Open Forum Infectious Diseases最新文献

[This corrects the article DOI: 10.1093/ofid/ofaf018.].

[This corrects the article DOI: 10.1093/ofid/ofae762.].

Leptospirosis is a globally distributed zoonotic disease transmitted from animal reservoirs to humans. It is particularly common in tropical regions of Africa, Asia, and Central and South America during heavy rainfall when bacterial spirochetes are released from soil into areas of flooding. Despite causing >1 million severe cases, 58 900 deaths, and 2.9 million disability-adjusted life-years annually-exceeding established neglected tropical diseases-leptospirosis remains underrecognized as a neglected tropical disease. It affects occupational groups like farmers due to high prevalence in livestock and is spread by rodents in urban settings that have poor sanitation and infrastructure. Although effectively treated with inexpensive antibiotics, neglect of leptospirosis research and development has led to a lack of awareness and unavailability of preventive and diagnostic approaches. This review covers the geographic prevalence, disproportionate impacts on marginalized communities, and opportunities for improving social, economic, and healthcare burdens for patients with leptospirosis.

Background: The real-world vaccine effectiveness (VE) of the diphtheria, tetanus, and acellular pertussis (DTaP), DTaP-Haemophilus influenzae type b (Hib), and DTaP-inactivated polio (IPV)/Hib vaccines has not been thoroughly evaluated in China. Additionally, there are limited data on the VE of acellular pertussis-containing vaccines (aPVs) when used interchangeably.

Methods: We conducted a matched case-control study to estimate the VE of aPVs against polymerase chain reaction-confirmed pertussis infection in Lu'an in 2024. A conditional logistic regression model was used to compare the odds ratios (ORs) of vaccination between cases and controls. VE was calculated as [(1 - adjusted OR) × 100%], and 95% confidence intervals (CIs) were computed around the estimates.

Results: A total of 1936 children aged 3 months to 16 years were included in the study. The overall VE was 77.3% (95% CI, 35.2%-92.1%). The VE for fully vaccinated children was 88.4% (95% CI, 57.3%-96.8%), while the VE for partially vaccinated children was 77.4% (95% CI, 35.5%-92.1%). The VE of DTaP, DTaP-Hib, and DTaP-IPV/Hib was 75.8% (95% CI, 29.7%-91.7%), 83.2% (95% CI, 47.8%-94.6%), and 79.8% (95% CI, 36.5%-93.6%), respectively. Compared with mixed vaccination (65.3%.), the incremental VE of DTaP, DTaP-Hib, and DTaP-IPV/Hib was 31.0% (95% CI, 1.0%-51.9%), 52.9% (95% CI, 19.1%-72.6%), and 41.1% (95% CI, -18.7% to 71.8%), respectively. We observed a decline in VE over time, decreasing from 76.5% (95% CI, 33.0%-91.7%) within the first 2 years to -5.5% (95% CI, -495.2% to 81.3%) after 6 years or more.

Conclusions: All aPVs provide significant protection against pertussis infection, although this protection wanes over time. The VE appears to decrease materially if these vaccines are administered alternately in an individual's routine immunization schedule.

Mycobacterium bovis bacillus Calmette-Guérin (BCG) infection following intravesical BCG instillation is a rare complication of therapy that is associated with significant morbidity and mortality. We conducted a multicenter retrospective review of microbiologically confirmed M.bovis BCG infections in Western Australia over 22 years. Thirty-three patients were included in our study. All patients were male with a median age of 72 years. Localized infections accounted for 22/33 cases while disseminated infections accounted for 11/33 cases. The majority (n = 21) of positive isolates were cultured from urine specimens, followed by tissue and blood. The median time between first BCG instillation and infection was 7.5 months (95% CI, 3.5-11.5). The median duration of antimycobacterial therapy for localized infections was 6 months (95% CI, 4.1-7.9) as compared with 9 months (95% CI, 7.9-10.1) for disseminated infections (P = .039). The attributed mortality was 14.3%. M.bovis BCG infections have diverse clinical presentations and clinicians must have a high index of suspicion when assessing patients with a history of intravesical BCG instillation.

Background: The underlying cause of fever of unknown origin (FUO) remains unidentified in up to 51% of cases despite systematic evaluation. Microbial cell-free DNA next-generation sequencing (mcfDNA-NGS) offers an agnostic, noninvasive approach to pathogen identification, but the utility and clinical impact of this assay in FUO remain unknown.

