Efficacy of vaccination with La Sota strain vaccine to control Newcastle disease in village chickens in Nepal.

The efficacy of vaccination with Newcastle disease (ND) La Sota and R2B (Mukteswar) modified live strain vaccines was determined by experimental challenge and with ND La Sota vaccine under field conditions in Nepal. Booster vaccination with ND La Sota vaccine after a primary vaccination with ND La Sota vaccine, induced a geometric mean titre (GMT) of 5.0 log2 haemagglutination inhibition (HI) units, compared to a GMT of 6.0 log2 HI units following booster vaccination with R2B vaccine 1 month after primary vaccination with ND La Sota vaccine. Both vaccines provided 100% protection against challenge with a local field ND strain. Furthermore, booster vaccination with ND La Sota vaccine induced protective levels of antibody after field use in villages in Jhapa, and no outbreaks of ND occurred during the study period. The ND La Sota modified live vaccine is immunogenic and efficacious and is a suitable vaccine for use in vaccination programmes in village chickens in the rural areas of Nepal.

Development, characterization and optimization of a new suspension chicken-induced pluripotent cell line for the production of Newcastle disease vaccine.

Traditionally, substrates for production of viral poultry vaccines have been embryonated eggs or adherent primary cell cultures. The difficulties and cost involved in scaling up these substrates in cases of increased demand have been a limitation for vaccine production. Here, we assess the ability of a newly developed chicken-induced pluripotent cell line, BA3, to support replication and growth of Newcastle disease virus (NDV) LaSota vaccine strain. The characteristics and growth profile of the cells were also investigated. BA3 cells could grow in suspension in different media to a high density of up to 7.0 × 10(6) cells/mL and showed rapid proliferation with doubling time of 21 h. Upon infection, a high virus titer of 1.02 × 10(8) EID50/mL was obtained at 24 h post infection using a multiplicity of infection (MOI) of 5. In addition, the cell line was shown to be free of endogenous and exogenous Avian Leukosis viruses, Reticuloendotheliosis virus, Fowl Adenovirus, Marek's disease virus, and several Mycoplasma species. In conclusion, BA3 cell line is potentially an excellent candidate for vaccine production due to its highly desirable industrially friendly characteristics of growing to high cell density and capability of growth in serum free medium.

Developing One Health surveillance systems.

The health of humans, domestic and wild animals, plants, and the environment are inter-dependent. Global anthropogenic change is a key driver of disease emergence and spread and leads to biodiversity loss and ecosystem function degradation, which are themselves drivers of disease emergence. Pathogen spill-over events and subsequent disease outbreaks, including pandemics, in humans, animals and plants may arise when factors driving disease emergence and spread converge. One Health is an integrated approach that aims to sustainably balance and optimize human, animal and ecosystem health. Conventional disease surveillance has been siloed by sectors, with separate systems addressing the health of humans, domestic animals, cultivated plants, wildlife and the environment. One Health surveillance should include integrated surveillance for known and unknown pathogens, but combined with this more traditional disease-based surveillance, it also must include surveillance of drivers of disease emergence to improve prevention and mitigation of spill-over events. Here, we outline such an approach, including the characteristics and components required to overcome barriers and to optimize an integrated One Health surveillance system.

Field survey of major infectious and reproductive diseases responsible for mortality and productivity losses of ruminants amongst Nigerian Fulani pastoralists.

Background: Animal disease constitutes a major hurdle to improved livelihoods in rural Nigeria through the challenges of loss of productivity, livestock morbidity and mortality including reproductive losses. In order to design and implement impactful interventions, baseline data on the causes of such losses are needed. Therefore, the objective of the present study was to carry out targeted field surveys, including interviews with ruminant farmers, veterinary professionals and other stakeholders in livestock farming to establish the main causes of disease and mortality including abortions in cattle and small ruminants (SR). Methods: Northern Nigeria was selected because the majority of the nation's ruminants belong to pastoralists who are primarily resident in this region. Seven states; Bauchi, Kaduna, Kano, Nasarawa, Niger, Sokoto and Zamfara states were surveyed. The responses were collated and a comprehensive descriptive analysis was carried out. Results: Average cattle herd sizes ranged from 28 in Zamfara to 103 in Nasarawa; and from 27 in Kano to 128 in Sokoto for SR. In cattle, Trypanosomosis (with 4.27% mortality rate), foot and mouth disease (3.81%), nutritional insufficiency (1.93%) and contagious bovine pleuropneumonia (CBPP; 1.44%) were the top four diseases/health problems that resulted in the highest mortality due to diseases within each state surveyed. For SR, trypanosomosis (with 6.85% mortality rate), Peste des Petits Ruminants (4.99%), orf (3.06%), foot rot (2.97%) and foot and mouth disease (2.94%) were the most important diseases responsible for the highest number of mortalities and culling for disease. Conclusions: The study revealed that there are significant losses via mortalities due to the occurrence of disease amongst the ruminant populations countrywide, as evidenced by the high overall mortality rates of both cattle (15.3%) and small ruminants (30.9%) from various diseases. Also, reproductive losses of 8.7% and 16.6% in cattle and SR, respectively, were recorded amongst the farmers involved.

