ResearchPad - rabies https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Vaccination and monitoring strategies for epidemic prevention and detection in the Channel Island fox (<i>Urocyon littoralis</i>)]]> https://www.researchpad.co/article/elastic_article_15750 Disease transmission and epidemic prevention are top conservation concerns for wildlife managers, especially for small, isolated populations. Previous studies have shown that the course of an epidemic within a heterogeneous host population is strongly influenced by whether pathogens are introduced to regions of relatively high or low host densities. This raises the question of how disease monitoring and vaccination programs are influenced by spatial heterogeneity in host distributions. We addressed this question by modeling vaccination and monitoring strategies for the Channel Island fox (Urocyon littoralis), which has a history of substantial population decline due to introduced disease. We simulated various strategies to detect and prevent epidemics of rabies and canine distemper using a spatially explicit model, which was parameterized from field studies. Increasing sentinel monitoring frequency, and to a lesser degree, the number of monitored sentinels from 50 to 150 radio collared animals, reduced the time to epidemic detection and percentage of the fox population infected at the time of detection for both pathogens. Fox density at the location of pathogen introduction had little influence on the time to detection, but a large influence on how many foxes had become infected by the detection day, especially when sentinels were monitored relatively infrequently. The efficacy of different vaccination strategies was heavily influenced by local host density at the site of pathogen entry. Generally, creating a vaccine firewall far away from the site of pathogen entry was the least effective strategy. A firewall close to the site of pathogen entry was generally more effective than a random distribution of vaccinated animals when pathogens entered regions of high host density, but not when pathogens entered regions of low host density. These results highlight the importance of considering host densities at likely locations of pathogen invasion when designing disease management plans.

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<![CDATA[Neglected tropical diseases in children: An assessment of gaps in research prioritization]]> https://www.researchpad.co/article/5c59fef6d5eed0c484135851

Background

Despite the known burden of neglected tropical diseases (NTDs) on child health, there is limited information on current efforts to increase pediatric therapeutic options. Our objective was to quantify and characterize research activity and treatment availability for NTDs in children in order to inform the prioritization of future research efforts.

Methodology/Principal findings

We conducted a review of the World Health Organization’s (WHO) International Clinical Trials Registry Platform to assess research activity for NTDs. The burden of disease of each NTD was measured in terms of disability adjusted life years (DALYs), which was extracted from the Global Health Data Exchange. First- and second-line medications for each NTD were identified from WHO guidelines. We reviewed FDA drug labels for each medication to determine whether they were adequately labeled for use in children. Descriptive statistics, binomial tests, and Spearman’s rank order correlations were calculated to assess research activity compared to burden of disease. Children comprised 34% of the 20 million DALYs resulting from NTDs, but pediatric trials contributed just 17% (63/369) of trials studying these conditions (p<0.001 for binomial test). Conditions that were particularly under-represented in pediatric populations compared to adults included rabies, leishmaniasis, scabies, and dengue. Pediatric drug trial activity was poorly correlated with pediatric burden of disease across NTDs (Spearman’s rho = 0.41, p = 0.12). There were 47 medications recommended by the WHO for the treatment of NTDs, of which only 47% (n = 22) were adequately labeled for use in children. Of the 25 medications lacking adequate pediatric labeling, three were under study in pediatric trials.

Conclusions/Significance

There is a substantial gap between the burden of disease for NTDs in children and research devoted to this population. Most medications lack adequate pediatric prescribing information, highlighting the urgency to increase pediatric research activity for NTDs with high burden of disease and limited treatment options.

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<![CDATA[Knowledge, attitudes, and practices regarding rabies in Grenada]]> https://www.researchpad.co/article/5c59febfd5eed0c48413538b

Objective

While Grenada attained a zero-human-rabies case status since 1970, the authors conducted the first study to assess knowledge, attitudes, and practices that may contribute to this status as well as to receive feedback on the rabies control program in Grenada.

