Search

Background: Japanese encephalitis (JE) virus is the leading cause of vaccine-preventable encephalitis and a significant cause of disability in Asia and the western Pacific. Many countries have introduced JE vaccination programs, including several low resource countries following WHO's prioritization of JE vaccination in 2006. We sought to characterize the public health impact of JE vaccination programs. Methodology/Principal findings: JE case data and vaccination coverage rates, were requested from country health officials in 23 JE endemic countries and Chinese Taipei. Additional data were extracted from meeting presentations and published literature. JE incidence was compared before and after vaccination using a minimum three year period pre and post program introduction or expansion. Data suitable for analysis were available for 13 JE-endemic countries and Chinese Taipei, for either all age groups or for children aged under 15 years only. Five countries and Chinese Taipei introduced vaccine prior to 2006 and the all-age JE incidence was reduced by 73–100% in about 5–20 years following introduction. Six countries have introduced JE vaccine since 2006, and JE incidence in children aged younger than 15 years has been reduced by 14–79% as of 2015–2021. JE-specific data were unavailable before introduction in Thailand and Vietnam, but vaccination programs reduced acute encephalitis incidence by 80% and 74%, respectively. Even in the programs with greatest impact, it took several years to achieve their results. Conclusions/Significance: JE vaccination has greatly reduced JE in 13 JE-endemic countries and Chinese Taipei. Highest impact has been observed in countries that introduced prior to 2006, but it often took roughly two decades and substantial resources to achieve that level of success. For greatest possible impact, more recently introducing countries and funding agencies should commit to continuous improvements in delivery systems to sustain coverage after initial vaccine introduction. Author summary: While JE has been controlled by vaccination in a handful of economically developed countries endemic for JE transmission with disease reductions of 73–100%, introduction of JE vaccines has ocurred later in low and low-middle income countries (LLMIC) endemic for JE. Since 2006 focused effort has been undertaken to assist with establishment of sustained vaccination efforts against JE in LLMIC. The outcome has been growing evidence of the impact of vaccination against JE in LLMIC endemic for JE transmission with disease reductions of 14–79% among children aged under 15 years. We describe the public health impact of JE vaccination programs in both economically developed and LLMIC JE endemic countries and discuss how time and sustained effort on JE vaccination in LLMIC has high potential to reach the level of control seen in earlier decades in economically developed countries. [ABSTRACT FROM AUTHOR]

Despite continuous efforts of veterinary services to control rabies in dogs since 1982, rabies remains a cause of death in Tunisia, with more than five reported human cases in 2022. As little is known on the determinants of transmission of rabies in dogs, better understand which factors contribute to its spatial heterogeneity in Tunisia is critical for developing bespoke mitigation activities. In this context, we developed Bayesian Poisson mixed-effect spatio-temporal model upon all cases of rabid dogs reported in each delegation during the period from 2019 to 2021. The best fitting model highlighted the association between the risk of rabies and the mean average monthly temperature, the density of markets and the density of dogs in delegations. Interestingly, no relationship was found between intensity of vaccination in dogs and the risk of rabies. Our results provided insights into the spatio-temporal dynamics of dog rabies transmission and highlighted specific geographic locations where the risk of infection was high despite correction for associated explanatory variables. Such an improved understanding represent key information to design bespoke, cost-efficient, rabies prevention and control strategies to support veterinary services activities and policymaking. Author summary: Rabies, a deadly zoonotic disease, remains a public health concern in Tunisia despite ongoing prevention efforts. Our study, the first of its kind in Tunisia, aimed to analyze the spatiotemporal distribution of dog rabies and identify factors influencing its spread. Using a Bayesian approach, we examined the relationships between epidemiological, socio-economic, and environmental factors and the occurrence of rabies cases in different regions (delegations) of Tunisia. Our study revealed that variations in the risk of rabies were primarily associated with spatial effects rather than temporal trends. We found a negative association between average monthly temperature and dog rabies cases, consistent with decreased viral survival and dog activity in warmer temperatures. The risk of rabies cases had a non-linear relationship with dog density. We also found that dog rabies risk was positively associated with the density of slaughterhouses, indicating that these locations might contribute to interactions between infected and susceptible animals. Surprisingly, vaccination coverage did not show a significant association with rabies risk. Our findings contribute to the global goal of eradicating rabies by 2030 and underscore the importance of adapting strategies based on the unique factors influencing disease transmission in specific regions. [ABSTRACT FROM AUTHOR]

Rabies control remains challenging in low and middle-income countries, mostly due to lack of financial resources, rapid turnover of dog populations and poor accessibility to dogs. Rabies is endemic in Cambodia, where no national rabies vaccination program is implemented. The objective of this study was to assess the short and long-term vaccination-induced immunity in Cambodian dogs under field conditions, and to propose optimized vaccination strategies. A cohort of 351 dogs was followed at regular time points following primary vaccination only (PV) or PV plus single booster (BV). Fluorescent antibody virus neutralization test (FAVNT) was implemented to determine the neutralizing antibody titer against rabies and an individual titer ≥0·5 IU/mL indicated protection. Bayesian modeling was used to evaluate the individual duration of protection against rabies and the efficacy of two different vaccination strategies. Overall, 61% of dogs had a protective immunity one year after PV. In dogs receiving a BV, this protective immunity remained for up to one year after the BV in 95% of dogs. According to the best Bayesian model, a PV conferred a protective immunity in 82% of dogs (95% CI: 75–91%) for a mean duration of 4.7 years, and BV induced a lifelong protective immunity. Annual PV of dogs less than one year old and systematic BV solely of dogs vaccinated the year before would allow to achieve the 70% World Health Organization recommended threshold to control rabies circulation in a dog population in three to five years of implementation depending on dog population dynamics. This vaccination strategy would save up to about a third of vaccine doses, reducing cost and time efforts of mass dog vaccination campaigns. These results can contribute to optimize rabies control measures in Cambodia moving towards the global goal of ending human death from dog-mediated rabies by 2030. Author summary: Rabies is a fatal zoonotic viral disease. Dog vaccination is recognized as the most cost-effective and sustainable solution to rabies prevention. Cambodia is endemic with canine mediated rabies, that would cause to around 800 human death each year. This country also has a large owned but mostly free-roaming dog population that makes efficient massive vaccination hard to achieve. In this study, we vaccinated 351 dogs with or without booster one year later. We then used serological assessed the short and long-term vaccination-induced immunity in these dogs, and Bayesian modeling to identify a vaccination strategy adapted to the Cambodian dog population characteristics. Yearly primary vaccinations for young dogs, supplemented with a single booster injection of these dogs promises to achieve 70% dog vaccination coverage effectively and efficiently, and control rabies circulation in dog populations. Applying this new strategy running for five more years after the vaccination coverage of at least 70% is achieved, this implies per 1,000 dogs between 2000 and 5 000 saved vaccine doses depending on dog population characteristics. Our results could help controlling rabies in Cambodia and potentially be adopted by other countries facing similar challenges. [ABSTRACT FROM AUTHOR]

Control of dog-mediated rabies relies on raising awareness, access to post-exposure prophylaxis (PEP) and mass dog vaccination. To assess rabies awareness in Moramanga district, Madagascar, where rabies is endemic, two complementary quantitative and qualitative approaches were carried out in 2018. In the quantitative approach, a standardized questionnaire was administered to 334 randomized participants living in 170 households located less than 5 km from the anti-rabies treatment center (ARTC) located in Moramanga city (thereafter called the central area), and in 164 households located more than 15 km away from the ARTC in two rural communes (thereafter called the remote area). Logistic regression models were fitted to identify factors influencing knowledge and practice scores. The qualitative approach consisted in semi-structured interviews conducted with 28 bite victims who had consulted the ARTC, three owners of biting dogs, three ARTC staff and two local authorities. Overall, 15.6% (52/334) of households owned at least one dog. The dog-to-human ratio was 1:17.6. The central area had a significantly higher dog bite incidence (0.52 per 100 person-years, 95% CI: 0.31–0.84) compared to the remote area (0.22 per 100 person-years, 95% CI: 0.09–0.43) (p = 0.03). The care pathway following a bite depended on wound severity, how the dog was perceived and its owner's willingness to cover costs. Rabies vaccination coverage in dogs in the remote area was extremely low (2.4%). Respondents knew that vaccination prevented animal rabies but owners considered that their own dogs were harmless and cited access and cost of vaccine as main barriers. Most respondents were not aware of the existence of the ARTC (85.3%), did not know the importance of timely access to PEP (92.2%) or that biting dogs should be isolated (11.1%) and monitored. Good knowledge scores were significantly associated with having a higher socio-economic status (OR = 2.08, CI = 1.33–3.26) and living in central area (OR = 1.91, CI = 1.22–3.00). Good practice scores were significantly associated with living in central area (OR = 4.78, CI = 2.98–7.77) and being aware of the ARTC's existence (OR = 2.29, CI = 1.14–4.80). In Madagascar, knowledge on rabies was disparate with important gaps on PEP and animal management. Awareness campaigns should inform communities (i) on the importance of seeking PEP as soon as possible after an exposure, whatever the severity of the wound and the type of biting dog who caused it, and (ii) on the existence and location of ARTCs where free-of-charge PEP is available. They should also encourage owners to isolate and monitor the health of biting dogs. Above all, awareness and dog vaccination campaigns should be designed so as to reach the more vulnerable remote rural populations as knowledge, good practices and vaccination coverage were lower in these areas. They should also target households with a lower socio-economic status. If awareness campaigns are likely to succeed in improving access to ARTCs in Madagascar, their impact on prompting dog owners to vaccinate their own dogs seems more uncertain given the financial and access barriers. Therefore, to reach the 70% dog vaccination coverage goal targeted in rabies elimination programs, awareness campaigns must be combined with free-of-charge mass dog vaccination. Author summary: Despite effective animal and human vaccines, rabies causes over 59,000 human deaths annually, mainly in children and in poor rural communities in Asia and Africa. World Health Organization and partners have recently launched the "Zero by 30" global plan which aims to end human deaths by dog-mediated rabies by 2030 by raising awareness, increasing access to post-exposure prophylaxis (PEP) and mass dog vaccination. In Madagascar, where rabies is endemic, a network of anti-rabies treatment centers (ARTC) delivers free-of-charge vaccines to exposed patients. As little is known on rabies awareness in Malagasy communities, we set up quantitative and qualitative surveys on rabies knowledge, attitudes and practices (KAP). Results showed that major hosts, main transmission routes, clinical signs and outcomes were known by most respondents. Yet knowledge on the existence of ARTC, the usefulness and availability of PEP, usefulness of confining and monitoring biting dogs was very low. Although bite incidence was lower, remote rural areas had more limited knowledge, poorer practices on rabies and extremely low dog vaccination coverage, so awareness campaigns should make sure remote rural populations are reached. If these campaigns are likely to succeed in improving access to ARTCs, their impact on dog vaccination seems more uncertain. Therefore, to reach dog vaccination coverage goals, the center-piece of rabies elimination strategies, awareness campaigns must be combined with free-of-charge mass dog vaccination. [ABSTRACT FROM AUTHOR]

