Career stage differences in mental health symptom burden and help seeking among veterinarians during COVID-19.

OBJECTIVE: To explore veterinarians' mental health symptom burden during COVID-19 and identify differences in symptom burden, social support, help seeking, and incentives and barriers associated with receiving help across career stages. SAMPLE: Online survey responses from 266 veterinarians between June 4 and September 8, 2021. PROCEDURES: Respondents were grouped by career stage (early [< 5 years of experience], middle [5 to 19 years of experience], or late [≥ 20 years of experience]), and results were compared across groups. RESULTS: Of the 262 respondents who reported years of experience, 26 (9.9%) were early career, 130 (49.6%) were midcareer, and 106 (40.4%) were late career. The overall mean anxiety and depression symptom burden score was 3.85 ± 3.47 (0 to 2 = normal; 3 to 5 = mild; 6 to 8 = moderate; and 9 to 12 = severe), with 62 of 220 (28.1%) respondents reporting moderate to severe symptom burden. Most (164/206 [79.6%]) reported not accessing behavioral health providers, and of these, 53.6% (88/164) reported at least mild symptom burden. There were significant differences in both symptom burden and mental health help-seeking intentions across career stages, with early- and midcareer (vs late-career) veterinarians reporting higher symptom burden (P = .002) and midcareer (vs late-career) veterinarians reporting higher help-seeking intentions (P = .006). Barriers and incentives for seeking mental health care were identified. CLINICAL RELEVANCE: Findings revealed differences in symptom burden and intentions to seek mental health care across veterinary career stages. Incentives and barriers identified serve to explain these career stage differences.

Veterinarians show resilience during COVID-19: challenges faced and successful coping strategies.

OBJECTIVE: To identify challenges veterinarians faced during the COVID-19 pandemic, explore how they coped, identify coping strategies associated with greater resilience, and determine incentives and barriers to performing healthy coping behaviors. SAMPLES: 266 surveys completed by veterinarians in the Potomac region. PROCEDURES: A cross-sectional survey was distributed electronically through veterinary medical boards and professional associations between June and September 2021. RESULTS: Most survey responses came from veterinarians working in Maryland (128/266 [48%]) and Virginia (63/266 [24%]) who were predominantly white (186/266 [70%]), female (162/266 [61%]), and working in small-animal clinical practice (185/266 [70%]). The greatest workplace challenges experienced were increased workloads (195/266 [73%]) and reevaluating existing workflows (189/266 [71%]). Separation from loved ones (161/266 [61%]) was the greatest personal challenge. Of the veterinarians who completed the 10-point Connor-Davidson Resilience Scale (n = 219), which measures resilience on a scale from 0 (no resilience) to 40 (greatest resilience), the mean score was 29.6 (SD, 6.9), with a median of 30 (IQR = 10). Intrinsic factors most strongly associated with greater resilience were increasing age (P = .01) and later career stage (P = .002). Job satisfaction, autonomy, good work-life balance, and approach-focused coping strategies were positively associated with resilience. Overwhelmingly, the primary reported barrier to performing healthy coping behaviors was limited time to devote to self-care (177/266 [67%]). CLINICAL RELEVANCE: A combination of individual approach-focused coping strategies and organizational interventions are crucial to support a resilient veterinary workforce.

Distribution of Theileria orientalis in Virginia Market Cattle, 2018-2020.

Theileria orientalis, genotype Ikeda, was recently detected in North America. Determining the emerging distribution of this pathogen is critical for understanding spread and developing management strategies. Whole blood samples were collected from cattle at Virginia livestock markets from September 2018 through December 2020. Animals were tested for T. orientalis using a universal and then genotype specific real-time PCR based on the MPSP gene. Prevalence for each genotype was analyzed for temporal trends and mapped by county. Spatial patterns were compared between genotypes and assessed for associations with habitat features, cattle movements through cattle markets and county proximity. Overall, 212 of 1980 samples tested positive for T. orientalis with an overall prevalence of 8.7% (172/1980) for genotype Ikeda, 1.8% (36/1980) for genotype Chitose, 0.2% (3/1980) for genotype Buffeli. The Ikeda genotype increased over time in northern and southwestern Virginia markets. The Ikeda and Chitose genotypes occurred in different regions, with little overlap, but for each genotype, spatial distribution was associated with a combination of cattle movements and environmental factors. Genotype specific qPCR testing and surveillance of cattle from across a wide area of Virginia are providing information on temporal, spatial, and other patterns for this emerging disease.

