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Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Science Advances, Volume 8, Issue 47, November 2022.

Science Advances, Volume 8, Issue 47, November 2022.

Science Advances, Volume 8, Issue 47, November 2022.

Science Advances, Volume 8, Issue 47, November 2022.

Science Advances, Volume 8, Issue 47, November 2022.

Science Advances, Volume 8, Issue 47, November 2022.

Science Advances, Volume 8, Issue 47, November 2022.

Science Advances, Volume 8, Issue 47, November 2022.

Science Advances, Volume 8, Issue 47, November 2022.

Chlamydia trachomatis causes the most common bacterial sexually transmitted disease worldwide. It is also the causative agent of blinding trachoma, which is the leading cause of preventable blindness. For genital infections, 70–80% of infections in women and 40–50% in men are asymptomatic, which means that these infections regularly go unnoticed and untreated. Both untreated and repeat infections increase the risk of developing chronic sequelae, which disproportionately impact women between the ages of 15 and 24.

Genomic epidemiology has guided research and policy for various viral pathogens and there has been a parallel effort towards using genomic epidemiology to combat diseases that are caused by eukaryotic pathogens, such as the malaria parasite. However, the central concept of viral genomic epidemiology, namely that of measurably mutating pathogens, does not apply easily to sexually recombining parasites. Here we introduce the related but different concept of measurably recombining malaria parasites to promote convergence around a unifying theoretical framework for malaria genomic epidemiology.

AbstractBackgroundUnderstanding the immunity against omicron infection and severe outcomes conferred by Covid-19 vaccination, prior SARS-CoV-2 infection, and monoclonal antibody therapy will inform intervention strategies.MethodsWe considered 295,691 patients who were tested for SARS-CoV-2 at Cleveland Clinic between October 1, 2021 and January 31, 2022. We used logistic regression to investigate the association of vaccination and prior infection with the risk of SARS-CoV-2 infection and used Cox regression to investigate the association of vaccination, prior infection and monoclonal antibody therapy with the risks of intensive care unit (ICU) stay and death.ResultsVaccination and prior infection were less effective against omicron than delta infection but provided strong protection against ICU admission and death. Boosting greatly increased vaccine effectiveness against omicron infection and severe outcomes, though the effectiveness waned rapidly over time. Monoclonal antibody therapy considerably reduced the risks of ICU admission and death. Finally, the relatively low mortality of the omicron variant was due to both the reduced lethality of this variant and the increased population immunity acquired from booster vaccination and previous infection.ConclusionsBooster vaccination and prior SARS-CoV-2 infection provide strong protection against ICU admission and death from omicron infection. Monoclonal antibody therapy is also beneficial.

AbstractBackgroundWe assessed COVID-19 vaccination impact on illness severity among adults hospitalized with COVID-19 August 2021–March 2022.MethodsWe evaluated differences in intensive care unit (ICU) admission, in-hospital death, and length of stay among vaccinated (2 or 3 mRNA vaccine doses) versus unvaccinated patients aged ≥18 years hospitalized for ≥24 hours with COVID-19-like illness (CLI) and positive SARS-CoV-2 molecular testing. We calculated odds ratios for ICU admission and death and subdistribution hazard ratios (SHR) for time to hospital discharge adjusted for age, geographic region, calendar time, and local virus circulation.ResultsWe included 27,149 SARS-CoV-2 positive hospitalizations. During both Delta and Omicron-predominant periods, protection against ICU admission was strongest among 3-dose vaccinees compared with unvaccinated patients (Delta OR [CI]: 0.52 [0.28–0.96]); Omicron OR [CI]: 0.69 [0.54–0.87]). During both periods, risk of in-hospital of death was lower among vaccinated compared with unvaccinated but ORs were overlapping; during Omicron, lowest among 3-dose vaccinees (OR [CI] 0.39 [0.28–0.54]). We observed SHR >1 across all vaccination strata in both periods indicating faster discharge for vaccinated patients.ConclusionsCOVID-19 vaccination was associated with lower rates of ICU admission and in-hospital death in both Delta and Omicron periods compared with being unvaccinated.

