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.

Modelling to inform prophylaxis regimens to prevent human rabies.

BACKGROUND: The Strategic Advisory Group of Experts (SAGE) Working Group on rabies vaccines and immunoglobulins was established in 2016 to develop practical and feasible recommendations for prevention of human rabies. To support the SAGE agenda we developed models to compare the relative costs and potential benefits of rabies prevention strategies. METHODS: We examined Post-Exposure Prophylaxis (PEP) regimens, protocols for administration of Rabies Immunoglobulin (RIG) and inclusion of rabies Pre-Exposure Prophylaxis (PrEP) within the Expanded Programme on Immunization (EPI). For different PEP regimens, clinic throughputs and consumables for vaccine administration, we evaluated the cost per patient treated, costs to patients and potential to treat more patients given limited vaccine availability. RESULTS: We found that intradermal (ID) vaccination reduces the volume of vaccine used in all settings, is less costly and has potential to mitigate vaccine shortages. Specifically, the abridged 1-week 2-site ID regimen was the most cost-effective PEP regimen, even in settings with low numbers of bite patients presenting to clinics. We found advantages of administering RIG to the wound(s) only, using considerably less product than when the remaining dose is injected intramuscularly distant to the wound(s). We found that PrEP as part of the EPI programme would be substantially more expensive than use of PEP and dog vaccination in prevention of human rabies. CONCLUSIONS: These modeling insights inform WHO recommendations for use of human rabies vaccines and biologicals. Specifically, the 1-week 2-site ID regimen is recommended as it is less costly and treats many more patients when vaccine is in short supply. If available, RIG should be administered at the wound only. PrEP is highly unlikely to be an efficient use of resources and should therefore only be considered in extreme circumstances, where the incidence of rabies exposures is extremely high.

[Rabies knowledge, attitudes, and practices of human and animal healthcare providers in Chad]. / Connaissances-Attitudes-Pratiques des agents de santé humaine et animale sur la rage au Tchad.

INTRODUCTION: Rabies, an infectious disease mainly transmitted by dog bites, is fatal due to lack of appropriate knowledge-attitudes-practices (KAP). The KAP of healthcare providers are particularly important because of their presence in the communities and their profession and were evaluated in the present study. METHODS: A cross-sectional, questionnaire-based descriptive study was conducted in healthcare providers recruited from four health districts in Chad in 2015. Data were analysed with Epi Info. 7. RESULTS: 270 health care providers were interviewed. 87% defined rabies as a disease transmitted from dogs to man. The main reservoir of rabies was the dog (96.7%), the cat (68.9%), but also other animals (35%). All respondents reported dogs to be a vector and 79.6% reported cats. Healthcare providers considered that the virus was transmitted by bites (99.3%) and scratches (50%). The primary means of prevention was vaccination of dogs (82.1%) and post-exposure prophylaxis (16.4%). Immediate washing of the wounds was reported by 65.2% of respondents. CONCLUSION: Healthcare providers have a good knowledge of the dog as a reservoir and vector of rabies. However, continuous training is needed to enable them to acquire knowledge about the role of cats and the importance of scratching in the transmission of rabies virus, the need for wound washing, and appropriate bite management based on collaboration between human and veterinary health sectors.

Vaccination of dogs in an African city interrupts rabies transmission and reduces human exposure.

Despite the existence of effective rabies vaccines for dogs, dog-transmitted human rabies persists and has reemerged in Africa. Two consecutive dog vaccination campaigns took place in Chad in 2012 and 2013 (coverage of 71% in both years) in the capital city of N'Djaména, as previously published. We developed a deterministic model of dog-human rabies transmission fitted to weekly incidence data of rabid dogs and exposed human cases in N'Djaména. Our analysis showed that the effective reproductive number, that is, the number of new dogs infected by a rabid dog, fell to below one through November 2014. The modeled incidence of human rabies exposure fell to less than one person per million people per year. A phylodynamic estimation of the effective reproductive number from 29 canine rabies virus genetic sequences of the viral N-protein confirmed the results of the deterministic transmission model, implying that rabies transmission between dogs was interrupted for 9 months. However, new dog rabies cases appeared earlier than the transmission and phylodynamic models predicted. This may have been due to the continuous movement of rabies-exposed dogs into N'Djaména from outside the city. Our results show that canine rabies transmission to humans can be interrupted in an African city with currently available dog rabies vaccines, provided that the vaccination area includes larger adjacent regions, and local communities are informed and engaged.

[Evaluation of Knowledge-Attitudes-Practices of the populations in the health districts of Benoye, Laoukassy, Moundou and South N'Djamena towards canine rabies in Chad]. / Evaluation des Connaissances-Attitudes-Pratiques des populations des districts sanitaires de Benoye, Laoukassy, Moundou et N'Djaména Sud sur la rage canine au Tchad.

