Identification of Sero-Diagnostic Antigens for the Early Diagnosis of Johne’s Disease using MAP Protein Microarrays

Considerable effort has been directed toward controlling Johne’s disease (JD), a chronic granulomatous intestinal inflammatory disease caused by Mycobacterium avium subsp. paratuberculosis (MAP) in cattle and other ruminants. However, progress in controlling the spread of MAP infection has been impeded by the lack of reliable diagnostic tests that can identify animals early in the infection process and help break the transmission chain. To identify reliable antigens for early diagnosis of MAP infection, we constructed a MAP protein array with 868 purified recombinant MAP proteins, and screened a total of 180 well-characterized serum samples from cows assigned to 4 groups based on previous serological and fecal test results: negative low exposure (NL, n = 30); negative high exposure (NH, n = 30); fecal- positive, ELISA-negative (F + E−, n = 60); and both fecal- and ELISA-positive (F + E+, n = 60). The analyses identified a total of 49 candidate antigens in the NH, F + E−, and F + E+ with reactivity compared with the NL group (p \u3c 0.01), a majority of which have not been previously identified. While some of the antigens were identified as reactive in only one of the groups, others showed reactivity in multiple groups, including NH (n = 28), F + E− (n = 26), and F + E+ (n = 17) groups. Using combinations of top reactive antigens in each group, the results reveal sensitivities of 60.0%, 73.3%, and 81.7% in the NH, F + E−, and F + E+, respectively at 90% specificity, suggesting that early detection of infection in animals may be possible and enable better opportunities to reduce within herd transmission that may be otherwise missed by traditional serological assays that are biased towards more heavily infected animals. Together, the results suggest that several of the novel candidate antigens identified in this study, particularly those that were reactive in the NH and F + E− groups, have potential utility for the early sero-diagnosis of MAP infection

Divergent water requirements partition exposure risk to parasites in wild equids

For grazing herbivores, dung density in feeding areas is an important determinant of exposure risk to fecal- orally transmitted parasites. When host species share the same parasite species, a nonrandom distribution of their cumulative dung density and/or nonrandom ranging and feeding behavior may skew exposure risk and the relative selection pressure parasites impose on each host. The arid-adapted Grevy\u27s zebra ( Equus grevyi ) can range more widely than the water-dependent plains zebra ( Equus quagga ), with which it shares the same species of gastrointestinal nematodes. We studied how the spatial distribution of zebra dung relates to ranging and feeding behavior to assess parasite exposure risk in Grevy\u27s and plains zebras at a site inhabited by both zebra species. We found that zebra dung density declined with distance from water, Grevy\u27s zebra home ranges (excluding those of territorial males) were farther from water than those of plains zebras, and plains zebra grazing areas had higher dung density than random points while Grevy\u27s zebra grazing areas did not, suggest - ing a greater exposure risk in plains zebras associated with their water dependence. Fecal egg counts increased with home range proximity to water for both species, but the response was stronger in plains zebras, indicating that this host species may be particularly vulnerable to the elevated exposure risk close to water. We further ran experiments on microclimatic effects on dung infectivity and showed that fewer nematode eggs embryonated in dung in the sun than in the shade. However, only 5% of the zebra dung on the landscape was in shade, indicating that the microclimatic effects of shade on the density of infective larvae is not a major influence on exposure risk dynamics. Ranging constraints based on water requirements appear to be key mediators of nematode parasite exposure in free-ranging equids

Corrigendum: A Meta-Analysis of the Effect of Bacillus Calmette-Guérin Vaccination Against Bovine Tuberculosis:Is Perfect the Enemy of Good?

