(@id-journal) — Bluesky Profile

7 hours ago

[Articles] Post-discharge sequelae of Lassa fever survivors in Nigeria: an analysis of the LASCOPE prospective cohort Patient-reported symptoms suggest good recovery with few hearing or neurosensory disorders in most survivors of Lassa fever. Future research would benefit from extended follow-up periods and standardised diagnostic assessments, including objective audiometry, to further characterise the full spectrum of post-Lassa fever complications.

Most Lassa fever survivors report good recovery with few hearing/neurosensory issues. Future studies need longer follow-up & standard audiometry to assess complications 🎧🩺.

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19 hours ago

Incidence of Herpes Zoster Infection (Shingles) Among Adults Living With and Without HIV in British Columbia, Canada: A Population-Based Study Herpes zoster (HZ) incidence is elevated among immunocompromised populations, including people living with HIV (PLWH). We evaluated HZ incidence, associated risk factors, recurrence, and post-vaccination HZ occurrence among PLWH compared with people living without HIV (PLWoH) in British Columbia, Canada.MethodsWe conducted a retrospective, population-based matched cohort study using data from the Comparative Outcomes and Service Utilization Trends (COAST) study (2000–2019). PLWH aged ≥19 years initiating antiretroviral therapy were propensity-score matched to PLWoH from the general population. Incident HZ was identified from administrative health records using a 12-month washout. Age-stratified time-to-event, competing-risk, and multivariable models were used to estimate incidence, risk factors, recurrence, and vaccination-associated outcomes.ResultsAmong 9,053 PLWH and 9,053 matched PLWoH, HZ incidence rates were higher among PLWH overall. Before vaccine availability, PLWH experienced substantially higher HZ hazards than PLWoH, particularly among participants aged <50 years. After 2009, HZ risk remained elevated among younger PLWH, while hazards were similar between groups among those aged ≥50 years. HZ recurrence was approximately twice as frequent among PLWH. Among PLWH, advanced immunosuppression, including low CD4 cell counts and unsuppressed viral load, and selected comorbidities were independently associated with higher HZ risk. Post-vaccination HZ incidence was low in both populations, with no meaningful difference between PLWH and PLWoH; breakthrough events were uncommon.ConclusionsPLWH remain at increased risk of HZ and recurrence, especially if younger or immunosuppressed. Vaccination was associated with a lower HZ risk supporting expanded access to recombinant zoster vaccination for immunocompromised adults irrespective of age.

PLWH had higher HZ incidence 🚑, especially <50 yrs. Recurrence was 2x greater. Low CD4 & unsuppressed viral load ⬆️ risk. Vaccination lowered HZ risk in both groups 💉.

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1 day ago

[Articles] A combined ELISA for infection-induced and vaccine-induced mpox antibodies during the clade Ib outbreak in Rwanda: an observational, cross-sectional, clinical validation study We show that an mpox ELISA can be implemented within a national reference laboratory in a resource-limited setting as part of outbreak-response measures. The assay is suitable for population-level surveys and can analyse both DBS and serum samples. These findings provide a platform for larger population studies and further work to explore immune correlates of protection in mpox.

Mpox ELISA 🧪 works in low-resource labs for outbreak response, testing DBS & serum samples. Enables large population surveys & studies on immune protection.

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1 day ago

[Articles] Immunogenicity and safety of MVA-BN vaccine administered 5 years after a two-dose primary series in DR Congo: a prospective cohort study These data show that primary MVA-BN vaccination induces sustained immunological memory up to 5 years after vaccination and that a booster dose strongly enhances circulating antibody levels and durability. Future studies should clarify the role of circulating antibody concentrations as a correlate of protection from monkeypox virus infection.

MVA-BN vaccine 🛡️ induces 5️⃣-year immunity; booster 📈 boosts antibodies & durability. Future research needed on antibody levels as protection markers vs. monkeypox.

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1 day ago

[Articles] Safety of MVA-BN vaccine in health-care personnel in DR Congo: a prospective cohort study This study adds to the growing body of literature on the safety of MVA-BN in different populations. Although limited by incomplete grading of specific adverse events, low numbers of pregnant participants, and differences in health-care access and infrastructure, the data from this cohort in DR Congo do show good safety outcomes for up to 2 years with both liquid and lyophilised vaccine formulations. Because MVA-BN vaccination campaigns are crucial to clade I and clade II mpox outbreak responses, the data from this study supporting safety of MVA-BN in this population are key to build vaccine confidence.

Study shows MVA-BN vaccine safe up to 2 yrs in DR Congo 🇨🇩, despite few pregnant participants & data gaps. Supports vaccine confidence in mpox outbreaks 🦠🔒.

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1 day ago

Diagnostic Yield of Tongue Swab- Compared to Sputum-Based Molecular Testing for Tuberculosis in Four High-Burden Countries Tongue swabs are a promising alternative specimen for tuberculosis (TB) diagnosis. Although test specificity exceeds 98%, sensitivity is lower than sputum-based molecular testing. We investigated whether the use of tongue swabs could increase sample availability, resulting in similar diagnostic yield.MethodsIn this cross-sectional study (July 2024–January 2025), we screened consecutive people with presumptive TB at health centers in the Philippines, Vietnam, Uganda, and Zambia. Participants were asked to provide tongue swabs and referred for routine sputum collection. Tongue swabs were tested in research laboratories using the MiniDock MTB Test (Guangzhou Pluslife Biotech Co., Ltd., China); sputum was tested using WHO-recommended molecular testing per national guidelines. We compared diagnostic yield, defined as proportion of positive test results among all participants, between tongue swab- and sputum-based molecular testing with a prespecified 3.0% non-inferiority margin.ResultsOf 1639 participants, 851 (51.9%) were female, 415 (25.3%) were living with HIV, and 132 (8.1%) were children <5 years. All provided tongue swabs, but only 1389 (84.7%) produced sputum. Diagnostic yield was 3.8% (63/1639) for tongue swabs and 4.1% (68/1639) for sputum-based (68/1639, 4.1%) molecular testing. The difference (0.3%, 95% CI −0.6 to +1.2) was within the prespecified non-inferiority margin. Results were consistent across countries and key subgroups (age, sex, and HIV status).ConclusionsTongue swab-based molecular testing with MiniDock MTB achieved non-inferior diagnostic yield compared with sputum-based molecular testing. These findings support scale-up of swab-based platforms as a cost-efficient alternative, particularly where sputum collection is challenging or smear microscopy remains the primary diagnostic method.