Strategies to increase adoption of animal vaccines by smallholder farmers with focus on neglected diseases and marginalized populations.

BACKGROUND: Most smallholder farmers (SHFs) and marginalized populations (MPs) in Africa, Asia, and Latin America depend on livestock for their livelihoods. However, significant numbers of these animals do not achieve their potential, die due to disease, or transmit zoonotic diseases. Existing vaccines could prevent and control some of these diseases, but frequently the vaccines do not reach SHFs, especially MPs, making it necessary for specific vaccine adoption strategies. PRINCIPAL FINDINGS: Several strategies that have the potential to increase the adoption of animal vaccines by SHFs and MPs have been identified depending on the type of vaccines involved. The strategies differed depending on whether the vaccines were aimed at diseases that cause economic losses, government-controlled diseases, or neglected diseases. The adoption of vaccines for neglected diseases presents a major challenge, because they are mostly for zoonotic diseases that produce few or no clinical signs in the animals, making it more difficult for the farmers to appreciate the value of the vaccines. Strategies can be aimed at increasing the availability of quality vaccines, so that they are produced in sufficient quantity, or aimed at increasing access and demand by SHFs and/or MPs. Some of the strategies to increase vaccine adoption might not provide a definite solution but might facilitate vaccine uptake by decreasing barriers. These strategies are varied and include technical considerations, policy components, involvement by the private sector (local and international), and innovation. CONCLUSIONS: Several strategies with the potential to reduce livestock morbidity and mortality, or prevent zoonoses in SHFs communities and MPs through vaccination, require the involvement of donors and international organisations to stimulate and facilitate sustainable adoption. This is especially the case for neglected zoonotic diseases. Support for national and regional vaccine manufacturers is also required, especially for vaccines against diseases of interest only in the developing world and public goods.

Rift Valley fever vaccines: current and future needs.

Rift Valley fever (RVF) is a zoonotic mosquito-borne bunyaviral disease associated with high abortion rates, neonatal deaths, and fetal malformations in ruminants, and mild to severe disease in humans. Outbreaks of RVF cause huge economic losses and public health impacts in endemic countries in Africa and the Arabian Peninsula. A proper vaccination strategy is important for preventing or minimizing outbreaks. Vaccination against RVF is not practiced in many countries, however, due to absence or irregular occurrences of outbreaks, despite serological evidence of RVF viral activity. Nonetheless, effective vaccination strategies, and functional national and international multi-disciplinary networks, remain crucial for ensuring availability of vaccines and supporting execution of vaccination in high risk areas for efficient response to RVF alerts and outbreaks.

Tackling human and animal health threats through innovative vaccinology in Africa.

Africa bears the brunt of many of the world's most devastating human and animal infectious diseases, a good number of which have no licensed or effective vaccines available. The continent's potential to generate novel interventions against these global health threats is however largely untapped. Strengthening Africa's vaccine research and development (R&D) sector could accelerate discovery, development and deployment of effective countermeasures against locally prevalent infectious diseases, many of which are neglected and have the capacity to spread to new geographical settings. Here, we review Africa's human and veterinary vaccine R&D sectors and identify key areas that should be prioritized for investment, and synergies that could be exploited from Africa's veterinary vaccine industry, which is surprisingly strong and has close parallels with human vaccine R&D.

Safety and immunogenicity of Onderstepoort Biological Products' Rift Valley fever Clone 13 vaccine in sheep and goats under field conditions in Senegal.

