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Introduction Globally, traditional medicine is widely used to treat a variety of injuries and illnesses, including dog bites, and exposures that are risky for rabies. However, efficacy of most traditional remedies used for rabies prevention or treatment has not been demonstrated in controlled trials or proven in community-based surveys. Methods Six databases were searched including the terms rabies, traditional treatment, traditional remedy, traditional therapy, traditional medicine, and medicinal treatment to review traditional remedies used in the prevention and treatment of rabies. In addition, published literature of rabies transmission dynamics was used to estimate statistical likelihood of dog bite victims developing rabies to provide clarity as to why traditional healers have a high apparent success rate when preventing death from rabies in victims bitten by suspected rabid dogs. Results Literature review yielded 50 articles, including three controlled experiments, that described use of traditional remedies for rabies prevention and treatment. Traditional remedies for rabies ranged from plant- or animal-based products to spiritual rituals; however, only a few controlled mice trials were conducted, and none of these trials demonstrated efficacy in preventing or treating rabies. Risk of dying from rabies after a bite from a dog with unknown rabies status is low, 1.90% (0.05%-29.60%). Therefore, traditional healers had a 98.10% (70.40%-99.95%) apparent success rate in preventing death from suspected rabid dog bites despite inefficaciousness of herbal remedies. Conclusion There was no universal plant species or route of administration that was consistently used for rabies prevention or treatment across countries. No traditional remedy was efficacious in the prevention or treatment of rabies in randomized controlled experiments. Understanding the cultural context under which traditional remedies are used may facilitate collaboration of traditional healers with the modern medical system to ensure timely and appropriate use of proven therapies for prevention and clinical management of rabies., Author summary Traditional medicine is commonly used worldwide for a variety of ailments and diseases, including animal bite wound care and pre-clinical rabies prevention. Traditional healers often use herbal-based remedies containing local plants. Other traditional remedies include animal-based or spiritual-based methods. This literature review included plant surveys, controlled mice experiments, and community-based studies concerning rabies prevention provided by traditional healers in multiple countries. There was no consistent remedy used across the published literature, and most importantly, there were no published studies supporting effective traditional medicine methods for use in the prevention or treatment of human rabies. Our review of rabies virus transmission rates show that traditional healers have a high apparent success rate of preventing rabies deaths from dog bites, but there is no scientific or medical basis for this perception. Educating communities about proven, effective rabies prevention through post-exposure prophylaxis while understanding the cultural importance of traditional medicine is needed for promoting effective rabies prevention.

Background In India, leprosy clusters at hamlet level but detailed information is lacking. We aim to identify high-incidence hamlets to be targeted for active screening and post-exposure prophylaxis. Methodology We paid home visits to a cohort of leprosy patients registered between April 1st, 2020, and March 31st, 2022. Patients were interviewed and household members were screened for leprosy. We used an open-source app(ODK) to collect data on patients’ mobility, screening results of household members, and geographic coordinates of their households. Clustering was analysed with Kulldorff’s spatial scan statistic(SaTScan). Outlines of hamlets and population estimates were obtained through an open-source high-resolution population density map(https://data.humdata.org), using kernel density estimation in QGIS, an open-source software. Results We enrolled 169 patients and screened 1,044 household contacts in Bisfi and Benipatti blocks of Bihar. Median number of years of residing in the village was 17, interquartile range(IQR)12-30. There were 11 new leprosy cases among 658 household contacts examined(167 per 10,000), of which seven had paucibacillary leprosy, one was a child under 14 years, and none had visible disabilities. We identified 739 hamlets with a total population of 802,788(median 163, IQR 65–774). There were five high incidence clusters including 12% of the population and 46%(78/169) of the leprosy cases. One highly significant cluster with a relative risk (RR) of 4.7(p Conclusions We found a high yield of active household contact screening. Our tools for identifying high-incidence hamlets appear effective. Focusing labour-intensive interventions such as door-to-door screening on such hamlets could increase efficiency.

Background An evaluation of postexposure prophylaxis (PEP) surveillance has not been conducted in over 10 years in the United States. An accurate assessment would be important to understand current rabies trends and inform public health preparedness and response to human rabies. Methodology/Principle findings To understand PEP surveillance, we sent a survey to public health leads for rabies in 50 U.S. states, Puerto Rico, Washington DC, Philadelphia, and New York City. Of leads from 54 jurisdictions, 39 (72%) responded to the survey; 12 reported having PEP-specific surveillance, five had animal bite surveillance that included data about PEP, four had animal bite surveillance without data about PEP, and 18 (46%) had neither. Although 12 jurisdictions provided data about PEP use, poor data quality and lack of national representativeness prevented use of this data to derive a national-level PEP estimate. We used national-level and state specific data from the Healthcare Cost & Utilization Project (HCUP) to estimate the number of people who received PEP based on emergency department (ED) visits. The estimated annual average of initial ED visits for PEP administration during 2012–2017 in the United States was 46,814 (SE: 1,697), costing upwards of 165 million USD. State-level ED data for initial visits for administration of PEP for rabies exposure using HCUP data was compared to state-level surveillance data from Maryland, Vermont, and Georgia between 2012–2017. In all states, state-level surveillance data was consistently lower than estimates of initial ED visits, suggesting even states with robust PEP surveillance may not adequately capture individuals who receive PEP. Conclusions Our findings suggest that making PEP a nationally reportable condition may not be feasible. Other methods of tracking administration of PEP such as syndromic surveillance or identification of sentinel states should be considered to obtain an accurate assessment., Author summary Although rabies is nearly always fatal, it is also almost 100% preventable. While thousands of people receive PEP each year, the total amount of PEP administered in the United States and whether it is administered correctly, is unknown. To understand PEP use nationally, the National Association of State Public Health Veterinarians in collaboration with the Centers for Disease Control and Prevention (CDC), sent a survey to public health professionals in the 50 U.S. states, Puerto Rico, Washington DC, Philadelphia, and New York City. Only half of responding jurisdictions had some method of tracking the number of people who had an animal bite or received rabies PEP; these methods differed in quality and completeness. For three states that had PEP data from their surveillance systems and also state-level emergency department (ED) data on the number of initial ED visits for PEP administration, discordant numbers suggested that the number of people who receive PEP may be much higher than estimated. Monitoring PEP administration through ED data could be one way to ensure that people receive appropriate PEP after an exposure and that costs are better understood.

Rabies is endemic in Cambodia. For exposed humans, post-exposure prophylaxis (PEP) is very effective in preventing this otherwise fatal disease. The Institut Pasteur du Cambodge (IPC) in Phnom Penh was the primary distributor of PEP in Cambodia until 2018. Since then, and to increase distribution of PEP, two new centers have been opened by IPC in the provinces of Battambang and Kampong Cham. Data on bitten patients, who sometimes bring the head of the biting animal for rabies analyses, have been recorded by IPC since 2000. However, human cases are not routinely recorded in Cambodia, making it difficult to establish a human burden of disease and generate a risk map of dog bites to inform the selection of future PEP center locations in high-risk areas. Our aim was to assess the impact of accessibility to rabies centers on the yearly rate of PEP patients in the population and generate a risk map to identify the locations where new centers would be the most beneficial to the Cambodian population. To accomplish this, we used spatio-temporal Bayesian regression models with the number of PEP patients as the outcome. The primary exposure variable considered was travel time to the nearest IPC center. Secondary exposure variables consisted of travel time to a provincial capital and urban proportion of the population. Between 2000 and 2016, a total of 293,955 PEP patient records were identified. Our results showed a significant negative association between travel time to IPC and the rate of PEP patients: an increase in one hour travel time from the living location to IPC PEP centers leads to a reduction in PEP rate of 70% to 80%. Five provinces were identified as the most efficient locations for future centers to maximize PEP accessibility: Banteay Meanchey, Siem Reap, Takeo, Kampot and Svay Rieng. Adding a PEP center in every provincial capital would increase the proportion of Cambodians living within 60 minutes of a PEP center from 26.6% to 64.9%, and living within 120 minutes from 52.8% to 93.3%, which could save hundreds of lives annually.

