Rabies Control Research Articles

Expert consensus on the clinical application of ormutivimab injection for use against the rabies virus

ABSTRACT Background There are no local or international guidelines or consensus on the use of mAbs against the rabies virus. Research design and methods An expert group in the field of rabies prevention and control formulated the consensus presented in this paper. Results Class III exposed persons to rabies for the first time; Identify type II exposed persons with immune deficiency; those who are first exposed to Class II and re-exposed to Class III within 7 days. They can use ormutivimab injection after completing the PEP wound treatment. In the case of injection restrictions or a wound that is difficult to detect, it is recommended that the entire Ormutivimab dose be infiltrated close to the wound. For severe multi-wound bites, the recommended dosage of ormutivimab is 20 IU/kg. If the recommended dose cannot meet all of the wound infiltration requirements, appropriate dilution can be conducted at a dilution ratio of 3 ~ 5 times. If the requirements for infiltration cannot be met after dilution, it is recommended that the dosage be increased with caution (maximum dosage, 40 IU/kg). The use of Ormutivimab is safe and effective without any contraindications by all age groups. Conclusions This consensus standardizes clinical use of Ormutivimab, improves post-exposure prophylaxis of rabies in China, reduces infection rate.

Cost-Effectiveness Analysis of Integrated Bite Case Management and Sustained Dog Vaccination for Rabies Control

The successful prevention, control, and elimination of dog-mediated rabies is challenging due to insufficient resource availability and inadequate placement. An integrated dog bite case management (IBCM) system plus dog vaccination can help address these challenges. Based on data from the IBCM system in Haiti, we conducted a cost-effectiveness evaluation of a newly established IBCM system plus sustained vaccination and compared it with 1) a no bite-case management (NBCM) and 2) a non-risk-based (NRB) program, where bite victims presenting at a health clinic would receive post-exposure prophylaxis regardless of risk assessment. We also provide cost-effectiveness guidance for an ongoing IBCM system and for sub-optimal dog vaccination coverages, considering that not all cost-effective interventions are affordable. Cost-effectiveness outcomes included average cost per human death averted (USD/death averted) and per life-year gained (LYG). The analysis used a governmental perspective. Considering a sustained 5-year implementation with 70% dog vaccination coverage, IBCM had a lower average cost per death averted (IBCM: $7,528, NBCM: $7,797, NRB: $15,244) and cost per LYG (IBCM: $152, NBCM: $158, NRB: $308) than NBCM and NRB programs. As sensitivity analysis, we estimated cost-effectiveness for alternative scenarios with lower dog-vaccination coverages (30%, 55%) and lower implementation costs. Our results suggest that better health and cost-effectiveness outcomes are achieved with the continued implementation of an IBCM program ($118 per life-year saved) compared with a newly established IBCM program ($152 per life-year saved). Our results suggest that IBCM is more cost-effective than non-integrated programs to eliminate dog-mediated human rabies.

Risk factors and molecular epidemiology of canine rabies in Beijing

Rabies is a serious public health problem in Asia and Africa. Approximately 99% of cases result from a bite by an infected dog. The high rabies risk countries are generally characterized by rapid urbanization; however, the prevalence and risk factors for rabies in urban dogs in developing countries remain unclear. Beijing, the capital of China, has been undergoing rapid urbanization, and implemented compulsory rabies immunization for dogs on October 1, 2014. We evaluated the effects of this immunization policy and investigated the dynamics and determinants of the spread of dog rabies virus (RABV) in Beijing. Between 2013 and 2018, the positive rate of rabies in biting dogs declined significantly; 79.6% of these were stray dogs. Reconstructed spatiotemporal diffusion for RABV presents a more central distribution within Beijing and a surrounding dissemination of virus lineage toward suburban areas, indicating that rabies is self-sustaining in Beijing. Continuous RABV phylogeographic reconstructions and logistic regression analysis of rabies cases revealed that rabies tended to remain in commercial areas, high-rise residences, demolition areas, and high-GDP, high-population and high-accessibility areas. Demolition areas, where many residents have abandoned their pets, are recognized as high-risk areas for rabies. Our findings reveal that the implementation of the immunization policy in Beijing has been effective in prevention and control of canine rabies, and because the prevalence of canine rabies results from multiple factors, emphasize the important role of multi-sectoral cooperation in rabies prevention and control.

