequent reduction in programme costs.

Introduction During the 2014 Ebola Virus Disease (EVD) epidemic, the Ebola-Tx trial evaluated the use of convalescent plasma (CP) in Guinea. The effectiveness of plasmapheresis trials depends on the recruitment of plasma donors. This paper describes what motivated or deterred EVD survivors to donate CP, providing insights for future plasmapheresis trials and epidemic preparedness. Methods This qualitative study, part of Ebola-Tx, researched and addressed emergent trial difficulties through interviewing, participant observation and focus group discussions. Sampling was theoretical and retroductive analysis was done in NVivo 10. Results Willingness or hesitance to participate in plasma donation depended on factors at the interface of pre-existing social dynamics; the impact of the disease and the consequent emergency response including the trial set-up. For volunteers, motivation to donate was mainly related to the feeling of social responsibility inspired by having survived EVD and to positive perceptions of plasmapheresis technology despite still unknown trial outcomes. Conversely, confidentiality concerns when volunteering due to stigmatization of survivors and perceived decrease in vital strength and in antibodies when donating, leading to fears of loss in protection against EVD, were main deterrents. The dynamic (dis)trust in Ebola Response Actors and in other survivors further determined willingness to participate and lead to the emergence/decline of rumours related to blood stealing and treatment effectiveness. Historic inter-ethnic relations in the health care setting further defined volunteering along socio-economic and ethnic lines. Finally, lack of follow-up and of dedicated care further impacted on motivation to volunteer. Conclusions Ebola-Tx was the first trial to solicit and evaluate blood-product donation as an experimental treatment on a large scale in Sub-Saharan Africa. An effective donation system requires directly engaging with emergent social barriers and providing an effective ethical response, including improved and transparent communication, effective follow-up after donation, assuring confidentiality and determining ethical incentives., Author summary During the 2014 West-African Ebola Virus Disease epidemic, the Ebola-Tx clinical trial in Guinea aimed to determine whether the administration of Ebola antibodies from the blood plasma of Ebola survivors could increase Ebola patients’ survival rate. Ebola-Tx was the first trial to solicit and evaluate blood-product donation as an experimental treatment on a large scale in Sub-Saharan Africa. In this qualitative study, part of the Ebola-Tx study, we report on factors of motivation and demotivation influencing Ebola survivors to donate their plasma. Understanding these factors is essential as the successful recruitment of this specific subgroup, providing the therapy itself, directly impacts the effectiveness of such a trial. We show that organizing an effective and ethical donation system requires directly engaging with emerging social barriers at the interface between pre-existing social dynamics, the impact of the disease, and the consequent emergency response including the trial set-up. These results provide insights that can be useful for future plasma trials but also for emergency clinical trials as part of general epidemic preparedness.

Introduction Individuals and communities affected by NTDs are often the poorest and most marginalised; ensuring a gender and equity lens is centre stage will be critical for the NTD community to reach elimination goals and inform Universal Health Coverage (UHC). NTDs amenable to preventive chemotherapy have been described as a ‘litmus test’ for UHC due to the high mass drug administration (MDA) coverage rates needed to be effective and their model of community engagement. However, until now highly aggregated coverage data may have masked inequities in availability, accessibility and acceptability of medicines, slowing down the equitable achievement of elimination goals. Methods We conducted qualitative programmatic analysis across different country contexts through the novel application of the Tanahashi Coverage Framework enhanced by gendered intersectional theory to interrogate different components of programme coverage: availability, accessibility, acceptability, contact and effective. Drawing on communities and health implementers perspectives (using focus groups, interviews, and participatory methods) from varying levels of the health system, across four African country contexts (Cameroon, Ghana, Liberia and Nigeria), we show who is left behind and provide recommendations for programmes to respond. Findings We have unmasked inequities in programme delivery that repeatedly leave vulnerable populations underserved in relation to the prevention and treatment of PC NTDs across all components of coverage explored within the Tanahashi framework. Inequities are influenced by health systems challenges and limitations, due to lack of consideration of gender, power and equity issues. Effective treatment for individuals and communities is shaped by individual identities and the intersecting axes of inequity that converge to shape these positions including gender, age, disability, and geography. Health systems are inherently social and gendered thus they become mediators in managing the impact that social and structural processes have on individual health outcomes. Significance To our knowledge this is the only paper which has combined a comprehensive equity framework with intersectional feminist theory, to establish a fuller understanding of who is left behind and why in MDA across countries and contexts. Ensuring the most vulnerable have continued access to future treatment options will contribute to the progressive realisation of UHC, allowing the NTD community to continue to support their vision of being a true ‘litmus test’., Author summary Individuals and communities affected by Neglected Tropical Diseases (NTDs) are often the poorest and most marginalised. Some NTDs (lymphatic filariasis, onchocerciasis, soil transmitted helminths, schistosomiasis and trachoma) have been given specific targets for control and elimination by the year 2020. Reaching these goals is important for the attainment of Universal Health Coverage (UHC) as well as the Sustainable Development Goals and has been described as a litmus test. However, few studies have considered how fair progress toward attainment of these goals has been to date. We used qualitative research methods to explore the equity of progress toward these targets across four countries (Ghana, Cameroon, Liberia and Ghana). We used a framework for assessing health services coverage (The Tanahashi Framework) and combined it with gendered intersectional theory (a theory that helps us think about how individuals position of power and privilege shape their experience) to understand who is left behind and why in NTD programme delivery. We found that health systems challenges and limitations due to lack of consideration of gender and equity issues have left vulnerable populations underserved in relation to the prevention and treatment of PC NTDs. Key steps need to be taken at different health system levels to ensure the most vulnerable have continued access to future treatment options. This will contribute to the attainment of UHC, allowing the NTD community to continue to support their vision of being a true ‘litmus test’.

