Open Forum Infectious Diseases最新文献

Background: Understanding the extent of cross-protection conferred by the historic smallpox vaccination and the immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) after the 2022 global mpox outbreak is essential to inform current prevention strategies. In this study, we assessed the seropositivity and neutralizing capacities of the vaccinia virus (VACV)- and monkeypox virus (MPXV)-specific antibodies in 260 Taiwanese individuals.

Methods: We analyzed serum samples from 260 individuals in Taiwan, stratified by their birth year, before or after 1979, the year of smallpox vaccination cessation. ELISA and plaque reduction neutralization tests were conducted to assess VACV- and MPXV-specific antibody responses. Furthermore, we evaluated an additional cohort of MVA-BN vaccines (n = 9) before and after vaccination.

Results: Over 80% of individuals born before 1979 retained VACV-reactive antibodies, with 84% of this seropositive subgroup exhibiting neutralizing activity. We detected cross-reactive MPXV antibodies in 69% of individuals who were VACV-seropositive; however, only 65% had MPXV-neutralizing capacity, with titers significantly lower than those against VACV. MVA-BN vaccination enhanced VACV and MPXV antibody levels; however, MPXV-neutralizing titers remained low, particularly in individuals without prior smallpox immunization.

Conclusions: Historical smallpox vaccination induces long-lasting humoral immunity, and a correlation between VACV and MPXV antibody levels further suggests that it provides some degree of cross-protection against MPXV infection. MVA-BN boosted orthopoxvirus immunity; however, it may be limited in MPXV neutralization in vaccine-naïve populations. These findings offer useful insights for future mpox vaccination strategies and public health planning in regions with varying smallpox vaccination histories.

Background: Emerging evidence suggests that human cytomegalovirus (HCMV) infection is associated with tuberculosis (TB) disease. This study aimed to assess the relationship between the dynamics of HCMV markers and TB disease in people with human immunodeficiency virus (PWH).

Methods: In a case-control study nested within a Thai HIV cohort, stored samples from people with HIV who were diagnosed with TB disease after antiretroviral therapy (ART) (cases) and TB-negative controls matched 1:2 on ART duration. HCMV DNA, immunoglobulin M (IgM), and immunoglobulin G (IgG) were measured at 3 timepoints: (i) 6-24 months before TB diagnosis (pre-TB visit), (ii) at TB diagnosis (TB visit), and (iii) 6-24 months after TB diagnosis (post-TB visit).

Results: We enrolled 34 TB cases and 68 controls, the majority of whom were male (56% vs 60%). At the pre-TB visit, all participants were IgG seropositive, and there were no significant differences in the proportion with HCMV viremia or in HCMV IgM or IgG levels. At the TB diagnosis visit, the proportion of HCMV viremia was higher among TB cases compared with controls (34.5% vs 13.8%; P = .028). HCMV IgM geometric mean concentration (GMC) was higher in cases (0.17 vs 0.12 AU/mL; geometric mean ratio, 1.38 [95% confidence interval, 1.01-1.87]; P = .039). At the post-TB visit, HCMV viremia remained more frequent in cases (31.8% vs 4.5%; P = .006).

Conclusions: HCMV viremia and serology measured 6-24 months before TB diagnosis in cases did not differ from those in matched controls. At TB diagnosis, people with HIV with TB had higher proportion of HCMV viremia and higher GMC of HCMV IgM, possibly reflecting HCMV reactivation due to TB disease.

Background: Data on clinical characteristics and prognosis of chronic pulmonary aspergillosis (CPA) in resource-limited, high tuberculosis (TB) burden settings, especially in Brazil, remain scarce.

Methods: This multicenter retrospective study evaluated all CPA cases diagnosed between 2012 and 2018 across eight centers in Brazil, examining clinical presentation, diagnosis, treatment, mortality, and factors associated with death, including differences related to pulmonary TB. To identify independent predictors of mortality, we conducted multivariate Cox regression. One-year mortality was analyzed using Kaplan-Meier survival curves.

Results: A total of 191 CPA cases were diagnosed, with a median age of 50 years (IQR 40-59) and 62% were male. TB was the most frequent predisposing condition (n = 138, 72%). Most patients (80%) received antifungal therapy, primarily itraconazole (n = 140, 73%). Surgery was performed in 34% of cases. According to Kaplan-Meier analysis, the cumulative mortality at 12 months was 6%. Compared to survivors, nonsurvivors had significantly lower rates of TB (52% vs 77%, P = .019) and higher rates of malignancies (13% vs 3%, P = .033). In multivariate analysis, only TB was independently associated with lower mortality (HR 0.413, 95% CI: .179-.954, P = .038). The TB group showed more hemoptysis (P = .008) and greater radiological involvement, suggesting delayed diagnosis.

