Objectives The Dual Path Platform (DPP) detects treponemal and lipoidal antibodies at the point of care, with an automated reader generating quantitative optical density (OD) values. We assessed the association between DPP OD and RPR titers and post-treatment DPP OD trajectories according to serological cure. Methods We conducted an observational study comprising cross-sectional and longitudinal analyses. The cross-sectional analysis assessed the association between DPP OD and RPR titers in anonymized serum samples. The longitudinal analysis assessed post-treatment changes in DPP OD according to RPR-based serological cure. Results The cross-sectional analysis included 1,222 samples. DPP OD increased with RPR titer, with a quadratic model showing attenuation of the increase at higher titers. Differences between consecutive RPR categories were significant through 1:64 but not at higher titers, with substantial overlap between categories. The longitudinal analysis included 118 participants. Mean DPP OD declined from 89.1 at baseline to 32.4 at week 12, 20.8 at week 24, and 17.0 at week 48. DPP OD declined after treatment in cases with serological cure and increased during recurrent RPR increases. Conclusions DPP OD was quantitatively associated with RPR titer and longitudinal changes reflected RPR-based serological response, supporting further evaluation as a complementary approach for treatment monitoring.
Mutations in genes controlling IFN-γ production or signaling underlie Mendelian susceptibility to mycobacterial disease (MSMD) and predispose affected individuals to mycobacterial and other infections. Autosomal dominant (AD) mutations in exon VI of IFNGR1, which encodes interferon-γ receptor 1 (IFN-γR1), have been associated with multifocal osteomyelitis. We report a Mexican male patient whose clinical course began with severe BCGitis at 2 years of age, followed by tuberculous lymphadenitis at age 3, disseminated tuberculosis with hepatitis at age 10, and disseminated Mycobacterium bovis infection with vertebral osteomyelitis at age 19. Subsequent manifestations included HPV-associated warts at age 21, pneumonia and vertebral osteomyelitis associated with M. colombiense at age 25, mesenteric fibrosis, hepatic abscesses, vertebral osteomyelitis associated with M. avium at age 28, and pneumonia associated with M. fortuitum at age 30. The patient responded to prolonged antimycobacterial therapy. Functional studies demonstrated deficient IL-12p40 production following BCG plus IFN-γ stimulation, impaired Stat-1 phosphorylation in response to IFN-γ, and increased cell-surface expression of CD119/IFN-γR1. Sanger sequencing identified the heterozygous IFNGR1 c.805delT (p.Tyr269Ilefs*8) variant in the patient but not in his parents, consistent with a de novo event. This truncating variant leads to cell-surface accumulation of a defective IFN-γR1 and exerts a dominant-negative effect on IFN-γ signaling. This case, together with our literature review, supports an association between impaired IFN-γ signaling due to AD IFNGR1 variants and susceptibility to recurrent infectious osteomyelitis.
OBJECTIVE:This systematic review and meta-analysis aimed to evaluate the pooled performance of the VISITECT-CD4 Advanced Disease lateral-flow assay (VISITECT-CD4-LFA) for diagnosing advanced HIV disease (AHD). METHODS:A search was conducted in PubMed, EMBASE, Google Scholar, and Scopus up to February 2, 2026, to identify studies that evaluated VISITECT-CD4-LFA. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Meta-analysis was conducted using a bivariate random-effects model to estimate pooled sensitivity and specificity compared to flow cytometry. RESULTS:Ten studies were included, comprising 6962 people with HIV. Pooled sensitivity and specificity were 98% (95% CI: 94-99%) and 71% (95% CI: 56-85%), respectively, with an area under the curve (AUC) of 0.95. Subgroup analysis revealed that VISITECT-CD4-LFA from capillary blood had similar sensitivity (96%, 95% CI: 93-97%) to venous blood (99%, 95% CI: 93-100%). CONCLUSIONS:VISITECT-CD4-LFA meets the ≥90% sensitivity requirement specified in the target product profile (TPP) for point-of-care CD4 tests for AHD. With robust sensitivity using both venous and capillary blood, it has the potential to facilitate timely screening and prophylaxis for opportunistic infections in decentralized settings. The assay's pooled specificity fell slightly below the ≥80% TTP target. Further research is needed for South American and Asian populations, with strategies to boost specificity. PROSPERO REGISTRATION:CRD420251272180.
