Surveillance to Establish Elimination of Transmission and Freedom from Dog-mediated Rabies

AbstractBackgroundWith a global target set for zero human deaths from dog-mediated rabies by 2030 and some regional programmes close to eliminating canine rabies, there is an urgent need for enhanced surveillance strategies suitable for declaring freedom from disease and elimination of transmission with known confidence.MethodsUsing exhaustive contact tracing across settings in Tanzania we generated detailed data on rabies incidence, rabid dog biting behaviour and health-seeking behaviour of bite victims. Using these data we compared case detection of sampling-based and enhanced surveillance methodologies and investigated elimination verification procedures.FindingsWe demonstrate that patients presenting to clinics with bite injuries are sensitive sentinels for identifying dog rabies cases. Triage of patients based on bite history criteria and investigation of suspicious incidents can confirm >10% of dog rabies cases and is an affordable approach that will enable validation of disease freedom following two years without case detection. Approaches based on sampling the dog population without using bite-injury follow-up were found to be neither sensitive nor cost-effective.InterpretationThe low prevalence of rabies, and short window in which disease can be detected, preclude sampling-based surveillance. Instead, active case finding guided by bite-patient triage is needed as elimination is approached. Our proposed methodology is affordable, practical and supports the goal of eliminating human rabies deaths by improving administration of lifesaving post-exposure prophylaxis for genuinely exposed but untreated contacts. Moreover, joint investigations by public health and veterinary workers will strengthen intersectoral partnerships and capacity for control of emerging zoonoses.

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Leprosy Post-Exposure Prophylaxis (LPEP) programme: study protocol for evaluating the feasibility and impact on case detection rates of contact tracing and single dose rifampicin

BMJ Open ◽

10.1136/bmjopen-2016-013633 ◽

2016 ◽

Vol 6 (11) ◽

pp. e013633 ◽

Cited By ~ 31

Author(s):

Tanja Barth-Jaeggi ◽

Peter Steinmann ◽

Liesbeth Mieras ◽

Wim van Brakel ◽

Jan Hendrik Richardus ◽

...

Keyword(s):

Single Dose ◽

Study Protocol ◽

Contact Tracing ◽

Post Exposure Prophylaxis ◽

Case Detection ◽

Detection Rates ◽

Post Exposure ◽

Exposure Prophylaxis

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How geographic access to care shapes disease burden: the current impact of post-exposure prophylaxis and potential for expanded access to prevent human rabies deaths in Madagascar

10.1101/2020.10.02.20205948 ◽

2020 ◽

Author(s):

Malavika Rajeev ◽

Hélène Guis ◽

Glenn Edosoa ◽

Chantal Hanitriniaina ◽

Anjasoa Randrianarijaona ◽

...

Keyword(s):

Rabies Vaccine ◽

Human Rabies ◽

Post Exposure Prophylaxis ◽

Travel Times ◽

Middle Income ◽

Geographic Access ◽

Post Exposure ◽

Canine Rabies ◽

Middle Income Countries ◽

Exposure Prophylaxis

AbstractBackgroundPost-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 FindingsWe use travel times to the closest clinic providing PEP (N=31) as a proxy for access. We find that travel times strongly predict reported bite incidence across the country. Using resulting estimates in an adapted decision tree framework 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: 800 (95% PI: 640 - 970) each year. Under these assumptions, we find that expanding PEP to one clinic per district could reduce deaths by 19%, but even with all major health centers 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 & SignificancePEP 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. Our framework could be used to guide PEP expansion and improve targeting of interventions in similar endemic settings where PEP access is geographically restricted. While better PEP access should save many lives, improved outreach and surveillance is needed and if rolled out with Gavi investment could catalyze progress towards achieving zero rabies deaths.Author SummaryCanine 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 bite incidence 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 suggest that expansion alone will not eliminate deaths. 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.

