International Journal of Infectious Diseases

The COVID-19 pandemic substantially disrupted tuberculosis (TB) prevention, diagnosis, and treatment services worldwide. Despite increased TB notifications in Nepal during the post-pandemic recovery period, the geographic distribution and temporal clustering of notifications remain poorly understood. This study examined the spatial and temporal patterns of TB notifications across Nepal during the COVID-19 recovery period. We conducted a nationwide retrospective ecological analysis of district-level TB notifications across all 77 districts of Nepal from FY 2019/20 to FY 2023/24. Space-time, purely spatial, and purely temporal scan statistics were performed using a discrete Poisson model in SaTScan. Statistical significance was assessed using Monte Carlo simulation with 999 replications. A total of 172,155 TB cases were notified during the study period. TB notification rates increased by 51%, from 92 to 139 per 100,000 population between FY 2019/20 and FY 2023/24. Four statistically significant high-notification space-time clusters were identified (all p < 0.001). The primary cluster included Kathmandu, Lalitpur, Bhaktapur, Makwanpur, Bara, and Parsa districts during FY 2021/22-FY 2023/24 (RR = 1.60). Additional clusters were identified in western Nepal, the eastern Terai, and Rupandehi district. Purely temporal analysis showed a nationwide increase in notifications during FY 2022/23-FY 2023/24 (RR = 1.26, p = 0.001). TB notifications increased substantially during Nepals post-pandemic recovery period, with marked geographic and temporal heterogeneity. Integrating spatial and temporal surveillance may help identify areas requiring geographically targeted TB control strategies.

Background: In 2026, the US Food and Drug Administration (FDA) identified uveitis as a potential signal of serious risk for the B-cell maturation antigen (BCMA) x CD3 bispecific antibodies teclistamab and elranatamab. Uveitis in this setting may reflect opportunistic infection or immune-mediated inflammation, which require opposite management. Methods: We analyzed FDA Adverse Event Reporting System (FAERS) reports from July 2020 to June 2026 (8,690,601 reports after deduplication) using a case-non-case design, calculating reporting odds ratios (RORs) and the information component for primary-suspect reports. Comparators were belantamab mafodotin, talquetamab and CD3 bispecific antibodies used outside myeloma. Every primary-suspect uveitis report (n = 76) was classified as infectious, probable immune-mediated (hereafter immune-mediated) or indeterminate by a physician blinded to a rule-based algorithm. Results: Uveitis was reported in 18 of 2,995 teclistamab and 29 of 1,691 elranatamab reports (ROR 4.10 [95% CI 2.58-6.52] and 11.85 [8.21-17.12]). Of these 47 cases, 20 were infectious (18 cytomegalovirus chorioretinitis; median onset 92 days), and infection-specified uveitis was disproportionately reported for both agents and for CD3 bispecific antibodies used outside myeloma. Thirteen were immune-mediated, arose early (median onset 4 days) and were co-reported with cytokine release syndrome in six; immune-mediated uveitis showed a signal only for elranatamab (8 cases; ROR 3.59, 1.79-7.18), not for teclistamab or any comparator. Six of the eight elranatamab cases originated from Japan. Agreement between physician and algorithm was 98.7%. Conclusions: The FDA uveitis signal appears to comprise a late infectious uveitis shared by most T-cell-redirecting bispecific antibodies examined and an early immune-mediated uveitis that showed a signal only with elranatamab. These hypothesis-generating findings support prompt ophthalmological assessment of new visual symptoms and exclusion of cytomegalovirus retinitis before corticosteroids are started.