Conclusions: In Brazil, the mortality of CPA was lower compared with that reported in previous studies, particularly among patients with TB. In TB-endemic, resource-limited settings, overlapping clinical and radiological features may delay diagnosis and antifungal treatment.

Background: Nocardiosis primarily affects immunocompromised hosts and those with chronic pulmonary disease but can also occur in immunocompetent patients. Predictors of dissemination and its role in long-term mortality remain unclear.

Methods: We conducted a retrospective cohort study of adults with nocardiosis diagnosed from January 1, 2010 to December 31, 2023. Patients were categorized into 3 groups: immunocompromised, immunocompetent with chronic lung disease, and immunocompetent without chronic lung disease. We evaluated risk factors associated with dissemination at the time of diagnosis and predictors of 1-year mortality. Multivariable logistic regression identified risk factors for dissemination. Cox regression assessed predictors of 1-year mortality.

Results: Among 232 patients, 44 (19.0%) had disseminated infection and 36 (15.5%) died within 1-year. Dissemination was more common among patients who were immunocompromised (odds ratio ([OR] 6.26, 95% confidence interval [CI] 2.26-20.53) or immunocompetent without chronic lung disease (OR 5.09, 95% CI 1.75-17.15). Lymphopenia and infection with Nocardia farcinica were also independently associated with dissemination. Dissemination was not associated with mortality overall (hazard ratio [HR] 1.58, P = .222), though interaction analysis revealed that dissemination was significantly associated with 1-year mortality only in immunocompetent patients with chronic lung disease (HR 9.43, 95% CI 1.73-51.52).

Conclusions: Immunocompromised patients and those without chronic lung disease are at increased risk for disseminated nocardiosis. While dissemination alone is not predictive of 1-year mortality overall, it is directly associated with mortality among immunocompetent patients with chronic lung disease. These findings highlight the need for tailored prognostic assessment and management in this subgroup.

Background: The Pragmatic Assessment of Influenza Vaccine Effectiveness in the Department of Defense (PAIVED) study is a multicenter trial assessing influenza vaccine effectiveness with annual enrollment over 4 consecutive influenza seasons (2018/2019-2021/2022). Data from PAIVED provides an opportunity to evaluate influenza-like illness (ILI) in healthcare workers (HCWs) compared to non-HCWs.

Methods: Participants in the PAIVED study were recruited from September to January in each influenza season and received egg-based, cell-based, or recombinant influenza vaccine. If a participant reported an ILI, they submitted a nasal swab for pathogen detection and a symptom diary for 7 days. For this analysis, vaccine groups were pooled and multivariable regression models were performed.

Results: Among the 13 959 participants included in this analysis, 35% were HCWs. Healthcare workers were more likely to be female, white, and 25-44 years of age. In addition, HCWs were more likely to report ILIs than non-HCWs (24.1% vs 17.4%, P < .01), and this difference persisted in our multivariable model (RR 1.16 [95% CI 1.08, 1.24]). No statistically significant differences were observed between HCWs and non-HCWs in specific pathogen detection. In terms of ILI severity, HCWs reported 0.28 more days of missed work (95% CI 0.01, 0.55), 0.36 fewer days with fever (-0.60, -0.13), and, in general, reported less severe ILI symptoms in the FLU-PRO diaries.

Conclusions: Healthcare workers enrolled in PAIVED reported more ILIs during the study period than non-HCWs, despite all participants receiving influenza vaccination. Further work is needed to reduce the risk of ILIs in HCWs.

Clinical trials registration: A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED): NCT03734237, Study Details | A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD | ClinicalTrials.gov.

Reliable prognostic biomarkers remain an unmet need in dengue. We evaluated urinary neutrophil gelatinase-associated lipocalin and soluble urokinase plasminogen activator receptor for severe dengue prediction in the febrile phase. Urinary neutrophil gelatinase-associated lipocalin and soluble urokinase plasminogen activator receptor demonstrated areas under the receiver operating curve of 0.88 and 0.79, respectively, in discriminating against severe dengue. The noninvasive sampling offers practical advantages as risk stratification tools.

Background: Engagement in pre-exposure prophylaxis (PrEP) care and routine screening for HIV and sexually transmitted infections (STIs) is critical to realizing the full benefits of this HIV prevention strategy.

Methods: We enrolled a cohort of individuals seeking PrEP services in two clinics in Missouri, an Ending the HIV Epidemic priority state, from June 2014 to November 2021. We used electronic health record and survey data to explore outcomes in the 2 years following linkage to care using multistate methods. We assessed transitions between eight mutually exclusive care states differentiated by receipt of a prescription, lab coverage status, and retention. We describe outcomes in the population overall and distinct sociodemographic subgroups.

