Journal of Infectious Diseases最新文献

Nipah virus (NiV) induces strong humoral immunity, but the durability of NiV-specific memory T cell responses remains unclear. We characterized cellular immunity approximately 25 years after infection in four survivors of the 1998 Malaysian outbreak. PBMCs were stimulated with overlapping peptide mini-pools spanning the NiV fusion (NiV-F) and attachment (NiV-G) glycoproteins, and responses were assessed using ELISpot and ICS. Durable cytokine-producing T cell responses were detected, with immunodominant epitopes in the NiV-G ectodomain. Survivors with neurological sequelae exhibited stronger T cell responses and cognitive impairment, highlighting persistent cellular immunity decades after infection with implications for vaccine development.

Syphilis is a sexually transmitted infection caused by Treponema pallidum, whose origin in Europe remains debated. Recent analysis of five ancient T. pallidum genomes from Central American surrounding Columbus's time revealed genetic diversity suggesting an emergence of syphilis in Europe, after the 16th century colonisation of the Americas. However, this study missed two pre-Columbian Mexican genomes, and paleopathological evidence of European treponematoses long before the 15th century. These discoveries challenge the notion of a single transatlantic introduction and point to a complex evolutionary history, marked by recombination events and genetic plasticity, suggesting a rhizomatic rather than linear model of evolution.

Background: Ghana introduced the Rotarix vaccine in April 2012 and switched to the Rotavac vaccine in January 2020. Evaluating the health impact of this change is essential for national policy and can inform decisions in other countries.

Methods: We applied a previously validated mathematical model of rotavirus transmission in Navrongo, Ghana, to quantify the health impact of switching from Rotarix to Rotavac among children under two. We first simulated the model from January 2007 to December 2019 using previously estimated model parameters from pre- and post-Rotarix surveillance data. We then refitted the model to data from January 2020 to March 2023 to estimate Rotavac vaccine effectiveness parameters. To assess overall vaccine effectiveness (OVE), we compared model simulations under the two vaccination scenarios (Rotarix and Rotavac) with a counterfactual scenario assuming no vaccination.

Results: The model accurately captured both the trend and seasonality of post-vaccination rotavirus cases, with a Spearman correlation of 0.70. Compared to the no-vaccination scenario, the estimated overall vaccine effectiveness (OVE) against moderate-to-severe rotavirus cases was 21.7% (95% prediction interval [PI]: 17.4%-26.1%) in children under 2 years in Navrongo. Annual OVE ranged from 8.4% (PI: 1.0-21.0%) to 63.5% (PI: 39.0-87.0%). Following the switch from Rotarix to Rotavac (2020-2023), we estimated a mean relative OVE of 37.1% (PI: 27.5-46.5%).

Conclusions: Our model offers a robust tool to support policymakers in Ghana and similar settings by evaluating current rotavirus vaccine effectiveness, guiding vaccine switching decisions, and informing introduction strategies in countries yet to adopt immunization.

Background: Severe bacterial infections (SBI) represent a major health issue worldwide. Many studies have explored patients' genetic predispositions to SBI, but most of them chose a candidate-gene design. Only few adopted a whole-exome sequencing (WES) approach. We aimed at reporting non-targeted WES studies describing genetic variants associated with SBI susceptibility in previously healthy patients without a known predisposition for infections.

Methods: We included studies using WES in previously healthy patients who suffered from SBI. We excluded studies about non-bacterial infections, or including patients with a known genetic or dysimmune disorders. We assessed certainty in the body of evidence and detected risk of bias. Studies were grouped according to the patients' infectious phenotype to present main common characteristics and compare results.

Results: Twelve studies were included, gathering 694 patients with WES data. They described genetic association with various infectious phenotypes, using heterogenous methods to prioritize genetic variants. This diversity led to the identification of different genes or pathways associated with infection susceptibility or severity, and supported WES use in SBI patients. WES was also a performant diagnostic tool. In this review, 42% of previously healthy SBI patients had putatively disease-causing variants in IEI genes.Discussion: Overall, included studies supported the use of WES as they successfully diagnosed inborn errors of immunity in SBI patients. Future studies should follow strict guidelines to correctly prioritize disease-causing variants. Because of the rarity of this disease, sample sizes are often limited. Collaboration between research teams should allow for large scale studies with robust statistical results.

Background: Receptive condomless anal sex (CAS) associates with elevated rectal inflammation and mucosal injury, increasing HIV acquisition risk. Although douching may amplify rectal inflammation and alter microbial communities, this has not been well characterized in sexual minority men (SMM).

Methods: Ninety-two SMM (median age, 34.6 years) who were HIV negative and reported receptive CAS provided rectal swabs during sexually transmitted infection (STI) clinic visits. Associations among rectal douching, rectal cytokine/chemokine levels, and microbial communities, evaluated via immunoassay and 16S rRNA gene sequencing, respectively, were assessed.

Results: When compared with nondouching SMM (n = 27), SMM who douched (n = 64) reported more receptive CAS partners and displayed elevations in rectal cytokine/chemokines linked to immune activation and inflammation. Lower microbial richness, evenness, and Shannon diversity in SMM who reported douching were observed. Significant associations were identified between microbial alpha diversity metrics and rectal chemokine/cytokine levels. Finally, significant correlations were observed between rectal cytokine/chemokine levels and individual microbial genera.