Background. Tuberculosis preventive treatment (TPT) with levofloxacin reduces tuberculosis disease incidence in multidrug-resistant or rifampicin-resistant (MDR/RR)-tuberculosis household contacts. However, with age, disease progression risk falls and the frequency of adverse events (AE) rises. Methods. To inform decision-makers, we evaluated the cost-effectiveness of expanding the use of MDR/RR-TPT by age, with and without tests of tuberculosis infection. We modelled MDR/RR-household contact management (HHCM) in 189 countries, incorporating age-dependent risks of disease progression, death and AEs. Incremental cost-effectiveness ratios were calculated as USD/disability-adjusted life year (DALY) averted, and as a fraction of per capita gross domestic product (GDP). Findings. Compared to baseline of MDR/RR-HHCM with TPT for those <15 years, adding TPT up to 45 years was cost-effective at a threshold of 30% GDP in 160/189 modelled countries including 17 of the 30 highest incidence countries. Of these 160 countries, the intervention was cost-saving in 46. Strategies targeting TPT to those testing positive for M. tuberculosis infection were dominated by those without testing. Globally, full use of MDR/RR-HHCM with TPT for all would avert 11,900 (10,400 to 13,800) episodes of tuberculosis, 9,960 (9,100 to 10,900) deaths, and 289,000 (262,000 to 321,000) DALYs, but would result in 71,000 (68,000 to 74,000) SAEs and cost $359 million (294 to 449). Interpretation. Expanding MDR/RR-TPT use to older ages without testing appears cost-effective in most settings, but may require substantial resources and result in large numbers of AEs. Funding. Unitaid

Background: A large increase in mortality from severe acute respiratory infections (SARI) in Brazil in 2025 was mainly driven by influenza A and respiratory syncytial virus (RSV) among children and the aged, but 2026 data remain largely unpublished. Methods: Secondary data on SARI by age group (<2, 2-4, 5-14, 15-49, 50-64, 65+ years) and virus (Influenza A/B, RSV, SARS-CoV-2, adenovirus, rhinovirus, bocavirus, and metapneumovirus) were retrieved for 35 weeks of 2026. Weekly variations in infection rate (IR) and mortality rate (MR) were described by virus and age group. Case fatality ratio (CFR) and vaccine-preventable deaths from influenza, RSV, and SARS-CoV-2 were analysed by age group. Missing virus classification was estimated by multinomial regression. Poisson-based 95% confidence intervals (CI) were calculated for MR. Results: Influenza A infections quintupled during February and March, with a mortality peak in April, mainly due to H2N3. RSV and rhinovirus caused more deaths than influenza viruses, especially among young children (<2) and the aged (65+). The former were most frequently infected by RSV and the latter by rhinovirus. For those 50 years or older, influenza B reached a CFR of about 20%, compared with 5-15% for influenza A, metapneumovirus, rhinovirus, and other non-subtyped viruses. The highest vaccine-preventable MRs per 100,000 were 17.23 for the oldest and 8.62 for the youngest. Under ideal conditions, 6418 lives could have been saved, about half among children and adolescents <15 years old. Conclusions: Vaccine-preventable SARI in Brazil exerted a high toll in fall and winter 2026, mainly due to influenza A, RSV, and rhinovirus. Better vaccine coverage may significantly reduce this toll.

Background: Age is an important determinant of tuberculosis (TB) risk, but population-level age patterns in TB prevalence have not been systematically quantified across settings. We conducted a systematic review of surveys conducted in low- and middle-income countries to quantify trends in TB prevalence across age groups. Methods: We collated age-stratified TB prevalence data for individuals aged 15+ years, from population-based surveys reported between 1993 and 2025. We analyzed data using Bayesian meta-regression models, estimating trends in bacteriologically confirmed pulmonary TB prevalence across age groups. We extended models to understand how age trends varied with alternative outcome definitions and data subsets, and examined correlations between TB age trends and sociodemographic determinants. We also estimated age-stratified notification-to-prevalence ratios as a measure of diagnostic delays for untreated TB. Findings: We included 82 unique surveys reporting age-stratified TB prevalence, spanning 30 countries and 4.6 million participants. These data demonstrated a pattern of increasing bacteriologically confirmed TB prevalence with older age, with each 10-year increase associated with a 30% (95% credible interval: 22, 38) increase in prevalence. TB prevalence for the oldest age group (75+: 796 per 100,000 [522, 1178]) was 6.4 (4.0, 10.4) times higher than the youngest (15-19: 127 per 100,000 [79, 186]), and positive age gradients were estimated for all countries (interquartile range: 23-40% increase per 10-year increase in age). Age gradients were lower in Africa compared to other regions, and for smear-positive compared to bacteriologically confirmed TB. Countries with HIV prevalence [&ge;]5% had flatter age gradients above 40 years of age. Age gradients declined slowly over the study period. Notification-to-prevalence ratios demonstrated a negative age gradient, declining by 10% (7, 14) per 10-year increase in age. Interpretation: The prevalence of untreated TB disease increases substantially throughout adulthood, and lower notification-to-prevalence ratios suggest poorer case detection among older individuals.

