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Scholarly Works (5 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2018)

Background: Transmission of avian mycobacteriosis is generally considered a contagious process, but is not well understood and environmental sources may be important. The large, dynamic population of birds at San Diego Zoo Global (SDZG) with complete population ascertainment over a 22-year period offered an opportunity to use social network analysis to understand disease epidemiology and test for patterns of contagion.

Objectives: Study one evaluated the social network structure of birds for evidence of a contagious process. Study two examined patterns of genetic similarities using whole genome sequencing (WGS) along pathways of network connectivity. Study three examined whether network connectivity predicts future disease.

Methods: Study one identified cases of mycobacteriosis and constructed a social network from enclosure histories (n=16,430) in the SDZG population. Stratification of network edges by spatial and temporal characteristics tested for contagion and other drivers of disease in directly- and indirectly-connected birds. Study two characterized mycobacteria isolated from 124/275 cases. For the subset with WGS (n=97), the probability of having similar genotypes given connectivity was estimated and significance determined from random permutation tests. Study three used longitudinal, mixed-effects logistic regression to evaluate the association between network exposure and mycobacteriosis development.

Results: Study one: Disease clustered significantly among directly- and indirectly-connected birds. The RR of disease given exposure to 2° contacts never housed in the same enclosure was 1.31 (p=0.004), providing strong evidence that a contagious process is present, because the association persisted when common environmental exposure was removed. Study two: Mycobacterium avium avium (MAA) and M. genavense were the most common species. The WGS showed genotypes of MAA were significantly related along paths of network connectivity; however, no significant patterns were identified for M. genavense. Study three: Results showed significant associations between direct (OR=2.15) and indirect (OR=1.56) exposure to positive birds (compared to no exposure) and mycobacteriosis. Risk-stratified models provided estimates with further characterization of exposure; not all findings were robust to model variation.

Conclusion: Social network analysis was a powerful method for evaluating complex contact patterns and mycobacteriosis. The data strongly support a contagious process, show low transmissibility, and provide new information on disease epidemiology.

    Cover page: The epidemiology of avian mycobacteriosis: Using social network analysis to uncover patterns of disease transmission
    • Article
    • Peer Reviewed
    UC San Diego Previously Published Works (2020)
    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.
      Cover page: Spatiotemporal network structure among “friends of friends” reveals contagious disease processCreative Commons 'BY' version 4.0 license
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2017)
      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.
        Cover page: Epidemiology of clinical feline herpesvirus infection in zoo-housed cheetahs (Acinonyx jubatus).
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2021)
        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.
          Cover page: Social network analysis and whole-genome sequencing to evaluate disease transmission in a large, dynamic population: A study of avian mycobacteriosis in zoo birdsCreative Commons 'BY' version 4.0 license
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (2019)

          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.
            Cover page: Brief Report
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