Challenges to improved animal rabies surveillance: Experiences from pilot implementation of decentralized diagnostic units in Chad.

Better surveillance is desperately needed to guide rabies prevention and control to achieve the goal of zero dog-mediated human rabies by 2030, defined by the World Health Organization (WHO) and partners in 2015. With the help of funding from the Vaccine Alliance (GAVI) learning agenda, we implemented animal rabies surveillance based on One Health communication, improved accessibility of diagnostic testing and facilitated sample transport to increase case detection in three regions of Chad. Through the project, rabies surveillance, previously only available in N'Djaména, was extended to selected provincial rural and urban areas. Nine decentralized diagnostic units (DDU) were established, hosted by veterinary district agencies (VDA) in four different administrative regions. Four additional VDAs in the study area were reinforced with facilitation of sample collection and transport. Staff from all these 13 veterinary facilities were trained in sample collection and diagnostics. DDUs performed Rapid Immunodiagnostic Tests (RIDT) providing a preliminary result before samples were sent to the central laboratory in N'Djamena for confirmation with the standard Florescent Antibody Test (FAT). Within the project period from June 2016 to March 2018, 115 samples were reported by veterinary facilities in the study areas compared to 63 samples received from outside the study area, the vast majority of them originating from the capital city N'Djaména (N=61). Eighty nine percent of all 178 samples reported to IRED during the project period tested positive. Most of the samples originated from dogs (92%). Other confirmed rabies positive animals observed were cats, a donkey and a pig. Although surveillance of animal rabies was the focus, four human saliva samples were also submitted for diagnosis. We observed high differences in reporting rates between the four study regions. This could be attributable to differences in rabies epidemiology but are also influenced by the distance to the central laboratory in N'Djaména, the cultural background and the level of public awareness. The possibility for local testing through RIDT was very welcomed by local veterinary staff and preliminary insights suggest a positive influence on One Health communication and PEP initiation. However, these aspects as well as the relative impact of local testing on sample collection in comparison to reinforcement of sample collection and transport alone, need to be further investigated. Challenges encountered related to poor infrastructure (buildings, appliances, materials) and low logistic capacity (lacking means and material for transport and communication) of veterinary services in Chad. In addition, veterinary personnel lack experience in data management. Together with staff turnover, this leads to a need for repeated training. Major shortcoming of the approach was the high cost per sample and limited sustainability beyond the project timeframe.

Identification of risk factors for rabies exposure and access to post-exposure prophylaxis in Chad.

Rabies remains a global public health problem, with Africa as one of the most affected continents. Endemic transmission in the unvaccinated domestic dog population of developing countries leads to many exposures with subsequent death in humans due to lack of access to existing effective prevention tools. The presented study identifies factors of exposure and rabies risk in Chad on the household and health facility levels and highlights the challenges of access to Post Exposure Prophylaxis (PEP). Data on bite exposure and prevention was collected through a representative cross-sectional survey in rural and urban households and through a continuous bite reporting survey in public health facilities. During the household survey 8000 homes were visited, including 3241 (41%) in urban areas and 4759 (59%) in rural areas. The frequency of dog ownership was similar in both rural and urban areas, with around 24% households owning at least one dog. Knowledge of rabies as a disease transmitted mainly from dogs to humans was generally good, but higher in urban (86%) compared to rural areas (73%). The need for early prevention and medical care after a bite was less well known with 35% of respondents believing that rabies is curable after onset of symptoms and only one in three bite victims seeking help in a health facility. Exposure risk based on bite incidence on the population level was increased for Christian compared to Muslim predominant religious context. During the health facility study, 1540 bite cases were registered, of which 58% originated from urban areas and 42% from rural areas. Demographic characteristics of the health facility data subset matched the household survey data subset for the majority of parameters. Only bites from known animals (same household or from neighbourhood) and bites from animals known to be alive were underrepresented, suggesting that such bites are regarded as less dangerous than bites from unknown animals and animals that died, were killed or disappeared. Since human vaccine was provided free of charge during the study, most victims received PEP (84%). However, not all patients completed treatment, with a higher risk of non-compliance observed in rural areas. Access to vaccine before the study was alarmingly low, with only 8.5% accessing PEP. Despite facilitated collaboration between human health and veterinary services through the project, consultation with veterinary services remained generally low. The observed challenges can inform future rabies control programmes on the national level to effectively increase access to PEP exceeding the expected improved availability of human vaccine through the upcoming GAVI investment.