AbstractBackgroundHigh-level BK polyomavirus (BKPyV) replication in allogeneic hematopoietic cell transplantation (HCT) predicts failing immune control and BKPyV-associated hemorrhagic cystitis (BKPyV-HC).MethodsTo identify molecular markers of BKPyV-replication and disease, we scrutinized BKPyV-DNA loads in longitudinal urine and plasma pairs from 20 HCT-patients using quantitative nucleic-acid-testing (QNAT), DNase-I treatment prior to QNAT, next-generation-sequencing (NGS) and tested cell-mediated immunity.ResultsWe found that larger QNAT amplicons led to under-quantification and false-negatives results (p < 0.001). DNase-I reduced urine and plasma BKPyV-loads by >90% (p < 0.001) indicating non-encapsidated BKPyV-genomes. DNase-resistant urine BKPyV-loads remained infectious in cell culture. BKPyV-genome fragmentation of ≤250 bp impaired NGS-coverage of genetic variation using 1000 bp and 5000 bp targets. Conversely, 250bp-amplicons captured viral minority variants. We identified genotype-specific and genotype-independent changes in capsid-Vp1 or large T-antigen predicted to escape from antibody neutralization or HLA-presentation to CD8 T-cells, respectively. Genotype-specific changes in immunodominant 9mers were associated with reduced or absent CD8 T-cell responses. Thus, failure to control BKPyV-replication in HCT-patients may involve insufficient genotype-specific cytotoxic CD8 T-cell responses potentially predictable by low neutralizing antibodies as well as genotype-independent immune escape of variants.ConclusionOur results provide new insights for patient evaluation and for designing immune protection through neutralizing antibodies, adoptive T-cell therapy or vaccines.

Abstract Background Epidemiology of febrile illness in Uganda is shifting due to increased HIV treatment access, emerging viruses, and increased surveillance. We investigated the aetiology and outcomes of acute febrile illness in adults presenting to hospital using a standardized testing algorithm of available assays in at Arua and Mubende tertiary care hospitals in Uganda. Methods We recruited adults with a ≥ 38.0 °C temperature or history of fever within 48 h of presentation from August 2019 to August 2020. Medical history, demographics, and vital signs were recorded. Testing performed included a complete blood count, renal and liver function, malaria smears, blood culture, and human immunodeficiency virus (HIV). When HIV positive, testing included cryptococcal antigen, CD4 count, and urine lateral flow lipoarabinomannan assay for tuberculosis. Participants were followed during hospitalization and at a 1-month visit. A Cox proportional hazard regression was performed to evaluate for baseline clinical features and risk of death. Results Of 132 participants, the median age was 33.5 years (IQR 24 to 46) and 58.3% (n = 77) were female. Overall, 73 (55.3%) of 132 had a positive microbiologic result. Among those living with HIV, 31 (68.9%) of 45 had at least one positive assay; 16 (35.6%) had malaria, 14 (31.1%) tuberculosis, and 4 (8.9%) cryptococcal antigenemia. The majority (65.9%) were HIV-negative; 42 (48.3%) of 87 had at least one diagnostic assay positive; 24 (27.6%) had positive malaria smears and 1 was Xpert MTB/RIF Ultra positive. Overall, 16 (12.1%) of 132 died; 9 (56.3%) of 16 were HIV-negative, 6 died after discharge. High respiratory rate (≥ 22 breaths per minute) (hazard ratio [HR] 8.05; 95% CI 1.81 to 35.69) and low (i.e., < 92%) oxygen saturation (HR 4.33; 95% CI 1.38 to 13.61) were identified to be associated with increased risk of death. Conclusion In those with hospitalized fever, malaria and tuberculosis were common causes of febrile illness, but most deaths were non-malarial, and most HIV-negative participants did not have a positive diagnostic result. Those with respiratory failure had a high risk of death. …