Tongue swabs for TB tested 3.8% positive vs 4.1% for sputum in 1639 pts. Difference 0.3% within non-inferiority margin. Useful where sputum hard to get.🦷🦠

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1 day ago

[Articles] Case presentation of patients hospitalised with mpox (subclade Ib/2023sh) including children, adolescents, and adults in South Kivu, Democratic Republic of the Congo: an observational cohort study The high proportion of children and adolescents (aged ≤15 years) differentiates our cohort from other clinical descriptions of the novel MPXV subclade Ib/2023sh. Given that, we hypothesise a demographic shift in the target population that contributes to the community spread of mpox in the South Kivu region of DR Congo. Targeted public health measures should consider ways to reduce transmission among children and adolescents.

The cohort has a high proportion of ≤15 yrs, unlike other MPXV Ib/2023sh studies. This may drive mpox spread in South Kivu, DR Congo. Targeted kids' measures needed.🦠👧👦

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1 day ago

HIV Preexposure Prophylaxis Utilization and Reasons for Never Using Preexposure Prophylaxis Among Transfeminine Persons in the United States: Findings From the Transgender Women’s Internet Survey and Testing (TWIST) Study Transfeminine persons in the United States face a high burden of human immunodeficiency virus (HIV), yet national data on preexposure prophylaxis (PrEP) use remain limited. We examined PrEP utilization, adherence, and persistence and reasons for never using PrEP among a national sample of transfeminine persons.MethodsSexually active transfeminine persons aged ≥15 years without HIV were recruited online through the Transgender Women's Internet Survey and Testing (TWIST) Study, a national cross-sectional survey conducted between June 2023 and October 2024. Multivariable Poisson regression was used to estimate adjusted prevalence ratios for characteristics associated with current PrEP use. Reasons for never using PrEP were examined descriptively by age group.ResultsAmong 1656 participants, 6% were currently using PrEP and 86% had never used PrEP. Among current users (n = 96), 94% used oral PrEP and 6% used long-acting injectable (LA) PrEP. Among the 32 participants who reported using <30 daily PrEP doses in the past 30 days, 25% indicated that they were using event-driven (on-demand) PrEP, taking it only when they anticipated having sex. In multivariable models, current PrEP use was higher among participants aged ≥40 years, Black participants, and participants reporting a sexually transmitted infection diagnosis, multiple sexual partners, illicit drug use, or prescribed medication use. Common reasons for never using PrEP among participants aged 15–24 years included insurance-related privacy and disclosure concerns and transportation barriers, while among participants aged ≥25 years, reasons included loss of insurance, side-effect concerns, and monogamous partnerships.ConclusionsPrEP uptake among transfeminine persons remains low, with distinct age-specific barriers. Tailored interventions are needed. LA PrEP may help address challenges related to adherence and disclosure, particularly among younger individuals.

Transfeminine US persons show 6% 🙋‍♀️PrEP use; 86% never used. Use higher in ≥40yo, Black, STI dx. Barriers: youth—privacy🚫, transport🚗; adults—insurance📉, side effects⚠️.

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1 day ago

Escherichia coli ST131 Drives Carbapenem Use for E. Coli Bloodstream Infections Ceftriaxone-resistant Escherichia coli infections are increasingly common, partially due to the emergence of E. coli sequence type 131 (ST131) including its subclade C2/H30Rx that produce extended-spectrum β-lactamases (ESBL).MethodsA prospective cohort including 14 US sites, which enrolled monomicrobial ceftriaxone-resistant and susceptible E. coli BSI cases in a 1:1 ratio, was used to compare ST131 versus non-ST131 E. coli BSI, with specific attention to E. coli ST131 C2/H30Rx. Desirability of outcome ranking (DOOR) was determined at 30 days after infection onset.ResultsThis analysis included 282 patients with E. coli BSI; 43% (121/282) were E. coli ST131, and 23% (66/282) belonged to the C2/H30Rx subclade. Resistance to ceftriaxone was present in 79% (96/121) ST131, 86% (57/66) E. coli ST131 C2/H30Rx, and 27% (43/161) E. coli non-ST131. Compared to patients with non-ST131 E. coli BSI, patients with ST131 BSI were older (median 70 years, [Q1 62, Q3 76] years vs. 65 years, [51, 74]; p = 0.005) and more often admitted from long-term care facilities (21/121 [17%] vs 7/161 [4%], p <0.001). Overall and empiric carbapenem use was more frequent in the treatment of patients with ST131 BSI compared with non-ST131 BSI (overall 89/121 [74%] vs 50/161 [31%]; empiric: 58/121 [48%] vs. 31/161 [19%], p <0.001). DOOR outcomes were similar between groups.ConclusionsMost ceftriaxone-resistant E. coli from US patients with E. coli BSI belong to ST131, particularly E. coli ST131 C2/H30Rx, serving as an important driver of carbapenem use.

43% of E. coli BSI were ST131 (79% ceftriaxone-resistant); 23% were ST131 C2/H30Rx (86% resistant). ST131 pts older, more long-term care, ↑ carbapenem use (74% vs 31%).🔬🦠

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1 day ago

Effectiveness of Doxycycline in Combination With Other Antibiotics for Gram-Positive Periprosthetic Joint Infections: A Causal Inference Study Doxycycline is occasionally used as step-down therapy in periprosthetic joint infections (PJI), but evidence supporting its efficacy is limited. This study aimed to estimate the effect of doxycycline on 12-month treatment failure in patients with gram-positive PJI.MethodsAdult patients with hip, knee, or shoulder PJI caused by Staphylococcus, Corynebacterium, or Cutibacterium who underwent surgery between April 2013 and April 2023 at Dijon University Hospital (France) were included. Demographic, clinical, biological, and therapeutic data were collected retrospectively. Treatment failure at 12 months was defined as clinical recurrence, new intraoperative microorganisms, surgical revision for infection, or death. The average treatment effect (ATE) of doxycycline was estimated using causal inference methods.ResultsThree hundred and eighty-six patients with PJI (median age 72 years, interquartile range [IQR] = 65–80) were analyzed. Most infections involved the hip (62%) were caused by Staphylococcus aureus (64%) and/or polymicrobial (42%). Doxycycline was prescribed in 19% of patients (n = 72), for a median of 64 days (IQR = 42–84). At 12 months, treatment failure occurred in 35%, without significant difference between exposed and unexposed patients (33% vs 36%, P = .68). Overall, doxycycline was not significantly associated with treatment failure (ATE(IPTW) = −0.09; 95% CI = −0.24 to 0.05; P = .19). Subgroup analyses suggested that doxycycline reduced treatment failure by 23%–26% in S. aureus infections (P < .001), 25%–28% in patients without fever (P < .001), and 34%–35% when both conditions were present (P < .001).ConclusionsDoxycycline in combination with other antibiotics was not associated with 12-month treatment failure in PJI caused by Staphylococcus, Corynebacterium, or Cutibacterium, with potential benefits in S. aureus infection warranting confirmation in prospective studies.