OBJECTIVES:Mortality remains a major barrier to tuberculosis (TB) control, as many deaths occur shortly after diagnosis. We aimed to identify determinants of mortality and develop diagnosis-time risk-prediction models for patients with TB. METHODS:We conducted a nationwide population-based cohort study using data from South Korea's public-private mix TB program, including patients diagnosed between January 2019 and December 2022. Two models were developed in the 2019-2021 cohort and validated in the independent 2022 cohort: TREAT-TB, incorporating demographic, clinical, radiologic, and microbiological variables, and SCREEN-TB, based only on demographic characteristics, symptoms, and comorbidity data. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), Brier score, and calibration analysis. RESULTS:Among 24,745 patients, 2,667 (10.8%) died during treatment. Nearly half of the deaths occurred within two months of diagnosis. Older age, lower body mass index, and organ-specific comorbidities, particularly cardiovascular, neurological, and renal diseases, were associated with mortality. TREAT-TB and SCREEN-TB showed similar discrimination and good calibration in the validation cohort (AUCs 0.807 and 0.805, respectively), with mortality increasing across risk scores. CONCLUSIONS:Diagnosis-time risk stratification is feasible without radiologic or microbiological results and may support early triage and targeted monitoring within TB control programs.
OBJECTIVE:The objective of our study was to evaluate the longitudinal humoral immune response following booster regimens in Malaysia during the Omicron outbreak. METHODS:In this prospective cohort study, 268 healthcare professionals and medical students in Malaysia were followed up for 24 weeks following homologous (mRNA-mRNA (mR-mR), viral vector-viral vector (VV-VV), inactivated virus-inactivated virus (IV-IV) and heterologous (inactivated virus-mRNA (IV-mR), viral vector-mRNA (VV-mR) booster vaccines. Of them, 190 recipients underwent longitudinal immunogenicity study. Anti-S IgG and anti-RBD response were assessed by ADVIA Centaur SARS-CoV-2 chemiluminescent immunoassay followed by surrogate virus neutralization test using Omicron-variant across all boosters. RESULTS:Compared to homologous boosters, heterologous regimens, particularly the IV-mR booster, elicited significantly higher and sustained anti-S IgG and anti-RBD antibody (P<0.0001) responses. Over 24 weeks, the heterologous IV-mR booster had 100% seropositive anti-S IgG and anti-RBD antibodies, conversely, in the homologous (IV-IV) booster, the seropositivity of anti-S IgG and anti-RBD antibody reduced to 15.63% and 18.75% respectively. Omicron-virus neutralizing activity was observed as high as 95.92% (IV-mR) and 83.87% (VV-mR) following W24 of the heterologous booster, while virus neutralization was found as low as 9.38% in the IV-IV homologous booster. Age, gender, and ethnicity were not found as confounding factors for antibody kinetics following booster vaccine. CONCLUSION:In conclusion, heterologous booster vaccines induced superior prolonged humoral-immune response against COVID-19 infection.
Objectives : The rifampicin and isoniazid (RIF-INH) testing provides simultaneous detection of RIF-INH resistance, yet its economic implications in Indonesia have not been evaluated. This study assessed the economic impact of implementing RIF-INH testing compared with rifampicin-only (RIF-only) testing. Methods : An economic evaluation was conducted using a decision-tree model simulating diagnostic and treatment pathways for 1,670,317 adults with presumptive pulmonary tuberculosis (TB). All TB subtypes were modeled through the first treatment cycle, capturing treatment success, treatment failure, death, and loss to follow-up (LTFU). The second cycle was limited to downstream consequences of isoniazid-resistant tuberculosis (Hr-TB) arising from the first cycle. Results : RIF-INH testing was projected to increase first-cycle direct medical costs by 8.1% while improving treatment success by 5.9%. Although first-cycle direct non-medical costs were 24.3% higher, second-cycle Hr-TB-related direct medical and non-medical costs were projected to be 57.3% and 61.0% lower, respectively, than with RIF-only testing. Probabilistic uncertainty analysis consistently showed lower downstream Hr-TB costs, whereas differences in first-cycle and total model costs remained uncertain. Conclusions : RIF-INH testing requires higher upfront costs but may reduce downstream Hr-TB-related costs. However, the overall total cost difference remains uncertain after accounting for parameter uncertainty.
