One Health compartment analysis of ESBL-producing Escherichia coli reveals multiple transmission events in a rural area of Madagascar.

BACKGROUND: ESBL-producing Escherichia coli (ESBL-Ec) is considered a key indicator for antimicrobial resistance (AMR) epidemiological surveillance in animal, human and environment compartments. There is likelihood of ESBL-Ec animal-human transmission but proof of cross-compartment transmission is still unclear. OBJECTIVES: To characterize ESBL-Ec genetic similarity in various compartments (humans, animals and environment) from a rural area of Madagascar. METHODS: We collected ESBL-Ec isolates prospectively from humans, animals and the environment (water) between April and October 2018. These isolates were subject to WGS and analysed with cutting-edge phylogenomic methods to characterize population genetic structure and infer putative transmission events among compartments. RESULTS: Of the 1454 samples collected, 512 tested positive for ESBL-Ec. We successfully sequenced 510 samples, and a phylogenomic tree based on 179 365 SNPs was produced. Phylogenetic distances between and amongst compartments were indistinguishable, and 104 clusters of recent transmission events between compartments were highlighted. Amongst a large diversity of ESBL-Ec genotypes, no lineage host specificity was observed, indicating the regular occurrence of ESBL-Ec transfer among compartments in rural Madagascar. CONCLUSIONS: Our findings stress the importance of using a phylogenomic approach on ESBL-Ec samples in various putative compartments to obtain a clear baseline of AMR transmissions in rural settings, where one wants to identify risk factors associated with transmission or to measure the effect of 'One Health' interventions in low- and middle-income countries.

COVID-19 in Africa: Underreporting, demographic effect, chaotic dynamics, and mitigation strategy impact.

The epidemic of COVID-19 has shown different developments in Africa compared to the other continents. Three different approaches were used in this study to analyze this situation. In the first part, basic statistics were performed to estimate the contribution of the elderly people to the total numbers of cases and deaths in comparison to the other continents; Similarly, the health systems capacities were analysed to assess the level of underreporting. In the second part, differential equations were reconstructed from the epidemiological time series of cases and deaths (from the John Hopkins University) to analyse the dynamics of COVID-19 in seventeen countries. In the third part, the time evolution of the contact number was reconstructed since the beginning of the outbreak to investigate the effectiveness of the mitigation strategies. Results were compared to the Oxford stringency index and to the mobility indices of the Google Community Mobility Reports. Compared to Europe, the analyses show that the lower proportion of elderly people in Africa enables to explain the lower total numbers of cases and deaths by a factor of 5.1 on average (from 1.9 to 7.8). It corresponds to a genuine effect. Nevertheless, COVID-19 numbers are effectively largely underestimated in Africa by a factor of 8.5 on average (from 1.7 to 20. and more) due to the weakness of the health systems at country level. Geographically, the models obtained for the dynamics of cases and deaths reveal very diversified dynamics. The dynamics is chaotic in many contexts, including a situation of bistability rarely observed in dynamical systems. Finally, the contact number directly deduced from the epidemiological observations reveals an effective role of the mitigation strategies on the short term. On the long term, control measures have contributed to maintain the epidemic at a low level although the progressive release of the stringency did not produce a clear increase of the contact number. The arrival of the omicron variant is clearly detected and characterised by a quick increase of interpeople contact, for most of the African countries considered in the analysis.

Antimicrobial Resistance in Africa-How to Relieve the Burden on Family Farmers.

Although currently available data indicate that Africa has the lowest usage of antimicrobials in animals in the world (adjusted by animal biomass), data show a high prevalence of antimicrobial resistance in foodborne pathogens isolated from animals and animal products. Apart from the lack of solid data on antimicrobial use in many countries in Africa, different hypotheses could explain this situation. Qualitative interviews of farmers show a lack of knowledge and uninformed use of antimicrobials. Considering the development of animal farming to meet an increasing demand for proteins, this deficiency represents a serious public health issue. We advocate for policies that consider the specific challenges faced by family farmers in Africa, to simultaneously improve access to veterinary drugs while strengthening the regulation of their use. We propose a global approach targeting the agri-food system, offering innovative social and technical interventions on antimicrobial usage, adapted to family farmers.