In 2021, a comprehensive dog demographic questionnaire combined with a KAP survey were conducted in the northern communal areas (NCAs) of Namibia with the aim of gaining a better understanding of dog populations, owner behaviour, and knowledge, attitudes and practices (KAP) relating to rabies. The survey of 3,726 households across the eight regions of the NCAs provided insights that will inform interventions in order to improve human rabies prevention and Namibia's dog rabies control strategy. The results showed a relatively low average human/dog ratio (HDR) of 5.4:1 indicating a surprisingly high dog population of at least 272,000 dogs in the NCAs, 93% of which appear to be owned but are free-roaming. Data analysis revealed opportunities but also highlighted needs for improvements in rabies surveillance and mass dog vaccinations. Although knowledge, attitude, and practice scores towards epidemiologic and clinical aspects, human rabies prevention, and dog rabies vaccination were deemed to be acceptable, the survey nevertheless revealed deficiencies in certain aspects in some of the population. Interestingly, data seemed to indicate relatively high dog bite incidences per 100,000 people, ranging between 262 and 1,369 and a certain number of unreported human rabies cases. Despite the very high number of dogs, only 50% of dog-owning households reported having vaccinated their dogs. In order to address these issues, the planning, announcement, and implementation of mass dog vaccination campaigns needs to be adapted to achieve adequate vaccination coverage. Another focus needs to be on rabies awareness and education if Namibia is to be significantly contributing to the global goal of "Zero by 30". Author summary: As a neglected disease, rabies remains a major problem in Africa and Asia. Here we report the results of an extensive community survey on dog ownership and knowledge, attitudes and practices (KAP) related to rabies control and prevention, covering the Northern Communal Areas (NCAs) of Namibia. The survey conducted in 2021 included more than 3,700 households and provided useful insights that will inform interventions in order to improve human rabies prevention and Namibia's dog rabies control strategy. Our results show that there was 1 dog for about every 5 humans, of which the vast majority is free-roaming. This surprisingly high dog population is not only supporting disease transmission but further complicating control efforts. Most people were aware that dog-mediated rabies is present in this part of Namibia and had an acceptable attitude and behavior towards it. Depending on the region, between 262 and 1,369 people per 100,000 inhabitants were bitten by dogs during the survey period. Although the number of dog bites is relatively high, more than 90% of victims stated that they had sought hospital treatment after being bitten. However, there are still gaps in laboratory-based surveillance of dog-mediated rabies, and incomplete or lack of rabies prophylaxis after dog bite injuries have led to unreported human deaths. Therefore, improved vaccination measures for dogs, consistent rabies prophylaxis after dog bite injuries as well as awareness-raising measures to increase people's knowledge and awareness are necessary if human deaths caused by rabies are to be permanently prevented. [ABSTRACT FROM AUTHOR]

Introduction: Hepatitis E (HEV) genotypes 1 and 2 are the common cause of jaundice and acute viral hepatitis that can cause large-scale outbreaks. HEV infection is associated with adverse fetal outcomes and case fatality risks up to 31% among pregnant women. An efficacious three-dose recombinant vaccine (Hecolin) has been licensed in China since 2011 but until 2022, had not been used for outbreak response despite a 2015 WHO recommendation. The first ever mass vaccination campaign against hepatitis E in response to an outbreak was implemented in 2022 in Bentiu internally displaced persons camp in South Sudan targeting 27,000 residents 16–40 years old, including pregnant women. Methods: We conducted a vaccination coverage survey using simple random sampling from a sampling frame of all camp shelters following the third round of vaccination. For survey participants vaccinated in the third round in October, we asked about the onset of symptoms experienced within 72 hours of vaccination. During each of the three vaccination rounds, passive surveillance of adverse events following immunisation (AEFI) was put in place at vaccination sites and health facilities in Bentiu IDP camp. Results: We surveyed 1,599 individuals and found that self-reported coverage with one or more dose was 86% (95% CI 84–88%), 73% (95% CI 70–75%) with two or more doses and 58% (95% CI 55–61%) with three doses. Vaccination coverage did not differ significantly by sex or age group. We found no significant difference in coverage of at least one dose between pregnant and non-pregnant women, although coverage of at least two and three doses was 8 and 14 percentage points lower in pregnant women. The most common reasons for non-vaccination were temporary absence or unavailability, reported by 60% of unvaccinated people. Passive AEFI surveillance captured few mild AEFI, and through the survey we found that 91 (7.6%) of the 1,195 individuals reporting to have been vaccinated in October 2022 reported new symptoms starting within 72 hours after vaccination, most commonly fever, headache or fatigue. Conclusions: We found a high coverage of at least one dose of the Hecolin vaccine following three rounds of vaccination, and no severe AEFI. The vaccine was well accepted and well tolerated in the Bentiu IDP camp community and should be considered for use in future outbreak response. Author summary: Hepatitis E virus can cause large, protracted outbreaks in populations with limited access to safe water and sanitation. Hepatitis E infection is particularly dangerous for pregnant women in their third trimester. A vaccine, Hecolin, exists but it was never used in outbreak response despite a recommendation from the World Health Organization. In 2022, the Ministry of Health of South Sudan and Médecins Sans Frontières used the vaccine during an outbreak for the first time in an internally displaced persons camp with more than 100,000 people. We report on the results of the vaccination campaign, which show a high uptake of the vaccine and no serious side effects. We show that a vaccination campaign with Hecolin during an outbreak can reach many people at risk and is well tolerated. This will hopefully inspire confidence to use this vaccine again in the future. [ABSTRACT FROM AUTHOR]

Zoonotic pathogens spread by wildlife continue to spill into human populations and threaten human lives. A potential way to reduce this threat is by vaccinating wildlife species that harbor pathogens that are infectious to humans. Unfortunately, even in cases where vaccines can be distributed en masse as edible baits, achieving levels of vaccine coverage sufficient for pathogen elimination is rare. Developing vaccines that self-disseminate may help solve this problem by magnifying the impact of limited direct vaccination. Although models exist that quantify how well these self-disseminating vaccines will work when introduced into temporally stable wildlife populations, how well they will perform when introduced into populations with pronounced seasonal population dynamics remains unknown. Here we develop and analyze mathematical models of fluctuating wildlife populations that allow us to study how reservoir ecology, vaccine design, and vaccine delivery interact to influence vaccine coverage and opportunities for pathogen elimination. Our results demonstrate that the timing of vaccine delivery can make or break the success of vaccination programs. As a general rule, the effectiveness of self-disseminating vaccines is optimized by introducing after the peak of seasonal reproduction when the number of susceptible animals is near its maximum. Author summary: Pathogens such as Ebola, rabies, and Lassa virus that usually infect wildlife can jump to the human population. In the worst case, this can lead to outbreaks or pandemics such as happened in 2014 with Ebola and 2019 with SARS-CoV-2. One approach to mitigate the threat of pathogens spilling into the human population is to proactively vaccinate wildlife harboring these pathogens before the pathogens infect humans. With traditional vaccines, administering enough vaccines to the wildlife population to limit pathogen spread is challenging. To address this challenge, recent technological advances have allowed the development of vaccines that allow some degree of spread of the vaccine from animal to animal. However, for a vaccination campaign using these self-disseminating vaccines to be implemented successfully, we need to know when vaccines should be administered. We used mathematical models to explore how the reservoir host's population ecology and properties of the vaccine affect the success of a vaccination campaign. Our results demonstrate that the timing of vaccine delivery relative to seasonal reproduction can make or break the success of vaccination programs. The effectiveness of self-disseminating vaccines is optimized by introducing vaccine after the peak of seasonal reproduction when the number of animals available for vaccination is highest. [ABSTRACT FROM AUTHOR]

BackgroundAs 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.MethodsFor 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.ResultsDuring 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.ConclusionsOur 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.

The tetravalent dengue vaccine CYD-TDV (Dengvaxia) is the first licensed vaccine against dengue, but recent findings indicate an elevated risk of severe disease among vaccinees without prior dengue virus (DENV) exposure. The World Health Organization currently recommends CYD-TDV only for individuals with serological confirmation of past DENV exposure. Our objective was to evaluate the potential health impact and cost-effectiveness of vaccination following serological screening. To do so, we used an agent-based model to simulate DENV transmission with and without vaccination over a 10-year timeframe. Across a range of values for the proportion of vaccinees with prior DENV exposure, we projected the proportion of symptomatic and hospitalized cases averted as a function of the sensitivity and specificity of serological screening. Scenarios about the cost-effectiveness of screening and vaccination were chosen to be representative of Brazil and the Philippines. We found that public health impact depended primarily on sensitivity in high-transmission settings and on specificity in low-transmission settings. Cost-effectiveness could be achievable from the perspective of a public payer provided that sensitivity and the value of a disability-adjusted life-year were both high, but only in high-transmission settings. Requirements for reducing relative risk and achieving cost-effectiveness from an individual perspective were more restricted, due to the fact that those who test negative pay for screening but receive no benefit. Our results predict that cost-effectiveness could be achieved only in high-transmission areas of dengue-endemic countries with a relatively high per capita GDP, such as Panamá (13,680 USD), Brazil (8,649 USD), México (8,201 USD), or Thailand (5,807 USD). In conclusion, vaccination with CYD-TDV following serological screening could have a positive impact in some high-transmission settings, provided that screening is highly specific (to minimize individual harm), at least moderately sensitive (to maximize population benefit), and sufficiently inexpensive (depending on the setting).

Objectives: Dog vaccination can eliminate rabies in dogs, but annual delivery strategies do not sustain vaccination coverage between campaigns. We describe the development of a community-based continuous mass dog vaccination (CBC-MDV) approach designed to improve and maintain vaccination coverage in Tanzania and examine the feasibility of delivering this approach as well as lessons for its optimization. Methods: We developed three delivery strategies of CBC-MDV and tested them against the current annual vaccination strategy following the UK Medical Research Council's guidance: i) developing an evidence-based theoretical framework of intervention pathways and ii) piloting to test feasibility and inform optimization. For our process evaluation of CBC-MDV we collected data using non-participant observations, meeting reports and implementation audits and in-depth interviews, as well as household surveys of vaccination coverage to assess potential effectiveness. We analyzed qualitative data thematically and quantitative data descriptively. Results: The final design included delivery by veterinary teams supported by village-level one health champions. In terms of feasibility, we found that less than half of CBC-MDV's components were implemented as planned. Fidelity of delivery was influenced by the strategy design, implementer availability and appreciation of value intervention components, and local environmental and socioeconomic events (e.g. elections, funerals, school cycles). CBC-MDV activities decreased sharply after initial campaigns, partly due to lack of supervision. Community engagement and involvement was not strong. Nonetheless, the CBC-MDV approaches achieved vaccination coverage above the critical threshold (40%) all-year-round. CBC-MDV components such as identifying vaccinated dogs, which village members work as one health champions and how provision of continuous vaccination is implemented need further optimization prior to scale up. Interpretation: CBC-MDV is feasible to deliver and can achieve good vaccination coverage. Community involvement in the development of CBC-MDV, to better tailor components to contextual situations, and improved supervision of activities are likely to improve vaccination coverage in future. Author summary: Annual mass dog vaccination campaigns that reach at least 70% of the dog population, should maintain sufficient herd immunity (sustain vaccination coverage above 40%) between campaigns to interrupt rabies transmission. However, it is often challenging to reach 70% of the dog population with annual vaccination campaigns. We hypothesized that a community-based continuous approach to dog vaccination could better maintain high levels of vaccination coverage all-year-round. We describe the development of a community-based continuous approach to dog vaccination in Tanzania, and assessed the feasibility of delivering its components, its potential effectiveness and lessons for its optimization. We found that the approach was well accepted, as its development involved key stakeholders. Although less than half of the components of the community-based continuous approach were delivered exactly as planned, over 70% of dogs were vaccinated and the approach maintained coverage above the critical vaccination threshold throughout the year. We conclude that it is feasible to deliver a community-based continuous approach to dog vaccination, but that some components need further improvement; more supervision and community involvement should lead to better outcomes. [ABSTRACT FROM AUTHOR]