Optimizing Pooled Testing for Estimating the Prevalence of Multiple Diseases.

Pooled testing can enhance the efficiency of diagnosing individuals with diseases of low prevalence. Often, pooling is implemented using standard groupings (2, 5, 10, etc.). On the other hand, optimization theory can provide specific guidelines in finding the ideal pool size and pooling strategy. This article focuses on optimizing the precision of disease prevalence estimators calculated from multiplex pooled testing data. In the context of a surveillance application of animal diseases, we study the estimation efficiency (i.e., precision) and cost efficiency of the estimators with adjustments for the number of expended tests. This enables us to determine the pooling strategies that offer the highest benefits when jointly estimating the prevalence of multiple diseases, such as theileriosis and anaplasmosis. The outcomes of our work can be used in designing pooled testing protocols, not only in simple pooling scenarios but also in more complex scenarios where individual retesting is performed in order to identify positive cases. A software application using the shiny package in R is provided with this article to facilitate implementation of our methods. Supplementary materials accompanying this paper appear online. Supplementary materials for this article are available at 10.1007/s13253-022-00511-4.

Subsewershed SARS-CoV-2 Wastewater Surveillance and COVID-19 Epidemiology Using Building-Specific Occupancy and Case Data.

To evaluate the use of wastewater-based surveillance and epidemiology to monitor and predict SARS-CoV-2 virus trends, over the 2020-2021 academic year we collected wastewater samples twice weekly from 17 manholes across Virginia Tech's main campus. We used data from external door swipe card readers and student isolation/quarantine status to estimate building-specific occupancy and COVID-19 case counts at a daily resolution. After analyzing 673 wastewater samples using reverse transcription quantitative polymerase chain reaction (RT-qPCR), we reanalyzed 329 samples from isolation and nonisolation dormitories and the campus sewage outflow using reverse transcription digital droplet polymerase chain reaction (RT-ddPCR). Population-adjusted viral copy means from isolation dormitory wastewater were 48% and 66% higher than unadjusted viral copy means for N and E genes (1846/100 mL to 2733/100 mL/100 people and 2312/100 mL to 3828/100 mL/100 people, respectively; n = 46). Prespecified analyses with random-effects Poisson regression and dormitory/cluster-robust standard errors showed that the detection of N and E genes were associated with increases of 85% and 99% in the likelihood of COVID-19 cases 8 days later (incident-rate ratio (IRR) = 1.845, p = 0.013 and IRR = 1.994, p = 0.007, respectively; n = 215), and one-log increases in swipe card normalized viral copies (copies/100 mL/100 people) for N and E were associated with increases of 21% and 27% in the likelihood of observing COVID-19 cases 8 days following sample collection (IRR = 1.206, p < 0.001, n = 211 for N; IRR = 1.265, p < 0.001, n = 211 for E). One-log increases in swipe normalized copies were also associated with 40% and 43% increases in the likelihood of observing COVID-19 cases 5 days after sample collection (IRR = 1.403, p = 0.002, n = 212 for N; IRR = 1.426, p < 0.001, n = 212 for E). Our findings highlight the use of building-specific occupancy data and add to the evidence for the potential of wastewater-based epidemiology to predict COVID-19 trends at subsewershed scales.

A retrospective analysis of bull:cow ratio effects on pregnancy rates of beef cows previously enrolled in fixed-time artificial insemination protocols.