Abstract Background Human brucellosis has become one of the major public health problems in China, and increases atypical manifestations, such as fever of unknown origin (FUO), and misdiagnosis rates has complicated the diagnosis of brucellosis. To date, no relevant study on the relationship between brucellosis and FUO has been conducted. Methods We retrospectively reviewed the medical charts of 35 patients with confirmed human brucellosis and prospectively recorded their outcomes by telephone interview. The patients were admitted to the Second Affiliated Hospital of Nanchang University between January 01, 2013 and October 31, 2019. Patient data were collected from hospital medical records. Results The percentage of males was significantly higher than that of female in FUO (78.95% vs. 21.05%, P < 0.05), and 80% of the patients had a clear history of exposure to cattle and sheep. Moreover, 19 (54%) cases were hospitalized with FUO, among which the patients with epidemiological histories were significantly more than those without (P < 0.05). The incidence of toxic hepatitis in FUO patients was higher than that in non-FUO patients (89% vs. 50%, P < 0.05). Meanwhile, the misdiagnosis rate was considerably higher in the FUO group than in the non-FUO group (100% vs. 63%; P < 0.05). Conclusion Brucellosis is predominantly FUO admission in a non-endemic area of China, accompanied by irregular fever and toxic hepatitis. Careful examination of the epidemiological history and timely improvement of blood and bone marrow cultures can facilitate early diagnosis and prevent misdiagnosis. …

Acute vibriosis led to serious adverse events in more than one third of patients with underlying conditions.…

The neglected zoonosis cystic echinococcosis affects mainly pastoral and rural communities in both low-income and upper-middle-income countries. In Europe, it should be regarded as an orphan and rare disease. Although human cystic echinococcosis is a notifiable parasitic infectious disease in most European countries, in practice it is largely under-reported by national health systems. To fill this gap, we extracted data on the number, incidence, and trend of human cases in Europe through a systematic review approach, using both the scientific and grey literature and accounting for the period of publication from 1997 to 2021.

The omicron variant (B.1.1.529) of severe acute respiratory virus 2 (SARS-CoV-2) was first identified in November 2021 (Viana et al., 2022) and has dramatically increased the transmission of Coronavirus disease 2019 (COVID-19) globally. The COVID-19 vaccine protects against serious disease, hospitalization, and death. However, vaccination does not entirely prevent infection and transmission to others. Massive two-dose vaccination campaigns cannot prevent breakthrough infections caused by the variants (Cele et al., 2022, Kuhlmann et al., 2022).

: The aim of this study was to explore whether indoor or outdoor relative humidity (RH) modulates the influenza epidemics transmission in temperate and subtropical climates.

Fungal infections of the CNS present a variety of clinical syndromes, such as meningitis; encephalitis; raised intracranial pressure (ICP) with a nonspecific presentation, and, in the last two decades, have increased the incidence of these infections (Góralska et al., 2020). They are characterized by recurrent headaches, changes in mental faculties, focal neurological deficits, and deterioration in the level of consciousness (Góralska et al., 2020). It is important to highlight that the expansion of immunosuppression conditions, as HIV/AIDS, among others, constitutes a host condition that can influence the severity of a disease (Khanna et al., 2016), however, fungi has also emerged as causal agents of infection in immunocompetent hosts (Sharma and Jakati, 2020).

Journal of Medical Virology, Accepted Article.

C. Phillip Miller, M.D., Chicago…

The first-in-human study of intranasal COVID-19 vaccination with an adenovirus-vector vaccine did not induce a consistent mucosal antibody response or a strong systemic response.

A shorter course of oral doxycycline is effective in treating erythema migrans, the most frequent manifestation of early Lyme borreliosis, and can reduce harmful antibiotic use, trialists recently reported.

In a new Vital Signs report, the CDC is calling for collaborations with trusted organizations serving American Indian or Alaska Native, Black, and Hispanic communities and culturally appropriate vaccination campaigns to reverse disparities in flu hospitalizations.

Three-quarters of US adolescents reported at least 1 adverse experience, such as abuse, neglect, witnessing violence, or having a family member attempt or die by suicide during the COVID-19 pandemic, according to a CDC report. Youths reporting multiple adverse childhood experiences, or ACEs, were substantially more likely to report poor current mental health or a past-year suicide attempt than those without these experiences.

This study examines adverse events and durability of response of SER-109, an investigational microbiome therapeutic comprised of purified Firmicutes spores, compared with placebo for Clostridioides difficile infection.

This study uses electronic medical record data to describe monkeypox infections after a single dose of Modified Vaccinia Ankara-Bavarian Nordic vaccine, a live, nonreplicating vaccine indicated for prevention of smallpox and monkeypox infection in adults.