Methods: This retrospective cohort study evaluated adult patients referred for FUO evaluation at a tertiary medical center between November 2019 and November 2023. Patients underwent both standard microbiologic testing (ST) and mcfDNA-NGS. Diagnostic impact was assessed in 4 domains: new diagnoses, earlier time to diagnosis, avoidance of invasive procedures, and non-hypothesis-driven diagnoses. Logistic regression was used to identify predictors of positive mcfDNA-NGS testing.

Results: Among 176 patients, mcfDNA-NGS was positive in 44.3%, with 49% of these cases considered clinically significant. Infectious cause of FUO was identified in 39% of patients, noninfectious in 35%, and unknown in 26%. mcfDNA-NGS contributed to a positive diagnostic impact in 30% of cases, mainly by earlier diagnosis (16%) and potential for avoidance of invasive procedures (10%). Positive mcfDNA-NGS was significantly associated with higher Charlson comorbidity index score (odds ratio [OR], 1.22; P < .001) and white blood cell (WBC) count ≤4.5 × 10⁹ cells/L (OR, 8.61; P < .001). Conversely, FUO without localization was associated with a decreased likelihood of positive mcfNDA testing (OR, 0.18; P < .001).

Conclusions: mcfDNA-NGS effectively complements ST in diagnosing FUO, providing earlier detection and minimizing invasive testing. Clinical predictors such as high comorbidity and low WBC count may guide the optimal use of mcfDNA-NGS in FUO. Prospective evaluation of optimal timing and use of mcfDNA-NGS and cost-benefit analysis in FUO is needed.

Background: The immunogenicity of the 15-valent pneumococcal conjugate vaccine (PCV15) and PCV20 in older adults was approved on the basis of comparative data with PCV13, although their relative immunogenicity and safety in this population remain undetermined. A systematic review and meta-analysis were conducted to provide insights, addressing the lack of large-scale efficacy studies.

Methods: This analysis included phase 2 and 3 randomized controlled trials evaluating the immunogenicity of a single dose of PCV15 or PCV20 in older adults by opsonophagocytic assay geometric mean titer (GMT) response at 1 month postvaccination as compared with PCV13.

Results: In total, 8 trials were eligible. PCV15 demonstrated superior immunogenicity vs PCV13 among older adults (GMT ratio, 1.11; 95% CI, 1.02-1.20). In immunogenicity vs PCV13, PCV20 demonstrated noninferiority, exceeding 0.5 at 1 month postvaccination (GMT ratio, 0.84; 95% CI, .81-.87). The incidence of local and systemic reactions was higher in the PCV15 group as compared with the PCV13 group, with risk ratios of 1.23 (95% CI, 1.14-1.32) and 1.15 (95% CI, 1.02-1.29), respectively. PCV20 is well tolerated and exhibits a comparable rate of local and systemic reactions to PCV13.

Conclusions: These findings support the immunogenicity and safety of PCV15 and PCV20 for pneumococcal vaccination in older adults. Given its superior immune response, PCV15 may address the gaps left by PCV13. Despite higher antibody levels, the clinical effectiveness of these vaccines remains uncertain. Ongoing surveillances are essential to evaluate the impact of both vaccines on remaining vaccine-type pneumococcal disease.

Background: Pregnancy increases Mycobacterium tuberculosis (Mtb) reactivation risk and alters immune responses. We assessed Mtb-specific CD4+ T-cell responses in pregnant women with HIV (WLHIV) and without, including those receiving isoniazid preventive therapy (IPT).

Methods: We measured adaptive immune responses from 33 participants (HIV+ 21, HIV- 12) with positive interferon-gamma release assay during pregnancy (20-34 weeks' gestation), 6 weeks, and 12 months postpartum by intracellular cytokine staining. We measured overall responses using COMPASS and made comparisons by nonparametric analysis of variance.

Result: We observed diminished Mtb-specific CD4+ T-cell responses in WLHIV during pregnancy versus 12 months postpartum (COMPASS median functional score [FS] .009 vs 0.12, P = .03). WLHIV who received IPT (n = 8) during concurrent pregnancy had attenuated Mtb-specific CD4+ T-cell responses during pregnancy versus 12 months postpartum (median FS 8.3 × 10^-7 vs 0.13, P = .02), but WLHIV who did not receive IPT during pregnancy had similar responses in pregnancy and postpartum. Mtb-specific CD8+ FS was increased postpartum in all groups. We found preexisting Mtb-specific CD4+ T-cell responses in participants who converted interferon-gamma release assay tests postpartum (n = 10).

Conclusions: Pregnant WLHIV, especially those on IPT, showed reduced Mtb-specific CD4+ T-cell responses. Understanding the impact of pregnancy on Mtb-specific T-cell responses may improve diagnostic approaches.