Short communication on the use of a free rabies hotline service in Chad.

As part of the activities of a project to estimate burden of rabies and vaccine demand in Chad, funded by the GAVI Alliance, we set up a free hotline service to guide the population and related public services in the event of an animal bite. This short communication presents the data collected on use of the hotline and describes the value of such a mobile phone service. Flyers, posters and radio advertisements distributed information on the hotline. Not every conversation was systematically registered, but we gathered information from 345 calls in total, including caller location and reason for the call as well as the advice and recommendation given. Although more calls were received from urban zones, the hotline was also accessed from rural locations. More than half of the calls came from the public followed by about 1/3 of calls from health workers and 10% of calls from veterinary workers. Background information on the animal bites mirror results from previous studies, especially the alarming lack of access to health and veterinary facilities in the country. Based on network provider information on incoming and outgoing calls, we estimate that on average 11 queries were handled per day. The hotline enabled the study team to give guidance to the public and to health and veterinary professionals and to monitor vaccine stock in the study areas of the project.

Rabies knowledge and practices among human and veterinary health workers in Chad.

To prevent human rabies deaths close communication between the veterinary and human health sector is needed for timely and adequate treatment after a bite exposure. Good practice treatment and efficient One Health communication depends heavily on the knowledge and practices (KP) of both human health and veterinary workers. We have evaluated the level of KP of both these sectors during a one-day joint training program to kick start a large scale rabies burden and vaccine demand study in selected regions of Chad. Participants were evaluated through a questionnaire before and after training to get insight into the basic knowledge of rabies and the improvement of this knowledge after the training session. In addition to 20 questions on rabies derived from the educational platform of the Global Alliance for Rabies Control, the questionnaires included a pre-training knowledge self-evaluation and a post-training evaluation of the course. Overall 247 workshop participants with varied level of educational background responded to at least one questionnaire. Around 75% of respondents were from the human health sector and 20% from the veterinary sector. Knowledge level did not differ significantly between the two sectors nor between rural or urban working backgrounds. Respondents with a university degree scored significantly higher in pre-and post-training questionnaire compared to respondents with high school level degree or lower. Knowledge was also dependent on study region and sex of the respondent. In general, the importance of a One Health approaches, such as vaccination of dogs to prevent human rabies, is well understood in both sectors. Regarding treatment, many participants did not know the adequate number of doses required for a full course of PEP, but through the training, this knowledge improved. Detailed knowledge of atypical transmission routes and pathophysiology (neurotropism of the virus) was generally lacking and did not significantly improve through the training. The study revealed considerable deficiencies and challenges in the knowledge level of both veterinary and human health workers in Chad. Rabies control programs need to anticipate these challenges to implementation and provide sufficient time and funds for training workshops and follow-up.

A metapopulation model of dog rabies transmission in N'Djamena, Chad.

Rabies transmission was interrupted for several months in N'Djamena, the capital city of Chad, after two mass vaccination campaigns of dogs. However, there was a resurgence in cases, which was not predicted by previous models of rabies transmission. We developed a deterministic metapopulation model with importation of latent dogs, calibrated to four years of weekly incidence data from passive surveillance, to investigate possible causes for the early resurgence. Our results indicate that importation of latently infective dogs better explains the data than heterogeneity or underreporting. Stochastic implementations of the model suggest that the two vaccination campaigns averted approximately 67 cases of dog rabies (out of an estimated 74 cases without vaccination) and 124 human exposures (out of an estimated 148 human exposures without vaccination) over two years. Dog rabies vaccination is therefore an effective way of preventing rabies in the dog population and to subsequently reduce human exposure. However, vaccination campaigns have to be repeated to maintain the effect or reintroduction through importation has to be prevented.

Cost Description and Comparative Cost Efficiency of Post-Exposure Prophylaxis and Canine Mass Vaccination against Rabies in N'Djamena, Chad.

