"When a dog bites someone": Community and service provider dynamics influencing access to integrated bite case management in Chad.

This study aims to identify factors on the community, the human health and the animal health provider level that determine access to Post Exposure Prophylaxis (PEP) and animal rabies diagnosis in the light of a future integrated bite case management (IBCM) approach for rabies control in Chad. The study was embedded in an overall project conducted from 2016 to 2018, to determine rabies burden and vaccine demand in West and Central Africa. Data collection took place during the projects closing workshops with stakeholders organized between August and September 2018 in the three study zones in Chad covering Logone Occidental and Ouaddaï province and parts of Hadjer Lamis and Chari Baguirmi province. A qualitative approach based on focus group discussion and in-depth interviews was used to get insights on access to care and animal investigation after suspected rabies exposure. A total of 96 participants, including 39 from the community (bite victims, dog owners) and 57 human and animal health providers (health center managers, chief veterinary officers, chief district medical officers, chiefs of livestock sectors) contributed to the study. Based on an existing conceptual framework of access to health care, several points of dissatisfaction were identified, in particular the unaffordability of human rabies vaccine for PEP (affordability) and the distance to travel to a health facility in case of a bite (accessibility). In addition, there are unfavorable attitudes observed highlighted by the importance given to traditional or local rabies care practices to the detriment of PEP (acceptability) and a low level of knowledge among Chadian communities regarding bite prevention, coupled with a very inadequate information and awareness system regarding the disease (adequacy). As for human and veterinary health services, both sectors suffer from insufficient resources for PEP on the human health and rabies diagnosis on the veterinary side impacting negatively on availability and accessibility of both these services. Action to improving provision of rabies health services and increasing knowledge about risk and prevention of the disease among the population need to be undertaken to implement IBCM, improve access to PEP and achieve the goal of eliminating dog mediated human rabies by 2030 in Chad.

General insights on obstacles to dog vaccination in Chad on community and institutional level.

Domestic dogs are responsible for 95% of all human rabies cases worldwide and continue to be the main reservoir for this fatal virus in African and Asian countries. Interrupting the spread of the disease in the domestic dog population is therefore necessary for long-term, sustainable rabies control. Chad has been recognized as a rabies-endemic country since 1961, but no national control strategy is in place to date and dog vaccination coverage is very low. This qualitative, descriptive study aims to describe the main barriers to dog vaccination on both the community and the institutional level from a socio-anthropological point of view in Chad. The study was embedded in an overall project conducted from 2016 to 2018, to determine rabies burden and vaccine demand in West and Central Africa, funded by GAVI, the vaccine alliance. Data collection was conducted on the occasion of the project's closing workshops with stakeholders organized between August to September 2018 in the four (4) project areas: Logone Occidental, Ouaddaï, Hadjer Lamis and Chari Baguirmi. We conducted interviews and focus group discussions (FGD) among veterinary officers and dog owners. Participants were selected purposively based on their place of residence (dog owners) or work place (veterinary officers) and their previous contact with the project through reporting (dog owner) or management (veterinary officers) of a suspect dog rabies case. In each region, one FGD was organized with dog owners, and one FGD with heads of veterinary posts. At the end of the FGDs, a few participants were randomly selected for interviews. In addition, in each region an interview was conducted with the head of the livestock sector, the chief district medical officers and the head of a civil society association. The identified barriers to dog vaccination access are grouped into three main aspects: the economic, the socio-cultural and the institutional level. Economic constraints encountered relate to the cost of the vaccine itself and the expenses for transporting the dogs to the vaccination site. The cultural belief that the vaccine will have an impact on the therapeutic properties of dog meat for consumers (observed in Southern Chad), and the fact that dogs are considered impure animals in Muslim faith, which prohibits handling of dogs, are obstacles identified on the sociocultural level. At the institutional level, the unavailability of vaccines in veterinary services, the lack of communication about the law on dog vaccination, the absence of rabies in the training curricula of veterinary agents, and the lack of intersectoral collaboration limit vaccination coverage. In order to improve vaccination coverage and rabies surveillance with a view to eradicate rabies by 2030, communication strategies that are adapted to the context and that take cultural obstacles into account must be put in place in a synergy of interdisciplinary action. In addition, factors such as affordability, geographical access and availability of dog rabies vaccines needs to be addressed throughout the country. Although our study design did not allow a detailed analysis of obstacles related to socio-economic level, gender and age the broad insights gained can provide general guidance for future interventions in Chad and similar countries.