Mapping of Ebola virus spillover: Suitability and seasonal variability at the landscape scale.

The unexpected Ebola virus outbreak in West Africa in 2014 involving the Zaire ebolavirus made clear that other regions outside Central Africa, its previously documented niche, were at risk of future epidemics. The complex transmission cycle and a lack of epidemiological data make mapping areas at risk of the disease challenging. We used a Geographic Information System-based multicriteria evaluation (GIS-MCE), a knowledge-based approach, to identify areas suitable for Ebola virus spillover to humans in regions of Guinea, Congo and Gabon where Ebola viruses already emerged. We identified environmental, climatic and anthropogenic risk factors and potential hosts from a literature review. Geographical data layers, representing risk factors, were combined to produce suitability maps of Ebola virus spillover at the landscape scale. Our maps show high spatial and temporal variability in the suitability for Ebola virus spillover at a fine regional scale. Reported spillover events fell in areas of intermediate to high suitability in our maps, and a sensitivity analysis showed that the maps produced were robust. There are still important gaps in our knowledge about what factors are associated with the risk of Ebola virus spillover. As more information becomes available, maps produced using the GIS-MCE approach can be easily updated to improve surveillance and the prevention of future outbreaks.

Typological analysis of public-private partnerships in the veterinary domain.

Public-Private Partnerships (PPPs) are defined as a collaborative approach in which the public and private sector share resources, responsibilities and risks to achieve common objectives and mutual benefits in a sustainable manner. PPPs are identified as a key solution to reinforce Veterinary Services. However only limited information is available on the scope, added value and enabling factors of PPPs in this sector. The aims of this study were to develop a typology of PPPs in the veterinary field and to identify key success factors and obstacles to their implementation. A structured questionnaire was sent to all 181 World Organisation for Animal Health (OIE) Member Countries and to 47 private contacts. 36 different variables characterizing PPP initiatives were collected. 97 examples of PPPs were retrieved from 76 countries. Dimensionality reduction techniques were combined with clustering and discrimination methods to establish a typology of PPPs and to derive a set of simple rules to classify new instances of PPPs. Three clusters were identified, separated according to two main variables: the type of private partners and the type of interaction. Cluster 1, transactional PPPs, represented the traditional understanding of PPPs by Veterinary Services, initiated and funded by the public sector, giving service delivery accreditation to mostly private veterinarians; cluster 2, collaborative PPPs, included partnerships between producer associations and public Veterinary Services, driven by trade interests; cluster 3, transformational PPPs, represented joint programs initiated and funded by private companies and initially driven by business development objectives. Specific success factors and key obstacles affecting the performances and sustainability of these initiatives were identified for each cluster. This study represents the first practical attempt to develop a meaningful typology of PPPs in the field of animal health and to identify fundamental obstacles currently inhibiting the development of PPPs, and suggests ways to support national Veterinary Services in overcoming these obstacles.

Epidemiological Survey of Peste des Petits Ruminants in Ethiopia: Cattle as Potential Sentinel for Surveillance.