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History of Rabies Incidence and Rabies Control in Serbia in Support of the Zero by 2030 Campaign to Eliminate Dog-Mediated Human Rabies

Viruses ◽

10.3390/v14010075 ◽

2021 ◽

Vol 14 (1) ◽

pp. 75

Author(s):

Srđan Stankov ◽

Dušan Lalošević ◽

Anthony R. Fooks

Keyword(s):

Health Department ◽

Human Rabies ◽

Surveillance Program ◽

Post Exposure Prophylaxis ◽

Canine Rabies ◽

Rabies Control ◽

Novi Sad ◽

Exposure Prophylaxis ◽

Rabies Prevention ◽

Rabies Vaccination

Urban (principally canine-mediated) rabies has been a public health risk for people living in Serbia for centuries. The first legal act in urban rabies prevention in Serbia was established in 1834 by introducing high taxes for pet dog owners. Five years later in 1839, the first set of literature describing rabies prevention was issued by the health department from The Serbian Ministry of Interior. An overview of cauterization of rabies wounds was presented as the principal method of rabies post exposure prophylaxis. In 1890, a human rabies vaccination was introduced in Serbia with the royal government directive which ordered patients to be treated at the Pasteur Institute in Budapest in receipt of rabies vaccination. Urban (canine) rabies was eliminated during the 1980s, but sylvatic (principally fox-mediated) rabies still prevailed. The last human rabies case was recorded in the Province of Kosovo and Metohija in 1980. Sylvatic rabies in Serbia is in the final stages of elimination by orally vaccinating foxes (Vulpes vulpes). The only published finding of a lyssavirus among Serbian bats was made in 1954 by Dr Milan Nikolić in the vicinity of Novi Sad. In 2006, a comprehensive two-year active surveillance program of lyssaviruses in bats in Serbia was undertaken. In this single study, all of the bats from Serbia tested negative for a lyssavirus.

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Behavioral and structural barriers to human post-exposure prophylaxis and other preventive practices during a canine rabies epidemic

10.1101/2020.01.16.20016394 ◽

2020 ◽

Cited By ~ 2

Author(s):

Ricardo Castillo-Neyra ◽

Alison M. Buttenheim ◽

Joanna Brown ◽

James F. Ferrara ◽

Claudia Arevalo-Nieto ◽

...

Keyword(s):

Urban Communities ◽

Human Rabies ◽

Post Exposure Prophylaxis ◽

Structural Barriers ◽

Group Discussions ◽

Post Exposure ◽

Canine Rabies ◽

Preventive Practices ◽

Exposure Prophylaxis ◽

Successful Prevention

AbstractA canine rabies epidemic started in early 2015 in Arequipa, Peru; 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 were to qualitatively assess knowledge about rabies, and preventive practices, such as PEP vaccination, following a dog bite. We conducted eight focus group discussions in peri-urban and urban communities with 70 total participants. We observed low awareness of rabies severity and fatality. Participants, especially those in per-urban communities, recounted applying herbs or the hair of the dog that bit them to wounds rather than seeking appropriate care. Misconceptions about rabies vaccines and mistreatment at health centers also commonly prevents initiating or completing PEP vaccination. 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.

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In Vivo Efficacy of SYN023, an Anti-Rabies Monoclonal Antibody Cocktail, in Post-Exposure Prophylaxis Animal Models

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed5010031 ◽

2020 ◽

Vol 5 (1) ◽

pp. 31 ◽

Cited By ~ 1

Author(s):

Tzu-Yuan Chao ◽

Shou-feng Zhang ◽

Li Chen ◽

Eric Tsao ◽

Charles E. Rupprecht

Keyword(s):

Animal Models ◽

Standard Dose ◽

Neutralizing Antibody ◽

Cost Effective ◽

Human Rabies ◽

Post Exposure Prophylaxis ◽

Vaccine Response ◽

Post Exposure ◽

Exposure Prophylaxis

Rabies immune globulin (RIG) is an indispensable component of rabies post-exposure prophylaxis (PEP) because it provides passive immunity to prevent this otherwise inescapably fatal disease in Category III exposed patients. Even with decades of development, RIG products are still criticized for their high cost, lot-to-lot variation, and potential safety issues. They remain largely unattainable in most developing regions of the world, where demand is highest. In recent years, monoclonal antibodies (MAbs) have become widely accepted as safer and more cost-effective alternatives to RIG products. As an example, SYN023 is a 1:1 cocktail of two humanized anti-rabies MAbs previously shown to display extensive neutralizing capabilities. Here, we further assessed the efficacy of SYN023 in animal models of rabies, and found that SYN023 afforded protection equal to a standard dose of human RIG (HRIG) at 0.03 mg/kg in Syrian hamsters and 0.1 mg/kg in beagles. Potential interference with vaccine-induced immunity was analyzed for the MAbs at these concentrations. While individual MAbs did not interfere with vaccine response, SYN023 at dosages of 0.1 mg/kg and above resulted in reduced neutralizing antibody titers similar to HRIG. Thus, the in vivo characterization of SYN023 supports its utility in human rabies PEP as an efficacious alternative to RIG products.