This retrospective study aimed to determine if the number of cows exposed per bull affects pregnancy rates of cows returning to estrus after fixed-time artificial insemination (FTAI). Data were compiled over the course of 13 breeding seasons (six fall and seven spring seasons) between 2010 and 2017 from the Virginia Department of Corrections herd. Available records contained data from 17 farms and 324 groups of cows (average 47 cows/group). Multiparous cows and heifers (average age per group: 5.11 ± 0.14 yr; n = 14,868) were exposed to FTAI. After FTAI, animals were placed on pasture with bulls diagnosed as fertile by a breeding soundness exam for natural service of cows who did not become pregnant to FTAI (n = 7,248; average 22 cows/group). Animals were classified as pregnant to FTAI, to natural service on first return to estrus, or to natural service on second or subsequent estrus determined by fetal aging at pregnancy diagnosis. The bull:cow ratio for the total number of cows exposed ranged from 1:9 to 1:73 with an average of 1:31. The bull:cow ratio considering only open cows exposed after FTAI ranged from 1:2 to 1:44 with an average of 1:14. There was significant negative, small correlation between the bull:cow ratio for total number of cows exposed and return to estrus pregnancy rate in fall breeding seasons (P = 0.01, r 2 = 0.04) but not in spring (P = 0.90). There was a significant negative, small correlation between bull:cow ratio of open cows exposed and pregnancy rates to first return to estrus in fall herds with a single sire (P < 0.001, r 2 = 0.11). There was no correlation in fall herds using multiple sires or spring herds (P ≥ 0.12). Bull:cow ratio accounted for only 1-11% of variation in the pregnancy rates, thus we conclude that a decreased bull:cow ratio (up to 1:73) did not affect natural service return to estrus pregnancy rate. Cattlemen may consider a reduced number of bulls needed for natural service breeding after FTAI, which can decrease bull related costs and increase the economic feasibility of adopting FTAI protocols.

Longitudinal social network analysis of avian mycobacteriosis incidence in a large population of zoo birds.

The goal of this study was to evaluate longitudinal patterns of avian mycobacteriosis spread through a social network. Specifically, we wanted to determine whether the patterns of connectivity over time can predict future infections, and whether this pattern can distinguish between different sources of infection. The study population included 13,409 individuals nested in a larger population of birds that were closely monitored in zoological facilities for over 22 years (1992-2014). A retrospective cohort study design and social network connectivity were used to estimate the association between exposure to an infected bird, and development of mycobacteriosis. Avian mycobacteriosis was diagnosed from histopathology and network connectivity was defined by enclosure histories over discrete time periods. Single-variable and multivariable longitudinal, mixed effects logistic regression models examined whether exposure to infected birds, both directly- and indirectly-connected, was associated with development of mycobacteriosis at the next time step. Our adjusted model showed an increased odds of developing mycobacteriosis (odds ratio = 2.15; 95 % CI: 1.48-3.12; p < 0.001) for birds that were directly exposed (i.e., housed in the same aviary) to another infected bird, compared to those with no exposure. Exposure to a positive, indirectly-connected bird at a previous time step was independently associated with an increased risk of mycobacteriosis (odds ratio = 1.56; 95 % CI: 1.11-2.19). This association persisted in adjusted models even when the indirect contacts were housed in distinctly different aviaries and never had contact with the subject of interest or its environment. Adjusted, risk-stratified models further characterized the type of exposure that increased the risk of avian mycobacteriosis. Birds that were exposed in small aviaries were more likely to develop mycobacteriosis than those exposed in larger aviaries and those with no exposure. The lesion distribution and species of the contact (same species versus different species) were also significant predictors of disease risk. Some findings were sensitive to model variation of time divisions and initiation time. Our study shows avian mycobacteriosis spread through the social network in quantifiable and discernable patterns. We provide empirical evidence that a contagious process drives some of the observed infection, but we also show low transmissibility based on sustained patterns of low incidence over time even when large groups of birds are exposed. Targeted risk mitigation efforts based on the characteristics of the exposure may be effective at reducing risk of avian mycobacteriosis while enhancing population sustainability.

Social network analysis and whole-genome sequencing to evaluate disease transmission in a large, dynamic population: A study of avian mycobacteriosis in zoo birds.