INTRODUCTION: Canine rabies remains a concern in Africa as well as in Chad. Our study aimed to evaluate the knowledge, attitudes and practices of the populations towards the appropriate management of people exposed to canine rabies and effective fight against it. METHODS: We conducted a cross-sectional, descriptive study in four health districts in Chad in July and in September 2015. Data were collected from households recruited by three-stage random sampling by means of a questionnaire. RESULTS: We conducted a survey of 2428 individuals having completed at least primary education level (54,12%). The average age was 36 ± 13.50 years. Surveyed individuals were farmers (35,17%), merchants (18,04%), households (12.81%). Rabies was defined as a disease transmitted from the dog to the man (41.43%), an alteration in brain function (41.27%), an undernourishment (10.26%). The cat was little-known to be a reservoir(13.84%) and a vector (19,77%) as well as licking was little-known to be a transmission medium (4.61%) and cat vaccination to be a preventive measure (0.49%). First aid for a bite at home was the traditional practice (47,69%), wounds washing (19.48%) or no action undertaken (20.43%). Households consulted the Health Service (78.50%), the Animal Health Service (5.35%) and the traditional healers (27%). CONCLUSION: A communication campaing for implementing first aid at home in the event of a bite, knowledge about the cat as a reservoir and a vector and licking as a transmission medium as well as the promotion of the consultation of veterinary services in the event of a bite are necessary.

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.

Cost-estimate and proposal for a development impact bond for canine rabies elimination by mass vaccination in Chad.

Close to 69,000 humans die of rabies each year, most of them in Africa and Asia. Clinical rabies can be prevented by post-exposure prophylaxis (PEP). However, PEP is commonly not available or not affordable in developing countries. Another strategy besides treating exposed humans is the vaccination of vector species. In developing countries, the main vector is the domestic dog, that, once infected, is a serious threat to humans. After a successful mass vaccination of 70% of the dogs in N'Djaména, we report here a cost-estimate for a national rabies elimination campaign for Chad. In a cross-sectional survey in four rural zones, we established the canine : human ratio at the household level. Based on human census data and the prevailing socio-cultural composition of rural zones of Chad, the total canine population was estimated at 1,205,361 dogs (95% Confidence interval 1,128,008-1,736,774 dogs). Cost data were collected from government sources and the recent canine mass vaccination campaign in N'Djaména. A Monte Carlo simulation was used for the simulation of the average cost and its variability, using probability distributions for dog numbers and cost items. Assuming the vaccination of 100 dogs on average per vaccination post and a duration of one year, the total cost for the vaccination of the national Chadian canine population is estimated at 2,716,359 Euros (95% CI 2,417,353-3,035,081) for one vaccination round. A development impact bond (DIB) organizational structure and cash flow scenario were then developed for the elimination of canine rabies in Chad. Cumulative discounted cost of 28.3 million Euros over ten years would be shared between the government of Chad, private investors and institutional donors as outcome funders. In this way, the risk of the investment could be shared and the necessary investment could be made available upfront - a key element for the elimination of canine rabies in Chad.

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.

Owner valuation of rabies vaccination of dogs, Chad.

We estimated the association between amount charged and probability that dog owners in N'Djaména, Chad, would have their dogs vaccinated against rabies. Owners would pay approximately 400-700 CFA francs (US $0.78-$1.36)/animal. To vaccinate >or=70% of dogs, and thus interrupt rabies transmission, health officials should substantially subsidize these vaccinations.

Rabies diagnosis for developing countries.

BACKGROUND: Canine rabies is a neglected disease causing 55,000 human deaths worldwide per year, and 99% of all cases are transmitted by dog bites. In N'Djaména, the capital of Chad, rabies is endemic with an incidence of 1.71/1,000 dogs (95% C.I. 1.45-1.98). The gold standard of rabies diagnosis is the direct immunofluorescent antibody (DFA) test, requiring a fluorescent microscope. The Centers for Disease Control and Prevention (CDC, Atlanta, United States of America) developed a histochemical test using low-cost light microscopy, the direct rapid immunohistochemical test (dRIT). METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the dRIT in the Chadian National Veterinary Laboratory in N'Djaména by testing 35 fresh samples parallel with both the DFA and dRIT. Additional retests (n = 68 in Chad, n = 74 at CDC) by DFA and dRIT of stored samples enhanced the power of the evaluation. All samples were from dogs, cats, and in one case from a bat. The dRIT performed very well compared to DFA. We found a 100% agreement of the dRIT and DFA in fresh samples (n = 35). Results of retesting at CDC and in Chad depended on the condition of samples. When the sample was in good condition (fresh brain tissue), we found simple Cohen's kappa coefficient related to the DFA diagnostic results in fresh tissue of 0.87 (95% C.I. 0.63-1) up to 1. For poor quality samples, the kappa values were between 0.13 (95% C.I. -0.15-0.40) and 0.48 (95% C.I. 0.14-0.82). For samples stored in glycerol, dRIT results were more likely to agree with DFA testing in fresh samples than the DFA retesting. CONCLUSION/SIGNIFICANCE: The dRIT is as reliable a diagnostic method as the gold standard (DFA) for fresh samples. It has an advantage of requiring only light microscopy, which is 10 times less expensive than a fluorescence microscope. Reduced cost suggests high potential for making rabies diagnosis available in other cities and rural areas of Africa for large populations for which a capacity for diagnosis will contribute to rabies control.