Rabies claims approximately 59,000 human lives annually and is a potential risk to 3.3 billion people in over 100 countries worldwide. Despite being fatal in almost 100% of cases, human rabies can be prevented by vaccinating dogs, the most common vector, and the timely administration of post-exposure prophylaxis (PEP) to exposed victims. For the control and prevention of human rabies in N'Djamena, the capital city of Chad, a free mass vaccination campaign for dogs was organized in 2012 and 2013. The campaigns were monitored by parallel studies on the incidence of canine rabies based on diagnostic testing of suspect animals and the incidence of human bite exposure recorded at selected health facilities. Based on the cost description of the campaign and the need for PEP registered in health centers, three cost scenarios were compared: cumulative cost-efficiency of (1) PEP alone, (2) dog mass vaccination and PEP, (3) dog mass vaccination, PEP, and maximal communication between human health and veterinary workers (One Health communication). Assuming ideal One Health communication, the cumulative prospective cost of dog vaccination and PEP break even with the cumulative prospective cost of PEP alone in the 10th year from the start of the calculation (2012). The cost efficiency expressed in cost per human exposure averted is much higher with canine vaccination and One Health communication than with PEP alone. As shown in other studies, our cost-effectiveness analysis highlights that canine vaccination is financially the best option for animal rabies control and rabies prevention in humans. This study also provides evidence of the beneficial effect of One Health communication. Only with close communication between the human and animal health sectors will the decrease in animal rabies incidence be translated into a decline for PEP. An efficiently applied One Health concept would largely reduce the cost of PEP in resource poor countries and should be implemented for zoonosis control in general.

The Importance of a Participatory and Integrated One Health Approach for Rabies Control: The Case of N'Djaména, Chad.

This study compares data on animal rabies cases from the Chadian national rabies laboratory, hosted at the Insitut de Recherche en Elevage pour le Developpement (IRED), with bite case reporting from health facilities. The data collection accompanied a mass dog vaccination intervention over two years in N'Djaména, Chad. This allowed for a comparison of the dynamics of the incidence of animal rabies cases, human bite exposure incidence and post-exposure prophylaxis (PEP) demand during a dog rabies elimination attempt. Following the mass vaccination, the monthly animal rabies incidence dropped from 1.1/10,000 dogs, as observed prior to the campaign in 2012, to 0.061/10,000 dogs in 2014. However, the PEP demand was found to be largely unaffected. The suspicion of the rabies exposure as reported by health personnel in most cases did not reflect the status of the biting animal but rather the severity of the bite wound, resulting in inappropriate PEP recommendations. In addition, the levels of reporting dead or killed animals to the rabies laboratory was found to be very low. These results reveal a profound lack of communication between health facilities and veterinary structures and the absence of an integrated bite case management (IBCM) approach. Improved communication between human health and veterinary workers is imperative to prevent human rabies deaths through the appropriate use of PEP and to further translate success in animal rabies control into cost savings for the public health sector through a lower PEP demand. Improved training of health and veterinary personnel and the sensitisation of the public are needed to achieve good IBCM practice, to increase the rate of diagnostic testing, to provide adequate and timely PEP, and to reduce the wastage of scarce vaccine resources.

Validation of a Rapid Rabies Diagnostic Tool for Field Surveillance in Developing Countries.

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.

Operational performance and analysis of two rabies vaccination campaigns in N'Djamena, Chad.

Transmission of rabies from animals to people continues despite availability of good vaccines for both human and animal use. The only effective strategy to achieve elimination of dog rabies and the related human exposure is to immunize dogs at high coverage levels. We present the analysis of two consecutive parenteral dog mass vaccination campaigns conducted in N'Djamena in 2012 and 2013 to advocate the feasibility and effectiveness for rabies control through proof of concept. The overall coverage reached by the intervention was >70% in both years. Monthly reported rabies cases in dogs decreased by more than 90% within one year. Key points were a cooperative collaboration between the three partner institutions involved in the control program, sufficient information and communication strategy to access local leaders and the public, careful planning of the practical implementation phase and the effective motivation of staff. The dynamic and semi to non-restricted nature of dog populations in most rabies endemic areas is often considered to be a major obstacle to achieve sufficient vaccination coverage. However, we show that feasibility of dog mass vaccination is highly dependent on human determinants of dog population accessibility and the disease awareness of dog owners. Consequently, prior evaluation of the human cultural and socio-economic context is an important prerequisite for planning dog rabies vaccination campaigns.