Evaluating serological tests for foot-and-mouth disease while accounting for different serotypes and uncertain vaccination status.

Controlling foot-and-mouth disease (FMD) by vaccination requires adequate population coverage and high vaccine efficacy under field conditions. To assure veterinary services that animals have acquired sufficient immunity, strategic post-vaccination surveys can be conducted to monitor the coverage and performance of the vaccine. Correct interpretation of these serological data and an ability to derive exact prevalence estimates of antibody responses requires an awareness of the performance of serological tests. Here, we used Bayesian latent class analysis to evaluate the diagnostic sensitivity and specificity of four tests. A non-structural protein (NSP) ELISA determines vaccine independent antibodies from environmental exposure to FMD virus (FMDV), and three assays measuring total antibodies derived from vaccine antigen or environmental exposure to two serotypes (A, O): the virus neutralisation test (VNT), a solid phase competitive ELISA (SPCE), and a liquid phase blocking ELISA (LPBE). Sera (n = 461) were collected by a strategic post-vaccination monitoring survey in two provinces of Southern Lao People's Democratic Republic (PDR) after a vaccination campaign in early 2017. Not all samples were tested by every assay and each serotype: VNT tested for serotype A and O, whereas SPCE and LPBE tested for serotype O, and only NSP-negative samples were tested by VNT, with 90 of them not tested (missing by study design). These data challenges required informed priors (based on expert opinion) for mitigating possible lack of model identifiability. The vaccination status of each animal, its environmental exposure to FMDV, and the indicator of successful vaccination were treated as latent (unobserved) variables. Posterior median for sensitivity and specificity of all tests were in the range of 92-99 %, except for the sensitivity of NSP (∼66%) and the specificity of LPBE (∼71 %). There was strong evidence that SPCE outperformed LPBE. In addition, the proportion of animals recorded as having been vaccinated that showed a serological immune response was estimated to be in the range of 67-86 %. The Bayesian latent class modelling framework can easily and appropriately impute missing data. It is important to use field study data as diagnostic tests are likely to perform differently on field survey samples compared to samples obtained under controlled conditions.

Preparation and Optimization of Liposome Containing Thermosensitive In Situ Nasal Hydrogel System for Brain Delivery of Sumatriptan Succinate.

Drug absorption is improved by the intranasal route's wide surface area and avoidance of first-pass metabolism. For the treatment of central nervous system diseases such as migraine, intranasal administration delivers the medication to the brain. The study's purpose was to develop an in situ nasal hydrogel that contained liposomes that were loaded with sumatriptan succinate (SS). A thin-film hydration approach was used to create liposomes, and a 32 factorial design was used to optimize them. The optimized liposomes had a spherical shape, a 171.31 nm particle size, a high drug encapsulation efficiency of 83.54%, and an 8-h drug release of 86.11%. To achieve in situ gel formation, SS-loaded liposomes were added to the liquid gelling system of poloxamer-407, poloxamer-188, and sodium alginate. The final product was tested for mucoadhesive strength, viscosity, drug content, gelation temperature, and gelation time. Following intranasal delivery, in vivo pharmacokinetic investigations showed a significant therapeutic concentration of the medication in the brain with a Cmax value of 167 ± 78 ng/mL and an area under the curve value of 502 ± 63 ng/min·mL. For SS-loaded liposomal thermosensitive nasal hydrogel, significantly higher values of the nose-to-brain targeting parameters, that is, drug targeting index (2.61) and nose-to-brain drug direct transport (57.01%), confirmed drug targeting to the brain through the nasal route. Liposomes containing thermosensitive in situ hydrogel demonstrated potential for intranasal administration of SS.

Socioeconomic impacts of clinical foot-and-mouth disease and a risk-based partial vaccination campaign for smallholders in Lao People's Democratic Republic.

