Development of vaccines against peste des petits ruminants: CIRAD's achievements and future challenges

CIRAD, France, in collaboration with the Pirbright Institute, United Kingdom, was the first laboratory to develop a live attenuated vaccine against peste des petits ruminants (PPR). This vaccine available in the 1980s was shown to provide a life-long immunity after a single injection [5] and is now widely used in sheep and goats. New vaccines are in development, more specifically thermotolerant vaccines for use in tropical conditions and DIVA (differentiating infected from vaccinated animals) vaccines to gain virus-free status more easily and rapidly. This paper reviews most of the current and recently developed vaccines at CIRAD and emphasises their adequate delivery and utilisation in the field, for successfully decreasing the incidence of PPR. (Résumé d'auteur

Risk of introduction of Lumpy Skin Disease in France by the import of cattle. [C7]

Background: The lumpy skin disease (LSD) virus belongs to the genus Capripoxvirus and causes a disease in cattle with economic impacts. In November 2014, the disease was first reported in Europe (in Cyprus); it was then reported in Greece (in August 2015) and has spread through different Balkan countries in 2016. Although indirect vector transmission is predominant in at-risk areas, long-distance transmission usually occurs through movements of infected cattle. Methods and principal findings: In order to estimate the threat for France, a quantitative import risk analysis (QIRA) model was developed according to international standard (OIE, 2004) and to assess the risk of LSD being introduced in France by imports of cattle. Based on available information and using a stochastic model, the probability of a first outbreak of LSD in France following the import of batches of infected live cattle for breeding was estimated to be between 4 x 10-5 and 3.3 x 10-3 (in 95% of cases). Conclusion and significance: The development of a stochastic QIRA made it possible to quantify the risk of LSD being introduced in France through the import of live cattle. This tool is of prime importance because the LSD situation in the Balkans is continuously changing. Indeed, this model can be updated to process new information on the changing health situation in addition to new data from the TRAde Control and Expert System (TRACES, EU database). This model is easy to adapt to different countries and to other diseases. (Résumé d'auteur

Fièvre catarrhale du mouton. Convention d'appui technique du CIRAD-EMVT à la DGAL, rapport technique 2001

Ce rapport technique présente l'ensemble des résultats de surveillance sérologique et entomologique en Corse et sur le continent prévus par la convention DGAL-CIRAD 2001 et détaille les activités complémentaires réalisées par le CIRAD à la demande de la DGAL pour faire face à l'évolution de la fièvre catarrhale dans le pays (suspicion de fièvre catarrhale dans le Cantal, enquête écotoxicologique en Corse, enquête sur les causes des échecs vaccinaux en Corse, enquête sérologique sur ovins vaccinés en Corse, programme européen d'éradication). (Résumé d'auteur

Modelling the spread of emerging infectious diseases in animal health: case study of lumpy skin disease in the Balkans, 2015–2016

The spatial and temporal study of the spread of emerging infectious diseases is crucial to understand their epidemiology and evaluate the risk of introduction into disease-free areas. In this paper, we present a generic method that models the spread rate of emerging infectious diseases that we applied to Lumpy Skin Disease (LSD), a current epizooty affecting cattle in the Balkans, from May 2015 to July 2016. In the study period, 824 outbreaks of LSD were reported in eight countries. Hotspots of viral transmission were identified mainly south of the Turkish/Greek border, southwest of Bulgaria and south of the Serbian/Bulgarian border. By using Thin Plate Spline Regression (TPSR) to interpolate the week of first invasion, we estimated the spread rate based on the mean duration of time for the infection to spread across a given area (1km). The median spread rate was 7.8km per week, with an interquartile interval of 4.6 to 13.7km and a maximum value reaching 375.6km. The distribution of spread rate indicates two diffusion processes: a localised diffusion covering small distances and suggesting vector transmission, and a diffusion at greater distances possibly due to anthropogenic movement of infected animals. Further research should focus on identifying environmental and socio-economic factors that might influence the spread of LSD to better understand the disease epidemiology and suggest targeted control measures. (Résumé d'auteur

Risk of introduction of lumpy skin disease in France by the import of vectors in animal trucks