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Benefit–Risk Assessment of the French Surveillance Protocol of Apparently Healthy Biting Dogs and Cats for Human Rabies Prevention

Veterinary Sciences ◽

10.3390/vetsci8070132 ◽

2021 ◽

Vol 8 (7) ◽

pp. 132

Author(s):

Guillaume Crozet ◽

Tiffany Charmet ◽

Florence Cliquet ◽

Emmanuelle Robardet ◽

Barbara Dufour ◽

...

Keyword(s):

Risk Assessment ◽

Traffic Accidents ◽

Scenario Tree ◽

Human Rabies ◽

Post Exposure Prophylaxis ◽

Policy Makers ◽

Benefit Risk Assessment ◽

Surveillance Protocol ◽

Exposure Prophylaxis ◽

Apparently Healthy

In France, apparently healthy dogs and cats that bite humans must undergo an observation period of 15 days with three veterinary visits to ascertain that they remain healthy, indicating that no zoonotic transmission of rabies virus occurred via salivary presymptomatic excretion. This surveillance protocol is mandatory for all pets that have bitten humans, despite France’s rabies-free status in non-flying mammals (i.e., a very low rabies risk). In this context, we aimed to perform a benefit–risk assessment of the existing regulatory surveillance protocol of apparently healthy biting animals, as well as alternative surveillance protocols. A scenario-tree modelling approach was used to consider the possible successions of events between a dog or cat bite and a human death attributed to either rabies or to lethal harm associated with the surveillance protocol (e.g., lethal traffic accidents when traveling to veterinary clinics or anti-rabies centers). The results demonstrated that the current French surveillance protocol was not beneficial, as more deaths were generated (traffic accidents) than avoided (by prompt post-exposure prophylaxis administration). We showed here that less stringent risk-based surveillance could prove more appropriate in a French context. The results in this study could allow policy-makers to update and optimize rabies management legislation.

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Post-exposure prophylaxis vaccination rate and risk factors of human rabies in mainland China: a meta-analysis

Epidemiology and Infection ◽

10.1017/s0950268818003175 ◽

2018 ◽

Vol 147 ◽

Author(s):

D. L. Wang ◽

X. F. Zhang ◽

H. Jin ◽

X. Q. Cheng ◽

C. X. Duan ◽

...

Keyword(s):

Risk Factors ◽

Rural Areas ◽

Meta Analysis ◽

Mainland China ◽

Vaccination Rate ◽

Human Rabies ◽

Post Exposure Prophylaxis ◽

Eastern Region ◽

Post Exposure ◽

Exposure Prophylaxis

AbstractRabies is one of the major public health problems in China, and the mortality rate of rabies remains the highest among all notifiable infectious diseases. A meta-analysis was conducted to investigate the post-exposure prophylaxis (PEP) vaccination rate and risk factors for human rabies in mainland China. The PubMed, Web of Science, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodical and Wanfang databases were searched for articles on rabies vaccination status (published between 2007 and 2017). In total, 10 174 human rabies cases from 136 studies were included in this meta-analysis. Approximately 97.2% (95% confidence interval (CI) 95.1–98.7%) of rabies cases occurred in rural areas and 72.6% (95% CI 70.0–75.1%) occurred in farmers. Overall, the vaccination rate in the reported human rabies cases was 15.4% (95% CI 13.7–17.4%). However, among vaccinated individuals, 85.5% (95% CI 79.8%–83.4%) did not complete the vaccination regimen. In a subgroup analysis, the PEP vaccination rate in the eastern region (18.8%, 95% CI 15.9–22.1%) was higher than that in the western region (13.3%, 95% CI 11.1–15.8%) and this rate decreased after 2007. Approximately 68.9% (95% CI 63.6–73.8%) of rabies cases experienced category-III exposures, but their PEP vaccination rate was 27.0% (95% CI 14.4–44.9%) and only 6.1% (95% CI 4.4–8.4%) received rabies immunoglobulin. Together, these results suggested that the PEP vaccination rate among human rabies cases was low in mainland China. Therefore, standardised treatment and vaccination programs of dog bites need to be further strengthened, particularly in rural areas.