Background Rabies is a viral zoonosis that imposes a substantial disease and economic burden in many developing countries. Dogs are the primary source of rabies transmission; eliminating dog rabies reduces the risk of exposure in humans significantly. Through mass annual dog rabies vaccination campaigns, the national program of rabies control in Mexico progressively reduced rabies cases in dogs and humans since 1990. In 2019, the World Health Organization validated Mexico for eliminating rabies as a public health problem. Using a governmental perspective, we retrospectively assessed the economic costs, effectiveness, and cost-effectiveness of the national program of rabies control in Mexico, 1990–2015. Methodology Combining various data sources, including administrative records, national statistics, and scientific literature, we retrospectively compared the current scenario of annual dog vaccination campaigns and post-exposure prophylaxis (PEP) with a counterfactual scenario without an annual dog vaccination campaign but including PEP. The counterfactual scenario was estimated using a mathematical model of dog rabies transmission (RabiesEcon). We performed a thorough sensitivity analysis of the main results. Principal findings Results suggest that in 1990 through 2015, the national dog rabies vaccination program in Mexico prevented about 13,000 human rabies deaths, at an incremental cost (MXN 2015) of $4,700 million (USD 300 million). We estimated an average cost of $360,000 (USD 23,000) per human rabies death averted, $6,500 (USD 410) per additional year-of-life, and $3,000 (USD 190) per dog rabies death averted. Results were robust to several counterfactual scenarios, including high and low rabies transmission scenarios and various assumptions about potential costs without mass dog rabies vaccination campaigns. Conclusions Annual dog rabies vaccination campaigns have eliminated the transmission of dog-to-dog rabies and dog-mediated human rabies deaths in Mexico. According to World Health Organization standards, our results show that the national program of rabies control in Mexico has been highly cost-effective., Author summary Rabies is a virus that affects wild and domestic animals that can affect humans. Rabies infection is almost certainly fatal once clinical symptoms appear but can be prevented with timely post-exposure prophylaxis administration. Dogs are the primary source of rabies transmission; eliminating dog rabies reduces the risk of exposure in humans significantly. In Mexico, the national program of dog rabies vaccination has accomplished a progressive reduction of rabies episodes since 1990. The impact of these campaigns has not been systematically assessed, and that evaluation is critical to inform public health decisions. Using a mathematical model of rabies transmission, we estimated the costs and effectiveness of the dog rabies vaccination program in Mexico, compared to a scenario with no vaccination. Our results suggest that from 1990 through 2015, the national dog rabies vaccination program in Mexico prevented about 13,000 human rabies deaths, at an additional cost (MXN 2015) of $4,700 million (USD 300 million). We estimated an average cost of $360,000 (USD 23,000) per human rabies death averted, $6,500 (USD 410) per additional year-of-life, and $3,000 (USD 190) per dog rabies death averted. According to World Health Organization standards, the annual dog vaccination campaign in Mexico is highly cost-effective.

Ebola virus (EBOV) is one of the most virulent pathogens that causes hemorrhagic fever and displays high mortality rates and low prognosis rates in both humans and nonhuman primates. The post-exposure antibody therapies to prevent EBOV infection are considered effective as of yet. However, owing to the poor thermal stability of mammalian antibodies, their application in the tropics has remained limited. Therefore, a thermostable therapeutic antibody against EBOV was developed modelled on the poultry(chicken) immunoglobulin Y (IgY). The IgY antibodies retaining their neutralising activity at 25°C for one year, displayed excellent thermal stability, opposed to conventional polyclonal antibodies (pAbs) or monoclonal antibodies (mAbs). Laying hens were immunised with a variety of EBOV vaccine candidates and it was confirmed that VSVΔG/EBOVGP encoding the EBOV glycoprotein could induce high titer neutralising antibodies against EBOV. The therapeutic efficacy of immune IgY antibodies in vivo was evaluated in the newborn Balb/c mice who have been challenged with the VSVΔG/EBOVGP model. Mice that have been challenged with a lethal dose of the pseudovirus were treated 2 or 24 h post-infection with different doses of anti-EBOV IgY. The group receiving a high dose of 106 NAU/kg (neutralising antibody units/kilogram) showed complete protection with no symptoms of a disease, while the low-dose group was only partially protected. Conversely, all mice receiving naive IgY died within 10 days. In conclusion, the anti-EBOV IgY exhibits excellent thermostability and protective efficacy. Anti-EBOV IgY shows a lot of promise in entering the realm of efficient Ebola virus treatment regimens., Author summary Despite the amount of efficient Ebola virus therapeutic antibodies reported in recent years, their application in tropical endemic areas has remained limited due to the low thermal stability of mammalian antibodies. A highly thermostable therapeutic polyclonal antibody against EBOV was developed based on chicken immunoglobulin Y (IgY). The EBOV specific IgY antibodies displayed excellent thermal stability, retaining their neutralising activity at 25°C for one year. The newborn mice receiving the passive transfer of IgY achieved complete protection against a lethal dose of virus challenge proving that the anti-EBOV IgY provides a promising recourse to solve some of the current clinical application hindrances of Ebola antibody-based treatments in Africa due to thermal stability.

Background Post-exposure prophylaxis (PEP) is highly effective at preventing human rabies deaths, however access to PEP is limited in many rabies endemic countries. The 2018 decision by Gavi to add human rabies vaccine to its investment portfolio should expand PEP availability and reduce rabies deaths. We explore how geographic access to PEP impacts the rabies burden in Madagascar and the potential benefits of improved provisioning. Methodology & principal findings We use spatially resolved data on numbers of bite patients seeking PEP across Madagascar and estimates of travel times to the closest clinic providing PEP (N = 31) in a Bayesian regression framework to estimate how geographic access predicts reported bite incidence. We find that travel times strongly predict reported bite incidence across the country. Using resulting estimates in an adapted decision tree, we extrapolate rabies deaths and reporting and find that geographic access to PEP shapes burden sub-nationally. We estimate 960 human rabies deaths annually (95% Prediction Intervals (PI): 790–1120), with PEP averting an additional 800 deaths (95% PI: 640–970) each year. Under these assumptions, we find that expanding PEP to one clinic per district (83 additional clinics) could reduce deaths by 19%, but even with all major primary clinics provisioning PEP (1733 additional clinics), we still expect substantial rabies mortality. Our quantitative estimates are most sensitive to assumptions of underlying rabies exposure incidence, but qualitative patterns of the impacts of travel times and expanded PEP access are robust. Conclusions & significance PEP is effective at preventing rabies deaths, and in the absence of strong surveillance, targeting underserved populations may be the most equitable way to provision PEP. Given the potential for countries to use Gavi funding to expand access to PEP in the coming years, this framework could be used as a first step to guide expansion and improve targeting of interventions in similar endemic settings where PEP access is geographically restricted and baseline data on rabies risk is lacking. While better PEP access should save many lives, improved outreach, surveillance, and dog vaccination will be necessary, and if rolled out with Gavi investment, could catalyze progress towards achieving zero rabies deaths., Author summary Canine rabies causes an estimated 60,000 deaths each year across the world, primarily in low- and middle-income countries where people have limited access to both human vaccines (post-exposure prophylaxis or PEP) and dog rabies vaccines. Given that we have the tools to prevent rabies deaths, a global target has been set to eliminate deaths due to canine rabies by 2030, and recently, Gavi, a multilateral organization that aims to improve access to vaccines in the poorest countries, added human rabies vaccine to it’s portfolio. In this study, we estimated reported incidence of patients seeking PEP in relation to travel times to clinics provisioning PEP and extrapolate human rabies deaths in Madagascar. We find that PEP currently averts around 800 deaths each year, but that the burden remains high (1000 deaths/year), particularly in remote, hard-to-reach areas. We show that expanding PEP availability to more clinics could significantly reduce rabies deaths in Madagascar, but our results reaffirm that expansion alone is will not achieve the global goal of zero human deaths from dog-mediated rabies by 2030. Combining PEP expansion with outreach, surveillance, and mass dog vaccination programs will be necessary to move Madagascar, and other Low- and Middle-Income countries, forward on the path to rabies elimination.