Peste des petits ruminants (PPR) is a highly contagious viral disease of small ruminants; it emerged in countries previously free of the disease following the eradication of rinderpest. PPR is classified by international organizations as the next priority animal disease for global eradication campaign. Assessment of the local situations is the first step in the eradication efforts. The objective of this study was to investigate and compare the seroprevalence of PPR in cattle, sheep, and goats under two livestock production systems in Ethiopia: North Shewa zone of Amhara region represents a highland sedentary life style characterized by mixed livestock-crop production system; Zone Three of Afar region represents a lowland nomadic life style characterized by pastoral livestock production system. N-competitive ELISA PPR test was performed on sera from 2,993 animals ≥6 months old sampled at watering and grazing points. Multivariable logistic regression models comparing the seropositivity between the two production systems were built by classifying doubtful results as positive, negative, or excluding them from the data. The odds ratio (OR) comparing overall PPR seroprevalence in the sedentary North Shewa Zone compared to the nomadic Zone Three ranged from 19 to 27 (P < 0.001), depending on how doubtful results were classified, which contrasts with what has been reported in the literature. This is not likely to be related solely to vaccination, since seroprevalences in cattle and small ruminants were similarly high or low in the respective zones (0-4% for Zone Three and 20-40% for North Shewa Zone), and cattle were not likely to be vaccinated. The OR of seropositivity for goats compared to cattle ranged from 1.9 [95% confidence interval (CI): 1.3-2.7; P < 0.001] to 2.2 (95% CI: 1.5-3.1; P < 0.001) when doubtful results were excluded or classified as negative, respectively. When doubtful results were classified as positive, association between seropositivity and animal species was not significant (P > 0.05). Our results suggest to further investigate cattle as sentinel animals for PPR surveillance.

Diversity of Dromedary Camel Coronavirus HKU23 in African Camels Revealed Multiple Recombination Events among Closely Related Betacoronaviruses of the Subgenus Embecovirus.

Genetic recombination has frequently been observed in coronaviruses. Here, we sequenced multiple complete genomes of dromedary camel coronavirus HKU23 (DcCoV-HKU23) from Nigeria, Morocco, and Ethiopia and identified several genomic positions indicative of cross-species virus recombination events among other betacoronaviruses of the subgenus Embecovirus (clade A beta-CoVs). Recombinant fragments of a rabbit coronavirus (RbCoV-HKU14) were identified at the hemagglutinin esterase gene position. Homolog fragments of a rodent CoV were also observed at 8.9-kDa open reading frame 4a at the 3' end of the spike gene. The patterns of recombination differed geographically across the African region, highlighting a mosaic structure of DcCoV-HKU23 genomes circulating in dromedaries. Our results highlighted active recombination of coronaviruses circulating in dromedaries and are also relevant to the emergence and evolution of other betacoronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV).IMPORTANCE Genetic recombination is often demonstrated in coronaviruses and can result in host range expansion or alteration in tissue tropism. Here, we showed interspecies events of recombination of an endemic dromedary camel coronavirus, HKU23, with other clade A betacoronaviruses. Our results supported the possibility that the zoonotic pathogen MERS-CoV, which also cocirculates in the same camel species, may have undergone similar recombination events facilitating its emergence or may do so in its future evolution.

Ebola Virus Maintenance: If Not (Only) Bats, What Else?

The maintenance mechanisms of ebolaviruses in African forest ecosystems are still unknown, but indirect evidences point at the involvement of some bat species. Despite intense research, the main bat-maintenance hypothesis has not been confirmed yet. The alternative hypotheses of a non-bat maintenance host or a maintenance community including, or not, several bat and other species, deserves more investigation. However, African forest ecosystems host a large biodiversity and abound in potential maintenance hosts. How does one puzzle out? Since recent studies have revealed that several bat species have been exposed to ebolaviruses, the common denominator to these hypotheses is that within the epidemiological cycle, some bats species must be exposed to the viruses and infected by these potential alternative hosts. Under this constraint, and given the peculiar ecology of bats (roosting behaviour, habitat utilisation, and flight mode), we review the hosts and transmission pathways that can lead to bat exposure and infection to ebolaviruses. In contrast to the capacity of bats to transmit ebolaviruses and other pathogens to many hosts, our results indicate that only a limited number of hosts and pathways can lead to the transmission of ebolaviruses to bats, and that the alternative maintenance host, if it exists, must be amongst them. A list of these pathways is provided, along with protocols to prioritise and investigate these alternative hypotheses. In conclusion, taking into account the ecology of bats and their known involvement in ebolaviruses ecology drastically reduces the list of potential alternative maintenance hosts for ebolaviruses. Understanding the natural history of ebolaviruses is a health priority, and investigating these alternative hypotheses could complete the current effort focused on the role of bats.