More than 50 million cattle are likely exposed to bovine tuberculosis (bTB) worldwide, highlighting an urgent need for bTB control strategies in low- and middle-income countries (LMICs) and other regions where the disease remains endemic and test-and-slaughter approaches are unfeasible. While Bacillus Calmette-Guérin (BCG) was first developed as a vaccine for use in cattle even before its widespread use in humans, its efficacy against bTB remains poorly understood. To address this important knowledge gap, we conducted a systematic review and meta-analysis to determine the direct efficacy of BCG against bTB challenge in cattle, and performed scenario analyses with transmission dynamic models incorporating direct and indirect vaccinal effects (“herd-immunity”) to assess potential impact on herd level disease control. The analysis shows a relative risk of infection of 0.75 (95% CI: 0.68, 0.82) in 1,902 vaccinates as compared with 1,667 controls, corresponding to a direct vaccine efficacy of 25% (95% CI: 18, 32). Importantly, scenario analyses considering both direct and indirect effects suggest that disease prevalence could be driven down close to Officially TB-Free (OTF) status (<0.1%), if BCG were introduced in the next 10-year time period in low to moderate (<15%) prevalence settings, and that 50–95% of cumulative cases may be averted over the next 50 years even in high (20–40%) disease burden settings with immediate implementation of BCG vaccination. Taken together, the analyses suggest that BCG vaccination may help accelerate control of bTB in endemic settings, particularly with early implementation in the face of dairy intensification in regions that currently lack effective bTB control programs

Identification of Sero-Diagnostic Antigens for the Early Diagnosis of Johne’s Disease using MAP Protein Microarrays

Considerable effort has been directed toward controlling Johne’s disease (JD), a chronic granulomatous intestinal inflammatory disease caused by Mycobacterium avium subsp. paratuberculosis (MAP) in cattle and other ruminants. However, progress in controlling the spread of MAP infection has been impeded by the lack of reliable diagnostic tests that can identify animals early in the infection process and help break the transmission chain. To identify reliable antigens for early diagnosis of MAP infection, we constructed a MAP protein array with 868 purified recombinant MAP proteins, and screened a total of 180 well-characterized serum samples from cows assigned to 4 groups based on previous serological and fecal test results: negative low exposure (NL, n = 30); negative high exposure (NH, n = 30); fecal- positive, ELISA-negative (F + E−, n = 60); and both fecal- and ELISA-positive (F + E+, n = 60). The analyses identified a total of 49 candidate antigens in the NH, F + E−, and F + E+ with reactivity compared with the NL group (p \u3c 0.01), a majority of which have not been previously identified. While some of the antigens were identified as reactive in only one of the groups, others showed reactivity in multiple groups, including NH (n = 28), F + E− (n = 26), and F + E+ (n = 17) groups. Using combinations of top reactive antigens in each group, the results reveal sensitivities of 60.0%, 73.3%, and 81.7% in the NH, F + E−, and F + E+, respectively at 90% specificity, suggesting that early detection of infection in animals may be possible and enable better opportunities to reduce within herd transmission that may be otherwise missed by traditional serological assays that are biased towards more heavily infected animals. Together, the results suggest that several of the novel candidate antigens identified in this study, particularly those that were reactive in the NH and F + E− groups, have potential utility for the early sero-diagnosis of MAP infection

Regression Discontinuity Analyses of the Community Reinvestment and GSE Acts By

In this dissertation, I provide evidence of the causal impact on mortgage supply of the Community Reinvestment Act (CRA) and the &quot;Government-Sponsored Enterprises (GSE) Act&quot;, laws requiring banks and the GSEs (Fannie Mae and Freddie Mac), respectively, to help improve credit access for low-income households and neighborhoods. While financial markets evolved rapidly since the early 1990&apos;s, I use discontinuities in the laws &apos; eligibility rules to identify their effects. To implement the analyses, I use a census of mortgage applications collected under the Home Mortgage Disclosure Act. Overall, these programs appear to have had limited impact. I first analyze CRA&apos;s effect on mortgage lending in targeted neighborhoods: census tracts with a median family income (MFI) under 80 % of MSA MFI. The regression discontinuity (RD) estimates suggest an overall credit supply shift of at least $6 billion ($2007) from 1994 and 2002 in targeted neighborhoods. In addition to CRA&apos;