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For decades, human brucellosis has been recognized worldwide as a significant cause of morbidity, yet the annual incidence of this disease remains unknown. We analyzed this frequency, using international reports (2005-2019), identifying information gaps, and distinguishing a possible path forward. A novel approach to estimating the incidence of this disease was explored. We utilized annual health data extracted from the World Organization for Animal Health (OIE)-World Animal Health Information System (WAHIS) database, assessing the dataset completeness and representativeness of the data for the world population. Additionally, we assessed the reported country level human brucellosis case counts and the factors that influenced the observed changes over time. Our analysis revealed incomplete and unrepresentative information, preventing the estimation of annual human brucellosis case incidence at the global level. In the OIE-WAHIS database, only 48.4% of the required reports have been submitted as of 2019, with approximately 47.3% of the world population represented. Additionally, geographic regions were disproportionate in completeness, representativeness, and actual reported case counts. Africa and Asia constituted the majority of reported cases, while simultaneously submitting the lowest percentage of reports as well as covering the lowest percentage of their populations within those reports, when compared to the rest of the world. The global annual frequency of human brucellosis cases remains elusive. Furthermore, there exists great heterogeneity in diagnostic, surveillance, and reporting systems worldwide, calling into question the validity of available information. This study reveals that the Neglected Zoonotic Disease priority status for brucellosis should be restored.

A pair-matched longitudinal study conducted on three dairy farms in the U.S. High-Plains explored the temporal effects of two-dose ceftiofur crystalline-free acid (CCFA) treatment for metritis on third-generation cephalosporin (3GC) resistance among enteric E. coli in Holstein-Friesian cows. The current 13-day slaughter withholding period does not account for rising populations of third-generation cephalosporin (3GC) resistant bacteria in feces of animals following CCFA treatment. A total of 124 matched-pairs of cows were enrolled in the study. Cows diagnosed with postpartum metritis received the product twice at the labeled dose of 6.6 mg/kg subcutaneously at the base of alternating ears. Untreated cows-absent clinical metritis-were matched on lactation number and calving date. Feces were collected per rectum on days 0 (baseline), 6, 16, 28, and 56. Environmental samples, from watering troughs as well as surface manure from fresh-cow, hospital, maternity, and milking pens, and from the compost pile were collected prior to the animal sample collection period. Historical data on metritis rates and CCFA use were compiled from herd records. On day 0, cows exhibited an overall mean difference of over 4 log10 colony forming units (CFU) comparing 3GC resistant E. coli to the general E. coli population. At the first eligible slaughter date, the difference declined to 3.31 log10 CFU among cows in the CCFA group (P<0.01 compared to control cows). Such differences were no longer observed between the treated and control groups by day 28. Results suggest a 13-day withholding period following the final treatment is insufficient to allow levels of 3GC resistant E. coli to return to baseline. This effect varied by farm and was dependent upon the starting level of resistance. A farm-specific extended slaughter-withholding period could reduce the microbial risk to food products at slaughter.

Objective Maternal morbidity and mortality is a global concern despite advances in medical care and technology and improved economic resources of nations worldwide. The primary objective of our study was to describe racial/ethnic disparities in severe maternal morbidity by using admission to an intensive care unit (ICU) as a marker. The secondary objective was to evaluate associations between patient characteristics, including obstetric outcomes, and severe maternal morbidity. Methods This retrospective cohort study used a large inpatient database to identify pregnancy and postpartum hospitalizations in Hawai‘i from January 2012 through September 2017. We evaluated associations between sociodemographic and clinical characteristics and race/ethnicity by using χ2 tests. We used multivariable logistic regression to assess associations between race/ethnicity and ICU admission. We used a post hoc analysis to assess associations between ICU admission and obstetric outcomes by race/ethnicity. Results After adjustment, we found a significantly higher ICU admission rate among Asian (adjusted odds ratio [aOR] = 1.30; 95% CI, 1.04-1.62; P = .02), Filipino (aOR = 1.45; 95% CI, 1.17-1.79; P < .001), and Native Hawaiian/Other Pacific Islander (aOR = 1.39; 95% CI, 1.15-1.68; P < .001) women compared with non-Hispanic White women. Multiple clinical characteristics and outcomes were associated with ICU admission, such as preexisting chronic conditions and pregnancy-induced hypertensive disorders. Conclusion We found that severe maternal morbidity represented by ICU admission is higher among Asian, Filipino, and Native Hawaiian/Other Pacific Islander women than among non-Hispanic White women in Hawai’i. Our findings reemphasize the need for health care providers to be vigilant in caring for members of racial/ethnic minority groups and managing their comorbidities.