Microbiology and Molecular Biology Reviews, Ahead of Print.

AbstractBackgroundWe report primary results of a phase 3 trial of AZD7442 (tixagevimab/cilgavimab) for post-exposure prophylaxis to prevent symptomatic coronavirus disease 2019 (COVID-19)MethodsAdults without prior SARS-CoV-2 infection or COVID-19 vaccination were enrolled within 8 days of exposure to a SARS-CoV-2–infected individual and randomized 2:1 to a single 300-mg AZD7442 dose (one 1.5-mL intramuscular injection each of tixagevimab and cilgavimab consecutively) or placebo. Primary endpoints were safety and first post-dose SARS-CoV-2 reverse-transcription–polymerase-chain-reaction (RT-PCR)–positive symptomatic COVID-19 event before day 183.Results1121 participants were randomized and dosed (mean age 46 years; 49% females; AZD7442, n=749; placebo, n=372). Median (range) follow-up was 49 (5–115) and 48 (20–113) days for AZD7442 and placebo, respectively. Adverse events occurred in 162/749 (21.6%) and 111/372 (29.8%) participants with AZD7442 and placebo, respectively, mostly mild/moderate. RT-PCR–positive symptomatic COVID-19 occurred in 23/749 (3.1%) and 17/372 (4.6%) AZD7442- and placebo-treated participants, respectively (relative risk reduction 33.3%; 95% confidence interval [CI] –25.9 to 64.7; P=.21). In predefined subgroup analyses of 1073 (96%) participants who were SARS-CoV-2 RT-PCR–negative (n=974 [87%]) or missing an RT-PCR result (n=99 [9%]) at baseline, AZD7442 reduced RT-PCR–positive symptomatic COVID-19 by 73.2% (95% CI 27.1 to 90.1) versus placebo.ConclusionsThis study did not meet the primary efficacy endpoint of post-exposure prevention of symptomatic COVID-19 with AZD7442 versus placebo. However, predefined analysis of participants who were SARS-CoV-2 RT-PCR–negative or missing an RT-PCR result at baseline support a role for AZD7442 in preventing symptomatic COVID-19.

ABSTRACTBackgroundHealthcare transition from pediatric to adult-oriented clinical settings is often viewed as a high-risk time for care disengagement. However, there is a paucity of prospective, longitudinal research documenting HIV care outcomes after HCT.MethodsWe conducted a prospective, observational cohort study of healthcare transition among youth enrolled at an HIV care center in Atlanta, Georgia. Pediatric clinic patients (average age 24 years) were enrolled up to three months prior to expected transition, and followed to determine linkage, retention, and viral suppression in adult care through electronic medical record abstractions at: baseline, 6-, 12-, 18- and 24-months.ResultsThe majority of our cohort (N = 70) was male (88.6%), Black (92.9%) and acquired HIV horizontally (80%). Most of our cohort was linked to adult care by 12 months (84%) after enrollment. Of those who linked to adult care by 12 months, retention rates were 86% (95% CI: 78-94%) at 6 months, 76% (95% CI: 66-86%) at 12 months, and 66% (95% CI: 55-78%) at 18- and 24-months. Once in adult care, the proportion with viral suppression was stable (73% at baseline, 74% at 6 months, 77% at 12 months, 67% at 18 months, and 78% at 24 months).ConclusionsAlthough most youth successfully linked to adult care, retention rates decreased over the 24-month follow up period. Rates of viral suppression were stable for those who remained in care. Strategies to support retention in adult care will be critical to optimizing transition for youth with HIV.

Journal of Medical Virology, Accepted Article.

