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Background: Until recently, the Chagas disease vector, Triatoma infestans, was widespread in Arequipa, Perú, but as a result of a decades-long campaign in which over 70,000 houses were treated with insecticides, infestation prevalence is now greatly reduced. To monitor for T. infestans resurgence, the city is currently in a surveillance phase in which a sample of houses is selected for inspection each year. Despite extensive data from the control campaign that could be used to inform surveillance, the selection of houses to inspect is often carried out haphazardly or by convenience. Therefore, we asked, how can we enhance efforts toward preventing T. infestans resurgence by creating the opportunity for vector surveillance to be informed by data? Methodology/principal findings: To this end, we developed a mobile app that provides vector infestation risk maps generated with data from the control campaign run in a predictive model. The app is intended to enhance vector surveillance activities by giving inspectors the opportunity to incorporate the infestation risk information into their surveillance activities, but it does not dictate which houses to surveil. Therefore, a critical question becomes, will inspectors use the risk information? To answer this question, we ran a pilot study in which we compared surveillance using the app to the current practice (paper maps). We hypothesized that inspectors would use the risk information provided by the app, as measured by the frequency of higher risk houses visited, and qualitative analyses of inspector movement patterns in the field. We also compared the efficiency of both mediums to identify factors that might discourage risk information use. Over the course of ten days (five with each medium), 1,081 houses were visited using the paper maps, of which 366 (34%) were inspected, while 1,038 houses were visited using the app, with 401 (39%) inspected. Five out of eight inspectors (62.5%) visited more higher risk houses when using the app (Fisher’s exact test, p < 0.001). Among all inspectors, there was an upward shift in proportional visits to higher risk houses when using the app (Mantel-Haenszel test, common odds ratio (OR) = 2.42, 95% CI 2.00–2.92), and in a second analysis using generalized linear mixed models, app use increased the odds of visiting a higher risk house 2.73-fold (95% CI 2.24–3.32), suggesting that the risk information provided by the app was used by most inspectors. Qualitative analyses of inspector movement revealed indications of risk information use in seven out of eight (87.5%) inspectors. There was no difference between the app and paper maps in the number of houses visited (paired t-test, p = 0.67) or inspected (p = 0.17), suggesting that app use did not reduce surveillance efficiency. Conclusions/significance: Without staying vigilant to remaining and re-emerging vector foci following a vector control campaign, disease transmission eventually returns and progress achieved is reversed. Our results suggest that, when provided the opportunity, most inspectors will use risk information to direct their surveillance activities, at least over the short term. The study is an initial, but key, step toward evidence-based vector surveillance. [ABSTRACT FROM AUTHOR]

Background: Spatial modelling of STH and schistosomiasis epidemiology is now commonplace. Spatial epidemiological studies help inform decisions regarding the number of people at risk as well as the geographic areas that need to be targeted with mass drug administration; however, limited attention has been given to propagated uncertainties, their interpretation, and consequences for the mapped values. Using currently published literature on the spatial epidemiology of helminth infections we identified: (1) the main uncertainty sources, their definition and quantification and (2) how uncertainty is informative for STH programme managers and scientists working in this domain. Methodology/Principal Findings: We performed a systematic literature search using the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) protocol. We searched Web of Knowledge and PubMed using a combination of uncertainty, geographic and disease terms. A total of 73 papers fulfilled the inclusion criteria for the systematic review. Only 9% of the studies did not address any element of uncertainty, while 91% of studies quantified uncertainty in the predicted morbidity indicators and 23% of studies mapped it. In addition, 57% of the studies quantified uncertainty in the regression coefficients but only 7% incorporated it in the regression response variable (morbidity indicator). Fifty percent of the studies discussed uncertainty in the covariates but did not quantify it. Uncertainty was mostly defined as precision, and quantified using credible intervals by means of Bayesian approaches. Conclusion/Significance: None of the studies considered adequately all sources of uncertainties. We highlighted the need for uncertainty in the morbidity indicator and predictor variable to be incorporated into the modelling framework. Study design and spatial support require further attention and uncertainty associated with Earth observation data should be quantified. Finally, more attention should be given to mapping and interpreting uncertainty, since they are relevant to inform decisions regarding the number of people at risk as well as the geographic areas that need to be targeted with mass drug administration. [ABSTRACT FROM AUTHOR]

Through national efforts and regional cooperation under the umbrella of the Regional Program for the Elimination of Rabies, dog and human rabies have decreased significantly in Latin America and Caribbean (LAC) countries over the last three decades. To achieve this decline, LAC countries had to develop national plans, and consolidate capabilities such as regular mass dog vaccination, opportune post-exposure prophylaxis and sensitive surveillance. This paper presents longitudinal data for 21 LAC countries on dog vaccination, PEP and rabies surveillance collected from the biannual regional meeting for rabies directors from 1998–2014 and from the Regional Epidemiologic Surveillance System for Rabies (SIRVERA). Differences in human and dog rabies incidence rates and dog vaccination rates were shown between low, middle and high-income countries. At the peak, over 50 million dogs were vaccinated annually in national campaigns in the countries represented. The reported number of animal exposures remained fairly stable during the study period with an incidence rate ranging from 123 to 191 reported exposures per 100,000 people. On average, over 2 million doses of human vaccine were applied annually. In the most recent survey, only 37% of countries reported that they had sufficient financial resources to meet the program objectives. The data show a sufficient and sustained effort of the LAC countries in the area of dog vaccination and provide understanding of the baseline effort required to reduce dog-mediated rabies incidence. [ABSTRACT FROM AUTHOR]

Background: Despite being the most widely distributed mosquito-borne viral infection, estimates of dengue transmission intensity and associated burden remain ambiguous. With advances in the development of novel control measures, obtaining robust estimates of average dengue transmission intensity is key for assessing the burden of disease and the likely impact of interventions. Methodology/Principle Findings: We estimated the force of infection (λ) and corresponding basic reproduction numbers (R0) by fitting catalytic models to age-stratified incidence data identified from the literature. We compared estimates derived from incidence and seroprevalence data and assessed the level of under-reporting of dengue disease. In addition, we estimated the relative contribution of primary to quaternary infections to the observed burden of dengue disease incidence. The majority of R0 estimates ranged from one to five and the force of infection estimates from incidence data were consistent with those previously estimated from seroprevalence data. The baseline reporting rate (or the probability of detecting a secondary infection) was generally low (<25%) and varied within and between countries. Conclusions/Significance: As expected, estimates varied widely across and within countries, highlighting the spatio-temporally heterogeneous nature of dengue transmission. Although seroprevalence data provide the maximum information, the incidence models presented in this paper provide a method for estimating dengue transmission intensity from age-stratified incidence data, which will be an important consideration in areas where seroprevalence data are not available. [ABSTRACT FROM AUTHOR]

Background: Zika virus transmission dynamics in urban environments follow a complex spatiotemporal pattern that appears unpredictable and barely related to high mosquito density areas. In this context, human activity patterns likely have a major role in Zika transmission dynamics. This paper examines the effect of host variability in the amount of time spent outdoors on Zika epidemiology in an urban environment. Methodology/Principal findings: First, we performed a survey on time spent outdoors by residents of Miami-Dade County, Florida. Second, we analyzed both the survey and previously published national data on outdoors time in the U.S. to provide estimates of the distribution of the time spent outdoors. Third, we performed a computational modeling evaluation of Zika transmission dynamics, based on the time spent outdoors by each person. Our analysis reveals a strong heterogeneity of the host population in terms of time spent outdoors–data are well captured by skewed gamma distributions. Our model-based evaluation shows that in a heterogeneous population, Zika would cause a lower number of infections than in a more homogenous host population (up to 4-fold differences), but, at the same time, the epidemic would spread much faster. We estimated that in highly heterogeneous host populations the timing of the implementation of vector control measures is the major factor for limiting the number of Zika infections. Conclusions/Significance: Our findings highlight the need of considering host variability in exposure time for managing mosquito-borne infections and call for the revision of the triggers for vector control strategies, which should integrate mosquito density data and human outdoor activity patterns in specific areas. [ABSTRACT FROM AUTHOR]