386 PJI pts (median 72y) studied; doxycycline (19%) showed no overall 12mo failure ↓ (33% vs 36%, P=.68). ↓ failure in S. aureus inf (23-35%, P<.001) & afebrile pts. 🦠🦵💊

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1 day ago

Induction of a Th1-Type Polyfunctional T Cell Response by the four-segmented Rift Valley Fever candidate vaccine in humans Rift Valley fever virus (RVFV) is a mosquito-borne virus that affects livestock and humans. The four-segmented live-attenuated human vaccine candidate hRVFV-4s has shown a strong safety profile and excellent tolerability in healthy adults during a first-in-human clinical trial, while also eliciting both neutralizing antibody and T-cell responses. Recognizing the critical role of cellular immunity in vaccine-induced protection and immune durability, this study aimed to comprehensively characterize the cytokine secretion profile, the antigen-specific breadth of RVFV-specific T-cell responses and memory T-cell formation, elicited by a single dose of hRVFV-4s, up to six months post-vaccination.MethodsPeripheral blood mononuclear cells collected during the first-in-human clinical trial at 0, 7, 14 and 180 days post hRVFV-4s vaccination were analysed for RVFV-specific T-cell responses using multiparametric flow cytometry and multiplex cytokine detection assays.ResultsA strong N-specific peripheral CD4+ and CD8+ T-cell response was detected among vaccinees, accompanied by Gn- and Gc-specific T cells, albeit the latter at comparatively lower frequencies. These responses were mediated by polyfunctional CD4+ and CD8+ T cells, which were detectable as early as at two weeks post-vaccination. The RVFV-specific T-cells were primarily of the effector memory phenotype and demonstrated cytokine secretion profiles characteristic of a T helper 1 (Th1)-type.ConclusionThis study demonstrates that the cell mediated immune response induced by a single dose of the hRVFV-4s vaccine is characterized by robust, virus-specific Th1-type CD4+ and CD8+ T-cell response. Together with previously reported virus-neutralizing antibody responses, these coordinated immune responses are expected to contribute to vaccine-mediated protection.

hRVFV-4s vaccine induces strong Th1-type CD4+/CD8+ T-cell response 💪 by 2 weeks, lasting 6 months, plus neutralizing antibodies, enhancing protection against RVFV 🦟.

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1 day ago

Leptospirosis Incidence at Four Sites in Sub-Saharan Africa and South East Asia: An International Multi-Site Hybrid Surveillance Study There are few leptospirosis incidence studies despite such estimates being central to accurate burden of disease estimation. We used data from the multicenter Febrile Illness Evaluation in a Broad Range of Endemicities (FIEBRE) study to make leptospirosis incidence estimates from new sites.MethodsFebrile patients aged ≥2 months in Laos, Malawi, Mozambique, and Zimbabwe were enrolled and underwent standardized clinical and exposure assessment. Acute and convalescent sera were tested by Leptospira microscopic agglutination test and acute plasma by lfb1 polymerase chain reaction (PCR). Participants with ≥4-fold rise in antibody titer between acute and convalescent sample, or Leptospira PCR positive for the lfb1, had confirmed leptospirosis. Leptospirosis incidence was estimated after adjusting for incomplete enrollment of febrile patients, availability of paired sera, and use of study healthcare facilities by febrile patients based on healthcare utilization data from community controls.ResultsLeptospirosis incidence (95% CI) per 100 000 population per year was 1302 (1011, 1677) in Laos, 1337 (874, 2044) in Malawi, 187 (85, 409) in Mozambique, and could not be calculated for Zimbabwe. Sensitivity analysis restricted to pre-COVID years of 2018 and 2019 produced similar estimates of incidence to that of the whole study period.ConclusionsLeptospirosis incidence was high at the Laos, Malawi, and Mozambique sites and at the upper end of published incidence estimates from the Asia and Africa regions. We recommend more leptospirosis incidence studies be done in areas lacking data to strengthen leptospirosis global burden of disease estimates and to stimulate progress on diagnosis, management, and control.

Leptospirosis incidence/100k/year: Laos 1302️⃣, Malawi 1337️⃣, Mozambique 187️⃣; Zimbabwe not calculated. High rates suggest need for more global studies.🌍🦠

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1 day ago

Safety, Efficacy, and Immunogenicity of a Multivalent Adjuvanted S. aureus Vaccine in Adults with Recent Skin And Soft Tissue Infections: An Observer-blind, Randomized, Placebo-controlled, Multinational Phase 1/2 Trial A vaccine that prevents Staphylococcus aureus skin and soft tissue infections (SA-SSTIs) would have a major impact on public health.MethodsA two-part randomized study began with a phase 1, first-in-human, dose-escalation that tested the safety of the five-antigen S. aureus vaccine (SA5Ag), half or full antigen doses, unadjuvanted or with AS01E adjuvant, in 32 healthy volunteers aged 18–50 years. In the phase 2, proof-of-principle part, 194 participants aged 18–64 years with recent SA-SSTI were administered two full doses of AS01E-adjuvanted SA5Ag (SA5Ag-Adj) or placebo, 2 months apart, and followed for 12 months. Vaccine safety (primary objective), vaccine efficacy (VE; secondary/tertiary objectives), and immunogenicity (tertiary objectives) were evaluated.ResultsFollowing a positive safety evaluation in phase 1, participants were enrolled into phase 2 until predefined futility criteria were met at the interim efficacy analysis. Twelve months post-dose 2, SA5Ag-Adj showed no efficacy in preventing recurrent SA-SSTIs (VE: -38.1% [95% confidence interval -245.8, 40.9]), despite inducing robust functional immune responses against three (CP5, CP8, Hla) of the five vaccine antigens. Solicited local adverse events (AEs) were more frequent in the SA5Ag-Adj versus placebo group but were mostly mild or moderate in intensity. Frequencies of medically-attended AEs and serious AEs were similar across groups.ConclusionsIn participants with recent history of SA-SSTI, SA5Ag-Adj vaccine had an acceptable safety profile, induced robust functional immune responses against CP5, CP8, and Hla antigens, but did not reduce the rate of recurrent SA-SSTIs at 12 months from last dose.Clinical Trial RegistrationNCT04420221

Vaccine SA5Ag-Adj 🚫 efficacy for SA-SSTIs recurrence (VE: -38.1%, CI -245.8 to 40.9). Safe, induced strong immune response, mild/moderate local AEs ↑ vs placebo.