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Human rabies post-exposure prophylaxis relative to the disease epidemiological status

Ciência & Saúde Coletiva ◽

10.1590/1413-81232018241.32832016 ◽

2019 ◽

Vol 24 (1) ◽

pp. 315-322 ◽

Cited By ~ 1

Author(s):

Bruno Fonseca Martins da Costa Andrade ◽

Taísa Santos de Melo Andrade ◽

Luzia Helena Queiroz

Keyword(s):

Rabies Vaccine ◽

Human Rabies ◽

Post Exposure Prophylaxis ◽

Post Exposure ◽

Paulo State ◽

Technical Manual ◽

Prophylactic Measures ◽

Exposure Prophylaxis ◽

Main City ◽

Technical Recommendations

Abstract This study evaluated the prophylactic measures adopted after attacks by dogs and cats in the main city of Northwester São Paulo State, based on the technical manual for post-exposure treatment, considering the not controlled (1990-1996) and controlled (1997-2010) rabies status. A retrospective analysis was done using the data from the SINAN records (W64-CID10) between 1990 and 2010. In most cases, the accidents were mild (76.9%), and biting animals were healthy (75.4%); therefore, no treatment was needed in 53.3% of the cases. In 64.6% of cases, the prescribed PEP treatment was inappropriate. The most indicated PEP treatments consisted of vaccine and RIG (43.4%), and either three doses of mouse brain vaccine or two doses of cell culture vaccine (76.5%), during the not controlled and controlled rabies periods, respectively. The treatment was more appropriate and followed the technical recommendations during controlled rabies periods compared to not controlled (p < 0.0001) periods. However, excessive application of RIG and rabies vaccine was observed in both periods.

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Human rabies post exposure prophylaxis at the Pasteur Institute of Dakar, Senegal: trends and risk factors

BMC Infectious Diseases ◽

10.1186/s12879-019-3928-0 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 3

Author(s):

Mamadou Korka Diallo ◽

Alpha Oumar Diallo ◽

Anta Dicko ◽

Vincent Richard ◽

Emmanuelle Espié

Keyword(s):

Risk Factors ◽

Human Rabies ◽

Post Exposure Prophylaxis ◽

Pasteur Institute ◽

Post Exposure ◽

Exposure Prophylaxis

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Current Rabies Vaccines Do Not Confer Protective Immunity against Divergent Lyssaviruses Circulating in Europe

Viruses ◽

10.3390/v11100892 ◽

2019 ◽

Vol 11 (10) ◽

pp. 892 ◽

Cited By ~ 1

Author(s):

Juan E. Echevarría ◽

Ashley C. Banyard ◽

Lorraine M. McElhinney ◽

Anthony R. Fooks

Keyword(s):

Protective Immunity ◽

Rabies Vaccine ◽

Human Rabies ◽

Post Exposure Prophylaxis ◽

Efficient Tool ◽

Imported Case ◽

Health Authorities ◽

European Health ◽

Preventive Vaccination ◽

Exposure Prophylaxis

The use of the rabies vaccine for post-exposure prophylaxis started as early as 1885, revealing a safe and efficient tool to prevent human rabies cases. Preventive vaccination is the basis for the control of canine-mediated rabies, which has already been eliminated from extensive parts of the world, including Europe. Plans to eliminate canine-mediated human rabies by 2030 have been agreed upon by international organisations. However, rabies vaccines are not efficacious against some divergent lyssaviruses. The presence in European indigenous bats of recently described lyssaviruses, which are not neutralised by antibody responses to existing vaccines, as well as the declaration of an imported case of an African lyssavirus, which also escapes vaccine-derived protection, leaves the European health authorities unable to provide efficacious protective vaccines to some potential situations of human exposure. All these circumstances highlight the need for a universal pan-lyssavirus rabies vaccine, able to prevent human rabies in all circumstances.

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