Yasutoshi Kido

Background: When laboratory testing is constrained, suspected-case definitions guide mpox triage, isolation, contact tracing, and surveillance. In clade Ia-endemic settings, children and adults may differ in exposure context, clinical presentation, and the diagnostic value of syndromic features. Methods: We prospectively enrolled patients meeting the national case definition of suspected mpox in Équateur province, Democratic Republic of the Congo. We collected standardized epidemiological and clinical data. Multivariable logistic regression analyses adjusted for age, sex, and residence were used to assess associations, age-by-feature interactions, and age-specific likelihood ratios. Findings: Of 151 suspected cases, 90 (60%) were PCR-positive; all cases were classified as clade Ia MPXV. PCR-positive participants were older than PCR-negative participants (median, 24·5 years [IQR,15·0 – 32·0 years] vs 9·00 years [IQR, 2·00 –20·0 years]), and positivity increased with age. Contact with a suspected case was strongly associated with PCR-confirmed mpox (adjusted OR, 13·8; 95% CI, 4·02–58·5), whereas wild animal contact appeared more relevant in younger patients. Contact history and genital or inguinal manifestations became more informative diagnostically with age; ocular, musculoskeletal, and palmoplantar features were relatively more informative in younger patients. Interpretation: The diagnostic relevance of epidemiological and clinical features varied substantially across age groups. In this clade Ia-endemic setting, age-informed interpretation of suspected mpox cases may improve triage, prioritisation of laboratory testing, and surveillance where diagnostic resources are limited.

Messenger RNA (mRNA) vaccines effectively induce protective immunity, but antigen-specific CD8+ T cell responses exhibit limited persistence. In this study, we aimed to assess CD8+ T cell responses following a third dose of the Pfizer BNT162b2 COVID-19 vaccine and identify factors contributing to their longevity. Using HLA tetramers, we analyzed antigen-specific CD8+ T cells in 141 vaccinated individuals (86.5% female) and identified 2 groups: those with strong responses (strong group) and those with weak responses (weak group) 6 mo after the third mRNA vaccination. Transcriptomic analysis revealed that Notch signaling was upregulated in the strong group, and in vitro, the inhibition of Notch signaling significantly reduced CD8+ T cell expansion. These findings suggest that Notch signaling may contribute to maintain long-term antigen-specific CD8+ T cell responses following mRNA vaccination. Targeting this pathway could offer novel strategies for enhancing vaccine-induced cellular immunity and long-lasting protection.

Background: Despite global elimination targets set for 2030, Hepatitis B virus (HBV) infection remains a major public health challenge in low-income countries, including the Democratic Republic of Congo (DRC). Limited evidence on the regional transmission pathways precludes progress towards HBV elimination. This study aimed to assess the prevalence, molecular characteristics, and transmission dynamics of HBV in the Lukelenge health district, a peri-urban area in central DRC. Methods: We employed a two-tiered recruitment strategy: community member volunteers were enrolled during the first phase, and upon notification of HBV positivity in an index case, family contacts were subsequently recruited in the second phase. Participants were screened for hepatitis B surface antigen (HBsAg), followed by PCR amplification of HBV DNA and sequencing. Genotyping and phylogenetic analysis of preS/S sequences were performed to explore regional HBV diversity and transmission patterns. Results: A total of 751 participants from 677 households were included. The overall HBsAg prevalence was 3.8% [95% CI 2.6–5.7], with the highest rate (10.1% [95% CI 4.9–18.2]) found in children aged 5 years and younger. All 42 HBV isolates belonged to genotype E, with 97.6% sharing the ayw4 serotype. Mutations with relevancy to immune escape were detected in 9.5% of strains, while those possibly linked to antiviral resistance were found in 4.7%. Maximum likelihood phylogenetic analysis showed intra-familial clustering of preS/S sequences, suggesting that parent-to-child transmission was the most frequent mode of HBV spread in the study population. Conclusions: HBV in Lukelenge shows intermediate endemicity, especially affecting young children. Intra-familial transmission is revealed to be predominant, likely involving both vertical and horizontal pathways. Family-targeted interventions, including maternal screening and universal birth-dose vaccination, should be prioritized to eliminate HBV in this region.