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1 day ago

Exposure-QTc modeling of bedaquiline, pretomanid, and clofazimine in adults with tuberculosis ABSTRACTDrug resistance (DR) poses a critical challenge to global efforts to manage tuberculosis (TB). Limited information is available on the combined cardiotoxicity of bedaquiline (BDQ), pretomanid (Pa), and clofazimine (CFZ), key drugs in current DR-TB treatment regimens. All of those prolong the QT interval. We aimed to describe this interaction to predict possible toxicities with established and novel dosing regimens to identify patients at higher risk of QT prolongation. The data for this analysis were obtained from an early-bactericidal activity study in drug-susceptible-TB of several TB drugs. We developed a competitive interaction model to evaluate combined concentration-QTc effect of all three drugs. The model was developed using ECG-matched PK measurements (105 patients, 2,062 observations). The model identified a maximum QT increase by all three drugs of 44.5 ms with respective EC50 values for BDQ, Pa, and CFZ of 0.57, 0.903, and 26.9 mg/L. For patients aged 70 years with non-black ancestry, at risk of increased BDQ exposure, simulations showed that 39.1% had a drug-induced QT change >30 ms after the loading period; this was 29.4% for following BDQ 400 mg daily regimen (part of UNITE4TB program). Reassuringly, no simulations resulted in a QTcF >500 ms, and less than 1% exceeded 480 ms or a change from baseline of >60 ms. We present a joint concentration-QT model of BDQ, Pa, and CFZ. The competitive interaction model serves as a tool to predict possible combined exposure-induced QT prolongation of these drugs in different dosing regimen and identify patients at high risk of significant QT-prolongation.

DR-TB drugs BDQ, Pa, CFZ ↑QT by max 44.5ms. In elderly, 39.1% had >30ms QT rise post-loading. <1% exceeded 480ms QT or >60ms change. Model predicts QT risk.📊❤️

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1 day ago

Associations Between B-Cell Subsets and Subclinical Coronary Artery Disease in Ugandans With and Without HIV People living with HIV (PLWH) have an increased risk of cardiovascular disease (CVD), influenced by chronic inflammation, immune dysregulation, and antiretroviral therapy (ART). B cells regulate immune responses, but their contribution to HIV-associated atherosclerosis remains poorly defined.MethodsIn a cross-sectional study, we enrolled 40 PLWH and 60 people without HIV (PWoH) in Uganda, matched 1:1.5 for age and CVD risk. Peripheral blood mononuclear cells were profiled by mass cytometry to define immune cell subsets. Coronary computed tomography angiography quantified coronary artery disease (CAD) using the segment stenosis score (SSS). We used multivariable hurdle regression to estimate the effect sizes of immune clusters, ASCVD risk score, HIV status, and gender.ResultsMedian age was 60 years, with no difference by HIV status. PLWH had a lower proportion of CCR7− naïve B cells than PWoH (median 1.5% vs. 1.8%; p-value adjusted (padj) = 0.03). Across all participants, higher CCR7− naïve B cells (Ratio=0.55, p=0.02), CXCR3+CX3CR1+ B cells (Ratio=0.54, p=0.03), and plasmablasts (Ratio=0.57, p=0.003) were associated with lower SSS. HIV-positive status was linked to nearly threefold higher SSS (p<0.01). In stratified analyses, classical monocytes (CD14+CD16−) correlated with higher SSS among PLWH. When classical monocytes were held at the median, higher CCR7− naïve B cells were protective in PLWH (Ratio=0.55, p=0.02).ConclusionThis exploratory study suggests that lower frequencies of naïve B cells in PLWH are associated with differences in subclinical atherosclerosis. However, the mechanisms cannot be inferred from this study.

PLWH (n=40) had 1.5% CCR7⁻ naïve B cells vs 1.8% in PWoH (n=60, p=0.03). Higher CCR7⁻ naïve B, CXCR3⁺CX3CR1⁺ B, plasmablasts linked to ↓CAD (p≤0.03). HIV+ had 3x higher CAD (p<0.01).❤️

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1 day ago

Clinical Insights and Severity of Enterovirus D68 Respiratory Infections in Vietnamese Children Enterovirus D68 (EVD68) causes respiratory disease, yet the risk of severe respiratory disease remains incompletely quantified, especially when stratified by comorbidity status. This study aims to describe the clinical features and risk of severe disease in children with EVD68 compared with those with other Rhinoviruses/Enteroviruses, accounting for comorbidity.MethodsWe analyzed 1100 pediatric EV-positive cases from surveillance in Vietnam (2019–2022), excluding viral coinfections. EVD68 was confirmed by real-time PCR. We examined clinical features, treatments, and comorbidities. Standardization methods estimated risk differences (RDs) and risk ratios (RRs) stratified by (1) general comorbidity, (2) asthma, and (3) either of these. Time-to-recovery in intensive care unit (ICU) was compared using Kaplan–Meier methods.ResultsEVD68 was detected in 55/1100 cases (5.0%). Children with EVD68 more often had wheeze, pneumonia, oxygen therapy, and ICU admission. For wheeze, EVD68 was associated with similar elevated risk with and without general comorbidity (RR 1.40 in both; RD 0.27). Pneumonia risk was likewise elevated with EVD68 (with comorbidity: RR 1.17; RD 0.12; without: RR 1.73; RD 0.14). By asthma status, EVD68 increased wheeze risk in both groups; however, the excess was smaller in asthma (RR 1.10; RD 0.09) than non-asthma (RR 1.43; RD 0.29), consistent with baseline wheeze susceptibility in asthma. Pneumonia risk was similar regardless of asthma status. During ICU stay, wheeze persisted longest in both groups. Time-to-recovery was similar between groups.ConclusionsEVD68 infection was associated with a higher risk of severe disease than Rhinoviruses/Enteroviruses, independent of documented comorbidity, indicating substantial risk even among previously healthy children.

