Determinants of Rabies Post-exposure Prophylaxis Drop-Out in the Region of San-Pedro, Côte d'Ivoire.

Abstract: Despite the fact that death from rabies is 100% preventable with a course of post-exposure prophylaxis (PEP) treatment, canine rabies still causes about 59,000 human deaths worldwide annually, half of which are occurring in Africa. In Côte d'Ivoire, rabies remains a threat partly due to the high drop-out rate of the life-saving human PEP treatment among people exposed to dog bites. Each year, half of the victims starting treatment, do not complete the course. The current study therefore assessed the determinants for drop-out of the life-saving treatment among people exposed to rabies in the department of San-Pedro in Côte d'Ivoire. Methods: A mixed-methods approach was used, including questionnaires, observation, individual interviews and focus group discussions, to gather socio-demographic and economic data from 235 participants about possible reasons for abandoning treatment. The study population consisted of patients and medical and veterinary health professionals who were selected using stratified sampling and purposive selection from a database available at the Rabies Center of San Pedro. Result: The drop-out of PEP treatment was related to perception bias and a habit of low attendance of health care and vaccination centers in the population. Quantitative analysis shows differences between rural and urban areas and an association with age when it comes to treatment completion. The dropout rate was most significant among patients who, in case of other illness, did not routinely see a doctor or go to vaccination centers. The rate of abandonment was higher among those who believed that dog-related injuries could be easily treated at home, and who believed that a person with rabies could be cured without completing the preventive treatment. Insufficient provision of health information on rabies and logistic constraints related to the practical organization of treatment, including the long distance to the anti-rabies center and weaknesses in the patient follow-up procedure, did not contribute to the completion of PEP. Conclusion: Established determinants for drop-out provide a framework for effective design and implementation of rabies control strategies to accelerate rabies deaths elimination efforts. In particular, access to PEP and community knowledge about rabies need to be improved and integrated in the health system and education system, respectively.

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.

From reverse innovation to global innovation in animal health: A review.

Reverse innovation refers to learning from or diffusion of innovations developed in low income settings and further translated to industrialized countries. There is lack of consensus regarding terminology, but the idea that innovations in low-income countries are promising for adoption in high-income contexts is not new. However, in healthcare literature globally, the vast majority of publications referring to 'disruptive innovation' were published in the last ten years. To assess the potential of innovative developments and technologies for improving animal health, we initiated a literature review in 2020. We used a combined approach, incorporating targeted searching in PubMed using a key word algorithm with a snowball technique, to identify 120 relevant publications and extract data for qualitative coding. Heterogeneity of articles precluded meta-analysis, quality scoring and risk of bias analysis. We can distinguish technical innovations like new digital devices, diagnostic tests and procedures, and social innovations of intersectoral cooperation. We profile two case studies to describe potential global innovations: an integrated surveillance and response system in Somali Regional State, Ethiopia and a blockchain secured One Health intervention to optimally provide post-exposure prophylaxis for rabies exposed people in West Africa. Innovation follows no borders and can also occur in low-income settings, under constraints of cost, lack of services and infrastructure. Lower administrative and legal barriers may contribute to produce innovations that would not be possible under conditions of high density of regulation. We recommend using the term global innovation, which highlights those emanating from international partnership to solve problems of global implications.

Antibiotic resistance of Escherichia coli and Salmonella spp. strains isolated from healthy poultry farms in the districts of Abidjan and Agnibilékrou (Côte d'Ivoire).

BACKGROUND AND AIM: Antimicrobial resistance (AMR) is a serious challenge to animal and human health worldwide. Therefore, this study aims to determine levels and patterns of AMR of Escherichia coli and Salmonella spp. strains isolated from poultry farms in Côte d'Ivoire. MATERIALS AND METHODS: A cross-sectional study was conducted in two districts of Côte d'Ivoire with high poultry production: Abidjan and Agnibilékrou. A total of 231 fecal samples were collected in 124 poultry farms in both districts. Enterobacteria were isolated and tested for susceptibility to 14 antimicrobial agents using the disk-diffusion method. RESULTS: A total of 212 E. coli and 36 Salmonella strains were isolated. In Abidjan, 139 collected samples generated 101 E. coli and 23 Salmonella strains, whereas in Agnibilékrou, 92 collected samples generated 111 E. coli and 13 Salmonella strains. Variable resistance levels were recorded for the antibiotics tested. The resistance prevalence of E. coli and Salmonella, respectively, was high: Doxycycline (98%/94%), sulfonamide (84%/86%), trimethoprim-sulfamethoxazole (80%/41%), and streptomycin (71%/52%). Average resistance rates were recorded for flumequine (38%/66%), ampicillin (49%/33%), amoxicillin (25%/44%), colistin (26%/2%), chloramphenicol (21%/2%), and gentamicin (4%/47%). The antibiotics least affected by resistance were cefuroxime (4%/5%), ceftriaxone (2%/0.00%), and nitrofurantoin (1%/0.00%). CONCLUSION: In this study, it was observed that resistance to important antibiotics is emerging in poultry production in Côte d'Ivoire. Policies promoting the rational use of antibiotics should be implemented to manage antibiotic resistance in animal production.

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.

Dog rabies control in West and Central Africa: A review.