Assessment of Perception of Rabies Infection Risk among Dog Handlers and ‎Dog Meat Consumers in Plateau State, Nigeria

The risk of rabies exposure via atypical means such as handling dogs that have uncertain vaccination status, handling/processing and eating dog meat make public enlightenment inevitable. A cross-sectional study was conducted among dog handlers, dog meat handlers, and consumers at dog sales/slaughter locations and sales points of dog meat in the three major dog markets in Plateau State, Nigeria. Structured questionnaires were randomly administered to 150 respondents via face-to-face interviews or self-administered. Data collected were analyzed using IBM® SPSS® statistics version 23.0. Chi-squared test of association was conducted to determine the relationship between socio-demographic characteristics and perceived risk of rabies exposure among respondents. Binary logistic regression models were used to determine the strength of the association. Logistic regression models were statistically significant for the combination of sex and tertiary educational background to predict likelihood that respondents would eat all parts of dog meat, χ2 (2) = 7.023, P-value = 0.03. The effect size was between 6.2% (Cox and Snell R2) and 8.4% (Nagelkerke R2) of the variance in likelihood to eat all parts of dog meat and correctly classified as 60.9% of cases. Educational background was the only statistically significant predictor variable (p-value=0.016; 95% CI: 0.16– 0.83), as respondents in the higher educational cadre (tertiary) have a better perception of risk of rabies and are not likely to eat all parts of the dog meat nor a rabid dog. The study reveals the significance of taking appropriate actions to ensure rabies control and prevention, rather than having mere head knowledge of the disease. Strict policies against indiscriminate dog trade, uninspected slaughter, and improper processing of dog meat, are necessary steps to prevent disease incursions via atypical means.

Effect of Phone Text Message Reminders on Compliance with Rabies Post-Exposure Prophylaxis following Dog Bites in Rural Kenya.

The prompt administration of post-exposure prophylaxis (PEP) is one of the key strategies for ending human deaths from rabies. A delay in seeking the first dose of rabies PEP, or failure to complete the recommended dosage, may result in clinical rabies and death. We assessed the efficacy of short message system (SMS) phone texts in improving the adherence to scheduled PEP doses among bite patients in rural eastern Kenya. We conducted a single-arm, before-after field trial that compared adherence among bite patients presenting at Makueni Referral Hospital between October and December 2018 (control) and between January and March 2019 (intervention). Data on their demographics, socio-economic status, circumstances surrounding the bite, and expenditures related to the bite were collected. A total of 186 bite patients were enrolled, with 82 (44%) in the intervention group, and 104 (56%) in the control group. The odds of PEP completion were three times (OR 3.37, 95% CI 1.28, 10.20) more likely among patients who received the SMS reminder, compared to the control. The intervention group had better compliance on the scheduled doses 2 to 5, with a mean deviation of 0.18 days compared to 0.79 days for the control group (p = 0.004). The main reasons for non-compliance included lack of funds (30%), and forgetfulness (23%) on days for follow-up treatment, among others. Nearly all (96%, n = 179) the bite patients incurred indirect transport costs, at an average of USD 4 (USD 0-45) per visit. This study suggests that the integration of SMS reminders into healthcare service delivery increases compliance with PEP, and may strengthen rabies control and elimination strategies.

Health professionals KAP study on rabies exposure assessment and NTV administration in Ethiopia

Background: Globally, it’s estimated 60,000 human deaths occur due to rabies with 95% of cases occurring in Africa and Asia. Annually, thousands of people are infected with rabies in Ethiopia and more than 2700 people die. In Ethiopia, the neural-based vaccine has been used since the 1950’s. Due to the old method of production, low immunogenicity and vaccine associated adverse events, WHO discourage the use of this vaccine and recommend replacing it with a safe and effective modern cell culture vaccine. There was no specific guidelines and training for this vaccine and health professional mismanage the nerve tissue vaccine (NTV) with cell culture vaccine resulting in vaccination failure. This study identifies professional knowledge, attitude and practice (KAP), vaccine related adverse events and the burden of rabies cases in humans. Methods: Data were collected from health professionals in selected health facilities using structured questionnaire to identify the level of KAP. Results: The study identified overall gaps in the professionals KAP as below standard which is not more than 25%. The majority of the respondents (97%) reported vaccine associated local adverse events followed by 20% systemic complications during vaccination. Only 2.4% of the respondents reported post-vaccine complications. Rabies cases in humans at those covered health facilities were reported to be 32 during the one-year study period with an average of two cases at each facility. Conclusions: Gaps identified in the professional KAP result indicate the need to provide specific training based on standard guidelines. Generally, the study indicates the need to strengthen rabies prevention and control efforts through inter-sectoral collaboration, and facilitating the establishment of facility-based rabies palliative care centers. In addition, it is recommended to work on technology transfer to replace old method of NTV production with safe and effective modern cell culture based anti-rabies vaccine production for effective rabies PEP.