EVD68 found in 5% of 1100 kids; linked to ↑wheeze (RR 1.40), pneumonia (RR 1.17-1.73), ICU stays vs other EVs, risk ↑ even without comorbidities. 🦠👶

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1 day ago

Pharmacokinetic and pharmacogenomic predictors of hepatotoxicity in the HIRIF trial for drug-susceptible tuberculosis Hepatotoxicity is frequent in the standard-of-care regimen for drug-susceptible tuberculosis, yet the association of each companion drug with hepatotoxicity has not been fully characterized. We examined the association between hepatotoxicity and the pharmacokinetics of rifampin and its companion drugs in standard therapy, as well as N-acetyltransferase 2 (NAT2) genotype.MethodsWe evaluated HIRIF trial participants who were randomized to receive rifampin 10, 15, or 20 mg/kg/day during the intensive phase of tuberculosis treatment. We fitted Cox proportional hazards models to identify risk factors for grade 2 or higher (grade 2+) alanine transaminase (ALT) or aspartate transaminase (AST) elevation, and considered pharmacokinetic exposure of each antituberculosis drug and NAT2 genotype as potential covariates.ResultsAmong 168 participants with pharmacokinetic data, neither rifampin dose nor exposure were associated with the risk of grade 2+ ALT or AST elevation. Higher pyrazinamide exposure (hazard ratio [HR] 1.85 for every 50 mg*h/L AUC0-6h increase), higher isoniazid exposure (HR 1.40 for every 5 mg*h/L AUC0-6h increase), and among a subset with known NAT2 genotype, slow NAT2 acetylator status (HR 9.32 relative to fast, n=90) were associated with grade 2+ ALT or AST elevation in univariable analysis. In multivariable analysis, only pyrazinamide exposure was associated with hepatotoxicity.ConclusionsWhile higher pyrazinamide and isoniazid exposures and slow NAT2 acetylator status were each associated with increased hepatotoxicity, only pyrazinamide exposure was associated when considering pharmacokinetic variables together. Rifampin exposure was not associated with hepatotoxicity, supporting further evaluation of doses up to 20 mg/kg/day in a larger trial.

In 168 TB patients, higher pyrazinamide (HR 1.85) & isoniazid (HR 1.40) exposures ↑ hepatotoxicity; slow NAT2 acetylators (HR 9.32) too. Rifampin dose ⚠️ no risk.

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1 day ago

RSV in adults ≥60 caused symptoms lasting 2-19 days, HRQoL scores 0.81–0.90. 27.8% missed work; treatment lasted 16.3 days. Lower respiratory disease worsened HRQoL. 🦠📉

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1 day ago

Burden of respiratory syncytial virus among older adults with an acute respiratory infection: a prospective study in six European countries Respiratory syncytial virus (RSV) primarily affects the respiratory tract, with a high burden among older adults. We aimed to estimate the prevalence and characteristics of RSV-associated respiratory infections in community-dwelling older adults across Europe.MethodsA prospective, observational study was conducted in six European countries over three consecutive RSV seasons (October 2021 until April 2024). Non-RSV vaccinated participants (age ≥60 years) presenting with symptoms of acute respiratory infection (ARI) at general practitioners and outpatient clinics/outpatient hospitals were recruited. RSV and other respiratory viruses were detected using a combined nasal and throat swab. Diary cards and regular phone contacts were used to collect information on onset and resolution of symptoms. The prevalence of RT-PCR confirmed RSV-ARI (cRSV-ARI) was estimated, as well as symptom duration, underlying comorbidities, prevalence of RT-PCR confirmed RSV lower respiratory tract disease (cRSV-LRTD), complications, hospitalizations, and co-infections.ResultsA total of 2573 participants were enrolled (139 with cRSV-ARI). The prevalence of cRSV-ARI varied by season: 3.6% in Season 1, 9.3% in Season 2, and 4.2% in Season 3. The most frequently reported upper respiratory, lower respiratory, and systemic symptoms were nasal congestion/rhinorrhea, cough, and fatigue (cRSV-ARI: 83.1%, 97.8%, and 64.0%; non-cRSV-ARI: 78.0%, 95.0%, and 68.2%). The overall prevalence of cRSV-LRTD was 3.9% in Season 1, 12.5% in Season 2, and 7.3% in Season 3.ConclusionsThis study highlights the substantial burden of RSV among older adults in Europe and reflects the shift in RSV epidemiology due to the COVID-19 pandemic, indicating a return to pre-pandemic seasonality trends.

RSV-ARI prevalence in older EU adults: 3.6%🔹9.3%🔹4.2% over 3 seasons. Common symptoms: nasal congestion 83.1%, cough 97.8%, fatigue 64%. LRTD: 3.9%, 12.5%, 7.3%.

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2 days ago

Patient and healthcare professionals’ perceptions of educational tools to reduce urine culture contamination in outpatient clinics: a qualitative study View abstract Objective:Iteratively develop educational tools (instructional video and flyer) to improve midstream clean catch (MSCC) urine sample collection using patient and healthcare professionals’ input.Design:Multi-method qualitative study.Setting:Outpatient clinics in Houston, Texas, United States.Participants:Adult patients recruited from public and private clinics (n = 12). Healthcare professionals (HCP; nurses and medical assistants) (n = 12) providing care at participating clinics.Methods:Twelve patient interviews and three focus groups with HCPs (May 2024–November 2024). Interviews discussed patient experiences using the educational tools to guide urine specimen collection. Focus groups elicited HCPs’ perspectives on the comprehensibility and utility of the tools in their respective clinics. We identified themes using directed content analysis.Results:We garnered insight into knowledge gaps and barriers for completing the MSCC process. MSCC instructions in existing educational tools were poorly understood by patients, especially among those with limited understanding of urogenital anatomy. Patient barriers to MSCC collection included physical difficulties due to poor urine stream control, mobility issues, and obesity. Patients and HCPs reported that our tools addressed patient gaps in understanding of MSCC instructions. Patients and HCPs also suggested that we accompany our tools with assistive devices and dedicated surfaces in the clinic bathrooms, to better meet patients’ needs in urine specimen collection.Conclusions:Initial feedback was promising that our educational tools would improve the MSCC collection process for patients. In next steps, we will conduct feasibility pilot testing followed by a randomized controlled trial to test the effectiveness of reducing urine culture contamination.