Dog-mediated rabies is responsible for tens of thousands of human deaths annually, and in resource-constrained settings, vaccinating dogs to control the disease at source remains challenging. Currently, rabies elimination efforts rely on mass dog vaccination by the parenteral route. To increase the herd immunity, free-roaming and stray dogs need to be specifically addressed in the vaccination campaigns, with oral rabies vaccination (ORV) of dogs being a possible solution. Using a third-generation vaccine and a standardized egg-flavoured bait, bait uptake and vaccination was assessed under field conditions in Namibia. During this trial, both veterinary staff as well as dog owners expressed their appreciation to this approach of vaccination. Of 1,115 dogs offered a bait, 90% (n = 1,006, 95%CI:91–94) consumed the bait and 72.9% (n = 813, 95%CI:70.2–75.4) of dogs were assessed as being vaccinated by direct observation, while for 11.7% (n = 130, 95%CI:9.9–17.7) the status was recorded as "unkown" and 15.4% (n = 172, 95%CI: 13.4–17.7) were considered as being not vaccinated. Smaller dogs and dogs offered a bait with multiple other dogs had significantly higher vaccination rates, while other factors, e.g. sex, confinement status and time had no influence. The favorable results of this first large-scale field trial further support the strategic integration of ORV into dog rabies control programmes. Given the acceptance of the egg-flavored bait under various settings worldwide, ORV of dogs could become a game-changer in countries, where control strategies using parenteral vaccination alone failed to reach sufficient vaccination coverage in the dog population. Author summary: Rabies in dogs can be prevented by vaccination, and this approach has become a cornerstone in the control and eventual elimination of the disease. However, vaccinating hard-to-reach often free-roaming dogs are a challenge and represents one of the challenges to reach sufficient herd-immunity. A potential solution would be to vaccinate these dogs using oral baits filled with a vaccine. In this study we have assessed the acceptability of oral rabies vaccination (ORV) in Namibian dogs under field conditions. The results demonstrate that the method is acceptable both for the owners and the dogs, with a very high uptake of the egg-flavored bait. This supports the potential of ORV to contribute to vaccination programs where parenteral vaccination alone failed to reach sufficient vaccination coverage in the dog population. [ABSTRACT FROM AUTHOR]

Guatemala has held dog rabies mass vaccination campaigns countrywide since 1984, yet the virus remains endemic. To eliminate dog-mediated human rabies, dog vaccination coverage must reach at least 70%. The Guatemala rabies program uses a 5:1 human:dog ratio (HDR) to estimate the vaccination coverage; however, this method may not accurately reflect the heterogeneity of dog ownership practices in Guatemalan communities. We conducted 16 field-based dog population estimates in urban, semi-urban and rural areas of Guatemala to determine HDR and evaluate the standard 5:1. Our study-derived HDR estimates varied from 1.7–11.4:1 (average 4.0:1), being higher in densely populated sites and lowest in rural communities. The community-to-community heterogeneity observed in dog populations could explain the persistence of rabies in certain communities. To date, this is the most extensive dog-population evaluation conducted in Guatemala, and can be used to inform future rabies vaccination campaigns needed to meet the global 2030 rabies elimination targets. Author summary: Standard dog population estimates used for planning and evaluating dog vaccination campaigns in Guatemala are prone to error due to spatial and ownership heterogeneity among dog populations; advanced population estimation methods should be implemented in areas with persistent endemicity of dog-mediated rabies. [ABSTRACT FROM AUTHOR]

Background: Japanese Encephalitis (JE) is known for its high case fatality ratio (CFR) and long-term neurological sequelae. Over the years, efforts in JE treatment and control might change the JE fatality risk. However, previous estimates were from 10 years ago, using data from cases in the 10 years before this. Estimating JE disease severity is challenging because data come from countries with different JE surveillance systems, diagnostic methods, and study designs. Without precise and timely JE disease severity estimates, there is continued uncertainty about the JE disease burden and the effect of JE vaccination. Methodology: We performed a systematic review to collate age-stratified JE fatality and morbidity data. We used a stepwise model selection with BIC as the selection criteria to identify JE CFR drivers. We used stacked regression, to predict country-specific JE CFR from 1961 to 2030. JE morbidity estimates were grouped from similar study designs to estimate the proportion of JE survivors with long-term neurological sequelae. Principal findings: We included 82 and 50 peer-reviewed journal articles published as of March 06 2021 for JE fatality and morbidity with 22 articles in both analyses. Results suggested overall JE CFR estimates of 26% (95% CI 22, 30) in 1961–1979, 20% (95% CI 17, 24) in 1980–1999, 14% (95% CI 11, 17) in 2000–2018, and 14% (95% CI 11, 17) in 2019–2030. Holding other variables constant, we found that JE fatality risk decreased over time (OR: 0.965; 95% CI: 0.947–0.983). Younger JE cases had a slightly higher JE fatality risk (OR: 1.012; 95% CI: 1.003–1.021). The odds of JE fatality in countries with JE vaccination is 0.802 (90% CI: 0.653–0.994; 95% CI: 0.62–1.033) times lower than the odds in countries without JE vaccination. Ten percentage increase in the percentage of rural population to the total population was associated with 15.35% (95% CI: 7.71, 22.57) decrease in JE fatality odds. Ten percentage increase in population growth rate is associated with 3.71% (90% CI: 0.23, 7.18; 95% CI: -0.4, 8.15) increase in JE fatality odds. Adjusting for the effect of year, rural population percent, age of JE cases, and population growth rate, we estimated that there was a higher odds of JE fatality in India compared to China. (OR: 5.46, 95% CI: 3.61–8.31). Using the prediction model we found that, in 2000–2018, Brunei, Pakistan, and Timor-Leste were predicted to have the highest JE CFR of 20%. Bangladesh, Guam, Pakistan, Philippines, and Vietnam had projected JE CFR over 20% for after 2018, whereas the projected JE CFRs were below 10% in China, Indonesia, Cambodia, Myanmar, Malaysia, and Thailand. For disability, we estimated that 36% (min-max 0–85) JE patients recovered fully at hospital discharge. One year after hospital discharge, 46% (min-max 0%-97%) JE survivors were estimated to live normally but 49% (min-max 3% - 86%)till had neurological sequelae. Conclusion: JE CFR estimates were lower than 20% after 2000. Our study provides an updated estimation of CFR and proportion of JE cases with long-term neurological sequelae that could help to refine cost-benefit assessment for JE control and elimination programs. Author summary: Japanese Encephalitis (JE) is known for its high case fatality ratio (CFR) and long-term neurological sequelae. Although JE fatality and morbidity risk might change as the characteristics of the population change with the strengthened surveillance scales, expanded immunization coverage, and healthcare improvements, there have not been any updates in the estimates for JE mortality and morbidity estimates for 10 years. In this paper, we made updated estimates of the JE CFR and the proportion of JE survivors with long-term neurological sequelae by performing a systematic review and developing statistical and machine learning models. We estimated JE CFR decreased over time, with estimates of 26% (95% CI 22, 30) in 1961–1979, 20% (95% CI 17, 24) in 1980–1999, 14% (95% CI 11, 17) in 2000–2018, and 14% (95% CI 11, 17) in 2019–2030. countries without JE vaccination, younger JE cases, higher population growth rate, and lower rural population percentage were associated with higher JE CFR. We estimated that 36% (min-max 0–85) JE patients recovered fully at hospital discharge. One year after hospital discharge, 46% (min-max 0%-97%) JE survivors were estimated to live normally but 49% (min-max 3% - 86%) JE patients still had neurological sequelae. The insights gained will be important in evaluating and updating current JE disease burden among all endemic areas and effectively channeling resources to most needed areas. [ABSTRACT FROM AUTHOR]

Rabies is a fatal disease that has been a serious health concern, especially in developing countries. Although rabies is preventable by vaccination, the spread still occurs sporadically in many countries, including Thailand. Geographical structures, habitats, and behaviors of host populations are essential factors that may result in an enormous impact on the mechanism of propagation and persistence of the disease. To investigate the role of geographical structures on the transmission dynamics of canine rabies, we developed a stochastic individual-based model that integrates the exact configuration of buildings and roads. In our model, the spatial distribution of dogs was estimated based on the distribution of buildings, with roads considered to facilitate dog movement. Two contrasting areas with high- and low-risk of rabies transmission in Thailand, namely, Hatyai and Tepha districts, were chosen as study sites. Our modeling results indicated that the distinct geographical structures of buildings and roads in Hatyai and Tepha could contribute to the difference in the rabies transmission dynamics in these two areas. The high density of buildings and roads in Hatyai could facilitate more rabies transmission. We also investigated the impacts of rabies intervention, including reducing the dog population, restricting owned dog movement, and dog vaccination on the spread of canine rabies in these two areas. We found that reducing the dog population alone might not be sufficient for preventing rabies transmission in the high-risk area. Owned dog confinement could reduce more the likelihood of rabies transmission. Finally, a higher vaccination coverage may be required for controlling rabies transmission in the high-risk area compared to the low-risk area. Author summary: Canine rabies is responsible for tens of thousands of human deaths annually worldwide, primarily in Asia and Africa. In Thailand, a sharp increasing trend of animal rabies cases was recently observed during 2014 and 2018, in which the numbers of cases were 250 and 1,105, respectively. As a directly transmitted disease, geographical distributions of buildings where dogs can live in, and road networks could inevitably influence the spatiotemporal spread of rabies. To investigate the role of these geographical structures on the transmission dynamics of canine rabies, we developed a stochastic individual-based model that integrates the exact geographical distributions of buildings and roads. The spatial distribution of dogs was assumed according to the distribution of buildings, with roads included to help dogs travel around. The model was then applied to investigate rabies transmission in the low-risk and high-risk areas in Thailand. Our modeling results highlighted that only differences in the geographical structures of buildings and roads could result in the difference in rabies transmission dynamics in these two areas. We also explored the impacts of reducing dog population, restriction of owned dog movement, and dog vaccination on the rabies spread. We discovered that lowering the dog population alone might not be enough to keep rabies from spreading in the high-risk area. Owned dog confinement may lower the risk of rabies transmission even more. In addition, different levels of vaccination coverages are probably required to control rabies in different geographical settings. [ABSTRACT FROM AUTHOR]