Survey of Ebola Viruses in Frugivorous and Insectivorous Bats in Guinea, Cameroon, and the Democratic Republic of the Congo, 2015-2017.

To clarify the role of bats in the ecology of Ebola viruses, we assessed the prevalence of Ebola virus antibodies in a large-scale sample of bats collected during 2015-2017 from countries in Africa that have had previous Ebola outbreaks (Guinea, the Democratic Republic of the Congo) or are at high risk for outbreaks (Cameroon). We analyzed 4,022 blood samples of bats from >12 frugivorous and 27 insectivorous species; 2-37 (0.05%-0.92%) bats were seropositive for Zaire and 0-30 (0%-0.75%) bats for Sudan Ebola viruses. We observed Ebola virus antibodies in 1 insectivorous bat genus and 6 frugivorous bat species. Certain bat species widespread across Africa had serologic evidence of Zaire and Sudan Ebola viruses. No viral RNA was detected in the subset of samples tested (n = 665). Ongoing surveillance of bats and other potential animal reservoirs are required to predict and prepare for future outbreaks.

A dynamic model of transmission and elimination of peste des petits ruminants in Ethiopia.

Peste des petits ruminants (PPR), a devastating viral disease of sheep and goats, has been targeted by the global community for eradication within the next 15 years. Although an efficacious attenuated live vaccine is available, the lack of knowledge about the transmission potential of PPR virus (PPRV) may compromise eradication efforts. By fitting a metapopulation model simulating PPRV spread to the results of a nationwide serological survey in Ethiopia, we estimated the level of viral transmission in an endemic setting and the vaccination coverage required for elimination. Results suggest that the pastoral production system as a whole acts as a viral reservoir, from which PPRV spills over into the sedentary production system, where viral persistence is uncertain. Estimated levels of PPRV transmission indicate that viral spread could be prevented if the proportion of immune small ruminants is kept permanently above 37% in at least 71% of pastoral village populations. However, due to the high turnover of these populations, maintaining the fraction of immune animals above this threshold would require high vaccine coverage within villages, and vaccination campaigns to be conducted annually. Adapting vaccination strategies to the specific characteristics of the local epidemiological context and small ruminant population dynamics would result in optimized allocation of limited resources and increase the likelihood of PPR eradication.

MERS coronaviruses from camels in Africa exhibit region-dependent genetic diversity.

Middle East respiratory syndrome coronavirus (MERS-CoV) causes a zoonotic respiratory disease of global public health concern, and dromedary camels are the only proven source of zoonotic infection. Although MERS-CoV infection is ubiquitous in dromedaries across Africa as well as in the Arabian Peninsula, zoonotic disease appears confined to the Arabian Peninsula. MERS-CoVs from Africa have hitherto been poorly studied. We genetically and phenotypically characterized MERS-CoV from dromedaries sampled in Morocco, Burkina Faso, Nigeria, and Ethiopia. Viruses from Africa (clade C) are phylogenetically distinct from contemporary viruses from the Arabian Peninsula (clades A and B) but remain antigenically similar in microneutralization tests. Viruses from West (Nigeria, Burkina Faso) and North (Morocco) Africa form a subclade, C1, that shares clade-defining genetic signatures including deletions in the accessory gene ORF4b Compared with human and camel MERS-CoV from Saudi Arabia, virus isolates from Burkina Faso (BF785) and Nigeria (Nig1657) had lower virus replication competence in Calu-3 cells and in ex vivo cultures of human bronchus and lung. BF785 replicated to lower titer in lungs of human DPP4-transduced mice. A reverse genetics-derived recombinant MERS-CoV (EMC) lacking ORF4b elicited higher type I and III IFN responses than the isogenic EMC virus in Calu-3 cells. However, ORF4b deletions may not be the major determinant of the reduced replication competence of BF785 and Nig1657. Genetic and phenotypic differences in West African viruses may be relevant to zoonotic potential. There is an urgent need for studies of MERS-CoV at the animal-human interface.