India has the highest burden of leprosy in the world. Following a recent WHO guideline, the Indian National Leprosy Programme is introducing post-exposure prophylaxis with single-dose rifampicin (SDR-PEP) in all high-endemic districts of the country. The aim of this study is to estimate the long-term cost-effectiveness of SDR-PEP in different leprosy disability burden situations. We used a stochastic individual-based model (SIMCOLEP) to simulate the leprosy new case detection rate trend and the impact of implementing contact screening and SDR-PEP from 2016 to 2040 (25 years) in the Union Territory of Dadra Nagar Haveli (DNH) in India. Effects of the intervention were expressed as disability adjusted life years (DALY) averted under three assumption of disability prevention: 1) all grade 1 disability (G1D) cases prevented; 2) G1D cases prevented in PB cases only; 3) no disability prevented. Costs were US$ 2.9 per contact. Costs and effects were discounted at 3%. The incremental cost per DALY averted by SDR-PEP was US$ 210, US$ 447, and US$ 5,673 in the 25th year under assumption 1, 2, and 3, respectively. If prevention of G1D was assumed, the probability of cost-effectiveness was 1.0 at the threshold of US$ 2,000, which is equivalent to the GDP per capita of India. The probability of cost-effectiveness was 0.6, if no disability prevention was assumed. The cost per new leprosy case averted was US$ 2,873. Contact listing, screening and the provision of SDR-PEP is a cost-effective strategy in leprosy control in both the short (5 years) and long term (25 years). The cost-effectiveness depends on the extent to which disability can be prevented. As the intervention becomes increasingly cost-effective in the long term, we recommend a long-term commitment for its implementation., Author summary Leprosy is an infectious disease caused by the Mycobacterium leprae and is one of the major causes of preventable disability in low- and middle-income countries. Disabled people face lifelong socioeconomic challenges and are often excluded from society. It brings people affected by leprosy in a vicious cycle of poverty and disability. This cycle needs to be curbed through scientific evidence on health economic aspects of leprosy. Unfortunately, there is not much literature available on cost or cost-effectiveness of leprosy prevention. New prevention methods such as post-exposure chemoprophylaxis are now available, providing opportunity to collect up-to-date health economic evidence to support health policy and planning. Here, we present a cost-effectiveness study of contact screening in combination of post-exposure prophylaxis with single-dose rifampicin in the Union Territory of Dadra Nagar Haveli in India. We compare the intervention with the continuation of the routine leprosy control programme. As leprosy is moving towards elimination, evidence from this study will contribute to an investment case for leprosy elimination.

Rabies, caused by RNA viruses in the Genus Lyssavirus, is the most fatal of all infectious diseases. This neglected zoonosis remains a major public health problem in developing countries, causing the death of an estimated 25,000–159,000 people each year, with more than half of them in children. The high incidence of human rabies in spite of effective vaccines is mainly linked to the lack of compliance with the complicated administration schedule, inadequacies of the community public health system for local administration by the parenteral route and the overall costs of the vaccine. The goal of our work was the development of a simple, affordable and effective vaccine strategy to prevent human rabies virus infection. This next generation vaccine is based on a replication-defective chimpanzee adenovirus vector belonging to group C, ChAd155-RG, which encodes the rabies glycoprotein (G). We demonstrate here that a single dose of this vaccine induces protective efficacy in a murine model of rabies challenge and elicits strong and durable neutralizing antibody responses in vaccinated non-human primates. Importantly, we demonstrate that one dose of a commercial rabies vaccine effectively boosts the neutralizing antibody responses induced by ChAd155-RG in vaccinated monkeys, showing the compatibility of the novel vectored vaccine with the current post-exposure prophylaxis in the event of rabies virus exposure. Finally, we demonstrate that antibodies induced by ChAd155-RG can also neutralize European bat lyssaviruses 1 and 2 (EBLV-1 and EBLV-2) found in bat reservoirs., Author summary Rabies still remains a neglected zoonosis after a long history of vaccination. Considering the severity of the disease and its continued high incidence in low-income countries, the development of a next generation vaccine is warranted. We utilized a group C, replication-defective chimpanzee adenovirus vector to develop a novel vaccine against rabies. Mice vaccinated with ChAd155-RG survived after rabies infection and non-human primates injected with a single dose of this vaccine developed strong and durable neutralizing antibody responses which could be effectively boosted with a licensed vaccine, demonstrating the compatibility of the novel vectored vaccine with the current post-exposure prophylaxis in the event of rabies virus exposure. Importantly, we show that ChAd155-RG induced neutralizing antibodies can neutralize also lyssavirus species (EBLV-1 and EBLV-2) found in bat reservoirs. These studies paved the way to the clinical testing of the ChAd155-RG based rabies vaccine as a single-dose, low cost, preventative rabies vaccine candidate.

Background Subclinical infection with Mycobacterium leprae is one potential source of leprosy transmission, and post-exposure prophylaxis (PEP) regimens have been proposed to control this source. Because PEP trials require considerable investment, we applied a sensitive variation of the kinetic mouse footpad (MFP) screening assay to aid in the choice of drugs and regimens for clinical trials. Methodology/Principal findings Athymic nude mice were inoculated in the footpad (FP) with 6 x 103 viable M. leprae and treated by gastric gavage with a single dose of Rifampin (SDR), Rifampin + Ofloxacin + Minocycline (SD-ROM), or Rifapentine + Minocycline + Moxifloxacin (SD-PMM) or with the proposed PEP++ regimen of three once-monthly doses of Rifampin + Moxifloxacin (RM), Rifampin + Clarithromycin (RC), Rifapentine + Moxifloxacin (PM), or Rifapentine + Clarithromycin (PC). At various times post-treatment, DNA was purified from the FP, and M. leprae were enumerated by RLEP quantitative PCR. A regression analysis was calculated to determine the expected RLEP value if 99.9% of the bacilli were killed after the administration of each regimen. SDR and SD-ROM induced little growth delay in this highly susceptible murine model of subclinical infection. In contrast, SD-PMM delayed measurable M. leprae growth above the inoculum by 8 months. The four multi-dose regimens delayed bacterial growth for >9months post-treatment cessation. Conclusions/Significance The delay in discernable M. leprae growth post-treatment was an excellent indicator of drug efficacy for both early (3–4 months) and late (8–9 months) drug efficacy. Our data indicates that multi-dose PEP may be required to control infection in highly susceptible individuals with subclinical leprosy to prevent disease and decrease transmission., Author summary While multi-drug therapy (MDT) has been successful in decreasing the worldwide prevalence of leprosy, the new case detection rate, or incidence, remains consistent. These circumstances indicate that leprosy transmission is still occurring. Subclinical asymptomatic leprosy infections are considered a leading cause of ongoing transmission. One means to control this source is an effective post-exposure prophylaxis (PEP) regimen that would prevent both subsequent progression to clinical leprosy for the individual and transmission of the disease to others. Therefore, in this study, we used a modified kinetic mouse footpad screening assay and sensitive molecular bacterial enumeration in a susceptible-subclinical mouse model to identify effective potential PEP drug regimens for leprosy. Using these methods, we showed that a single dose PEP regimen is not effective in a susceptible host, and multiple intermittent doses of combination therapies are required. This model could provide useful pre-clinical information for the development of PEP regimens for leprosy.