Background: As Bangladesh, India and Nepal progress towards visceral leishmaniasis (VL) elimination, it is important to understand the role of asymptomatic Leishmania infection (ALI), VL treatment relapse and post kala-azar dermal leishmaniasis (PKDL) in transmission. Methodology/ Principal Finding: We reviewed evidence systematically on ALI, relapse and PKDL. We searched multiple databases to include studies on burden, risk factors, biomarkers, natural history, and infectiveness of ALI, PKDL and relapse. After screening 292 papers, 98 were included covering the years 1942 through 2016. ALI, PKDL and relapse studies lacked a reference standard and appropriate biomarker. The prevalence of ALI was 4–17-fold that of VL. The risk of ALI was higher in VL case contacts. Most infections remained asymptomatic or resolved spontaneously. The proportion of ALI that progressed to VL disease within a year was 1.5–23%, and was higher amongst those with high antibody titres. The natural history of PKDL showed variability; 3.8–28.6% had no past history of VL treatment. The infectiveness of PKDL was 32–53%. The risk of VL relapse was higher with HIV co-infection. Modelling studies predicted a range of scenarios. One model predicted VL elimination was unlikely in the long term with early diagnosis. Another model estimated that ALI contributed to 82% of the overall transmission, VL to 10% and PKDL to 8%. Another model predicted that VL cases were the main driver for transmission. Different models predicted VL elimination if the sandfly density was reduced by 67% by killing the sandfly or by 79% by reducing their breeding sites, or with 4–6y of optimal IRS or 10y of sub-optimal IRS and only in low endemic setting. Conclusion/ Significance: There is a need for xenodiagnostic and longitudinal studies to understand the potential of ALI and PKDL as reservoirs of infection. [ABSTRACT FROM AUTHOR]

Epidemics of communicable diseases place a huge burden on public health infrastructures across the world. Producing accurate and actionable forecasts of infectious disease incidence at short and long time scales will improve public health response to outbreaks. However, scientists and public health officials face many obstacles in trying to create such real-time forecasts of infectious disease incidence. Dengue is a mosquito-borne virus that annually infects over 400 million people worldwide. We developed a real-time forecasting model for dengue hemorrhagic fever in the 77 provinces of Thailand. We created a practical computational infrastructure that generated multi-step predictions of dengue incidence in Thai provinces every two weeks throughout 2014. These predictions show mixed performance across provinces, out-performing seasonal baseline models in over half of provinces at a 1.5 month horizon. Additionally, to assess the degree to which delays in case reporting make long-range prediction a challenging task, we compared the performance of our real-time predictions with predictions made with fully reported data. This paper provides valuable lessons for the implementation of real-time predictions in the context of public health decision making. [ABSTRACT FROM AUTHOR]

An effective surveillance system is critical for the elimination of canine rabies in Latin America. Brazil has made substantial progress towards canine rabies elimination, but outbreaks still occurred in the last decade in two states. Brazil uses a health information system (SINAN) to record patients seeking post-exposure prophylaxis (PEP) following contact with an animal suspected of having rabies. This study evaluated: (i) whether SINAN can be reliably used for rabies surveillance; (ii) if patients in Brazil are receiving appropriate PEP and (iii) the benefits of implementing the latest World Health Organization (WHO) recommendations on PEP. Analysing SINAN records from 2008 to 2017 reveals an average of 506,148 bite-injury patients/year [range: 437k -545k] in the country, equivalent to an incidence of 255 bite-injuries/100,000 people/year [range: 231–280]. The number of reports of bites from suspect rabid dogs generally increased over time. In most states, records from SINAN indicating a suspect rabid dog do not correlate with confirmed dog rabies cases reported to the Regional Information System for Epidemiological Surveillance of Rabies (SIRVERA) maintained by the Pan American Health Organization (PAHO). Analyses showed that in 2017, only 45% of patients received appropriate PEP as indicated by the Brazilian Ministry of Health guidance. Implementation of the latest WHO guidance using an abridged intradermal post-exposure vaccination regimen including one precautionary dose for dog bites prior to observation would reduce the volume of vaccine required by up to 64%, with potential for annual savings of over USD 6 million from reduced vaccine use. Our results highlight the need to improve the implementation of SINAN, including training of health workers responsible for delivering PEP using an Integrated Bite Case Management approach so that SINAN can serve as a reliable surveillance tool for canine rabies elimination. [ABSTRACT FROM AUTHOR]

Background: As of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October 2018, the outbreak has largely shifted into regions in which active armed conflict has occurred, and in which EVD cases and their contacts have been difficult for health workers to reach. We used available data on the current outbreak, with case-count time series from prior outbreaks, to project the short-term and long-term course of the outbreak. Methods: For short- and long-term projections, we modeled Ebola virus transmission using a stochastic branching process that assumes gradually quenching transmission rates estimated from past EVD outbreaks, with outbreak trajectories conditioned on agreement with the course of the current outbreak, and with multiple levels of vaccination coverage. We used two regression models to estimate similar projection periods. Short- and long-term projections were estimated using negative binomial autoregression and Theil-Sen regression, respectively. We also used Gott’s rule to estimate a baseline minimum-information projection. We then constructed an ensemble of forecasts to be compared and recorded for future evaluation against final outcomes. From August 20, 2018 to February 25, 2019, short-term model projections were validated against known case counts. Results: During validation of short-term projections, from one week to four weeks, we found models consistently scored higher on shorter-term forecasts. Based on case counts as of February 25, the stochastic model projected a median case count of 933 cases by February 18 (95% prediction interval: 872–1054) and 955 cases by March 4 (95% prediction interval: 874–1105), while the auto-regression model projects median case counts of 889 (95% prediction interval: 876–933) and 898 (95% prediction interval: 877–983) cases for those dates, respectively. Projected median final counts range from 953 to 1,749. Although the outbreak is already larger than all past Ebola outbreaks other than the 2013–2016 outbreak of over 26,000 cases, our models do not project that it is likely to grow to that scale. The stochastic model estimates that vaccination coverage in this outbreak is lower than reported in its trial setting in Sierra Leone. Conclusions: Our projections are concentrated in a range up to about 300 cases beyond those already reported. While a catastrophic outbreak is not projected, it is not ruled out, and prevention and vigilance are warranted. Prospective validation of our models in real time allowed us to generate more accurate short-term forecasts, and this process may prove useful for future real-time short-term forecasting. We estimate that transmission rates are higher than would be seen under target levels of 62% coverage due to contact tracing and vaccination, and this model estimate may offer a surrogate indicator for the outbreak response challenges. [ABSTRACT FROM AUTHOR]

The article offers information on the prevention of Cholera and control in refugee settings. Topics discussed Cholera is considered as a serious threat for refugee populations; mentions the humanitarian community developed the sphere standards for the living conditions and availability of health services in refugee camps; and highlights several historic outbreaks in refugee camps.

The preparedness of health systems to detect, treat, and prevent onward transmission of Ebola virus disease (EVD) is central to mitigating future outbreaks. Early detection of outbreaks is critical to timely response, but estimating detection rates is difficult because unreported spillover events and outbreaks do not generate data. Using three independent datasets available on the distributions of secondary infections during EVD outbreaks across West Africa, in a single district (Western Area) of Sierra Leone, and in the city of Conakry, Guinea, we simulated realistic outbreak size distributions and compared them to reported outbreak sizes. These three empirical distributions lead to estimates for the proportion of detected spillover events and small outbreaks of 26% (range 8–40%, based on the full outbreak data), 48% (range 39–62%, based on the Sierra Leone data), and 17% (range 11–24%, based on the Guinea data). We conclude that at least half of all spillover events have failed to be reported since EVD was first recognized. We also estimate the probability of detecting outbreaks of different sizes, which is likely less than 10% for single-case spillover events. Comparing models of the observation process also suggests the probability of detecting an outbreak is not simply the cumulative probability of independently detecting any one individual. Rather, we find that any individual’s probability of detection is highly dependent upon the size of the cluster of cases. These findings highlight the importance of primary health care and local case management to detect and contain undetected early stage outbreaks at source. [ABSTRACT FROM AUTHOR]