Background: A global stockpile of oral cholera vaccine (OCV) was established in 2013 for use in outbreak response and are licensed as two-dose regimens. Vaccine availability, however, remains limited. Previous studies have found that a single dose of OCV may provide substantial protection against cholera. Methods: Using a mathematical model with two age groups paired with optimization algorithms, we determine the optimal vaccination strategy with one and two doses of vaccine to minimize cumulative overall infections, symptomatic infections, and deaths. We explore counterfactual vaccination scenarios in three distinct settings: Maela, the largest refugee camp in Thailand, with high in- and out-migration; N'Djamena, Chad, a densely populated region; and Haiti, where departments are connected by rivers and roads. Results: Over the short term under limited vaccine supply, the optimal strategies for all objectives prioritize one dose to the older age group (over five years old), irrespective of setting and level of vaccination coverage. As more vaccine becomes available, it is optimal to administer a second dose for long-term protection. With enough vaccine to cover the whole population with one dose, the optimal strategies can avert up to 30% to 90% of deaths and 36% to 92% of symptomatic infections across the three settings over one year. The one-dose optimal strategies can avert 1.2 to 1.8 times as many cases and deaths compared to the standard two-dose strategy. Conclusions: In an outbreak setting, speedy vaccination campaigns with a single dose of OCV is likely to avert more cases and deaths than a two-dose pro-rata campaign under a limited vaccine supply. Author summary: Cholera is a major global burden, with 21,000–143,000 deaths annually. The oral cholera vaccine (OCV) is given as two doses and is less effective in children under five years old than in those aged five years and older. However, supply is limited. In this study, we used mathematical models paired with optimization algorithms to find the optimal strategies to allocate vaccines in order to minimize the number of cases and deaths for three distinct settings in Chad, Thailand, and Haiti. We found that in the short term (1 year) when there is limited vaccine supply, it is optimal to vaccinate individuals over five years old with one dose and young children under five years old with two doses. Across the three settings, these optimal strategies prevent the most cases, save the most lives, and avert 1.2 to 1.8 times as many cases and deaths as the standard two-dose untargeted strategy. Our results support that if vaccine supply is limited, under an outbreak setting, mass vaccination campaigns with a single dose of OCV may prevent more cases and save more lives than would a standard two-dose untargeted campaign. [ABSTRACT FROM AUTHOR]

An increasing number of countries are committing to meet the global target to eliminate human deaths from dog-mediated rabies by 2030. Mass dog vaccination is central to this strategy. To interrupt rabies transmission from dogs to humans, the World Health Organization recommends that vaccination campaigns should be carried out every year in all dog-owning communities vaccinating 70% of their susceptible dogs. Monitoring and evaluation of dog vaccination campaigns are needed to measure progress towards elimination. In this study, we measured the delivery performance of large-scale vaccination campaigns implemented in 25 districts in south-east Tanzania from 2010 until 2017. We used regression modelling to infer the factors associated with, and potentially influencing the successful delivery of vaccination campaigns. During 2010–2017, five rounds of vaccination campaigns were carried out, vaccinating in total 349,513 dogs in 2,066 administrative vaccination units (rural villages or urban wards). Progressively more dogs were vaccinated over the successive campaigns. The campaigns did not reach all vaccination units each year, with only 16–28% of districts achieving 100% campaign completeness (where all units were vaccinated). During 2013–2017 when vaccination coverage was monitored, approximately 20% of vaccination units achieved the recommended 70% coverage, with average coverage around 50%. Campaigns were also not completed at annual intervals, with the longest interval between campaigns being 27 months. Our analysis revealed that districts with higher budgets generally achieved higher completeness, with a twofold difference in district budget increasing the odds of a vaccination unit being reached by a campaign by slightly more than twofold (OR: 2.29; 95% CI: 1.69–3.09). However, higher budgets did not necessarily result in higher coverage within vaccination units that were reached. We recommend national programs regularly monitor and evaluate the performance of their vaccination campaigns, so as to identify factors hindering their effective delivery and to guide remedial action. Author summary: Globally there are approximately 59,000 annual human rabies deaths, with more than 99% of these resulting from dog-mediated rabies. Mass dog vaccination is known to be the cornerstone of effective control of dog rabies. Empirical and theoretical evidence shows that annual vaccination campaigns need to achieve 70% coverage of the susceptible dog population to interrupt transmission and ensure the dog population is protected until the next campaign. Recently, international organizations announced their commitment to reaching the global target of zero human deaths from dog-mediated rabies by 2030. Scaling-up of vaccinations is now underway in more than 100 rabies-endemic countries. However, there are operational and logistical challenges associated with scaling-up these operations in different geographical and cultural settings. This study monitored and evaluated the performance large-scale vaccinations in Tanzania. We found that vaccinations were not implemented in all villages, which resulted in coverage gaps. Additionally, vaccinations were not implemented annually and, as a result, coverage dropped below the critical vaccination threshold. We conclude that there is a need to improve the delivery of dog vaccinations for achieving the global target of zero dog-mediated human rabies deaths by 2030. [ABSTRACT FROM AUTHOR]

Background: Despite the effort to eradicate rabies in the Philippines, human rabies cases have not decreased in the past decade. Rabid dogs pose the most significant hazard in the countries with the highest burden of rabies, and 70% rabies vaccine coverage is recommended for dogs in high-risk areas. Ascertaining the owned dog population and community knowledge on rabies can help improve vaccine coverage and information campaigns. Methodology/Principal findings: We conducted a cross-sectional survey in six randomly selected communities (five urban, one rural) in Central Luzon, Philippines. We first conducted the complete mapping of 9,173 households and then randomly selected 727 households. More than half (54.1%) of the households owned dogs (1.21 dogs/household). In the 727 households, we identified 878 owned dogs and 3256 humans. According to these results, the dog-to-human ratio was approximately 1:3.7. Only 8.8% of households reported a history of dog bite in 2019. Among dog-owning households, 31% reported that they allow their dogs to roam freely. Of the recorded dogs, 35.9% have never been vaccinated, and only 3.5% were spayed or castrated. Factors associated with lower rabies knowledge include (1) no education aOR: 0.30 (0.16–0.59), and (2) only primary school education aOR: 0.33 (0.22–0.49). In contrast, factors associated with higher knowledge include (1) owning a dog and not allowing them to roam freely aOR: 2.01 (1.41–2.87) and (2) owning a dog and allowing them to roam freely aOR: 1.84 (1.17–2.92), when compared to those with no dogs. Conclusions/Significance: We identified a larger dog population in the community than the usual estimates (1:10), suggesting that annual vaccine needs in the Philippines must be reassessed. Our survey shows a relatively good understanding of rabies; however, awareness of the concept of rabies as a disease, and how animals and humans can acquire it, is lacking. Author summary: Rabies is a fatal disease primarily transmitted by rabid dogs. It is estimated that 59 000 human deaths occur worldwide annually because of rabies. Prevention is possible using pre-exposure prophylaxis or post-exposure prophylaxis (PEP). Despite this, rabies remains a neglected disease and a burden, particularly in developing countries. In this study, we found that the current estimated dog to human ratio of 1:10 may be incorrect. Our data show that the ratio of 1:3.7 may more closely reflect real-world figures. This finding is supported by previous studies on dog populations. We provide compelling evidence that there is a need to revise the current guidelines for estimating the dog population to provide adequate vaccine coverage. Our findings on community knowledge about rabies show that there is relatively good understanding regarding rabies; however, awareness of the concept of rabies as a disease and how animals and humans can acquire it is lacking. This should be a point of focus for future education campaigns. [ABSTRACT FROM AUTHOR]

Many countries implemented measures to control the COVID-19 pandemic, but the effects of these measures have varied greatly. We evaluated the effects of different policies, the prevalence of dominant variants (e.g., Delta), and vaccination on the characteristics of the COVID-19 pandemic in eight countries. We quantified the lag times of different non-pharmaceutical interventions (NPIs) and vaccination using a distributed lag non-linear model (DLNM). We also tested whether these lag times were reasonable by analyzing changes in daily cases and the effective reproductive number (Rt)over time. Our results indicated that the response to vaccination in countries with continuous vaccination programs lagged by at least 40 days, and the lag time for a response to NPIs was at least 14 days. A rebound was most likely to occur during the 40 days after the first vaccine dose. We also found that the combination of school closure, workplace closure, restrictions on mass gatherings, and stay-at-home requirements were successful in containing the pandemic. Our results thus demonstrated that vaccination was effective, although some regions were adversely affected by new variants and low vaccination coverage. Importantly, relaxation of NPIs soon after implementation of a vaccination program may lead to a rebound. Author summary: In response to contain the COVID-19 pandemic, countries worldwide have implemented multiple non-pharmaceutical interventions (NPIs) that restrict movement, such as school closure and stay-at-home requirements, and introduced large nationwide COVID-19 vaccination campaigns. However, there were variations in population compliance and vaccine coverage worldwide. The virus is continuously spreading and new genetic variants are emerging. In this context, we chose eight countries as being representative of the worldwide ranges of population density, variant spread, vaccination, population compliance to countermeasures, and effectiveness of implemented measures. Our study identified the most common effective countermeasures and estimated the lag times for a response to NPIs and for the onset of a vaccination effect. We found a rebound was most likely to occur during the 40 days after the first vaccine dose and both NPIs and vaccine coverage are indispensable in the current context of Delta variant high prevalence. We hope that the results of this study could provide some guidance for controlling the pandemic. [ABSTRACT FROM AUTHOR]

Background: The first community transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant of concern (VOC) in Guangzhou, China occurred between May and June 2021. Herein, we describe the epidemiological characteristics of this outbreak and evaluate the implemented containment measures against this outbreak. Methodology/Principal findings: Guangzhou Center for Disease Control and Prevention provided the data on SARS-CoV-2 infections reported between 21 May and 24 June 2021. We estimated the incubation period distribution by fitting a gamma distribution to the data, while the serial interval distribution was estimated by fitting a normal distribution. The instantaneous effective reproductive number (Rt) was estimated to reflect the transmissibility of SARS-CoV-2. Clinical severity was compared for cases with different vaccination statuses using an ordinal regression model after controlling for age. Of the reported local cases, 7/153 (4.6%) were asymptomatic. The median incubation period was 6.02 (95% confidence interval [CI]: 5.42–6.71) days and the means of serial intervals decreased from 5.19 (95% CI: 4.29–6.11) to 3.78 (95% CI: 2.74–4.81) days. The incubation period increased with age (P<0.001). A hierarchical prevention and control strategy against COVID-19 was implemented in Guangzhou, with Rt decreasing from 6.83 (95% credible interval [CrI]: 3.98–10.44) for the 7-day time window ending on 27 May 2021 to below 1 for the time window ending on 8 June and thereafter. Individuals with partial or full vaccination schedules with BBIBP-CorV or CoronaVac accounted for 15.3% of the COVID-19 cases. Clinical symptoms were milder in partially or fully vaccinated cases than in unvaccinated cases (odds ratio [OR] = 0.26 [95% CI: 0.07–0.94]). Conclusions/Significance: The hierarchical prevention and control strategy against COVID-19 in Guangzhou was timely and effective. Authorised inactivated vaccines are likely to contribute to reducing the probability of developing severe disease. Our findings have important implications for the containment of COVID-19. Author summary: On 11 May 2021, the WHO reclassified the B.1.617.2 variant as a "variant of concern" (VOC) from being a "variant of interest", considering its global public health significance. On 21 May 2021, the first local case infected with the Delta variant (i.e. lineage B.1.617.2) in Guangzhou, China, was reported. In response to the resurgence of COVID-19, the local government implemented a series of containment measures. This provides a valuable opportunity to understand the characteristics of the Delta variant and to evaluate the performance of inactivated COVID-19 vaccines (BBIBP-CorV and CoronaVac) and other interventions. We estimated that the median incubation period was 6.02 days and the means of serial intervals decreased from 5.19 to 3.78 days. The incubation period increased with age. The vaccination coverage in the COVID-19 cases was 15.3%. Clinical symptoms were milder in cases with partial or full vaccination than in those who were unvaccinated (odds ratio [OR] = 0.26). We found that the effective reproductive number decreased from 6.83 for the 7-day time window ending on 27 May 2021 to below 1 for the time window ending on 8 June and thereafter. Our findings have important implications for the containment of COVID-19. [ABSTRACT FROM AUTHOR]