This paper presents the development of an agent-based model (ABM) to investigate Trypanosoma brucei rhodesiense human African trypanosomiasis (rHAT) disease transmission. The ABM model, fitted at a fine spatial scale, was used to explore the impact of a growing host population on the spread of disease along a 75 km transect in the Luangwa Valley, Zambia. The model was used to gain a greater understanding of how increases in human and domestic animal population could impact the contact network between vector and host, the subsequent transmission patterns, and disease incidence outcomes in the region. Modelled incidence rates showed increases in rHAT transmission in both humans and cattle. The primary demographic attribution of infection switched dramatically from young children of both sexes attending school, to adult women performing activities with shorter but more frequent trips, such as water and firewood collection, with men more protected due to the presence of cattle in their routines. The interpretation of model output provides a plausible insight into both population development and disease transmission in the near future in the region and such techniques could aid well-targeted mitigation strategies in the future., Author summary African trypanosomiasis is a parasitic disease which affects humans and other animals in 36 sub-Saharan African countries. The disease is transmitted by the tsetse fly, and the human form of the disease is known as sleeping sickness. With human and animal populations growing across Africa, demand for space to settle is on the rise, and people are being forced to occupy increasingly marginal spaces. This behaviour has the potential to increase exposure to pre-existing biological hazards, including vector-borne diseases. This investigation utilises agent-based modelling techniques to investigate the implications of a growing and spreading human and animal population in a region affected by Rhodesian human African trypanosomiasis. The model incorporates previously developed spatial data for the Luangwa Valley case study in Zambia, along with demographic data for its current inhabitants, and a detailed, seasonally-driven tsetse lifecycle. Tsetse and potential human and animal hosts are modelled at the individual level, allowing each contact and infection to be recorded through time. By modelling at a fine-scale, we can incorporate detailed mechanisms for tsetse birth, feeding, reproduction and death, as well as a realistic theoretical human and domestic animal population increase, before considering the possible spatial and demographic impact.

Background The goal of the global lymphatic filariasis (LF) program is to eliminate the disease as a public health problem by the year 2020. The WHO mapping protocol that is used to identify endemic areas in need of mass drug administration (MDA) uses convenience-based sampling. This rapid mapping has allowed the global program to dramatically scale up treatment, but as the program approaches its elimination goal, it is important to ensure that all endemic areas have been identified and have received MDA. In low transmission settings, the WHO mapping protocol for LF mapping has several limitations. To correctly identify the LF endemicity of woredas, a new confirmatory mapping tool was developed to test older school children for circulating filarial antigen (CFA) in settings where it is uncertain. Ethiopia is the first country to implement this new tool. In this paper, we present the Ethiopian experience of implementing the new confirmatory mapping tool and discuss the implications of the results for the LF program in Ethiopia and globally. Methods Confirmatory LF mapping was conducted in 1,191 schools in 45 woredas, the implementation unit in Ethiopia, in the regions of Tigray, Amhara, Oromia, SNNP, Afar and Harari, where the results of previous mapping for LF using the current WHO protocol indicated that LF endemicity was uncertain. Within each woreda schools were selected using either cluster or systematic sampling. From selected schools, a total of 18,254 children were tested for circulating filarial antigen (CFA) using the immuno-chromatographic test (ICT). Results Of the 18,254 children in 45 woredas who participated in the survey, 28 (0.16%) in 9 woredas tested CFA positive. According to the confirmatory mapping threshold, which is ≥2% CFA in children 9–14 years of age, only 3 woredas out of the total 45 had more CFA positive results than the threshold and thus were confirmed to be endemic; the remaining 42 woredas were declared non-endemic. These results drastically decreased the estimated total population living in LF-endemic woredas in Ethiopia and in need of MDA by 49.1%, from 11,580,010 to 5,893,309. Conclusion This study demonstrated that the new confirmatory mapping tool for LF can benefit national LF programs by generating information that not only can confirm where LF is endemic, but also can save time and resources by preventing MDA where there is no evidence of ongoing LF transmission., Author summary Lymphatic filariasis (LF) is a mosquito-borne parasitic disease, caused by 3 nematode parasites, Wuchereria bancrofti, Brugia malayi and Brugia timori. The aim of the Global Program to Eliminate LF (GPELF) is to interrupt LF transmission through mass drug administration (MDA) by 2020 and to alleviate the suffering of affected people. Mapping is the first programmatic step to determining areas of LF endemicity and establishing a national program. Ethiopia was believed to be endemic for LF, but until recently the distribution of LF in the country was unknown. From 2008–2013, mapping for LF was conducted using the current WHO protocol, and 112 woredas were identified as endemic or possibly endemic. In 45 of these 112 woredas, only a single CFA positive result was found (

Introduction The CDTI model is known to have enhanced community participation in planning and resource mobilization toward the control of onchocerciasis. These effects were expected to translate into better individual acceptance of the intervention and hence high Treatment Coverage, leading to a sustainable community-led strategy and reduction in the disease burden. A survey revealed that after 10–12 rounds of treatment, prevalence of onchocerciasis was still high in three drainage basins of South West Cameroon and transmission was going on. Methods We designed a three (3)-year retrospective (2012, 2013 and 2014), descriptive cross-sectional study to explore the roles of operational challenges in the failure of CDTI to control the disease as expected. We administered 83 semi-structured questionnaires and conducted 12 in-depth interviews with Chiefs of Bureau Health, Chiefs of Centers, CDDs and Community Heads. Descriptive statistics was used to explore indicators of performance which were supported with views from in-depth interviews. Results We found that community participation was weak; communities were not deciding time and mode of distributions. Only 6 (15.0%) of 40 Community Drug Distributors reported they were selected at general community meetings as required. The health service was not able to meet and discuss Community-Directed Treatment with Ivermectin activities with individual communities partly due to transportation challenges; this was mostly done through letters. Funding was reported to be inadequate and not timely. Funds were not available to conduct Community-Self Monitoring after the 2014 Mass Drug Administration. There was inadequate health staff at the frontline health facility levels, and some Chiefs of Center reported that Community-Directed Treatment with Ivermectin work was too much for them. The mean operational Community Drug Distributor-population ratio was 1 Community Drug Distributor per 317 populations (range: 194–464, expected is 1:250). Community Drug Distributor attrition rate was 14% (2012), 11% (2013) and 12% (2014) of total Community Drug Distributors trained in the region. Lack of incentive for Community Drug Distributor was primary reason for Community Drug Distributor attrition. Number of Community Drug Distributors trained together by health area ranged from 14 to 127 (mean ± SD = 51 ±32) with duration of training ranging from 4–7 hours (mean ± SD = 5.05 ± 1.09). The trainings were conducted at the health centers. Community Drug Distributors always conducted census during the past three distributions (Mean ± SD = 2.85 ± 0.58). Community-Self Monitoring was facing challenge. Several of the community heads, Chiefs of Bureau Health and Chiefs of Center agreed that Community-Self Monitoring was not being carried out effectively due to lack of incentives for monitors in the communities. Conclusion Inadequate human resource, funding issues and transportation challenges during distribution periods reduced the ability of the health service to thoroughly sensitize communities and supervise CDTI activities. This resulted in weak community understanding, acceptance and participation in the process. CDTI in our study area did not achieve sustainable community-led campaign and this may have led to the reduced impact on Onchocerciasis., Author summary River blindness is caused by a very tiny, thread-like worm. The disease is better controlled when affected communities are included in the planning and carrying out of distribution of Ivermectin used to treat the disease. For a community to be able to prevent people from getting this disease, members must take Ivermectin once or twice a year, continuously for about 20 years. Hence, the organization in charge of controlling river blindness (African Programme for Onchocerciasis Control–APOC) decided that when a control programme is started in a community, the community must be involved and assisted to take full charge of the programme so that within 12 years the community can sustain the distribution of Ivermectin for as long as necessary. This community directed strategy prevented river blindness in many communities. However, after 10–12 years of implementation, studies found that river blindness largely persists in communities in three drainage basins in South West Region of Cameroon. This paper discussed the operational challenges that the programme may have faced in these areas.