A canine rabies epidemic started in early 2015 in Arequipa, Peru and the rabies virus continues to circulate in the dog population. Some city residents who suffer dog bites do not seek care or do not complete indicated post-exposure prophylaxis (PEP) regimens, increasing the risk of human rabies. The objectives of our study are to qualitatively assess knowledge about rabies, and preventive practices, such as rabies vaccine administration, following a dog bite. We conduct eight focus group discussions in peri-urban and urban communities with 70 total participants. In our results, we observe low awareness of rabies severity and fatality, and different practices following a dog bite, depending on the community type: for example, whereas participants in the urban communities report cleaning the wound with hydrogen peroxide rather than soap and water, participants in peri-urban areas cover the wound with herbs and hair from the dog that bit them. Misconceptions about rabies vaccines and mistreatment at health centers also commonly prevent initiating or completing PEP. We identify important behavioral and structural barriers and knowledge gaps that limit evidence-based preventive strategies against rabies and may threaten successful prevention of dog-mediated human rabies in this setting., Author summary The city of Arequipa, Peru has been experiencing an outbreak of dog rabies since 2015. The Peruvian Ministry of Health has implemented measures to prevent human infection, including no-cost rabies vaccinations for people bitten by dogs, but health posts report that many people do not utilize the service or complete treatment. We conduct focus groups in urban and peri-urban areas of Arequipa to examine community perceptions and attitudes towards PEP, and organizational and behavioral barriers to initiate and complete the PEP regimen. We observe low awareness of rabies severity, and different practices following a dog bite depending on the community type. Misconceptions about rabies vaccines and mistreatment at health centers also commonly prevent participants from initiating or completing PEP. We identify important behavioral and structural barriers and knowledge gaps that limit preventive strategies against rabies and may threaten successful prevention of dog-mediated human rabies in this setting. Finally, disparate landscapes and topography seem to have different effects on urban and peri-urban participants’ use of healthcare resources. Thus, strategies should target the specific needs of each population.

Background Timely and appropriate administration of post-exposure prophylaxis (PEP) is an essential component of human rabies prevention programs. We evaluated patient care at rabies clinics in a high-risk county in Hunan Province, China to inform strategies needed to achieve dog-mediated human rabies elimination by 2030. Methods We collected information on PEP, staff capacity, and service availability at the 17 rabies clinics in the high-risk county during onsite visits and key staff interviews. Additionally, we conducted observational assessments at five of these clinics, identified through purposive sampling to capture real-time information on patient care during a four-week period. Wound categories assigned by trained observers were considered accurate per national guidelines for comparison purposes. We used the kappa statistic and an alpha level of 0.05 to assess agreement between observers and clinic staff. Results In 2015, the 17 clinics provided PEP to 5,261 patients. Although rabies vaccines were available at all 17 clinics, rabies immune globulin (RIG) was only available at the single urban clinic in the county. During the assessment period in 2016, 196 patients sought care for possible rabies virus exposures. According to observers, 88 (44%) patients had category III wounds, 104 (53%) had category II wounds and 4 (2%) had category I wounds. Observers and PEP clinic staff agreed on approximately half of the assigned wound categories (kappa = 0.55, p-value< 0.001). Agreement for the urban county-level CDC clinic (kappa = 0.93, p-value, Author summary Members of the United Nations agreed on a goal of eliminating dog-mediated rabies by 2030. To achieve this goal, China and other endemic rabies countries will need to increase dog rabies vaccination coverage as well as ensure proper administration of rabies post-exposure prophylaxis (PEP) for patients with animal wounds. PEP includes wound washing, timely vaccination, and rabies immune globulin (RIG) according to the type and severity of patients’ wounds. The authors conducted an observational assessment of PEP clinics in a high-risk county in Hunan Province. Most patients at these clinics received PEP according to the national guidelines; however, certain patients received PEP, when not warranted, and others did not receive RIG, as recommended for severe animal wounds. Wound type categorization and corresponding use of PEP were most accurate at the single urban clinic and least accurate at the rural clinics in the project county. RIG was only available at the single urban clinic. These findings highlight the importance of improving the use of PEP and access to RIG, particularly in rural areas, and exploring the use of risk-based approaches for evaluating human rabies virus exposures. These steps can contribute to eliminating dog-mediated rabies in the project county as well as elsewhere in China.

An effective surveillance system is critical for the elimination of canine rabies in Latin America. Brazil has made substantial progress towards canine rabies elimination, but outbreaks still occurred in the last decade in two states. Brazil uses a health information system (SINAN) to record patients seeking post-exposure prophylaxis (PEP) following contact with an animal suspected of having rabies. This study evaluated: (i) whether SINAN can be reliably used for rabies surveillance; (ii) if patients in Brazil are receiving appropriate PEP and (iii) the benefits of implementing the latest World Health Organization (WHO) recommendations on PEP. Analysing SINAN records from 2008 to 2017 reveals an average of 506,148 bite-injury patients/year [range: 437k-545k] in the country, equivalent to an incidence of 255 bite-injuries/100,000 people/year [range: 231–280]. The number of reports of bites from suspect rabid dogs generally increased over time. In most states, records from SINAN indicating a suspect rabid dog do not correlate with confirmed dog rabies cases reported to the Regional Information System for Epidemiological Surveillance of Rabies (SIRVERA) maintained by the Pan American Health Organization (PAHO). Analyses showed that in 2017, only 45% of patients received appropriate PEP as indicated by the Brazilian Ministry of Health guidance. Implementation of the latest WHO guidance using an abridged intradermal post-exposure vaccination regimen including one precautionary dose for dog bites prior to observation would reduce the volume of vaccine required by up to 64%, with potential for annual savings of over USD 6 million from reduced vaccine use. Our results highlight the need to improve the implementation of SINAN, including training of health workers responsible for delivering PEP using an Integrated Bite Case Management approach so that SINAN can serve as a reliable surveillance tool for canine rabies elimination., Author summary Dog-mediated rabies has declined to only a few cases in Latin America over the last decade. Brazil has the largest human and dog population of Latin America. Despite the decline of canine rabies, the country’s public health system still spends millions of dollars annually on half a million patients seeking health care for dog bites. In this study, we analysed a decade of national surveillance data on dog bites. These data suggest that health workers report dog rabies in many states where the disease is likely to be absent, with false positive cases frequently reported into the surveillance system. In addition, only half of patients appear to receive the appropriate rabies post-exposure prophylaxis as recommended by the Ministry of Health. We estimated that Brazil could save up to USD 6 million per annum on vaccine by reducing the number of doses administered during prophylaxis and adopting the intradermal vaccine delivery technique following the latest WHO recommendations. Our study highlights an urgent need for updating health care workers on canine rabies knowledge, prophylaxis and assessment of dog bites to improve prophylaxis provision and surveillance of dog rabies.

The World Health Organization, the World Organization for Animal Health, and the Food and Agriculture Organization have resolved to eliminate human rabies deaths due to dog bites by 2030, and the Vaccine Alliance (Gavi) has added human rabies vaccines to their investments for 2021–2025. Implementing these goals cost-effectively and sustainably requires understanding the complex connections between dog rabies vaccination and human risk and response. The objective of this paper is to estimate how dog rabies vaccinations affect human rabies deaths, mediated through dog rabies cases, dog bite reporting, and post-exposure human rabies vaccination. To approach this objective, we apply multivariate regression analysis over five rabies-related outcomes: (a) dog vaccinations, (b) dog rabies cases, (c) reported human exposures, (d) human post-exposure prophylaxis (PEP) use, and (e) human rabies cases. Analysis uses aggregate annual data over 1995–2005 for seven Latin American countries that experienced dramatic declines in canine and human rabies. Among other results, we estimate the following. (i) A 10% increase in dog vaccinations decreases dog rabies cases by 2.3%. (ii) Reported exposures decline as concurrent dog rabies cases decline, but these declines are more than offset by increases in reported exposures per dog rabies case, which may result from higher rabies awareness due to anti-rabies campaigns. (iii) A 10% increase in PEP use decreases human deaths by 7%, but a 10% increase in dog vaccination induces a 2.8% decrease in PEP use. The net effect is that a 10% increase in dog vaccination reduces human deaths by 12.4% overall, although marginal effectiveness declines as dog rabies incidence declines. (iv) Increases in income and public health expenditures increase PEP demand. The findings highlight the importance of mass dog vaccination, heightened awareness, treatment access, and clinical algorithms to reduce both false negatives leading to death and false positives leading to costly unnecessary PEP prescriptions., Author summary Several global health organizations have prioritized investment for global elimination of human death from canine rabies. Cost-effective deployment requires understanding complex connections between rabies risk and healthcare seeking behavior. During 1995–2005, there was a rapid decline in dog and human rabies cases in several Latin American countries following concerted investment in mass dog vaccinations and human post-exposure vaccination. Using data from this period, we econometrically estimate relationships between dog vaccinations, dog rabies cases, human exposure reports, human post-exposure prophylaxis (PEP) use, and human rabies deaths. We estimate quantitatively how dog vaccinations indirectly reduce human rabies deaths, mediated through dog rabies cases, dog bite reporting, and PEP use. We find that reported human exposures decline as dog rabies cases decline, but these declines are offset by increases in reported exposures per dog rabies case, which may be driven by increased rabies awareness through anti-rabies campaigns. Furthermore, while PEP demand declines as dog rabies cases decline, increases in income and public health expenditures concurrently increase demand for PEP. These findings provide better understanding of the underlying factors driving PEP demand and exposure (under)reporting to inform cost-effective policy design to reduce unnecessary PEP prescription and false negatives leading to human death.

