This study aimed to understand hospital doctors’ priorities (target use cases and aetiologies) for the development of a new rapid diagnostic test for patients with fever.

A cross-sectional online survey.

Europe-wide.

Secondary and tertiary care doctors involved in patient assessment and diagnosis across Europe.

Online survey from April to September 2024.

Importance of developing a new test on a scale of 1–10 for up to 19 ‘use cases’ (types of febrile presentations in specific demographic groups): use case scores and ranks and differences across subgroups of respondents, with free text to capture additional suggestions; respondents’ preferences (multiple choice) regarding which aetiologies should be included in a new test.

265 respondents from 30 European countries (out of 270 starting the survey) were included in the analysis. Top priorities included febrile immunocompromised patients and fever without a focus for both paediatric and adult use cases, and 1–3 months old febrile infants. Rankings were similar across clinician subgroups despite some differences in average scores. 92% (243/263), 95% CI 89% to 95%, of respondents would find a ‘generic’ test for bacterial aetiology useful, even if it does not differentiate between Gram-positive and Gram-negative aetiologies. 54% (63/116), 95% CI 45% to 63%, of respondents would find a ‘generic’ test for inflammatory aetiology useful when seeking to diagnose children for whom Kawasaki’s disease (KD) is on the differential, even in the absence of any KD-specific test, 83% (96/116), 95% CI 75% to 89%, would find such a ‘generic’ test useful if they could use it alongside a KD test when desired.

Clinicians prioritise the most vulnerable patients (because of age or comorbidities) and unclear presentations (fever without a focus) for the development of a new fever diagnostic test. Even relatively simple (eg, bacterial, inflammatory) tests could provide added value to most clinicians.

This study aims to estimate the prevalence of long-lasting severe fatigue and identify possible risk factors in a 2-year follow-up of patients with predominantly mild-to-moderate SARS-CoV-2 infection.

Prospective cohort study.

A community-based cohort from Telemark and Agder Counties, Norway.

A total of 159 PCR-confirmed SARS-CoV-2 positive individuals in the period between 28 February and 17 December 2020 were included at 12 months after SARS-CoV-2 infection, and 93 responded at 24 months follow-up.

Fatigue was assessed using the Fatigue Severity Scale (FSS), and health-related quality of life using the RAND version of health-related quality of life Short Form 36 (SF-36), developed by the RAND Corporation. SARS-CoV-2 antibodies were measured at 12 and 24 months.

Severe fatigue (FSS ≥5) was reported by 36% at 12 months and 31% at 24 months. A higher proportion of women than men reported severe fatigue at 12 months (p=0.08). The number of acute-phase symptoms was associated with severe fatigue. No association was found between severe fatigue and anti-SARS-CoV-2 antibody levels, demographic variables or reinfection status. The severe fatigue group scored significantly lower on all domains of SF-36.

In this cohort, severe fatigue was common, greatly impacted quality of life and persisted for up to 2 years following SARS-CoV-2 infection. Fatigue severity was associated with symptom burden in the acute phase but not with antibody levels or other demographic variables. These findings underscore the need for long-term follow-up and support for affected individuals.

Administration of antibiotics before incising the skin (‘surgical antimicrobial prophylaxis’) is a critical infection prevention strategy in surgery. Extending doses of prophylaxis into the postoperative period is a common practice in cardiac surgery; however, the benefit has not been clearly established and may lead to emergence of antimicrobial resistance and patient harm. We present the protocol for a large international multicentre, adaptive, pragmatic, double-blind, three-arm, placebo-controlled, randomised, non-inferiority clinical trial to compare the incidence of surgical site infection after three different durations of postoperative surgical antimicrobial prophylaxis in patients undergoing cardiac surgery.

This adaptive, multi-arm multistage non-inferiority trial will compare intraoperative only (Arm A), to intraoperative and 24 hours (Arm B) and, to intraoperative and 48 hours (Arm C) of intravenous cefazolin and placebo as surgical antimicrobial prophylaxis in 9180 patients undergoing cardiac surgery. The adaptive design allows for potential dropping of any of the three arms if clear inferiority is indicated at any of the scheduled interim analyses. The trial will evaluate the clinical and cost-effectiveness of the three different antibiotic prophylaxis durations.

