Epidemic disease risks and implications for Veterinary Services.

Growth in the livestock sector is associated with heightened risk for epidemic diseases. The increasing spillover of new diseases from wildlife is being driven by wide-scale anthropogenic changes allowing for more frequent and closer wildlife-human and wildlife-livestock contacts. An increasing number of epidemics in livestock are associated with rapid transition of livestock systems from extensive to intensive, and local to global movement of livestock and their products through value chain networks with weak biosecurity. Major livestock epidemics in the past two decades have had substantial economic impacts, and the COVID-19 pandemic highlights the devastating socio-economic consequences that spillovers can have when not identified and controlled early in the process of emergence. This highlights the importance of Veterinary Services to integrated, whole-of-society efforts to control infectious diseases in animals. Emphasis within Veterinary Services must be placed on prevention and preparedness. The authors suggest four areas for continued improvement in Veterinary Services to meet this challenge. These are a) continued development of staff capacity for risk assessment and value chain analysis, together with improved policies and communication, b) appropriate adaptation of approaches to prevention and control in resource-poor settings, c) improved multi-sectoral and transboundary cooperation, which enables the sharing of resources and expertise, and d) systematic approaches that enable Veterinary Services to influence decisionmaking for trade, markets, business, public health, and livelihood development at the national and regional levels.

La croissance du secteur de l'élevage est associée à un risque accru de maladies épidémiques. Les changements anthropiques à grande échelle sont à l'origine du nombre croissant de maladies émergentes atteignant de nouvelles espèces réceptives (spillover) à partir de réservoirs sauvages, à la faveur de contacts plus fréquents et plus rapprochés entre la faune sauvage et les humains, d'une part, et entre la faune sauvage et les animaux domestiques, d'autre part. On considère qu'un nombre croissant d'épidémies affectant le bétail sont dues à la transition rapide des systèmes d'élevage extensif vers des systèmes intensifs, et aux mouvements du bétail et des produits de l'élevage de l'échelle locale à l'échelle mondiale par le biais de réseaux de chaînes de valeur dotés d'un faible niveau de biosécurité. Au cours des deux dernières décennies, d'importantes épidémies affectant le bétail ont eu un impact économique considérable ; en outre, la pandémie de COVID-19 a mis en évidence les conséquences socio-économiques dévastatrices des atteintes de nouvelles espèces réceptives par des agents pathogènes, lorsque ces maladies ne sont pas détectées et maîtrisées dès le processus d'émergence. Cela souligne l'importance cruciale des Services vétérinaires dans les efforts de lutte contre les maladies infectieuses chez les animaux, qui doivent être intégrés et mobiliser la société entière. Les Services vétérinaires doivent mettre un accent particulier sur la prévention et la préparation. Les auteurs proposent quatre aspects d'amélioration continue pour que les Services vétérinaires puissent relever ce défi. Il s'agit : a) du développement permanent des compétences des personnels vétérinaires en matière d'évaluation du risque et d'analyse des chaînes de valeur, et leur articulation avec de meilleures politiques et une communication plus performante ; b) une adaptation adéquate des méthodes de prévention et de contrôle dans les configurations faiblement dotées en ressources ; c) une meilleure coopération multisectorielle et transfrontalière afin de partager les ressources et les compétences ; d) des dispositifs systémiques permettant aux Services vétérinaires d'influencer les prises de décision en matière d'échanges internationaux, de marchés, de commerce, de santé publique et de développement des moyens de subsistance, à l'échelle nationale et régionale.

El crecimiento del sector pecuario está condicionado por la existencia de un mayor riesgo de enfermedades epidémicas. La creciente diseminación de nuevas enfermedades a partir de animales silvestres es consecuencia de transformaciones antrópicas a gran escala que posibilitan un contacto más frecuente y estrecho de la fauna silvestre con el ser humano y el ganado. Cada vez son más las epidemias del ganado que tienen que ver con la rápida transición de los sistemas pecuarios de un régimen de producción extensiva a otro de producción intensiva y con el paso de la dimensión local a la mundial de la circulación de animales y sus derivados a través de redes de cadenas de valor que presentan una endeble seguridad biológica. En los últimos dos decenios ha habido grandes epidemias que han afectado al ganado y tenido importantes consecuencias económicas. La pandemia de COVID-19 es un elocuente ejemplo de los devastadores efectos socioeconómicos que puede tener la extensión de un patógeno cuando no se detecta y controla en un momento lo bastante precoz del proceso de emergencia. Ello pone de relieve la importancia que revisten los Servicios Veterinarios para que toda la sociedad pueda reaccionar de forma integrada a la hora de combatir las enfermedades infecciosas de los animales. Dentro de los Servicios Veterinarios, conviene poner el acento en la prevención y la preparación. Para lograr este objetivo los autores señalan cuatro ámbitos que exigen una constante mejora: a) el desarrollo continuo de la capacidad del personal en materia de determinación de riesgos y análisis de cadenas de valor, ligado a la mejora de las políticas y la comunicación; b) la adecuada adaptación de los métodos de prevención y control en contextos de escasos recursos; c) una mejor cooperación multisectorial y transfronteriza, que permita poner en común recursos y competencias técnicas; y d) enfoques sistemáticos que hagan posible que los Servicios Veterinarios influyan en los procesos decisorios relativos al desarrollo del comercio, los mercados, las empresas, la salud pública y los medios de sustento a escala tanto nacional como regional.

Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine administered concomitantly with other paediatric vaccines in toddlers: a phase III randomised study.

Invasive meningococcal disease has high morbidity and mortality, with infants and young children among those at greatest risk. This phase III, open-label, randomised study in toddlers aged 12-23 months evaluated the immunogenicity and safety of meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT), a tetanus toxoid conjugated vaccine against meningococcal serogroups A, C, W and Y, when coadministered with paediatric vaccines (measles, mumps and rubella [MMR]; varicella [V]; 6-in-1 combination vaccine against diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b [DTaP-IPV-HepB-Hib] and pneumococcal conjugate vaccine [PCV13])(NCT03205371). Immunogenicity to each meningococcal serogroup was assessed by serum bactericidal antibody assay using human complement (hSBA). Vaccine safety profiles were described up to 30 days post-vaccination. A total of 1183 participants were enrolled. The proportion with seroprotection (hSBA ≥1:8) to each meningococcal serogroup at Day 30 was comparable between the MenACYW-TT and MenACYW-TT + MMR + V groups (≥92 and ≥96%, respectively), between the MenACYW-TT and MenACYW-TT + DTaP-IPV-HepB-Hib groups (≥90% for both) and between the MenACYW-TT and MenACYW-TT + PCV13 groups (≥91 and ≥84%, respectively). The safety profiles of MenACYW-TT, and MMR + V, DTaP-IPV-HepB-Hib, and PCV13, with or without MenACYW-TT, were generally comparable. Coadministration of MenACYW-TT with paediatric vaccines in toddlers had no clinically relevant effect on the immunogenicity and safety of any of the vaccines.

Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) vs. a licensed quadrivalent meningococcal tetanus toxoid-conjugate vaccine in meningococcal vaccine-naïve and meningococcal C conjugate vaccine-primed toddlers: a phase III randomised study.

Vaccination remains the best strategy to reduce invasive meningococcal disease. This study evaluated an investigational tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MenACYW-TT) vs. a licensed tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MCV4-TT) (NCT02955797). Healthy toddlers aged 12-23 months were included if they were either meningococcal vaccine-naïve or MenC conjugate (MCC) vaccine-primed (≥1 dose of MCC prior to 12 months of age). Vaccine-naïve participants were randomised 1:1 to either MenACYW-TT (n = 306) or MCV4-TT (n = 306). MCC-primed participants were randomised 2:1 to MenACYW-TT (n = 203) or MCV4-TT (n = 103). Antibody titres against each of the four meningococcal serogroups were measured by serum bactericidal antibody assay using the human complement. The co-primary objectives of this study were to demonstrate the non-inferiority of MenACYW-TT to MCV4-TT in terms of seroprotection (titres ≥1:8) at Day 30 in both vaccine-naïve and all participants (vaccine-naïve and MCC-primed groups pooled). The immune response for all four serogroups to MenACYW-TT was non-inferior to MCV4-TT in vaccine-naïve participants (seroprotection: range 83.6-99.3% and 81.4-91.6%, respectively) and all participants (seroprotection: range 83.6-99.3% and 81.4-98.0%, respectively). The safety profiles of both vaccines were comparable. MenACYW-TT was well-tolerated and demonstrated non-inferior immunogenicity when administered to MCC vaccine-primed and vaccine-naïve toddlers.

Evaluation of safety and immunogenicity of a live attenuated tetravalent (G1-G4) Bovine-Human Reassortant Rotavirus vaccine (BRV-TV) in healthy Indian adults and infants.

BACKGROUND: Rotavirus infections, prevalent in human populations worldwide are mostly caused by Group A viruses. Live attenuated rotavirus vaccines are highly effective in preventing severe rotavirus gastroenteritis. However, the cost of these vaccines and local availability can be a barrier for widespread adoption in public health programs in developing countries where infants suffer a heavy burden of rotavirus related morbidity and mortality. A phase I/II study was carried out with the long term aim to produce a locally licensed vaccine which is equally safe and immunogenic as compared to available licensed vaccines. METHODS: This study was conducted in two cohorts. In the first cohort, 20 healthy adults were administered a single dose of the rotavirus vaccine (highest antigen concentration planned for infants) or placebo and were followed up for 10 days for safety. Following demonstration of safety in adult volunteers, 100 healthy infants were recruited (cohort 2) and randomly divided into five equal study groups. They were administered three doses of either the investigational rotavirus vaccine (BRV-TV) at one of the three antigen concentrations or Rotateq or Placebo at 6-8, 10-12 and 14-16 weeks of age. All infants were followed up for safety till 28 days after the third dose. Immune response to the vaccine, in terms of seroresponse and geometric mean concentrations, was compared across the five study groups. RESULTS: Increase in anti-rotavirus serum IgA antibodies from baseline, demonstrated higher immune response for all the three antigen concentrations of BRV-TV vaccine and RotaTeq in comparison with the placebo. Sero-response rates for placebo, BRV-TV dose-levels 10(5.0) FFU, 10(5.8) FFU, 10(6.4) FFU, and Rotateq at 28 days post third dose were 11.1%, 27.8%, 41.2%, 83.3%, and 63.2% respectively using the four-fold or more criteria. The BRV-TV vaccine arm corresponding to the highest antigen concentration of 10(6.4) FFU had a higher sero-response rate compared to the active comparator arm (RotaTeq), 28 days post each vaccine dose. The safety profile was comparable across the treatment groups. CONCLUSIONS: Overall, the results showed that all three doses of BRV-TV vaccine were safe, well tolerated and displayed good immunogenicity (dose-response) in healthy Indian infants.