Background Uganda has reported five (5) Ebola virus disease outbreaks and three (3) Marburg virus disease outbreaks from 2000 to 2016. Peoples’ knowledge and attitude towards Ebola and Marburg virus disease impact on control and prevention measures especially during outbreaks. We describe knowledge and attitude towards Ebola and Marburg virus outbreaks in two affected communities in Uganda to inform future outbreak responses and help in the design of health education and communication messages. Methods The study was a community survey done in Luweero, Ibanda and Kamwenge districts that have experienced outbreaks of Ebola and Marburg virus diseases. Quantitative data were collected using a structured questionnaire and triangulated with qualitative participatory epidemiology techniques to gain a communities’ knowledge and attitude towards Ebola and Marburg virus disease. Results Out of 740 respondents, 48.5% (359/740) were categorized as being knowledgeable about Ebola and Marburg virus diseases, whereas 60.5% (448/740) were having a positive attitude towards control and prevention of Ebola and Marburg virus diseases. The mean knowledge and attitude percentage scores were 54.3 (SD = 23.5, 95%CI = 52.6–56.0) and 69.9 (SD = 16.9, 95%CI = 68.9–71.1) respectively. People educated beyond primary school were more likely to be knowledgeable about Ebola and Marburg virus disease than those who did not attain any formal education (OR = 3.6, 95%CI = 2.1–6.1). Qualitative data revealed that communities describe Ebola and Marburg virus diseases as very severe diseases with no cure and they believe the diseases spread so fast. Respondents reported fear and stigma suffered by survivors, their families and the broader community due to these diseases. Conclusion Communities in Uganda affected by filovirus outbreaks have moderate knowledge about these diseases and have a positive attitude towards practices to prevent and control Ebola and Marburg viral diseases. The public health sector should enhance this community knowledge gap to empower them more by supplying educational materials for epidemic preparedness in future using appropriate communication channels as proposed by the communities., Author summary Ebola Virus Disease (EVD) and Marburg Virus Disease (MVD) are caused by a family of viruses known as Filoviruses. When they occur, they cause high lethality among infected people, which causes panic to the population, as well as interfering with the health care delivery system, especially in developing countries. Usually, at the beginning of these infections, the affected communities tend to think that witchcraft or some bad luck has befallen their community. Because of limited knowledge about these diseases, it becomes hard for local authorities to institute control and prevention measures. We administered a questionnaire to individual participants and held focus group discussions to help us tease out the communities’ understanding of these diseases. We found that people have moderate knowledge about EVD and MVD, and a positive attitude towards the prevention and control measures instituted by health authorities in Uganda. However, they still reported stigma subjected to the survivors of these diseases and affected families at large. EVD still causes much fear which drives some of the irrational actions by communities during outbreaks. Communities highlighted early sensitization as a means of controlling outbreaks. We recommend the findings in this paper to public health authorities in epidemic-prone countries like Uganda to aid in control and epidemic preparedness of filovirus outbreaks.

Background Mycobacterium ulcerans infection, commonly known as Buruli ulcer (BU), is a debilitating neglected tropical disease. Its management remains complex and has three main components: antibiotic treatment combining rifampicin and streptomycin for 56 days, wound dressings and skin grafts for large ulcerations, and physical therapy to prevent functional limitations after care. In Benin, BU patient care is being integrated into the government health system. In this paper, we report on an innovative pilot program designed to introduce BU decentralization in Ouinhi district, one of Benin’s most endemic districts previously served by centralized hospital-based care. Methodology/Principal findings We conducted intervention-oriented research implemented in four steps: baseline study, training of health district clinical staff, outreach education, outcome and impact assessments. Study results demonstrated that early BU lesions (71% of all detected cases) could be treated in the community following outreach education, and that most of the afflicted were willing to accept decentralized treatment. Ninety-three percent were successfully treated with antibiotics alone. The impact evaluation found that community confidence in decentralized BU care was greatly enhanced by clinic staff who came to be seen as having expertise in the care of most chronic wounds. Conclusions/Significance This study documents a successful BU outreach and decentralized care program reaching early BU cases not previously treated by a proactive centralized BU program. The pilot program further demonstrates the added value of integrated wound management for NTD control., Author summary The management of Buruli ulcer (BU) is complex, resulting in high costs to families and health systems. Early detection and treatment heals lesions without functional limitations. Decentralization of the management of this disease into the peripheral health system remains a challenge for national control programs. We report here on an innovative pilot intervention of decentralization of the management of BU in one of the most BU-endemic districts in Benin. The intervention was preceded by a culturally sensitive outreach campaign, which explained the disease’s symptoms and treatment options, and increased self-referral. It also included the treatment of all chronic ulcers free of charge. While serious cases of BU were still referred to the reference hospital for treatment, study results showed that 71% of BU cases could be treated in decentralized care; of these, 93% were successfully treated without functional limitations with antibiotics alone. The decentralized treatment option brought in new cases not previously treated by a proactive centralized BU program, and maintained total patient adherence to treatment protocols, in part through the support of community volunteer groups. The model developed in this pilot study may serve as the foundation and proof of concept for a larger community-based decentralized wound care agenda.

