Pre-exposure rabies prophylaxis: a systematic review

Kessels, J A; Recuenco, Sergio; Navarro-Vela, Ana Maria; Deray, Raffy; Vigilato, Marco Antonio Natal; Ertl, Hildegund C. J.; Dürrheim, David N; Rees, Helen; Nel, Louis Hendrik; Abela-Ridder, Bernadette; Briggs, Deborah J.

doi:10.2471/blt.16.173039

Cited by 102 publications

(88 citation statements)

References 43 publications

(52 reference statements)

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“…Fourteen laboratories operating within the framework of either the Ministry of Agriculture or the Ministry of Health in thirteen African countries were invited to participate in the PT exercise and they all accepted. Laboratory directors were required to ensure that all laboratory staff likely to be in contact with rabies suspected samples were immunized against rabies as recommended by the WHO guidelines [27]. However, five out of the fourteen (5/14, 35.7%) participating laboratories did not present satisfactory vaccination coverage.…”

Section: Resultsmentioning

confidence: 99%

An inter-laboratory trial as a tool to increase rabies diagnostic capabilities of Sub-Saharan African Veterinary laboratories

et al. 2020

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To achieve the goal of eliminating dog-mediated human rabies deaths by 2030, many African countries have agreed to list rabies as a priority zoonotic disease and to undertake both short and long-term control programs. Within this context, reliable local diagnosis is essential for the success of field surveillance systems. However, a harmonized, sustainable and supportive diagnostic offer has yet to be achieved in the continent. We herewith describe the organization and outcome of a proficiency test (PT) for the post-mortem diagnosis of rabies in animals, involving thirteen veterinary laboratories and one public health laboratory in Africa. Participants were invited to assess both the performance of the Direct Fluorescent Antibody (DFA) test and of a conventional RT-PCR. From the submitted results, while thirteen laboratories proved to be able to test the samples through DFA test, eleven performed the RT-PCR method; ten applied both techniques. Of note, the number of laboratories able to apply rabies RT-PCR had increased from four to ten after the exercise. Importantly, results showed a higher proficiency in applying the molecular test compared to the DFA test (concordance, sensitivity and specificity: 98.2%, 96.97% and 100% for RT-PCR; 87.69%, 89.23% and 86.15% for DFA test), indicating the feasibility of molecular methods to diagnose animal pathogens in Africa. Another positive outcome of this approach was that negative and positive controls were made available for further in-house validation of new techniques; in addition, a detailed questionnaire was provided to collect useful and relevant information on the diagnostic procedures and biosafety measures applied at laboratory level.

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Section: Resultsmentioning

confidence: 99%

An inter-laboratory trial as a tool to increase rabies diagnostic capabilities of Sub-Saharan African Veterinary laboratories

et al. 2020

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“…Strategies for rabies prevention in vulnerable populations in Amazon regions have been previously reviewed in the literature [1,3,4]. In fact, it has already been proposed that the SINAN form be changed to include fields related to dog and cat behavior to support animal rabies surveillance and prophylactic measures [13].…”

Section: Discussionmentioning

confidence: 99%

“…Many researchers consider contact with the wild reservoir, human population mobility, and the social and cultural characteristics of a population as the main determinants for onset of the disease. The high impact of rabies transmission by vampire bats in the Amazon region is unquestionable [1–3].…”

Section: Introductionmentioning

confidence: 99%

Crab fisherman communities in north Brazil: a new high risk population for vampire bat rabies

Silva

Andrade

Cardoso

et al. 2019

Preprint

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19An outbreak of human rabies transmitted by hematophagous bats occurred in 2018 in the 20 state of Pará, Brazil, eastern Amazon, after 14 years with no record of the disease. It is 21 necessary to understand the epidemiological characteristics of these attacks to protect the 22 local population. This study aimed to characterize attacks of humans by vampire bats in 23 the municipality of São João da Ponta, Pará state, Brazil, from 2013 to 2015. All 24 individuals attacked by bats who sought medical care during the study period (n=5) were 25 identified in the Notifiable Diseases Information System (SINAN) database and answered 26 a questionnaire about the circumstances of the attack. Using snowball sampling, seed 27 cases identified other individuals who were attacked in the same period but did not seek 28 medical care (n=61), totalizing 66 people attacked in the same period. The interviewees 29 were male (92.4%), adults between 20 and 50 years old (69.6%) and had completed 30 elementary education (86.3%). Most were rural residents (92.4%) and crab fishermen 31 (79.3%). The interviewees (92.4%) identified the mangrove of the Mãe Grande de Curuçá 32 extractive reserve as an area conducive to attacks by vampire bats, where groups of 33 fishermen sometimes concentrate for days for crab fishing, often living in improvised 34 dwellings without walls and covered by tarps or straw (88.8%). The wounds were single 35 bites (71.2%) and were located on the lower limbs (93.9%). Overall, 42.4% of participants 36 had been bitten more than four times throughout their life (range 1-23 attacks). 37Participants were unaware of the risk of contracting rabies by the bite (95.4%). Using São 38 João da Ponta as a model, this study shows that bat attacks are an essentially occupational 39 problem in the study region. Indeed, for each reported attack, there are 12.2 unreported 40 cases. It is necessary to develop strategies to reach this population for prophylactic 41 treatment. 42 43 Author Summary 44 45 Different from which occurs worldwide in relation to rabies transmission, in Amazon 46 region, vampire bat is involved on direct transmission of rabies virus to humans when 47 searching for bloodmeal. It is common in the state of Pará, Eastern Amazon, large areas 48 inhabited near forests and mangroves. People living there use forest natural resources as 49 a way of income and sustenance and these working conditions is what our study points 50 out as an important factor for aggressions predisposition. Here this subject is shown as an 51 occupational problem. This study also quantified for the first time underreported human's 52 aggressions by bats in Amazon, using the snowball sampling, which valued the 53 relationship between individuals to reach the target population. Based on these results, 54 rabies surveillance may direct actions for prevention and health education for these 55 individuals, including changes in notifications forms and suggesting pre-exposure 56 prophylaxis in vaccination calendar of the Brazilian Ministry of Health...