This blinded field safety study was conducted in Senegal to assess safety and immunogenicity of administration of the registered dose of Rift Valley fever virus (RVFV) Clone 13 vaccine (Onderstepoort Biological Products) to sheep and goats of West African breeds under natural conditions. A total of 267 small ruminants (220 sheep, 47 goats) were included; half received RVFV Clone 13 vaccine at the recommended dose and half received the diluent (as placebo) only. The study was performed on three commercial farms in the northern and eastern region of Senegal in accordance with veterinary good clinical practices. The animals were observed daily for 3 days after vaccination, and then weekly for 1 year. In both sheep and goats vaccinated against RVFV seroconversion rates above 70% were recorded. No seroconversion related to RVFV was observed in placebo-treated animals. No statistically significant differences were determined between placebo and vaccinated groups for mean rectal temperatures for the first 3 days after administration (p > 0.05). No abnormal clinical signs related to treatment were noted, and only one slight injection site reaction was observed in one vaccinated animal for 2 days after vaccination. Out of 176 births assessed over 1 year (93 from the vaccinated group, 83 from the placebo group), 9 were abnormal in the placebo group and 3 in the vaccinated group (p > 0.05). The frequency of adverse events was similar in the placebo and vaccinated groups. RVFV Clone 13 vaccine administered according to the manufacturer's instructions was safe and well tolerated in West African breeds of sheep and goats, including animals of approximately 6 months of age and pregnant females, under field conditions in Senegal. Antibody levels persisted up to 1 year after vaccination.

Randomized controlled field trial to assess the immunogenicity and safety of rift valley fever clone 13 vaccine in livestock.

BACKGROUND: Although livestock vaccination is effective in preventing Rift Valley fever (RVF) epidemics, there are concerns about safety and effectiveness of the only commercially available RVF Smithburn vaccine. We conducted a randomized controlled field trial to evaluate the immunogenicity and safety of the new RVF Clone 13 vaccine, recently registered in South Africa. METHODS: In a blinded randomized controlled field trial, 404 animals (85 cattle, 168 sheep, and 151 goats) in three farms in Kenya were divided into three groups. Group A included males and non-pregnant females that were randomized and assigned to two groups; one vaccinated with RVF Clone 13 and the other given placebo. Groups B included animals in 1st half of pregnancy, and group C animals in 2nd half of pregnancy, which were also randomized and either vaccinated and given placebo. Animals were monitored for one year and virus antibodies titers assessed on days 14, 28, 56, 183 and 365. RESULTS: In vaccinated goats (N = 72), 72% developed anti-RVF virus IgM antibodies and 97% neutralizing IgG antibodies. In vaccinated sheep (N = 77), 84% developed IgM and 91% neutralizing IgG antibodies. Vaccinated cattle (N = 42) did not develop IgM antibodies but 67% developed neutralizing IgG antibodies. At day 14 post-vaccination, the odds of being seropositive for IgG in the vaccine group was 3.6 (95% CI, 1.5 - 9.2) in cattle, 90.0 (95% CI, 25.1 - 579.2) in goats, and 40.0 (95% CI, 16.5 - 110.5) in sheep. Abortion was observed in one vaccinated goat but histopathologic analysis did not indicate RVF virus infection. There was no evidence of teratogenicity in vaccinated or placebo animals. CONCLUSIONS: The results suggest RVF Clone 13 vaccine is safe to use and has high (>90%) immunogenicity in sheep and goats but moderate (> 65%) immunogenicity in cattle.

Efficacy of a single high oxfendazole dose against gastrointestinal nematodes in naturally infected pigs.

The goal of the current experiment was to assess the clinical efficacy of oxfendazole (OFZ) administered as a single oral dose (30 mg/kg) to pigs naturally parasitized with Ascaris suum, Oesophagostomum spp., Metastrongylus spp. and Trichuris suis. Thirty-six local ecotype piglets were divided into three independent experiments, named I, II and III (n=12 each), respectively. Each experiment involved two different groups (n=6): Untreated Control and OFZ treated. Animals were naturally parasitized with A. suum (Experiments I, II and III), Oesophagostomum spp. (Experiments I and II), T. suis (Experiments II and III) and Metastrongylus spp. (Experiment I). Pigs in the treated group received OFZ (Synanthic(®), Merial Ltd., 9.06% suspension) orally at 30 mg/kg dose. At five (5) days post-treatment, animals were sacrificed and the clinical efficacy of the OFZ treatment was established following the currently available WAAVP guidelines for a controlled efficacy test. None of the animals involved in this experiment showed any adverse events during the study. OFZ treatment given as a single 30 mg/kg oral dose showed a 100% efficacy against all the nematode parasites present in the three experiments. In conclusion, under the current experimental conditions, OFZ orally administered to naturally parasitized piglets at a single dose of 30 mg/kg was safe and highly efficacious (100%) against adult stages of A. suum, Oesophagostomum spp., T. suis and Metastrongylus spp.

