Clostridium difficile: the increasingly difficult pathogen

The epidemiology of Clostridium difficile infection is changing as a result of the epidemic spread of the hypervirulent North American Pulsefield type 1 strain. Clinicians are likely to encounter this disease more frequently than ever in their practice, and should be familiar with the updates in its diagnosis and treatment

Toxin Genotypes and Plasmid Profiles as Determinants of Systemic Sequelae in \u3ci\u3eEscherichia coli\u3c/i\u3e 0157:H7 Infections

In 1987, 93 Escherichia coli 0157:H7 isolates were collected during routine surveillance for this pathogen in the state of Washington. Toxin genotypes and plasmid profiles were correlated with the clinical sequelae of illness in 88 of the 93 patients from whom these strains were isolated. Thirteen plasmid patterns were observed among the 88 tested isolates; four patterns accounted for 82(7o of the isolates. Genetic probing for Shiga-like toxins (SLT) I and II demonstrated the presence of both genes in 67 (76%), SLT I alone in three (3%), and SLT II alone in 18 (20%). The hemolytic uremic syndrome or throm-botic thrombocytopenic purpura developed in seven (39%) of 18 patients infected with isolates having only the SLT II gene, while these complications occurred in only four (6%) of 70 patients infected with isolates having the other two genotypes (relative risk, 6.8; 95% confidence interval, 1.9, 26.4). This study shows that E. coli 0157:H7 isolates systematically collected from a single geographic region over a defined time period exhibit considerable diversity in plasmid content and toxin genotype and that the toxin genotype of the infecting strain may influence the risk of developing micro-angiopathic sequelae

Burden of typhoid fever in Sulaimania, Iraqi Kurdistan

Background: Typhoid fever imposes a high disease burden worldwide, but resource limitations mean that the burden of typhoid fever in many countries is poorly understood. Methods: The authors conducted a prospective surveillance study at the adult and pediatric teaching hospitals in Sulaimania, Iraqi Kurdistan. All patients presenting with an undifferentiated febrile illness consistent with typhoid were eligible for enrollment. Enrolled patients had blood cultures and Brucella serologies performed. Incidence was calculated with reference to census data. Results: Both typhoid fever and brucellosis were common, and the incidence of typhoid fever was 21 cases/100 000 patient-years. Classic disease symptoms were uncommonly observed. Discussion: Cost-effective surveillance projects to calculate disease burden of typhoid fever are practical and replicable. Typhoid has successfully adapted to the healthcare environment in Sulaimania. Additional work in the region should focus on antibiotic resistance and other enteric pathogens such as Brucella spp

Risk of COVID-19 after natural infection or vaccinationResearch in context

Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health

Risk of COVID-19 after natural infection or vaccinationResearch in context

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health