Pig empire under infectious threat: risk of African swine fever introduction into the People's Republic of China.

Pig production and pork consumption are very important to the People's Republic of China for both economic and cultural reasons. The incursion and spread of a disease such as African swine fever (ASF), which emerged in Eastern Europe in 2007, could have devastating socioeconomic consequences for both the Chinese and the global pig industry. The Chinese government consequently attributes a very high priority to ASF and is actively seeking to improve its preparedness. This paper discusses different drivers and pathways of potential emergence of ASF in China in light of the country's specificities, including international movements of people, pigs and pig products, swill feeding practices and wild boar populations. It suggests that effective ASF risk management in China will require a comprehensive and integrated approach linking science and policy and will need to involve all relevant stakeholders to develop realistic policies.

A pilot study to delimit tsetse target populations in Zimbabwe.

BACKGROUND: Tsetse (Glossina sensu stricto) are cyclical vectors of human and animal trypanosomoses, that are presently targeted by the Pan African Tsetse and Trypanosomiasis Eradication Campaign (PATTEC) coordinated by the African Union. In order to achieve effective control of tsetse, there is need to produce elaborate plans to guide intervention programmes. A model intended to aid in the planning of intervention programmes and assist a fuller understanding of tsetse distribution was applied, in a pilot study in the Masoka area, Mid-Zambezi valley in Zimbabwe, and targeting two savannah species, Glossina morsitans morsitans and Glossina pallidipes. METHODOLOGY/PRINCIPAL FINDINGS: The field study was conducted between March and December 2015 in 105 sites following a standardized grid sampling frame. Presence data were used to study habitat suitability of both species based on climatic and environmental data derived from MODIS and SPOT 5 satellite images. Factors influencing distribution were studied using an Ecological Niche Factor Analysis (ENFA) whilst habitat suitability was predicted using a Maximum Entropy (MaxEnt) model at a spatial resolution of 250 m. Area Under the Curve (AUC), an indicator of model performance, was 0.89 for G. m. morsitans and 0.96 for G. pallidipes. We then used the predicted suitable areas to calculate the probability that flies were really absent from the grid cells where they were not captured during the study based on a probability model using a risk threshold of 0.05. Apart from grid cells where G. m. morsitans and G. pallidipes were captured, there was a high probability of presence in an additional 128 km2 and 144 km2 respectively. CONCLUSIONS/SIGNIFICANCE: The modelling process promised to be useful in optimizing the outputs of presence/absence surveys, allowing the definition of tsetse infested areas with improved accuracy. The methodology proposed here can be extended to all the tsetse infested parts of Zimbabwe and may also be useful for other PATTEC national initiatives in other African countries.

Risk factors for MERS coronavirus infection in dromedary camels in Burkina Faso, Ethiopia, and Morocco, 2015.

Understanding Middle East respiratory syndrome coronavirus (MERS-CoV) transmission in dromedary camels is important, as they consitute a source of zoonotic infection to humans. To identify risk factors for MERS-CoV infection in camels bred in diverse conditions in Burkina Faso, Ethiopia and Morocco, blood samples and nasal swabs were sampled in February-March 2015. A relatively high MERS-CoV RNA rate was detected in Ethiopia (up to 15.7%; 95% confidence interval (CI): 8.2-28.0), followed by Burkina Faso (up to 12.2%; 95% CI: 7-20.4) and Morocco (up to 7.6%; 95% CI: 1.9-26.1). The RNA detection rate was higher in camels bred for milk or meat than in camels for transport (p = 0.01) as well as in younger camels (p = 0.06). High seropositivity rates (up to 100%; 95% CI: 100-100 and 99.4%; 95% CI: 95.4-99.9) were found in Morocco and Ethiopia, followed by Burkina Faso (up to 84.6%; 95% CI: 77.2-89.9). Seropositivity rates were higher in large/medium herds (≥51 camels) than small herds (p = 0.061), in camels raised for meat or milk than for transport (p = 0.01), and in nomadic or sedentary herds than in herds with a mix of these lifestyles (p < 0.005).