The Promotion and Development of One Health at Swiss TPH and Its Greater Potential.

One Health, an integrated health concept, is now an integral part of health research and development. One Health overlaps with other integrated approaches to health such as EcoHealth or Planetary Health, which not only consider the patient or population groups but include them in the social-ecological context. One Health has gained the widest foothold politically, institutionally, and in operational implementation. Increasingly, One Health is becoming part of reporting under the International Health Legislation (IHR 2005). The Swiss Tropical and Public Health Institute (Swiss TPH) has played a part in these developments with one of the first mentions of One Health in the biomedical literature. Here, we summarise the history of ideas and processes that led to the development of One Health research and development at the Swiss TPH, clarify its theoretical and methodological foundations, and explore its larger societal potential as an integrated approach to thinking. The history of ideas and processes leading to the development of One Health research at the Swiss TPH were inspired by far-sighted and open ideas of the directors and heads of departments, without exerting too much influence. They followed the progressing work and supported it with further ideas. These in turn were taken up and further developed by a growing number of individual scientists. These ideas were related to other strands of knowledge from economics, molecular biology, anthropology, sociology, theology, and linguistics. We endeavour to relate Western biomedical forms of knowledge generation with other forms, such as Mayan medicine. One Health, in its present form, has been influenced by African mobile pastoralists' integrated thinking that have been taken up into Western epistemologies. The intercultural nature of global and regional One Health approaches will inevitably undergo further scrutiny of successful ways fostering inter-epistemic interaction. Now theoretically well grounded, the One Health approach of seeking benefits for all through better and more equitable cooperation can clearly be applied to engagement in solving major societal problems such as social inequality, animal protection and welfare, environmental protection, climate change mitigation, biodiversity conservation, and conflict transformation.

Seasonal fishery facilitates a novel transmission pathway in an emerging animal reservoir of Guinea worm.

Exploitation of natural resources is a driver of human infectious disease emergence. The emergence of animal reservoirs of Guinea worm Dracunculus medinensis, particularly in domestic dogs Canis familiaris, has become the major impediment to global eradication of this human disease. 93% of all Guinea worms detected worldwide in 2020 were in dogs in Chad. Novel, non-classical pathways for transmission of Guinea worm in dogs, involving consumption of fish, have been hypothesized to support the maintenance of this animal reservoir. We quantified and analyzed variation in Guinea worm emergence in dogs in Chad, across three climatic seasons, in multiple villages and districts. We applied forensic stable isotope analyses to quantify dietary variation within and among dogs and GPS tracking to characterize their spatial ecology. At the end of the hot-dry season and beginning of the wet season, when fishing by people is most intensive, Guinea worm emergence rates in dogs were highest, dogs ate most fish, and fish consumption was most closely associated with disease. Consumption of fish by dogs enables a non-classical transmission pathway for Guinea worm in Chad. Seasonal fisheries and the facilitation of dogs eating fish are likely contributing to disease persistence and to this key impediment to human disease eradication. Interrelated natural resource use, climatic variation, companion animal ecology, and human health highlight the indispensability of One Health approaches to the challenges of eradicating Guinea worm and other zoonotic diseases.

Rabies burden in Côte d'Ivoire.