OBJECTIVES:This study aimed to investigate scarlet fever epidemiology in Liaoning Province, China (2005-2024), and assess COVID-19 pandemic impacts. METHODS:Individual-level data on scarlet fever cases from the National Notifiable Infectious Disease Reporting System (NNIDRS) were analyzed for temporal, demographic and spatiotemporal features across pre-, peri- and post-pandemic stages. RESULTS:A total of 73,102 scarlet fever cases were reported. Incidence remained stable during the pre-pandemic period, from 2005 (8.9 per 100,000 population per year) to 2019 (10.8), sharply declined during the pandemic period (2020-2022; range: 1.4-0.6), and rebounded markedly post-pandemic (2023: 1.9; 2024: 7.7). Most cases (79.4%) occurred in children under 15 years of age from urban areas. During 2005-2019, incidence significantly increased among children aged 3-6 years (AAPC: 7.4%; 95% CI: 3.0%-11.9%) and in rural populations (AAPC: 4.3%; 95% CI: 1.1%-7.6%). Compared with the pre-pandemic period (2005-2019), the proportion of cases among children aged 7-14 years significantly increased during the post-pandemic period (2023-2024) (31.4% vs. 54.1%, p < 0.01). CONCLUSION:Scarlet fever incidence in Liaoning Province showed a resurgence after the pandemic, with an age distribution shifting toward older children. These evolving epidemiological patterns highlight the need for enhanced, age-targeted surveillance and adaptive prevention strategies.
Objectives : Cysteine proteases, the major components of excretory-secretory substances excreted from adult Paragonimus worms, are known as useful diagnostic antigens for human paragonimiasis. In this study, we develop immunochromatography-based kits to detect specific IgG and IgG4 antibodies against recombinant cysteine protease-6 (rCP-6), and to evaluate their diagnostic performance. Methods : The rCP-6 was expressed in Escherichia coli, affinity-purified, and evaluated for immunoreactivity. The rCP-6-based immunochromatographic kits were evaluated for detection of IgG and IgG4 using simulated whole-blood and serum samples from paragonimiasis patients, healthy individuals, and patients with other infectious diseases. The diagnostic performance was evaluated. Results : The IgG detection kit exhibited sensitivity of 76.7%, specificity of 90.5%, and accuracy of 87.3% for both simulated whole-blood and serum samples. In comparison, the IgG4 detection kit demonstrated higher performance, with 85.0% sensitivity, 100% specificity, and 96.5% accuracy across both sample types. Conclusions : Both IgG and IgG4 detection kits were useful for diagnosing paragonimiasis. The IgG4 detection kit showed superior diagnostic performance. These ICT tools possible be applying for diagnosing outpatients in clinical laboratories in paragonimiasis caused by different Paragonimus species (P. heterotremus, P. westermani, and P. skrjabini miyazakii).
OBJECTIVES:To assess microbiological concordance, antimicrobial susceptibility testing (AST) agreement, and associated clinical characteristics of suspected urosepsis episodes using paired urine (UC) and blood cultures (BC). METHODS:We retrospectively analyzed 2,572 paired UC-BC episodes from 2,302 adults at a tertiary-care laboratory (2018-2024). Episodes were considered concordant when UC and BC shared at least one identical pathogen. We compared pathogen spectra, culture dynamics, AST results, laboratory referral information, inflammatory markers, and survival. Multivariable logistic regression was used to identify factors associated with concordance. RESULTS:Of 2,572 episodes, 1,405 (54.6%) were concordant. UC reports were finalized earlier than BC reports, with 50.4% available within one day. Concordant episodes showed shorter BC time-to-positivity than discordant episodes (7.8h vs 14.1h). Documented clinical suspicion and detection of Escherichia coli or Staphylococcus aureus in UC were associated with concordance. Among concordant Enterobacterales episodes, UC AST showed high agreement with BC AST. In exploratory analyses, concordant episodes were associated with faster decline of inflammatory markers and better survival. CONCLUSIONS:In suspected urosepsis, UC frequently identified the same pathogen as BC while providing earlier microbiological and susceptibility information. These findings support the potential early diagnostic and antimicrobial stewardship value of UC while BC results remain pending.