Methodology

A cross-sectional survey was conducted in July, 2017 with 996 households on the mainland. A questionnaire was administered to collect information on knowledge of rabies and prevention, vaccination practices, perception of institutional responsibilities for rabies control, and evaluation of the anti-rabies program.

Results

Of the 996 households, 617 (62%) had owners of animals that can be infected with rabies and were included in the analysis. Respondents were very aware of rabies as a disease that can infect animals and humans. The rate of participation in the vaccination program was 51.6% for pets and 38.0% for livestock. About 40% of respondents were knowledgeable about the extent of protection from the rabies vaccine. Respondents did not demonstrate exceptionally high levels of knowledge about animals that were likely to be infected with rabies, neither the anti-rabies programs that were conducted in Grenada. The three most frequent recommendations made to improve the rabies-control programs were: increase education programs, control the mongoose population, and expand the vaccination period each year.

Conclusions

Conducting a comprehensive national rabies education program, expanding the vaccination program, and increasing the rate of animal vaccination are important steps that need to be taken to maintain the current zero-human-case status.

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<![CDATA[Utility of rabies neutralizing antibody detection in cerebrospinal fluid and serum for ante-mortem diagnosis of human rabies]]> https://www.researchpad.co/article/5c59fef7d5eed0c48413585e

Background

Early ante-mortem laboratory confirmation of human rabies is essential to aid patient management and institute public health measures. Few studies have highlighted the diagnostic value of antibody detection in CSF/serum in rabies, and its utility is usually undermined owing to the late seroconversion and short survival in infected patients. This study was undertaken to examine the ante-mortem diagnostic utility and prognostic value of antibody detection by rapid fluorescent focus inhibition test (RFFIT) in cerebrospinal fluid (CSF)/serum samples received from clinically suspected human rabies cases from January 2015 to December 2017.

Methodology/Principal findings

Samples collected ante-mortem and post-mortem from 130 and 6 patients with clinically suspected rabies respectively, were received in the laboratory during the study period. Ante-mortem laboratory confirmation was achieved in 55/130 (42.3%) cases. Real time PCR for detection of viral nucleic acid performed on saliva, nuchal skin, brain tissue and CSF samples could confirm the diagnosis in 15 (27.2%) of the 55 laboratory confirmed cases. Ante-mortem diagnosis could be achieved by RFFIT (in CSF and/or serum) in 45 (34.6%) of the 130 clinically suspected cases, accounting for 81.8% of the total 55 laboratory confirmed cases. The sensitivity of CSF RFFIT increased with the day of sample collection (post-onset of symptoms) and was found to be 100% after 12 days of illness. Patients who had received prior vaccination had an increased probability of a positive RFFIT and negative PCR result. Patients who were positive by RFFIT alone at initial diagnosis had longer survival (albeit with neurological sequelae) than patients who were positive by PCR alone or both RFFIT and PCR.

Conclusions/Significance

Detection of antibodies in the CSF/serum is a valuable ante-mortem diagnostic tool in human rabies, especially in patients who survive beyond a week. It was also found to have a limited role as a prognostic marker to predict outcomes in patients.

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<![CDATA[The reemergence of human rabies and emergence of an Indian subcontinent lineage in Tibet, China]]> https://www.researchpad.co/article/5c46652fd5eed0c484517e13

Coordinated surveillance, vaccination and public information efforts have brought the Chinese rabies epizootic under control, but significant numbers of fatalities are still reported annually with some cases occurring in previously rabies free regions. Tibet has remained virtually rabies free for 16 years, but since 2015 one human rabies case has been reported each year. To better understand the origins of these cases, we sequenced three human samples and an additional sample isolated from a dog in 2012. Three genomes were sequenced from brain samples: human case 1 (reported in 2015), human case 3 (2017), and the 2012 dog case. For human case 2 (2016), the rabies N gene was sequenced from a limited saliva sample. Phylogenetic analysis shows that Case 1 (CXZ1501H) and the dog case (CXZ1201D) belong to China IV lineage (equivalent to Arctic-like-2 in global rabies), suggesting an association with a wildlife spillover event. However, Case 2 (CXZ1601H) is placed within the dominant lineage China I, and was most similar with recent strains from neighboring Yunnan province, indicating the current epizootic has finally reached Tibet. Most surprisingly however, was the finding that Case 3 (CXZ1704H) is distinct from other Chinese isolates. This isolate is placed in the Indian Subcontinent clade, similar to recent Nepal strains, indicating that cross-border transmission is a new source for rabies infections. Thus, the complex mixture of the rabies epizootic in Tibet represents a major new challenge for Tibet and national rabies control.

