Introduction: Rabies is a serious, neglected tropical disease. Zoonotic agents are RNA viruses (Genus Lyssavirus, Family Rhabdoviridae), global in distribution. As an acute, progressive, incurable encephalitis, rabies has the highest case fatality of any infectious disease. Warm-blooded vertebrates are susceptible hosts. Major mammalian reservoirs include mesocarnivores and bats. Given wildlife perpetuation, rabies is not eradicable, but is preventable and controllable, especially under newly available international guidelines. Areas covered: Literature review over the past 5 years reveals development of sensitive, specific diagnostic tests and safe and highly effective human and veterinary vaccines. Yet, tens of thousands of human fatalities occur annually, usually in Africa and Asia, primarily after canine exposure. Human and domestic animal vaccination, before or after exposure, is the single greatest preventative strategy following a rabid animal bite. Expert opinion: Significant progress occurred during the twenty-first century regarding vaccine development, doses, and schedules. Remaining barriers to widespread rabies vaccination include an inter-related set of economic, cultural, social, educational, ecological and technological factors. A basic understanding of local and regional root causes of cases historically allows for broader accessibility to vaccination in a trans-disciplinary fashion to meet the global elimination of human rabies caused via dogs (GEHRD) by 2030.

Current status of human rabies prevention: remaining barriers to global biologics accessibility and disease elimination.

Rabies is a fatal viral disease typically transmitted through the bite of rabid animal. Domestic dogs cause over 99% of human rabies deaths. Over half of the world’s population lives in a country where the canine rabies virus variant is endemic and dog bites are common. An estimated 29 million people worldwide receive post-bite vaccination after being exposed to animals suspected of rabies. Accurate and timely risk assessment of rabies in biting dogs is critical to ensure that rabies PEP is administered to all persons with a suspected rabies exposure, while avoiding PEP administration in situations where rabies can be definitively ruled out. In this study, a logistic regression model was developed to quantify the risk of rabies in biting dogs, using data from Haiti’s animal rabies surveillance program. Significant risk factors identified in the model were used to quantify the probability of rabies in biting dogs. The risk of rabies in a biting dog as assessed through Haiti’s rabies surveillance program was highly elevated when the dog displayed hypersalivation (OR = 34.6, 95% CI 11.3–106.5) or paralysis (OR = 19.0, 95% CI 4.8–74.8) and when the dog was dead at the time of the assessment (OR = 20.7, 95% CI 6.7–63.7). Lack of prior rabies vaccination, biting 2 or more people, and if the dog was a puppy also increased the probability that a biting dog would have rabies. The model showed high sensitivity (100%) and specificity (97%) when examined using validation data. This model enables us to project the risk of rabies in biting dogs in Haiti shortly after the bite event and make provisional PEP recommendations prior to laboratory testing or dog quarantine results. Application of this model may improve adherence to PEP for bite victims who can be educated on the quantitative risk of the exposure event. This model can also be used to reduce unnecessary PEP costs when the risk of rabies is determined as sufficiently low and the animal is available for observation.

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Quantifying the risk of rabies in biting dogs in Haiti

Zoonoses can cause a substantial burden on both human and animal health. Globally, estimates of the dual (human and animal) burden of zoonoses are scarce. Therefore, this study aims to quantify the dual burden of zoonoses using a comparable metric, "zoonosis Disability Adjusted Life Years" (zDALY).We systematically reviewed studies that quantify in the same article zoonoses in animals, through monetary losses, and in humans in terms of Disability Adjusted Life Years (DALYs). We searched EMBASE, Web of Science, Scopus, PubMed, and Google Scholar. We excluded articles that did not provide the data to estimate the zDALY or those for which full text was not available. This study was registered at PROSPERO, CRD42022313081.We identified 512 potentially eligible records. After deduplication and screening of the title and abstract, 23 records were assessed for full-text review. Fourteen studies were included in this systematic review. The data contains estimates from 10 countries, a study at continental level (Asia and Africa), and 2 studies on a global scale. Rabies was the most frequently reported zoonosis where zDALYs were calculated, based on the following included studies: for Kazakhstan 457 (95% CI 342-597), Viet Nam 5316 (95% CI 4382-6244), Asia 1,145,287 (90% CI 388,592-1,902,310), Africa 837,158 (90% CI 283,087-1,388,963), and worldwide rabies 5,920,014 (95% CI 1,547,860-10,290,815). This was followed by echinococcosis, the zDALYs in Peru were 2238 (95% CI 1931-2546), in China 1490 (95% CI 1442-1537), and worldwide cystic echinococcosis 5,935,463 (95% CI 4,497,316-7,377,636). Then, the zDALYs on cysticercosis for Mozambique were 2075 (95% CI 1476-2809), Cameroon 59,540 (95% CR 16,896-101,803), and Tanzania 34,455 (95% CI 12,993-76,193). Brucellosis in Kazakhstan were 2443 zDALYs (95% CI 2391-2496), and brucellosis and anthrax in Turkey 3538 zDALYs (95% CI 2567-6706). Finally, zDALYs on leptospirosis in New Zealand were 196, and Q fever in Netherlands 2843 (95% CI 1071-4603). The animal burden was superior to the human burden in the following studies: worldwide cystic echinococcosis (83%), brucellosis in Kazakhstan (71%), leptospirosis in New Zealand (91%), and brucellosis, and anthrax in Turkey (52%). Countries priorities on zoonoses can change if animal populations are taken into consideration. 