OBJECTIVES:To compare 12-month serologic responses to three benzathine penicillin G (BPG)-based regimens among people with HIV (PWH) and early syphilis. METHODS:We retrospectively included syphilis episodes treated with BPG, BPG plus 7-day doxycycline (BPG/doxycycline), or BPG/doxycycline plus single-dose ceftriaxone during 2018-2024. Episodes with baseline rapid plasma reagin (RPR) titers <1:4 or exposure to other Treponema pallidum-active antibiotics were excluded. Serologic response was defined as a ≥4-fold RPR decline at 12 months. Intention-to-treat (ITT) with last-observation-carried-forward and per-protocol analyses were performed. RESULTS:Among 1,077 episodes in 762 PWH, 453 received BPG, 570 BPG/doxycycline, and 54 BPG/doxycycline/ceftriaxone. ITT response rates were 74.6%, 83.2%, and 88.9%, respectively (P < .001); per-protocol rates were 74.4%, 83.4%, and 89.8% (P < .001). Higher baseline RPR titers and doxycycline-containing regimens were independently associated with response. In analyses directly comparing BPG/doxycycline with and without ceftriaxone, adding ceftriaxone to BPG/doxycycline was not significantly associated with a higher serologic response. CONCLUSIONS:BPG/doxycycline was associated with a higher likelihood of 12-month serologic response. The incremental association of ceftriaxone remained uncertain because of the small number of ceftriaxone-treated episodes.
BACKGROUND:Pneumococcal surveillance remains challenging due to limited invasive disease surveillance and logistically demanding nasopharyngeal carriage studies, particularly in low- and middle-income countries (LMICs). We evaluated indoor air sampling as a non-invasive approach for monitoring pneumococcal circulation and serotype distribution. METHODS:Monthly indoor air samples were collected over 20 months (January 2022-September 2023) in a Belgian childcare center. Samples were analyzed by qPCR for pneumococcal detection and serotype identification. RESULTS:Pneumococci were detected in all samples. After excluding serotypes with known specificity issues, 15 serotypes/serogroups were identified, with a mean of seven per sample. Commonly detected serotypes largely matched those reported in Belgian carriage studies and invasive disease surveillance. CONCLUSIONS:Indoor air sampling captured signals of community pneumococcal circulation and serotype dynamics. With further validation, it could provide a scalable, affordable surveillance tool to support vaccine policy, monitor vaccine impact, and strengthen respiratory pathogen surveillance, particularly in LMICs.
Objective The current study aims to evaluate the diagnostic utility of enterovirus PCR testing on throat and rectal swab /stool samples, along with neuroimaging, in the diagnosis of pediatric enterovirus (EV) Central Nervous System (CNS) infections. Methods This prospective observational study recruited 380 children aged <12 years with suspected CNS infection and 50 age-matched controls with non-infectious neurological disorders. All the patients underwent enterovirus real-time PCR testing on CSF, throat, and rectal swab samples, alongside brain MRIs. The diagnostic accuracy was assessed using EV-positive cases as true positives and patients with confirmed non-enteroviral or non-infectious aetiologies as true negatives. MRI patterns were classified as typical or atypical based on brainstem involvement. Results Infectious agents could be detected in 123/380 (32.3%) cases, out of these 33 (8.7%) had infections attributed to enterovirus while 90 (23.7%) were labelled as non-enterovirus CNS infections. In 257 (67.6%), no infectious agent could be identified, hence they were excluded from further analysis. Among the samples used for enterovirus testing, rectal swab/stool samples showed highest sensitivity (90.32%) followed by throat swab samples (32.3%). CSF PCR showed the lowest sensitivity (11.1%). MRIs were available for 26/33 patients, with characteristic brainstem involvement observed across probable and possible cases. Conclusion Rectal swab/stool PCR, together with neuroimaging, may improve the diagnosis of pediatric EV CNS infections and identify cases missed by CSF PCR alone.