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<![CDATA[Completion of multiple-dose travel vaccine series and the availability of pharmacist immunizers: A retrospective analysis of administrative data in Alberta, Canada]]> https://www.researchpad.co/article/5c5217d4d5eed0c484794659

Pharmacists in a number of countries are being trained in the administration of injections with the aim of improving access and adherence to vaccinations. However, little is known about population-level adherence to multiple-dose travel vaccines, and whether the availability of pharmacist immunizers is associated with adherence. Health administrative data from Alberta, Canada, from April 2008 to May 2017 identified adults dispensed at least one vaccine for hepatitis A, hepatitis B, Japanese encephalitis, or rabies. Individuals were coded as completers or non-completers of the vaccine series based on the number of doses dispensed over a time period comprising the duration of the standard series plus 6 months to account for late doses. The association between the proportion of Alberta pharmacists with injection authorization (according to pharmacist registration data) and completion of vaccine series was assessed using linear regression. Over the study period, 24,164 patients initiated a vaccine series for hepatitis A monovalent, 195,480 for hepatitis B monovalent, 169,802 for combined hepatitis A&B, 1,726 for Japanese encephalitis, and 1,908 for rabies. There were fewer than 5 individuals receiving Japanese encephalitis vaccine per year from 2008–2010 or rabies vaccine from 2008–2009. While statistically significant positive associations were seen across all vaccines except for Japanese encephalitis, the magnitude of these associations was small. Each 1% increase in the proportion of injections-authorized pharmacists saw a corresponding increase in the proportion of individuals with completed vaccine series by 0.31% for hepatitis A monovalent, 0.19% for hepatitis B monovalent, 0.22% for combined hepatitis A&B, and 0.21% for rabies. This may suggest that challenges remain with implementing reminder systems to ensure adherence among travellers. Strategies to develop or improve patient and clinician reminder systems in pharmacies for travel vaccines should therefore be explored.

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<![CDATA[The study of degradation mechanisms of glyco-engineered plant produced anti-rabies monoclonal antibodies E559 and 62-71-3]]> https://www.researchpad.co/article/5c25455ed5eed0c48442c5ec

Rabies is an ancient and neglected zoonotic disease caused by the rabies virus, a neurotropic RNA virus that belongs to the Rhabdoviridae family, genus Lyssavirus. It remains an important public health problem as there are cost and health concerns imposed by the current human post exposure prophylaxis therapy. The use of monoclonal antibodies (mAbs) is therefore an attractive alternative. Rabies mostly affects people that reside in resource-limited areas where there are occasional failures in the cold-chain. These environmental changes may upset the stability of the mAbs. This study focused on mAbs 62-71-3 and E559; their structures, responses to freeze/thaw (F/T) and exposure to reactive oxygen species were therefore studied with the aid of a wide range of biophysical and in silico techniques in order to elucidate their stability and identify aggregation prone regions. E559 was found to be less stable than 62-71-3. The complementarity determining regions (CDR) contributed the most to its instability, more specifically: peptides 99EIWD102 and 92ATSPYT97 found in CDR3, Trp33 found in CDR1 and the oxidised Met34. The constant region “158SWNSGALTGHTFPAVL175” was also flagged by the special aggregation propensity (SAP) tool and F/T experiments to be highly prone to aggregation. The E559 peptides “4LQESGSVL11 from the heavy chain and 4LTQSPSSL11 from the light chain, were also highly affected by F/T. These residues may serve as good candidates for mutation, in the aim to bring forward more stable therapeutic antibodies, thus paving a way to a more safe and efficacious antibody-based cocktail treatment against rabies.

