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'Djamena, 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'Djamena (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'Djamena, 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

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, Cote 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 Cote 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

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

Stereotypical Chronic Lymphocytic Leukemia B-Cell Receptors Recognize Survival Promoting Antigens on Stromal Cells

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Survival of CLL cells depends on their close contact with stromal cells in lymphatic tissues, bone marrow and blood. This microenvironmental regulation of CLL cell survival involves the stromal secretion of chemo- and cytokines as well as the expression of adhesion molecules. Since CLL survival may also be driven by antigenic stimulation through the B-cell antigen receptor (BCR), we explored the hypothesis that these processes may be linked to each other. We tested if stromal cells could serve as an antigen reservoir for CLL cells, thus promoting CLL cell survival by stimulation through the BCR. As a proof of principle, we found that two CLL BCRs with a common stereotyped heavy chain complementarity-determining region 3 (previously characterized as “subset 1”) recognize antigens highly expressed in stromal cells – vimentin and calreticulin. Both antigens are well-documented targets of autoantibodies in autoimmune disorders. We demonstrated that vimentin is displayed on the surface of viable stromal cells and that it is present and bound by the stereotyped CLL BCR in CLL-stroma co-culture supernatant. Blocking the vimentin antigen by recombinant soluble CLL BCR under CLL-stromal cell co-culture conditions reduces stroma-mediated anti-apoptotic effects by 20–45%. We therefore conclude that CLL BCR stimulation by stroma-derived antigens can contribute to the protective effect that the stroma exerts on CLL cells. This finding sheds a new light on the understanding of the pathobiology of this so far mostly incurable disease