BACKGROUND: In Côte d'Ivoire, just as in the majority of developing countries, rabies cases are underestimated. The official data are based on passive surveillance studies which cannot provide true estimates. Therefore, the economic and health burden of rabies is underestimated. To be able to better estimate the true burden of rabies, this study looked at surveillance data of bite records and household survey. METHODOLOGY: The data was collected from a cross-sectional survey of 8004 households, of which 4002 were in the Department of Bouaké and 4002 in the Department of San Pedro. Further data was collected from Human Rabies control centres and from the respective veterinary services. We estimate the burden of rabies through data from the bites surveillance records. Human deaths from rabies were estimated using a series of probability steps to determine the likelihood of clinical rabies in a person after being bitten by a suspected rabid dog. Monte Carlo simulations of a series of interconnected probabilities were used to estimate the rabies burden in the country. RESULTS: The number of deaths from rabies was estimated at 637deaths per year [95% CI 442-849] and human mortality from rabies was estimated at 2.61 per 100'000 [95% CI 1.81-3.56], which represents 24-47 times more cases than the official data. Deaths due to rabies are responsible for 23,252 Disability Adjusted Life Years (DALY) lost each year [95% CI 16,122-30,969]. The estimated annual cost of rabies is 40.15 million USD [95% CI 27.8-53.4]. Overall, 99% of the cost was due to premature deaths. The cost of post-exposure prophylaxis was estimated at 1.6 million USD and represented 1% of the overall cost of rabies. CONCLUSION: This study highlights the underreporting of rabies cases by the official health information system in Côte d'Ivoire and the annual financial losses related to rabies are equivalent to the estimated cost of the elimination of rabies by 2030. Thus, investing in the fight against in Côte d'Ivoire will be cost effective.

System Thinking and Citizen Participation Is Still Missing in One Health Initiatives - Lessons From Fifteen Evaluations.

Tackling complex public health challenges requires integrated approaches to health, such as One Health (OH). A key element of these approaches is the integration of knowledge across sectors, disciplines and stakeholders. It is not yet clear which elements of knowledge integration need endorsement to achieve best outcomes. This paper assesses 15 OH initiatives in 16 African, Asian and European countries to identify opportunities to improve knowledge integration and to investigate geographic influences on knowledge integration capacities. Two related evaluation tools, both relying on semi-quantitative questionnaires, were applied to two sets of case studies. In one tool, the questions relate to operations and infrastructure, while the other assigns questions to the three phases of "design," "implementation," and "evaluation" of the project life cycle. In both, the question scores are aggregated using medians. For analysis, extreme values were identified to highlight strengths and weaknesses. Seven initiatives were assessed by a single evaluator external to the initiative, and the other eight initiatives were jointly assessed by several internal and external evaluators. The knowledge integration capacity was greatest during the project implementation stage, and lowest during the evaluation stage. The main weaknesses pointing towards concrete potential for improvement were identified to be a lack of consideration of systemic characteristics, missing engagement of external stakeholders and poor bridging of knowledge, amplified by the absence of opportunities to learn and evolve in a collective process. Most users were unfamiliar with the systems approach to evaluation and found the use of the tools challenging, but they appreciated the new perspective and saw benefits in the ensuing reflections. We conclude that systems thinking and associated practises for OH require not only specific education in OH core competencies, but also methodological and institutional measures to endorse broad participation. To facilitate meta-analyses and generic improvement of integrated approaches to health we suggest including knowledge integration processes as elements to report according to the COHERE guidelines.

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.

Spatial and temporal dynamics of space use by free-ranging domestic dogs Canis familiaris in rural Africa.