BackgroundFebrile neutropenia requires rapid empirical antibiotic therapy, with regimen selection shaped by local prescribing practice and pathogen patterns. We described starting treatment, later drug changes, microbiological findings, and inpatient outcomes. MethodsThis ambispective cohort comprised 96 episodes from 90 patients admitted to a tertiary-level teaching hospital. Treatment and outcome analyses used each episode as the unit of observation. Recorded variables included the starting antibiotics, later regimen modification, microbiology, hospitalization length, invasive fungal infection (IFI) as captured in study records, and disposition. Comparisons based on escalation status were exploratory. ResultCefoperazone-sulbactam appeared in 62/96 initial regimens (64.6%), amikacin in 42 (43.8%), teicoplanin in 28 (29.2%), and meropenem in 14 (14.6%). Eighteen episodes (18.8%) required a change that broadened or substituted antibacterial therapy. Among 31 microbiologically documented infections, 22 (71.0%) yielded Gram-negative organisms and 9 (29.0%) were polymicrobial. Median length of admission was 18.5 days in the escalation group and 9 days in the remainder (p<0.001). Mortality was 27.8% (5/18) with escalation and 5.1% (4/78) without it (p=0.011), with nine inhospital deaths overall (9.4%). ConclusionAntibacterial management differed within this cohort, with treatment escalation required in 18 of 96 episodes. Gram-negative organisms comprised most microbiologically confirmed infections. Escalation marked a clinically complex course with prolonged hospitalization and greater observed mortality; the observational design does not establish comparative efficacy or causation.

Background: Treponema pallidum quantitative polymerase chain reaction (qPCR) positivity and cycle threshold (Ct) by rapid plasma reagin (RPR), disease stage, and other characteristics are poorly characterized in routine-care specimens, leaving it unclear when qPCR of such specimens is informative for diagnosis. Methods: This Japanese multicenter cross-sectional study explored qPCR positivity and Ct by these characteristics. Nonblood specimens collected during routine care underwent qPCR at a central laboratory for this study. Bayesian logistic and normal regressions modeled positivity and mean Ct of TP0574 and polA with stage-specific continuous automated RPR terms, patient characteristics, collection site, and facility random intercepts. Estimates were standardized over the analyzed specimens. Population-group predictions were instead averaged within each group. Results: Among 154 nonblood specimens from 145 patients (71.7% non-MSM men and women) at 14 facilities, 109 (70.8%) were qPCR positive. At RPR 1, adjusted positivity was 72.2% (95% credible interval, 60.9%--82.9%) in primary and 43.8% (16.7%--69.9%) in secondary syphilis. Positivity showed a modest downward trend with RPR in primary but increased in secondary syphilis, reflecting a stage-by-RPR interaction (secondary-to-primary ratio of odds ratios, 1.78; 1.25--2.65). Predicted positivity showed an upward trend with RPR values among MSM; adjusted positivity was relatively high for genital/urethral/urinary and anal/perianal/rectal specimens. Adjusted mean Ct increased with RPR in primary and followed an inverted-U pattern in secondary syphilis. Conclusions: In primary syphilis, nonblood qPCR positivity was high even at low RPR. When serologic findings remain inconclusive in this stage, qPCR is highly recommended for securing an early diagnosis.