This study combined a social network analysis and whole-genome sequencing (WGS) to test for general patterns of contagious spread of a mycobacterial infection for which pathways of disease acquisition are not well understood. Our population included 275 cases diagnosed with avian mycobacteriosis that were nested in a source population of 16,430 birds at San Diego Zoo Wildlife Alliance facilities from 1992 through mid-2014. Mycobacteria species were determined using conventional methods and whole genome sequencing (WGS). Mycobacterium avium avium (MAA) and Mycobacterium genavense were the most common species of mycobacteria identified and were present in different proportions across bird taxa. A social network for the birds was constructed from the source population to identify directly and indirectly connected cases during time periods relevant to disease transmission. Associations between network connectivity and genetic similarity of mycobacteria (as determined by clusters of genotypes separated by few single nucleotide polymorphisms, or SNPs) were then evaluated in observed and randomly generated network permutations. Findings showed that some genotypes clustered along pathways of bird connectivity, while others were dispersed throughout the network. The proportion of directly connected birds having a similar mycobacterial genotype was 0.36 and significant (p<0.05). This proportion was higher (0.58) and significant for MAA but not for M. genavense. Evaluations of SNP distributions also showed genotypes of MAA were more related in connected birds than expected by chance; however, no significant patterns of genetic relatedness were identified for M. genavense, although data were sparse. Integrating the WGS analysis of mycobacteria with a social network analysis of their host birds revealed significant genetic clustering along pathways of connectivity, namely for MAA. These findings are consistent with a contagious process occurring in some, but not all, case clusters.

RETROSPECTIVE REVIEW OF COPPER SULFATE IMMERSION TREATMENT IN MARINE TELEOSTS DURING QUARANTINE AT THE NATIONAL AQUARIUM OF BALTIMORE FROM 2004 TO 2016.

Copper sulfate immersion is common for the prevention and treatment of Cryptocaryon irritans during quarantine of marine teleosts. The National Aquarium in Baltimore has followed a consistent copper sulfate protocol for marine teleost quarantine since 2004. The protocol used copper sulfate pentahydrate as a slow drip to increase copper ions over 3-5 days to a level of 0.18-0.21 mg/L. This level was maintained for 21 days, and then copper ions were rapidly removed with activated carbon filtration and water changes. Quarantine records from 2004-2016 were used to examine mortality of marine teleosts during copper treatment and identify factors that might have influenced mortality. The following records were excluded: brackish and freshwater teleosts (salinity <25 g/L); long-term treatment at subtherapeutic levels (<0.18 mg/L); intentional short courses (<14 days); and use outside of quarantine. Species, system volume, temperature, parasitic outbreaks, concurrent medications, and water quality concerns were evaluated. During this period, 4,835 individual teleosts belonging to 347 different species were treated. From 2004 to 2016, mortality during copper treatment was 4.1% (199/4,835 individuals) and was higher when treatment was started during the first week of quarantine (7.7%, 68/884) rather than later (3.3%, 131/3,951 individuals). Of the mortalities, 24.1% (48/199) occurred during the initial subtherapeutic period, and 75.9% (151/199) occurred during the therapeutic period. No mortalities occurred in 75.5% (262/347) of species during copper treatment. When using a similar methodology, copper sulfate is a safe immersion for quarantine of marine teleosts. Mortalities during copper treatment can be reduced by increasing copper ion levels to therapeutic ranges more slowly (e.g., over 7 days) and starting copper treatment after the first week of quarantine.

Spatiotemporal network structure among "friends of friends" reveals contagious disease process.