MERS-CoV at the Animal-Human Interface: Inputs on Exposure Pathways from an Expert-Opinion Elicitation.

Nearly 4 years after the first report of the emergence of Middle-East respiratory syndrome Coronavirus (MERS-CoV) and nearly 1800 human cases later, the ecology of MERS-CoV, its epidemiology, and more than risk factors of MERS-CoV transmission between camels are poorly understood. Knowledge about the pathways and mechanisms of transmission from animals to humans is limited; as of yet, transmission risks have not been quantified. Moreover the divergent sanitary situations and exposures to animals among populations in the Arabian Peninsula, where human primary cases appear to dominate, vs. other regions in the Middle East and Africa, with no reported human clinical cases and where the virus has been detected only in dromedaries, represents huge scientific and health challenges. Here, we have used expert-opinion elicitation in order to obtain ideas on relative importance of MERS-CoV risk factors and estimates of transmission risks from various types of contact between humans and dromedaries. Fourteen experts with diverse and extensive experience in MERS-CoV relevant fields were enrolled and completed an online questionnaire that examined pathways based on several scenarios, e.g., camels-camels, camels-human, bats/other species to camels/humans, and the role of diverse biological substances (milk, urine, etc.) and potential fomites. Experts believed that dromedary camels play the largest role in MERS-CoV infection of other dromedaries; however, they also indicated a significant influence of the season (i.e. calving or weaning periods) on transmission risk. All experts thought that MERS-CoV-infected dromedaries and asymptomatic humans play the most important role in infection of humans, with bats and other species presenting a possible, but yet undefined, risk. Direct and indirect contact of humans with dromedary camels were identified as the most risky types of contact, when compared to consumption of various camel products, with estimated "most likely" incidence risks of at least 22 and 13% for direct and indirect contact, respectively. The results of our study are consistent with available, yet very limited, published data regarding the potential pathways of transmission of MERS-CoV at the animal-human interface. These results identify key knowledge gaps and highlight the need for more comprehensive, yet focused research to be conducted to better understand transmission between dromedaries and humans.

Quantitative assessment of a spatial multicriteria model for highly pathogenic avian influenza H5N1 in Thailand, and application in Cambodia.

The Highly Pathogenic Avian Influenza H5N1 (HPAI) virus is now considered endemic in several Asian countries. In Cambodia, the virus has been circulating in the poultry population since 2004, with a dramatic effect on farmers' livelihoods and public health. In Thailand, surveillance and control are still important to prevent any new H5N1 incursion. Risk mapping can contribute effectively to disease surveillance and control systems, but is a very challenging task in the absence of reliable disease data. In this work, we used spatial multicriteria decision analysis (MCDA) to produce risk maps for HPAI H5N1 in poultry. We aimed to i) evaluate the performance of the MCDA approach to predict areas suitable for H5N1 based on a dataset from Thailand, comparing the predictive capacities of two sources of a priori knowledge (literature and experts), and ii) apply the best method to produce a risk map for H5N1 in poultry in Cambodia. Our results showed that the expert-based model had a very high predictive capacity in Thailand (AUC = 0.97). Applied in Cambodia, MCDA mapping made it possible to identify hotspots suitable for HPAI H5N1 in the Tonlé Sap watershed, around the cities of Battambang and Kampong Cham, and along the Vietnamese border.