Interferon-gamma release assays detect Mycobacterium tuberculosis infection but cannot distinguish infection from active tuberculosis (TB). We evaluated the diagnostic information provided by QuantiFERON-TB Gold Plus (QFT-Plus) among adults investigated for active TB in Brazil and South Africa. Adults with presumptive TB were prospectively enrolled by convenience sampling. QFT-Plus was the index test, and diagnostic classification required microbiological confirmation of TB or an established alternative diagnosis. QFT-Plus results did not inform diagnostic classification. Accuracy was assessed among participants with determinate results, primarily using likelihood ratios. Of 723 participants tested, 48 (6.6%) had indeterminate results, all due to low mitogen responses. Among 675 participants with determinate results, 147 (21.8%) had confirmed TB. Sensitivity was 68.0% (95% CI, 60.1-75.0), specificity was 59.3% (95% CI, 55.0-63.4), and the negative likelihood ratio was 0.54 (95% CI, 0.42-0.69). At the observed prevalence, a negative result left a 13.1% probability of active TB. Negative likelihood ratio confidence intervals included 1 in both South African HIV strata. Specificity was higher among participants with HIV in both countries. Adding TB2 to TB1 alone identified 15 additional TB cases and generated 18 additional positive results among participants without active TB. HIV and active TB were independently associated with indeterminate results in exploratory regression. A negative QFT-Plus result provided insufficient information to exclude active TB. Higher negative predictive values among participants with HIV reflected lower disease prevalence and higher specificity rather than greater sensitivity. Negative or indeterminate results should not terminate diagnostic evaluation.

To deal with the COVID-19 pandemic, Denmark implemented an aggressive program aimed at controlling the pandemic which included both testing and contact tracing programs. The large amount of data collected in Denmark on the pandemic and its integrated nature made it possible to investigate the effectiveness of the testing and contact tracing effort. The results of that investigation and a discussion of the effectiveness and limitations of the different control efforts are reported herein, as are lessons learned concerning possible improvements for the future. The analysis is limited to the period from the start of the COVID-19 pandemic in Denmark (late Feb. 2020) into May 2021, at which time the impact of vaccination intervention was already playing a role with ~25% of the Danish population at least partially vaccinated. From the available data sets we estimate the national Infection Detection Efficiency (IDE) starting around July 1, 2020, the time at which the national infection detection program started to be implemented in a more robust form. The results rely on daily COVID-19 hospital admissions, PCR test results, and anti-body prevalence values for the Danish population. We find that for the long-term average, the combined Danish national testing and contact tracing program identified on average about 55 to 60% of the infected individuals during the period from Sept. 1, 2020, into early May 2021. However, higher infection detection efficiencies were achieved in localized areas for short time intervals. Our investigations further indicate that the Danish testing and contact tracing program, which was among the most ambitious in the world, could have had a better balance between voluntary probing on the one hand and focused contact tracing and targeted testing on the other hand. As typically implemented, it proved to be largely ineffective in controlling the pandemic. However, in at least one case when it was implemented in an enhanced and focused mode, it was able to bring a large local outbreak that dominated the country's cases under control. We have compiled a list of lessons learned regarding the use of contact tracing procedures to control potential future pandemics before vaccinations become available.

Objectives To evaluate the impact of COVID-19 vaccination on the prevention of long COVID (LC) in the Omicron era through an updated systematic review and meta-analysis. Methods We performed an update of our previously published systematic review and meta-analysis of vaccination and LC risk (searches between 1 January 2022 and 1 March 2024). Databases (Embase, MEDLINE, PubMed, Europe PMC, LILACS, Cochrane COVID-19 Study Register) were searched for studies published between 1 March 2024 and 13 July 2026. Observational studies assessing the impact of vaccination on the risk of LC four or more weeks after SARS-CoV-2 infection were included. Vaccines were restricted to those centrally authorised in the European Union. Random-effects meta-analyses, restricted to adults, were performed to calculate pooled odds ratios (OR) of LC in three comparisons: vaccinated (any dose) versus unvaccinated; booster vaccination versus unvaccinated; and booster vaccination versus primary course vaccination only. Results Nineteen new studies were identified, of which ten were included in the updated meta-analyses alongside eight studies from the original review. The pooled OR of LC in vaccinated adults (any dose) versus unvaccinated was 0.75 (95% confidence interval [CI] 0.67-0.84; 13 studies). ORs were also lower for booster vaccination versus unvaccinated (0.73; 95% CI 0.65-0.82; 6 studies), and booster vaccination versus primary course vaccination (0.63; 95% CI 0.53-0.75; 6 studies). Significant associations between vaccination and lower LC odds were observed in subgroup analyses of mRNA-only vaccination and LC outcomes three or more months after infection. Conclusions This updated review and meta-analysis reinforces our previous finding that vaccination may reduce the burden of LC in the Omicron era, with booster doses potentially providing additional protection. Although evidence in high-risk groups now prioritised for vaccination in most countries remains limited, these findings clearly demonstrate the benefits of vaccination and support current seasonal vaccination strategies.