BACKGROUND: The lumpy skin disease virus (LSDV) is a dsDNA virus belonging to the Poxviridae family and the Capripoxvirus genus. Lumpy skin diseases (LSD) is a highly contagious transboundary disease in cattle producing major economic losses. In 2014, the disease was first reported in the European Union (in Cyprus); it was then reported in 2015 (in Greece) and has spread through different Balkan countries in 2016. Indirect vector transmission is predominant at small distances, but transmission between distant herds and between countries usually occurs through movements of infected cattle or through vectors found mainly in animal trucks. METHODS AND PRINCIPAL FINDINGS: In order to estimate the threat for France due to the introduction of vectors found in animal trucks (cattle or horses) from at-risk countries (Balkans and neighbours), a quantitative import risk analysis (QIRA) model was developed according to the international standard. Using stochastic QIRA modelling and combining experimental/field data and expert opinion, the yearly risk of LSDV being introduced by stable flies (Stomoxys calcitrans), that travel in trucks transporting animals was between 6 x 10-5 and 5.93 x 10-3 with a median value of 89.9 x 10-5; it was mainly due to the risk related to insects entering farms in France from vehicles transporting cattle from the at-risk area. The risk related to the transport of cattle going to slaughterhouses or the transport of horses was much lower (between 2 x 10-7 and 3.73 x 10-5 and between 5 x 10-10 and 3.95 x 10-8 for cattle and horses, respectively). The disinsectisation of trucks transporting live animals was important to reduce this risk. CONCLUSION AND SIGNIFICANCE: The development of a stochastic QIRA made it possible to quantify the risk of LSD being introduced in France through the import of vectors that travel in trucks transporting animals. This tool is of prime importance because the LSD situation in the Balkans is continuously changing. Indeed, this model can be updated to process new information on vectors and the changing health situation, in addition to new data from the TRAde Control and Expert System (TRACES, EU database). This model is easy to adapt to different countries and to other vectors and diseases

A simple method to estimate the number of doses to include in a bank of vaccines. The case of Lumpy Skin Disease in France

A simple method to estimate the size of the vaccine bank needed to control an epidemic of an exotic infectious disease in case of introduction into a country is presented. The method was applied to the case of a Lumpy Skin disease (LSD) epidemic in France. The size of the stock of vaccines needed was calculated based on a series of simple equations that use some trigonometric functions and take into account the spread of the disease, the time required to obtain good vaccination coverage and the cattle density in the affected region. Assuming a 7-weeks period to vaccinate all the animals and a spread of the disease of 7.3 km/week, the vaccination of 740 716 cattle would be enough to control an epidemic of LSD in France in 90% of the simulations (608 196 cattle would cover 75% of the simulations). The results of this simple method were then validated using a dynamic simulation model, which served as reference for the calculation of the vaccine stock required. The differences between both models in different scenarios, related with the time needed to vaccinate the animals, ranged from 7% to 10.5% more vaccines using the simple method to cover 90% of the simulations, and from 9.0% to 13.8% for 75% of the simulations. The model is easy to use and may be adapted for the control of different diseases in different countries, just by using some simple formulas and few input data

Bronchoalveolar neutrophils, interferon gamma-inducible protein 10 and interleukin-7 in AIDS-associated tuberculosis

During advanced AIDS tuberculosis (TB) often presents atypically with smear-negative and non-cavitary disease, yet immune features associated with this change are poorly characterized. We examined the local immune response in a cohort of Tanzanian AIDS-associated TB patients who underwent bronchoalveolar lavage. TB infection was confirmed in bronchoalveolar lavage (BAL) fluid by culture, probe and polymerase chain reaction (PCR). Among TB patients CD4 count correlated positively with the extent of cavitary disease as well as BAL TB load (qPCR CT). TB patients had significantly higher granulocyte–macrophage colony-stimulating factor (GM-CSF) than non-TB patients, and those with non-cavitary TB had significantly higher BAL interferon gamma-inducible protein (IP-10) and interleukin (IL)-7 than those with cavities. BAL neutrophils were as prevalent as monocytes/macrophages or epithelial cells, and immunohistochemistry revealed that neutrophils, monocytes/macrophages, and epithelial cells were major sources of the IP-10 and IL-7. These data suggest a dysregulated cytokine profile may contribute to the TB of advanced AIDS