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“…As a result of these cost and delivery characteristics, rabies PrEP is not included in routine childhood immunization programmes in most rabies-endemic areas (15).…”

Section: Introductionmentioning

confidence: 99%

“…Child-population-wide PrEP is thus an attractive intervention in areas in which Expanded Programme on Immunization (EPI) vaccines are delivered but which have otherwise limited capacity for reliable urgent PEP or for control of rabies-transmitting animals. This role for mass PrEP has been recognised, Page 7 of 30 for example, in the Peruvian Amazon: in this setting, vampire bat rabies is problematic and difficult to control, access to PEP is limited, and a PrEP programme appears to have been successful (15).…”

Section: Introductionmentioning

confidence: 99%

A simian-adenovirus-vectored rabies vaccine suitable for thermostabilisation and clinical development for low-cost single-dose pre-exposure prophylaxis

Wang

Dulal

Zhou

et al. 2018

Preprint

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BackgroundEstimates of current global rabies mortality range from 26,000 to 59,000 deaths per annum. Although pre-exposure prophylaxis using inactivated rabies virus vaccines (IRVs) is effective, it requires two to three doses and is regarded as being too expensive and impractical for inclusion in routine childhood immunization programmes.Methodology/ Principal FindingsHere we report the development of a simian-adenovirus-vectored rabies vaccine intended to enable cost-effective population-wide pre-exposure prophylaxis against rabies. ChAdOx2 RabG uses the chimpanzee adenovirus serotype 68 (AdC68) backbone previously shown to achieve pre-exposure protection against rabies in non-human primates. ChAdOx2 differs from AdC68 in that it contains the human adenovirus serotype 5 (AdHu5) E4 orf6/7 region in place of the AdC68 equivalents, enhancing ease of manufacturing in cell lines which provide AdHu5 E1 proteins in trans.We show that immunogenicity of ChAdOx2 RabG in mice is comparable to that of AdC68 RabG and other adenovirus serotypes expressing rabies virus glycoprotein. High titers of rabies virus neutralizing antibody (VNA) are elicited after a single dose. The relationship between levels of VNA activity and rabies glycoprotein monomer-binding antibody differs after immunization with adenovirus-vectored vaccines and IRV vaccines, suggesting routes to further enhancement of the efficacy of the adenovirus-vectored candidates. We also demonstrate that ChAdOx2 RabG can be thermostabilised using a low-cost method suitable for clinical bio-manufacture and ambient-temperature distribution in tropical climates. Finally, we show that a dose-sparing effect can be achieved by formulating ChAdOx2 RabG with a simple chemical adjuvant. This approach could lower the cost of ChAdOx2 RabG and other adenovirus-vectored vaccines.Conclusions/ SignificanceChAdOx2 RabG may prove to be a useful tool to reduce the human rabies death toll. We have secured funding for Good Manufacturing Practice-compliant bio-manufacture and Phase I clinical trial of this candidate.Author summaryRabies was, after smallpox, the second human disease for which an efficacious vaccine was developed, by Pasteur in 1885. Although it is eminently preventable, with highly efficacious vaccines available for both humans and animals, it still causes considerable mortality in low and middle-income countries. It is a particular problem in areas with the weakest healthcare and veterinary infrastructure, where achieving prompt post-exposure vaccination or high-coverage dog vaccination are challenging.Here, we report the development of a new candidate rabies vaccine, designed to enable low-cost single-dose pre-exposure human rabies prophylaxis in such settings. ChAdOx2 RabG is based upon a simian adenovirus-vectored candidate previously shown to achieve protection after a single dose in non-human primates, now modified to allow clinical-grade bio-manufacture. We show that it induces a potent immune response in mice, that this response can be further enhanced by clinically-relevant adjuvant, and that we can stabilise it such that it can withstand temperatures of up to 45 °C for a month. We will be performing a clinical trial of this candidate in the near future.

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Pre-exposure rabies prophylaxis: a systematic review

Cited by 102 publications

References 43 publications

An inter-laboratory trial as a tool to increase rabies diagnostic capabilities of Sub-Saharan African Veterinary laboratories

An inter-laboratory trial as a tool to increase rabies diagnostic capabilities of Sub-Saharan African Veterinary laboratories

Crab fisherman communities in north Brazil: a new high risk population for vampire bat rabies

A simian-adenovirus-vectored rabies vaccine suitable for thermostabilisation and clinical development for low-cost single-dose pre-exposure prophylaxis

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