Background: Given that dengue disease is growing and may progress to dengue hemorrhagic fever (DHF), data on economic cost and disease burden are important. However, data for Mexico are limited. Methodology/Principal findings: Burden of dengue fever (DF) and DHF in Mexico was assessed using official databases for epidemiological information, disabilities weights from Shepard et al, the reported number of cases and deaths, and costs. Overall costs of dengue were summed from direct medical costs to the health system, cost of dengue to the patient (out-of-pocket expenses [medical and non-medical], indirect costs [loss of earnings, patient and/or caregiver]), and other government expenditures on prevention/surveillance. The first three components, calculated as costs per case by a micro-costing approach (PAATI; program, actions, activities, tasks, inputs), were scaled up to overall cost using epidemiology data from official databases. PAATI was used to calculate cost of vector control and prevention, education, and epidemiological surveillance, based on an expert consensus and normative construction of an ideal scenario. Disability-adjusted life years (DALYs) for Mexico in 2016 were calculated to be 2283.46 (1.87 per 100,000 inhabitants). Overall economic impact of dengue in Mexico for 2012 was US$144 million, of which US$44 million corresponded to direct medical costs and US$5 million to the costs from the patient’s perspective. The estimated cost of prevention/surveillance was calculated with information provided by federal government to be US$95 million. The overall economic impact of DF and DHF showed an increase in 2013 to US$161 million and a decrease to US$133, US$131 and US$130 million in 2014, 2015 and 2016, respectively. Conclusions/Significance: The medical and economic impact of dengue were in agreement with other international studies, and highlight the need to include governmental expenditure for prevention/surveillance in overall cost analyses given the high economic impact of these, increasing the necessity to evaluate its effectiveness. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO) has targeted yaws for global eradication. Eradication requires certification that all countries are yaws-free. While only 14 Member States currently report cases to WHO, many more are known to have a history of yaws and some of them may have ongoing transmission. We reviewed the literature and developed a model of case reports to identify countries in which passive surveillance is likely to find and report cases if transmission is still occurring, with the goal of reducing the number of countries in which more costly active surveillance will be required. Methods: We reviewed published and unpublished documents to extract data on the number of yaws cases reported to WHO or appearing in other literature in any year between 1945 and 2015. We classified countries as: a) having interrupted transmission; b) being currently endemic; c) being previously endemic (current status unknown); or d) having no history of yaws. We constructed a panel dataset for the years 1945–2015 and ran a regression model to identify factors associated with some countries not reporting cases during periods when there was ongoing (and documented) transmission. For previously endemic countries whose current status is unknown, we then estimated the probability that countries would have reported cases if there had in fact been transmission in the last three years (2013–2015). Results: Yaws has been reported in 103 of the 237 countries and areas considered. 14 Member States and 1 territory (Wallis and Futuna Islands) are currently endemic. 2 countries are believed to have interrupted transmission. 86 countries and areas are previously endemic (current status unknown). Reported cases peaked in the 1950s, with 55 countries reporting at least one case in 1950 and a total of 2.35 million cases reported in 1954. Our regression model suggests that case reporting during periods of ongoing transmission is positively associated with socioeconomic development and, in the short-term, negatively associated with independence. We estimated that for 66 out of the 86 previously endemic countries whose current status is unknown, the probability of reporting cases in the absence of active surveillance is less than 50%. Discussion: Countries with a history of yaws need to be prioritized so that international resources for global yaws eradication may be deployed efficiently. Heretofore, the focus has been on mass treatment in countries currently reporting cases. It is also important to undertake surveillance in the 86 previously endemic countries for which the current status is unknown. Within this large and diverse group, we have identified a group of 20 countries with more than a 50% probability of reporting cases in the absence of active surveillance. For the other 66 countries, international support for active surveillance will likely be required. [ABSTRACT FROM AUTHOR]

Background: Neglected tropical diseases (NTDs) are communicable diseases that impact approximately 1 billion people, but receive relatively little research, funding, and attention. Many NTDs have similar treatments, epidemiology, and geographic distribution, and as a result, the integration of control efforts can improve accountability, efficiency, and cost-effectiveness of programs. Here, we examine the landscape of efforts towards NTD integration across countries with the highest burden of disease, and review the administrative management of integration in order to identify approaches and pathways for integration. Methodology and principal findings: We utilized a standardized system to score countries for NTD endemnicity to create a list of 25 countries with the highest overall burden of NTDs. We then conducted a literature review to characterize the NTD control programs in the focus countries. Six countries were selected for key informant interviews to validate literature review results and gather additional data on opportunities and obstacles to NTD integration, from an administrative perspective. The majority of countries included in the study were located in Africa, with the remainder from Asia, North America, and South America. Multiple models and pathways were observed for the integration of NTD programs, in combination with other NTD programs, other diseases, or other health programs. Substantial heterogeneity existed with respect to the NTD control programs, and no country had integrated all of their NTD control efforts into a single program. NTDs that can be treated with preventative chemotherapy were frequently integrated into a single program. Leprosy control was also frequently integrated with those of other communicable diseases, and notably tuberculosis. Barriers to NTD integration may result from internal administrative obstacles or external obstacles. Conclusions: Although many countries have begun to integrate NTD control efforts, additional work will be required to realize the full benefits of integration in most of the countries examined here. Moving forward, NTD integration efforts must ensure that administrative structures are designed to maximize the potential success of integrated programs and account for existing administrative processes. [ABSTRACT FROM AUTHOR]

It is estimated that 190 million individuals are at risk of blindness from trachoma, and that control by mass drug administration (MDA) is reducing this risk in many populations. Programs are monitored using prevalence of follicular trachoma disease (TF) in children. However, as programs progress to low prevalence there are challenges interpreting this indirect measure of infection. PCR and sero-surveillance are being considered as complementary tools to monitor low-level transmission, but there are questions on how they can be most effectively used. We use a previously-published, mathematical model to explore the dynamic relationship between TF and PCR throughout a control program and a sero-catalytic model to evaluate the utility of two cross-sectional sero-surveys for estimating sero-conversion rates. The simulations show that whilst PCR is more sensitive than TF at detecting infection, the probability of detecting at least one positive individual declines during an MDA program more quickly for PCR than for TF (for the same sample size). Towards the end of a program there is a moderate chance of a random sample showing both low PCR prevalence and higher TF prevalence, which may contribute to the lack of correlation observed in epidemiological studies. We also show that conducting two cross-sectional sero-surveys 10 years apart can provide more precise and accurate estimation of epidemiological parameters than a single survey, supporting previous findings that whilst serology holds great promise, multiple cross-sections from the same community are needed to generate the most valuable information about transmission. These results highlight that the quantitative dynamics of infection and disease should be included alongside the many logistical and practical factors to be considered in designing a monitoring and evaluation strategy at the operational research level, in order to help subsequently inform data collection for individual country programs. Whilst our simulations provide some insight, they also highlight that some level of longitudinal, individual-level data on reinfection and disease may be needed to monitor elimination progress. [ABSTRACT FROM AUTHOR]

Background: Buruli Ulcer (BU) is one of the most neglected debilitating tropical diseases caused by Mycobacterium ulcerans, which causes considerable morbidity and disability. Building on earlier findings that community-based interventions could enhance case detection and reduce treatment dropout and defaulter rates, we established an active surveillance-response system in an endemic sub-district in the Ga West municipality of Ghana to enhance early case detection, diagnosis and treatment to reduce or eliminate severe ulcers and its related disabilities. Methods: We established surveillance response system, implemented in collaboration with the sub-district disease control officers, selected clinical staff and trained community-based volunteers. The active community-based surveillance- response system was implemented for 12 months. Also, pre and post intervention surveys were conducted to document any change in perceptions on BU in the study population over the period. The baseline and endline surveys were conducted in August 2016 and August 2017 respectively. Results: On average, each person was seen 11 times in 12 months. In all 75 skin lesions were detected during surveillance rounds, out of which 17 were suspected to be BU and 12 out of the 17 were confirmed as BU using Polymerase chain reaction (PCR). Out of the 12, five, three and four were categories I, II and III lesions respectively. Physical examination was done on 94% of the people seen during the surveillance rounds. Knowledge on BU has also increased in the communities at the end of the study. Conclusion: The findings from this study have demonstrated that it is possible to establish surveillance-response system for BU and by extension, other neglected tropical diseases to enhance control and elimination efforts through the use of community-based volunteers. [ABSTRACT FROM AUTHOR]

In Côte d’Ivoire, rabies is endemic and remains largely uncontrolled. The numbers of human exposures and rabies cases are unknown and are probably much higher than reported. Data on human rabies cases are collected by the National Institute of Public Health (NIPH) Anti-rabies Center in Abidjan through a network of 28 NIPH local units, which cover the population of the entire country. During 2014, the NIPH initiated a program to reinforce the human rabies surveillance system in those 28 NIPH local units, with specific goals of improving the infrastructure, training, communication, and government involvement. Here, we report the progress and findings during 2014–2016. The reinforced system recorded 50 cases of human rabies (15–18 cases/year; annual incidence = 0.06−0.08 per 100,000) and more than 30,000 animal exposures (annual incidence = 41.8−48.0 per 100,000). Almost one-half of the human rabies cases were in children ≤15 years old. All were fatal and dog bites were the most common route by which rabies virus was transmitted. In the 32 cases where samples of sufficient quality for analysis were available, rabies was confirmed by reverse transcription-polymerase chain reaction RT-PCR. Post-exposure prophylaxis with rabies vaccine was administered to all animal exposure victims presenting at the NIPH local units, although only about 57% completed the full immunization schedule. All available reports were provided by the NIPH local units, indicating effective communication between them and the NIPH Anti-rabies Center. These findings indicate that the reinforcements resulted in highly specific detection of human rabies, provided detailed epidemiological data about these cases, and improved estimates of animal exposure numbers. These represent substantial advances, but further improvements to the surveillance system are needed to increase disease awareness and capture cases that are currently missed by the system. In the future, better communication between local health centers and the NIPH units, surveillance at the local health center level, and increased veterinarian engagement will help provide a more complete picture of the rabies burden in Côte d’Ivoire. [ABSTRACT FROM AUTHOR]

