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

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 892 ◽  
Author(s):  
Juan E. Echevarría ◽  
Ashley C. Banyard ◽  
Lorraine M. McElhinney ◽  
Anthony R. Fooks

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.

2019 ◽  
Vol 24 (1) ◽  
pp. 315-322 ◽  
Author(s):  
Bruno Fonseca Martins da Costa Andrade ◽  
Taísa Santos de Melo Andrade ◽  
Luzia Helena Queiroz

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.


2020 ◽  
Author(s):  
Malavika Rajeev ◽  
Hélène Guis ◽  
Glenn Edosoa ◽  
Chantal Hanitriniaina ◽  
Anjasoa Randrianarijaona ◽  
...  

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.


1987 ◽  
Vol 99 (3) ◽  
pp. 755-765 ◽  
Author(s):  
Pravan Suntharasamai ◽  
M. J. Warrell ◽  
Chaisin Viravan ◽  
Pornthep Chanthavanich ◽  
Sornchai Looareesuwan ◽  
...  

SUMMARYThe standard six-dose intramuscular (i.m.) rabies post-exposure vaccine regimen using a new purified chick embryo cell (PCEC) vaccine was compared with two economical multisite intradermal (i.d.) PCEC regimens, a multisite i.m. PCEC schedule and a subcutaneous regimen using a suckling mouse brain (SMB) rabies vaccine manufactured in Thailand. The neutralizing antibody results for the four-site and eight-site i.d. and the standard i.m. PCEC regimens were similar over 3 months. A three-site i.m. PCEC regimen had no advantage. The SMB vaccine gave the lowest antibody levels. Human rabies immune globulin therapy significantly increased the GMT of all groups on day 7, unlike equine antirabies serum (EARS). Both antisera suppressed antibody responses to PCEC on days 14 and 28. Three generalized reactions probably related to EARS were the only serious side effects. An eight-site i.d. PCEC vaccine regimen proved as immunogenic as the routine i.m. schedule and, if implemented as post-exposure prophylaxis, would be the cheapest widely available tissue culture vaccine regimen. The protective efficiency should now be tested in patients bitten by rabid animals.


2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Roshan Arjun Ananda ◽  
Hooi-Leng Ser ◽  
Vengadesh Letchumanan

Even though rabies has been claiming more than 50,000 deaths annually worldwide, it is considered as a vaccine-preventable viral disease. More than 95 % of the total human rabies cases are caused by dogs. During the initial stage of infection, affected individuals usually show weakess at the bitten extremities and the virus can ultimately travel to the brain causing neurological signs. In attenuated (inactivated) form, the currently in use vaccines have been recommended by WHO for the prevention (i.e. pre-exposure prophylaxis, PrEP) and treatment (i.e. post-exposure prophylaxis, PEP) regime againstthe rabies virus (RABV). However, given that they normally require refrigeration and are costly, there have been discussions revolving around potential development of newer, safer and cheaper alternative that can perform better and more convenient than the ones that are currently in use. The current review aims to explore general characteristics of RABV before looking into potential candidates of vaccines that have been studied. Further studies on the pathogenic mechanism of RABV and therapeutic approaches are still required to prevent the deathly infection following clinical manifestation. In sum, integrated interventional strategy emphasizing human health and animal health is essential and requires collaboration between health authorities and the public.


2019 ◽  
Vol 9 (4-s) ◽  
pp. 730-735 ◽  
Author(s):  
P.V. Shelke ◽  
Punit R. Rachh

Rabies is a major cause of human death in many developing countries. There is a worldwide shortage of human and equine rabies immune globulin. The WHO recommends combined administration of rabies vaccine and rabies immune globulin to patients after exposure. The implementation of post exposure prophylaxis by vaccination and specific immunoglobulin therapy are largely hampered by its high cost. The equine rabies immunoglobulin is less expensive than human rabies immunoglobulin, and is used for rabies post-exposure prophylaxis in developing countries. Equine rabies immunoglobulin is a F(ab)2 with high specific activity, purity, and safety. Healthy horses are immunized with a rabies vaccine. Crude plasma is collected and immunoglobulin is converted into F(ab)2 fragments by pepsin digestion. The F(ab)2 fragments are purified using caprylic acid precipitation followed by ultrafiltration. Keywords: Rabies, Equine rabies immunoglobulin (ERIG), Human rabies immunoglobulin (HRIG), IgG, Caprylic acid, Pepsin.


Author(s):  
Deborah J Mills ◽  
Colleen L Lau ◽  
Christine Mills ◽  
Luis Furuya-Kanamori

Abstract Background Current guidelines for rabies pre-exposure prophylaxis (PrEP) recommend multiple vaccine doses. Travellers sometimes present for pre-travel consultation with insufficient time to complete standard PrEP schedules. We investigated the efficacy of one-dose intramuscular (IM) vaccine in priming the immune system (as PrEP) by measuring antibody response to simulated post-exposure prophylaxis (PEP). Methods A quasi-experimental pre–post intervention clinical trial was conducted at a specialist travel clinic in Australia. Adults (≥18 years) without a history of rabies vaccination were included. At Visit 1, seronegative status was confirmed and one dose of 0.5 ml IM rabies vaccine (Verorab®) administered. At Visit 2 (≥60 days after Visit 1), serology was repeated and a simulated PEP dose (0.5 ml IM) given on this day and again 3 days later (Visit 3). Serology was repeated at Visit 4 (7 days after Visit 2). Results A total of 94 antibody-negative participants were included (&lt;50 years [n = 50]; ≥50 years [n = 44]). At Visit 2, 38.0 and 31.8% of participants aged &lt;50 and ≥50 years were antibody-positive (≥0.5 EU/ml). At Visit 4, all participants were antibody-positive; 82.0 and 47.7% of participants aged &lt;50 and ≥50 years had antibody levels &gt;4 EU/ml, respectively. Conclusions One-dose IM vaccine was effective as PrEP for priming the immune system in both age groups, resulting in rapid development of antibodies 7 days after commencing simulated PEP. If there is insufficient time to complete a standard PrEP schedule, one-dose IM could be considered as an alternative schedule for short trips, rather than not offering travellers any doses at all. Clinical trials registration: ACTRN12619000946112.


2021 ◽  
Vol 8 (7) ◽  
pp. 132
Author(s):  
Guillaume Crozet ◽  
Tiffany Charmet ◽  
Florence Cliquet ◽  
Emmanuelle Robardet ◽  
Barbara Dufour ◽  
...  

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.


Vaccine ◽  
2011 ◽  
Vol 29 (21) ◽  
pp. 3742-3745 ◽  
Author(s):  
Ahmad Fayaz ◽  
Susan Simani ◽  
Alireza Janani ◽  
Firouzeh Farahtaj ◽  
Peyvand Biglari ◽  
...  

2018 ◽  
Vol 147 ◽  
Author(s):  
D. L. Wang ◽  
X. F. Zhang ◽  
H. Jin ◽  
X. Q. Cheng ◽  
C. X. Duan ◽  
...  

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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