Ethics approval will be obtained at all participating sites. Results of the study will be submitted for publication in peer-reviewed journals and the key findings presented at national and international conferences. Patients and members of the public will also be involved in the dissemination and translation of the trial results.

NCT05447559.

Debilitating Symptom Complexes Attributed to Ticks (DSCATT) is a new term for an unexplained Australian syndrome—people who suffer from a chronic, multifaceted and debilitating illness, characteristically attributed to tick bites, but in a country without endemic Lyme disease. Despite the profound morbidity of DSCATT, no single causative agent has been identified and there are no recognised treatments for the illness at present. An increasing body of evidence shows psychological therapies such as Acceptance and Commitment Therapy (ACT) can be effective in reducing symptom-related disability and improving quality of life for other unexplained syndromes. Here we present a study protocol to assess the feasibility of an ACT-informed intervention for patients suffering from DSCATT, to be used adjunctively to their pre-existing healthcare. The study aims to assess the acceptability, practicality and demand for the treatment. Additionally, we will examine the effects of therapy on participants’ health and well-being, its safety, potential mediators of response to therapy and its preliminary cost-effectiveness.

We will assess the feasibility of a 32-week, randomised, waitlist-controlled, parallel convergent mixed-methods pilot trial for DSCATT. Participants will be randomised in a 1:1 ratio to receive either 16 sessions of ACT-informed therapy adjunctive to their pre-existing healthcare, delivered one-to-one with a trial therapist within a 20-week period or be assigned to the waitlist control group where they will continue their treatments as usual. We will collect quantitative and qualitative data to address study aims, with retention rate being the primary feasibility outcome.

The study has ethical approval from Austin Health Human Research Ethics Committee (HREC). The outcomes will be published in peer-reviewed journals. Data from participants who have given extended consent will be available for other HREC-approved studies.

ACTRN12623000372684, prospectively registered 13 April 2023, URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385579&isReview=true; the last participant is expected to complete in November 2026.

This study aimed to quantify how patient risk factors relate to COVID-19 severity across categories 1–5 in a prospective, hospital-based cohort. We hypothesised that greater severity would be associated with higher odds of intensive care unit (ICU) admission and in-hospital mortality. Secondary aims were to assess associations with age, viral variants, symptom clusters, lymphocyte count, fasting blood glucose and cytokine profiles.

Prospective cohort study.

A secondary-care/tertiary-care hospital and linked community settings in Cheras, Kuala Lumpur, Malaysia.

This study was nested within the COVGEN project, a prospective COVID-19 cohort conducted at Hospital Canselor Tuanku Muhriz UKM (HCTM), Cheras Health Clinic and the Bandar Tun Razak COVID-19 Assessment Centre in Cheras, Kuala Lumpur, Malaysia, from 1 August 2021 to 31 October 2022. 2532 participants were enrolled at baseline. Eligible participants were Malaysian citizens aged 12–18 years (paediatric/adolescent) or ≥18 years who had reverse transcription-polymerase chain reaction–confirmed COVID-19 at recruitment and resided in Kuala Lumpur or Selangor. Patients who had a clinically unstable condition and those who declined participation (personally or via a next-of-kin or legal representative) were excluded. This analysis included 559 patients hospitalised at HCTM; after excluding five with incomplete questionnaires, 554 remained for analysis (413 admitted to general wards and 141 to ICUs). Categories 3–5 comprised hospitalised patients, whereas categories 1–2 included hospitalised individuals and a subset recruited from community settings.

Primary outcomes included disease severity (categories 4–5 vs 1–3), ICU admission and in-hospital mortality. Secondary outcomes included associations with age strata, viral variant (delta vs omicron), symptom clusters, lymphocyte count, fasting blood glucose and cytokines: interferon gamma-inducible protein 10, interferon gamma, interleukins 8, 10, 2, 6 and 7 and tumour necrosis factor alpha.

141 of 554 (25.5%) patients required ICU care. Compared with milder categories, category 5 was associated with markedly higher odds of ICU admission (OR 204.50; 95% CI 37.54 to 1114.18; p55 versus

An increasing clinical severity category was strongly associated with ICU admission and mortality. Age, delta infection, specific symptom clusters, lymphopenia, hyperglycaemia and pro-inflammatory cytokines identified higher-risk patients, supporting risk-stratified management and prioritisation for enhanced monitoring.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe, multisystem condition that often emerges after viral infections and affects physical and cognitive function. Severely affected patients are underrepresented in research due to immobility and exertional intolerance.