In 2015, China and other member states of the United Nations adopted the goal of eliminating dog-mediated rabies by 2030. China has made substantial progress in reducing dog-mediated human rabies since peaking with more than 3,300 reported cases in 2007. To further improve coordination and planning, the Chinese Center for Disease Control and Prevention, in collaboration with the United States Centers for Disease Control and Prevention, conducted a Stepwise Approach towards Rabies Elimination (SARE) assessment in March 2019. Assessment goals included outlining progress and identifying activities critical for eliminating dog-mediated rabies. Participants representing national, provincial and local human and animal health sectors in China used the SARE assessment tool to answer 115 questions about the current dog-mediated rabies control and prevention programs in China. The established surveillance system for human rabies cases and availability of post-exposure prophylaxis were identified as strengths. Low dog vaccination coverage and limited laboratory confirmation of rabid dogs were identified gaps, resulting in an overall score of 1.5 on a scale of 0 to 5. Participants outlined steps to increase cross-sectoral information sharing, improve surveillance for dog rabies, increase dog vaccination coverage, and increase laboratory capacity to diagnose rabies at the provincial level. All assessment participants committed to strengthening cross-sector collaboration using a One Health approach to achieve dog-mediated human rabies elimination by 2030., Author summary Rabies is an acute zoonosis with a mortality rate of almost 100% following the onset of symptoms. In China, the increased access to post-exposure prophylaxis has substantially reduced the number of human rabies deaths. However, rabies continues to circulate in many rural parts of the country, resulting in hundreds of rabid dog-related exposures and deaths each year. In 2015, member states of the United Nations adopted the goal of eliminating dog-mediated rabies by 2030. We conducted a Stepwise Approach towards Rabies Elimination (SARE) assessment to outline progress and identify steps needed to achieve the elimination goal in China. The assessment involved representatives from the national and 12 selected provincial-level human and animal health sectors. The 12 provinces were purposefully selected based on the current dog-mediated rabies burden, an interest in participating, and the ability to complete the SARE assessment tool. This cross-sector–or One Health—approach was useful for improving coordination and planning. In particular, the assessment identified opportunities to improve collaboration between sectors on laboratory diagnostic capacity, implementing mass dog vaccination campaigns and conducting epidemiologic investigations on dog-mediated rabies exposures. An integrated One Health strategy should be strengthened in China as well as in other countries aiming to eliminate dog-mediated rabies.

Rabies remains a public health challenge of unknown magnitude in Liberia in spite of the goal of ensuring that no human in the country dies of rabies by 2030. The annual prevalence of Dog Bite Victims (DBVs) and true load of Annual Human Deaths (AHDs) due to rabies were not known. We investigated three selected cities of Liberia for annual prevalence of DBVs and true load of AHD due to suspected rabies, using 10–year retrospective record, 2008–2017 obtained from Buchanan, Gbarnga, and Voinjama, three socio-economically important cities in post-conflict Liberia. Data were sourced at County Reference Hospitals and at the Liberia National Institute of Health for these cities and their local environs. In addition, household questionnaire survey was used to identify and audit data quality for unreported DBVs, and treatment received from traditional caregivers. The proportion was used to audit the 10-year data on unreported DBVs in the cities. Descriptive statistics was used to summarize annual DBVs over the 10-year period in the three cities, respectively. A standardized clinical decision tree model was used to estimate AHDs due to suspected rabies. Based on questionnaire survey, 140/365, 148/375 and 146/350 DBVs did not visit any orthodox health facility in Buchanan, Gbarnga and Voinjama cities, respectively in 2014. An estimated total of 559 DBVs died of suspected rabies in the three cities and their environs during the 10-year period. Mean yearly prevalence of DBVs was 179±106.82, 393±257.85 and 76.9±38.11 per 100,000 population, while mean AHDs due to suspected rabies was 14.3±8.47, 35.5±23.25, and 6.1±3.21 per 100,000 population in Buchanan, Gbarnga, and Voinjama cities, respectively. The present findings provide annual prevalence of suspected rabies cases, corrected for under-reporting in three selected cities of Liberia. The findings would be useful in planning for stepwise actions towards rabies elimination, ensuring that no human dies of rabies in Liberia by 2030., Author summary Care-seeking preferences of dog bite victims (DBVs) who would rather present to traditional caregivers in rural areas than to conventional hospitals have partly contributed to under-reported cases of suspected rabies in Liberia. For this reason, we reviewed cases of DBVs presented for treatment at human hospitals in Buchanan, Gbarnga and Voinjama cities, and their environs over a 10-year period, 2008–2017. We compared the findings with patronage of traditional caregivers for treatment of dog bite victims among representative households in each of the three cities, based on questionnaire survey and used the ratio derived to correct for under-reporting. Finally, we used a standardized clinical decision tree model to estimate the annual prevalence of human deaths due to suspected rabies cases. We then estimated 559 persons died of suspected rabies in the three cities and their environs during 2008–2017. The average annual prevalence of DBVs was 179±106.82, 393±257.85 and 76.9±38.11, respectively in the three cities, while average annual human deaths due to suspected rabies were 14.3±8.47, 35.5± 23.25, and 6.1±3.21 per 100,000 population, respectively. The mixed-method that we have used in this study for estimating chronologic annual prevalence of human deaths due to suspected rabies is adaptable to other cities of Liberia.

Dog bites in humans are a major public health problem in India in general and Kashmir in particular. Canine rabies is almost non-existent in developed countries and exists mainly in the poorer, low socioeconomic strata of society in the developing world. The objective of this study was to determine the characteristics, pattern, and burden of dog bite injuries in the Kashmir valley. Data from Anti-Rabies Clinic of a tertiary care hospital in Srinagar, the summer capital of the state of Jammu & Kashmir, was collated and analyzed. Analysis of records of all the patients who had reported between April 2016 and March 2017 was done. A total of 6172 patients had reported to the Anti-Rabies Clinic for management of animal bites from 1st April 2016 to 31st March 2017. Most of the patients were young males. Almost half (47.7%) of the patients were bitten in the afternoon. Lower limbs were the most common site of bite (71.7%). Most of the bites were of Category III (57.6%) followed by Category II (42.3%); only one case of Category I was recorded. Almost all (98.0%) cases reported being bitten by dogs. Conclusions: Category III dog bites on lower limbs were the most common type of animal bites presenting to the Anti-Rabies Clinic of a tertiary care hospital. Children have more chances of a bite on head and neck region. Serious and workable efforts have to be made to reduce the incidence and consequences of animal bites., Author summary In Kashmir, dog bite is an important public health problem. Thousands of people become victims of an animal bite, especially dog bite, and some of them develop rabies. Rabies is an invariably fatal viral disease resulting in approximately 59 000 human deaths per year globally, with 95% of cases occurring in Africa and Asia. The only way to prevent a rabies death is vaccination of an animal bite victim. In Kashmir, the burden and characteristics of dog bites are not routinely captured by the health system in place. We, therefore, attempted to find out the burden and characteristics of animal bite victims by analyzing one-year data from an Anti-Rabies Clinic at a tertiary care hospital in Kashmir. We found that 98% of the patients registered at the clinic during the period were victims of a dog bite. The victims were mostly young males but females and children were not shown any mercy either. Lower limbs were the most frequently reported site of the bite. Our analysis of the data also revealed that children under 15 years were more prone to a bite in the head and neck region. We concluded that the burden of animal bites, especially dog bites, is high in Kashmir and recommended that serious efforts need to be put into practice to decrease the number of animal bite victims and prevent any rabies deaths.