Background Contact tracing is one of the key response activities necessary for halting Ebola Virus Disease (EVD) transmission. Key elements of contact tracing include identification of persons who have been in contact with confirmed EVD cases and careful monitoring for EVD symptoms, but the details of implementation likely influence their effectiveness. In November 2015, several months after a major Ebola outbreak was controlled in Liberia, three members of a family were confirmed positive for EVD in the Duport Road area of Monrovia. The cluster provided an opportunity to implement and evaluate modified approaches to contact tracing. Methods The approaches employed for improved contact tracing included classification and risk-based management of identified contacts (including facility based isolation of some high risk contacts, provision of support to persons being monitored, and school-based surveillance for some persons with potential exposure but not listed as contacts), use of phone records to help locate missing contacts, and modifications to data management tools. We recorded details about the implementation of these approaches, report the overall outcomes of the contact tracing efforts and the challenges encountered, and provide recommendations for management of future outbreaks. Results 165 contacts were identified (with over 150 identified within 48 hours of confirmation of the EVD cases) and all initially missing contacts were located. Contacts were closely monitored and promptly tested if symptomatic; no contacts developed disease. Encountered challenges related to knowledge gaps among contact tracing staff, data management, and coordination of contact tracing activities with efforts to offer Ebola vaccine. Conclusions The Duport Road EVD cluster was promptly controlled. Missing contacts were effectively identified, and identified contacts were effectively monitored and rapidly tested. There is a persistent risk of EVD reemergence in Liberia; the experience controlling each cluster can help inform future Ebola control efforts in Liberia and elsewhere., Author summary Contact tracing is one of the key response actions necessary for controlling spread of Ebola Virus Disease (EVD). Contact tracing is comprised of several different activities: identification of persons who have been in contact with confirmed EVD cases, close monitoring contacts for EVD symptoms, and management of symptomatic persons. Closely monitoring contacts of confirmed EVD cases allows for the rapid identification of symptomatic individuals, which in turn facilitates early testing, medical intervention, and isolation of new cases. This reduces the possibility of the continued spread of the virus within communities. Delayed and ineffective contact tracing contributed to the extensive transmission of EVD during the 2014–2015 outbreak in West Africa. Clusters of EVD reemergence are likely to occur, therefore understanding and addressing the challenges of implementing and managing contact tracing remains essential to halting transmission and minimizing morbidity and mortality associated with EVD. This paper assessed the contact tracing activities in response to EVD reemergence to identify best practices for responses to future Ebola clusters. The work is also applicable to contact tracing for other infectious diseases.

During the large Ebola outbreak that affected West Africa in 2014 and 2015, studies were launched to evaluate potential treatments for the disease. A clinical trial to evaluate the effectiveness of the antiviral drug favipiravir was conducted in Guinea. This paper describes the main challenges of the implementation of the trial in the Ebola treatment center of Guéckédou. Following the principles of the Good Clinical Research Practices, we explored the aspects of the community's communication and engagement, ethical conduct, trial protocol compliance, informed consent of participants, ongoing benefit/risk assessment, record keeping, confidentiality of patients and study data, and roles and responsibilities of the actors involved. We concluded that several challenges have to be addressed to successfully implement a clinical trial during an international medical emergency but that the potential for collaboration between research teams and humanitarian organizations needs to be highlighted. ispartof: PLoS Neglected Tropical Diseases vol:11 issue:6 ispartof: location:United States status: published

Background Yaws is an infectious, debilitating and disfiguring disease of poverty that mainly affects children in rural communities in tropical areas. In Cameroon, mass-treatment campaigns carried out in the 1950s reduced yaws to such low levels that it was presumed the disease was eradicated. In 2010, an epidemiological study in Bankim Health District detected 29 cases of yaws. Five different means of detecting yaws in clinical and community settings were initiated in Bankim over the following five years. Methodology This observational study reviews data on the number of cases of yaws identified by each of the five yaws detection approaches: 1) passive yaws detection at local clinics after staff attended Neglected Tropical Disease awareness workshops, 2) community-based case detection carried out in remote communities by hospital staff who relied on community health workers to identify cases, 3) yaws screening following mass Buruli Ulcer outreach programs being piloted in the district, 4) school-based screening programs conducted as stand-alone and follow-up activities to mass outreach events, and 5) house to house active surveillance activities conducted in thirty-eight communities. Implementation of each of the four community-based approaches was observed by a team of health social scientists tasked with assessing the strengths and limitations of each detection method. Findings Eight hundred and fifteen cases of yaws were detected between 2012 and 2015. Only 7% were detected at local clinics. Small outreach programs and household surveys detected yaws in a broad spectrum of communities. The most successful means of yaws detection, accounting for over 70% of cases identified, were mass outreach programs and school based screenings in communities where yaws was detected. Conclusion The five interventions for detecting yaws had a synergistic effect and proved to be valuable components of a yaws eradication program. Well planned, culturally sensitive mass outreach educational programs accompanied by school-based programs proved to be particularly effective in Bankim. Including yaws detection in a Buruli Ulcer outreach program constituted a win-win situation, as the demonstration effect of yaws treatment (rapid cure) increased confidence in early Buruli ulcer treatment. Mass outreach programs functioned as magnets for both diseases as well as other kinds of chronic wounds that future outreach programs need to address., Author summary Yaws is an infectious and disfiguring disease of poverty primarily affecting children in rural communities in tropical areas. Yaws is easily treated by a single dose of antibiotics and is on the World Health Organization’s eradication list. Yaws was thought eradicated in the Cameroon in the 1950s following aggressive mass-treatment campaigns. In 2010, epidemiological research revealed a resurgence of the disease. This paper discusses the relative success of five different means of detecting yaws in rural areas of Bankim District between 2012 and 2015. While few cases of yaws were detected at local clinics during this time, many cases were detected in the community. The most successful means of detecting yaws were mass outreach programs designed to educate the public about neglected tropical diseases found in the region, and follow up school-based screening programs. These programs were supported by local chiefs and traditional healers and found to be the best way of increasing community awareness about yaws, motivating community health workers to participate in outreach, and fostering trust in the free medical treatment being provided.