Background: Child-friendly sample collection methods are needed to improve microbiological tuberculosis diagnosis in children. We assessed the feasibility, diagnostic yield, safety, tolerability, and acceptability of nasopharyngeal aspirates (NPA) and stool sample collection for XpertMTB/RIF Ultra (Ultra) testing in children <5 years with severe pneumonia in six high tuberculosis incidence countries. Methods: We conducted a cross-sectional mixed-methods study (10/2020-03/2021) nested within the TB-Speed Pneumonia trial (NCT03831906) in 15 tertiary hospitals. Uptake and diagnostic yield of NPA and stool, sampled by trained nurses, were computed. Nurses documented NPA feasibility and related adverse events. NPA tolerability was assessed through discomfort/distress/pain scales completed by nurses, parents/caregivers, and children >3 years. Individual interviews investigated nurses and parents/caregivers perceptions and experiences of both procedures. Results: Of 542 children enrolled, 541 (99.8%) and 423 (75.5%) had NPA and stool samples successfully collected, respectively; 8 (1.5%) had positive Ultra on any sample, 8 (1.5%) on NPA, and 3 (0.6%) on stool samples. Nurses reported that NPA was difficult to collect in 27 (5.0%) children. 130 (24%) children had bloodstained NPA samples and <5% experienced transient heart rate deceleration, digestive or respiratory distress during NPA. Median nurse-assessed tolerability scores were 1/10 [0,3] before and 5/10 [2,6] during NPA. Although most respondents perceived NPA as painful, all appreciated that NPA aimed to improve child health. Nurses reported that NPA and stool collection was quicker, less invasive than gastric aspiration. Parents/caregivers trusted nurses skills and valued the novelty of NPA. All respondents easily engaged in stool collection, but were frustrated to depend on children passing stool. Nurses underlined that continuous staff training and mentoring would sustain feasibility and self-efficacy in obtaining adequate samples. Conclusions: NPA and stool are viable specimen collection options for microbiological diagnosis of tuberculosis in young children <5 years with severe pneumonia in high tuberculosis incidence countries.

Low pathogenic avian influenza A(H7N7) virus detected in a poultry worker in Taiwan, 2026 was related to viruses circulating in Asian wild birds and possessed PB2 E627K, a mammalian adaptation marker. Enhanced surveillance for H7 viruses in poultry and rapid characterization of human cases are essential to assess pandemic potential.

Background: Following the global resurgence of cholera in 2022, 51 cholera cases were reported by European countries. We previously characterised 49 Vibrio cholerae O1 isolates from these cases using whole genome sequencing. In 2023 and 2024, 59 additional cholera cases were reported by 11 European countries. Aim: We aimed to confirm that V. cholerae O1 isolates associated with cholera cases reported in Europe in 2023-2024 belonged to the epidemic seventh pandemic El Tor (7PET) lineage rather than to non-epidemic V. cholerae O1 lineages, and to characterise their virulence, antimicrobial resistance (AMR) determinants and phylogenetic relationships. Methods: Fifty V. cholerae O1 isolates were available for whole genome sequencing, of which 49 yielded genomes of sufficient quality for analysis. Genomes were analysed together with more than 1,500 publicly available 7PET genomes to place the European isolates into a global phylogenetic context. Results: All 49 genomes belonged to the 7PET lineage and Wave 3. Four sub-lineages were identified: BD1.2 (2/49), AFR12 (6/49), AFR13 (8/49) and Pre-AFR15 (33/49). The predominance of Pre-AFR15 confirms its continued contribution to the ongoing global cholera resurgence. In contrast to our 2022 survey, eight highly drug-resistant AFR13 isolates were detected, documenting the international spread of this highly drug-resistant clone resistant to multiple first-line antimicrobial agents. Conclusion: Whole genome sequencing should be routinely used by reference laboratories to distinguish epidemic 7PET from non-epidemic V. cholerae O1 lineages and to monitor the emergence and international spread of AMR clones. Continued collaborative genomic surveillance of travel-associated cholera cases can provide early insights into the emergence, international spread and antimicrobial resistance of 7PET sub-lineages.