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<![CDATA[Benefit-cost analysis of the policy of mandatory annual rabies vaccination of domestic dogs in rabies-free Japan]]> https://www.researchpad.co/article/5c215187d5eed0c4843fa9e9

Japan is one of the few rabies-free countries/territories which implement the policy of mandatory vaccination of domestic dogs. In order to assess the economic efficiency of such policy in reducing the economic burden of a future canine rabies outbreak in Japan, a benefit-cost analysis (BCA) was performed using probabilistic decision tree modelling. Input data derived from simulation results of published mathematical model, field investigation conducted by the authors at prefectural governments, literature review, international or Japanese database and empirical data of rabies outbreaks in other countries/territories. The current study revealed that the annual costs of implementing the current vaccination policy would be US$160,472,075 (90% prediction interval [PI]: $149,268,935–171,669,974). The economic burden of a potential single canine rabies outbreak in Japan were estimated to be US$1,682,707 (90% PI: $1,180,289–2,249,283) under the current vaccination policy, while it would be US$5,019,093 (90% PI: $3,986,882–6,133,687) under hypothetical abolition of vaccination policy, which is 3-fold higher. Under a damage-avoided approach, the annual benefits of implementing the current vaccination policy in expected value were estimated to be US$85.75 (90% PI: $55.73–116.89). The benefit-cost ratio (BCR) was estimated to be 5.35 X 10−7 (90% PI: 3.46 X 10−7–7.37 X 10−7), indicating that the implementation of the current policy is very economically inefficient for the purpose of reducing the economic burden of a potential canine rabies outbreak. In worse-case scenario analysis, the BCR would become above 1 (indicating economic efficiency) if the risk of rabies introduction increased to 0.04 corresponding to a level of risk where rabies would enter Japan in 26 years while the economic burden of a rabies outbreak under the abolition of vaccination policy increased to $7.53 billion. Best-case analysis further revealed that under relatively extreme circumstances the economic efficiency of the current policy could be improved by decreasing the vaccination price charged to dog owners, relaxing the frequency of vaccination to every two to three years and implementing the policy on a smaller scale, e.g. only in targeted prefectures instead of the whole Japan.

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<![CDATA[<i>PLoS Neglected Tropical Diseases</i> Issue Image | Vol. 12(11) November 2018]]> https://www.researchpad.co/article/5c0ae48ad5eed0c484589ecf

Puppy Love

A young girl taking her best friends to get vaccinated against rabies at a mass canine vaccination campaign in Gonaïves, Haiti. Tran, et al. (2018)

Image Credit: Cuc H. Tran

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<![CDATA[A retrospective evaluation of bites at risk of rabies transmission across 7 years: The need to improve surveillance and reporting systems for rabies elimination]]> https://www.researchpad.co/article/5b4a08dd463d7e3fbe689130

The vast majority of rabies deaths occur in developing countries and rural areas. Due to the absence of surveillance and the lack of reliable information, many endemic countries are not able to assess their rabies burden and implement appropriate solutions. This study reports the incidence of animal bites considered at risk of rabies transmission, along with rates and determinants of the adherence to post-exposure prophylaxis (PEP) between 2008 and 2014 in Dodoma Region, Tanzania. A retrospective analysis of rabid animal bites considered at risk of rabies transmission at Dodoma Regional Referral Hospital (DRRH) during 2008–2014 was conducted. Data were collected from the registers of patients presenting to the hospital because of a potential rabies exposure. The patients were assessed by a trained health worker and each bite was considered as “at risk of rabies” based on the victim’s description of the event. Overall, 10,771 patients coming from Dodoma Region attended DRRH because of a bite from a suspected rabid animal, giving a mean incidence of 74 bites at risk of rabies transmission per 100,000 persons per year. Overall, only 46.0% of people exposed received a complete course of PEP and 61.6% attended the clinic within 48 hours after the bite. Multivariate analysis shows that people age >15 years, residence in rural areas and occurrence during the rainy season were independently associated to delayed access to care. Male gender, age below 15 years. and bites occurring during the dry season were associated with completion of PEP. In this area with a high rate of at-risk bites, several factors—mainly related to health care access and to the affordability and delivery of rabies vaccines—still need to be addressed in order to reduce gender and social inequalities in rabies prevention and control. Further efforts are required to establish an efficient rabies surveillance system in Dodoma Region.