Background Onchocerciasis is targeted for elimination in Africa through annual or biannual ivermectin mass drug administration (MDA). An immunodiagnostic test, based on the detection of human IgG4 antibodies in the blood to the Onchocerca volvulus-specific antigen Ov16, is one of the recommended tools for determining whether transmission is interrupted and mass treatment can stop. For different transmission settings, the relationship between post-MDA Ov16 antibody prevalence in children (measured 1 year after the last round of MDA) and the duration and coverage of MDA, the mf prevalence in the population, and the probability that onchocerciasis is eventually eliminated is explored through mathematical modelling. Methodology The ONCHOSIM model was extended with new output on the Ov16 antibody serostatus of individuals. Seroconversion was assumed to be triggered by the first worm establishing in the host, with seroconversion occurring either before maturation, after maturation or only after the start of mf production. We are mainly interested in seroconversion rates in children, and for now ignore the possibility of seroreversion to simplify the model. Principal findings Yearly repeated MDA leads to a strong reduction in the parasite acquisition rate in humans. This reduces the seroconversion rate in newborns and young children, while those who seroconverted before the start of control remain antibody positive. Both the microfiladermia prevalence in the population aged 5 years and above and the Ov16 antibody prevalence in children under 10 declined with increasing duration of MDA. The association between either of these indicators and the model-predicted probability of elimination was not influenced much by the assumed treatment coverage levels, but was found to depend on baseline endemicity levels, assumptions regarding the trigger of seroconversion, and diagnostic test characteristics (sensitivity and specificity). Conclusions Better understanding of the dynamics of Ov16 antibody responses is required for accurate interpretation of seroprevalence data and more precise estimation of endpoint for MDA. Our study demonstrates that this endpoint will be dependent on baseline endemicity levels, which should be taken into account in guidelines for defining when to stop MDA., Author Summary Onchocerciasis is targeted for elimination in Africa through annual or biannual ivermectin mass drug administration. The elimination target places high demands on monitoring and evaluation systems, for timely detection of ongoing transmission and possible recrudescence. Guidelines recommend using serological evaluation by Ov16, to determine the presence of IgG4 antibodies to the antigen Ov16 in children of less than 10 years in order to detect exposure to the O. volvulus parasite. In this paper, we use the mathematical model ONCHOSIM to explore how the post-MDA Ov16 antibody prevalence in children (measured 1 year after the last round of MDA) is related to local transmission conditions, observed trends in infection during mass drug administration the duration and coverage of mass treatment, test characteristics, mf prevalence and likelihood of interruption of transmission. The level of seroprevalence that is indicative of successful elimination was found to depend on local transmission conditions. This should be considered in survey methodology and criteria for defining whether mass drug administration can safely be interrupted. Remaining uncertainties about the dynamics of seroconversion and seroreversion further complicate the interpretation of seroprevalence data and the definition of thresholds.

Introduction The Global Strategy to Eliminate Lymphatic Filiariasis (GFELF) through Mass Drug Administration (MDA) has been implemented in Ghana since the year 2000 and transmission has been interrupted in 76 of 98 endemic districts. To improve the MDA in the remaining districts with microfilaria (MF) prevalence above the 1% threshold for the interruption of transmission, there is a need to identify and implement appropriate quality improvement (QI) strategies. This paper describes the use of intervention mapping to select QI strategies to improve an existing evidence-based MDA program in Northern Ghana. Methods Due to the complexities associated with implementing evidence-based programs (EBP) such as the lymphatic filariasis MDA and variability in the context, an initial assessment to identify implementation bottlenecks associated with the quality of implementation of lymphatic filariasis MDA in the Bole District of Ghana was conducted using a mixed methods approach. Based on the findings of the initial assessment, a context specific QI strategy was designed and operationalized using intervention mapping strategy in terms of seven domains: actor, the action, action targets, temporality, dose, implementation outcomes addressed, and theoretical justification. Results The initial needs assessment shows that the persistent transmission of lymphatic filariasis in the Bole District is characterized by high levels of refusal to ingest the drug, high levels of reported adverse drug reactions, low MDA coverage at community level, poor adherence to the MDA protocol and non-participants’ responsiveness. Conclusion This study has shown that it is feasible to develop a context specific QI strategy for an existing evidence-based intervention based on an initial needs assessment through stakeholder participation using the IM approach. However, working (towards) QI requires more time than is usually available in public health service. Sufficient theoretical knowledge of implementation research and experience with technical IM experts must be available., Author summary Lymphatic Filariasis is a significant health problem threatening 1.1 billion people in 55 countries globally. After 18 years of implementing MDA in Ghana, LF transmission still persist in some districts with microfilaria prevalence level high above the threshold needed for the interruption of transmission of the disease. For Ghana to meet the 2020 NTDs deadline, it is important to identify context specific need-based QI strategies to make the drug accessible to all eligible individuals in the endemic communities. Hence, this study has demonstrated the feasibility of using IM to develop and implement a context specific QI strategy for an existing evidence-based intervention (LF MDA) towards elimination of lymphatic filariasis as a public health challenge in Bole District of Northern Ghana.