Burkina Faso belongs to a group of countries in which human African trypanosomiasis (HAT), caused by Trypanosoma brucei gambiense, is no longer considered to be a public health problem. Although no native cases have been detected since 1993, there is still the risk of HAT re-emergence due to significant population movements between Burkina Faso and active HAT foci in Côte d’Ivoire. Since 2014, Burkina Faso receives support from the WHO to implement a passive surveillance program. This resulted in the detection in 2015 of the first putative native HAT case since two decades. However, epidemiological entomological and molecular biology investigations have not been able to identify with certainty the origin of this infection or to confirm that it was due to T. b. gambiense. This case emphasises the need to strengthen passive surveillance of the disease for sustained elimination of HAT as a public health problem in Burkina Faso. [ABSTRACT FROM AUTHOR]

Introduction: Dengue is the most extensively spread mosquito-borne disease; endemic in more than 100 countries. Information about dengue disease burden, its prevalence, incidence and geographic distribution is critical in planning appropriate control measures against dengue fever. We conducted a systematic review and meta-analysis of dengue fever in India Methods: We searched for studies published until 2017 reporting the incidence, the prevalence or case fatality of dengue in India. Our primary outcomes were (a) prevalence of laboratory confirmed dengue infection among clinically suspected patients, (b) seroprevalence in the general population and (c) case fatality ratio among laboratory confirmed dengue patients. We used binomial–normal mixed effects regression model to estimate the pooled proportion of dengue infections. Forest plots were used to display pooled estimates. The metafor package of R software was used to conduct meta-analysis. Results: Of the 2285 identified articles on dengue, we included 233 in the analysis wherein 180 reported prevalence of laboratory confirmed dengue infection, seven reported seroprevalence as evidenced by IgG or neutralizing antibodies against dengue and 77 reported case fatality. The overall estimate of the prevalence of laboratory confirmed dengue infection among clinically suspected patients was 38.3% (95% CI: 34.8%–41.8%). The pooled estimate of dengue seroprevalence in the general population and CFR among laboratory confirmed patients was 56.9% (95% CI: 37.5–74.4) and 2.6% (95% CI: 2–3.4) respectively. There was significant heterogeneity in reported outcomes (p-values<0.001). Conclusions: Identified gaps in the understanding of dengue epidemiology in India emphasize the need to initiate community-based cohort studies representing different geographic regions to generate reliable estimates of age-specific incidence of dengue and studies to generate dengue seroprevalence data in the country. [ABSTRACT FROM AUTHOR]

Introduction: Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted seven rounds of mass drug administration (MDA) from 2000–2006. The World Health Organization recommends systematic post-MDA surveillance using Transmission Assessment Surveys (TAS) for epidemiological assessment of recent LF transmission. We compared the effectiveness of two survey designs for post-MDA surveillance: a school-based survey of children aged 6–7 years, and a community-based survey targeting people aged ≥8 years. Methods: In 2016, we conducted a systematic school-based TAS in all elementary schools (N = 29) and a cluster survey in 28 villages on the two main islands of American Samoa. We collected information on demographics and risk factors for infection using electronic questionnaires, and recorded geo-locations of schools and households. Blood samples were collected to test for circulating filarial antigen (CFA) using the Alere Filariasis Test Strip. For those who tested positive, we prepared slides for microscopic examination of microfilaria and provided treatment. Descriptive statistics were performed for questionnaire variables. Data were weighted and adjusted to account for sampling design and sex for both surveys, and for age in the community survey. Results: The school-based TAS (n = 1143) identified nine antigen-positive children and found an overall adjusted CFA prevalence of 0.7% (95% CI: 0.3–1.8). Of the nine positive children, we identified one microfilariaemic 7-year-old child. The community-based survey (n = 2507, 711 households) identified 102 antigen-positive people, and estimated an overall adjusted CFA prevalence of 6.2% (95% CI: 4.5–8.6). Adjusted village-level prevalence ranged from 0–47.1%. CFA prevalence increased with age and was higher in males. Of 86 antigen-positive community members from whom slides were prepared, 22 (25.6%) were microfilaraemic. School-based TAS had limited sensitivity (range 0–23.8%) and negative predictive value (range 25–83.3%) but had high specificity (range 83.3–100%) and positive predictive value (range 0–100%) for identifying villages with ongoing transmission. Conclusions: American Samoa failed the school-based TAS in 2016, and the community-based survey identified higher than expected numbers of antigen-positive people. School-based TAS was logistically simpler and enabled sampling of a larger proportion of the target population, but the results did not provide a good indication of the overall CFA prevalence in older age groups and was not sensitive at identifying foci of ongoing transmission. The community-based survey, although operationally more challenging, identified antigen-positive individuals of all ages, and foci of high antigen prevalence. Both surveys confirmed recrudescence of LF transmission. [ABSTRACT FROM AUTHOR]

Background: During the West Africa Ebola outbreak, cultural practices have been described as hindering response efforts. The acceptance of control measures improved during the outbreak, but little is known about how and why this occurred. We conducted a qualitative study in two administrative districts of Sierra Leone to understand Ebola survivor, community, and health worker perspectives on Ebola control measures. We aimed to gain an understanding of community interactions with the Ebola response to inform future intervention strategies. Methodology/Principal findings: Participants (25 survivors, 24 community members, and 16 health workers) were recruited purposively. A flexible participatory method gathered data through field notes and in-depth, topic-led interviews. These were analysed thematically with NVivo10© by open coding, constant comparison, and the principles of grounded theory. The primary theme, ‘when Ebola is real’, centred on denial, knowledge, and acceptance. Ebola was denied until it was experienced or observed first-hand and thus health promotion was more effective if undertaken by those directly exposed to Ebola rather than by mass media communication. Factors that enabled acceptance and engagement with control measures included: access to good, proximate care and prevention activities; seeing that people can survive infection; and the co-option of trusted or influential local leadership, with bylaws implemented by community leaders being strongly respected. All participants noted that dignity, respect, and compassion were key components of effective control measures. Conclusions: Successful control approaches need strong community leadership, with the aim of achieving collective understanding between communities and health workers. Health promotion for communities at risk is best conducted through people who have had close interaction with or who have survived Ebola as opposed to reliance on broad mass communication strategies. [ABSTRACT FROM AUTHOR]

Background: The availability of a diagnostic test to detect subclinical leprosy cases is crucial to interrupt the transmission of M. leprae. In this study we assessed the minimum sensitivity level of such a (hypothetical) diagnostic test and the optimal testing strategy in order to effectively reduce the new case detection rate (NCDR) of leprosy. Methods and findings: We used the individual-based model SIMCOLEP, and based it on previous quantification using COLEP data, a cohort study of leprosy cases in Bangladesh. The baseline consisted of treatment with Multidrug therapy of clinically diagnosed leprosy cases, passive case detection and household contact tracing. We examined the use of a leprosy diagnostic test for subclinical leprosy in four strategies: testing in 1) household contacts, 2) household contacts with a 3-year follow-up, 3) a population survey with coverage 50%, and 4) a population survey (100%). For each strategy, we varied the test sensitivity between 50% and 100%. All analyses were conducted for a high, medium, and low (i.e. 25, 5 and 1 per 100,000) endemic setting over a period of 50 years. In all strategies, the use of a diagnostic test further reduces the NCDR of leprosy compared to the no test strategy. A substantial reduction could already be achieved at a test sensitivity as low as 50%. In a high endemic setting, a NCDR of 10 per 100,000 could be reached within 8–10 years in household contact testing, and 2–6 years in a population testing. Testing in a population survey could also yield the highest number of prevented new cases, but requires a large number needed to test and treat. In contrast, household contact testing has a smaller impact on the NCDR but requires a substantially lower number needed to test and treat. Conclusions: A diagnostic test for subclinical leprosy with a sensitivity of at least 50% could substantially reduce M. leprae transmission. To effectively reduce NCDR in the short run, a population survey is preferred over household contact tracing. However, this is only favorable in high endemic settings. [ABSTRACT FROM AUTHOR]

Background: Oral cholera vaccination is an approach to preventing outbreaks in at-risk settings and controlling cholera in endemic settings. However, vaccine-derived herd immunity may be short-lived due to interactions between human mobility and imperfect or waning vaccine efficacy. As the supply and utilization of oral cholera vaccines grows, critical questions related to herd immunity are emerging, including: who should be targeted; when should revaccination be performed; and why have cholera outbreaks occurred in recently vaccinated populations? Methods and findings: We use mathematical models to simulate routine and mass oral cholera vaccination in populations with varying degrees of migration, transmission intensity, and vaccine coverage. We show that migration and waning vaccine efficacy strongly influence the duration of herd immunity while birth and death rates have relatively minimal impacts. As compared to either periodic mass vaccination or routine vaccination alone, a community could be protected longer by a blended “Mass and Maintain” strategy. We show that vaccination may be best targeted at populations with intermediate degrees of mobility as compared to communities with very high or very low population turnover. Using a case study of an internally displaced person camp in South Sudan which underwent high-coverage mass vaccination in 2014 and 2015, we show that waning vaccine direct effects and high population turnover rendered the camp over 80% susceptible at the time of the cholera outbreak beginning in October 2016. Conclusions: Oral cholera vaccines can be powerful tools for quickly protecting a population for a period of time that depends critically on vaccine coverage, vaccine efficacy over time, and the rate of population turnover through human mobility. Due to waning herd immunity, epidemics in vaccinated communities are possible but become less likely through complementary interventions or data-driven revaccination strategies. [ABSTRACT FROM AUTHOR]