Variation in the spatial ecology of animals influences the transmission of infections and so understanding host behavior can improve the control of diseases. Despite the global distribution of free-ranging domestic dogs Canis familiaris and their role as reservoirs for zoonotic diseases, little is known about the dynamics of their space use. We deployed GPS loggers on owned but free-ranging dogs from six villages in rural Chad, and tracked the movements of 174 individuals in the dry season and 151 in the wet season. We calculated 95% and core home ranges using auto-correlated kernel density estimates (AKDE95 and AKDEcore ), determined the degree to which their movements were predictable, and identified correlates of movement patterns. The median AKDE95 range in the dry season was 0.54 km2 and in the wet season was 0.31 km2 , while the median AKDEcore range in the dry season was 0.08 km2 and in the wet season was 0.04 km2 . Seasonal variation was, in part, related to owner activities; dogs from hunting households had ranges that were five times larger in the dry season. At least 70% of individuals were more predictably "at home" (<50 m from the household) throughout the day in the dry season, 80% of dogs demonstrated periodicity in activity levels (speed), and just over half the dogs exhibited periodicity in location (repeated space use). In the wet season, dogs mostly exhibited 24-h cycles in activity and location, with peaks at midday. In the dry season, dogs exhibited both 12- and 24-h cycles, with either a single peak at midday, or one peak between 06:00 and 12:00 and a second between 18:00 and 22:00. Strategies to control canine-mediated zoonoses can be improved by tailoring operations to the local spatial ecology of free-ranging dogs. Interventions using a door-to-door strategy in rural Chad would best conduct operations during the dry season, when access to dogs around their household more reliably exceeds 70% throughout the day. Given the importance of use in hunting for explaining variation in dog space-use, targeting approaches to disease control at the household level on the basis of owner activities offers potential to improve access to dogs.

Increasing rabies data availability: The example of a One Health research project in Chad, Côte d'Ivoire and Mali.

Rabies is a fatal but preventable disease that remains notoriously underreported. Weak data availability hampers advocacy, constitutes a barrier to resource allocation and inhibits effective prevention and control. To gain better insight into the global rabies burden and human vaccine demand several studies were funded through the Vaccine Alliance (GAVI) learning agenda. With the help of this funding, Swiss TPH and local in country partner organizations implemented a One Health research project in Chad, Côte d'Ivoire and Mali to collect data at household, public health facility and veterinary level. This paper describes the implementation of this research project and evaluates its success on amount of information gained, achieved capacity building, impact on knowledge creation and influence on national and international policies. The project was based on the One Health concept and guided by the principles of transboundary research partnerships formulated by the Swiss Academy of Sciences. Data was collected on bite incidents and health seeking from over 24'000 households, on access to treatment of over 8'800 bite cases registered in public health facilities and on the status of over 1'800 rabies suspect animals. Selected country specific datasets have contributed to more than 10 scientific articles so far. On the international level, the multi-level data collection provided a unique set of indicators to inform, along with results from other studies, new WHO rabies immunization recommendations and a vaccine investment case scenario to prevent human rabies. New rabies burden estimates based on the data gathered are published for Mali and will be modelled for the whole West and Central African region. On the national level, the project facilitated communication between animal health and human health workers catalyzing creation of local and national committees and formulation of national action plans for Mali and Côte D'Ivoire. Major challenges arose from lack of data collection and documentation experience of human health and veterinary workers and weak infrastructural capacities of the veterinary and human health systems of the project countries. Through adherence to the principles of transboundary research partnerships, project team members acquired valuable research and networking skills despite language barriers, enabling them to play key roles in the future agenda towards national, regional and global canine rabies elimination. Project external collaborations with local public institutions was facilitated through long-term local partnerships. Both factors enabled success in project implementation and outcomes by identifying and mitigating risks in advance, resolving challenges amiably and enabling mutual knowledge creation as a fructuous ground for sustained commitment. Lack of immediate follow-up funding did not allow to maintain activities beyond the project timeframe. However, the national and international policy changes triggered, as well as the strengthened local disease control and research capacities provides sustainable basis for the elimination of dog transmitted human rabies.

Rabies control in Liberia: Joint efforts towards zero by 30.