Results: A total of 470 individuals were included (90.3% male; median age 29 (IQR, 25-36); 52.9% White, non-Hispanic) and contributed 879.5 person-years of follow-up. One week following linkage to care, 86.8% (95% CI: 83.6-90.0) of participants had a PrEP prescription. At month 6, 35.2% (95% CI: 30.7-39.7) were in care but had a lapse in HIV/STI screening, at month 12, 48.3% (95% CI: 43.7-53.1) were disengaged from care. Of those who disengaged, 28.3% (95% CI: 23.9-32.7) were re-engaged 6 months later. Females and uninsured individuals were the most likely to disengage during the first year of follow-up.

Conclusions: Lapses in clinic visits and lab screening are common among PrEP users in Missouri and most who disengage do not return. Females, uninsured individuals, and other marginalized groups may be particularly susceptible to poor persistence suggesting targeted interventions are warranted.

We report an adolescent with perinatal HIV-1 infection treated from 1 month of age. Despite persistent viremia until age 4, he exhibited negative or weakly reactive serologies and no detectable intact proviruses at 11 and 18 years. This case questions current definitions of seroconversion, HIV persistence and remission in children.

Background: Oropouche virus (OROV), an arbovirus causing acute febrile illness, was mostly restricted to the Amazon basin until 2023, when a reassortant lineage spread across Latin America. Increasing numbers of cases have subsequently been reported in extra-Amazonian regions of Brazil. However, follow-up and detailed clinical description is limited. This study aimed to describe viral, clinical, and epidemiological characteristics of OROV cases in the Brazilian states of Rio de Janeiro and Minas Gerais.

Methods: This longitudinal study enrolled adults with OROV exposure. Clinical and laboratorial data were assessed, and serum, urine, and saliva samples were tested for OROV RNA and sequenced.

Results: From December 2024 to May 2025, 55 OROV cases were recruited (median age: 46, 65% female). The novel OROV reassortant was confirmed by RNA sequencing. The acute phase was characterized by headache (87%), malaise (87%), fever (82%), myalgia (75%), and rash (45%). Recurrence of symptoms occurred in one-third of participants, including malaise (53%), fever (41%), arthralgia (41%), and chills (41%), but without resurgence of viral load. Viral RNA in serum and saliva was primarily detected in the first week of disease, and beyond the third week in urine.

Conclusions: Cases appeared in clusters and rash was frequently observed. Symptoms returned after 1 week, indicating the importance of patient follow-up. Cases either lived near banana plantations or participated in recreational activities at waterfalls, raising concerns about ecotourism in the Atlantic Forest. Since OROV RNA was detectable in urine for a prolonged period, urine samples may be useful for diagnosis.

Background: Carriage of Neisseria lactamica (Nlac), a harmless nasopharyngeal commensal, correlates inversely with carriage of Neisseria meningitidis (Nmen), a common cause of meningitis and sepsis outbreaks in sub-Saharan Africa. Nasally administered lyophilized Nlac (LyoNlac) might interrupt carriage and transmission of Nmen in sub-Saharan settings without requirement of a cold chain, but whether LyoNlac can establish colonization is undetermined.

Methods: Healthy adult volunteers aged 18-45 years were inoculated intranasally with 10⁴-10⁷ colony forming units (CFU) of reconstituted, lyophilized Nlac strain Y92-1009 (LyoNlac) in 2 dose-ranging controlled human infection studies conducted in the United Kingdom and Mali. Safety was measured as a primary objective. Secondary objectives included the dose achieving ≥70% colonization rates for each setting, colonization kinetics, and serological responses. Both trials were registered with ClinicalTrials.gov (United Kingdom: NCT04135053, Mali: NCT04665791) and are complete.

Results: Intranasal inoculation with LyoNlac was well tolerated with no significant safety concerns. In the United Kingdom, 10⁵ CFU yielded 100% colonization (n = 10/10) while in Mali, 10⁷ CFU achieved 65% colonization (n = 13/20). An increase in Nlac- and Nmen-specific IgG from pre-challenge to day 28 post-challenge was observed in colonized participants-median fold-change [interquartile range] United Kingdom: Nlac 2.24 [1.37-4.24], Nmen 1.39 [1.20-3.70] and Mali: Nlac 1.31 [1.04-1.94], Nmen 1.32 [0.99-1.73]. No significant seroconversion occurred in non-colonized participants.

Conclusions: Intranasal inoculation with LyoNlac was safe and induced immunogenic nasopharyngeal colonization in healthy adults in the United Kingdom and Mali. Future clinical trials to determine whether LyoNlac reduces meningococcal carriage and transmission in the meningitis belt are warranted.