Background: Mozambique suffers recurrent annual cholera outbreaks especially during the rainy season between October to March. The African Cholera Surveillance Network (Africhol) was implemented in Mozambique in 2011 to generate accurate detailed surveillance data to support appropriate interventions for cholera control and prevention in the country. Methodology/Principal findings: Africhol was implemented in enhanced surveillance zones located in the provinces of Sofala (Beira), Zambézia (District Mocuba), and Cabo Delgado (Pemba City). Data were also analyzed from the three outbreak areas that experienced the greatest number of cases during the time period under observation (in the districts of Cuamba, Montepuez, and Nampula). Rectal swabs were collected from suspected cases for identification of Vibrio cholerae, as well as clinical, behavioral, and socio-demographic variables. We analyzed factors associated with confirmed, hospitalized, and fatal cholera using multivariate logistic regression models. A total of 1,863 suspected cases and 23 deaths (case fatality ratio (CFR), 1.2%) were reported from October 2011 to December 2015. Among these suspected cases, 52.2% were tested of which 23.5% were positive for Vibrio cholerae O1 Ogawa. Risk factors independently associated with the occurrence of confirmed cholera were living in Nampula city district, the year 2014, human immunodeficiency virus infection, and the primary water source for drinking. Conclusions/Significance: Cholera was endemic in Mozambique during the study period with a high CFR and identifiable risk factors. The study reinforces the importance of continued cholera surveillance, including a strong laboratory component. The results enhanced our understanding of the need to target priority areas and at-risk populations for interventions including oral cholera vaccine (OCV) use, and assess the impact of prevention and control strategies. Our data were instrumental in informing integrated prevention and control efforts during major cholera outbreaks in recent years. [ABSTRACT FROM AUTHOR]

Background: Of the three diseases targeted for eradication by WHO, two are so-called Neglected Tropical Diseases (NTDs)–guinea worm disease (GWD) and yaws. The Guinea Worm Eradication Programme (GWEP) is in its final stages, with only 25 reported in 2016. However, global eradication still requires certification by WHO of the absence of transmission in all countries. We analyze the cost-effectiveness of the GWEP in the end game, when the number of cases is lower and the cost per case is higher than at any other time. Ours is the first economic evaluation of the GWEP since a World Bank study in 1997. Methods: Using data from the GWEP, we estimate the cost of the implementation, pre-certification and certification stages. We model cost-effectiveness in the period 1986–2030. We compare the GWEP to two alternative scenarios: doing nothing (no intervention since 1986) and control (only surveillance and outbreak response during 2016–2030). We report the cost per case averted, cost per disability adjusted life year (DALY) averted and cost per at-risk life year averted. We assess cost-effectiveness against a threshold of about one half GDP per capita (less than US$ 500 in low income countries). All costs are expressed in US$ of 2015. Results: The GWEP cost an estimated US$ 11 (95% uncertainty interval, 4.70–12.49) per case averted in the period 1986–2030. The pre-certification and certification phases can cost as much as US$ 0.0041 and US$ 0.0015 per capita per year. The cost per DALY averted by the GWEP relative to doing nothing is estimated at US$ 222 (118–372) in 1986–2030. The GWEP is probably more cost-effective than control by the year 2030. The GWEP is certainly more cost-effective than control if willingness to pay for one year of life lived without the risk of GWD exceeds US$ 0.10. Discussion: Even if economic costs are two times as high as the financial costs estimated for the period to 2020, the GWEP will still be cost-effective relative to doing nothing. Whether the GWEP turns out to be the most cost-effective alternative in the period beyond 2015 depends on the time horizon. When framed in terms of the number of years of life lived without the risk of GWD, a case can be made more easily for finishing the end game, including certification of the absence of transmission. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: In Mozambique, the majority of rabies outbreaks are unreported and data on the epidemiological features of human rabies and animal bites are scarce. An outbreak of human rabies in adjacent Maputo and Matola cities in 2014 prompted us to investigate the epidemiology, clinical features and risk factors of human rabies and animal bites in the two cities. Methodology/Principal findings: We reviewed cases of human rabies and animal bites from April to July 2014, and carried out a community investigation in July and August in the where cases of human rabies resided. This investigation included collection of clinical, demographic and epidemiological information and a case control study to investigate the risk factors associated with human rabies. Fourteen cases of human rabies were detected in Maputo (n = 10) and Matola (n = 3) cities and neighbouring Boane district (n = 1) between April and August 2014, all of whom had been admitted to hospital. All had a recent history of dog bite. Of the 14 rabid dogs, only one had been immunized. 819 cases of animal bites were registered, of which 64.6% (529/819) were from Maputo City. Dogs were responsible for 97.8% (801/819) of all animal bites, but only 27.0% (126/467) were immunized. Factors significantly associated with human rabies were: age <15 years (p = 0.05), bite by stray dog (p = 0.002), deep wound (p = 0.02), bite in the head (p = 0.001), bite by unimmunized dog (p = 0.01), no use of soap and water (p = 0.001), and no post-exposure prophylaxis (p = 0.01). Conclusions/Significance: Implementation of control measures for rabies is poor in Maputo and Matola cities, where cases of human rabies were strongly associated with bites by stray and unvaccinated dogs and irregular implementation of post-exposure measures. [ABSTRACT FROM AUTHOR]

Background: During the past 20 years, enormous efforts have been expended globally to eliminate lymphatic filariasis (LF) through mass drug administration (MDA). However, small endemic foci (microfoci) of LF may threaten the presumed inevitable decline of infections after MDA cessation. We conducted microsimulation modeling to assess the ability of different types of surveillance to identify microfoci in these settings. Methods: Five or ten microfoci of radius 1, 2, or 3 km with infection marker prevalence (intensity) of 3, 6, or 10 times background prevalence were placed in spatial simulations, run in R Version 3.2. Diagnostic tests included microfilaremia, immunochromatographic test (ICT), and Wb123 ELISA. Population size was fixed at 360,000 in a 60 x 60 km area; demographics were based on literature for Sub-Saharan African populations. Background ICT prevalence in 6–7 year olds was anchored at 1.0%, and the prevalence in the remaining population was adjusted by age. Adults≥18 years, women aged 15–40 years (WCBA), children aged 6–7 years, or children≤5 years were sampled. Cluster (CS), simple random sampling (SRS), and TAS-like sampling were simulated, with follow-up testing of the nearest 20, 100, or 500 persons around each infection-marker-positive person. A threshold number of positive persons in follow-up testing indicated a suspected microfocus. Suspected microfoci identified during surveillance and actual microfoci in the simulation were compared to obtain a predictive value positive (PVP). Each parameter set was referred to as a protocol. Protocols were scored by efficiency, defined as the most microfoci identified, the fewest persons requiring primary and follow-up testing, and the highest PVP. Negative binomial regression was used to estimate aggregate effects of different variables on efficiency metrics. Results: All variables were significantly associated with efficiency metrics. Additional follow-up tests beyond 20 did not greatly increase the number of microfoci detected, but significantly negatively impacted efficiency. Of 3,402 protocols evaluated, 384 (11.3%) identified all five microfoci (PVP 3.4–100.0%) and required testing 0.73–35.6% of the population. All used SRS and 378 (98.4%) only identified all five microfoci if they were 2–3 km diameter or high-intensity (6x or 10x); 374 (97.4%) required ICT or Wb123 testing to identify all five microfoci, and 281 (73.0%) required sampling adults or WCBA. The most efficient CS protocols identified two (40%) microfoci. After limiting to protocols with 1-km radius microfoci of 3x intensity (n = 378), eight identified all five microfoci; all used SRS and ICT and required testing 31.2–33.3% of the population. The most efficient CS and TAS-like protocols as well as those using microfilaremia testing identified only one (20%) microfocus when they were limited to 1-km radius and 3x intensity. Conclusion: In this model, SRS, ICT, and sampling of adults maximized microfocus detection efficiency. Follow-up sampling of more persons did not necessarily increase protocol efficiency. Current approaches towards surveillance, including TAS, may not detect small, low-intensity LF microfoci that could remain after cessation of MDA. The model provides many surveillance protocols that can be selected for optimal outcomes. [ABSTRACT FROM AUTHOR]