Optimizing Dog Rabies Vaccination Services to the Public: A Discrete Choice Experiment in Guangdong, China.

Vaccination for dogs is essential for controlling rabies and achieving the goal of eliminating dog-mediated rabies globally by 2030. This paper aims to investigate the preferences for public services regarding rabies vaccination, in an effort to optimize the existing rabies vaccination and prevention programs in China. The households investigated had significant preferences for dog rabies vaccination service attributes. The households can be classified into three types: resolute executors (52.13%), mischievous rebels (5.85%), and incentivized compliers (42.02%). The residence, the presence of children in the household, perception of the safety risks, and knowledge of rabies may be sources of heterogeneity. Supportive services on dog rabies vaccination should be made available, such as arranging weekend vaccination services, building mobile vaccination stations, providing home vaccination services, and increasing vaccine supply through multiple channels. Furthermore, multiple measures can be taken to increase rabies vaccination awareness among family members and facilitate dog management innovation to further increase the level of rabies prevention and control.

Modeling the dynamics and control of rabies in dog population within and around Lagos, Nigeria

Modeling the dynamics and control of rabies in dog population within and around Lagos, Nigeria

Rabies virus in white-nosed coatis (Nasua narica) in Mexico: what do we know so far?

Rabies is a neglected disease that affects all mammals. To determine the appropriate sanitary measures, the schedule of preventive medicine campaigns requires the proper identification of the variants of the virus circulating in the outbreaks, the species involved, and the interspecific and intraspecific virus movements. Urban rabies has been eradicated in developed countries and is being eradicated in some developing countries. In Europe and North America, oral vaccination programs for wildlife have been successful, whereas in Latin America, Asia, and Africa, rabies remains a public health problem due to the habitation of a wide variety of wild animal species that can act as rabies virus reservoirs in their environment. After obtaining recognition from the WHO/PAHO as the first country to eliminate human rabies transmitted by dogs, Mexico faces a new challenge: the control of rabies transmitted by wildlife to humans and domestic animals. In recent years, rabies outbreaks in the white-nosed coati (Nasua narica) have been detected, and it is suspected that the species plays a significant role in maintaining the wild cycle of rabies in the southeast of Mexico. In this study, we discussed cases of rabies in white-nosed coatis that were diagnosed at InDRE (in English: Institute of Epidemiological Diagnosis and Reference; in Spanish: Instituto de Diagnostico y Referencia Epidemiologicos) from 1993 to 2022. This study aimed to determine whether white-nosed coatis might be an emergent rabies reservoir in the country. A total of 13 samples were registered in the database from the Rabies laboratories of Estado de Mexico (n = 1), Jalisco (n = 1), Quintana Roo (n = 5), Sonora (n = 1), and Yucatan (n = 5). Samples from 1993 to 2002 from Estado de Mexico, Jalisco, and Sonora were not characterized because we no longer had any samples available. Nine samples were antigenically and genetically characterized. To date, coatis have not been considered important vectors of the rabies virus. The results from our research indicate that the surveillance of the rabies virus in coatis should be relevant to prevent human cases transmitted by this species.

Evaluation of country infrastructure as an indirect measure of dog-mediated human rabies deaths.

