The incidence of acute renal failure, defined by the risk, injury, or failure criteria of the RIFLE criteria (risk, injury, failure, loss, and end-stage kidney disease), in 66 patients who received colistimethate sodium was 45%, and 21% of patients stopped therapy because of nephrotoxicity. The RIFLE criteria should be used in the future to allow for comparison of nephrotoxicity among studies.
Background NVX-CoV2373 is an adjuvanted, recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019 (Covid-19) in phase 2b–3 trials in the United Kingdom and South Africa, but its efficacy had not yet been tested in North America. Methods We conducted a phase 3, randomized, observer-blinded, placebo-controlled trial in the United States and Mexico during the first half of 2021 to evaluate the efficacy and safety of NVX-CoV2373 in adults (≥18 years of age) who had not had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Participants were randomly assigned in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. The primary objective was to determine vaccine efficacy against reverse-transcriptase–polymerase-chain-reaction–confirmed Covid-19 occurring at least 7 days after the second dose. Vaccine efficacy against moderate-to-severe disease and against different variants was also assessed. Results Of the 29,949 participants who underwent randomization between December 27, 2020, and February 18, 2021, a total of 29,582 (median age, 47 years; 12.6% ≥65 years of age) received at least one dose: 19,714 received vaccine and 9868 placebo. Over a period of 3 months, 77 cases of Covid-19 were noted — 14 among vaccine recipients and 63 among placebo recipients (vaccine efficacy, 90.4%; 95% confidence interval [CI], 82.9 to 94.6; P<0.001). Ten moderate and 4 severe cases occurred, all in placebo recipients, yielding vaccine efficacy against moderate-to-severe disease of 100% (95% CI, 87.0 to 100). Most sequenced viral genomes (48 of 61, 79%) were variants of concern or interest — largely B.1.1.7 (alpha) (31 of the 35 genomes for variants of concern, 89%). Vaccine efficacy against any variant of concern or interest was 92.6% (95% CI, 83.6 to 96.7). Reactogenicity was mostly mild to moderate and transient but was more frequent among NVX-CoV2373 recipients than among placebo recipients and was more frequent after the second dose than after the first dose. Conclusions NVX-CoV2373 was safe and effective for the prevention of Covid-19. Most breakthrough cases were caused by contemporary variant strains. (Funded by Novavax and others; PREVENT-19 ClinicalTrials.gov number, NCT04611802 .)
The interaction between follicular T helper cells (TFH) and B cells in the lymph nodes and spleen has a major impact on the development of antigen-specific B cell responses during infection or vaccination. Recent studies described a functional equivalent of these cells among circulating CD4 T cells, referred to as peripheral TFH cells. Here, we characterize the phenotype and in vitro B cell helper activity of peripheral TFH populations, as well as the effect of HIV infection on these populations. In co-culture experiments we confirmed CXCR5+ cells from HIV-uninfected donors provide help to B cells and more specifically, we identified a CCR7highCXCR5highCCR6highPD-1high CD4 T cell population that secretes IL-21 and enhances isotype-switched immunoglobulin production. This population is significantly decreased in treatment-naïve, HIV-infected individuals and can be recovered after anti-retroviral therapy. We found impaired immunoglobulin production in co-cultures from HIV-infected individuals and found no correlation between the frequency of peripheral TFH cells and memory B cells, or with neutralization activity in untreated HIV infection in our cohort. Furthermore, we found that within the peripheral TFH population, the expression level of TFH-associated genes more closely resembles a memory, non-TFH population, as opposed to a TFH population. Overall, our data identify a heterogeneous population of circulating CD4 T cells that provides in vitro help to B cells, and challenges the origin of these cells as memory TFH cells.
