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Evidence is presented for an alternative to the superoxide dismutase (SOD)-catalase oxidative stress defense system in Desulfovibrio vulgaris (strain Hildenborough). This alternative system consists of the nonheme iron proteins, rubrerythrin (Rbr) and rubredoxin oxidoreductase (Rbo), the product of the rbo gene (also called desulfoferrodoxin). A ⌬rbo strain of D. vulgaris was found to be more sensitive to internal superoxide exposure than was the wild type. Unlike Rbo, expression of plasmid-borne Rbr failed to restore the aerobic growth of a SOD-deficient strain of Escherichia coli. Conversely, plasmid-borne expression of two different Rbrs from D. vulgaris increased the viability of a catalase-deficient strain of E. coli that had been exposed to hydrogen peroxide whereas Rbo actually decreased the viability. A previously undescribed D. vulgaris gene was found to encode a protein having 50% sequence identity to that of E. coli Fe-SOD. This gene also encoded an extended N-terminal sequence with high homologies to export signal peptides of periplasmic redox proteins. The SOD activity of D. vulgaris is not affected by the absence of Rbo and is concentrated in the periplasmic fraction of cell extracts. These results are consistent with a superoxide reductase rather than SOD activity of Rbo and with a peroxidase activity of Rbr. A joint role for Rbo and Rbr as a novel cytoplasmic oxidative stress protection system in D. vulgaris and other anaerobic microorganisms is proposed.

BackgroundAlthough advances in rehydration therapy have made cholera a treatable disease with low case-fatality in settings with appropriate medical care, cholera continues to impose considerable mortality in the world's most impoverished populations. Internationally licensed, killed whole-cell based oral cholera vaccines (OCVs) have been available for over a decade, but have not been used for the control of cholera. Recently, these vaccines were shown to confer significant levels of herd protection, suggesting that the protective potential of these vaccines has been underestimated and that these vaccines may be highly effective in cholera control when deployed in mass immunization programs. We used a large-scale stochastic simulation model to investigate the possibility of controlling endemic cholera with OCVs.Methods and FindingsWe construct a large-scale, stochastic cholera transmission model of Matlab, Bangladesh. We find that cholera transmission could be controlled in endemic areas with 50% coverage with OCVs. At this level of coverage, the model predicts that there would be an 89% (95% confidence interval [CI] 72%–98%) reduction in cholera cases among the unvaccinated, and a 93% (95% CI 82%–99%) reduction overall in the entire population. Even a more modest coverage of 30% would result in a 76% (95% CI 44%–95%) reduction in cholera incidence for the population area covered. For populations that have less natural immunity than the population of Matlab, 70% coverage would probably be necessary for cholera control, i.e., an annual incidence rate of ≤ 1 case per 1,000 people in the population.ConclusionsEndemic cholera could be reduced to an annual incidence rate of ≤ 1 case per 1,000 people in endemic areas with biennial vaccination with OCVs if coverage could reach 50%–70% depending on the level of prior immunity in the population. These vaccination efforts could be targeted with careful use of ecological data.

Importance Postnatal cytomegalovirus (CMV) infection can cause serious morbidity and mortality in very low birth weight (VLBW) infants. The primary sources of postnatal CMV infection in this population are breast milk and blood transfusion. The current risks attributable to these vectors, and the efficacy of approaches to prevent CMV transmission, are poorly characterized. Objectives To estimate the risk of postnatal CMV transmission from 2 sources: 1) transfusion of CMV-seronegative and leukoreduced blood and 2) maternal breast milk. Design Prospective, multicenter birth-cohort study conducted from January 2010 to June 2013. CMV serologic testing of enrolled mothers was performed to determine their status. CMV nucleic acid testing (NAT) of transfused blood components and breast milk was performed to identify sources of CMV transmission. Enrolled VLBW infants underwent serum and urine CMV NAT testing at birth, to evaluate congenital infection, and surveillance CMV NAT testing at 5 additional intervals between birth and 90 days, discharge or death. Setting Three neonatal intensive care units (2 academically-affiliated and 1 private) in Atlanta, Georgia. Participants 539 VLBW infants (birth weight ≤1500 grams) who had not received a blood transfusion were enrolled, with their mothers, within 5 days of birth. Exposure Blood transfusion and breast milk feeding Main Outcomes and Measures Cumulative incidence of postnatal CMV infection, detected by serum or urine NAT. Results CMV positive sero-prevalence among enrolled mothers was 76% (352/462). Among 539 enrolled VLBW infants, the cumulative incidence of postnatal CMV infection at 12 weeks was 6.9% (95% CI: 4.2%–9.2%); five infants with postnatal CMV infection developed symptomatic disease or died. Although 58% (310/539) of infants received 2061 transfusions, none of the CMV infections were linked to transfusion, resulting in a CMV infection incidence of 0.0% (95%CI: 0.0%–0.3%) per unit of CMV-seronegative and leukoreduced blood. Twenty-seven of 28 postnatal infections occurred among infants fed CMV-positive breast milk (12-week incidence: 15.3%; 95%CI: 9.3%–20.2%). Conclusions and Relevance Transfusion of CMV-seronegative and leukoreduced blood products effectively prevents transmission of CMV to VLBW infants. Among infants managed with this transfusion approach, maternal breast milk is the primary source of postnatal CMV infection. Trial Registration clinicaltrials.gov Identifier: NCT00907686

A high-dose vitamin D3 regimen safely corrected vitamin D deficiency but did not improve the rate of sputum Mtb clearance over 16 wk in this pulmonary tuberculosis cohort. This trial was registered at clinicaltrials.gov at NCT00918086.