Rabies is a neglected but preventable zoonotic disease that predominantly affects the most vulnerable populations living in remote rural areas of resource-limited countries. To date, every country on the African mainland is considered endemic for dog-mediated rabies with an estimated 21'500 human rabies deaths occurring each year. In 2018, the United Against Rabies collaboration launched the Global Strategic Plan to end human deaths from dog-mediated rabies by 2030. The epidemiology of rabies from most Western and Central African countries remains poorly defined, making it difficult to assess the overall rabies situation and progress towards the 2030 goal. In this review, we attempt to provide an overview of the current rabies situation in 22 West and Central African countries based on published scientific literature and information obtained from rabies focal points. To this end, information was collected on i) established surveillance, ii) diagnostic capacity, iii) post-exposure prophylaxis (PEP) availability and coverage, iv) dog population estimates, v) dog vaccination campaigns, vi) animal and human health communication (One Health), vii) molecular studies, viii) Knowledge, Attitude and Practices (KAP), ix) cost estimates and x) national control strategies. Although rabies is a notifiable disease in the majority of the studied countries, national surveillance systems do not adequately capture the disease. A general lack of rabies diagnostic capacity has an additional negative impact on rabies surveillance and attempts to estimate rabies burden. Recurrent shortages of human rabies vaccine are reported by all of the countries, with vaccine availability usually limited to major urban centers but no country has yet adopted the new WHO-recommended 1-week intradermal vaccination regimen. Most countries carry out subsidized mass dog vaccination campaigns on World Rabies Day. Such activities are indispensable to keep rabies in the public consciousness but are not of the scale and intensity that is required to eliminate rabies from the dog population. Countries will need to scale up the intensity of their campaigns, if they are to progress towards the 2030 goal. But more than half of the countries do not yet have reliable figures on their dog populations. Only two countries reached stage 2 on the Stepwise Approach towards Rabies Elimination ladder - indicating that their national governments have truly prioritized rabies elimination and are thus providing the necessary support and political buy-in required to achieve success. In summary, the sub-region of West and Central Africa seems to be divided into countries which have accepted the challenge to eliminate rabies with governments committed to pushing forward rabies elimination, while other countries have achieved some progress, but elimination efforts remain stuck due to lacking government commitment and financial constraints. The possibility to meet the 2030 goal without international solidarity is low, because more than two-thirds of the countries rank in the low human development group (HDI ≤ 152). Leading countries should act as role models, sharing their experiences and capacities so that no country is left behind. Unified and with international support it is possible to reach the common goal of zero human rabies deaths by 2030.

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.

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.

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.

Estimation of dog population and dog bite risk factors in departments of San Pedro and Bouake in Côte d'Ivoire.

Rabies is endemic in Côte d'Ivoire and was identified in January 2017 as a priority zoonosis by all stakeholders in public health. A well-designed integrated national rabies control is essential to attain the objective of zero human deaths from dog rabies by 2030. The current study describes the complementary elements of dog bite risk factors and the dog population estimate that are relevant for planning sustainable interventions. We conducted a transverse survey in 8'004 households in the departments of San Pedro (4'002) and Bouaké (4'002), covering both rural and urban areas. The dog-household ratio was estimated at one dog for three households (0.33) or one dog for 20 people (0.05). The owned canine population on a national level was estimated at 1'400'654 dogs (range 1'276'331 to 1'535'681). The main dog bite risk factors were dog ownership, being male, and living in urban San Pedro Department. The results lay a foundation for public engagement and further steps for mass vaccination of the household dog population to reach vaccination coverage of at least 80%. Stakeholders further recommend raising awareness of dog owners, reinforcing knowledge in school children and young boys, and behavior changes towards domestic animals.

Evaluation of the Fluorescence Polarization Assay as a Rapid On-Spot Test for Ruminant Brucellosis in Côte d'Ivoire.

Brucellosis is a zoonosis of economic and public health concern. While most diagnostic tests for brucellosis can only be performed in the laboratory, the Fluorescence Polarization Assay (FPA) was developed as a rapid point-of-care field test. This pilot project aimed to validate the use of FPA for rapid diagnosis of ruminant brucellosis on the field, and to compare the FPA performance with that of the more commonly used Rose Bengal Test (RBT). Blood samples were first collected from ruminants in a livestock market, and later from a nearby slaughterhouse in Port Bouët, Abidjan, Côte d'Ivoire. Samples collected in the livestock market were processed and tested with the FPA in a central laboratory, while samples collected in the slaughterhouse were processed immediately and the FPA was performed on site. To assess the FPA intra-test agreement, a portion of the serum samples tested at the slaughterhouse were re-tested with the FPA in the laboratory later the same day. To assess inter-test agreement, all serum samples were retested with the RBT. A total of 232 samples were tested with the FPA, 106 and 126 from the livestock market and slaughterhouse, respectively. Of these, 26 tested positive and 39 were doubtful for brucellosis. The FPA was repeated on 28 of the samples collected at the slaughterhouse, and comparison of results indicated a moderate intra-test agreement (Kappa = 0.41). The agreement improved when the doubtful category was treated as negative (Kappa = 0.65), and when cattle were excluded (Kappa = 0.56 to 0.61). The RBT was performed on 229 samples, and of these 10 tested positive. A comparison of FPA and RBT results indicated poor agreement (Kappa = 0.00); this improved to slight when only samples taken at the livestock market and tested in the laboratory were considered (Kappa = 0.14). The FPA did not perform well in tropical field conditions, possibly due to the high ambient temperatures in the slaughterhouse. Moreover, a difference in performance was noted in relation to the species tested, whereby the FPA seemed to perform better on sheep and goat samples, compared to cattle samples. These findings highlight that further adjustments are needed before implementing the FPA on the field.