Background: An estimated 75% or more of the human rabies cases in Africa occur in rural settings, which underscores the importance of rabies control in these areas. Understanding dog demographics can help design strategies for rabies control and plan and conduct canine mass vaccination campaigns effectively in African countries. Methodology/Principal findings: A cross-sectional survey was conducted to investigate domestic dog demographics in Kalambabakali, in the rural Mazabuka District of Zambia. The population of ownerless dogs and the total achievable vaccination coverage among the total dog population was estimated using the capture-recapture-based Bayesian model by conducting a canine mass vaccination campaign. This study revealed that 29% of the domestic dog population was under one year old, and 57.7% of those were under three months old and thus were not eligible for the canine rabies vaccination in Zambia. The population growth was estimated at 15% per annum based on the cross-sectional household survey. The population of ownerless dogs was estimated to be small, with an ownerless-to-owned-dog ratio of 0.01–0.06 in the target zones. The achieved overall vaccination coverage from the first mass vaccination was estimated 19.8–51.6%. This low coverage was principally attributed to the owners' lack of information, unavailability, and dog-handling difficulties. The follow-up mass vaccination campaign achieved an overall coverage of 54.8–76.2%. Conclusions/Significance: This paper indicates the potential for controlling canine rabies through mass vaccination in rural Zambia. Rabies education and responsible dog ownership are required to achieve high and sustainable vaccination coverage. Our findings also propose including puppies below three months old in the target population for rabies vaccination and emphasize that securing an annual enforcement of canine mass vaccination that reaches 70% coverage in the dog population is necessary to maintain protective herd immunity. Author summary: Because dogs are the main transmitter of rabies to humans, controlling rabies in dogs is essential for preventing rabies in humans. Canine vaccination is well-known as the most effective measure for controlling rabies in dogs. Understanding the demographics and dynamics of dog populations is important when designing efficient canine vaccination strategies. Furthermore, protective herd immunity in the total dog population should be attained through the vaccination of owned dogs since ownerless dogs are not usually covered in such campaigns. This study investigated domestic dog demographics and estimated the number of ownerless dogs to finally estimate the vaccination coverage among the overall dog population achievable through a mass vaccination campaign in a rural setting in Mazabuka District, Zambia. The target domestic dog population was young, and population growth was estimated at 15% annually based on the cross-sectional survey. The vaccination coverage attained by providing free canine mass vaccination campaigns was eventually estimated as 54.8–76.2% in the overall dog population, coupled with the estimate that the ownerless dog population was quite small. Our findings emphasize the necessity of conducting annual canine mass vaccinations, including puppies, that target 70% coverage in the dog population to maintain protective herd immunity. [ABSTRACT FROM AUTHOR]

Beginning January 2012, a humane method of dog population management using a Catch-Neuter-Vaccinate-Release (CNVR) program was implemented in Dhaka City, Bangladesh as part of the national rabies control program. To enable this program, the size and distribution of the free-roaming dog population needed to be estimated. We present the results of a dog population survey and a pilot assessment of the CNVR program coverage in Dhaka City. Free-roaming dog population surveys were undertaken in 18 wards of Dhaka City on consecutive days using mark-resight methods. Data was analyzed using Lincoln-Petersen index-Chapman correction methods. The CNVR program was assessed over the two years (2012–2013) whilst the coverage of the CNVR program was assessed by estimating the proportion of dogs that were ear-notched (processed dogs) via dog population surveys. The free-roaming dog population was estimated to be 1,242 (95 % CI: 1205–1278) in the 18 sampled wards and 18,585 dogs in Dhaka City (52 dogs/km2) with an estimated human-to-free-roaming dog ratio of 828:1. During the two year CNVR program, a total of 6,665 dogs (3,357 male and 3,308 female) were neutered and vaccinated against rabies in 29 of the 92 city wards. A pilot population survey indicated a mean CNVR coverage of 60.6% (range 19.2–79.3%) with only eight wards achieving > 70% coverage. Given that the coverage in many neighborhoods was below the WHO-recommended threshold level of 70% for rabies eradications and since the CNVR program takes considerable time to implement throughout the entire Dhaka City area, a mass dog vaccination program in the non-CNVR coverage area is recommended to create herd immunity. The findings from this study are expected to guide dog population management and the rabies control program in Dhaka City and elsewhere in Bangladesh. Author Summary: Rabies is a public health problem in Bangladesh. A CNVR program was commenced in Dhaka City in January 2012 as part of the Bangladesh national rabies control program. We describe the findings of a dog population survey that was conducted to estimate the free-roaming dog population using a mark-resight framework and the progress of the CNVR program. The free-roaming dog population in the 18 sampled wards was estimated to be 1,242 dogs, and 18,585 dogs in Dhaka City (52 dogs/km2). The estimated human-to-free-roaming dog ratio was 828:1. Between 2012 and 2013, 6,665 dogs (3,357 male, 3,308 female) were neutered and vaccinated against rabies in 29 of the 92 city wards. A pilot survey conducted in 18 wards indicated a CNVR coverage of 60.6% (range 19.2–79.5%). We recommend conducting an annual mass dog vaccination in the non-CNVR coverage area during the intervening period of the CNVR program to create herd immunity against rabies and break the cycle of rabies transmission. [ABSTRACT FROM AUTHOR]

Background: Rabies still poses a significant human health problem throughout most of Africa, where the majority of the human cases results from dog bites. Mass dog vaccination is considered to be the most effective method to prevent rabies in humans. Our objective was to systematically review research articles on dog rabies parenteral vaccination coverage in Africa in relation to dog accessibility and vaccination cost recovery arrangement (i.e.free of charge or owner charged). Methodology/Principal Findings: A systematic literature search was made in the databases of CAB abstracts (EBSCOhost and OvidSP), Scopus, Web of Science, PubMed, Medline (EBSCOhost and OvidSP) and AJOL (African Journal Online) for peer reviewed articles on 1) rabies control, 2) dog rabies vaccination coverage and 3) dog demography in Africa. Identified articles were subsequently screened and selected using predefined selection criteria like year of publication (viz. ≥ 1990), type of study (cross sectional), objective(s) of the study (i.e. vaccination coverage rates, dog demographics and financial arrangements of vaccination costs), language of publication (English) and geographical focus (Africa). The selection process resulted in sixteen peer reviewed articles which were used to review dog demography and dog ownership status, and dog rabies vaccination coverage throughout Africa. The main review findings indicate that 1) the majority (up to 98.1%) of dogs in African countries are owned (and as such accessible), 2) puppies younger than 3 months of age constitute a considerable proportion (up to 30%) of the dog population and 3) male dogs are dominating in numbers (up to 3.6 times the female dog population). Dog rabies parenteral vaccination coverage was compared between "free of charge" and "owner charged" vaccination schemes by the technique of Meta-analysis. Results indicate that the rabies vaccination coverage following a free of charge vaccination scheme (68%) is closer to the World Health Organization recommended coverage rate (70%) than the achieved coverage rate in owner-charged dog rabies vaccination schemes (18%). Conclusions/Significance: Most dogs in Africa are owned and accessible for parenteral vaccination against rabies if the campaign is performed "free of charge". Author Summary: Rabies is one of the most fatal diseases in both humans and animals. A bite by a rabid dog is the main cause of human rabies in Africa. Parenteral mass dog vaccination is the most cost-effective tool to prevent rabies in humans. Our main objective was to review research articles on the parenteral dog rabies vaccination coverage in Africa. We aimed to review published research articles on percentage of dogs owned and percentage of dogs vaccinated against rabies, and on the relation between vaccination coverage and cost recovery. We followed the standard procedures of a systematic literature review resulting in a final review of 16 scientific articles. Our review results indicate that only a small percentage of African dogs is ownerless. Puppies younger than 3 months of age constitute a considerable proportion of the African dog population. There are considerably more male dogs than female dogs present within the dog population. The dog rabies parenteral vaccination coverage following a "free of charge" vaccination scheme (68%) is closer to World Health Organization recommended threshold coverage rate (70%) compared to the coverage rate achieved in "owner-charged" dog rabies vaccination schemes (18%). In conclusion, most dogs in Africa are owned and accessible for vaccination once the necessary financial arrangements have been made. [ABSTRACT FROM AUTHOR]

Background: Killed, oral cholera vaccines have proven safe and effective, and several large-scale mass cholera vaccination efforts have demonstrated the feasibility of widespread deployment. This study uses a mathematical model of cholera transmission in Bangladesh to examine the effectiveness of potential vaccination strategies. Methods & Findings: We developed an age-structured mathematical model of cholera transmission and calibrated it to reproduce the dynamics of cholera in Matlab, Bangladesh. We used the model to predict the effectiveness of different cholera vaccination strategies over a period of 20 years. We explored vaccination programs that targeted one of three increasingly focused age groups (the entire vaccine-eligible population of age one year and older, children of ages 1 to 14 years, or preschoolers of ages 1 to 4 years) and that could occur either as campaigns recurring every five years or as continuous ongoing vaccination efforts. Our modeling results suggest that vaccinating 70% of the population would avert 90% of cholera cases in the first year but that campaign and continuous vaccination strategies differ in effectiveness over 20 years. Maintaining 70% coverage of the population would be sufficient to prevent sustained transmission of endemic cholera in Matlab, while vaccinating periodically every five years is less effective. Selectively vaccinating children 1–14 years old would prevent the most cholera cases per vaccine administered in both campaign and continuous strategies. Conclusions: We conclude that continuous mass vaccination would be more effective against endemic cholera than periodic campaigns. Vaccinating children averts more cases per dose than vaccinating all age groups, although vaccinating only children is unlikely to control endemic cholera in Bangladesh. Careful consideration must be made before generalizing these results to other regions. Author Summary: Bangladesh has a high burden of cholera and may become the first country to use cholera vaccine on a large scale. Mass cholera vaccination may be hard to justify to international funding agencies because of the modest efficacy of existing vaccines and their limited duration of protection. However, mass cholera vaccination can induce high levels of indirect protection in a population, i.e., protecting even unvaccinated individuals by lowering cholera incidence, and a case for cost-effective cholera vaccination could be made. Mathematical modeling is one way to predict the magnitude of indirect protection conferred by a proposed vaccination program. Here, we predict the effectiveness of various mass cholera vaccination strategies in Bangladesh using a mathematical model. We found that maintaining high levels of vaccination coverage in children could be very effective in reducing the burden of cholera, and secondary transmission of cholera would virtually stop when 70% of the population is vaccinated. Mathematical modeling may play a key role in planning widespread cholera vaccination efforts in Bangladesh and other countries. [ABSTRACT FROM AUTHOR]