Background Human African trypanosomiasis (HAT) is a neglected tropical disease targeted for elimination ‘as a public health problem’ by 2020. The indicators to monitor progress towards the target are based on the number of reported cases, the related areas and populations exposed at various levels of risk, and the coverage of surveillance activities. Based on data provided by the National Sleeping Sickness Control Programmes (NSSCP), Non-Governmental Organizations (NGOs) and research institutions—and assembled in the Atlas of HAT—the World Health Organization (WHO) provides here an update to 2016 for these indicators, as well as an analysis of the epidemiological situation. Results Trends for the two primary indicators of elimination are on track for the 2020 goal: 2,164 cases of HAT were reported in 2016 (as compared to the milestone of 4,000 cases), and for the period 2012–2016 280,000 km2 are estimated to be at moderate risk or higher (i.e. ≥ 1 case/10,000 people/year), as compared to the milestone of 230,000 km2. These figures correspond to reductions of 92% and 61% as compared to the respective baselines (i.e. 26,550 HAT cases in the year 2000, and 709,000 km2 exposed at various levels of risk for the period 2000–2004). Among the secondary indicators, an overall improvement in the coverage of at risk populations by surveillance activities was observed. Regarding passive surveillance, the number of fixed health facilities providing gambiense HAT diagnosis or treatment expanded, with 1,338 enumerated in endemic countries in 2017 (+52% as compared to the survey completed only sixteen months earlier). Concerning rhodesiense HAT, 124 health facilities currently provide diagnosis or treatment. The broadening of passive surveillance is occurring in a context of fairly stable intensity of active case finding, with between 1.8 million and 2.4 million people screened per year over the period 2012–2016. Discussion Elimination of HAT as a public health problem by 2020 seems within reach, as the epidemiological trends observed in previous years are confirmed in this latest 2016 monitoring update. However, looking beyond 2020, and in particular to the 2030 goal of elimination of transmission as zero cases for the gambiense form of the disease only, there is no room for complacency. Challenges still abound, including ensuring the effective integration of HAT control activities in the health system, sustaining the commitment of donors and HAT endemic countries, and clarifying the extent of the threat posed by cryptic reservoirs (e.g. human asymptomatic carriers and the possible animal reservoirs in gambiense HAT epidemiology). WHO provides through the network for HAT elimination the essential coordination of the wide range of stakeholders to ensure synergy of efforts., Author summary Human African trypanosomiasis (HAT), also known as sleeping sickness, is a rare disease today, but throughout the 20th century it has demonstrated its potential for devastating epidemics. Over the last twenty years, substantial efforts against HAT enabled to dramatically reduce its prevalence, and the disease is now targeted for elimination by the World Health Organization (WHO). In this paper we provide an update to 2016 of the epidemiological situation, focusing on the number of reported cases, the areas and populations exposed at various levels of risk, and the coverage and intensity of surveillance activities. The trends show that attaining the 2020 target of elimination as a public health problem is within reach, with 2,164 reported cases in 2016 (as compared to the targeted milestone for the same year of 4,000 cases), and with an improved coverage of at risk populations by surveillance activities. Beyond 2020, achieving elimination of transmission for the gambiense form of the disease (targeted for 2030) will be more challenging, and it will require the sustained commitment of HAT endemic countries and donors, the adoption of innovative disease control approaches, and the coordination of a broad range of stakeholders.

Together, the Hajj and Umrah rank among the leading global venues that host annual mass human migrations. The Hajj is an annual pilgrimage to the Islamic holy city of Makkah in Saudi Arabia (Fig 1). It is considered a religious obligation for all adult Muslims worldwide who have the physical and financial ability and draws an estimated 2–3 million people annually [1]. Umrah is an Islamic pilgrimage to Makkah, which occurs at times other than the period of the Hajj—the period of Ramadan (fasting month) is considered the peak period [2]. In 2018, the Hajj is scheduled to take place in August, while Ramadan will occur between May and June [2]. Open in a separate window Fig 1 Outline map of Saudi Arabia and surrounding countries. The capital Riyadh, the two holy cities Makkah and Medina, and other cities mentioned in this paper are shown. Original figure.

Background Conducting clinical trials to assess experimental treatments for potentially pandemic infectious diseases is challenging. Since many outbreaks of infectious diseases last only six to eight weeks, there is a need for trial designs that can be implemented rapidly in the face of uncertainty. Outbreaks are sudden and unpredictable and so it is essential that as much planning as possible takes place in advance. Statistical aspects of such trial designs should be evaluated and discussed in readiness for implementation. Methodology/Principal findings This paper proposes a generic ordinal sequential trial design (GOST) for a randomised clinical trial comparing an experimental treatment for an emerging infectious disease with standard care. The design is intended as an off-the-shelf, ready-to-use robust and flexible option. The primary endpoint is a categorisation of patient outcome according to an ordinal scale. A sequential approach is adopted, stopping as soon as it is clear that the experimental treatment has an advantage or that sufficient advantage is unlikely to be detected. The properties of the design are evaluated using large-sample theory and verified for moderate sized samples using simulation. The trial is powered to detect a generic clinically relevant difference: namely an odds ratio of 2 for better rather than worse outcomes. Total sample sizes (across both treatments) of between 150 and 300 patients prove to be adequate in many cases, but the precise value depends on both the magnitude of the treatment advantage and the nature of the ordinal scale. An advantage of the approach is that any erroneous assumptions made at the design stage about the proportion of patients falling into each outcome category have little effect on the error probabilities of the study, although they can lead to inaccurate forecasts of sample size. Conclusions/Significance It is important and feasible to pre-determine many of the statistical aspects of an efficient trial design in advance of a disease outbreak. The design can then be tailored to the specific disease under study once its nature is better understood., Author summary Since many outbreaks of infectious diseases last only six to eight weeks, there is a need for trial designs that can be implemented rapidly in the face of uncertainty. The Generic Ordinal Sequential Trial (GOST) is a flexible statistical design for a randomised clinical trial comparing an experimental treatment for an emerging infectious disease with standard care. The details of the design are derived to satisfy a generic power requirement using large sample theory. The accuracy of the approach for moderate sample sizes is then checked using million-fold simulations, and found to be very reliable under a wide range of circumstances. Total sample sizes (across both treatments) of between 150 and 300 patients prove to be adequate in many cases, although more patients may be needed if the majority of patients die or if the majority experience complete recovery, as there is then less evidence available to distinguish between treatments. An advantage of the approach is that any erroneous assumptions made at the design stage about the proportion of patients falling into each outcome category have little effect on the error probabilities of the study, although they can lead to inaccurate forecasts of sample size.