Rabies is a neglected disease, primarily due to poor detection stemming from limited surveillance and diagnostic capabilities in most countries. As a result, there is limited ability to monitor and evaluate country, regional, and global progress towards the WHO goal of eliminating human rabies deaths by 2030. There is a need for a low-cost, readily reproducible method of estimating rabies burden and elimination capacity in endemic countries. Publicly available economic, environmental, political, social, public health, and One Health indicators were evaluated to identify variables with strong correlation to country-level rabies burden estimates. A novel index was developed to estimate infrastructural rabies elimination capacity and annual case-burden for dog-mediated rabies virus variant (DMRVV) endemic countries. Five country-level indicators with superior explanatory value represent the novel "STOP-R index:" (1) literacy rate, (2) infant mortality rate, (3) electricity access, (4) political stability, and (5) presence/severity of natural hazards. Based on the STOP-R index, 40,111 (95% CI 25,854-74,344) global human rabies deaths are estimated to occur in 2022 among DMRVV-endemic countries and are projected to decrease to 32,349 (95% CI 21,110-57,019) in 2030. The STOP-R index offers a unique means of addressing the data gap and monitoring progress towards eliminating dog-mediated human rabies deaths. Results presented here suggest that factors external to rabies programs influence the successes of rabies elimination, and it is now possible to identify countries exceeding or lagging in expected rabies control and elimination progress based on country infrastructure.

Notifications of suspected rabies exposure increased in Finland: 26 years of one health surveillance, 1995–2020

Background Finland is a rabies virus-free country since 1991. Notification of suspected cases of rabies exposures, leading to post-exposure prophylaxis, is mandatory. We characterised suspected cases of rabies exposure, analysed animal surveillance data and calculated costs for vaccine and immunoglobulin and treatment to estimate the financial burden of rabies control in Finland. Methods The incidence rate ratios of suspected cases of rabies exposure were calculated from Finnish Infectious Disease Registry and Statistics Finland data. Animal surveillance data were obtained from the Finnish Food Authority’s registries. Calculation of costs were based on the medical and treatment costs of rabies control. Results In 2007, one human rabies infection linked to a dog bite in the Philippines and rabies infection in a dog imported from India were diagnosed in Finland. In 2009, 2016 and 2017, lyssaviruses were found in bats. Notifications of suspected rabies exposures increased during 2007–2019. Two-thirds of the exposures occurred abroad, mainly in Asian and African countries. Bats were the most frequent domestic exposing animal. The import of vaccine and immunoglobulin doses increased. The annual cost of Finnish rabies control is estimated to be over €1.65 million. Conclusions Increased awareness of rabies and bat lyssavirus infections probably increased post-exposure prophylaxis and reporting. Travellers need country-specific guidance on how to prevent exposures, and citizens need instructions on animal imports and how to handle bats.

Assessment of Immune Responses to Rabies Vaccination in Free-Ranging Dogs in Bengaluru, India.

Rabies is a fatal encephalomyelitis mainly transmitted to humans and other animals by rabid dog bites. Hence, vaccination programs are being instituted for the control of rabies in dogs. Though stray dogs have been vaccinated for years under various programs initiated for control of the disease, the effectiveness of these programs can be ascertained only by assessing the immunity of these dogs. With this in view, a study was conducted to assess the effectiveness of the ongoing mass dog vaccination (MDV) program by the Bengaluru City Municipal Corporation, Bengaluru, India. Whole blood and serum samples (n = 260) from vaccinated stray dogs in 26 wards of 8 corporation zones were tested by rapid fluorescent focus inhibition test (RFFIT) as well as an in-house quantitative indirect enzyme-linked immunosorbent assay (iELISA) for a humoral response and by interferon-gamma (IFN-γ) ELISA for a cellular response. As determined by the cut-off value of 0.5 IU/mL of serum, 71% and 87% of the samples from vaccinated dogs revealed adequate levels of antibodies presumed to confer protection by RFFIT and iELISA, respectively. The sensitivity and specificity of the iELISA were 100% and 63.3%, respectively. The IFN-γ ELISA revealed adequate cellular response in 50% of the samples. The quantitative iELISA was found to be useful in large-scale seromonitoring of MDV programs to aid in the elimination of dog-mediated rabies.