Antibiotic use in beef cattle is a risk factor for the expansion of antimicrobial-resistant Salmonella populations. However, actual changes in the quantity of Salmonella in cattle feces following antibiotic use have not been investigated. Previously, we observed an overall reduction in Salmonella prevalence in cattle feces associated with both ceftiofur crystalline-free acid (CCFA) and chlortetracycline (CTC) use; however, during the same time frame the prevalence of multidrug-resistant Salmonella increased. The purpose of this analysis was to quantify the dynamics of Salmonella using colony counting (via a spiral-plating method) and hydrolysis probe-based qPCR (TaqMan® qPCR). Additionally, we quantified antibiotic-resistant Salmonella by plating to agar containing antibiotics at Clinical & Laboratory Standards Institute breakpoint concentrations. Cattle were randomly assigned to 4 treatment groups across 16 pens in 2 replicates consisting of 88 cattle each. Fecal samples from Days 0, 4, 8, 14, 20, and 26 were subjected to quantification assays. Duplicate qPCR assays targeting the Salmonella invA gene were performed on total community DNA for 1,040 samples. Diluted fecal samples were spiral plated on plain Brilliant Green Agar (BGA) and BGA with ceftriaxone (4 μg/ml) or tetracycline (16 μg/ml). For comparison purposes, indicator non-type-specific (NTS) E. coli were also quantified by direct spiral plating. Quantity of NTS E. coli and Salmonella significantly decreased immediately following CCFA treatment. CTC treatment further decreased the quantity of Salmonella but not NTS E. coli. Effects of antibiotics on the imputed log10 quantity of Salmonella were analyzed via a multi-level mixed linear regression model. The invA gene copies decreased with CCFA treatment by approximately 2 log10 gene copies/g feces and remained low following additional CTC treatment. The quantities of tetracycline or ceftriaxone-resistant Salmonella were approximately 4 log10 CFU/g feces; however, most of the samples were under the quantification limit. The results of this study demonstrate that antibiotic use decreases the overall quantity of Salmonella in cattle feces in the short term; however, the overall quantities of antimicrobial-resistant NTS E. coli and Salmonella tend to remain at a constant level throughout.

Maternal morbidity and mortality is a global concern despite advances in medical care and technology and improved economic resources of nations worldwide. The primary objective of our study was to describe racial/ethnic disparities in severe maternal morbidity by using admission to an intensive care unit (ICU) as a marker. The secondary objective was to evaluate associations between patient characteristics, including obstetric outcomes, and severe maternal morbidity. This retrospective cohort study used a large inpatient database to identify pregnancy and postpartum hospitalizations in Hawai'i from January 2012 through September 2017. We evaluated associations between sociodemographic and clinical characteristics and race/ethnicity by using χ tests. We used multivariable logistic regression to assess associations between race/ethnicity and ICU admission. We used a post hoc analysis to assess associations between ICU admission and obstetric outcomes by race/ethnicity. After adjustment, we found a significantly higher ICU admission rate among Asian (adjusted odds ratio [aOR] = 1.30; 95% CI, 1.04-1.62; = .02), Filipino (aOR = 1.45; 95% CI, 1.17-1.79; < .001), and Native Hawaiian/Other Pacific Islander (aOR = 1.39; 95% CI, 1.15-1.68; < .001) women compared with non-Hispanic White women. Multiple clinical characteristics and outcomes were associated with ICU admission, such as preexisting chronic conditions and pregnancy-induced hypertensive disorders. We found that severe maternal morbidity represented by ICU admission is higher among Asian, Filipino, and Native Hawaiian/Other Pacific Islander women than among non-Hispanic White women in Hawai'i. Our findings reemphasize the need for health care providers to be vigilant in caring for members of racial/ethnic minority groups and managing their comorbidities.

The TREX1 gene encodes a potent DNA exonuclease, and mutations in TREX1 cause a spectrum of lupus-like autoimmune diseases. Most lupus patients develop autoantibodies to double-stranded DNA (dsDNA), but the source of DNA antigen is unknown. The TREX1 D18N mutation causes a monogenic, cutaneous form of lupus called familial chilblain lupus, and the TREX1 D18N enzyme exhibits dysfunctional dsDNA-degrading activity, providing a link between dsDNA degradation and nucleic acid-mediated autoimmune disease. We determined the structure of the TREX1 D18N protein in complex with dsDNA, revealing how this exonuclease uses a novel DNA-unwinding mechanism to separate the polynucleotide strands for single-stranded DNA (ssDNA) loading into the active site. The TREX1 D18N dsDNA interactions coupled with catalytic deficiency explain how this mutant nuclease prevents dsDNA degradation. We tested the effects of TREX1 D18N in vivo by replacing the TREX1 WT gene in mice with the TREX1 D18N allele. The TREX1 D18N mice exhibit systemic inflammation, lymphoid hyperplasia, vasculitis, and kidney disease. The observed lupus-like inflammatory disease is associated with immune activation, production of autoantibodies to dsDNA, and deposition of immune complexes in the kidney. Thus, dysfunctional dsDNA degradation by TREX1 D18N induces disease in mice that recapitulates many characteristics of human lupus. Failure to clear DNA has long been linked to lupus in humans, and these data point to dsDNA as a key substrate for TREX1 and a major antigen source in mice with dysfunctional TREX1 enzyme. Significance The TREX1 enzyme degrades DNA, and mutations in the TREX1 gene cause autoimmune diseases. The TREX1 D18N mutation causes a form of lupus called familial chilblain lupus. We solved the structure of TREX1 D18N bound to dsDNA, showing how the enzyme interacts with dsDNA. We also replaced the TREX1 WT gene in mice with the TREX1 D18N mutated gene and showed how this mutation causes a lupus-like disease. Together, the TREX1 D18N–dsDNA structure and the spontaneous disease exhibited in the TREX1 D18N mouse help to define how TREX1 degrades dsDNA to prevent this molecule from acting as an autoantigen in the mouse and, most likely, in humans to promote autoimmune disease.