Background Baloxavir treatment is associated with reduced influenza transmission within households, and the serial interval varies by treatment status. However, it remains unclear how baloxavir-induced changes in the serial interval relate to household transmission. We aimed to quantify the model-based association between baloxavir treatment timing and the serial interval and household transmission risk. Methods We conducted a household survey of influenza cases in Japan between October 2018 and February 2019. We defined the likelihood-based model integrating the serial interval distribution by treatment status and the secondary attack rate (SAR) using individual-level data from index cases. Using this model, we estimated the reduction in the serial interval associated with baloxavir treatment. Results Compared with untreated index cases, baloxavir-treated cases were estimated to have a serial interval density reduced by 21.42% following treatment. Treatment within 24 hours was associated with a 0.1685 reduction in the area under the curve, with smaller reductions as treatment was delayed. Earlier treatment was associated with a shorter, more concentrated distribution, whereas treatment 72 hours after onset resembled untreated cases. Conclusions Our findings highlight that baloxavir treatment is associated with a shorter serial interval and lower estimated secondary household transmission risk. We provide model-based estimates suggesting that earlier administration is associated with a greater reduction in serial interval density and estimated transmission risk, which may inform public health strategies for infection control.
Background Antimicrobial resistance is driven by inappropriate antibiotic use, particularly self-medication. The 2023 Gaza War disrupted healthcare services, increasing resistant infections and reliance on self-treatment practices. Objectives To determine the prevalence of antibiotic self-medication and assess public awareness during the 2023 Gaza War. Methods A cross-sectional survey was conducted between May and October 2025 among adults residing in the Gaza Strip during the 2023 Gaza War. A multistage non-probability recruitment strategy, organized across predefined governorate and residential-setting strata, was used to recruit 422 participants from primary healthcare centers, community pharmacies, and displacement shelters. The questionnaire demonstrated good internal consistency (Cronbach’s α = 0.857). Ethical approval was obtained from the relevant institutional review board, and informed consent was secured from all participants. Results The overall KAP score was moderate (67.46%), with attitudes scoring highest (74.62%), followed by knowledge (66.23%) and practices (61.52%). Reported antibiotic self-medication increased from 60.4% before the war to 80.6% during the war (p < 0.001), with significant changes in reasons for self-medication and antibiotic procurement sources. The mean antimicrobial-resistance perception score was 82.19 ± 11.10%, and knowledge was strongly correlated with the total KAP score (r = 0.836, p < 0.001). Conclusions Reported antibiotic self-medication was markedly higher during the 2023 Gaza War despite moderate public awareness, highlighting the urgent need for education, antibiotic stewardship, and improved healthcare accessibility.
We report recurrent Plasmodium falciparum infection following standard artemether-lumefantrine treatment in a patient with metabolic comorbidities carrying mutant parasites presenting pfkelch13 and pfmdr1 variants, underscoring the need for genomic surveillance of antimalarial resistance and further investigation of host factors that may influence antimalarial drug exposure.
OBJECTIVES:Melioidosis, caused by Burkholderia pseudomallei, is increasingly recognised as a travel-associated infection, yet the extent of exposure among international travellers remains unknown. We aimed to determine B. pseudomallei seroprevalence among travellers to Southeast Asia and explore risk factors. METHODS:We conducted a cross-sectional study at the Hospital for Tropical Diseases, Bangkok, enrolling travellers aged ≥18 years from non-endemic regions who had spent ≥1 month in Southeast Asia. Sera were tested by indirect ELISA using two B. pseudomallei antigens, Hcp1 and O-polysaccharide (OPS). Predefined diagnostic and exposure serological thresholds were applied. Risk factors were assessed by logistic regression. RESULTS:Between August 2025 and January 2026, 370 travellers were enrolled. Overall, 49 (13.2%) were seropositive, including 25 (6.8%) with probable melioidosis and 24 (6.5%) with probable environmental exposure. Independent risk factors were female sex (aOR 2.49; 95% CI 1.06-5.83), North American origin (aOR 2.78; 1.17-6.59), and underlying medical conditions (aOR 3.28; 1.39-7.75). CONCLUSION:B. pseudomallei exposure among travellers to Southeast Asia is not rare, with one in eight seropositive. Inclusion of melioidosis in the differential diagnosis of febrile returning travellers, complemented by diagnostic approaches beyond culture alone, is needed to reduce misdiagnosis and preventable mortality.