Conclusions: Among SMM engaging in receptive CAS, douching may identify those with amplified biobehavioral HIV and STI risk. Elucidating the mechanisms whereby douching dysregulates rectal immune function and alters rectal microbial communities could yield targets for biomedical approaches to optimize HIV/STI prevention in SMM during receptive CAS.

Background: Parasite importation remains a challenge to malaria elimination. The extent to which human travel contributes to sustained transmission in low-to-moderate burden areas of endemic African countries is poorly understood.

Methods: We conducted a 14-month longitudinal cohort study in Kamwezi subcounty, Southwest Uganda, an area targeted for malaria elimination. A total of 1,918 individuals from 400 households were followed bi-monthly. Travel histories and household characteristics were collected through structured surveys. Incident symptomatic and asymptomatic Plasmodium falciparum infections were captured through health facility surveillance and household reports (for symptomatic cases) and qPCR (for asymptomatic infections). Multilevel logistic regression models estimated associations between overnight travel and incident infection, adjusting for demographic and household factors. Population attributable fractions (PAF) quantified travel's contribution to malaria, stratified by transmission intensity, season, and village.

Results: Over the study period, 283 infections (244 symptomatic episodes and 39 asymptomatic infections) were recorded. Nearly one-third of participants reported at least one overnight trip. Associations between travel and malaria varied spatially and temporally, with positive associations in lower transmission villages OR = 4.38, 95% CI 1.80-10.64) and during periods of low transmission. Associations were strongest for short-distance trips to nearby areas of higher incidence. PAF analyses suggested travel accounted directly for 14% of malaria cases in low-transmission villages overall, rising to 30% during periods of low transmission.

Conclusion: Overnight travel contributed meaningfully to malaria burden, particularly in low-transmission villages and during low seasons. These findings highlight the need for surveillance and control strategies that address both local transmission and importation.

Background: Cytomegalovirus (CMV) reactivation occurs in the context of coronavirus disease 2019 (COVID-19); however, the viral kinetics, risk factors, and clinical outcomes are poorly defined.

Methods: We examined the association of CMV DNAemia with clinical outcomes among participants of a randomized trial of remdesivir with or without baricitinib (National Institute of Allergy and Infectious Diseases [NIAID], Adaptive COVID-19 Treatment Trial 2 [ACTT-2]). Plasma CMV DNAemia from CMV-seropositive participants with COVID-19 (NIAID ordinal scale [OS] 5, 6, or 7 at entry) were assessed longitudinally by quantitative polymerase chain reaction. Factors associated with CMV DNAemia, and clinical outcomes were analyzed by Cox regression and proportional odds models.

Results: Of 772 trial participants with available samples, 643 (83%) were CMV seropositive. Baseline CMV serostatus was not associated with COVID-19 outcomes. The cumulative incidence of CMV DNAemia among seropositive persons by day 28 was overall 11% (baseline OS 5, 6.3%; OS 6, 16.4%; OS 7, 24.7%), and was associated with older age, baseline OS, male sex, lymphopenia, and systemic corticosteroid use, while remdesivir and baricitinib did not affect risk. CMV DNAemia was associated with a lower probability of improvement by day 29 (adjusted hazard ratio, 0.3 [95% confidence interval, .17-.56]), with a more pronounced delay of recovery with higher CMV viral load. CMV DNAemia was also associated with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and death.

Conclusions: In hospitalized adults with COVID-19 requiring oxygen, CMV viremia occurs within well-defined clinical risks and is independently associated with delayed recovery from illness, higher SARS-CoV-2 viral load, and increased mortality.

Background: Human infection with Trypanosoma cruzi leads to Chagas disease, which induces profound changes in the immune response across different cell subsets, influencing parasite control and disease pathology. Dissecting the functional characteristics of distinct immune cells in patients with the asymptomatic (indeterminate, IND) or the cardiac (CCC) clinical forms is crucial for unveiling mechanisms of disease progression and pathology, and identifying disease markers.

Methods: Immune-gene targeted single-cell RNA sequencing was applied to peripheral blood mononuclear cells obtained from patients with IND and CCC to unravel the immune landscape in these polar, well-characterized, clinical groups.

Results: Our findings revealed different myeloid and lymphoid cell clusters in the cohorts, each exhibiting unique gene expression patterns. CCC was characterized by an increased frequency of KLRB1+CD4+, TBX21+CD8+ T cells, and NK cells, which exhibited upregulation of genes associated with cytotoxic and apoptotic responses. Furthermore, we observed monocyte, B-cell subsets, along with dendritic cells, expressing inflammatory and notably cytotoxic genes.

Conclusions: These results reveal cell-specific changes in patients with CCC compared to IND chronic Chagas disease, highlighted by distinct gene expression patterns. These nuanced changes indicate an immune signature linked to the clinical forms of chronic Chagas disease, which provide information regarding disease pathology, indicating potential markers related to the disease progression.