Abstract Background Highly active anti-retroviral therapy (HAART) can successfully suppress human immunodeficiency virus (HIV) viral replication and reconstruct immune function reconstruction in HIV-1-infected patients. However, about 15–30% of HIV-1-infected patients still fail to recover their CD4+ T cell counts after HAART treatment, which means immune reconstruction failure. Pyroptosis plays an important role in the death of CD4+ T cells in HIV-1- infected patients. The study aims to explore the association between the expression of pyroptosis in peripheral blood and immune function reconstruction in HIV-1- infected patients. Methods One hundred thirty-five HIV-1-infected patients including immunological non-responders (INR) group, immunological responders (IR) group and normal immune function control (NC) group were analyzed. The expression of GSDMD and Caspase-1 in peripheral blood of HIV-1-infected patients were measured by qPCR. The concentrations of GSDMD, Caspase-1, IL-1β and IL-18 in the peripheral serum were quantified by ELISA. The associations between the expression of pyroptosis in peripheral blood and immune function reconstruction were analyzed using multivariate logistic models. Results The relative expression of GSDMD mRNA and caspase-1 mRNA in peripheral blood, as well as the expression of IL-18 cytokine in the INR, were significantly higher than those in the IR and NC (P < 0.05). There was no significant difference in the expression of IL-1β cytokine (P > 0.05). Multivariate logistic analysis showed that the patients with baseline CD4+ T cell counts less than 100 cells/μL (aOR 7.051, 95% CI 1.115–44.592, P = 0.038), high level of expression of Caspase-1mRNA (aOR 2.803, 95% CI 1.065–7.377, P = 0.037) and IL-18 cytokine (aOR 10.131, 95% CI 1.616–63.505, P = 0.013) had significant poor CD4+ T cell recovery. Conclusions The baseline CD4+ T cell counts less than 100 cells/μL, high relative expression of Caspase-1 mRNA, and high expression of IL-18 cytokine are associated factors that affect the reconstruction of immune function. …

Abstract Background The efficacy of non-carbapenems as an empirical antibiotic for extended-spectrum β-lactamases (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia in children remains controversial. We compared clinical and microbial outcomes according to the types of empirical antibiotics for treating pediatric patients with ESBL-producing E. coli and K. pneumoniae bacteremia. Methods Data from pediatric patients aged ≤ 18 years who were hospitalized with monomicrobial ESBL-producing E. coli or K. pneumoniae bacteremia at Asan Medical Center Children’s Hospital, Seoul, Korea between January 2014 and May 2019 were analyzed retrospectively. The impact of empirical therapy was assessed as 30-day all-cause mortality and 2-day microbiological outcomes evaluated by the sterility of blood cultures collected on day 2 after empirical antibiotic administration. Logistic regression analysis was used to control for the effects of confounding variables. Results A total of 53 patients with bacteremia caused by ESBL-producing E. coli (n = 29) and K. pneumoniae (n = 24) were included in this study; the median age was 3.6 years, and all had underlying comorbidities. As empirical antibiotics, 27 patients were treated with meropenem, and non-carbapenem agents were administered to 26 patients; 84.6% (22/26) were converted to carbapenem antibiotics as the definitive antibiotic by day 2 after empirical antibiotic administration. Overall, the 30-day all-cause mortality of ESBL-producing E. coli and K. pneumoniae bacteremia was 17.0% (9/53). After adjustment, there was no statistically significant association of use of a non-carbapenem agent as an empirical antibiotic with microbiological failure on day 2 and 30-day all-cause mortality [adjusted odds ratio (OR) 1.0; 95% confidence interval (CI) 0.22–4.88, and adjusted OR 0.1; 95% CI 0.01–1.56]. Conclusions The empirical use of non-carbapenems might not be a risk factor for mortality and early microbiological outcomes in pediatric patients with ESBL-producing E. coli and K. pneumoniae BSI if early transition to appropriate antimicrobial therapy was possible. …

To characterize the timing and genotype distribution of symptomatic and asymptomatic sapovirus infections and re-infections in a Nicaraguan birth cohort.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Infection and Immunity, Ahead of Print.

AbstractAsymptomatic blood donors can transmit human parvovirus B19 (B19V). We assessed the B19V prevalence amongst a large cohort of blood donations collected in Germany during 2015-2018. In total, 167,123 donations were screened for B19V DNA with 22 cases of viraemia identified (0.013% positive). Infections peaked at a four-year interval and the highest number of cases occurred in the summer months. All 22 infections were found in rhesus D-antigen positive donations, suggesting a protective factor in donors who lack this antigen. These findings contribute to our understanding of risk factors for B19V infection among central European blood and plasma donors.