To characterise temporal changes in antimicrobial resistance (AMR) among clinically important bacterial pathogens in Iraq during 2021-2024 and examine their implications for empirical antimicrobial therapy and stewardship. We conducted a retrospective longitudinal analysis of aggregated national AMR surveillance data for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus. Annual resistance proportions were evaluated across clinically relevant antimicrobials. Temporal change was characterised using absolute percentage-point changes and exploratory linear regression. Resistance trajectories were interpreted in relation to empirical treatment options and antimicrobial stewardship. The analysis included 92,338 organism records: 40,496 (43.9%) E. coli, 24,621 (26.7%) S. aureus, 18,223 (19.7%) K. pneumoniae and 8,998 (9.7%) P. aeruginosa. In 2024, ceftriaxone resistance reached 82.9% in E. coli and 65.2% in K. pneumoniae, while ciprofloxacin resistance was 55.4% and 57.9%, respectively. Meropenem resistance reached 37.4% in K. pneumoniae and 62.3% in P. aeruginosa. Conversely, resistance declined for amoxicillin-clavulanate in E. coli (83.5% in 2021 to 57.2% in 2024) and piperacillin-tazobactam in P. aeruginosa (46.4% to 32.9%). Several pathogen-antimicrobial combinations showed marked year-to-year variation, and no temporal trend remained statistically significant after false discovery rate correction. Resistance to several agents central to empirical therapy remains high in Iraq, while substantial carbapenem resistance constrains reliance on carbapenem escalation when resistance to other {beta}-lactams is suspected. Heterogeneous trajectories indicate that empirical recommendations should not rely on single-year national antibiograms alone and support regular integration of national and local resistance surveillance into empirical treatment and antimicrobial stewardship strategies.

BackgroundPost-acute COVID-19 syndrome (PACS) can cause persistent disability involving fatigue, post-exertional malaise, neurocognitive symptoms, and autonomic manifestations. A clinically overlapping condition has been reported following COVID-19 vaccination and termed post-acute COVID-19 vaccination syndrome (PACVS), but its underlying mechanisms remain poorly understood. We investigated whether immune dysregulation, autoreactivity, antigen persistence, and viral reactivation--mechanisms implicated in PACS--are also present in PACVS. MethodsThis cross-sectional study included 28 PACS patients, 29 PACVS patients, and 16 convalescent controls (CCG). Clinical manifestations were assessed using ME/CFS-related symptom questionnaires and the Bell Score. T-cell phenotypes and T cells reactive to SARS-CoV-2 Spike, {beta}1/{beta}2-adrenergic receptor, and M3/M4 muscarinic receptor antigens were analyzed by multicolor flow cytometry. Circulating Spike protein and GPCR autoantibodies were quantified by ELISA, and EBV load by qPCR. ResultsPACS and PACVS showed substantial clinical overlap, although several symptoms were more severe in PACS. GPCR autoantibody profiles were comparable between patient groups, while {beta}2-adrenergic receptor autoantibodies were increased compared with CCG. Only three of 57 conventional immunophenotyping parameters differed between PACS and PACVS in unadjusted analyses, whereas both groups showed multiple alterations compared with CCG. Circulating Spike protein was detected in both patient groups, with the highest prevalence in PACVS. {beta}1/{beta}2- and M3/M4-reactive CD4+ T cells were increased, whereas Spike-specific CD4+ T cells were reduced compared with CCG. EBV reactivation was rare. ConclusionsPACS and PACVS exhibit substantial clinical and immunological overlap, including GPCR-directed autoreactivity and altered receptor-reactive T-cell responses. These shared immune-mediated features suggest overlapping pathophysiological mechanisms and warrant investigation of whether therapeutic strategies currently explored for PACS may also be relevant to PACVS.