ABSTRACT. Objective. The hemolytic uremic syndrome (HUS) consists of hemolytic anemia, thrombocytopenia, and renal failure. HUS is often precipitated by gastrointestinal infection with Shiga toxin-producing Escherichia coli and is characterized by a variety of prothrombotic host abnormalities. In much of the world, E coli O157:H7 is the major cause of HUS. HUS can be categorized as either oligoanuric (which probably signifies acute tubular necrosis) or nonoligoanuric. Children with oligoanuric renal failure during HUS generally require dialysis, have more complicated courses, and are probably at increased risk for chronic sequelae than are children who experience nonoligoanuric HUS. Oligoanuric HUS should be avoided, if possible. The presentation to medical care of a child with definite or possible E coli O157:H7 infections but before HUS ensues affords a potential opportunity to ameliorate the course of the subsequent renal failure. However, it is not known whether events that occur early in E coli O157:H7 infections, particularly measures to expand circulating volume, affect the likelihood of experiencing oligoanuric HUS if renal failure develops. We attempted to assess whether pre-HUS interventions and events, especially the volume and sodium content of intravenous fluids administered early in illness, affect the risk for developing oligoanuric HUS after E coli O157:H7 infections.Methods. We performed a prospective cohort study of 29 children with HUS that was confirmed microbiologically to be caused by E coli O157:H7. Infected children were enrolled when they presented with acute bloody diarrhea or as contacts of patients who were known to be infected with E coli O157:H7, or if they had cultureconfirmed infection, or if they presented with HUS. HUS was defined as hemolytic anemia (hematocrit <30%, with fragmented erythrocytes on peripheral-blood smear), thrombocytopenia (platelet count of <150 000/mm 3 ), and renal insufficiency (serum creatinine concentration that exceeded the upper limit of normal for age). A wide range of pre-HUS variables, including demographic factors, clinical history, medications given, initial laboratory values, and volume and content of parenteral fluid administered, were recorded and entered into analysis. Estimates of odds ratios were adjusted for possible confounding effects using logistic regression analysis. Twenty-nine children who were <10 years old, had HUS confirmed to be caused by E coli O157:H7, and were hospitalized at the Children's Hospital and Regional Medical Center, Seattle, were studied. The main outcome measured was development of oligoanuric renal failure. Oligoanuria was defined as a urine output <0.5 mL/kg per hour for at least 24 consecutive hours.Results. As a group, the children with oligoanuric renal failure presented to medical attention and were evaluated with laboratory testing later than the children with nonoligoanuric renal failure. On initial assessments, the children with oligoanuric outcomes had higher white blood cell counts, lower platelet counts...
Summary Background In January, 2014, the Same-Sex Marriage Prohibition Act was signed into law in Nigeria, further criminalising same-sex sexual relationships. We aimed to assess the immediate effect of this prohibition act on stigma, discrimination, and engagement in HIV prevention and treatment services in men who have sex with men (MSM) in Nigeria. Methods The TRUST cohort study uses respondent-driven sampling to assess the feasibility and effectiveness of engagement of MSM in HIV prevention and treatment services at a clinical site located with a community-based organisation trusted by the MSM community. TRUST is a prospective implementation research cohort of MSM (≥16 years) in Abuja, Nigeria. We compared HIV clinical outcomes and stigma, including fear and avoidance of health care, across baseline and quarterly visits before and after implementation of the the Same-Sex Marriage Prohibition Act. Outcomes assessed were measures of stigma and discrimination, loss to follow-up, antiretroviral therapy status, and viral load. We compared outcomes before and after the legislation with χ2 statistics, and estimated incident stigma-related events and loss to follow-up with Poisson regression. Findings Between March 19, 2013, and Aug 7, 2014, 707 MSM participated in baseline study procedures, contributing to 756 before legislation (prelaw) and 420 after legislation (postlaw) visits. Reported history of fear of seeking health care was significantly higher in postlaw visits than in prelaw visits (n=161 [38%] vs n=187 [25%]; p<0.0001), as was avoidance of health care (n=118 [28%] vs n=151 [20%]; p=0.001). In incidence analyses, of 192 MSM with follow-up data and no history of an event at baseline, reported fear of seeking health care was higher in the postlaw than the prelaw period (n=144; incidence rate ratio 2.57, 95% CI 1.29–5.10; p=0.007); loss to follow-up and incident healthcare avoidance were similar across periods. Of the 161 (89%) of 181 HIV-infected MSM with HIV viral loads available, those who had disclosed sexual behaviour with a health-care provider were more often virally suppressed at baseline than those with no previous disclosure (18 [29%] of 62 vs 13 [13%] of 99 men; p=0.013). Interpretation These analyses represent individual-level, quantitative, real-time prospective data for the health-related effects resulting from the enactment of legislation further criminalising same-sex practices. The negative effects of HIV treatment and care in MSM reinforce the unintended consequences of such legislation on global goals of HIV eradication. Strategies to reach MSM less likely to engage in HIV testing and care in highly stigmatised environments are needed to reduce time to HIV diagnosis and treatment. Funding National Institutes of Health.
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