Choice of immunoassay influences population seroprevalence estimates. Post hoc adjustments for assay performance could improve comparability of estimates across studies and enable pooled analyses. We assessed post hoc adjustment methods using data from 2021 to 2023 SARS-CoV-2 serosurveillance studies in Alberta, Canada: one that tested 124 008 blood donations using Roche immunoassays (SARS-CoV-2 nucleocapsid total antibody and anti–SARS-CoV-2 S) and another that tested 214 780 patient samples using Abbott immunoassays (SARS-CoV-2 IgG and anti–SARS-CoV-2 S). Comparing datasets, seropositivity for antibodies against nucleocapsid (anti-N) diverged after May 2022 due to differential loss of sensitivity as a function of time since infection. The commonly used Rogan-Gladen adjustment did not reduce this divergence. Regression-based adjustments using the assays’ semiquantitative results produced more similar estimates of anti-N seroprevalence and rolling incidence proportion (proportion of individuals infected in recent months). Seropositivity for antibodies targeting SARS-CoV-2 spike protein was similar without adjustment, and concordance was not improved when applying an alternative, functional threshold. These findings suggest that assay performance substantially impacted population inferences from SARS-CoV-2 serosurveillance studies in the Omicron period. Unlike methods that ignore time-varying assay sensitivity, regression-based methods using the semiquantitative assay resulted in increased concordance in estimated anti-N seropositivity and rolling incidence between cohorts using different assays.

Background: Current influenza A vaccines primarily induce neutralizing antibodies targeting the variable hemagglutinin (HA) head domain, limiting their effectiveness against diverse or emerging influenza A virus (IAV) subtypes. The conserved HA stem domain, particularly the long α-helix (LAH) epitope, is a focus of universal vaccine research due to its cross-protective potential. Additionally, Fc-mediated functions such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) are recognized as important protective immune mechanisms. This study evaluated IgG responses to the HA head, stem, and LAH regions and assessed cross-reactive potential through neutralization, ADCC, and ADCP assays. Methods: IgG responses to the HA head, stem, and LAH regions were measured in vaccinated individuals. Functional assays were conducted for neutralization, ADCC, and ADCP to evaluate the association between antibody levels and immune function. Results: The results showed that HA head-specific IgG increased significantly after vaccination in 50 individuals, whereas stem-specific IgG increased by 72% and LAH-specific IgG by 12–14%. Among the induced antibody subclasses, IgG1 was predominantly increased. Neutralization titers were detected in viruses of the same strain as the vaccine strain, but not in classical or pandemic strains (H5N1, H7N9). HA stem-specific IgG1 antibody titers showed a significant correlation with ADCC/ADCP activity breadth, but no correlation was observed with neutralization breadth. Conclusions: These findings suggest that although current influenza vaccines can induce HA stem-targeted cross-reactive antibodies, their quantity may be insufficient for broad cross-protection, underscoring the need for improved vaccine strategies.

Chagas disease is one of the most critical of the neglected tropical diseases in Latin America where it poses a serious public health issue. However, the current burden of vectorial transmission from natural reservoirs to humans is unclear. This study aimed to clarify the active mode of transmission to humans disentangled from the feeding pattern of Triatoma dimidiata (T. dimidiata) infected by Trypanosoma cruzi (T. cruzi). A total of 1,376 T. dimidiata specimens were collected across the 14 departments of El Salvador. From these specimens, 135 midgut samples from 37 households in eight departments were positive for T. cruzi (n = 135/1,376; 9.8% [95% confidential interval (CI): 8.35%-11.5%]). Using a universal vertebrate primer, vertebrate blood sources were positively identified by next-generation sequence analysis of deoxyribonucleic acid (DNA) extracted from the midgut contents of T. dimidiata. A total of 13 vertebrates were detected as blood sources; humans, and five domestic, three synanthropic, and four sylvatic species. Triatomines identified as having fed on human blood accounted for approximately 67% (n = 90/135 [95% CI: 58.3%-74.1%]) of the samples analyzed. In this study, a holistic understanding of the feeding patterns of T. cruzi-positive T. dimidiata in El Salvador is dated. The detection of human DNA in the midgut contents of T. dimidiata indicated the possibility of active vectorial transmission to humans.