Canine rabies can be effectively controlled by vaccination with readily available, high-quality vaccines. These vaccines should provide protection from challenge in healthy dogs, for the claimed period, for duration of immunity, which is often two or three years. It has been suggested that, in free-roaming dog populations where rabies is endemic, vaccine-induced protection may be compromised by immuno-suppression through malnutrition, infection and other stressors. This may reduce the proportion of dogs that seroconvert to the vaccine during vaccination campaigns and the duration of immunity of those dogs that seroconvert. Vaccination coverage may also be limited through insufficient vaccine delivery during vaccination campaigns and the loss of vaccinated individuals from populations through demographic processes. This is the first longitudinal study to evaluate temporal variations in rabies vaccine-induced serological responses, and factors associated with these variations, at the individual level in previously unvaccinated free-roaming dog populations. Individual-level serological and health-based data were collected from three cohorts of dogs in regions where rabies is endemic, one in South Africa and two in Indonesia. We found that the vast majority of dogs seroconverted to the vaccine; however, there was considerable variation in titres, partly attributable to illness and lactation at the time of vaccination. Furthermore, >70% of the dogs were vaccinated through community engagement and door-to-door vaccine delivery, even in Indonesia where the majority of the dogs needed to be caught by net on successive occasions for repeat blood sampling and vaccination. This demonstrates the feasibility of achieving population-level immunity in free-roaming dog populations in rabies-endemic regions. However, attrition of immune individuals through demographic processes and waning immunity necessitates repeat vaccination of populations within at least two years to ensure communities are protected from rabies. These findings support annual mass vaccination campaigns as the most effective means to control canine rabies. Author Summary: Canine-mediated rabies is a horrific disease that claims tens of thousands of human lives every year, particularly in Asia and Africa. The disease can be effectively controlled through mass vaccination of dogs with high-quality vaccines; however, questions remain over the effectiveness of vaccination where the health status of free-roaming dogs may be compromised and the life expectancy and access to these dogs may be limited. This study evaluated rabies-vaccine induced immune responses and vaccine delivery in previously unvaccinated, free-roaming dog populations in two rabies endemic regions in Asia and Africa, to better understand the effectiveness of vaccination campaigns. We found that the majority of dogs seroconverted to the vaccine regardless of health status. Excellent vaccination coverage was achieved through community engagement and door-to-door vaccine delivery, even where the majority of the dogs needed to be caught by net for vaccination. However, attrition of immune individuals through demographic processes and waning immunity reinforces the importance of frequent and regular vaccination campaigns to ensure effective vaccination coverage is maintained. [ABSTRACT FROM AUTHOR]

Background: Japanese encephalitis (JE) virus infection can cause severe disease in humans, resulting in death or permanent neurologic deficits among survivors. Studies indicate that the incidence of JE is high in northwestern Bangladesh. Pigs are amplifying hosts for JE virus (JEV) and a potentially important source of virus in the environment. The objectives of this study were to describe the transmission dynamics of JEV among pigs in northwestern Bangladesh and estimate the potential impact of vaccination to reduce incidence among pigs. Methodology/Principal Findings: We conducted a comprehensive census of pigs in three JE endemic districts and tested a sample of them for evidence of previous JEV infection. We built a compartmental model to describe JEV transmission dynamics in this region and to estimate the potential impact of pig vaccination. We identified 11,364 pigs in the study area. Previous JEV infection was identified in 30% of pigs with no spatial differences in the proportion of pigs that were seropositive across the study area. We estimated that JEV infects 20% of susceptible pigs each year and the basic reproductive number among pigs was 1.2. The model suggest that vaccinating 50% of pigs each year resulted in an estimated 82% reduction in annual incidence in pigs. Conclusions/Significance: The widespread distribution of historic JEV infection in pigs suggests they may play an important role in virus transmission in this area. Future studies are required to understand the contribution of pig infections to JE risk in humans and the potential impact of pig vaccination on human disease. Author Summary: Japanese encephalitis (JE) virus infection can cause severe neurological disease in man. More JE cases are seen in northwestern districts in Bangladesh. Pigs are the most common amplifying host of the virus and can act as a potential environmental source. We conducted a comprehensive census of pigs in three JE endemic districts and tested a sample of them for evidence of previous JEV infection. We built a compartmental model to describe JEV transmission dynamics in this region and to estimate the potential impact of pig vaccination. We identified 11,364 pigs in our study area, mostly raised in backyards. About 30% of the pigs had evidence of previous JE virus infection. Our model suggests that vaccinating 50% of pigs each year resulted in an estimated 82% reduction in annual incidence in pigs. Pigs in northwestern Bangladesh may play a significant role in JE virus transmission. JE incidence may be substantially reduced through reasonable pig vaccination coverage. [ABSTRACT FROM AUTHOR]

Background: In mass vaccination campaigns, large volumes of data must be managed efficiently and accurately. In a reactive oral cholera vaccination (OCV) campaign in rural Haiti during an ongoing epidemic, we used a mobile health (mHealth) system to manage data on 50,000 participants in two isolated communities. Methods: Data were collected using 7-inch tablets. Teams pre-registered and distributed vaccine cards with unique barcodes to vaccine-eligible residents during a census in February 2012. First stored on devices, data were uploaded nightly via Wi-fi to a web-hosted database. During the vaccination campaign between April and June 2012, residents presented their cards at vaccination posts and their barcodes were scanned. Vaccinee data from the census were pre-loaded on tablets to autopopulate the electronic form. Nightly analysis of the day's community coverage informed the following day's vaccination strategy. We generated case-finding reports allowing us to identify those who had not yet been vaccinated. Results: During 40 days of vaccination, we collected approximately 1.9 million pieces of data. A total of 45,417 people received at least one OCV dose; of those, 90.8% were documented to have received 2 doses. Though mHealth required up-front financial investment and training, it reduced the need for paper registries and manual data entry, which would have been costly, time-consuming, and is known to increase error. Using Global Positioning System coordinates, we mapped vaccine posts, population size, and vaccine coverage to understand the reach of the campaign. The hardware and software were usable by high school-educated staff. Conclusion: The use of mHealth technology in an OCV campaign in rural Haiti allowed timely creation of an electronic registry with population-level census data, and a targeted vaccination strategy in a dispersed rural population receiving a two-dose vaccine regimen. The use of mHealth should be strongly considered in mass vaccination campaigns in future initiatives. Author Summary: The World Health Organization (WHO) recently endorsed the creation of a global oral cholera vaccine (OCV) stockpile as part of an integrated, strategic framework to address the re-emerging threat that cholera causes worldwide. In conjunction, the WHO also called for continued monitoring and evaluation around the use of OCV in different settings. In response to the cholera epidemic in Haiti that began in October 2010, Partners In Health, an implementing partner of Haiti's Ministry of Health, vaccinated 50,000 Haitians in two rural communities in the Artibonite Valley in 2012. In this paper, the authors describe the use of mobile health (mHealth) technology for data collection and geospatial mapping to document this rural OCV campaign, focusing on the utility, benefits, and challenges of mHealth in a reactive campaign in the midst of the ongoing epidemic. [ABSTRACT FROM AUTHOR]

In Brazil, epizootics among New World monkey species may indicate circulation of yellow fever (YF) virus and provide early warning of risk to humans. Between 1999 and 2001, the southern Brazilian state of Rio Grande do Sul initiated surveillance for epizootics of YF in non-human primates to inform vaccination of human populations. Following a YF outbreak, we analyzed epizootic surveillance data and assessed YF vaccine coverage, timeliness of implementation of vaccination in unvaccinated human populations. From October 2008 through June 2009, circulation of YF virus was confirmed in 67 municipalities in Rio Grande do Sul State; vaccination was recommended in 23 (34%) prior to the outbreak and in 16 (24%) within two weeks of first epizootic report. In 28 (42%) municipalities, vaccination began more than two weeks after first epizootic report. Eleven (52%) of 21 laboratory-confirmed human YF cases occurred in two municipalities with delayed vaccination. By 2010, municipalities with confirmed YF epizootics reported higher vaccine coverage than other municipalities that began vaccination. In unvaccinated human populations timely response to epizootic events is critical to prevent human yellow fever cases. Author Summary: Yellow fever (YF) is a viral hemorrhagic disease that affects humans as well as several species of non-human primates, especially New World monkeys found in South America. Yellow fever virus (YFV) is maintained in a natural cycle involving tree-hole breeding mosquitoes and non-human primates hosts. Because YF is often fatal in susceptible New World monkey populations, sudden die-offs of New World monkeys or epizootics can signal YFV circulation in an environment where humans may be exposed. Surveillance for such events is an important tool to prevent human disease. The state of Rio Grande do Sul in southern Brazil was one of the first states to conduct passive and active surveillance for yellow fever virus circulation in non-human primates. During a rapidly-spreading YF outbreak in 2008–2009, surveillance for epizootics involving non-human primates informed vaccination of human populations in areas previously free of YF. In this study, we analyzed surveillance data to evaluate vaccine coverage, timeliness of notification, investigation and confirmation of epizootic events in relation to occurrence of human cases of YF. Epizootic surveillance is useful for directing the efforts of vaccine distribution. Prevention of YF in susceptible human populations requires immediate risk communication and implementation of vaccine recommendations after the first reports of epizootic activity when YF is suspected. [ABSTRACT FROM AUTHOR]

Background: Despite World Health Organization (WHO) prequalification of two safe and effective oral cholera vaccines (OCV), concerns about the acceptability, potential diversion of resources, cost and feasibility of implementing timely campaigns has discouraged their use. In 2012, the Ministry of Health of Guinea, with the support of Médecins Sans Frontières organized the first mass vaccination campaign using a two-dose OCV (Shanchol) as an additional control measure to respond to the on-going nationwide epidemic. Overall, 316,250 vaccines were delivered. Here, we present the results of vaccination coverage, acceptability and surveillance of adverse events. Methodology/Principal Findings: We performed a cross-sectional cluster survey and implemented adverse event surveillance. The study population included individuals older than 12 months, eligible for vaccination, and residing in the areas targeted for vaccination (Forécariah and Boffa, Guinea). Data sources were household interviews with verification by vaccination card and notifications of adverse events from surveillance at vaccination posts and health centres. In total 5,248 people were included in the survey, 3,993 in Boffa and 1,255 in Forécariah. Overall, 89.4% [95%CI:86.4–91.8%] and 87.7% [95%CI:84.2–90.6%] were vaccinated during the first round and 79.8% [95%CI:75.6–83.4%] and 82.9% [95%CI:76.6–87.7%] during the second round in Boffa and Forécariah respectively. The two dose vaccine coverage (including card and oral reporting) was 75.8% [95%CI: 71.2–75.9%] in Boffa and 75.9% [95%CI: 69.8–80.9%] in Forécariah respectively. Vaccination coverage was higher in children. The main reason for non-vaccination was absence. No severe adverse events were notified. Conclusions/Significance: The well-accepted mass vaccination campaign reached high coverage in a remote area with a mobile population. Although OCV should not be foreseen as the long-term solution for global cholera control, they should be integrated as an additional tool into the response. Author Summary: Two safe and effective oral cholera vaccines are recommended by the World Health Organization for cholera prevention and control; however, concerns about the acceptability, potential diversion of resources, cost and feasibility of implementing timely campaigns has discouraged their use. In 2012, the Ministry of Health of Guinea, with the support of Médecins Sans Frontières, organized the first mass vaccination campaign using a two-dose oral cholera vaccine (Shanchol) as an additional control measure to respond to an on-going nationwide epidemic. This was also the first time that Shanchol was used in a mass vaccination campaign on the African continent. High coverage was reached within a few weeks, and the campaigns were well accepted by the population. Synergies between different axes in cholera control interventions should be pursued as described here, and although oral cholera vaccines should not be foreseen as the long-term solution for global cholera control, they should be integrated as an additional tool into the outbreak response strategies. [ABSTRACT FROM AUTHOR]