This is a prospective, non-interventional observational study investigating the feasibility and tolerability of home-based diagnostics in patients with severe and very severe ME/CFS. Phase 1 includes remote identification using validated questionnaires. Phase 2 involves home visits for physiological, cognitive and biological assessments. The primary outcome is feasibility; secondary outcomes include tolerability and methodological barriers.

The study protocol was approved by the Ethics Committee of the University of Freiburg (No. 25-1031-S1). Written informed consent is obtained from all participants. Results will be disseminated via peer-reviewed publications and patient support groups.

DRKS00035231; FRKS005506.

Among the five hepatitis viruses, the hepatitis B virus (HBV) is a major cause of serious acute and chronic liver infections worldwide. The major public health impact of HBV infection arises from chronic liver disease, including cirrhosis and hepatocellular carcinoma, which predominantly affects young and middle-aged adults of both sexes. Therefore, preventive interventions focusing on mothers and infants are critical due to vertical and early childhood transmission dynamics.

HBV prevalence largely varies among pregnant women in Ethiopia because of multiple interrelated factors. This umbrella review will consolidate all existing systematic reviews and create a more reliable picture of HBV infection and its determinants among pregnant women in Ethiopia.

This umbrella review will be conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses reporting standards. The review will focus on identifying and integrating evidence from eligible systematic reviews and meta-analyses, with methodological quality appraised using the MeaSurement Tool to Assess systematic Reviews instrument. A comprehensive literature search strategy will be developed using relevant Medical Subject Headings alongside free-text keywords. Electronic searches will be conducted in PubMed/MEDLINE, African Journals Online, Web of Science, Scopus and Google Scholar. Statistical heterogeneity among the included reviews will be quantified using the I² statistic. Data management and meta-analytic procedures will be performed using STATA version 17, and effect estimates will be presented with corresponding 95% CIs to determine statistical precision.

This review uses only published or publicly available data, so ethics approval is not required. Findings will be disseminated via peer-reviewed publications, conference presentations and shared with policymakers, healthcare partners, clinicians and patients to inform policy, enhance education and guide future research.

PROSPERO (CRD420251118982).

Multidrug-resistant tuberculosis (MDR-TB) is an urgent public health challenge in Namibia, with profound socioeconomic consequences. The high burden of both tuberculosis and HIV complicates treatment and underscores the need for optimised drug therapies. Precision medicine, which leverages patient-specific genetic and molecular information, offers promise for improving MDR-TB outcomes. However, its effective application relies on population-specific data, particularly understanding how individuals metabolise tuberculosis drugs and how genetic diversity drives variability in treatment response. Currently, no pharmacokinetic (PK) or pharmacogenetic (PG) data on TB treatment exist for Namibian populations. This gap is particularly concerning, given the country’s genetic diversity, environmental factors and comorbidities that may uniquely influence drug metabolism. This study aims to generate PK and PG data to inform dose optimisation and support personalised treatment strategies for MDR-TB in Namibia. The findings will contribute to improved patient care and inform health system strengthening based on locally relevant evidence.

This cross-sectional study will consist of 100 Namibian participants with matched human DNA and PK data of MDR-TB cases receiving isoniazid, clofazimine, bedaquiline and the fluoroquinolones (levofloxacin or moxifloxacin). PK sampling will be divided as follows: 30 individuals will undergo intensive PK sampling, while the remaining (n=70) will undergo sparse PK sampling. DNA will be extracted at Stellenbosch University (SU), and samples will be genotyped using the H3Africa microarray. Sequences will be aligned to the human reference genome, hg38 (GRCh38p13), using the freely available Burrows-Wheeler Aligner. A subset of the samples (n=20–30) will undergo whole genome sequencing (WGS) to verify imputation results and identify novel genetic variants potentially affecting PK in this population.

Quality control and variant call format file generation will be performed using the Genome Analysis Toolkit best practices (V.3.5). Intensive and sparse PK data will be pooled for the development of a population PK (popPK) model using a non-linear mixed-effects modelling approach. The popPK model will characterise the relationship between TB drug dose and exposure, including quantifying covariates, including genetic variation, explaining PK variability, providing a foundation for dose optimisation and personalised treatment strategies.