Background: The 2014–6 West African Ebola epidemic highlights the need for rigorous, rapid clinical trial methods for vaccines. A challenge for trial design is making sample size calculations based on incidence within the trial, total vaccine effect, and intracluster correlation, when these parameters are uncertain in the presence of indirect effects of vaccination. Methods and findings: We present a stochastic, compartmental model for a ring vaccination trial. After identification of an index case, a ring of contacts is recruited and either vaccinated immediately or after 21 days. The primary outcome of the trial is total vaccine effect, counting cases only from a pre-specified window in which the immediate arm is assumed to be fully protected and the delayed arm is not protected. Simulation results are used to calculate necessary sample size and estimated vaccine effect. Under baseline assumptions about vaccine properties, monthly incidence in unvaccinated rings and trial design, a standard sample-size calculation neglecting dynamic effects estimated that 7,100 participants would be needed to achieve 80% power to detect a difference in attack rate between arms, while incorporating dynamic considerations in the model increased the estimate to 8,900. This approach replaces assumptions about parameters at the ring level with assumptions about disease dynamics and vaccine characteristics at the individual level, so within this framework we were able to describe the sensitivity of the trial power and estimated effect to various parameters. We found that both of these quantities are sensitive to properties of the vaccine, to setting-specific parameters over which investigators have little control, and to parameters that are determined by the study design. Conclusions: Incorporating simulation into the trial design process can improve robustness of sample size calculations. For this specific trial design, vaccine effectiveness depends on properties of the ring vaccination design and on the measurement window, as well as the epidemiologic setting. [ABSTRACT FROM AUTHOR]

Somalia, ravaged by conflict since 1991, has areas endemic for visceral leishmaniasis (VL), a deadly parasitic disease affecting the rural poor, internally displaced, and pastoralists. Very little is known about VL burden in Somalia, where the protracted crisis hampers access to health care. We reviewed evidence about VL epidemiology in Somalia and appraised control options within the context of this fragile state’s health system. VL has been reported in Somalia since 1934 and has persisted ever since in foci in the southern parts of the country. The only feasible VL control option is early diagnosis and treatment, currently mostly provided by nonstate actors. The availability of VL care in Somalia is limited and insufficient at best, both in coverage and quality. Precarious security remains a major obstacle to reach VL patients in the endemic areas, and the true VL burden and its impact remain unknown. Locally adjusted, innovative approaches in VL care provision should be explored, without undermining ongoing health system development in Somalia. Ensuring VL care is accessible is a moral imperative, and the limitations of the current VL diagnostic and treatment tools in Somalia and other endemic settings affected by conflict should be overcome. [ABSTRACT FROM AUTHOR]

Background: Visceral Leishmaniasis (VL) is a neglected tropical disease that afflicts some of the poorest populations in the world including people living in the Bihar state of India. Due to efforts from local governments, NGOs and international organizations, the number of VL cases has declined in recent years. Despite this progress, the reservoir for transmission remains to be clearly defined since it is unknown what role post kala-azar dermal leishmaniasis (PKDL) and asymptomatic infections play in transmission. This information is vital to establish effective surveillance and monitoring to sustainably eliminate VL. Methodology/Principal Findings: We performed a longitudinal study over a 24-month period to examine VL transmission and seroconversion in households with VL, PKDL and asymptomatic infections in the Saran and Muzaffarpur districts of Bihar. During the initial screening of 5,144 people in 16 highly endemic villages, 195 cases of recently treated VL, 116 healthy rK39 positive cases and 31 PKDL cases were identified. Approximately half of the rK39-positive healthy cases identified during the initial 6-month screening period were from households (HHs) where a VL case had been identified. During the 18-month follow-up period, seroconversion of family members in the HHs with VL cases, PKDL cases, and rK39-positive individuals was similar to control HHs. Therefore, seroconversion was highest in HHs closest to the time of VL disease of a household member and there was no evidence of higher transmission in households with PKDL or healthy rK39-positive HHs. Moreover, within the PKDL HHs, (the initial 31 PKDL cases plus an additional 66 PKDL cases), there were no cases of VL identified during the initial screen or the 18-month follow-up. Notably, 23% of the PKDL cases had no prior history of VL suggesting that infection resulting directly in PKDL is more common than previously estimated. Conclusions/Significance: These observations argue that acute VL cases represent the major reservoir for transmission in these villages and early identification and treatment of VL cases should remain a priority for VL elimination. We were unable to obtain evidence that transmission occurs in HHs with a PKDL case. [ABSTRACT FROM AUTHOR]

Background: Arboviral diseases are an important public health concerns. Vector control remains the sole strategy to fight against these diseases. Because of the important limits of methods currently used to assess human exposure to Aedes mosquito bites, much effort is being devoted to develop new indicators. Recent studies have reported that human antibody (Ab) responses to Aedes aegypti Nterm-34kDa salivary peptide represent a promising biomarker tool to evaluate the human-Aedes contact. The present study aims investigate whether such biomarker could be used for assessing the efficacy of vector control against Aedes. Methodology/Principal findings: Specific human IgG response to the Nterm-34kDa peptide was assessed from 102 individuals living in urban area of Saint-Denis at La Reunion Island, Indian Ocean, before and after the implementation of vector control against Aedes mosquitoes. IgG response decreased after 2 weeks (P < 0.0001), and remained low for 4 weeks post-intervention (P = 0.0002). The specific IgG decrease was associated with the decline of Aedes mosquito density, as estimated by entomological parameters and closely correlated to vector control implementation and was not associated with the use of individual protection, daily commuting outside of the house, sex and age. Our findings indicate a probable short-term decrease of human exposure to Aedes bites just after vector control implementation. Conclusion/Significance: Results provided in the present study indicate that IgG Ab response to Aedes aegypti Nterm-34kDa salivary peptide could be a relevant short-time indicator for evaluating the efficacy of vector control interventions against Aedes species. [ABSTRACT FROM AUTHOR]

The article presents a case study commissioned by the Neglected Infectious Disease dIAGnosis (NIDIAG) on rapid diagnostic tests (RDT) labeling and instructions for use in persistent fever, with emphasis on in vitro diagnostic tests (IVD). It highlights the need for proactive interest from IVD manufacturers in connection with ISO 13485 guidelines.

Background: Dengue is a frequent cause of acute febrile illness with an expanding global distribution. Since the 1960s, dengue in Sri Lanka has been documented primarily along the heavily urbanized western coast with periodic shifting of serotypes. Outbreaks from 2005–2008 were attributed to a new clade of DENV-3 and more recently to a newly introduced genotype of DENV-1. In 2007, we conducted etiologic surveillance of acute febrile illness in the Southern Province and confirmed dengue in only 6.3% of febrile patients, with no cases of DENV-1 identified. To re-evaluate the importance of dengue as an etiology of acute febrile illness in this region, we renewed fever surveillance in the Southern Province to newly identify and characterize dengue. Methodology/Principal Findings: A cross-sectional surveillance study was conducted at the largest tertiary care hospital in the Southern Province from 2012–2013. A total of 976 patients hospitalized with acute undifferentiated fever were enrolled, with 64.3% male and 31.4% children. Convalescent blood samples were collected from 877 (89.6%). Dengue virus isolation, dengue RT-PCR, and paired IgG ELISA were performed. Acute dengue was confirmed as the etiology for 388 (39.8%) of 976 hospitalizations, with most cases (291, 75.0%) confirmed virologically and by multiple methods. Among 351 cases of virologically confirmed dengue, 320 (91.2%) were due to DENV-1. Acute dengue was associated with self-reported rural residence, travel, and months having greatest rainfall. Sequencing of selected dengue viruses revealed that sequences were most closely related to those described from China and Southeast Asia, not nearby India. Conclusions/Significance: We describe the first epidemic of DENV-1 in the Southern Province of Sri Lanka in a population known to be susceptible to this serotype because of prior study. Dengue accounted for 40% of acute febrile illnesses in the current study. The emergence of DENV-1 as the foremost serotype in this densely populated but agrarian population highlights the changing epidemiology of dengue and the need for continued surveillance and prevention. [ABSTRACT FROM AUTHOR]