Study created edu tools for midstream urine collection. 12 patients & 12 HCPs gave feedback. Tools improved understanding, esp. for pts w/ anatomy gaps. Next: pilot & RCT. 🚻🎥📄

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2 days ago

Optimization of vancomycin use in hospitalized patients with pneumonia through implementation of informatics based antimicrobial stewardship program (ASP) intervention View abstract Objective:Vancomycin overuse in pneumonia should be a key target for antimicrobial stewardship according to Centers for Disease Control and Prevention. High negative predictive value of nasal Methicillin Resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) (nMP) screening for pneumonia has been shown. We implemented informatics-based ASP intervention to reduce vancomycin use in pneumonia by 20% in 6 months.Design:Quasi-experimental: Pre-intervention period (P1: 4/1/24–9/30/24) compared with post-intervention period (P2: 10/15/24–3/15/2025).Setting:Quality improvement (QI) initiative in a tertiary-care center in Upper Midwest.Patients:Hospitalized pneumonia patients.Interventions:Automated default nMP order was incorporated in pneumonia order-set in electronic medical record while ordering vancomycin for hospital acquired/ventilator associated pneumonia, severe community acquired pneumonia.Results:Outcome measures declined significantly: Average vancomycin use density as reported with days of therapy (DOT)/1,000 patient days decreased by 49.5% (from 72.2 DOT/1,000 patient days in P1 to 36.3 DOT/1,000 patient days in P2; p < .0001). Average vancomycin drug inventory cost decreased by 50% (from 1,089.5 U.S. Dollars (USD)/1,000 patient days in P1 to 546.3 USD/1,000 patient days in P2; p < .0001). All process measures showed significant changes: nMP ordering increased to 100% in P2 (p < .0001); proportion of pneumonia patients with negative PCR results with discontinuation of vancomycin within 48–72 hours increased to 71% (p < .0001) and time to vancomycin discontinuation declined by 46% (p < .001). Balancing measures (readmissions; nMP order-to-result time) remained unchanged.Conclusions:Informatics-based ASP intervention was transformative leading to significant decline in vancomycin utilization, considerable healthcare-cost savings and significant increase in nMP screening among pneumonia patients.

Vancomycin use in pneumonia dropped 49.5% (72.2→36.3 DOT/1,000 days), cost cut 50% ($1089.5→$546.3), nMP screening ↑100%, vancomycin stop ↑71%, time↓46%.📉💊💰

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2 days ago

Randomized double-blind clinical trial evaluating the effectiveness and safety of secondary prophylaxis with oral vancomycin versus placebo in the prevention of recurrence of clostridioides difficile infection in patients receiving systemic antibiotic therapy (PREVAN trial) Recurrence of Clostridioides difficile infection (CDI) is frequent, particularly in patients requiring subsequent systemic antibiotics. Observational studies suggest that secondary prophylaxis with oral vancomycin (SPV) may reduce recurrence risk, but randomized evidence remains scarce.MethodsPREVAN (NCT05320068) was a phase III, double-blind, placebo-controlled randomized clinical trial conducted at a tertiary hospital in Spain. Adults with documented CDI within the previous 180 days who required hospitalization and systemic antibiotics were randomized (2:1) to receive oral vancomycin (125 mg every 6 h) or placebo for 10 days, stratified by type of index CDI episode. Primary endpoints were CDI recurrence within 60 days after end of therapy and CDI recurrence-free survival.ResultsTwenty-one patients were enrolled (14 SPV; 7 placebo). Mean age was 73.5 years and 76.7% had malignancy and/or immunosuppression. CDI recurrence occurred in 5 patients (23.8%): 2 (14.3%) in the SPV group and 3 (42.9%) in the placebo group (P = 0.30). CDI recurrence-free survival at 60 days was 83% (95% CI 48–95) with SPV versus 42% (95% CI 6–77) with placebo (log-rank P = 0.09). No treatment-related serious adverse events were observed; one mild diarrhoeal event occurred in a placebo-treated patient.ConclusionsIn high-risk patients with recent CDI requiring systemic antibiotics, SPV appeared safe and was associated with a clinically relevant reduction in recurrence, although the trial was underpowered. These findings support further adequately powered randomized studies to define the role of SPV in preventing CDI recurrence.

In 21 pts (avg age 73.5), SPV ↓ CDI recurrence (14.3% vs 42.9%) & ↑ recurrence-free survival (83% vs 42%) but not sig (P=0.30; P=0.09). No serious AEs.🦠💊

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2 days ago

Changes in Cellular Senescence Biomarkers Across Individuals at Different Stages of HIV Infection Before and After a Year on Antiretroviral Therapy People with HIV (PWH) experience chronic inflammation and more age-related comorbidities despite antiretroviral therapy (ART). Classical senescence biomarkers (e.g., SA-βGal, p16INK4a, γH2AX and Bcl-2) and senescence-associated secretory phenotype (SASP) factors such as IL-6 reflect cellular senescence. This study assesses those markers in a male cohort of PWH across infection stages, pre/post-ART.MethodsWe analyzed blood samples from 39 PWH at primary, chronic and advanced HIV infection, before and after one year on ART, and 13 age- and sex-matched HIV-negative controls. Classical cellular senescence biomarkers in T-cells and monocytes, along with plasma SASP factors and immune checkpoints, were assessed via flow cytometry and Luminex.ResultsPWH exhibited elevated cellular senescence, SASP and immune checkpoint markers (such as SA-βGal, p16INK4a, γH2AX, Bcl-2, CD87, IL-6, IL-10, TNF-RI/RII, CD30, IL-8, RANTES, CXCL1, PD-1, PD-L1, PD-L2, LAG-3, CTLA-4 and TIM-3) particularly in chronic and advanced stages, which generally persisted after ART, but not in PWH treated in primary HIV infection. Senescence biomarkers in T-cells and SASP components in plasma positively correlated with immunosenescence, T-cell activation, HIV p24 expression and negatively correlated with CD4 count and CD4/CD8 ratio.ConclusionsHIV infection promotes persistent cellular senescence despite ART in advanced and chronic infection. Thus, future senolytic or senomorphic strategies against cellular senescence may reduce chronic inflammation and aging-related complications in PWH.