Palpalis group tsetse flies are the major vectors of human African trypanosomiasis, and visually-attractive targets and traps are important tools for their control. Considerable efforts are underway to optimise these visual baits, and one factor that has been investigated is coloration. Analyses of the link between visual bait coloration and tsetse fly catches have used methods which poorly replicate sensory processing in the fly visual system, but doing so would allow the visual information driving tsetse attraction to these baits to be more fully understood, and the reflectance spectra of candidate visual baits to be more completely analysed. Following methods well established for other species, I reanalyse the numbers of tsetse flies caught at visual baits based upon the calculated photoreceptor excitations elicited by those baits. I do this for large sets of previously published data for Glossina fuscipes fuscipes (Lindh et al. (2012). PLoS Negl Trop Dis 6: e1661), G. palpalis palpalis (Green (1988). Bull Ent Res 78: 591), and G. pallidipes (Green and Flint (1986). Bull Ent Res 76: 409). Tsetse attraction to visual baits in these studies can be explained by a colour opponent mechanism to which the UV-blue photoreceptor R7y contributes positively, and both the green-yellow photoreceptor R8y, and the low-wavelength UV photoreceptor R7p, contribute negatively. A tool for calculating fly photoreceptor excitations is made available with this paper, and this will facilitate a complete and biologically authentic description of visual bait reflectance spectra that can be employed in the search for more efficacious visual baits, or the analysis of future studies of tsetse fly attraction., Author Summary Tsetse flies transmit sleeping sickness (human African trypanosomiasis), and visually attractive targets and traps are important tools for the control of the flies and prevention of disease. Previous studies have tried to determine the best colour for visual baits by relating their light reflectance properties to their attractiveness to tsetse. However, these methods represent only part of the visual information captured by the fly's eye, which is encoded by five different types of photoreceptor with varying sensitivities to different wavelengths of light. I use established methods to calculate the excitation of each fly photoreceptor type by the visual baits used to catch tsetse flies in three previous field studies. This method more completely describes the visual information captured by the fly's eye. Tsetse fly attraction can then be largely explained by a comparison of the excitations of three different photoreceptor types within the fly's nervous system. This knowledge and approach will allow for the more complete quantification of visual bait reflectance spectra, so that more efficient bait materials can be identified and employed to control tsetse flies.

Background One root cause of the neglect of rabies is the lack of adequate diagnostic tests in the context of low income countries. A rapid, performance friendly and low cost method to detect rabies virus (RABV) in brain samples will contribute positively to surveillance and consequently to accurate data reporting, which is presently missing in the majority of rabies endemic countries. Methodology/Principal findings We evaluated a rapid immunodiagnostic test (RIDT) in comparison with the standard fluorescent antibody test (FAT) and confirmed the detection of the viral RNA by real time reverse transcription polymerase chain reaction (RT-qPCR). Our analysis is a multicentre approach to validate the performance of the RIDT in both a field laboratory (N’Djamena, Chad) and an international reference laboratory (Institut Pasteur, Paris, France). In the field laboratory, 48 samples from dogs were tested and in the reference laboratory setting, a total of 73 samples was tested, representing a wide diversity of RABV in terms of animal species tested (13 different species), geographical origin of isolates with special emphasis on Africa, and different phylogenetic clades. Under reference laboratory conditions, specificity was 93.3% and sensitivity was 95.3% compared to the gold standard FAT test. Under field laboratory conditions, the RIDT yielded a higher reliability than the FAT test particularly on fresh and decomposed samples. Viral RNA was later extracted directly from the test filter paper and further used successfully for sequencing and genotyping. Conclusion/Significance The RIDT shows excellent performance qualities both in regard to user friendliness and reliability of the result. In addition, the test cassettes can be used as a vehicle to ship viral RNA to reference laboratories for further laboratory confirmation of the diagnosis and for epidemiological investigations using nucleotide sequencing. The potential for satisfactory use in remote locations is therefore very high to improve the global knowledge of rabies epidemiology. However, we suggest some changes to the protocol, as well as careful further validation, before promotion and wider use., Author Summary The high fatality and burden of rabies stands in contrast to the very low performance of laboratory-based surveillance in resource-challenged countries. The absence of reliable human and animal rabies incidence data ultimately result in neglect of disease prevention and control and the perpetuation of RABV transmission despite the existence of powerful management tools. Rapid, easy to perform rabies diagnostic tests that do not require expensive equipment or special storage conditions, which can be reliably performed by trained ordinary veterinary professionals, are needed urgently for use in low income countries. Such novel methods will help to accurately assess the global rabies burden and are necessary to monitor rabies control and elimination. The present study evaluates the performance and reliability of a rapid, easy to use rabies diagnostic tool. Overall, the validated test was in high accordance with the standard reference method for the detection of RABV by immunofluorescence microscopy and showed even higher reliability when applied in resource poor laboratory conditions. The obtained results support the high potential for the use of this test in the field but suggest a change of the original technical protocol and a need for wider validation.

Konzo is a distinct neurological entity with selective upper motor neuron damage, characterized by an abrupt onset of an irreversible, non-progressive, and symmetrical spastic para/tetraparesis. Despite its severity, konzo remains a neglected disease. The disease is associated with high dietary cyanogen consumption from insufficiently processed roots of bitter cassava combined with a protein-deficient diet. Epidemics occur when these conditions coincide at times of severe food shortage. Up to 1993, outbreaks in poor rural areas in Africa contributed to more than 3,700 cases of konzo. The number of affected people is underestimated. From unofficial reports, the number of cases was estimated to be at least 100,000 in 2000, in contrast to the 6,788 cases reported up to 2009 from published papers.