A simple method to evaluate the number of doses to include in a bank of vaccines. The case of Lumpy Skin in France. [P2 4]

The preparedness for a good and rapid response against some exotic diseases includes the availability of vaccines. The objective of this paper is to describe a simple method to estimate the size that a vaccine bank should have to manage an emergency vaccination campaign against Lumpy Skin Disease (LSD) in France. Methods: To determine the size of the vaccine bank, the following factors were taken into account: 1) The average speed of the LSD through the affected area, estimated by Mercier et al. (2017) in 7.3 km / week. 2) The time required to obtain a full vaccination coverage, and 3) The cattle density in the area. It was assumed that all cattle present in the area will be vaccinated using a single dose per animal. An Excel file with a macro was used to simulate ten thousands scenarios of LSD spread in France. To simplify the calculations, the French departments were considered as squares, and the index case was located randomly in the department. If the radius around the index case exceeded the department, it extended through the other departments in the region. Results were validated using a more complex model developed in R (R Development Core Team., 2013), which reproduced the real geography of France. Results: The median of the vaccine doses need by both methods are significantly different (between 19% and 23% more vaccines are needed according the simple method). But both methods fit quite good when determining the number of doses that would be necessary in 90% of the cases. For a 7 weeks period (radius of 51.1 km), 750 000 doses of vaccine would be enough for 90% of the simulations, while for the more refined method the number of doses was 680 000 (difference of 10% ). Discussion: The method is simple and easy to use, and can be adapted to different conditions and diseases. It fits reasonable good with a more sophisticated method that takes into account de farms actually present in the zone. No jumps of the disease to long distances have been considered. At the department level, the results present more important differences (in some cases the number of vaccine needed are two folds higher using one method than using the other one). (Résumé d'auteur

Dermatose nodulaire contagieuse des bovins : état des connaissances et situation épidémiologique dans les Balkans au 31 juillet 2016

La dermatose nodulaire contagieuse des bovins (DNCB), maladie virale enzootique en Afrique sub-saharienne et classée comme danger sanitaire de catégorie I, a été détectée pour la première fois en Turquie en novembre 2013. Elle s'est ensuite étendue à l'Europe : tout d'abord dans la partie européenne de la Turquie en mai 2015, puis dans les Balkans. Au 31 juillet 2016, elle touchait la Grèce, la Bulgarie, la Macédoine (ARYM), le Monténégro, l'Albanie et la Serbie, avec 747 foyers notifiés au total. La diffusion du virus se poursuit depuis son introduction en Europe, malgré les mesures de lutte mises en place dans les pays touchés (restrictions de mouvements, abattages, vaccinations…). La vigilance quant à la diffusion de l'infection en Europe ainsi que les propositions de mise en oeuvre d'une surveillance dédiée sur le territoire national s'exercent dans le cadre de la Plateforme ESA. Cet article fait le point sur la situation épidémiologique de la DNCB dans les Balkans et propose une synthèse des connaissances épidémio-cliniques sur cette maladie. (Résumé d'auteur

IL-15 Participates in the Respiratory Innate Immune Response to Influenza Virus Infection

Following influenza infection, natural killer (NK) cells function as interim effectors by suppressing viral replication until CD8 T cells are activated, proliferate, and are mobilized within the respiratory tract. Thus, NK cells are an important first line of defense against influenza virus. Here, in a murine model of influenza, we show that virally-induced IL-15 facilitates the trafficking of NK cells into the lung airways. Blocking IL-15 delays NK cell entry to the site of infection and results in a disregulated control of early viral replication. By the same principle, viral control by NK cells can be therapeutically enhanced via intranasal administration of exogenous IL-15 in the early days post influenza infection. In addition to controlling early viral replication, this IL-15-induced mobilization of NK cells to the lung airways has important downstream consequences on adaptive responses. Primarily, depletion of responding NK1.1+ NK cells is associated with reduced immigration of influenza-specific CD8 T cells to the site of infection. Together this work suggests that local deposits of IL-15 in the lung airways regulate the coordinated innate and adaptive immune responses to influenza infection and may represent an important point of immune intervention