Despite declaration as a national priority disease, dog rabies remains endemic in Liberia, with surveillance systems and disease control activities still developing. The objective of these initial efforts was to establish animal rabies diagnostics, foster collaboration between all rabies control stakeholders, and develop a short-term action plan with estimated costs for rabies control and elimination in Liberia. Four rabies diagnostic tests, the direct fluorescent antibody (DFA) test, the direct immunohistochemical test (dRIT), the reverse transcriptase polymerase chain reaction (RT-PCR) assay and the rapid immunochromatographic diagnostic test (RIDT), were implemented at the Central Veterinary Laboratory (CVL) in Monrovia between July 2017 and February 2018. Seven samples (n=7) out of eight suspected animals were confirmed positive for rabies lyssavirus, and molecular analyses revealed that all isolates belonged to the Africa 2 lineage, subgroup H. During a comprehensive in-country One Health rabies stakeholder meeting in 2018, a practical workplan, a short-term action plan and an accurately costed mass dog vaccination strategy were developed. Liberia is currently at stage 1.5/5 of the Stepwise Approach towards Rabies Elimination (SARE) tool, which corresponds with countries that are scaling up local-level interventions (e.g. dog vaccination campaigns) to the national level. Overall an estimated 5.3 - 8 million USD invested over 13 years is needed to eliminate rabies in Liberia by 2030. Liberia still has a long road to become free from dog-rabies. However, the dialogue between all relevant stakeholders took place, and disease surveillance considerably improved through implementing rabies diagnosis at the CVL. The joint efforts of diverse national and international stakeholders laid important foundations to achieve the goal of zero dog-mediated human rabies deaths by 2030.

Development of a Multiplex Bead Assay for the Detection of Canine IgG4 Antibody Responses to Guinea Worm.

Increased levels of guinea worm (GW) disease transmission among dogs in villages along the Chari River in Chad threaten the gains made by the GW Eradication Program. Infected dogs with preemergent worm blisters are difficult to proactively identify. If these dogs are not contained, blisters can burst upon submersion in water, leading to the contamination of the water supply with L1 larvae. Guinea worm antigens previously identified using sera from human dracunculiasis patients were coupled to polystyrene beads for multiplex bead assay analysis of 41 non-endemic (presumed negative) dog sera and 39 sera from GW-positive dogs from Chad. Because commercially available anti-dog IgG secondary antibodies did not perform well in the multiplex assay, dog IgGs were partially purified, and a new anti-dog IgG monoclonal antibody was developed. Using the new 4E3D9 monoclonal secondary antibody, the thioredoxin-like protein 1-glutathione-S-transferase (GST), heat shock protein (HSP1)-GST, and HSP2-GST antigen multiplex assays had sensitivities of 69-74% and specificities of 73-83%. The domain of unknown function protein 148 (DUF148)-GST antigen multiplex assay had a sensitivity of 89.7% and a specificity of 85.4%. When testing samples collected within 1 year of GW emergence (n = 20), the DUF148-GST assay had a sensitivity of 90.0% and a specificity of 97.6% with a receiver-operating characteristic area under the curve of 0.94. Using sera from two experimentally infected dogs, antibodies to GW antigens were detected within 6 months of exposure. Our results suggest that, when used to analyze paired, longitudinal samples collected 1-2 months apart, the DUF148/GST multiplex assay could identify infected dogs 4-8 months before GW emergence.

Risk factors for rabies in Côte d'Ivoire.

Rabies affects more than 150 countries worldwide. Côte d'Ivoire is one of the rabies-endemic countries that has recorded deaths every year since 2006. The evolution of these deaths is almost constant with an average of 18 annual deaths (annual incidence = 0.06-0.08 per 100,000). Children predominate among these victims. However, prevention measures exist in anti-rabies centers distributed throughout the country. The objective of this study was to determine the factors related to rabies risk in Côte d'Ivoire through Gavi rabies project entitled 'Impact of rabies and immunization in Central and West Africa'. The implementation was conducted from 2016 to 2018 in two departments of Côte d'Ivoire (Bouake and San Pedro). The study population was dog-bite victims vaccinated in anti-rabies centers of project sites from January to December 2016. Two non-free rabies immunization protocols are used in the country (Essen and Zagreb). Information was collected from bites victims for an adequate follow-up. It was to apprciate the risk of developing rabies through access to care, the immunization status of biting animal, the category of exposure and the result of rabies post exposure prophylaxis (compliance). Local program implementers responsible for these bite-management activities and veterinary staff had receved training and the necessary material. The public health education and information dissemination activities were carried out in support of promoting a wide spread of rabies prevention messages. Household surveys were conducted by sociology students in 4002 households each in urban and in rural areas. This activity helped to find people exposed by dogs and who did not receive any Post Exposure Prophylaxis (PEP). The study registered 1,263 bite victims in pilot anti-rabies centers in 2016, 51% of them were children. People living in urban areas were strongly represented (87%) because of anti-rabies centers proximity. Dog was the most animal associated to exposure (94%). Seventy-two percent (72%) of them had owners, but only 14% were vaccinated against rabies. More than half of dog bite victims had category III of exposure (58%). PEP compliance record was very low (37%), which means that 63% of bite victims have not completed the protocol. This study conducted in Bouaké and San Pedro showed somes factors responsible for rabies deaths evolution in Côte d'Ivoire. Main issues identified are the geographical accessibility of anti-rabies centers, frequent bites caused by unvaccinated dogs, often category III of exposure and many non-completions of rabies PEP in ignorance context. The establishment of national comprehensive and integrated rabies control program is needed in Côte d'Ivoire. It must take into account all these factors by focusing on public awareness, dog vaccination and adoption of modern intradermal vaccination regimens to better manage rabies situation in Côte d'Ivoire.