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<![CDATA[Critical linkages between land use change and human health in the Amazon region: A scoping review]]> https://www.researchpad.co/article/5b297b72463d7e06147f8d69

Land use change (LUC) is a main cause of global environmental change, and is an important activity to be studied. Our research aims to examine the current state of evidence on the link between LUC and human health in the Amazon region. We conducted a scoping review of literature in two research databases, resulting in 14 papers for analysis. Our analysis demonstrated a lack of clear definitions for LUC, a wide variety of negative health effects from LUC, the lack of qualitative articles, a lack of studies exploring the potential positive health effects of LUC, and the predominance of studies coming from the Brazilian Amazon. Our study validated the prevailing idea that LUC can lead to negative health consequences, if not managed properly.

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<![CDATA[Enhanced Passive Bat Rabies Surveillance in Indigenous Bat Species from Germany - A Retrospective Study]]> https://www.researchpad.co/article/5989da76ab0ee8fa60b96999

In Germany, rabies in bats is a notifiable zoonotic disease, which is caused by European bat lyssaviruses type 1 and 2 (EBLV-1 and 2), and the recently discovered new lyssavirus species Bokeloh bat lyssavirus (BBLV). As the understanding of bat rabies in insectivorous bat species is limited, in addition to routine bat rabies diagnosis, an enhanced passive surveillance study, i.e. the retrospective investigation of dead bats that had not been tested for rabies, was initiated in 1998 to study the distribution, abundance and epidemiology of lyssavirus infections in bats from Germany. A total number of 5478 individuals representing 21 bat species within two families were included in this study. The Noctule bat (Nyctalus noctula) and the Common pipistrelle (Pipistrellus pipistrellus) represented the most specimens submitted. Of all investigated bats, 1.17% tested positive for lyssaviruses using the fluorescent antibody test (FAT). The vast majority of positive cases was identified as EBLV-1, predominately associated with the Serotine bat (Eptesicus serotinus). However, rabies cases in other species, i.e. Nathusius' pipistrelle bat (Pipistrellus nathusii), P. pipistrellus and Brown long-eared bat (Plecotus auritus) were also characterized as EBLV-1. In contrast, EBLV-2 was isolated from three Daubenton's bats (Myotis daubentonii). These three cases contribute significantly to the understanding of EBLV-2 infections in Germany as only one case had been reported prior to this study. This enhanced passive surveillance indicated that besides known reservoir species, further bat species are affected by lyssavirus infections. Given the increasing diversity of lyssaviruses and bats as reservoir host species worldwide, lyssavirus positive specimens, i.e. both bat and virus need to be confirmed by molecular techniques.

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<![CDATA[Moving from Rabies Research to Rabies Control: Lessons from India]]> https://www.researchpad.co/article/5989da96ab0ee8fa60ba1e6a

Background

Despite the availability of effective interventions and public recognition of the severity of the problem, rabies continues to suffer neglect by programme planners in India and other low and middle income countries. We investigate whether this state of ‘policy impasse’ is due to, at least in part, the research community not catering to the information needs of the policy makers.