https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0010540&type=printable

The dual burden of animal and human zoonoses: A systematic review

Lab-attenuated rabies virus (RABV) is a highly cellular adaptation and less pathogenic than wild-type RABV However, the molecular mechanisms that regulate the cellular adaptation and pathogenicity remain obscure In this work, we isolated a wild-type RABV (CNIM1701) from a rabid bovine in northern China The original CNIM1701 was lethal in adult mice and restricted replication in cell cultures After 20 serial passages in the brains of suckling mice, the virus was renamed CNIM1701-P20, which was safe in adult mice and replicated well in cell cultures In addition, sequence comparison analysis of the original CNIM1701 and CNIM1701-P20 identified 2 amino acid substitutions on G protein (Lys83 → Arg83 and Pro367 → Ser 367) related to pathogenesis and cellular adaptation Using site-directed mutagenesis to exchange Lys83 with Arg83 and Pro367 with Ser 367 in the G protein of the RABV SAD strain, the pathogenicity of rSAD-K83R was significantly decreased Our data indicate that the decreased pathogenicity of rSAD-K83R is due to increasing the expression of RABV-G, which also induced a higher level of apoptosis in infected cells Furthermore, the K83 mutation induced high expression of MMP-2 and MMP-9 on DCs and promoted blood-brain barrier (BBB) permeability These results demonstrate that the pathogenesis of RABV is partially dependent on G expression and BBB permeability, which may help in the design and development of highly safe, live-RABV vaccines

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Change in the Single Amino Acid Site 83 in Rabies Virus Glycoprotein Enhances the BBB Permeability and Reduces Viral Pathogenicity.

Bu calismada “Kuduz” anahtar kelimesi kullanilarak, 01.01.2005-30.06.2019 tarihleri arasindaki Google Trends internet tarama verileri ile ayni donem Uluslararasi Salgin Hastaliklar Ofisi Kuduz mihrak verileri kullanilarak il duzeyinde mihrak sayilari, hastaligin yillar itibariyle gorulme sikligi ve Google Trends verilerinde alt bolge olarak bildirilen iller arasindaki iliski arastirilmistir. Calismada bolgelerin belirlenmesinde frekans dagilimi icinde en cok yer alan il sayilari dikkate alinmistir. Oran analizi yontemi ile yapilan degerlendirmelerde; mihrak sayisi, frekans dagilimi ve alt bolge icin buyukten kucuge dogru yapilan siralama ile ilk 25, 15 ve 10 il degerlendirilmistir. Google Trends verilerinde aramalarin %52 oraninda (13/25 Il), %66,6 (9/15 Il) ve %80 (8/10 Il) oraninda hastaligin frekans dagiliminda en cok sayida yer alan illerin bulundugu bolgelerde gerceklestigi tespit edilmistir. Elde edilen calisma bulgulari Google Trends veri siralamasinin hastalik koruma ve kontrolunde kullaniminin onemini ortaya koymustur.

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Google trends kuduz tarama veri̇leri̇ i̇le kuduz hastaliği mi̇hrak ve frekans veri̇leri̇ arasindaki̇ i̇li̇şki̇ni̇n anali̇zi̇

The global economic impact of canine rabies has been estimated by several studies. Asia bears a disproportionate burden of this zoonosis due to high levels of human deaths and rates of post-exposure prophylaxis (PEP), but low investment in preventative dog vaccination. The same factors that cause rabies to burden much of Asia are also present in Viet Nam. This study estimated the economic burden of canine rabies in a societal perspective including direct and indirect cost of rabies in dogs, livestock, and humans. Using data collected from personal interviews, published literature, published and supplementary reports, and primary data collection, we estimated the economic impact of canine rabies in Viet Nam over a ten year period (2005–2014). We incorporated the direct and indirect costs for PEP, dog vaccination efforts, livestock losses, and disability adjusted life years (DALYs) into the analysis. General findings from this analysis indicated that over the 10 year study period, the total economic impact of canine rabies was over $719 million USD. The largest portion of impacts (92%) were made up of PEP-related costs. Canine rabies created between 36,560 and 45,700 DALYs, measured in years of life lost (YLL). A total of 914 human deaths were reported over the study period. Deaths/100,000 people were 0.11, which is lower than the reported level for Asian countries. The cost per dog vaccinated was $1.75 USD. Our results indicate that canine rabies impacts in Viet Nam are consistent with the burden elsewhere reported in Asia, with large expenditures on PEP and very small investments in dog vaccination.

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David Payne

Papers

Estimating the economic impact of canine rabies to Viet Nam 2005-2014.