The Thai Red Cross protocol experience in Côte d'Ivoire.

Rabies is a public health problem in the world especially in Côte d'Ivoire. The epidemiological surveillance of rabies revealed 10,197 exposures with 17 deaths in 2015 and 11,481 exposures with 18 deaths in 2016. The management of exposed people was based on WHO's intramuscular (IM) protocols (Essen and Zagreb). The usual results from these anti-rabies protocols showed low compliance corresponding to 45-50% exposed people who did not complete the Post Exposure Prophylaxis (PEP) schedule,mainly due to the cost of vaccines. The main objective of the project was to test the feasibility of a free rabies PEP based on the Thai Red Cross (TRC) protocol used by intradermal route. The study population was exposed people (patients) vaccinated in the anti-rabies center of Bouake and San Pédro which were two departments selected for this study. The TRC protocol was implemented in y ear 2017. Patients have been vaccinated according to IM post exposure protocols or by the TRC schedule.This new protocol was administered free of charge to exposed people with their consent. Patients who did not complete the PEP schedule were researched and interviewed for having the reasons related to this non-completion. In 2017, 1625 exposures were registered including 1121 in Bouaké and 504 in San Pedro. Overall immunization compliance was 63%. Patients who received the TRC schedule were 829 (52%)With 70% PEP compliance The PEP compliance of Zagreb protocol was 67%%and the Essen protocol recorded 38% of PEP compliance. The research of exposed people who did not complete the PEP schedule has shown that cost effectively remains the major limiting factor among exposed people vaccinated by Essen or Zagreb protocols. But negligencewas main cause for the non-completion PEP among exposed people who accepted the TRC schedule. Introduction of free rabies PEP through the TRC protocol has found the population support. This experience has been successful with a better PEP compliance, which means safe protection of people from rabies.This study has demonstrate that free rabies vaccine used by ID route is one of the best solutions to improve the PEP compliance in Côte d'Ivoire.Nevertheless, alternatives ways should be provided in order to minimize vaccine wastage rates in anti-rabies center receiving very few exposed persons.Community engagementwould be necessary for more rabies awareness raising and improving bite victim's follow-up.

Field Postmortem Rabies Rapid Immunochromatographic Diagnostic Test for Resource-Limited Settings with Further Molecular Applications.