Ethics approval was obtained from the University of Namibia Human Research Ethics Committee for Health (Ref. SOM18/2024), the Ministry of Health and Social Services (Ref. 22/4/2/3), the SU Health Research Ethics Committee (Ref. N21/11/136) and the University of Cape Town Human Research Ethics Committee (Ref. 500/2022).

To estimate tuberculosis (TB) incidence trends in the high-altitude Xizang, China, and to explore the key intervention strategies on achieving the WHO 2030 TB control target.

We developed a susceptible–exposed–infectious–recovered transmission model using routinely reported TB surveillance data from 2004 to 2022. Scenario-based simulations were conducted to project future TB incidence under alternative intervention strategies. Model assumptions are as follows: (1) a stable population, (2) lifelong vaccine-induced immunity, (3) infectiousness of active TB cases, (4) relapse risk after recovery and (5) homogeneous mixing within the population.

Seven prefectures of Xizang Autonomous Region on the Tibetan Plateau, China.

An estimated population of approximately 3 million individuals residing in Xizang.

We assessed the epidemiological impact of four interventions implemented independently: increasing vaccine efficacy rate, reducing transmission rates of susceptible individuals, decreasing progression rate from latent TB infection to active disease and reducing relapse rate among successfully treated patients, compared with continuation of current control measures.

The estimated basic reproduction number (R₀ ) for TB in Xizang was 0.39 (95% CI 0.21 to 0.71) in the absence of additional interventions, which was the highest among all regions of China. Model simulations indicated that all four evaluated interventions were each likely to reduce TB incidence, but only reducing the latent-to-active TB progression had a substantial effect. A 50% reduction in the progression rate was predicted to lower TB incidence from 66.56 (62.00–70.11) to 40.54 (37.15–43.77) cases per 100 000 population, meeting the WHO 2030 TB control target.

Targeted management of individuals with latent TB infection should be strengthened to substantially reduce TB transmission in high-altitude areas.

Onchocerciasis, commonly known as river blindness, is a parasitic disease caused by Onchocerca volvulus affecting millions predominantly in sub-Saharan Africa. Robust epidemiological evidence points to a clinical relationship between onchocerciasis and epilepsy, a condition termed onchocerciasis-associated epilepsy (OAE). Despite extensive research and various successful elimination programmes over the past decades, the pathogenesis of OAE is still unknown. Current hypotheses propose that O. volvulus microfilaria, their excretory-secretory products or the newly discovered filarial O. volvulus RNA virus 1 (OVRV1) virus may traverse the blood-brain barrier, triggering seizures or immune responses that result in neurological damage. However, direct evidence of microfilaria or their DNA in cerebrospinal fluid (CSF) or brain tissue remains elusive, likely due to immune-mediated parasite clearance. Additionally, investigations into the potential neurotoxicity of these novel filarial viruses have yet to be pioneered.

This prospective cohort study will involve 100 ivermectin-naïve children aged 2–5 years, recruited from rural communities in the Aketi health zone, located in the Democratic Republic of Congo. This region is known to be an onchocerciasis-endemic area with a high prevalence and transmission of OAE, despite years of community-directed treatment with ivermectin. Lumbar punctures (LP) will be performed in children presenting with complex febrile seizures according to WHO’s paediatric guidelines. CSF samples will be examined for white blood cells, protein levels, glycorrhachia, microfilaria, OVRV1 and O. volvulus biomarkers. Children will be followed annually, monitoring the development of epilepsy and O. volvulus infection. This approach aims to elucidate the presence of O. volvulus and OVRV1 in the brain and their role in the pathogenesis of epileptic seizures and the myriad of clinical symptoms observed in OAE.

The protocol has been approved by the Ethics Committee of the University of Kisangani (UNIKIS/CE/KGB/001/2025) and the University of Antwerp (project ID 7323-Edge n/a-BUN B3002025000078). Written informed consent will be obtained from all parents and/or legal guardians of children for whom an LP is considered. Findings will be disseminated at national and international levels via meetings and peer-reviewed open-source publications. Study data will be stored in an open repository.

Pan African Clinical Trials Registry (PACTR202507670131109).

Post-COVID-19 syndrome (PCS) is characterised by persistent symptoms, such as fatigue, dyspnoea, depression and sleep problems, following SARS-CoV-2 infection. The long-term course and impact on quality of life remain unclear. This review aims to synthesise evidence on longitudinal changes in symptom prevalence, severity and health-related quality of life (HRQoL) in adults with PCS.