Methods & Findings

Our objective was to review the research output on rabies from India and examine its alignment with national policy priorities. A systematic literature review of all rabies research articles published from India between 2001 and 2011 was conducted. The distribution of conducted research was compared to the findings of an earlier research prioritization exercise. It was found that a total of 93 research articles were published from India since 2001, out of which 61% consisted of laboratory based studies focussing on rabies virus. Animals were the least studied group, comprising only 8% of the research output. One third of the articles were published in three journals focussing on vaccines and infectious disease epidemiology and the top 4 institutions (2 each from the animal and human health sectors) collectively produced 49% of the national research output. Biomedical research related to development of new interventions dominated the total output as opposed to the identified priority domains of socio-politic-economic research, basic epidemiological research and research to improve existing interventions.

Conclusion

The paper highlights the gaps between rabies research and policy needs, and makes the case for developing a strategic research agenda that focusses on rabies control as an expected outcome.

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<![CDATA[Imported Human Rabies Cases Worldwide, 1990&#8211;2012]]> https://www.researchpad.co/article/5989d9fbab0ee8fa60b71db3

Sixty cases of human rabies in international travelers were reviewed from 1990–2012. A significant proportion of the cases were observed in migrants or their descendants when emigrating from their country of origin or after a trip to visit friends and relatives or for other reasons (43.3%). The cases were not necessarily associated with long-term travel or expatriation to endemic countries; moreover, cases were observed in travelers after short trips of two weeks or less. A predominance of male patients was observed (75.0%). The proportion of children was low (11.7%). Cases from India and Philippines were frequent (16 cases/60). In a significant proportion of cases (51.1%), diagnosis was challenging, with multiple missed diagnoses and transfers from ward to ward before the final diagnosis of rabies. Among the 28 patients whose confirmed diagnosis was obtained ante-mortem, the mean time between hospitalization and diagnosis was 7.7 days (median time: 6.0 days, range 2–30) including four cases with a diagnosis delayed by 15 or more days. In five cases, a patient traveled through one or more countries before ultimately being hospitalized. Three factors played a role in delaying the diagnosis of rabies in a number of cases: (i) a low index of suspicion for rabies in countries where the disease has been eradicated for a long time or is now rare, (ii) a negative history of animal bites or exposure to rabies, and (iii) atypical clinical presentation of the disease. Clinical symptomatology of rabies is complex and commonly confuses physicians. Furthermore, failure in diagnosing imported cases in more developed countries is most likely related to the lack of medical familiarity with even the typical clinical features of the disease.

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<![CDATA[Bat Rabies in Guatemala]]> https://www.researchpad.co/article/5989da21ab0ee8fa60b7eeab

Rabies in bats is considered enzootic throughout the New World, but few comparative data are available for most countries in the region. As part of a larger pathogen detection program, enhanced bat rabies surveillance was conducted in Guatemala, between 2009 and 2011. A total of 672 bats of 31 species were sampled and tested for rabies. The prevalence of rabies virus (RABV) detection among all collected bats was low (0.3%). Viral antigens were detected and infectious virus was isolated from the brains of two common vampire bats (Desmodus rotundus). RABV was also isolated from oral swabs, lungs and kidneys of both bats, whereas viral RNA was detected in all of the tissues examined by hemi-nested RT-PCR except for the liver of one bat. Sequencing of the nucleoprotein gene showed that both viruses were 100% identical, whereas sequencing of the glycoprotein gene revealed one non-synonymous substitution (302T,S). The two vampire bat RABV isolates in this study were phylogenetically related to viruses associated with vampire bats in the eastern states of Mexico and El Salvador. Additionally, 7% of sera collected from 398 bats demonstrated RABV neutralizing antibody. The proportion of seropositive bats varied significantly across trophic guilds, suggestive of complex intraspecific compartmentalization of RABV perpetuation.