Background: Dengue is an increasingly incident disease across many parts of the world. In response, an evidence-based handbook to translate research into policy and practice was developed. This handbook facilitates contingency planning as well as the development and use of early warning and response systems for dengue fever epidemics, by identifying decision-making processes that contribute to the success or failure of dengue surveillance, as well as triggers that initiate effective responses to incipient outbreaks. Methodology/Principal findings: Available evidence was evaluated using a step-wise process that included systematic literature reviews, policymaker and stakeholder interviews, a study to assess dengue contingency planning and outbreak management in 10 countries, and a retrospective logistic regression analysis to identify alarm signals for an outbreak warning system using datasets from five dengue endemic countries. Best practices for managing a dengue outbreak are provided for key elements of a dengue contingency plan including timely contingency planning, the importance of a detailed, context-specific dengue contingency plan that clearly distinguishes between routine and outbreak interventions, surveillance systems for outbreak preparedness, outbreak definitions, alert algorithms, managerial capacity, vector control capacity, and clinical management of large caseloads. Additionally, a computer-assisted early warning system, which enables countries to identify and respond to context-specific variables that predict forthcoming dengue outbreaks, has been developed. Conclusions/Significance: Most countries do not have comprehensive, detailed contingency plans for dengue outbreaks. Countries tend to rely on intensified vector control as their outbreak response, with minimal focus on integrated management of clinical care, epidemiological, laboratory and vector surveillance, and risk communication. The Technical Handbook for Surveillance, Dengue Outbreak Prediction/ Detection and Outbreak Response seeks to provide countries with evidence-based best practices to justify the declaration of an outbreak and the mobilization of the resources required to implement an effective dengue contingency plan. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO) now requires a second surveillance survey for trachoma after an impact assessment has found follicular trachoma (TF) <5% to determine if re-emergence has occurred. Using new WHO guidelines, we undertook surveillance surveys, and determined the prevalence of infection and antibody positivity, in two districts in Nepal. Methods: 20 clusters were randomly selected within each district, 15 were randomly selected for antibody testing. In each cluster, we randomly selected 50 children ages 1–9 years and 100 adults ≥15 years. TF and trachomatous trichiasis (TT) were evaluated. Conjunctival swabs to test for chlamydial infection using GenXpert platform were obtained, and dried blood spots were collected to test for antibodies to Chlamydia Trachomatis pgp3 using the Luminex platform. Findings: 3 cases of TF were found in the two districts, and one case of infection. Pgp3 antibody positivity was 2·4% (95% confidence interval: 1·4%, 3·7%), and did not increase with age (P = 0.24). No clustering of antibody positivity within communities was found. TT prevalence was <1/1,000 population. Interpretation: The surveillance surveys, as proposed by WHO, showed no evidence for re-emergence of trachoma in two districts of Nepal. The low level and no significant increase by age in seroprevalence of antibodies to C trachomatis pgp3 antigen deserve further investigation as a marker of interruption of transmission. [ABSTRACT FROM AUTHOR]

Dengue has a negative impact in low- and lower middle-income countries, but also affects upper middle- and high-income countries. Despite the efforts at controlling this disease, it is unclear why dengue remains an issue in affluent countries. A better understanding of dengue epidemiology and its burden, and those of chikungunya virus and Zika virus which share vectors with dengue, is required to prevent the emergence of these diseases in high-income countries in the future. The purpose of this review was to assess the relative burden of dengue in four high-income countries and to appraise the similarities and differences in dengue transmission. We searched PubMed, ISI Web of Science, and Google Scholar using specific keywords for articles published up to 05 May 2016. We found that outbreaks rarely occur where only Aedes albopictus is present. The main similarities between countries uncovered by our review are the proximity to dengue-endemic countries, the presence of a competent mosquito vector, a largely nonimmune population, and a lack of citizens’ engagement in control of mosquito breeding. We identified important epidemiological and environmental issues including the increase of local transmission despite control efforts, population growth, difficulty locating larval sites, and increased human mobility from neighboring endemic countries. Budget cuts in health and lack of practical vaccines contribute to an increased risk. To be successful, dengue-control programs for high-income countries must consider the epidemiology of dengue in other countries and use this information to minimize virus importation, improve the control of the cryptic larval habitat, and engage the community in reducing vector breeding. Finally, the presence of a communicable disease center is critical for managing and reducing future disease risks. [ABSTRACT FROM AUTHOR]

The authors discuss aspects of the prevalence of Chikungunya virus in the urban areas in French Guiana. They examine the risk of exposure to mosquitoes due to virus transmission wherein the virus has no specific treatment or vaccine. The authors cite the development of trapping systems with substrates impregnated with sugar on which mosquitoes come to feed and expel virus particles for the surveillance of virus transmission.

Background: An explosive outbreak of dengue fever occurred in Guangdong Province, China in 2014. A community-based integrated intervention was applied to control this outbreak in the capital city Guangzhou, where dengue epidemic was mainly caused by imported cases. Methodology/Principal Findings: We used a time series generalized additive model based on meteorological factors to assess the effectiveness of this intervention. The results showed that there was significant reduction in mosquito density following the intervention, and there was a 70.47% (95% confidence interval: 66.07%, 74.88%) reduction in the reported dengue cases compared with the predicted cases after 12 days since the beginning of the intervention, we estimated that a total of 23,302 dengue cases were prevented. Conclusions: This study suggests that an integrated dengue intervention program has significant effects to control a dengue outbreak in areas where dengue epidemic was mainly caused by imported dengue cases. [ABSTRACT FROM AUTHOR]

Dengue incidence has increased globally, but empirical burden estimates are scarce. Prospective methods are best-able to capture all severities of disease. CYD14 was an observer-blinded dengue vaccine study conducted in children 2–14 years of age in Indonesia, Malaysia, Thailand, the Philippines, and Vietnam. The control group received no vaccine and resembled a prospective, observational study. We calculated the rates of dengue according to different laboratory or clinical criteria to make inferences about dengue burden, and compared with rates reported in the passive surveillance systems to calculate expansion factors which describe under-reporting. Over 6,933 person-years of observation in the control group there were 319 virologically confirmed dengue cases, a crude attack rate of 4.6%/year. Of these, 92 cases (28.8%) were clinically diagnosed as dengue fever or dengue hemorrhagic fever by investigators and 227 were not, indicating that most symptomatic disease fails to satisfy existing case definitions. When examining different case definitions, there was an inverse relationship between clinical severity and observed incidence rates. CYD14’s active surveillance system captured a greater proportion of symptomatic dengue than national passive surveillance systems, giving rise to expansion factors ranging from 0.5 to 31.7. This analysis showed substantial, unpredictable and variable under-reporting of symptomatic dengue, even within a controlled clinical trial environment, and emphasizes that burden estimates are highly sensitive to case definitions. These data will assist in generating disease burden estimates and have important policy implications when considering the introduction and health economics of dengue prevention and control interventions. [ABSTRACT FROM AUTHOR]

Background: Rabies in China remains a public health problem. In 2014, nearly one thousand rabies-related deaths were reported while rabies geographic distribution has expanded for the recent years. This report used surveillance data to describe the epidemiological characteristics of human rabies in China including determining high-risk areas and seasonality to support national rabies prevention and control activities. Methods: We analyzed the incidence and distribution of human rabies cases in mainland China using notifiable surveillance data from 1960–2014, which includes a detailed analysis of the recent years from 2004 to 2014. Results: From 1960 to 2014, 120,913 human rabies cases were reported in mainland China. The highest number was recorded in 1981(0.7/100,000; 7037 cases), and in 2007(0.3/100,000; 3300 cases). A clear seasonal pattern has been observed with a peak in August (11.0% of total cases), Human rabies cases were reported in all provinces with a yearly average of 2198 from 1960 to 2014 in China, while the east and south regions were more seriously affected compared with other regions. From2004 to 2014, although the number of cases decreased by 65.2% since 2004 from 2651 to 924 cases, reported areas has paradoxically expanded from 162 prefectures to 200 prefectures and from southern to the central and northern provinces of China. Farmers accounted most of the cases (65.0%); 50–59 age group accounted for the highest proportion (20.5%), and cases are predominantly males with a male-to-female ratio of 2.4:1 on average. Conclusions: Despite the overall steady decline of cases since the peak in 2007, the occurrence of cases in new areas and the spread trend were obvious in China in recent years. Further investigations and efforts are warranted in the areas have high rabies incidence to control rabies by interrupting transmission from dogs to humans and in the dog population. Furthermore, elimination of rabies should be eventually the ultimate goal for China. [ABSTRACT FROM AUTHOR]

Background: Two large-scale efficacy studies with the recombinant yellow fever-17D–dengue virus, live-attenuated, tetravalent dengue vaccine (CYD-TDV) candidate undertaken in Asia (NCT01373281) and Latin America (NCT01374516) demonstrated significant protection against dengue disease during two years’ active surveillance (active phase). Long-term follow up of participants for breakthrough disease leading to hospitalization is currently ongoing (hospital phase). Methodology/Principal findings: We assessed the cytokine profile in acute sera from selected participants hospitalized (including during the active phase) up to the beginning of the second year of long-term follow up for both studies. The serum concentrations of 38 cytokines were measured in duplicate using the Milliplex Human Cytokine MAGNETIC BEAD Premixed 38 Plex commercial kit (Millipore, Billerica, MA, USA). Partial least squares discriminant analyses did not reveal any difference in the overall cytokine profile of CYD-TDV and placebo recipients hospitalized for breakthrough dengue regardless of stratification used. In addition, there was no difference in the cytokine profile for breakthrough dengue among those aged <9 years versus those aged ≥ 9 years. Conclusions/Significance: These exploratory findings show that CYD-TDV does not induce a particular immune profile versus placebo, corroborating the clinical profile observed. [ABSTRACT FROM AUTHOR]