Households’ Practices towards Rabies Prevention and Control in Rural Nepal

Rabies is a vaccine-preventable, zoonotic, viral disease and a major public health concern for developing countries such as Nepal. A study was conducted from October-December 2021 among 308 household heads from three districts in Nepal (Siraha, Parsa, and Nawalparasi West) through an in-person interview to examine the rural people's practices towards rabies. Of 70 respondents owning pet animals, 82.9% vaccinated them against rabies but 87.9% (51/58) of them kept a vaccination record. Nearly all respondents (99.7%, 307/308) said they would visit hospitals after being bitten by rabid or rabies suspected animals, and 18.2% (56/308) of them said they would also opt to visit traditional healers seeking treatment against rabies. Seven in ten respondents knew that they should wash bitten body area with soap and water. Around 60% (184/308) of respondents said they would not bother to notify or report to the local authorities if they saw someone bitten by a presumed rabid dog or observed animal behavior suggestive of rabies. The Chi-square test showed a significant association between the socio-demographic characteristics of respondents with practices (good practice and poor practice) towards rabies. The study findings suggest that rural people in Nepal need to be educated with applied rabies control and prevention practices and made aware of health seeking behavior and the role that a community members have to play to control, prevent, and eradicate rabies.

Mapping rabies distribution in China: a geospatial analysis of national surveillance data

ObjectivesDog-mediated human rabies remains an important public health problem in China. In this study, we aimed to understand the spatiotemporal variation of rabies and examine its nonmedical ecological factors. MethodsIn this study, we used the annual incidence data for rabies at the province level in China to describe the incidence trends for the period 2004-2019 and used a Bayesian hierarchical spatiotemporal model to determine the impacts of environmental, economic, and demographic factors. ResultsFrom 2004 to 2019, there were 26,593 cases reported in 31 provinces in Mainland China, and the annual incidence increased from 0.02 per 100,000 in 2004 to 0.14 in 2007, substantially decreased in 2008, and was gradually declining thereafter. Guizhou, Guangxi, Hunan, and Hainan were four high-risk provinces, and Yunnan and Anhui provinces showed an increased risk in 2018 and 2019. Temperature and per capita gross domestic product were significantly positively correlated with the disease risk. The standardized morbidity ratio of rabies is likely to increase by 28% (relative risk: 1.28, 95% credible interval: 1.13-1.36) for every 1°C rise in temperature, and 17% (relative risk: 1.17, 95% credible interval: 1.01-1.34) for every 10,000 yuan increase in per capita gross domestic product. ConclusionIn most provinces in China, the risk of rabies has been reduced to a persistently low level. However, the progress of rabies control in six provinces have been less than satisfactory. The study highlights interventions, such as enhancing animal vaccination need to be implemented in these priority areas.

Dog demography, rabies awareness and dog bite cases in Bishoftu town, Ethiopia

Rabies is a zoonotic viral disease that affects humans and animals and dogs are the primary source of infection. Information on domestic dog populations is vitally important for rabies control. The present study is to assess the demography of dogs, the incidence of dog bites, and the knowledge, attitude, and practice (KAP) of the communities concerning rabies in Bishoftu town. Cross-sectional household surveys were conducted from April to June 2021 involving a questionnaire survey and collection of retrospective patient records from healthcare facilities. A total of 244 respondents were interviewed using a structured questionnaire format to determine their KAP about rabies and dog ownership. Data on the incidence of dog bites and suspected cases of rabies from November 2019 to June 2021 were retrieved from the records of four health centers in Bishoftu town. In interviewed households (HH) 51.2 % owned at least one dog with a dog: human ratio of 1:9 and 1.54 dogs/household. In the participating households, 71% of dogs had been vaccinated against rabies. Almost all, 99% of the respondents had heard of rabies and identified the mode of transmission of rabies. However, 61.8%, had a moderate level of knowledge and 59.8% had an intermediate level of attitude, and 64.3% satisfactory level of appropriate rabies prevention practices score. There was a statistically significant association between knowledge score and age, occupation, and source of information as well as attitude score with age and source of information (p<0.05). Respondents who attend higher education were more likely to have higher practice scores in the prevention of rabies (p <0.05). There were significant correlations among the participant’s knowledge, attitude, and practice (p<0.01). A total of 612 victims were registered and received the post-exposure vaccine in Bishoftu over two years (2019 to 2021). We identified critical knowledge gaps related to factors influencing rabies prevention and control. The veterinary and public health sectors should play an important role in educating and raising community awareness. Moreover, the production and use of the banned nerve tissue vaccine in the public health sector in Ethiopia need attention.