HIV⬆️senescence (SA-βGal, p16, IL-6) in 39 men, esp. chronic/advanced stages; persists post-ART except early tx. Senescence↔️low CD4/CD8, high T-cell activation.

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2 days ago

MHC-I upregulation and increased glucose dependence define innate antifungal immune responses to Cryptococcus neoformans Cryptococcus neoformans, the etiological agent of cryptococcosis, can survive and replicate within host immune cells, contributing to development of cryptococcal meningitis. Within the lung, C. neoformans interacts with innate immune subsets, including macrophages and dendritic cells (DCs). Our previous work demonstrated that Ly6c– monocyte-like macrophages restrict fungal proliferation, whereas CD11b+ DCs promote fungal growth. Transcriptomic profiling revealed differential expression of MHC class I gene H2-K1, Calreticulin (Calr), and metabolic genes. Therefore, we hypothesized that H2-K1 and metabolic pathways modulate the intracellular fungal fate within pulmonary macrophages and DCs.MethodsH2-K1 expression was knocked down using siRNA in J774 macrophages and GM-CSF-induced bone marrow-derived DCs (BMDCs). Antifungal activity was determined by CFU enumeration. Phagocytic uptake, cathepsin B activity, Nos2 expression and reactive oxygen species (ROS) production were quantified by flow cytometry. Metabolic dependencies were evaluated using SCENITH assay.ResultsH2-K1 KD in J774 cells significantly reduced antifungal activity compared to controls. H2-K1 knockdown also decreased Calr gene expression, suggesting H2-k1 has downstream effects in the pathway. H2-K1 silencing did not significantly alter phagocytic uptake, cathepsin B activity, or Nos2 expression. However, ROS production was significantly reduced in H2-K1 KD J774 cells, indicating impaired responses. SCENITH analysis revealed that antifungal macrophages shift their metabolism toward glucose oxidation for ATP generation, which is important for antifungal activity.ConclusionThese findings indicate that metabolic reprogramming is critical for effective antifungal responses. Our data provide a foundation for future studies aimed at targeting host immune and metabolic pathways to enhance antifungal immunity.

H2-K1 KD in macrophages⬇️antifungal activity; ROS⬇️; Calr⬇️. Antifungal cells rely on glucose oxidation⚡ for ATP. Metabolic reprogramming key for antifungal defense🦠🔥.

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3 days ago

A Large Dengue Outbreak in Taiwan, 2023: Driven by Imported Cases, Serotype Cocirculation, and Climate Variability Taiwan, a region traditionally considered non-endemic for dengue, experienced an unexpected and large-scale outbreak in 2023. We investigated the multifactorial drivers of this outbreak, including cross-border viral importation, serotype cocirculation, vector ecology, and climate variability.MethodsWe analyzed national dengue surveillance data (2013–2023), meteorological records, and Breteau Index (BI) values, alongside molecular serotyping and whole-genome sequencing of clinical isolates. Time-lagged Poisson regression was used to identify predictors of indigenous dengue transmission in Kaohsiung and Tainan. Full-genome comparisons were conducted between 2023 strains and historical epidemic isolates.ResultsA total of 26 706 laboratory-confirmed cases were reported, primarily in Tainan (80.7%) and Kaohsiung (11.9%). Real-time RT-PCR identified cocirculating DENV-1 and DENV-2 strains. Phylogenetic analysis confirmed the 2023 DENV-1 and DENV-2 strains were genetically linked to contemporary strains from Southeast Asian countries. Whole-genome sequencing identified several nonsynonymous mutations in the NS2A, NS3, and NS5 regions when compared with historical outbreak isolates. Time-lagged regression showed that imported cases, precipitation, and the BI were associated with incidence in univariate models. In Kaohsiung, the best-fitting multivariable model included the BI, but temperature and precipitation were the independent predictors. In Tainan, precipitation and, at longer lags, imported cases were more influential, while the BI lost significance after adjustment.ConclusionsThe 2023 dengue outbreak in Taiwan was driven by a complex interplay between viral introductions, climatic conditions, and vector dynamics. The differing transmission drivers observed between cities highlight the need for region-specific vector surveillance, climate-informed early warning systems, and sustained genomic monitoring to prevent future re-emergence of dengue in this non-endemic setting.

📊26,706 dengue cases in 2023 Taiwan; 80.7% in Tainan, 11.9% Kaohsiung. DENV-1/2 from SE Asia. Climate🌧️, vectors🦟, imports linked. City-specific factors differ.

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3 days ago

Baseline Procalcitonin and C-Reactive Protein Levels in Asymptomatic Individuals From West Africa With and Without P. falciparum Parasitemia AbstractWe assessed baseline C-reactive protein (CRP) and procalcitonin levels in asymptomatic individuals from malaria-endemic West Africa. C-reactive protein remained unaffected by Plasmodium falciparum parasitemia, while procalcitonin (PCT) was more frequently detectable among malaria-positive individuals. These findings support that CRP thresholds remain valid and highlight the need to explore parasite density–PCT associations.

In malaria-endemic West Africa, CRP levels🚫affected by Plasmodium falciparum; PCT detected more in malaria+ cases💉. CRP thresholds valid; PCT-parasite density link needs study🔬.

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3 days ago

The Immunosuppression Paradox in Multiple Sclerosis: Are We Fueling the Fire by Suppressing Immunity in an Epstein–Barr Virus–Linked Disease? AbstractRecent studies strongly implicate Epstein–Barr virus (EBV) as a necessary trigger for multiple sclerosis (MS). Longitudinal data show that EBV seroconversion precedes MS onset, while mechanistic studies identify molecular mimicry between EBV antigens and central nervous system proteins. Yet, MS treatments remain largely immunosuppressive, potentially impairing antiviral surveillance required to control EBV latency. Therapies that deplete T cells or impair lymphocyte trafficking have been linked to EBV-driven lymphoproliferative complications, potentially leading to EBV reactivation and exacerbation of MS. In contrast, B-cell–depleting therapies may reduce EBV reservoirs by targeting infected memory B cells and thus be more suited to treating EBV-associated MS. In this Review, we examine the paradox of treating an EBV-associated disease with immunosuppression, highlight data suggesting EBV reactivation under certain MS therapies, and propose that future MS management may require integration of EBV-targeted strategies, including vaccines and virus-directed immunotherapies, to address the underlying viral etiology.