Objective Type 2 diabetes (T2D) increases the risk of tuberculosis (TB) and TB severity; however, its effects on B-cells in the TB-T2D syndemic are not fully understood. Methods We evaluated by flow cytometry, the distribution of circulating B-cell subsets in patients with TB disease, TB-T2D, subjects with TB infection (TBI), TBI-T2D, healthy controls (HCs), T2D, patients with pulmonary respiratory diseases other than TB (ORDs), and ORD-T2D. Plasma levels of unspecific or PPD-specific IgG and B-cell-related soluble factors were measured by multiplex assays. Results Total B-cell frequency was similar across groups. TB-T2D patients showed decreased transitional B cells compared to TB, TBI-T2D, HC, and T2D. Transitional B-cell frequency significantly and negatively correlated with HbA1c levels in the TB-T2D group. Moreover, plasmablast frequency was increased in TB-T2D compared to TB, TBI-T2D, and T2D. Unspecific or PPD-specific IgG levels were not modulated by T2D. BAFF levels increased in TB and TB-T2D compared to the other groups, whereas the levels of SDF-1 were decreased in TB and TBI irrespective of T2D, compared to the controls. Conclusions Overall, T2D reshapes B-cell compartments in TB, reducing potentially anti-inflammatory transitional B-cells and increasing plasmablasts, possibly reinforcing inflammation and impacting B-cell development and humoral immunity in TB-T2D.
BACKGROUND:Dengue infection frequently causes thrombocytopenia and bleeding complications. Patients with cardiovascular disease who receive antiplatelet or anticoagulant therapy represent a clinically challenging population during acute dengue infection. Data regarding clinical outcomes and platelet recovery in these patients remain limited. METHODS:This observational study included a single-center retrospective cardiovascular dengue cohort and an exploratory platelet-monitoring cohort. In the retrospective cohort, patients were classified according to pre-existing antithrombotic therapy (ATT) at dengue diagnosis: no antithrombotic therapy (No ATT), single antiplatelet therapy (SAPT), dual antiplatelet therapy (DAPT), or oral anticoagulant therapy (OAC). Major bleeding was assessed within 7 and 30 days after dengue diagnosis. In the exploratory platelet-monitoring cohort, serial platelet count and platelet function were assessed during dengue illness. RESULTS:The retrospective cohort included 1,693 patients (No ATT, n = 1,493; SAPT, n = 163; DAPT, n = 22; OAC, n = 15). ATT users were older and had a greater burden of cardiovascular comorbidities and more frequent severe dengue manifestations. The observed 7-day major bleeding rates in the No ATT, SAPT, DAPT, and OAC groups were 0.34%, 0.61%, 4.55%, and 6.67%, respectively (P = 0.011), with corresponding 30-day rates of 1.15%, 1.84%, 9.09%, and 13.33% (P = 0.002). In the exploratory platelet-monitoring cohort (6 non-antiplatelet users and 2 aspirin users), aspirin users had a longer platelet count nadir-to-recovery time than non-antiplatelet users [median (IQR), 7.5 (6.0-9.0) vs 4.0 (3.75-4.25) days; P = 0.04] and a longer interval from the lowest platelet function value to recovery [median (IQR), 9.5 (8.0-11.0) vs 4.0 (3.75-4.25) days; P = 0.04]. CONCLUSIONS:Pre-existing ATT users had a greater comorbidity burden and more severe dengue manifestations. SAPT users showed similar observed short-term major bleeding rates to patients without ATT. Exploratory monitoring suggested delayed platelet count and function recovery among aspirin users.