Canine rabies is endemic in Cameroon, but human rabies exposures and cases are likely underreported because of inadequate surveillance. In 2014, the surveillance network in the West region of Cameroon was reinforced by introducing a new anti-rabies center, a framework for data collection and evaluation, provisions for sample collecting and laboratory confirmation, and training for health professionals. The objective of this observational cohort study was to describe the incidence and characteristics of reported exposures and human and animal rabies cases following this reinforcement of the existing rabies surveillance system. The surveillance network consisted of local, regional, and national health and veterinary authorities in 11 of the 20 West region districts, and was completely integrated within the existing national rabies surveillance network. Animal exposures and suspected rabies exposures, the suspected rabid animals involved, and laboratory confirmation of human and animal rabies cases were recorded in a centralized information database. Between January 2014 and June 2016, the network recorded 1340 animal exposure cases for an overall incidence rate of 38.2 animal exposures per 100,000 people, four confirmed rabies-positive animals, and one confirmed human rabies case out of four clinically suspected cases. In contrast, 62 animal exposures and an overall incidence rate of 6.1 exposures per 100,000 people were reported for the West region districts not participating in the reinforced surveillance. Of the 925 animal exposure victims for whom a detailed case report form was completed, 703 were considered to be at risk of rabies and only 428 (61%) of these received any post-exposure prophylaxis in the form of rabies vaccine. Obstacles encountered within the network included low rates of animal sample submission and animal follow-up by veterinarians. Reinforced rabies surveillance in the West region of Cameroon has provided the most accurate estimate of the region's disease and exposure burdens to date, and indicates that animal exposures are substantially underreported. The reinforced network also signaled that greater access to post-exposure prophylaxis is needed. Integration of regions not covered by the surveillance network and efforts to improve engagement of veterinary services will be needed to reveal the true burden of rabies in Cameroon.

Background Approximately 59,000 people die from rabies worldwide annually. Haiti is one of the last remaining countries in the Western Hemisphere with endemic canine rabies. Canine-mediated rabies deaths are preventable with post-exposure prophylaxis (PEP): wound treatment, immunoglobulin, and vaccination. In countries where PEP is available, variability in healthcare seeking behaviors and lack of adherence to recommended treatment guidelines could also contribute to these deaths. Yet, few studies have addressed these issues. Methods We examined animal-bite reporting and assessed adherence to treatment guidelines at nine healthcare facilities in Haiti. We analyzed individual-level, de-identified patient data (demographic characteristics, geographic location, healthcare facility type, vaccine administration, and bite injury information) using descriptive analyses and logistic regression to examine factors associated with receiving PEP. Findings During the 6 month study period, we found 2.5 times more animal-bite case-patients than reported by the national surveillance system (690 versus 274). Of the 690 animal-bite patients identified, 498 (72%) sought care at six PEP providing facilities. Of the case-patients that sought care, 110 (22%) received at least one rabies vaccine. Of the 110 patients, 60 (55%) received all five doses. Delays were observed for three events: when patients presented to a facility after an animal-bite (3.0 days, range: 0–34 days), when patients received their fourth dose (16.1 days, range: 13–52 days), and when patients received their fifth dose (29 days, range: 26–52). When comparing vaccination status and patient characteristics, we found a significant association for bite location (p < .001), severity rank score (p < .001), geographic location (p < .001), and healthcare facility type (p = .002) with vaccination. Conclusion High levels of underreporting identified here are of concern since vaccine distribution may, in part, be based on the number of animal-bite cases reported. Given that the Haitian government provides PEP to the population for free and we found animal-bite victims are seeking care in a timely manner─ reducing rabies deaths is an achievable goal., Author summary Human rabies deaths are preventable with timely provision of rabies post-exposure prophylaxis: wound treatment, rabies immunoglobulin, and vaccinations. In countries where resources are available, variability in healthcare seeking behaviors and lack of adherence to recommended treatment guidelines may also contribute rabies deaths. In our study, we examined animal-bite reporting to the national surveillance system, and patient’s adherence to treatment guidelines at nine healthcare facilities in Haiti, a high rabies burden country. Our study found 2.5 times more patients than reported by the national surveillance system. This underreporting can unintentionally impact rabies awareness and the allocation of resources to animal-bite victims. Furthermore, our study found that among patients who received care, a majority of them are seeking care in a timely manner, suggesting that reducing rabies deaths is an achievable goal in Haiti.

Background Dog rabies annually causes 24,000–70,000 deaths globally. We built a spreadsheet tool, RabiesEcon, to aid public health officials to estimate the cost-effectiveness of dog rabies vaccination programs in East Africa. Methods RabiesEcon uses a mathematical model of dog-dog and dog-human rabies transmission to estimate dog rabies cases averted, the cost per human rabies death averted and cost per year of life gained (YLG) due to dog vaccination programs (US 2015 dollars). We used an East African human population of 1 million (approximately 2/3 living in urban setting, 1/3 rural). We considered, using data from the literature, three vaccination options; no vaccination, annual vaccination of 50% of dogs and 20% of dogs vaccinated semi-annually. We assessed 2 transmission scenarios: low (1.2 dogs infected per infectious dog) and high (1.7 dogs infected). We also examined the impact of annually vaccinating 70% of all dogs (World Health Organization recommendation for dog rabies elimination). Results Without dog vaccination, over 10 years there would a total of be approximately 44,000–65,000 rabid dogs and 2,100–2,900 human deaths. Annually vaccinating 50% of dogs results in 10-year reductions of 97% and 75% in rabid dogs (low and high transmissions scenarios, respectively), approximately 2,000–1,600 human deaths averted, and an undiscounted cost-effectiveness of $451-$385 per life saved. Semi-annual vaccination of 20% of dogs results in in 10-year reductions of 94% and 78% in rabid dogs, and approximately 2,000–1,900 human deaths averted, and cost $404-$305 per life saved. In the low transmission scenario, vaccinating either 50% or 70% of dogs eliminated dog rabies. Results were most sensitive to dog birth rate and the initial rate of dog-to-dog transmission (Ro). Conclusions Dog rabies vaccination programs can control, and potentially eliminate, dog rabies. The frequency and coverage of vaccination programs, along with the level of dog rabies transmission, can affect the cost-effectiveness of such programs. RabiesEcon can aid both the planning and assessment of dog rabies vaccination programs., Author summary Dog rabies causes, globally, approximately 55,000 human deaths per year. Mass vaccination programs can control dog rabies. We built a spreadsheet-based tool, RabiesEcon, to aid public health officials in planning large-scale dog rabies vaccination programs. We used RabiesEcon to estimate the cost-effectiveness of dog rabies control programs in East Africa for a human population of one million (approximately 2/3 urban, 1/3 rural). We evaluated three different vaccination options: no vaccination, annual vaccination of 50% of dogs, and semi-annual vaccination of 20% of dogs. Over a 10-year period, no dog vaccination results in approximately 44,000–65,000 rabid dogs and 2,000 human deaths. Annually vaccinating 50% of dogs for 10 years resulted in approximately 42,000–48,000 fewer rabid dogs and approximately 2,000–1,600 fewer human deaths. These reductions cost approximately $450-$385 per life saved. Semi-annual vaccination of 20% of dogs for 10 years resulted in approximately 41,000–50,000 fewer rabid dogs and approximately 2,000–1,900 fewer human deaths. These reductions cost approximately $400–$300 per life. In certain scenarios, 70% of dogs vaccinated eliminated dog rabies. Dog rabies vaccination programs can control, and potentially eliminate, dog rabies.