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<![CDATA[The Vaccination of 35,000 Dogs in 20 Working Days Using Combined Static Point and Door-to-Door Methods in Blantyre, Malawi]]> https://www.researchpad.co/article/5989d9fdab0ee8fa60b72dd9

An estimated 60,000 people die of rabies annually. The vast majority of cases of human rabies develop following a bite from an infected dog. Rabies can be controlled in both human and canine populations through widespread vaccination of dogs. Rabies is particularly problematic in Malawi, costing the country an estimated 13 million USD and 484 human deaths annually, with an increasing paediatric incidence in Blantyre City. Consequently, the aim of this study was to vaccinate a minimum of 75% of all the dogs within Blantyre city during a one month period. Blantyre’s 25 administrative wards were divided into 204 working zones. For initial planning, a mean human:dog ratio from the literature enabled estimation of dog population size and dog surveys were then performed in 29 working zones in order to assess dog distribution by land type. Vaccination was conducted at static point stations at weekends, at a total of 44 sites, with each operating for an average of 1.3 days. On Monday to Wednesday, door-to-door vaccination sessions were undertaken in the areas surrounding the preceding static point stations. 23,442 dogs were vaccinated at static point stations and 11,774 dogs were vaccinated during door-to-door vaccinations. At the end of the 20 day vaccination programme, an assessment of vaccination coverage through door-to-door surveys found that of 10,919 dogs observed, 8,661 were vaccinated resulting in a vaccination coverage of 79.3% (95%CI 78.6–80.1%). The estimated human:dog ratio for Blantyre city was 18.1:1. Mobile technology facilitated the collection of data as well as efficient direction and coordination of vaccination teams in near real time. This study demonstrates the feasibility of vaccinating large numbers of dogs at a high vaccination coverage, over a short time period in a large African city.

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<![CDATA[Validation of a Rapid Rabies Diagnostic Tool for Field Surveillance in Developing Countries]]> https://www.researchpad.co/article/5989da35ab0ee8fa60b85ce1

Background

One root cause of the neglect of rabies is the lack of adequate diagnostic tests in the context of low income countries. A rapid, performance friendly and low cost method to detect rabies virus (RABV) in brain samples will contribute positively to surveillance and consequently to accurate data reporting, which is presently missing in the majority of rabies endemic countries.

Methodology/Principal findings

We evaluated a rapid immunodiagnostic test (RIDT) in comparison with the standard fluorescent antibody test (FAT) and confirmed the detection of the viral RNA by real time reverse transcription polymerase chain reaction (RT-qPCR). Our analysis is a multicentre approach to validate the performance of the RIDT in both a field laboratory (N’Djamena, Chad) and an international reference laboratory (Institut Pasteur, Paris, France). In the field laboratory, 48 samples from dogs were tested and in the reference laboratory setting, a total of 73 samples was tested, representing a wide diversity of RABV in terms of animal species tested (13 different species), geographical origin of isolates with special emphasis on Africa, and different phylogenetic clades. Under reference laboratory conditions, specificity was 93.3% and sensitivity was 95.3% compared to the gold standard FAT test. Under field laboratory conditions, the RIDT yielded a higher reliability than the FAT test particularly on fresh and decomposed samples. Viral RNA was later extracted directly from the test filter paper and further used successfully for sequencing and genotyping.

Conclusion/Significance

The RIDT shows excellent performance qualities both in regard to user friendliness and reliability of the result. In addition, the test cassettes can be used as a vehicle to ship viral RNA to reference laboratories for further laboratory confirmation of the diagnosis and for epidemiological investigations using nucleotide sequencing. The potential for satisfactory use in remote locations is therefore very high to improve the global knowledge of rabies epidemiology. However, we suggest some changes to the protocol, as well as careful further validation, before promotion and wider use.

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<![CDATA[Evaluation of Six Commercially Available Rapid Immunochromatographic Tests for the Diagnosis of Rabies in Brain Material]]> https://www.researchpad.co/article/5989daf8ab0ee8fa60bc39bf