Functional rabies surveillance systems are crucial to provide reliable data and increase the political commitment necessary for disease control. To date, animals suspected as rabies-positive must be submitted to a postmortem confirmation using classical or molecular laboratory methods. However, most endemic areas are in low- and middle-income countries where animal rabies diagnosis is restricted to central veterinary laboratories. Poor availability of surveillance infrastructure leads to serious disease underreporting from remote areas. Several diagnostic protocols requiring low technical expertise have been recently developed, providing opportunity to establish rabies diagnosis in decentralized laboratories. We present here a complete protocol for field postmortem diagnosis of animal rabies using a rapid immunochromatographic diagnostic test (RIDT), from brain biopsy sampling to the final interpretation. We complete the protocol by describing a further use of the device for molecular analysis and viral genotyping. RIDT easily detects rabies virus and other lyssaviruses in brain samples. The principle of such tests is simple: brain material is applied on a test strip where gold conjugated antibodies bind specifically to rabies antigens. The antigen-antibody complexes bind further to fixed antibodies on the test line, resulting in a clearly visible purple line. The virus is inactivated in the test strip, but viral RNA can be subsequently extracted. This allows the test strip, rather than the infectious brain sample, to be safely and easily sent to an equipped laboratory for confirmation and molecular typing. Based on a modification of the manufacturer's protocol, we found increased test sensitivity, reaching 98% compared to the gold standard reference method, the direct immunofluorescence antibody test. The advantages of the test are numerous: rapid, easy-to-use, low cost and no requirement for laboratory infrastructure, such as microscopy or cold-chain compliance. RIDTs represent a useful alternative for areas where reference diagnostic methods are not available.

RABIES IMMUNOGLOBULIN: Brief history and recent experiences in Côte d'Ivoire.

BACKGROUND: Rabies is a fatal viral zoonosis mainly transmitted via dog bites. The estimated 59'000 annual deaths caused by the disease are preventable through correct and timely administration of post-exposure prophylaxis (PEP). PEP should be initiated as soon as possible after an exposure to a rabies suspected animal and consists of a course of active vaccinations and administration of rabies immunoglobulin (RIG) in case of severe exposure. However, RIG is not accessible in most rabies endemic countries and its impact on survival in combination with modern vaccines and its cost-effectiveness is unclear. We examined the effect of equine RIG (eRIG) in a field-trial in Côte d'Ivoire, a developing country with low but chronic rabies burden and persistent lack of RIG, similar to a majority of rabies endemic countries attempting elimination of the disease. METHODS: Data from 3367 patients attending anti-rabies centers (Centres Anti-Rabiques, CARs) of the National Institute for Public Hygiene (Institut National d'Hygiène Publique, INHP) in the departments of Bouaké and San Pédro in Côte d'Ivoire was prospectively collected between April 2016 and March 2018. We identified 1594 patients at risk of rabies infection as eligible for RIG administration. Depending on local availability of eRIG and vaccination protocol applied, PEP consisted of active immunization only (non-eRIG group, n = 1145) or active and passive immunization (eRIG group, n = 449). Patients were followed-up by phone interviews at least 15 months after their exposure to assess for rabies suspected deaths. RESULTS: Follow-up data was available for 641 patients in the non-eRIG group (56%) and 242 in the eRIG group (54%). Three suspected or possible rabies deaths occurred in each of the two groups, corresponding to a possible rabies mortality of 1.2% (95% CI 0.3-3.6%) in the eRIG group and 0.5% (95% CI 0.1-1.4%) in the non-eRIG group. The difference in proportions was small and not statistically significant (0.7%, p = 0.21). Deaths in both groups were associated with treatment delay after exposure and non-compliance to PEP protocol. No death occurred after correct and timely active immunization independent of eRIG administration. CONCLUSION: The provision of eRIG did not lead to a measurable reduction of rabies burden in our study population. This underlines that improved access to active vaccines will be effective in reducing rabies deaths even if access to eRIG remains difficult in developing countries. A possible benefit of eRIG administration for severely exposed patients cannot be excluded based on these results.

Burden of rabies in Mali.