EBV triggers MS; EBV seroconversion precedes MS. Immunosuppressive MS treatments risk EBV reactivation. B-cell depletion may reduce EBV. Future: EBV-targeted MS therapies 🦠✨

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3 days ago

Clinical Presentation, Management, and Outcomes of Mycobacterium Bovis Bacillus Calmette-Guérin (BCG) Infections: A Single-center Retrospective Review Intravesical Mycobacterium bovis bacillus Calmette-Guérin (BCG) is standard therapy for high-risk nonmuscle-invasive bladder cancer. However, M bovis infections can occur and are not well understood. We aimed to characterize clinical phenotypes, diagnosis, management, and outcomes of culture-confirmed M bovis BCG infections following intravesical therapy for urothelial carcinoma.MethodsA retrospective single-center review of adults with culture-confirmed M bovis infection after intravesical BCG (May 2009–July 2024) was conducted, abstracting clinical, microbiologic, treatment, and outcome data.ResultsTwenty-two White male patients (median age, 77 years) were included; 8 (36.4%) had localized genitourinary infection, 6 (27.3%) had dissemination limited to blood, and 8 (36.4%) had dissemination to other organs. Patients with bloodstream-only infection presented acutely (median 1.5 days after last BCG), whereas those with localized or organ-disseminated disease presented months to years after BCG, with the longest diagnostic delays in organ-disseminated infection. Despite all cases had culture-proven M bovis BCG infection, acid-fast smear, Mycobacterium tuberculosis complex polymerase chain reaction, and histopathology had limited sensitivity. All isolates were susceptible to rifampin, isoniazid, and ethambutol; all were resistant to pyrazinamide. Median treatment duration exceeded 9 months, 94.7% achieved cure, and attributable mortality was 5.0% (1 vascular graft infection).ConclusionsM bovis BCG infections following intravesical therapy have favorable outcomes but are often associated with diagnostic delays and prolonged treatment. Early suspicion, comprehensive diagnostic evaluation, and timely surgical source control when indicated are critical. Management strategies should be tailored based on the extent of disease dissemination and individual host factors.

22 pts (median 77yo) had M. bovis BCG infection post-bladder cancer tx: 36% GU-only, 27% blood-only, 36% organ-disseminated. 95% cured after 9+ mos tx; 5% mortality.⏳🦠💊

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3 days ago

Successful Control of Refractory Coccidioides Meningitis With MAT2203 Coccidioides meningitis is a life-threatening complication with Coccidioides spp that requires lifelong antifungal therapy. While some cases respond to azoles, others are refractory and require periodic treatment with intravenous and/or intrathecal (IT) amphotericin B. MAT2203 is a novel formulation of amphotericin B that uses a rolled phosphatidylserine lipid nanocrystal bilayer that is orally absorbed. MAT2203 has been successfully used to treat cryptococcal meningitis and Histoplasma meningitis.Case PresentationIn 2017 a previously healthy construction worker developed coccidioidal pneumonia and meningitis and was treated with liposomal amphotericin B and oral fluconazole. His pneumonia resolved, but his meningitis worsened. Imaging showed vasculitis of his middle cerebral artery and arachnoiditis at the base of the brain and eventually throughout his spine. He required multiple changes in azoles and eventually an Ommaya reservoir so that he could receive periodic IT amphotericin B plus corticosteroids while continuing oral isavuconazole. Treatment response was monitored with symptoms, cerebral spinal fluid (CSF) cell counts, CSF Coccidioides antigen, and imaging. Frequency of IT treatment varied over the course of his illness from 3 times per week to monthly, increasing with symptom flares. A trial of the investigational antifungal olorofim also failed. In 2024, 1 month after his last dose of IT amphotericin B, the patient started treatment with MAT2203. After 6 months of MAT2203 (without any IT or intravenous amphotericin B), Coccidioides antigen in the ventricular CSF was undetectable for the first time and remained so with normalization of glucose and cell counts.ConclusionsMAT2203 may offer an oral therapeutic option for refractory cases of Coccidioides meningitis.

Coccidioides meningitis often needs lifelong antifungals. MAT2203, oral amphotericin B, made CSF antigen undetectable in 6 months, stopping IT/IV therapy.🧠💊 #CocciMeningitis

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4 days ago

Indirect effect of pneumococcal conjugate vaccines on pneumococcal colonization: persistence and dynamics of vaccine serotypes in Sicily (Italy) eleven years post-introduction, 2009 to 2020 In Italy, evidence on the long-term impact of pneumococcal conjugate vaccines on nasopharyngeal carriage remains limited. This study investigates pneumococcal carriage prevalence, serotype distribution, and temporal trends in the decade following the introduction of PCV13 and preceding the onset of the COVID-19 pandemic (2009–2020).MethodsOropharyngeal samples were collected from 12,733 individuals of all ages presenting with influenza-like illness within the national surveillance network for respiratory pathogens. Streptococcus pneumoniae detection and serotyping were performed using real-time PCR-based assays.ResultsOverall pneumococcal carriage was 27.1%. The maximum value was observed in children aged 2-4 years (51.6%), whereas colonization was about 10% in adults, including those aged ≥75 years. Following vaccine implementation, a marked decline in PCV-covered serotypes was observed, accompanied by the rise of non-vaccine serotypes. After several years of sustained pediatric immunization, vaccine serotypes re-emerged, replacing previously expanding non-PCV types. Some persistent vaccine serotypes, including those associated with a higher risk of invasive disease, continued to circulate despite high and longstanding vaccination coverage. Serotype distribution varied significantly by age, and concurrent viral infections, particularly with hRSV, appeared to increase pneumococcal colonization risk.ConclusionsDespite sustained high pediatric vaccination, pneumococcal carriage remained substantial across all ages, with persistent circulation of vaccine and non-vaccine serotypes. Viral co-infection, particularly with hRSV, appeared to facilitate colonization. These findings underscore the need for ongoing carriage surveillance and evolving vaccine strategies to address changing pneumococcal ecology.

In Italy, 27.1% pneumococcal carriage found; 51.6% in kids 2-4 yrs, ~10% in adults. Vaccine serotypes dropped then re-emerged; hRSV ↑ colonization risk.🦠📊

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