This systematic review will include longitudinal studies (randomised controlled trials, non-randomised trials, prospective and retrospective cohort studies) of adults (≥18 years) with PCS, defined by symptoms persisting beyond 4 weeks after acute infection. Eligible studies must report changes in prevalence or severity of fatigue, dyspnoea, depression, sleep problems or HRQoL from baseline to at least one follow-up visit.

We will systematically search MEDLINE, Embase, PsycINFO, Web of Science, Scopus, CINAHL and Epistemonikos, with no restrictions on language, date or publication status. Two reviewers will independently screen studies, extract data and assess risk of bias using validated tools appropriate to study design. Disagreements will be resolved by consensus or a third reviewer.

A narrative synthesis will summarise study characteristics and symptom trajectories. Where sufficient data are available, random-effects meta-analyses will be conducted to estimate pooled changes in symptom prevalence (ORs), severity ((standardised) mean differences) and HRQoL ((standardised) mean differences). Meta-regression and subgroup analyses will explore potential effect modifiers. Certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

No ethical approval is required. Findings will be disseminated via peer-reviewed publication, conference presentations and plain language summaries.

CRD420251011612.

The Infant Gut Bacterial Study in Nigeria (INBUGS-NG) investigates how delivery mode, antibiotic exposure, feeding practices and environmental factors shape gut microbiome development and acquisition of antibiotic resistance genes (ARGs) during the first year of life in northern Nigeria.

Between February and July 2024, 90 mother–infant dyads were enrolled at a tertiary hospital in Kano city, Nigeria. This was a prospective longitudinal cohort with follow-ups at 10 scheduled time points: days 0, 1, 3, 5, 7, 14, 28, 90, 180 and 365. We also intensified stool sampling after infant antibiotic administration, enabling dense early-life sampling. To date, the cohort has contributed 480 infant stool samples, 232 maternal rectal swabs, 254 breast milk samples and 806 environmental samples (total 1772). In parallel, socio-demographic, clinical and cultural data were collected using Research Electronic Data Capture (REDCap) and household visit diaries.

Baseline data show that 84/90 mothers (93.3%) received postpartum antibiotics, and 26/90 infants (28.9%) received antibiotics within the first 3 months of life. Only 8% of infants were exclusively breastfed, with early water supplementation common. Caesarean deliveries accounted for 25% of births, and the mean gestational age was 38.5 weeks. Across the cohort, high retention was achieved, and the study has generated a unique long-read metagenomic resource from an African infant population, with analyses ongoing.

Shotgun long-read metagenomic sequencing (Oxford Nanopore) will enable strain-level and plasmid-level profiling of microbial communities and ARGs. Planned analyses include associations between early-life exposures and resistome dynamics, as well as cross-cohort comparisons with a parallel study in Pakistan. Follow-up will continue through 12 months.

Young children and children living with HIV are at high risk of progressing to tuberculosis (TB) disease following Mycobacterium tuberculosis (Mtb) exposure and infection, and also of developing severe forms of disease and TB-related mortality. Identifying children who have very early (sub-clinical) TB disease, prior to progression to clinically apparent TB, would mean that TB preventive treatment (TPT) could be more efficiently targeted to this group. Identifying biomarker changes on drug therapy in children with Mtb infection or very early disease could pave the way for the development of tests that can identify which children have viable bacilli and are therefore at increased risk of disease progression.

The INTREPID study will use already collected samples taken from well-phenotyped paediatric cohorts in three clinical studies conducted in South Africa in children Mtb exposure to disease and from children treated for Mtb infection and early TB disease, as well as targeted Mtb antibody analysis. Data on viral co-infections and relevant clinical and epidemiological parameters will be integrated and evaluated to identify the optimal biosignatures that can predict future progression to clinically overt disease in children below 5 years of age, including those living with HIV.

The study protocol received ethical approval from the Stellenbosch University Health Research Ethics Committee (N23/03/025). The study findings will be disseminated through peer-reviewed publications, scientific conferences and formal presentations to healthcare professionals and to local communities, in collaboration with the Desmond Tutu TB Centre Community Advisory Board.