Objective To assess differences in the rates of preeclampsia among a multiethnic population in Hawaii. Methods We performed a retrospective study on statewide inpatient data for delivery hospitalizations in Hawaii between January 1995 and December 2013. Multivariable logistic regression was used to assess the impact of maternal race/ethnicity on the rates of preeclampsia after adjusting for age, multiple gestation, multiparity, chronic hypertension, pregestational diabetes, obesity and smoking. Results A total of 271,569 hospital discharges for delivery were studied. The rates of preeclampsia ranged from 2.0 % for Chinese to 4.6 % for Filipinos. Preeclampsia rates were higher among Native Hawaiians who are age <35 and non-obese (OR 1.54; 95 % CI 1.43–1.66), age ≥35 and non-obese (OR 2.31; 95 % CI 2.00–2.68), age ≥35 and obese (OR 1.80; 95 % CI 1.24–2.60); other Pacific Islanders who are age <35 and non-obese (OR 1.40; 95 % CI 1.27–1.54), age ≥35 and non-obese (OR 2.18; 95 % CI 1.79–2.64), age ≥35 and obese (OR 1.68; 95 % CI 1.14–2.49); and Filipinos who are age <35 and non-obese (OR 1.55; 95 % CI 1.43–1.67), age ≥35 and non-obese (OR 2.26; 95 % CI 1.97–2.60), age ≥35 and obese (OR 1.64; 95 % CI 1.04–2.59) compared to whites. Pregestational diabetes (OR 3.41; 95 % CI 3.02–3.85), chronic hypertension (OR 5.98; 95 % CI 4.98–7.18), and smoking (OR 1.19; 95 % CI 1.07–1.33) were also independently associated with preeclampsia. Conclusions for Practice In Hawaii, Native Hawaiians, other Pacific Islanders and Filipinos have a higher risk of preeclampsia compared to whites. For these high-risk ethnic groups, more frequent monitoring for preeclampsia may be needed.

In two sequential replicates (n = 90 and n = 96 feedlot finisher cattle, respectively) we measured the impact of an Enterococcus faecium-based probiotic (DFM) and an altered feedlot pen environment on antimicrobial resistance among fecal enterococci in cattle fed (or, not fed) the macrolide tylosin. Diluted fecal samples were spiral-plated on plain and antibiotic-supplemented m-Enterococcus agar. In the first replicate, tylosin significantly (p < 0.05) increased the relative quantity of erythromycin-resistant enterococci. This effect was diminished in cattle fed the DFM in conjunction with tylosin, indicating a macrolide susceptible probiotic may help mitigate resistance. A similar observed effect was not statistically significant (p > 0.05) in the second replicate. Isolates were speciated and resistance phenotypes were obtained for E. faecium and E. hirae. Susceptible strains of bacteria fed as DFM may prove useful for mitigating the selective effects of antibiotic use; however, the longer-term sustainability of such an approach remains unclear.

Antibiotic resistance represents a growing crisis in both human and veterinary medicine. We evaluated the use of antibiotic alternatives—heavy metals and essential oils—in beef cattle feeding, and their effects on Gram-negative and Gram-positive bacteria. In this randomized controlled field trial, we measured the impact of supplemental zinc and menthol on antibiotic resistance among commensal enteric bacteria of feeder cattle. Fecal suspensions were plated onto plain- and antibiotic-supplemented MacConkey and m-Enterococcus agar for quantification of total and antibiotic-resistant Escherichia coli and Enterococcus spp., respectively. Temporal effects on overall E. coli growth were significant (p < 0.05), and menthol was associated with decreased growth on tetracycline-supplemented agar. Zinc was associated with significant increases in growth on erythromycin-supplemented m-Enterococcus agar. Cattle fed zinc exhibited significantly higher levels of macrolide resistance among fecal enterococci isolates.