Foot-and-mouth disease (FMD) is endemic in Lao People's Democratic Republic (PDR). A risk-based partial vaccination campaign was implemented in Champasak, Savannakhet and Xiengkhouang Provinces in Lao PDR in 2016-2020, which had limited effects on reducing the circulation of FMD virus. The objectives of this study were to measure the socioeconomic effects of (i) a clinical FMD occurrence and (ii) the vaccination campaign on livestock production performance of smallholders in Lao PDR in 2016-2020. Two questionnaire surveys were conducted at the beginning (2016) and the end (2020) of the campaign, involving 1609 smallholders in 160 villages comparing areas with and without FMD control. Mixed-effect multivariable regression models were fitted to measure the association between livestock production parameters at the household level (rates of birth, sale, purchase, and death, sale price, costs, gross gains and net gains) and (i) a clinical FMD occurrence and (ii) the vaccination campaign, while adjusting for village, herd size, province, vaccination status and FMD knowledge. We found no significant difference in annual household-level costs, gains and net gains by due absence of FMD. However, smallholders with FMD had a 52% higher cattle death rate, a 43% lower goat sale rate and a 78% lower pig sale price than those without FMD. Smallholders with FMD also had a lower purchase rate of livestock (cattle -15% and pigs -93%) compared with those without FMD. There was a general improvement in livestock production in target villages over the 5 years of the vaccination campaign, whereas there was an overall decline in non-target villages, resulting in USD 218 higher net gains in target villages in 2020 compared with non-target villages, possibly due to reduced severity of disease and improved awareness on FMD and general livestock health. The findings of this study will help improve strategies for sustainable and efficient FMD control in Lao PDR, while the challenges and importance of gaining participation by smallholders are highlighted.

Impact of risk-based partial vaccination on clinical incidence and seroprevalence of foot and mouth disease in Lao PDR.

Foot and mouth disease (FMD) is endemic in the Lao People's Democratic Republic (PDR) and it causes economic loss to smallholder husbandry systems. An intervention programme based on a risk-based partial vaccination strategy was implemented in three provinces of Lao PDR (Champasak, Savannakhet and Xiangkhouang) to immunise domestic cattle and buffalo during 2016-2020. Two cross-sectional surveys were conducted in 2016/17 and 2020 to evaluate the impact of the vaccination programme on the prevalence of FMD virus exposure and clinical incidence of the disease. A total of 212 villages were visited during the two surveys, collecting 1609 household-level questionnaire results and 5931 blood samples of domestic cattle and buffalo. Blood samples were tested for the presence of antibodies to the non-structural proteins of FMD virus, and seroprevalence of 42.5 and 47.5% in 2016/17 and 2020, respectively were found. Multivariable regression analysis indicated that the efficacy of the FMD vaccination programme for reducing FMD virus circulation varied by province. In general, the incidence of clinical FMD increased toward the end of the 5-year intervention period, coinciding with a reduction of vaccine coverage in the last 2 years of the period. The findings suggest that the risk-based vaccination strategy achieved a marginally protective effect against the circulation of FMD virus with the possible limiting factors being operational constraints of public veterinary services, lack of farmers' compliance and unsustainable funding. We conclude that consistent resource availability and higher vaccination coverage is required to successfully control FMD with a risk-based vaccination strategy in Lao PDR.

Detection of Foot-and-Mouth Disease Virus in the Absence of Clinical Disease in Cattle and Buffalo in South East Asia.

Foot-and-mouth disease virus (FMDV) is widespread throughout much of the world, including parts of South East Asia. Surveillance is often limited in endemic areas, relying predominantly on passive outbreak reporting. As part of the World Organisation for Animal Health (OIE)'s South East Asia and China Foot-and-Mouth Disease Project (SEACFMD), field sampling was performed to help understand evidence of widespread virus exposure observed in previous studies. Serum and dry mucosal swabs were collected to evaluate the presence of FMDV RNA on the nasal, oral, and dorsal nasopharyngeal mucosal surfaces of 262 healthy cattle (n = 84 in Laos; n = 125 in Myanmar) and buffalo (n = 48 in Laos; n = 5 in Myanmar) immediately following slaughter in three slaughterhouses. Swabs and serum were tested by the OIE/FAO World Reference Laboratory for foot-and-mouth disease (WRLFMD) using pan-serotypic real-time reverse transcription-PCR (rRT-PCR) and serum was evaluated using the FMD PrioCHECK non-structural protein (NSP) ELISA. In total, 7.3% of animals had detectable FMDV RNA in one or more of the three sites including 5.3% of nasopharyngeal swabs, 2.3% of oral swabs, and 1.5% of nasal swabs. No FMDV RNA was detected in serum. Overall, 37.8% of animals were positive for NSP antibodies, indicating likely past natural exposure to FMDV. Results were comparable for Laos and Myanmar, and for both cattle and buffalo, and were not significantly different between age groups. Detectable FMDV RNA present on the oral and nasal mucosa of clinically-healthy large ruminants in Laos and Myanmar demonstrates the importance of sampling asymptomatic animals as part of surveillance, and may indicate that subclinical infection plays a role in the epidemiology of FMD in these countries.