Background: TB vaccine development is hampered by the natural history of M. tuberculosis: most infected people rarely progress to disease, so trials must be very large and long to accrue sufficient disease endpoints. Current trials enrol IGRA-positive participants (IGRA: Interferon-Gamma Release Assays), but IGRAs remain positive for many years and cannot distinguish recent from remote infection. Tests for recent infection are now in development, and we argue they could make trials substantially more efficient. Here, we investigate how screening participants prior to enrolment with a test for recent M.tb infection could impact the total number of enrollees required for an adequately-powered TB vaccine trial. Methods: Using a statistical model of vaccine trial recruitment, we estimated the number needed to contact, test, and enrol to achieve an 'effective' trial (defined as 50 disease endpoints), under IGRA-gated enrolment (life-long duration of positivity) vs. enrolment with a test for recent infection. We considered five recruitment strategies: non-test-based enrolment for ages 15-49, ages 12-34, and household contacts of recent cases; and test-based enrolment using IGRA, and a test for recent infection with two-year duration of positivity. The model explored trial recruitment in South Africa, Kenya, and India. Results: Compared with an extended-positivity test, a test for recent infection reduced the median number needed to enrol by 4.2- to 6-fold under favourable conditions. It also outperformed non-test-based strategies, including enrolling household contacts. This comes at the cost of substantially more testing, but crude estimates suggest recency-based enrolment would still be cheaper overall provided the new test does not cost more than roughly 5-10 times an IGRA. Conclusions: Diagnostics for recent M.tb infection have the potential to improve vaccine trial efficiency, but more research is now needed to understand test characteristics and to evaluate their use in this setting. Our Viewpoint sets out the test attributes that would need to be established, such as time to positivity, duration of positivity, sensitivity, and specificity, before such tests could be used in vaccine trials.

BACKGROUND: Indigenous tribes face a disproportionately high tuberculosis (TB) burden due to deep-rooted socioeconomic disadvantage, highlighting the need for strengthened, culturally sensitive control strategies. METHODS: We conducted a 21-year retrospective study (2005-2025) among tribal and neighboring non-tribal populations attending a tribal-serving hospital in Karnataka. Pre-Nikshay data were transcribed from paper registers, and post-Nikshay data were obtained from the digital system. We assessed negative binomial interrupted time-series regression model, data completeness, TB risk factors, and used multivariable logistic regression to identify determinants of poor treatment outcomes and household contact screening yield. RESULTS: We analyzed 1,512 TB cases (tribal = 1,021; non-tribal = 491). TB detection increased significantly over time, with a steeper rise among tribal populations (p<0.001). Nikshay implementation significantly improved data completeness (Wilcoxon W = 9900, p<0.001). Among tribal patients, males had higher odds of poor treatment outcome (aOR 2.81, 95% CI 1.70- 4.85; p<0.001). Diabetes (aOR 2.10, 95% CI 1.05- 4.03; p=0.029) was independently associated with poor treatment outcome. Among 503 index cases, 1,535 household contacts were identified and 1,161 (75.6%) screened; coverage was lower among tribal contacts (69.8% vs 87.2%; p<0.001). CONCLUSIONS: Nikshay strengthened TB surveillance and improved assessment of TB burden and risk factors in tribal communities.