Safety and efficacy of Rift Valley fever Smithburn and Clone 13 vaccines in calves.

Two modified live attenuated vaccines against the disease Rift Valley fever (RVF) have been tested for safety and efficacy in young calves. The RVF Smithburn vaccine produced in South Africa and used successfully to prevent and control the disease in endemic sub-Saharan countries was compared to the candidate vaccine RVF Clone 13. Five sero-negative calves per vaccine group were vaccinated with a single dose of each vaccine and tested for antibody response. All vaccinated calves were challenged with a highly virulent RVF virus together with five unvaccinated calves used as control of the challenge. Protection was confirmed in all vaccinated animals as they did not show any clinical signs typical of RVF. A good neutralizing antibody response was induced post-vaccination and no viraemia could be detected post-challenge in calves of both vaccine groups. All non-vaccinated control animals showed clinical symptoms of RVF, high viraemia and were euthanized. This study reported the first case of blindness in cattle resulting from virulent RVF virus infection in unvaccinated calves used as negative controls.

In vivo cross-protection to African horse sickness Serotypes 5 and 9 after vaccination with Serotypes 8 and 6.

The polyvalent African horsesickness (AHS) attenuated live virus (AHS-ALV) vaccine produced at Onderstepoort Biological Products incorporates 7 of the 9 known serotypes circulating in southern Africa. Serological cross-reaction has been shown in vitro to Serotypes 5 and 9 by Serotypes 8 and 6 respectively, but the degree of in vivo cross-protection between these serotypes in vaccinated horses has not previously been reported. Due to the increasing incidence of AHS Serotypes 5 and 9 in the field, over the last 3-4 seasons of AHS in South Africa, and the absence of Serotypes 5 and 9 in the AHS-ALV vaccine, it was necessary to conduct a vaccination-challenge study to determine in vivo cross-protection of vaccine-incorporated Serotypes 8 and 6 respectively. Groups of horses were vaccinated with either the polyvalent AHS-ALV vaccine or a monovalent Serotype 6 (vAHSV6) or 8 (vAHSV8) vaccine to determine the cross-protection of vaccinated horses following challenge with virulent AHS virus (AHSV) of either Serotype 5, 6, 8 or 9. Serial vaccination of naive horses with the polyvalent AHS-ALV vaccine generated a broad neutralizing antibody response to all vaccine strains as well as cross-neutralizing antibodies to Serotypes 5 and 9. Booster vaccination of horses with monovalent vaccine vAHSV6 or vAHSV8 induced an adequate protective immune response to challenge with homologous and heterologous virulent virus. In vivo cross-protection between AHSV6 and AHSV9 and AHSV8 and AHSV5 respectively, was demonstrated.

Evaluation of the efficacy and safety of the Rift Valley Fever Clone 13 vaccine in sheep.

The efficacy and safety of the naturally attenuated Rift Valley Fever (RVF) Clone 13 vaccine were evaluated in ovines in three different experiments involving 38 ewes at different stages of pregnancy, their offsprings and four rams. In Experiment 1, 4 rams and a total of 13 pregnant ewes were vaccinated and monitored during vaccination and after a challenge with a virulent RVF virus. The ewes were vaccinated at either 50 or 100 days of pregnancy and some were challenged after lambing. In Experiment 2, nine oestrus-synchronized ewes were vaccinated at 50 days of pregnancy and challenged at 100 days of pregnancy together with 5 unvaccinated ewes at the same stage of pregnancy. In Experiment 3, 16 oestrus-synchronized ewes were vaccinated with 3 different doses of the RVF Clone 13 vaccine and challenged together with unvaccinated pregnant ewes at either 30 or 50 days of pregnancy. The results from the three experiments indicated that the vaccine did not induce clinical manifestation of RVF such as abortion in pregnant ewes, teratogeny in their offsprings, or pyrexia in all vaccinated animals. Vaccination with RVF Clone 13 vaccine also prevented clinical RVF following virulent challenge at different stages of pregnancy while unvaccinated control ewes showed pyrexia, aborted or died of RVF. A vaccine dose-response effect was also observed.