Rabies is the most dreaded neglected zoonosis worldwide. It affects mostly developing countries with limited access to post-exposure prophylaxis and a low coverage of dog vaccination. OBJECTIVE: This study estimates the burden of human rabies in Mali from the extrapolation of animal bite surveillance, mostly dogs, in the region of Sikasso and the District of Bamako in 2016 and 2017. MATERIAL AND METHODS: Monte Carlo simulations of a series of interconnected probabilities were used to estimate the burden of rabies. The data was collected from cross-sectional surveys of 8775 households of which 4172 were in the District of Bamako and 4603 in the region of Sikasso. Further data was collected in health centres and from the respective veterinary services. RESULTS: We estimate that in the year 2016 133 [95% Confidence Interval (95%CI) 87-186] people died and that 5'366 [95%CI 3'510-7'504] years of life (YLL) were lost and in 2017 et 136 [95%CI 96-181] people died and that 5530 [IC 95% 3'913-7'377] YLLs were lost. The loss of income was estimated at 3.2 million USD [95%CI 2,1-4,5] en 2016, and 3,3 million USD [95%CI 2,3-4,4] in 2017. This represents the highest financial loss from rabies, followed by the cost of postexposure prophylaxis (PEP) of 86'848 $USD and 89'371 $ USD respectively. From the whole cost of rabies in Mali, 92% of the cost in 2016 and 94% of those in 2017 were attributable to premature mortality and the cost of help seeking. The proportion of cost of PEP was 3% in 2016 and 2017 of the total cost of disease. The cost related to dog vaccination changed from 3% to 1% in the same time period. CONCLUSION: This study shows that despite the possibility of preventing human rabies by PEP, its burden remains important in Malian communities. Rabies control by mass vaccination of dogs is hardly done and access to PEP is difficult. However, Rabies elimination by mass vaccination of dogs has been demonstrated to be feasible. Hence a coordinated regional effort between countries by funding dog mass vaccination and full access to PEP can eliminate rabies in West Africa.

Rabies surveillance-response in Mali in the past 18 years and requirements for the future.

CONTEXT: Rabies is endemic in Mali, but little is known about the distribution of rabies and its surveillance across the country. Documenting the evolution of rabies and the problems related to surveillance is useful to facilitate elimination of human rabies by 2030. METHOD: Data collected at the Central Veterinary Laboratory (LCV) from 1999 to 2017 and through the surveillance system functioning at household, health and veterinary structure levels, as established by the Global Vaccine Alliance funded project on the burden of rabies, between 2016 and 2017 in Bamako and the Sikasso region were used in this study. All data on animals examined for rabies by the direct fluorescence antibody test (DFA) during the specified time period were summarized, and the proportion of rabies positive tested among animals suspected of rabies was estimated. From the number of dogs tested positive for rabies, a cumulative incidence was estimated for the total canine population. The number of positive tested samples was divided by the product of the estimated canine population and number of years (18). In addition, the number of human rabies cases was analyzed to estimate a cumulative incidence. RESULTS: Among all animal samples suspected for rabies, 93.2% [95% CI 90.6-95.3] were positive by the DFA test. From the 486 included animal samples, 94.7% [95% CI 92.3-96.5] were domestic dogs with 90.9% [95% CI 87.9-93.3] positive, which stands out as the main reservoir of rabies in Mali. Cats, cattle, sheep and donkeys also tested positive using the DFA test. The cumulative incidence of canine rabies was estimated at 0.371 [95% CI: 0.336-0.408] / 10'000 dogs. The highest incidence was observed in Bamako, the capital of Mali, with a cumulative incidence of 2.242 [95% CI: 2.001-2.504] / 10'000 dogs, followed by Koulikoro with 0.335 [95% CI: 0.258-0.429] / 10'000 dogs. For other areas far from LCV, the cumulative incidence was low, with zero in Kidal. Nationally reported cases of human rabies declined in recent years with an average of 12.6 [95% CI: 8.7-16.5] deaths per year. This result gives an annual incidence of 0.1047 [0.0742-0.1352] / 100'000 inhabitants. CONCLUSION: Over the past 18 years, rabies is endemically stable in Mali despite the decrease in reported human cases. The disparity among regions in number of samples tested indicates a low level of clinical and laboratory surveillance and likely a high level of underreporting. Dogs play the main role in rabies transmission in Mali. Monitoring of and decisions for post-exposure prophylaxis (PEP) includes other animals (cats, cattle, and monkeys) involved in transmission. Mali should develop a national rabies strategy to include better communication between the public health and animal health sectors, strengthening of laboratory surveillance capacity, mass vaccination of dogs and guaranteed access to PEP.