Background: Aedes aegypti is a primary vector of dengue virus (DENV), the causative agent of dengue fever, an arthropod-borne disease of global importance. Although a vaccine has been recommended for prevention, current dengue prevention strategies rely on vector control. Recently, volatile pyrethroids—spatial repellents—have received interest as a novel delivery system for adult Ae. aegypti control. Understanding the full range of behavioral effects spatial repellents elicit in mosquito species will be critical to understanding the overall impact these products have on vector populations and will guide expectations of efficacy against DENV transmission. Methodology/Principal Findings: The current study quantified changes in attraction of gravid Ae. aegypti to experimental oviposition sites following exposure to the spatial repellent transfluthrin. Responses were measured with two-choice olfaction bioassays using ‘sticky-screens’ covering cups to prevent contact with the oviposition substrate. Two cups contained a bacterial attractant composed of four species of bacteria in calcium alginate beads in water and two cups contained only deionized water. Results from 40 replicates (n = 780 females total per treatment) indicated an estimated difference in attraction of 9.35% ± 0.18 (p ≤ 0.003), implying that the transfluthrin-exposed mosquitoes were more attracted to the experimental oviposition sites than the non-exposed mosquitoes. Conclusions/Significance: Findings from this study will further characterize the role of spatial repellents to modify Ae. aegypti behavior related to dengue prevention specifically, and encourage innovation in vector control product development more broadly. [ABSTRACT FROM AUTHOR]

The release of Wolbachia infected mosquitoes is likely to form a key component of disease control strategies in the near future. We investigated the potential of using near-infrared spectroscopy (NIRS) to simultaneously detect and identify two strains of Wolbachia pipientis (wMelPop and wMel) in male and female laboratory-reared Aedes aegypti mosquitoes. Our aim is to find faster, cheaper alternatives for monitoring those releases than the molecular diagnostic techniques that are currently in use. Our findings indicate that NIRS can differentiate females and males infected with wMelPop from uninfected wild type samples with an accuracy of 96% (N = 299) and 87.5% (N = 377), respectively. Similarly, females and males infected with wMel were differentiated from uninfected wild type samples with accuracies of 92% (N = 352) and 89% (N = 444). NIRS could differentiate wMelPop and wMel transinfected females with an accuracy of 96.6% (N = 442) and males with an accuracy of 84.5% (N = 443). This non-destructive technique is faster than the standard polymerase chain reaction diagnostic techniques. After the purchase of a NIRS spectrometer, the technique requires little sample processing and does not consume any reagents. [ABSTRACT FROM AUTHOR]

We evaluated the sensitivity of the dengue surveillance system in detecting hospitalized cases in ten capital cities in Brazil from 2008 to 2013 using a probabilistic record linkage of two independent information systems hospitalization (SIH-SUS) adopted as the gold standard and surveillance (SINAN). Sensitivity was defined as the proportion of cases reported to the surveillance system amid the suspected hospitalized cases registered in SIH-SUS. Of the 48,174 hospitalizations registered in SIH-SUS, 24,469 (50.7%) were reported and registered in SINAN, indicating an overall sensitivity of 50.8% (95%CI 50.3–51.2). The observed sensitivity for each of the municipalities included in the study ranged from 22.0% to 99.1%. The combination of the two data sources identified 71,161 hospitalizations, an increase of 97.0% over SINAN itself. Our results allowed establishing the proportion of underreported dengue hospitalizations in the public health system in Brazil, highlighting the use of probabilistic record linkage as a valuable tool for evaluating surveillance systems. [ABSTRACT FROM AUTHOR]

The epidemiology of dengue fever is characterized by highly seasonal, multi-annual fluctuations, and the irregular circulation of its four serotypes. It is believed that this behaviour arises from the interplay between environmental drivers and serotype interactions. The exact mechanism, however, is uncertain. Constraining mathematical models to patterns characteristic to dengue epidemiology offers a means for detecting such mechanisms. Here, we used a pattern-oriented modelling (POM) strategy to fit and assess a range of dengue models, driven by combinations of temporary cross protective-immunity, cross-enhancement, and seasonal forcing, on their ability to capture the main characteristics of dengue dynamics. We show that all proposed models reproduce the observed dengue patterns across some part of the parameter space. Which model best supports the dengue dynamics is determined by the level of seasonal forcing. Further, when tertiary and quaternary infections are allowed, the inclusion of temporary cross-immunity alone is strongly supported, but the addition of cross-enhancement markedly reduces the parameter range at which dengue dynamics are produced, irrespective of the strength of seasonal forcing. The implication of these structural uncertainties on predicted vulnerability to control is also discussed. With ever expanding spread of dengue, greater understanding of dengue dynamics and control efforts (e.g. a near-future vaccine introduction) has become critically important. This study highlights the capacity of multi-level pattern-matching modelling approaches to offer an analytic tool for deeper insights into dengue epidemiology and control. [ABSTRACT FROM AUTHOR]

Background: New approaches to preventing chikungunya virus (CHIKV) are needed because current methods are limited to controlling mosquito populations, and they have not prevented the invasion of this virus into new locales, nor have they been sufficient to control the virus upon arrival. A promising candidate for arbovirus control and prevention relies on the introduction of the intracellular bacterium Wolbachia into Aedes aegypti mosquitoes. This primarily has been proposed as a tool to control dengue virus (DENV) transmission; however, evidence suggests Wolbachia infections confer protection for Ae. aegypti against CHIKV. Although this approach holds much promise for limiting virus transmission, at present our understanding of the ability of CHIKV to infect, disseminate, and be transmitted by wMel-infected Ae. aegypti currently being used at Wolbachia release sites is limited. Methodology/Principal Findings: Using Ae. aegypti infected with the wMel strain of Wolbachia that are being released in Medellin, Colombia, we report that these mosquitoes have reduced vector competence for CHIKV, even with extremely high viral titers in the bloodmeal. In addition, we examined the dynamics of CHIKV infection over the course of four to seven days post feeding. Wolbachia-infected mosquitoes remained non-infective over the duration of seven days, i.e., no infectious virus was detected in the saliva when exposed to bloodmeals of moderate viremia, but CHIKV-exposed, wild type mosquitoes did have viral loads in the saliva consistent with what has been reported elsewhere. Finally, the presence of wMel infection had no impact on the lifespan of mosquitoes as compared to wild type mosquitoes following CHIKV infection. Conclusions/Significance: These results could have an impact on vector control strategies in areas where Ae. aegypti are transmitting both DENV and CHIKV; i.e., they argue for further exploration, both in the laboratory and the field, on the feasibility of expanding this technology beyond DENV. [ABSTRACT FROM AUTHOR]

Introduction: The scale and geographical distribution of the current outbreak in West Africa raised doubts as to the effectiveness of established methods of control. Ebola Virus Disease (EVD) was first detected in Sierra Leone in May 2014 in Kailahun district. Despite high case numbers elsewhere in the country, transmission was eliminated in the district by December 2014. We describe interventions underpinning successful EVD control in Kailahun and implications for EVD control in other areas. Methods: Internal service data and published reports from response agencies were analysed to describe the structure and type of response activities, EVD case numbers and epidemic characteristics. This included daily national situation reports and District-level data and reports of the Sierra Leone Ministry of Health and Sanitation, and Médecins Sans Frontières (MSF) patient data and internal epidemiological reports. We used EVD case definitions provided by the World Health Organisation over the course of the outbreak. Characteristics assessed included level of response activities and epidemiological features such as reported exposure (funeral-related or not), time interval between onset of illness and admission to the EVD Management Centre (EMC), work-related exposures (health worker or not) and mortality. We compared these characteristics between two time periods—June to July (the early period of response), and August to December (when coverage and quality of response had improved). A stochastic model was used to predict case numbers per generation with different numbers of beds and a varying percentage of community cases detected. Results: There were 652 probable/confirmed EVD cases from June-December 2014 in Kailahun. An EMC providing patient care opened in June. By August 2014 an integrated detection, treatment, and prevention strategy was in place across the district catchment zone. From June-July to August-December 2014 surveillance and contact tracing staff increased from 1.0 to 8.8 per confirmed EVD case, EMC capacity increased from 32 to 100 beds, the number of burial teams doubled, and health promotion activities increased in coverage. These improvements in response were associated with the following changes between the same periods: the proportion of confirmed/probable cases admitted to the EMC increased from 35% to 83% (χ2 p-value<0·001), the proportion of confirmed patients admitted to the EMC <3 days of symptom onset increased from 19% to 37% (χ2 p-value <0·001), and reported funeral contact in those admitted decreased from 33% to 16% (χ2 p-value <0·001). Mathematical modelling confirmed the importance of both patient management capacity and surveillance and contact tracing for EVD control. Discussion: Our findings demonstrate that control of EVD can be achieved using established interventions based on identification and appropriate management of those who are at risk of and develop EVD, including in the context of ongoing transmission in surrounding regions. Key attributes in achieving control were sufficient patient care capacity (including admission to specialist facilities of suspect and probable cases for assessment), integrated with adequate staffing and resourcing of community-based case detection and prevention activities. The response structure and coverage targets we present are of value in informing effective control in current and future EVD outbreaks. [ABSTRACT FROM AUTHOR]