Sepsis is a substantial contributor to neonatal mortality in Africa, with Klebsiella pneumoniae as the leading causative pathogen. Incorporating molecular tools such as whole genome sequencing (WGS) into routine surveillance of important bacterial pathogens, including those causing neonatal sepsis, can support targeted deployment of infection prevention and control measures and treatment interventions. This study aimed to understand the current practices and capacity for culture, identification and genomic analysis of bacterial pathogens in Africa, with a particular focus on K. pneumoniae, to support standardised genomic surveillance. A cross-sectional online survey was distributed to various clinician and scientist networks across Africa. All respondents completed a demographics section, while sections on laboratory test capacity, blood culture practices, WGS, and bioinformatics analysis were completed based on experience in these aspects. Responses were received from 52 institutions in 25 African countries. Among 51 institutions completing the laboratory test capacity section, 61% reported performing blood cultures, with the majority using manual commercial biochemical systems for species identification (71%) and manual disk diffusion for antibiotic susceptibility testing (82%). Participating institutions reported near-universal access to a -80{degrees}C freezer, centrifuge and thermocycler, but shaking incubators were less commonly available (67%). More than half of respondents (54%) indicated that they perform the entire WGS workflow (including DNA extraction, library preparation and WGS) internally, with most performing DNA extraction internally (88%) using column-based kits (70%). Outsourcing was progressively more common at later workflow stages. Infrastructure challenges that limit bioinformatics analysis capabilities were reported by all 23 respondents who completed this question, including limited access to high-performance computing and data storage space. This survey found sufficient capacity to support genomic surveillance of neonatal sepsis pathogens across participating African institutions. However, investments in blood culture, supply chains, sequencing, bioinformatics, and data dissemination capacity are needed to realise its full potential. These findings will support the development of standardised genomic surveillance protocols tailored to the diverse capacities of African laboratories.

ObjectivesRespiratory Syncytial Virus (RSV) vaccine policies have varied globally since their approval in 2023. In the UK, policy has adapted in line with National evidence generation such that from Autumn 2026 at-risk persons [&ge;]65 years old will become eligible for vaccination. Immunosuppressed persons <65 years will still not be offered protection. The objective of this study is to investigate the relative burden of RSV infection by age and immunosuppressed status (IC). DesignRetrospective observational cohort study using routine healthcare data from North West London Integrated Care System. ParticipantsPatients with a confirmed diagnosis of a respiratory viral infection (RSV, Influenza A and B, SARS-CoV2) between October 2021 and July 2025. Main outcomes measuresPrevalence and severity of RSV infection in immunosuppressed persons <65 years old, and to provide a comparative analysis with Influenza and SARS-CoV2 in a sub-cohort tested using a 4-in-1 combined rapid PCR test. ResultsDuring the study period, 1226 patients were diagnosed with RSV of whom 596 (48.6%) were <65 years old. In 1091 patients with clinical data, 341 (31.3%) were IC. Fifty (9.9%) patients <65 years old had severe infection (ICU admission or death within 28 days of diagnosis), of whom 14 (28.0%) were IC. Proportionally, 16.7% of all RSV-associated deaths and 55.1% of all ICU RSV-admissions occurred in adult patients <65 years old. RSV accounted for 665 (10.1%) infections confirmed by 4-in-1 viral PCR testing. Eight-nine (13.4%), 172 (9.3%) and 448 (12.0%) patients with RSV, Influenza A and SARS-COV2 experienced severe infection, of whom 32 (36.0%), 82 (47.7%) and 156 (34.8%) were <65 years old respectively. Eight (25.0%), 20 (24.4%) and 52 (33.3%) of patients <65 years old with severe infection were IC. On adjusted analysis, having an immunosuppressive condition increased the odds of a severe SARS-CoV2 infection, OR (95% CI) 1.36 (1.08-1.71) but not a severe RSV or Influenza infection. ConclusionsSevere RSV infections occur in persons <65 years old, with a significant proportion of patients having an immunosuppressive condition. Urgent research is needed to investigate the potential benefit of extending the current UK RSV vaccine policy to protect younger immunosuppressed adults.

Bundibugyo ebolavirus (BDBV) is causing an ongoing outbreak in the Democratic Republic of Congo (DRC) with no licensed vaccine available. Recent reports have shown the presence of BDBV-cross-reactive antibody responses in humans vaccinated against the related Ebola virus (EBOV). Here, we used an IFN-{gamma} ELISpot assay to assess T cell responses against the EBOV, BDBV and SUDV glycoproteins in clinical trial participants vaccinated with the licensed VSV-EBOV vaccine. We could show that BDBV-cross-reactive T cell responses are detectable in the majority of individuals and that conserved regions within the glycoprotein are targeted. In the absence of a BDBV-specific vaccine, these data support efficacy trials of the VSV-EBOV vaccine during the current outbreak.