Background: Canine rabies is one of the most important and feared zoonotic diseases in the world. In some regions rabies elimination is being successfully coordinated, whereas in others rabies is endemic and continues to spread to uninfected areas. As epidemics emerge, both accepted and contentious control methods are used, as questions remain over the most effective strategy to eliminate rabies. The Indonesian island of Bali was rabies-free until 2008 when an epidemic in domestic dogs began, resulting in the deaths of over 100 people. Here we analyze data from the epidemic and compare the effectiveness of control methods at eliminating rabies. Methodology/Principal Findings: Using data from Bali, we estimated the basic reproductive number, R0, of rabies in dogs, to be ∼1·2, almost identical to that obtained in ten–fold less dense dog populations and suggesting rabies will not be effectively controlled by reducing dog density. We then developed a model to compare options for mass dog vaccination. Comprehensive high coverage was the single most important factor for achieving elimination, with omission of even small areas (<0.5% of the dog population) jeopardizing success. Parameterizing the model with data from the 2010 and 2011 vaccination campaigns, we show that a comprehensive high coverage campaign in 2012 would likely result in elimination, saving ∼550 human lives and ∼$15 million in prophylaxis costs over the next ten years. Conclusions/Significance: The elimination of rabies from Bali will not be achieved through achievable reductions in dog density. To ensure elimination, concerted high coverage, repeated, mass dog vaccination campaigns are necessary and the cooperation of all regions of the island is critical. Momentum is building towards development of a strategy for the global elimination of canine rabies, and this study offers valuable new insights about the dynamics and control of this disease, with immediate practical relevance. Author Summary: Canine rabies continues to cause tens of thousands of horrific deaths worldwide, primarily in Asia and Africa. Momentum is building towards development of a global elimination strategy for canine rabies, but questions remain over how best to eliminate rabies epidemics. This paper uses data generated from the recent high-profile rabies outbreak in Bali, Indonesia to evaluate different control options. We find that, despite high dog densities, the spread of rabies on the island was remarkably similar to canine rabies spread elsewhere, suggesting that the practice of dog culling is an ineffective control strategy. We then simulate rabies transmission and spread across the island and compare the effectiveness of mass dog vaccination strategies in terms of how many lives are saved and how long it will take for elimination to be achieved. We find that the effectiveness of campaigns is not improved by being more reactive or synchronized but depends almost entirely upon reaching sufficient coverage (70%) across the population in successive campaigns. Even small 'gaps' in vaccination coverage can significantly impede the prospects of elimination. The outputs of this study provide the kind of evidence needed by rabies program coordinators to help design effective national control programmes, and to build the evidence-base to drive forward the development and implementation of effective global rabies policy. [ABSTRACT FROM AUTHOR]

Background: Japanese encephalitis (JE) is the leading cause of viral encephalitis across Asia with approximately 70,000 cases a year and 10,000 to 15,000 deaths. Because JE incidence varies widely over time, partly due to inter-annual climate variability effects on mosquito vector abundance, it becomes more complex to assess the effects of a vaccination programme since more or less climatically favourable years could also contribute to a change in incidence post-vaccination. Therefore, the objective of this study was to quantify vaccination effect on confirmed Japanese encephalitis (JE) cases in Sarawak, Malaysia after controlling for climate variability to better understand temporal dynamics of JE virus transmission and control. Methodology/principal findings: Monthly data on serologically confirmed JE cases were acquired from Sibu Hospital in Sarawak from 1997 to 2006. JE vaccine coverage (non-vaccine years vs. vaccine years) and meteorological predictor variables, including temperature, rainfall and the Southern Oscillation index (SOI) were tested for their association with JE cases using Poisson time series analysis and controlling for seasonality and long-term trend. Over the 10-years surveillance period, 133 confirmed JE cases were identified. There was an estimated 61% reduction in JE risk after the introduction of vaccination, when no account is taken of the effects of climate. This reduction is only approximately 45% when the effects of inter-annual variability in climate are controlled for in the model. The Poisson model indicated that rainfall (lag 1-month), minimum temperature (lag 6-months) and SOI (lag 6-months) were positively associated with JE cases. Conclusions/significance: This study provides the first improved estimate of JE reduction through vaccination by taking account of climate inter-annual variability. Our analysis confirms that vaccination has substantially reduced JE risk in Sarawak but this benefit may be overestimated if climate effects are ignored. Author Summary: Japanese encephalitis (JE) virus is a mosquito-borne virus which is the leading cause of viral encephalitis in Asia. The cumulative attack rate for human JE cases is seemingly low (2-cases/105/year); however, epidemics are focal and intense, being concentrated in children 1 to 15 years of age and highly clustered spatially. Despite the availability of a vaccine against JE virus (JEV), a significant number of JE cases still occur in Asia. Increases in disease cases may occur in some countries, such as Indonesia and Bangladesh, due to increasing rice cultivation, pig husbandry and lack of vaccination or vector control programs in these areas. However, given the sensitivity of JEV transmission to climate through impacts on the mosquito vectors, changes in climate may increase or decrease JEV transmission. Clearly, JE vaccination has substantially reduced JE cases, but it is not clear if climate has any confounding impact on our ability to estimate vaccine effect. We found that approximately one quarter of the reduction in JE cases since vaccination was introduced might be attributable to climatically unfavourable years for the disease, rather than the effect of vaccination. Vaccination studies involving climate-sensitive diseases may be made more accurate by taking climate effects into account. [ABSTRACT FROM AUTHOR]

Background: Kyasanur forest disease (KFD), a tick-borne viral disease with hemorrhagic manifestations, is localised in five districts of Karnataka state, India. Annual rounds of vaccination using formalin inactivated tissue-culture vaccine have been conducted in the region since 1990. Two doses of vaccine are administered to individuals aged 7–65 years at an interval of one month followed by periodic boosters after 6–9 months. In spite of high effectiveness of the vaccine reported in earlier studies, KFD cases among vaccinated individuals have been recently reported. We analysed KFD vaccination and case surveillance data from 2005 to 2010. Methodology/Principal Findings: We calculated KFD incidence among vaccinated and unvaccinated populations and computed the relative risk and vaccine effectiveness. During 2005–2010, a total of 343,256 individuals were eligible for KFD vaccination (details of vaccination for 2008 were not available). Of these, 52% did not receive any vaccine while 36% had received two doses and a booster. Of the 168 laboratory-confirmed KFD cases reported during this 5-year period, 134 (80%) were unvaccinated, nine each had received one and two doses respectively while 16 had received a booster during the pre-transmission season. The relative risks of disease following one, two and booster doses of vaccine were 1.06 (95% CI = 0.54–2.1), 0.38 (95% CI = 0.19–0.74) and 0.17 (95% CI = 0.10–0.29) respectively. The effectiveness of the vaccine was 62.4% (95% CI = 26.1–80.8) among those who received two doses and 82.9% (95% CI = 71.3–89.8) for those who received two doses followed by a booster dose as compared to the unvaccinated individuals. Conclusions: Coverage of KFD vaccine in the study area was low. Observed effectiveness of the KFD vaccine was lower as compared to the earlier reports, especially after a single dose administration. Systematic efforts are needed to increase the vaccine coverage and identify the reasons for lower effectiveness of the vaccine in the region. Author Summary: Kyasanur forest disease (KFD), a tick-borne viral disease with hemorrhagic manifestations, occurs as seasonal outbreaks in five districts of Karnataka state, India. Vaccination with formalin inactivated tissue-culture vaccine is the key strategy for the prevention of the disease in the region. In spite of high effectiveness of the vaccine reported in earlier studies, KFD cases among vaccinated individuals have been recently reported. We analysed KFD vaccination and case surveillance data from 2005 to 2010 to estimate the coverage and efficacy of the vaccine under programme conditions. Vaccination coverage was low with less than 50% of the population vaccinated. The effectiveness of the vaccine was 62.4% (95% CI = 26.1–80.8) among those who received two doses and 82.9% (95% CI = 71.3–89.8) for those who received an additional booster dose as compared to the unvaccinated individuals. Systematic efforts are needed to increase the vaccine coverage and identify the reasons for lower efficacy of the vaccine in the region. [ABSTRACT FROM AUTHOR]

Canine vaccination has been successful in controlling rabies in diverse settings worldwide. However, concerns remain that coverage levels which have previously been sufficient might be insufficient in systems where transmission occurs both between and within populations of domestic dogs and other carnivores. To evaluate the effectiveness of vaccination targeted at domestic dogs when wildlife also contributes to transmission, we applied a next-generation matrix model based on contract tracing data from the Ngorongoro and Serengeti Districts in northwest Tanzania. We calculated corresponding values of R0, and determined, for policy purposes, the probabilities that various annual vaccination targets would control the disease, taking into account the empirical uncertainty in our field data. We found that transition rate estimates and corresponding probabilities of vaccination-based control indicate that rabies transmission in this region is driven by transmission within domestic dogs. Different patterns of rabies transmission between the two districts exist, with wildlife playing a more important part in Ngorongoro and leading to higher recommended coverage levels in that district. Nonetheless, our findings indicate that an annual dog vaccination campaign achieving the WHO-recommended target of 70% will control rabies in both districts with a high level of certainty. Our results support the feasibility of controlling rabies in Tanzania through dog vaccination. Author Summary: The vaccination of dogs against rabies is an effective method for the control of the disease and its transmission to humans in many locations, including in North America and Europe. However, vaccination coverage for only dogs might be insufficient in countries such as Tanzania, where wildlife has been shown to also carry and transmit rabies. To address this concern, we developed a model parameterized with field data on rabies in dogs and wildlife from two districts of Tanzania, Ngorongoro and Serengeti. Our study found significant variation in the patterns of rabies transmission between the two districts, with wildlife playing a more important part in rabies transmission in Ngorongoro. Based on these findings, a higher vaccination coverage level against rabies is necessary in Ngorongoro more than in Serengeti, although it is still possible to achieve the required level of vaccination coverage for Ngorongoro through dog vaccination alone. An annual dog vaccination campaign at the WHO-recommended target of 70% would control rabies in both districts. [ABSTRACT FROM AUTHOR]