Disease transmission can be identified in a social network from the structural patterns of contact. However, it is difficult to separate contagious processes from those driven by homophily, and multiple pathways of transmission or inexact information on the timing of infection can obscure the detection of true transmission events. Here, we analyze the dynamic social network of a large, and near-complete population of 16,430 zoo birds tracked daily over 22 years to test a novel "friends-of-friends" strategy for detecting contagion in a social network. The results show that cases of avian mycobacteriosis were significantly clustered among pairs of birds that had been in direct contact. However, since these clusters might result due to correlated traits or a shared environment, we also analyzed pairs of birds that had never been in direct contact but were indirectly connected in the network via other birds. The disease was also significantly clustered among these friends of friends and a reverse-time placebo test shows that homophily could not be causing the clustering. These results provide empirical evidence that at least some avian mycobacteriosis infections are transmitted between birds, and provide new methods for detecting contagious processes in large-scale global network structures with indirect contacts, even when transmission pathways, timing of cases, or etiologic agents are unknown.

Incidence of Health and Behavior Problems in Service Dog Candidates Neutered at Various Ages.

Saint Francis Service Dogs (SFSD) trains dogs to aid people with multiple sclerosis, brain injury, and many other conditions. Organizations like SFSD must carefully consider when to neuter dogs to give them the best chance at successfully completing lengthy and expensive training. The objective of this retrospective cohort study was to assess differences in the incidence of health or behavior problems leading to dismissal between dogs neutered at different ages. Data on 245 dogs-including birth date, sex, neuter date, dismissal or successful completion of training, and (where applicable) reason for dismissal-were collected from SFSD records. Age-at-neuter was grouped (<7 months; 7-11 months; > 11 months) and compared for dogs who successfully completed training and dogs who were dismissed. Dogs neutered from 7 to 11 months of age were dismissed at a significantly lower overall rate than dogs neutered at an older or younger age. There were no differences between males and females. Labrador and golden retrievers were less likely to be dismissed than other breeds. This pattern was the same for dismissals for behavioral reasons. Dogs neutered at <7 months had more than twice the risk for health-related dismissals as dogs neutered at any older age and this pattern held for orthopedic dismissals. Labradors were at higher risk for orthopedic-related dismissal than golden retrievers and all other breeds. This study suggests that there is a relationship between dogs' age at neuter and the incidence of health and behavioral problems that can lead to dismissal from service dog training.

Brief Report: Body Mass Index and Cognitive Function Among HIV-1-Infected Individuals in China, India, and Nigeria.

BACKGROUND: Risk of cognitive impairment is increased among persons with high or low body mass index in HIV- and HIV+ populations in resource-rich settings. We examined this association among HIV+ patients in 3 resource-limited settings. METHODS: This secondary analysis included data of 761 HIV+ volunteers pooled from 3 prospective cohort studies conducted in China (n = 404; 53%), India (n = 200; 26%), and Nigeria (n = 157; 21%). World Health Organization (WHO) weight classifications were based on body mass index. T scores, adjusted for demographics and practice effects, were derived from a 7-domain neuropsychological battery. Neurocognitive impairment (NCI) was defined as global deficit score of ≥0.5. RESULTS: Overall, prevalence of NCI at baseline was 27.7% (similar across all cohorts). The overweight/obese and underweight constituted 37.3% and 15.5% of the total participants, respectively. In a multivariable logistic regression of pooled longitudinal data, adjusting for clinical and demographic variables, the odds of global NCI were 38% higher among the overweight/obese as compared to normal weight participants [odds ratio: 1.38 (95% confidence interval: 1.1 to 1.72); P = 0.005]. Similarly, the odds of global NCI were 39% higher among the underweight as compared to normal weight participants [odds ratio: 1.39 (95% confidence interval: 1.03 to 1.87); P = 0.029]. CONCLUSIONS: NCI among HIV-1-infected patients was more prevalent in both overweight/obese and underweight than normal weight individuals in 3 resource-limited settings, confirming observations in resource-rich settings. Mechanisms underlying these associations are unclear but likely differ for underweight and overweight persons.

Plasma HIV RNA level is associated with neurocognitive function among HIV-1-infected patients in Nigeria.