Temporal trend and high-risk areas of rabies occurrences in animals in Nepal from 2005 to 2018

Rabies is an important zoonosis in both the public and animal health domains. The occurrences of animal rabies have been continuously reported in Nepal. For the effective control and management of animal rabies, a better understanding of rabies epidemiology is essential. Therefore, the objectives of this study were to determine the spatial distribution and to describe the epidemiological characteristics of animal rabies occurrences in Nepal. Official reports of rabies occurrences from 2005 to 2018 were analyzed using the Global Moran’s Index and Local Moran’s Index. The study revealed an increasing trend in the later years of the study period after 2014 with occurrences clustered around the southern region of the country. For the overall period, the high—high clustering areas were mostly found in Dailekh and Kailali. In addition, different areas were visualized as high-risk areas in various years. This study identified the high-risk areas of rabies; thus, authorities and stakeholders can utilize this finding in enhancing the rabies control program in the country

Bacillus subtilis vector based oral rabies vaccines induced potent immune response and protective efficacy in mice.

Rabies is a worldwide epidemic that poses a serious threat to global public health. At present, rabies in domestic dogs, cats, and some pets can be effectively prevented and controlled by intramuscular injection of rabies vaccine. But for some inaccessible animals, especially stray dogs, and wild animals, it is difficult to prevent with intramuscular injection. Therefore, it is necessary to develop a safe and effective oral rabies vaccine. We constructed recombinant Bacillus subtilis (B. subtilis) expressing two different strains of rabies virus G protein, named CotG-E-G and CotG-C-G, immunogenicity was studied in mice. The results showed that CotG-E-G and CotG-C-G could significantly increase the specific SIgA titers in feces, serum IgG titers, and neutralizing antibodies. ELISpot experiments showed that CotG-E-G and CotG-C-G could also induce Th1 and Th2 to mediate the secretion of immune-related IFN-γ and IL-4. Collectively, our results suggested that recombinant B. subtilis CotG-E-G and CotG-C-G have excellent immunogenicity and are expected to be novel oral vaccine candidates for the prevention and control of wild animal rabies.

Cost analysis of implementation of a population level rabies control programme for children in India

BackgroundRabies is an endemic and major public health problem in India. This paper reports cost of implementation of various Pre-Exposure Prophylaxis (PrEP) and Post-Exposure Prophylaxis (PEP) strategies at programmatic level to avert rabies deaths in children in India. MethodsThe cost of implementation of various PrEP + PEP and PEP only regimens recommended by WHO and national guidelines was calculated separately for the first year of implementation for children in the age group of 0–5 years (U-5) and 5–15 years (U-15). The cost was calculated at the level of health facility from government's perspective considering the implementation of the strategies under National Rabies Control Program. All costs were converted into 2020 Indian National Rupee and International Dollars' value using implicit price deflators for Purchasing Power Parities. Base case, scenario and one-way sensitivity analyses were conducted. ResultsThe cost of implementation of PrEP regimen is several times higher than all other PEP regimens in children in the age groups of 0–5 years and 5–15 years for the first year of implementation. However, the study also reported use of intradermal route of vaccination and local infiltration of ERIG in wounds only as a cost-saving approach to prevent rabies deaths in children in situations where PEP only strategies are implemented. ConclusionsThere is a need to conduct primary studies in order to obtain data for cost of implementation of shorter regimens in real-time settings.

Epidemiological and Clinical Features of Human Rabies in Dazu District, Chongqing, China from 2014 to 2021

The epidemiological and clinical data of human rabies cases in the Dazu District of Chongqing from 2014 to 2021 were analyzed retrospectively to determine the epidemiological and clinical features of human rabies cases in Chonqing, China. Nine cases were reported. All cases occurred in farmers from rural areas associated with lower rabies awareness, and eight cases had a definitive history of animal exposure, most commonly in the form of domestic dog bites. All nine patients presented as manic and died within 1–8 days from disease onset (mortality rate of 100%). Increased public awareness of rabies prevention and control is needed, especially among middle-aged and elderly populations in rural areas.

Human rabies control in the era of post-COVID-19: a call for action.

Following the COVID-19 pandemic, there has been a sharp increase in rabies cases and deaths. Rabies outbreaks are being reported worldwide. Multiple disruptions in Rabies control occurred during the pandemic, significantly affecting lower-income countries. Countries need to develop specific action plans to become 'rabies free' by 2030.