Rabies is a neglected zoonotic disease that causes an estimated 60,000 human deaths annually. The main burden lies on developing countries in Asia and Africa, where surveillance and disease detection is hampered by absence of adequate laboratory facilities and/or the difficulties of submitting samples from remote areas to laboratories. Under these conditions, easy-to-use tests such as immunochromatographic assays, i.e. lateral flow devices (LFD), may increase surveillance and improve control efforts. Several LFDs for rabies diagnosis are available but, except for one, there are no data regarding their performance. Therefore, we compared six commercially available LFDs for diagnostic and analytical sensitivity, as well as their specificity and their diagnostic agreement with standard rabies diagnostic techniques using different sample sets, including experimentally infected animals and several sets of field samples. Using field samples the sensitivities ranged between 0% up to 100% depending on the LFD and the samples, while for experimentally infected animals the maximum sensitivity was 32%. Positive results in LFD could be further validated using RT-qPCR and sequencing. In summary, in our study none of the tests investigated proved to be satisfactory, although the results somewhat contradict previous studies, indicating batch to batch variation. The high number of false negative results reiterates the necessity to perform a proper test validation before being marketed and used in the field. In this respect, marketing authorization and batch release control could secure a sufficient quality for these alternative tests, which could then fulfil their potential.

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<![CDATA[Rabies in the Baltic States: Decoding a Process of Control and Elimination]]> https://www.researchpad.co/article/5989da3cab0ee8fa60b88365

Rabies is a fatal zoonosis that still causes nearly 70, 000 human deaths every year. In Europe, the oral rabies vaccination (ORV) of red foxes (Vulpes vulpes) was developed in the late 1970s and has demonstrated its effectiveness in the eradication of the disease in Western and some Central European countries. Following the accession of the three Baltic countries—Estonia, Latvia and Lithuania—to the European Union in 2004, subsequent financial support has allowed the implementation of regular ORV campaigns since 2005–2006. This paper reviews ten years of surveillance efforts and ORV campaigns in these countries resulting in the near eradication of the disease. The various factors that may have influenced the results of vaccination monitoring were assessed using generalized linear models (GLMs) on bait uptake and on herd immunity. As shown in previous studies, juveniles had lower bait uptake level than adults. For the first time, raccoon dogs (Nyctereutes procyonoides) were shown to have significantly lower bait uptake proportion compared with red foxes. This result suggests potentially altered ORV effectiveness in this invasive species compared to the red foxes. An extensive phylogenetic analysis demonstrated that the North-East European (NEE) rabies phylogroup is endemic in all three Baltic countries. Although successive oral vaccination campaigns have substantially reduced the number of detected rabies cases, sporadic detection of the C lineage (European part of Russian phylogroup) underlines the risk of reintroduction via westward spread from bordering countries. Vaccine induced cases were also reported for the first time in non-target species (Martes martes and Meles meles).

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<![CDATA[Management and modeling approaches for controlling raccoon rabies: The road to elimination]]> https://www.researchpad.co/article/5989db54ab0ee8fa60bdd0b5

Rabies is an ancient viral disease that significantly impacts human and animal health throughout the world. In the developing parts of the world, dog bites represent the highest risk of rabies infection to people, livestock, and other animals. However, in North America, where several rabies virus variants currently circulate in wildlife, human contact with the raccoon rabies variant leads to the highest per capita population administration of post-exposure prophylaxis (PEP) annually. Previous rabies variant elimination in raccoons (Canada), foxes (Europe), and dogs and coyotes (United States) demonstrates that elimination of the raccoon variant from the eastern US is feasible, given an understanding of rabies control costs and benefits and the availability of proper tools. Also critical is a cooperatively produced strategic plan that emphasizes collaborative rabies management among agencies and organizations at the landscape scale. Common management strategies, alone or as part of an integrated approach, include the following: oral rabies vaccination (ORV), trap-vaccinate-release (TVR), and local population reduction. As a complement, mathematical and statistical modeling approaches can guide intervention planning, such as through contact networks, circuit theory, individual-based modeling, and others, which can be used to better understand and predict rabies dynamics through simulated interactions among the host, virus, environment, and control strategy. Strategies derived from this ecological lens can then be optimized to produce a management plan that balances the ecological needs and program financial resources. This paper discusses the management and modeling strategies that are currently used, or have been used in the past, and provides a platform of options for consideration while developing raccoon rabies virus elimination strategies in the US.

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