Plasma HIV RNA level has been shown to correlate with HIV disease progression, morbidity, and mortality. We examined the association between levels of plasma HIV RNA and cognitive function among patients in Nigeria. A total of 179 HIV-1-infected participants with available plasma HIV RNA results and followed longitudinally for up to 2 years were included in this study. Blood samples from participants were used for the measurement of plasma HIV RNA and CD4+ T cell count. Utilizing demographic and practice effect-adjusted T scores obtained from a seven-domain neuropsychological test battery, cognitive status was determined by the global deficit score (GDS) approach, with a GDS ≥ 0.5 indicating cognitive impairment. In a longitudinal multivariable linear regression analysis, adjusting for CD4 cell count, Beck's Depression Score, age, gender, years of education, and antiretroviral treatment status, global T scores decreased by 0.35 per log10 increase in plasma HIV RNA [p = 0.033]. Adjusting for the same variables in a multivariable logistic regression, the odds of neurocognitive impairment were 28% higher per log10 increase in plasma HIV RNA (OR 1.28 [95% CI 1.08, 1.51]; p = 0.005). There were statistically significant associations for the speed of information processing, executive, and verbal fluency domains in both linear and logistic regression analyses. We found a significant association between plasma HIV RNA levels and cognitive function in both baseline (cross-sectional) and longitudinal analyses. However, the latter was significantly attenuated due to weak association among antiretroviral-treated individuals.

Postmarket Safety Outcomes for New Molecular Entity (NME) Drugs Approved by the Food and Drug Administration Between 2002 and 2014.

We ascertained a comprehensive list of postmarket safety outcomes, defined as a safety-related market withdrawal or an update to a safety-related section of product label for 278 new molecular entity drugs (NMEs) with a follow-up period of up to 13 years. At least one safety-related update was added to 195 (70.1%) labels of the drugs studied. Updates occurred as early as 160 days after approval and throughout the follow-up period. The period between the second and eighth postapproval year was the most active, with a slight attenuation thereafter. The times to the first safety outcome were significantly shorter for NMEs approved with a fast-track designation (P = 0.02) or under an accelerated approval using a surrogate endpoint (P = 0.03). Our findings underscore the importance of a robust safety surveillance system throughout a drug's lifecycle and for practitioners and patients to remain updated on drug safety profiles.

Cognitive Function Among Antiretroviral Treatment-Naive Individuals Infected With Human Immunodeficiency Virus Type 1 Subtype G Versus CRF02_AG in Nigeria.

Background: Human immunodeficiency virus type 1 (HIV-1) subtype has been shown to be associated with disease progression. We compared cognitive function between individuals infected with HIV-1 subtype G and CRF02_AG in Nigeria. Methods: For this cross-sectional study, samples were analyzed from 146 antiretroviral-naive participants. Genotypic analysis of plasma HIV RNA was performed by nested polymerase chain reaction of protease and reverse transcriptase genes, and sequences were aligned with curated HIV-1 subtype references. Cognitive status was determined using demographically adjusted T scores and global deficit score (GDS) obtained from a comprehensive neuropsychological test battery. Results: A total of 76 (52.1%) participants were infected with CRF02_AG, 48 (32.8%) with subtype G, and 22 (15.1%) with other HIV-1 strains. In a multivariable linear regression adjusting for plasma HIV RNA, CD4 count, and depression score, mean global T score was lower among subtype G-infected compared with CRF02_AG-infected participants (mean difference, -3.0 [95% confidence interval {CI}, -5.2, to -.7]; P = .011). Also, T scores were significantly lower among subtype G- than CRF02_AG-infected participants for the speed of information processing, executive function, and verbal fluency ability domains. Adjusting for similar variables in a logistic regression, the odds of global cognitive impairment (GDS ≥0.5) were 2.2 times higher among subtype G compared with CRF02_AG-infected participants (odds ratio, 2.2 [95% CI, .9-5.4]; P = .078). Conclusions: Cognitive performance was significantly worse among antiretroviral-naive individuals with HIV-1 subtype G vs CRF02_AG infection. Further studies are required to characterize the mechanistic basis for these differences.

Immunologic response to antiretroviral therapy by age among treatment-naive patients in Sub-Saharan Africa.