A multicenter prospective hospital-based surveillance to estimate the burden of rotavirus gastroenteritis in children less than five years of age in India.

BACKGROUND: Rotavirus is the leading cause of severe, dehydrating diarrhea in children aged <5 years globally, with an estimated 25 million outpatient visits and 2 million hospitalizations attributable to rotavirus infections each year. The aim of this hospital-based surveillance was to summarize the local epidemiological and virological features of rotavirus and to estimate the disease burden in the population under surveillance in India. METHODS: During the 16 months surveillance period from April 2011 through July 2012, a total of 4711 children under the age of 5 years were admitted with acute diarrhea at 12 medical centers attached to medical schools throughout India. Stool samples were randomly collected from 2051 (43.5%) subjects and were analyzed for rotavirus positivity using commercial enzyme immunoassay kit (Premier Rotaclone Qualitative Elisa) at the respective study centers. Rotavirus positive samples were genotyped for VP7 and VP4 by reverse-transcription polymerase chain reaction (RT-PCR) at a central laboratory. RESULTS: During the study period, maximum number of rotavirus related hospitalizations were reported from December 2011 through February 2012. Out of the 2051 stool samples tested for rotavirus, overall 541 (26.4%) samples were positive for rotavirus VP6 antigen in stool. The highest positivity was observed in the month of December, 2011 (52.5%) and lowest in the month of May, 2011 (10.3%). We found that majority of the rotavirus positive cases (69.7%) were in children <24 months of age. The most common genotypes reported were G1 (38%), G2 (18%), G9 (18%), G12 (9%) and mixed strains (17%). CONCLUSIONS: The results of this study confirm the significant burden of acute rotavirus gastroenteritis as a cause of hospitalizations in under five children in India.

Retrospective surveillance for intussusception in children aged less than five years at two tertiary care centers in India.

BACKGROUND: A rotavirus vaccine could soon become part of India's national immunization program. However the occurrence of intussusception due to rotavirus vaccine is a potential safety concern. This surveillance aimed at the collection of baseline data on childhood intussusception which would facilitate the monitoring of intussusception cases after the introduction of rotavirus vaccines. METHODS: We retrospectively reviewed medical records of confirmed intussusception cases in children under the age of five, treated during 2007-2012 at two tertiary care hospitals attached to medical schools in India. Demographic, clinical, diagnostic and treatment practices data were obtained from hospital records. RESULTS: Over a five to six year observation period, we identified 187 confirmed cases of intussusception, of which 75% were males. The median age of intussusception was 8 months, and we observed a possible trend in the distribution of cases with the highest number of cases being reported in the month of April and lowest in the month of October. The most common diagnostic methods used were ultrasonography and abdominal radiography with most cases being treated surgically (71%). The median length of hospital stay was 8 days (range 1-40) and mean was 10.2 days. Records of any fatality due to intussusception were not found during the review of the records. CONCLUSIONS: This analysis provides an estimate of the baseline data of childhood intussusception prior to the introduction of the rotavirus vaccination as a part of routine immunization in India. A prospective surveillance system using a standardized case definition is needed in order to better examine the incidence of intussusception in developing countries.

Spectroscopic and microscopic studies of buffalo-bull (Bubalus bubalis) spermatozoa.

We have examined the epididymal (caput, corpus and cauda) and ejaculated spermatozoa of bufallo-bull (Bubalus bubalis) employing microscopic and spectroscopic techniques. Fluorescein isothiocyanate conjugated lectins namely concanavalin A (Con A), Dolichos biflorus (DBA), Maclura pomifera (MPA), peanut agglutinin (PNA), soybean agglutinin (SBA) and wheat germ agglutinin (WGA) were used to study the changes in the sperm surface carbohydrate make up as the spermatozoa mature. Quantitative analysis of the lectin binding was made flow cytometrically. 31P-NMR (nuclear magnetic resonance) spectra of the sperms obtained from different regions (head, body and tail) of the epididymis and of the ejaculate were analyzed to assess their metabolic activity. And the kinetics of spin label reduction of these samples was monitored with ESR (electron spin resonance) spectroscopy. These observations are supplemented with the electron microscopic (SEM and TEM) examination of the epididymal and ejaculated spermatozoa.