Background Canine rabies causes many thousands of human deaths every year in Africa, and continues to increase throughout much of the continent. Methodology/Principal Findings This paper identifies four common reasons given for the lack of effective canine rabies control in Africa: (a) a low priority given for disease control as a result of lack of awareness of the rabies burden; (b) epidemiological constraints such as uncertainties about the required levels of vaccination coverage and the possibility of sustained cycles of infection in wildlife; (c) operational constraints including accessibility of dogs for vaccination and insufficient knowledge of dog population sizes for planning of vaccination campaigns; and (d) limited resources for implementation of rabies surveillance and control. We address each of these issues in turn, presenting data from field studies and modelling approaches used in Tanzania, including burden of disease evaluations, detailed epidemiological studies, operational data from vaccination campaigns in different demographic and ecological settings, and economic analyses of the cost-effectiveness of dog vaccination for human rabies prevention. Conclusions/Significance We conclude that there are no insurmountable problems to canine rabies control in most of Africa; that elimination of canine rabies is epidemiologically and practically feasible through mass vaccination of domestic dogs; and that domestic dog vaccination provides a cost-effective approach to the prevention and elimination of human rabies deaths., Author Summary Elimination of canine rabies has been achieved in some parts of the world, but the disease still kills many thousands of people each year in Africa. Here we counter common arguments given for the lack of effective canine rabies control in Africa presenting detailed data from a range of settings. We conclude that (1) rabies substantially affects public and animal health sectors, hence regional and national priorities for control ought to be higher, (2) for practical purposes domestic dogs are the sole maintenance hosts and main source of infection for humans throughout most of Africa and Asia and sufficient levels of vaccination coverage in domestic dog populations should lead to elimination of canine rabies in most areas, (3) the vast majority of domestic dog populations across sub-Saharan Africa are accessible for vaccination with community sensitization being of paramount importance for the success of these programs, (4) improved local capacity in rabies surveillance and diagnostics will help evaluate the impact of control and elimination efforts, and (5) sustainable resources for effective dog vaccination campaigns are likely to be available through the development of intersectoral financing schemes involving both medical and veterinary sectors.

Background The recent emergence of zoonotic diseases such as Highly Pathogenic Avian Influenza (HPAI) and Severe Acute Respiratory Syndrome (SARS) have contributed to dominant Global Health narratives around health securitisation and pandemic preparedness, calling for greater co-operation between the health, veterinary and environmental sectors in the ever-evolving One Health movement. A decade later, One Health advocates face increasing pressure to translate the approach from theory into action. Methodology/Principal Findings A qualitative case study methodology was used to examine the emerging relationships between international One Health dialogue and its practical implementation in the African health policy context. A series of Key Informant Interviews (n = 32) with policy makers, government officials and academics in Nigeria, Tanzania and Uganda are presented as three separate case studies. Each case examines a significant aspect of One Health operationalisation, framed around the control of both emerging and Neglected Zoonotic Diseases including HPAI, Human African Trypanosomiasis and rabies. The research found that while there is general enthusiasm and a strong affirmative argument for adoption of One Health approaches in Africa, identifying alternative contexts away from a narrow focus on pandemics will help broaden its appeal, particularly for national or regionally significant endemic and neglected diseases not usually addressed under a “global” remit. Conclusions/Significance There is no ‘one size fits all’ approach to achieving the intersectoral collaboration, significant resource mobilisation and political co-operation required to realise a One Health approach. Individual country requirements cannot be underestimated, dismissed or prescribed in a top down manner. This article contributes to the growing discussion regarding not whether One Health should be operationalised, but how this may be achieved., Author Summary The One Health movement requires more robust evidence around its practical implementation if it is to truly become a way forwards for addressing health issues at the human, animal and ecosystem interface. The research in this paper discusses some of the recent successes and challenges with both Emerging and Neglected zoonoses in the sub-Saharan Africa context. Through speaking to various human and animal health practitioners and policy makers in Uganda, Nigeria and Tanzania, the authors have created three case studies highlighting the various successes of the approach to date, but also clarifying areas where the approach will take longer to implement, often as a result of the wide institutional and policy changes required in many countries. The authors conclude that whilst the “goodwill” is certainly there, the reality of planning, executing and budgeting for joint interventions – particularly at the national or regional level – proves in many cases more difficult than first thought. It is hoped however that through gaining better insight from those charged with the decision-making in these countries, One Health practitioners will be encouraged to build on the momentum through addressing some of the issues that arise with its implementation.

Background West Nile virus is a mosquito-borne flavivirus which has been posing continuous challenges to public health worldwide due to the identification of new lineages and clades and its ability to invade and establish in an increasing number of countries. Its current distribution, genetic variability, ecology, and epidemiological pattern in the African continent are only partially known despite the general consensus on the urgency to obtain such information for quantifying the actual disease burden in Africa other than to predict future threats at global scale. Methodology and principal findings References were searched in PubMed and Google Scholar electronic databases on January 21, 2020, using selected keywords, without language and date restriction. Additional manual searches of reference list were carried out. Further references have been later added accordingly to experts’ opinion. We included 153 scientific papers published between 1940 and 2021. This review highlights: (i) the co-circulation of WNV-lineages 1, 2, and 8 in the African continent; (ii) the presence of diverse WNV competent vectors in Africa, mainly belonging to the Culex genus; (iii) the lack of vector competence studies for several other mosquito species found naturally infected with WNV in Africa; (iv) the need of more competence studies to be addressed on ticks; (iv) evidence of circulation of WNV among humans, animals and vectors in at least 28 Countries; (v) the lack of knowledge on the epidemiological situation of WNV for 19 Countries and (vii) the importance of carrying out specific serological surveys in order to avoid possible bias on WNV circulation in Africa. Conclusions This study provides the state of art on WNV investigation carried out in Africa, highlighting several knowledge gaps regarding i) the current WNV distribution and genetic diversity, ii) its ecology and transmission chains including the role of different arthropods and vertebrate species as competent reservoirs, and iii) the real disease burden for humans and animals. This review highlights the needs for further research and coordinated surveillance efforts on WNV in Africa., Author summary Since its discovery in the African continent in 1937, West Nile virus expansion and invasion into new regions represent a serious concern today for an increasing number of countries worldwide. Although about 80% of infected individuals are asymptomatic, this zoonotic virus is pathogenic for humans other than for some animal species, displaying a range of clinical manifestation spanning from influenza-like symptoms to severe neurological complication and death. This study provides an updated overview on the current knowledge of WNV epidemiology in each African country, summarizing available data on incidence of the infection in humans and animals, the circulating lineages and clades, other than an updated list of the principal arthropod vectors found naturally infected and the availability of vector competence studies. However, this review highlights also the lack of knowledge regarding the occurrence and intensity of circulation of WNV in many African countries. Therefore, considering the sensitivity of WNV transmission system to climate and other environmental changes, along with the increasing level of interconnections among continents due to globalization, the intensification of the research activities on WNV and a promotion of a coordinated surveillance actions across African and European countries would provide the information of utility for a better evaluation of the actual risk of WNV and disease burden at trans-continental scale.