Background: Human outbreaks of Ebola virus (EBOV) are a serious human health concern in Central Africa. Great apes (gorillas/chimpanzees) are an important source of EBOV transmission to humans due to increased hunting of wildlife including the 'bush-meat' trade. Cytomegalovirus (CMV) is an highly immunogenic virus that has shown recent utility as a vaccine platform. CMV-based vaccines also have the unique potential to re-infect and disseminate through target populations regardless of prior CMV immunity, which may be ideal for achieving high vaccine coverage in inaccessible populations such as great apes. Methodology/Principal Findings: We hypothesize that a vaccine strategy using CMV-based vectors expressing EBOV antigens may be ideally suited for use in inaccessible wildlife populations. To establish a 'proof-of-concept' for CMV-based vaccines against EBOV, we constructed a mouse CMV (MCMV) vector expressing a CD8+ T cell epitope from the nucleoprotein (NP) of Zaire ebolavirus (ZEBOV) (MCMV/ZEBOV-NPCTL). MCMV/ZEBOV-NPCTL induced high levels of long-lasting (>8 months) CD8+ T cells against ZEBOV NP in mice. Importantly, all vaccinated animals were protected against lethal ZEBOV challenge. Low levels of anti-ZEBOV antibodies were only sporadically detected in vaccinated animals prior to ZEBOV challenge suggesting a role, at least in part, for T cells in protection. Conclusions/Significance: This study demonstrates the ability of a CMV-based vaccine approach to protect against an highly virulent human pathogen, and supports the potential for 'disseminating' CMV-based EBOV vaccines to prevent EBOV transmission in wildlife populations. Author Summary: Human outbreaks of hemorrhagic disease caused by Ebola virus (EBOV) are a serious health concern in Central Africa. Great apes (gorillas/chimpanzees) are an important source of EBOV transmission to humans. Candidate EBOV vaccines do not spread from the initial vaccinee. In addition to being highly immunogenic, vaccines based on the cytomegalovirus (CMV) platform have the unique potential to re-infect and disseminate through target populations. To explore the utility of CMV-based vaccines against EBOV, we constructed a mouse CMV (MCMV) vector expressing a region of nucleoprotein (NP) of Zaire ebolavirus (ZEBOV) (MCMV/ZEBOV-NPCTL). MCMV/ZEBOV-NPCTL induced high levels of long-lasting CD8+ T cells against ZEBOV NP in mice. Importantly, all vaccinated animals were protected against lethal ZEBOV challenge. The absence of ZEBOV neutralizing and only low, sporadic levels of total anti-ZEBOV IgG antibodies in protected animals prior to ZEBOV challenge indicate a role, albeit perhaps not exclusive, for CD8+ T cells in mediating protection. This study demonstrates the ability of a CMV-based vaccine approach to protect against ZEBOV, and provides a 'proof-of-concept' for the potential for a 'disseminating' CMV-based EBOV vaccine to prevent EBOV transmission in wild animal populations. [ABSTRACT FROM AUTHOR]

Introduction: The outbreak of cholera in Zimbabwe intensified interest in the control and prevention of cholera. While there is agreement that safe water, sanitation, and personal hygiene are ideal for the long term control of cholera, there is controversy about the role of newer approaches such as oral cholera vaccines (OCVs). In October 2009 the Strategic Advisory Group of Experts advised the World Health Organization to consider reactive vaccination campaigns in response to large cholera outbreaks. To evaluate the potential benefit of this pivotal change in WHO policy, we used existing data from cholera outbreaks to simulate the number of cholera cases preventable by reactive mass vaccination. Methods: Datasets of cholera outbreaks from three sites with varying cholera endemicity—Zimbabwe, Kolkata (India), and Zanzibar (Tanzania)—were analysed to estimate the number of cholera cases preventable under differing response times, vaccine coverage, and vaccine doses. Findings: The large cholera outbreak in Zimbabwe started in mid August 2008 and by July 2009, 98,591 cholera cases had been reported with 4,288 deaths attributed to cholera. If a rapid response had taken place and half of the population had been vaccinated once the first 400 cases had occurred, as many as 34,900 (40%) cholera cases and 1,695 deaths (40%) could have been prevented. In the sites with endemic cholera, Kolkata and Zanzibar, a significant number of cases could have been prevented but the impact would have been less dramatic. A brisk response is required for outbreaks with the majority of cases occurring during the early weeks. Even a delayed response can save a substantial number of cases and deaths in long, drawn-out outbreaks. If circumstances prevent a rapid response there are good reasons to roll out cholera mass vaccination campaigns well into the outbreak. Once a substantial proportion of a population is vaccinated, outbreaks in subsequent years may be reduced if not prevented. A single dose vaccine would be of advantage in short, small outbreaks. Conclusions: We show that reactive vaccine use can prevent cholera cases and is a rational response to cholera outbreaks in endemic and non-endemic settings. In large and long outbreaks a reactive vaccination with a two-dose vaccine can prevent a substantial proportion of cases. To make mass vaccination campaigns successful, it would be essential to agree when to implement reactive vaccination campaigns and to have a dynamic and determined response team that is familiar with the logistic challenges on standby. Most importantly, the decision makers in donor and recipient countries have to be convinced of the benefit of reactive cholera vaccinations. Author Summary: Cholera outbreaks have had catastrophic impact on societies for centuries. Despite more than half a century of advocacy for safe water, sanitation and hygiene, approximately 100,000 cholera cases and 5,000 deaths were reported in Zimbabwe between August 2008 and by July 2009. Safe and effective oral cholera vaccines have been licensed and used by affluent tourists for more than a decade to prevent cholera. We asked whether oral cholera vaccines could be used to protect high risk populations at a time of cholera. We calculated how many cholera cases could have been prevented if mass cholera vaccinations would have been implemented in reaction to past cholera outbreaks. We estimate that determined, well organized mass vaccination campaigns could have prevented 34,900 (40%) cholera cases and 1,695 deaths (40%) in Zimbabwe. In the sites with endemic cholera, Kolkata and Zanzibar, a significant number of cases could have been prevented but the impact would have been less dramatic. The barriers which currently prevent the implementation of mass vaccinations, including but not only the cost to purchase the vaccine, seem insurmountable. A concerted effort of donors and key decision makers will be needed to offer better protection to populations at risk. [ABSTRACT FROM AUTHOR]

Introduction: Subacute sclerosing panencephalitis (SSPE) is a late, rare and usually fatal complication of measles infection. Although a very high incidence of SSPE in Papua New Guinea (PNG) was first recognized 20 years ago, estimated measles vaccine coverage has remained at ≤70% since and a large measles epidemic occurred in 2002. We report a series of 22 SSPE cases presenting between November 2007 and July 2009 in Madang Province, PNG, including localized clusters with the highest ever reported annual incidence. Methodology/Principal Findings: As part of a prospective observational study of severe childhood illness at Modilon Hospital, the provincial referral center, children presenting with evidence of meningo-encephalitis were assessed in detail including lumbar puncture in most cases. A diagnosis of SSPE was based on clinical features and presence of measles-specific IgG in cerebrospinal fluid and/or plasma. The estimated annual SSPE incidence in Madang province was 54/million population aged <20 years, but four sub-districts had an incidence >100/million/year. The distribution of year of birth of the 22 children with SSPE closely matched the reported annual measles incidence in PNG, including a peak in 2002. Conclusions/Significance: SSPE follows measles infections in very young PNG children. Because PNG children have known low seroconversion rates to the first measles vaccine given at 6 months of age, efforts such as supplementary measles immunisation programs should continue in order to reduce the pool of non-immune people surrounding the youngest and most vulnerable members of PNG communities. Author Summary: Subacute sclerosing panencephalitis (SSPE) is a disabling and usually fatal brain disorder that typically occurs 3–10 years after acute measles infection. Papua New Guinea (PNG) has particularly high rates of SSPE. We report 22 cases of PNG children presenting to the provincial referral hospital in Madang Province who probably contracted acute measles when <12 months of age during a national epidemic in 2002 and who developed SSPE 5–7 years later. Based on these cases, the estimated annual SSPE incidence in Madang province in 2007–2009 was 54/million population aged <20 years. Four sub-districts had an annual incidence >100/million population aged <20 years, the highest rates ever reported. Young PNG children do not respond well to measles vaccine. Because of this, efforts such as supplementary measles immunisation programs should continue in order to reduce the pool of non-immune older people surrounding the youngest and most vulnerable members of PNG communities. [ABSTRACT FROM AUTHOR]

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

In Latin America, there has been tremendous progress towards eliminating canine rabies. Major components of rabies elimination programs leading to these successes have been constant and regular surveillance for rabid dogs and uninterrupted yearly mass dog vaccination campaigns. Unfortunately, vital measures to control COVID-19 have had the negative trade-off of jeopardizing these rabies elimination and prevention activities. We aimed to assess the effect of interrupting canine rabies surveillance and mass dog vaccination campaigns on rabies trends. We built a deterministic compartment model of dog rabies dynamics to create a conceptual framework for how different disruptions may affect rabies virus transmission. We parameterized the model for conditions found in Arequipa, Peru, a city with active rabies virus transmission. We examined our results over a range of plausible values for R0 (1.36-2.0). Also, we prospectively evaluated surveillance data during the pandemic to detect temporal changes. Our model suggests that a decrease in canine vaccination coverage as well as decreased surveillance could lead to a sharp rise in canine rabies within months. These results were consistent over all plausible values of R0. Surveillance data from late 2020 and early 2021 confirms that in Arequipa, Peru, rabies cases are on an increasing trajectory. The rising rabies trends in Arequipa, if indicative to the region as whole, suggest that the achievements made in Latin America towards the elimination of dog-mediated human rabies may be in jeopardy., Competing Interests: The authors have declared that no competing interests exist.

Oral cholera vaccine (OCV) has increasingly been used as an outbreak control measure, but vaccine shortages limit its application. A two-dose OCV campaign targeting residents aged over 1 year was launched in three rural Communes of Southern Haiti during an outbreak following Hurricane Matthew in October 2016. Door-to-door and fixed-site strategies were employed and mobile teams delivered vaccines to hard-to-reach communities. This was the first campaign to use the recently pre-qualified OCV, Euvichol. The study objective was to estimate post-campaign vaccination coverage in order to evaluate the campaign and guide future outbreak control strategies. We conducted a cluster survey with sampling based on random GPS points. We identified clusters of five households and included all members eligible for vaccination. Local residents collected data through face-to-face interviews. Coverage was estimated, accounting for the clustered sampling, and 95% confidence intervals calculated. 435 clusters, 2,100 households and 9,086 people were included (99% response rate). Across the three communes respectively, coverage by recall was: 80.7% (95% CI:76.8-84.1), 82.6% (78.1-86.4), and 82.3% (79.0-85.2) for two doses and 94.2% (90.8-96.4), 91.8% (87-94.9), and 93.8% (90.8-95.9) for at least one dose. Coverage varied by less than 9% across age groups and was similar among males and females. Participants obtained vaccines from door-to-door vaccinators (53%) and fixed sites (47%). Most participants heard about the campaign through community 'criers' (58%). Despite hard-to-reach communities, high coverage was achieved in all areas through combining different vaccine delivery strategies and extensive community mobilisation. Emergency OCV campaigns are a viable option for outbreak control and where possible multiple strategies should be used in combination. Euvichol will help alleviate the OCV shortage but effectiveness studies in outbreaks should be done., Competing Interests: The authors have declared that no competing interests exist.

To control and prevent rabies in Latin America, mass dog vaccination campaigns (MDVC) are implemented mainly through fixed-location vaccination points: owners have to bring their dogs to the vaccination points where they receive the vaccination free of charge. Dog rabies is still endemic in some Latin-American countries and high overall dog vaccination coverage and even distribution of vaccinated dogs are desired attributes of MDVC to halt rabies virus transmission. In Arequipa, Peru, we conducted a door-to-door post-campaign survey on >6,000 houses to assess the placement of vaccination points on these two attributes. We found that the odds of participating in the campaign decreased by 16% for every 100 m from the owner's house to the nearest vaccination point (p = 0.041) after controlling for potential covariates. We found social determinants associated with participating in the MDVC: for each child under 5 in the household, the odds of participating in the MDVC decreased by 13% (p = 0.032), and for each decade less lived in the area, the odds of participating in the MDVC decreased by 8% (p<0.001), after controlling for distance and other covariates. We also found significant spatial clustering of unvaccinated dogs over 500 m from the vaccination points, which created pockets of unvaccinated dogs that may sustain rabies virus transmission. Understanding the barriers to dog owners' participation in community-based dog-vaccination programs will be crucial to implementing effective zoonotic disease preventive activities. Spatial and social elements of urbanization play an important role in coverage of MDVC and should be considered during their planning and evaluation., Competing Interests: The authors have declared that no competing interests exist.

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.