Through national efforts and regional cooperation under the umbrella of the Regional Program for the Elimination of Rabies, dog and human rabies have decreased significantly in Latin America and Caribbean (LAC) countries over the last three decades. To achieve this decline, LAC countries had to develop national plans, and consolidate capabilities such as regular mass dog vaccination, opportune post-exposure prophylaxis and sensitive surveillance. This paper presents longitudinal data for 21 LAC countries on dog vaccination, PEP and rabies surveillance collected from the biannual regional meeting for rabies directors from 1998–2014 and from the Regional Epidemiologic Surveillance System for Rabies (SIRVERA). Differences in human and dog rabies incidence rates and dog vaccination rates were shown between low, middle and high-income countries. At the peak, over 50 million dogs were vaccinated annually in national campaigns in the countries represented. The reported number of animal exposures remained fairly stable during the study period with an incidence rate ranging from 123 to 191 reported exposures per 100,000 people. On average, over 2 million doses of human vaccine were applied annually. In the most recent survey, only 37% of countries reported that they had sufficient financial resources to meet the program objectives. The data show a sufficient and sustained effort of the LAC countries in the area of dog vaccination and provide understanding of the baseline effort required to reduce dog-mediated rabies incidence., Author summary Globally, dog-mediated rabies kills over 55,000 people on an annual basis and disproportionally affects socio-economically disadvantaged populations. For over 4 decades, the Latin America and Caribbean (LAC) region have worked towards the elimination of dog-mediated rabies succeeding in a substantial reduction of both human and dog rabies cases. This paper summarizes the last 15 years of the national and regional rabies elimination efforts, through a series of performance indicators, including government mass dog vaccination campaigns and post-exposure prophylaxis for humans. The most important message from the tail of the rabies epidemic in the LAC Region is one of endurance by the countries and the region to achieve rabies control and elimination. The performance indicators shown in this paper are tools for the LAC region to evaluate its progress and refine its approach, and for other regions to understand the scope of the effort required to reach elimination.

Background Rabies is a major public health problem with a fatality rate close to 100%; however, complete prevention can be achieved through pre- or post-exposure prophylaxis. The rapid fluorescent focus inhibition test (RFFIT) is one of the recommended testing methods to determine the production of neutralizing antibodies after vaccination. Here, we report the development of a new monoclonal antibody (mAb) designed to react specifically with Rabies virus (RABV) phosphoprotein (P protein), and the evaluation of its applicability to the RFFIT and its effectiveness as a diagnostic reagent for human rabies. Methodology/principal findings The mAb KGH P 16B8 was produced to target the P protein of the Korean KGH RABV strain. An indirect immunofluorescence assay (IFA) was conducted to detect various strains of RABV in various cell lines. Alexa-conjugated KGH P 16B8 (16B8-Alexa) was developed for the RFFIT. The IFA test could detect RABV up to a 1:2,500 dilution, with a detection limit comparable to that of a commercial diagnostic reagent. The sensitivity, specificity, positive predictive value, and negative predictive value of the RFFIT using 16B8-Alexa in 414 clinical specimens were 98.67%, 99.47%, 99.55%, and 98.42%, respectively. The results of the RFFIT with 16B8-Alexa were strongly correlated with those obtained using an existing commercial diagnostic reagent (r = 0.995, p, Author summary Rabies represents a significant cause of fatality upon presentation of symptoms; however, pre- or timely post-exposure prophylaxis can provide complete protection to a population. The current reagents available for laboratory tests to determine the level of Rabies virus (RABV) neutralizing antibodies are not readily accessible in several regions, including Korea, and are associated with time and economic constraints owing to the import process. To resolve these issues, we developed a new monoclonal antibody with a fluorescent marker (16B8-Alexa) that targets the RABV phosphoprotein from a recent Korean isolate. We show its good detection ability, specificity, and sensitivity, demonstrating highly concordant results with those obtained with a standard commercial reagent using over 400 clinical samples applied to a World Health Organization-recommended diagnostic test. Thus, 16B8-Alexa shows great potential to resolve the current limitations in rabies diagnosis and monitoring in Korea, and is expected to serve as a valuable research tool for immunological studies on RABV.

Background Human rabies is a notifiable condition in Thailand, and 46 confirmed and probable cases were reported from 2010–2015; eleven were reported from Eastern Thailand. Although rabies is vaccine preventable, more than 90% of persons who died of rabies in Thailand either did not receive or inappropriately discontinued post-exposure prophylaxis (PEP). In 2012 Thailand launched a national animal rabies elimination program with the goal of elimination by 2020. One of the policies of this national program is to improve detection of animal rabies exposures, access to PEP, and adherence to vaccine schedules. To achieve this goal, several hospital-based electronic PEP surveillance systems have been instituted throughout Thailand. Method Data from a voluntary, electronic hospital-based, rabies exposure and PEP surveillance system was analyzed from eight provinces in Eastern Thailand for the time period January 1 –December 31, 2015. The surveillance system collects data from all persons who present to an R36-integrated healthcare facility with a suspected rabies exposure, including characteristics of the biting animals, categorization of the rabies exposure, and adherence to PEP recommendations. The crude rate of healthcare seeking for a suspected rabies exposure was assessed by province, and a multivariable linear regression model was developed to determine the potential extent of undetected rabies exposures due to bite treatment at healthcare facilities that do not utilize the R36 system. Suspected rabies exposures were described by patient demographics, location of wound, and disposition of the offending animal. A comparison of adherence to intramuscular and intradermal vaccination regimens was performed and odds ratios were calculated for factors related to unadvised PEP discontinuation. Result 6,204 suspected rabies exposures were reported from eight Eastern Thailand provinces, yielding a crude exposure rate of 106 reported rabies exposures per 100,000 population. When adjusted for under-detection due to non-participating hospitals and province-level demographic differences, the estimated suspected rabies exposure rate was 204/100,000. Dogs were the main source of exposure (77.8%) and children age 60 years had the highest overall reported exposure rate (189.7 and 189.2/100,000). Adherence to either the intramuscular 5-dose or the intradermal 4-dose PEP regimen was low (15.8% and 46.5%, respectively); rabies immunoglobulin was received by only 15% of persons for whom it was indicated. Persons with rabies exposures were more likely to discontinue the vaccination series against medical advice if they were male, aged 16–45, if they received immunoglobulin, or if received the intramuscular regimen. Conclusion When adjusting for number of reporting hospitals, province population density, number of hospitals per population and average family income, the expected report rate increased 1.9-fold, indicating that there is likely a high level of under-detection of persons seeking medical care for suspected rabies exposures. Expanded implementation of electronic surveillance systems will likely improve reporting and the epidemiologic knowledge of rabies exposures. Analysis of data collected from this system revealed very low rates of adherence to rabies vaccination recommendations. PEP adherence was better by the intradermal route, which provides more support for its use in situations where it is economically feasible., Author summary While rabies is a vaccine preventable disease, and despite tremendous improvements in access to healthcare, human rabies fatalities continue to occur in Thailand. Data from a voluntary, electronic hospital-based, rabies exposure and PEP surveillance system was analyzed from eight provinces in Eastern Thailand. In total 6,204 suspected rabies exposures were reported between January 1 –December 31, 2015, yielding a crude exposure rate of 106 reported rabies exposures per 100,000 population or 204/100,000 when adjusted for under-reporting. Dogs were the main sources of exposure and children age < 15 years and elderly aged > 60 years had the highest overall reported exposure rate. Adherence to either the intramuscular or the intradermal PEP regimen was low (15.8% for IM and 46.5% for ID). There is likely a high level of under-detection of persons seeking medical care for suspected rabies exposures in Eastern Thailand, but expanded implementation of electronic surveillance systems will likely improve reporting. Further investigation is needed to understand why rates of adherence to PEP were low. Adherence was better by the intradermal route, which provides more support for its use in situations where it is economically feasible.