OBJECTIVE: To estimate the association between age at antiretroviral therapy (ART) initiation and immunologic response over time by stratum of baseline CD4 cell counts. DESIGN: Retrospective cohort analysis of data pooled from four President's Emergency Plan for AIDS Relief funded countries in Sub-Saharan Africa. METHODS: General linear models were used to estimate the mean CD4 cell count by age group within groups defined by baseline CD4 cell count. Kaplan-Meier methods were used to estimate time to achieving a CD4 cell count of at least 500 cells/µl by age group and stratified by baseline CD4 cell count. RESULTS: A total of 126 672 previously treatment-naive patients provided 466 482 repeated CD4 cell count measurements over 4 years of ART. The median baseline CD4 cell count for all age groups was less than 200 cells/µl. Patients aged 30-39, 40-49, 50-59, and 60 and older at ART initiation had significantly lower mean CD4 cell counts in most strata and at most time points than those 20-29 years old. Compared with those 20-29, all older age groups had a significantly longer time to, and lower rate of, achieving a CD4 cell count of 500 cells. CONCLUSION: Age is associated with the magnitude of CD4 cell gain and the amount of time it takes to gain cells at different levels of baseline CD4 cell count. The delay in achieving a robust immune response could have significant implications for the risk of tuberculosis reactivation as well as comorbidities associated with age in the management of older HIV-infected patients.

Epidemiology of clinical feline herpesvirus infection in zoo-housed cheetahs (Acinonyx jubatus).

OBJECTIVE To determine the incidence of and risk factors for clinical feline herpesvirus (FHV) infection in zoo-housed cheetahs and determine whether dam infection was associated with offspring infection. DESIGN Retrospective cohort study. ANIMALS 144 cheetah cubs born in 6 zoos from 1988 through 2007. PROCEDURES Data were extracted from the health records of cheetahs and their dams to identify incident cases of clinical FHV infection and estimate incidence from birth to 18 months of age. Univariate and multivariable Cox proportional hazards models, controlling for correlations among cheetahs with the same dam, were used to identify risk factors for incident FHV infection. RESULTS Cumulative incidence of FHV infection in cheetah cubs was 35% (50/144). No significant association between dam and offspring infection was identified in any model. Factors identified as significant through multivariable analysis varied by age group. For cheetahs up to 3 months of age, the most important predictor of FHV infection was having a dam that had received a preparturition FHV vaccine regimen that included a modified-live virus vaccine versus a dam that had received no preparturition vaccine. Other risk factors included being from a small litter, being born to a primiparous dam, and male sex. CONCLUSIONS AND CLINICAL RELEVANCE This study provided the first population-level characterization of the incidence of and risk factors for FHV infection in cheetahs, and findings confirmed the importance of this disease. Recognition that clinical FHV infection in the dam was not a significant predictor of disease in cubs and identification of other significant factors have implications for disease management.

Peripheral blood lymphocyte HIV DNA levels correlate with HIV associated neurocognitive disorders in Nigeria.

Mononuclear cells play key roles in the pathogenic mechanisms leading to HIV-associated neurocognitive disorders (HANDs). We examined the association between HIV DNA within peripheral blood mononuclear cell (PBMC) subsets and HAND in Nigeria. PBMCs were collected at baseline from 36 antiretroviral naive participants. CD14+ cells and T&B lymphocyte fractions were isolated by, respectively, positive and negative magnetic bead separation. Total HIV DNA within CD14+ and T&B cells were separately quantified using real-time PCR assay targeting HIV LTR-gag and cell input numbers determined by CCR5 copies/sample. Utilizing demographically adjusted T scores obtained from a 7-domain neuropsychological test battery, cognitive status was determined by the global deficit score (GDS) approach, with a GDS of ≥0.5 indicating cognitive impairment. In a linear regression adjusting for plasma HIV RNA, CD4 and lymphocyte count, Beck's depression score, and years of education, there was 0.04 lower log10 HIV DNA copies within T&B lymphocytes per unit increase in global T score (p = 0.02). Adjusting for the same variables in a logistic regression, the odds of cognitive impairment were 6.2 times greater per log10 increase in HIV DNA within T&B lymphocytes (p = 0.048). The association between cognitive impairment and HIV DNA within CD14+ monocytes did not reach statistical significance. In this pretreatment cohort with mild cognitive dysfunction, we found a strong association between levels of HIV DNA within the lymphocyte subset and HAND independent of plasma HIV RNA. These findings likely reflect the neurologic impact of a larger HIV reservoir and active viral replication.