AbstractVaccination against SARS-CoV-2 is an important prophylactic measure in kidney transplant recipients (KTRs), however, the immune response is often impaired. Here, we examined the T cell immune response against SARS-CoV-2 in 148 KTRs after three or four vaccine doses including 35 KTRs with subsequent SARS-CoV-2 infection. The frequency of spike-specific T cells was lower in KTRs compared to immunocompetent controls and correlated with the level of spike-specific antibodies. Positive predictors for detection of vaccine-induced T cells were detection of spike-specific antibodies, heterologous immunization with mRNA and a vector vaccine and longer time past transplant. In vaccinated KTRs with subsequent SARS-CoV-2 infection, the T-cell response was greatly enhanced and was significantly higher than in vaccinated KTRs without SARS-CoV-2 infection. Overall, the data show a correlation between impaired humoral and T-cell immunity to SARS-CoV-2 vaccination and provide evidence for greater robustness of hybrid immunity in KTRs.

AbstractWe assessed changes in sexual behaviour among people with HIV (PWH) over 20 years. Condom use with stable partners steadily declined from over 90% to 29% since the Swiss U = U statement with similar trajectories between men who have sex with men (MSM) and heterosexuals. Occasional partnership remained higher among MSM compared to heterosexuals even during COVID-19 social distancing.

AbstractBackgroundThough Modified Vaccinia Ankara - Bavarian Nordic (MVA-BN®). vaccination is approved for smallpox and monkeypox prevention, immunological persistence and booster effects remain undescribed.MethodsParticipants naïve to smallpox vaccination were randomized to 1 dose MVA-BN (1×MVA, N = 181), 2 doses MVA-BN (2×MVA, N = 183), or placebo (N = 181). Participants with previous smallpox vaccination received 1 MVA-BN booster (HSPX+, N = 200). Subsets of the formerly naïve groups (∼75 each) received an MVA-BN booster 2 years later.ResultsNeutralizing antibody (nAb) geometric mean titers (GMTs) increased from 1.1 (baseline, both naïve groups) to 7.2 and 7.5 (Week 4, 1×MVA and 2×MVA, respectively), and further to 45.6 (Week 6, 2×MVA after second vaccination). In HSPX+, nAb GMT rapidly increased from 21.6 (baseline) to 175.1 (Week 2). At 2 years, GMTs for 1×MVA, 2×MVA, and HSPX+ were 1.1, 1.3, and 10.3, respectively. After boosting in the previously naïve groups, nAb GMTs increased rapidly in 2 weeks to 80.7 (1×MVA) and 125.3 (2×MVA), higher than after primary vaccination and comparable to boosted HSPX+ subjects. Six months after boosting, GMTs were 25.6 (1×MVA) and 49.3 (2×MVA). No safety concerns were identified.ConclusionAnamnestic responses without sustained high nAb titers support presence of durable immunological memory following MVA-BN immunization.

AbstractBackgroundThe impact variant-specific immune evasion and waning protection have on declining COVID-19 vaccine effectiveness remains unclear. Using whole-genome-sequencing (WGS), we examined the contribution of these factors on the decline observed following the introduction of the Delta variant. Further, we evaluated the utility of calendar-period-based classification as an alternative to WGS.MethodsWe conducted a test-negative-case-control study among people who received SARS-CoV-2 RT-PCR testing in the Yale New Haven Health System between April 1 and August 24, 2021. Variant classification was performed using WGS and calendar-period.ResultsOverall, 2,029 cases (RT-PCR positive, sequenced samples [infections]) and 343,985 controls (negative RT-PCRs) were included. VE 14-89 days after 2nd dose was significantly higher against WGS-classified Alpha-infection (84.4%, CI: 75.6-90.0%) than Delta-infection (68.9%, CI: 58.0-77.1%, p-value = 0.013). The odds of WGS-classified Delta-infection were significantly higher 90-149 than 14-89 days after 2nd dose (p-value = 0.003). VE estimates against calendar-period-classified infections approximated estimates against WGS-classified infections, however, calendar-period-based classification was subject to outcome misclassification (35%: Alpha-period, 4%: Delta-period).ConclusionsBoth waning protection and variant-specific immune evasion contributed to the lower effectiveness. While VE estimates against calendar-period-classified infections mirrored those against WGS-classified infections, our analysis highlights the need for WGS when variants are co-circulating and misclassification is likely.