Background In Mozambique, the majority of rabies outbreaks are unreported and data on the epidemiological features of human rabies and animal bites are scarce. An outbreak of human rabies in adjacent Maputo and Matola cities in 2014 prompted us to investigate the epidemiology, clinical features and risk factors of human rabies and animal bites in the two cities. Methodology/Principal findings We reviewed cases of human rabies and animal bites from April to July 2014, and carried out a community investigation in July and August in the neighborhoods where cases of human rabies resided. This investigation included collection of clinical, demographic and epidemiological information and a case control study to investigate the risk factors associated with human rabies. Fourteen cases of human rabies were detected in Maputo (n = 10) and Matola (n = 3) cities and neighbouring Boane district (n = 1) between April and August 2014, all of whom had been admitted to hospital. All had a recent history of dog bite. Of the 14 rabid dogs, only one had been immunized. 819 cases of animal bites were registered, of which 64.6% (529/819) were from Maputo City. Dogs were responsible for 97.8% (801/819) of all animal bites, but only 27.0% (126/467) were immunized. Factors significantly associated with human rabies were: age, Author summary Rabies is a deadly neglected virus that causes an estimated 59,000 deaths each year worldwide. In 2014, an outbreak of human rabies in adjacent Maputo and Matola cities prompted us to investigate the epidemiology and risk factors of human rabies and animal bites in the two cities. We reviewed cases of human rabies and animal bites through both health facility and community investigations and carried out a case control study in affected neighborhoods. We found a total of 14 unreported human rabies cases in a four month period, and 819 cases of animal bites in a three month retrospective review of records. Dogs were responsible for all rabid bites and for 97.8% of animal bites. None of the rabid dogs had been vaccinated. Factors significantly associated with human rabies were: age

Background Australian bat lyssavirus (ABLV) belongs to the genus Lyssavirus which also includes classic rabies virus and the European lyssaviruses. To date, the only three known human ABLV cases, all fatal, have been reported from Queensland, Australia. ABLV is widely distributed in Australian bats, and any bite or scratch from an Australian bat is considered a potential exposure to ABLV. Methodology/Principal Findings Potential exposure to ABLV has been a notifiable condition in Queensland since 2005. We analysed notification data for potential exposures occurring between 2009 and 2014. There were 1,515 potential exposures to ABLV notified in Queensland, with an average annual notification rate of 5.6 per 100,000 population per year. The majority of notified individuals (96%) were potentially exposed to ABLV via bats, with a small number of cases potentially exposed via two ABLV infected horses and an ABLV infected human. The most common routes of potential exposure were through bat scratches (47%) or bites (37%), with less common routes being mucous membrane/broken skin exposure to bat saliva/brain tissue (2.2%). Intentional handling of bats by the general public was the major cause of potential exposures (56% of notifications). Examples of these potential exposures included people attempting to rescue bats caught in barbed wire fences/fruit tree netting, or attempting to remove bats from a home. Following potential exposures, 1,399 cases (92%) were recorded as having appropriate post-exposure prophylaxis (PEP) as defined in national guidelines, with the remainder having documentation of refusal or incomplete PEP. Up to a quarter of notifications occurred after two days from the potential exposure, but with some delays being more than three weeks. Of 393 bats available for testing during the reporting period, 20 (5.1%) had ABLV detected, including four species of megabats (all flying foxes) and one species of microbats (yellow-bellied sheathtail bat). Conclusions/Significance Public health strategies should address the strong motivation of some members of the public to help injured bats or bats in distress, by emphasising that their action may harm the bat and put themselves at risk of the fatal ABLV infection. Alternative messaging should include seeking advice from professional animal rescue groups, or in the event of human contact, public health units. Further efforts are required to ensure that when potential exposure occurs, timely reporting and appropriate post-exposure prophylaxis occur., Author Summary Australian bat lyssavirus (ABLV), closely related to classic rabies virus, is widely distributed in bats in Australia. So far, the only three known human ABLV cases, all fatal, have been reported in Queensland, Australia. Any Australian bat-related injury (bite or scratch), or contact of bat saliva/neural tissue with eyes, mouth, nose, or broken skin of humans, is considered a potential exposure to ABLV. Use of timely, appropriate rabies vaccine and human rabies immunoglobulin is recommended to prevent fatal human ABLV disease. Based on notification data for potential exposures to ABLV in Queensland, we found that intentional handling of bats by the general public was the major cause of bat-related injuries; for example, people reported attempting to rescue bats caught in barbed wire fences or fruit tree netting, or attempting to remove bats from a home. This highlights a need to address the strong motivation of some members of the public to help injured bats or bats in distress and the lack of awareness of the risks of contact with or handling of bats, underscoring the importance of avoidance of bat handling by contacting vaccinated, experienced, and well-equipped professional animal rescue groups to deal with bats. There is a need to improve timeliness of notification to ensure immediate post-exposure management. Queensland Health bat testing results revealed the detection of ABLV in four common species of megabats (all flying foxes) and one species of microbats (yellow-bellied sheathtail bat), further reinforcing the message of avoiding all bat-related injuries. Once a potential exposure to ABLV occurs, immediate cleansing of wound (with soap and water for at least 5 minutes and application of povidone-iodine or alcohol) is required; and appropriate and timely rabies vaccine and human rabies immunoglobulin should be administered.

Raccoon rabies is endemic in the eastern U.S.; however, an epizootic had not been confirmed on Long Island, New York until 2004. An oral rabies vaccination (ORV) program was initiated soon after the first rabies-positive raccoon was discovered, and continued until raccoon rabies was eliminated from the vaccination zone. The cost-effectiveness and economic impact of this rabies control program were unknown. A public health surveillance data set was evaluated following the ORV program on Long Island, and is used here as a case study in the health economics of rabies prevention and control efforts. A benefit-cost analysis was performed to determine the cost-effectiveness of the program, and a regional economic model was used to estimate the macroeconomic impacts of raccoon rabies elimination to New York State. The cost of the program, approximately $2.6 million, was recovered within eight years by reducing costs associated with post-exposure prophylaxis (PEP) and veterinary diagnostic testing of rabies suspect animals. By 2019, the State of New York is projected to benefit from the ORV program by almost $27 million. The benefit-cost ratio will reach 1.71 in 2019, meaning that for every dollar spent on the program $1.71 will be saved. Regional economic modeling estimated employment growth of over 100 jobs and a Gross Domestic Product (GDP) increase of $9.2 million through 2019. This analysis suggests that baiting to eliminate rabies in a geographically constrained area can provide positive economic returns., Author Summary Raccoon rabies, a type of rabies found most frequently in raccoons, is common in the eastern U.S. Raccoon rabies is at times controlled through oral rabies vaccination (ORV) programs, in which baits containing rabies vaccine are distributed throughout the affected area to be consumed by wildlife, which then develop immunity limiting their ability to spread the disease in the population. A rabies outbreak was not detected in Nassau and Suffolk Counties on Long Island until 2004, when an ORV program was rapidly initiated in response to the discovery of a rabies-positive raccoon. As a result, raccoon rabies was eliminated in January 2009. Some questioned whether the benefits of the ORV program outweighed its costs. To find out, we performed a benefit-cost analysis of the program using avoided medical and animal testing costs to value the benefits. We also used a regional economic model to estimate the effect of the program on the economy of New York State. The results of both analyses indicated that the program had a positive economic impact, increasing employment and income in the region. The ORV program also benefited public health by reducing the need for medical treatment after possible rabies exposures. This study provides insight into the economic value of a program to eliminate rabies from an isolated area.