Modeling the Potential for Vaccination to Diminish the Burden of Invasive Non-typhoidal Salmonella Disease in Young Children in Mali, West Africa.

BACKGROUND: In sub-Saharan Africa, systematic surveillance of young children with suspected invasive bacterial disease (e.g., septicemia, meningitis) has revealed non-typhoidal Salmonella (NTS) to be a major pathogen exhibiting high case fatality (~20%). Where infant vaccination against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae has been introduced to prevent invasive disease caused by these pathogens, as in Bamako, Mali, their burden has decreased markedly. In parallel, NTS has become the predominant invasive bacterial pathogen in children aged <5 years. While NTS is believed to be acquired orally via contaminated food/water, epidemiologic studies have failed to identify the reservoir of infection or vehicles of transmission. This has precluded targeting food chain interventions to diminish disease transmission but conversely has fostered the development of vaccines to prevent invasive NTS (iNTS) disease. We developed a mathematical model to estimate the potential impact of NTS vaccination programs in Bamako. METHODOLOGY/PRINCIPAL FINDINGS: A Markov chain transmission model was developed utilizing age-specific Bamako demographic data and hospital surveillance data for iNTS disease in children aged <5 years and assuming vaccine coverage and efficacy similar to the existing, successfully implemented, Hib vaccine. Annual iNTS hospitalizations and deaths in children <5 years, with and without a Salmonella Enteritidis/Salmonella Typhimurium vaccine, were the model's outcomes of interest. Per the model, high coverage/high efficacy iNTS vaccination programs would drastically diminish iNTS disease except among infants age <8 weeks. CONCLUSIONS/SIGNIFICANCE: The public health impact of NTS vaccination shifts as disease burden, vaccine coverage, and serovar distribution vary. Our model shows that implementing an iNTS vaccine through an analogous strategy to the Hib vaccination program in Bamako would markedly reduce cases and deaths due to iNTS among the pediatric population. The model can be adjusted for use elsewhere in Africa where NTS epidemiologic patterns, serovar prevalence, and immunization schedules differ from Bamako.

Regulatory Considerations for the Approval of Drugs Against Histomoniasis (Blackhead Disease) in Turkeys, Chickens, and Game Birds in the United States.

Histomoniasis, commonly referred to as blackhead disease, is a serious threat to the turkey and game bird industries worldwide, and it is having an increasingly negative impact on the chicken industry as well. The Food and Drug Administration's (FDA) Center for Veterinary Medicine (CVM), charged with the approval and regulation of new animal drugs in the United States, understands the rising need for the availability of therapeutic options against histomoniasis. CVM has actively engaged in discussions with the poultry industry, academic institutions, and animal health companies regarding the current status of histomoniasis in the United States and varied success of past and current management, prophylactic, and therapeutic interventions that have been used against the disease. As effective options against the disease are severely limited, CVM encourages the poultry industry, academic institutions, and animal health companies to work together to research and develop viable management, prophylactic, and therapeutic strategies, such as litter management, deworming programs, vaccines or other biologics, novel technologies, and animal drugs. CVM also recognizes the potential challenges that the poultry industry, academic institutions, and animal health companies may encounter while working towards the approval of safe and effective drug products for the treatment and control of histomoniasis. With that recognition, CVM encourages interested parties to begin discussions with CVM early in order to align research of the drug product against histomoniasis with the drug approval requirements, such that it leads to the approval of a new animal drug in an efficient and expedient manner. This article provides information about the FDA's regulatory process for the approval of new animal drugs in the United States, with especial emphasis on drug products for the treatment and control of histomoniasis in turkeys, chickens, and game birds.