Increasing evidence suggests that dolutegravir (DTG), endorsed by the WHO since 2018 for first-line antiretroviral therapy (ART), is associated with significant weight gain and potentially also with cardiometabolic disorders. In an effort to expand therapeutic options for people living with HIV (PLHIV), the EvaLuating the non-inferiority of DORAvirine vs DOlutegravir trial aims to compare the virologic efficacy of doravirine (DOR) and DTG-based regimens and to assess their safety, including a focus on cardiometabolic effects.

This is an international, phase III, multicentre, open-label, non-inferiority, randomised trial that will enrol 610 ART-naïve PLHIV (HIV RNA≥1000 copies/mL at screening) across six countries (Brazil, Cameroon, France, Côte d’Ivoire, Mozambique and Thailand) spanning four continents. Key inclusion criteria include age ≥18 years, confirmed HIV-1 infection with plasma RNA levels ≥1000 copies/mL, indication for ART initiation and no prior ART exposure. Participants will be randomised in a 1:1 ratio to receive either DOR 100 mg once daily in combination with tenofovir disoproxil fumarate (TDF) (300 mg daily) plus lamivudine (3TC) (300 mg daily) or DTG (50 mg daily) in combination with TDF (300 mg once daily) plus either emtricitabine (FTC) (200 mg daily) or 3TC (300 mg daily). Randomisation will be stratified by screening HIV-1 RNA load (≤100 000 or >100 000 copies/mL) and by country. The primary outcome is virological efficacy, defined as the proportion of participants achieving HIV-1 RNA

Primary outcome results (week 48) are expected in early 2028. The project was submitted to and approved by national ethics committees and pharmaceutical regulatory authorities in all participating countries: Brazil (CEP INI FIOCRUZ (21.040-900)/CEP HGNI (26.030-380)); Cameroon (CNERSH (2024/09/1717/CE/CNERSH/SP)/Ministry of Public Health (D30-1464/AAR/MINSANTE/SG/DROS/CRC); Côte d'Ivoire: (CNESVS (0018224/MSHPCMU/CNESVS-km)/AIRP (1329/AIRP/DISMP/Om/kbaag); France (CTIS CPP/ANSM (2023-508626-10-00)); Mozambique (CNBS (20/CNBS/25)/ANARME (4635/380/ANARME)); Thailand: (IHRP (08/1944)/Thai FDA: ongoing on 19 January 2026). The trial received authorisation from the French National Commission for Data Protection and Liberties (CNIL) under approval number 924 302. Written informed consent is obtained from all participants prior to any study-specific procedures and trial enrolment, in accordance with the Declaration of Helsinki and applicable national regulations. Study findings will be disseminated through publication in peer-reviewed journals and presentations at national and international scientific conferences. Results will also be communicated to policymakers, healthcare professionals, community stakeholders and study participants through appropriate dissemination activities, including policy briefs, stakeholder meetings and lay summaries on dedicated and easily accessible platforms.

NCT06203132; EU-CT, 2023-508626-10-00.

Enteric fever, primarily caused by Salmonella enterica Typhi and Salmonella enterica Paratyphi A (SPA), is endemic mainly in South Asia, disproportionately affecting school-age children. Although typhoid conjugate vaccines (TCVs) are effective and implemented in many countries, no licensed vaccine exists against paratyphoid A. Bivalent vaccines targeting both S. Typhi and SPA may address this gap. Although field efficacy trials are not considered feasible, controlled human infection models (CHIMs) offer an alternative pathway for evaluating vaccine efficacy. This will be the first efficacy study of a bivalent vaccine against typhoid and paratyphoid A using a paratyphoid CHIM.

This is a phase II multicentre, double-blind, randomised controlled trial assessing the efficacy and immunogenicity of a bivalent conjugate vaccine candidate, Serum Institute of India Typhoid Conjugate Vaccine (Bivalent) (SII-TCV(B)), against SPA using a CHIM in healthy UK adults aged 18–55 years. A total of 192 participants will be randomised 1:1 to receive either SII-TCV(B) or a licensed Vi-polysaccharide typhoid vaccine (Vi-PS). All participants will be orally challenged with S. Paratyphi A (strain NVGH308) 28 days postvaccination. Participants will be monitored closely for 14 days and treated at 14 days postchallenge or promptly on diagnosis, according to prespecified criteria. The primary objective is to evaluate vaccine efficacy of SII-TCV(B) against paratyphoid infection using a CHIM. The coprimary immunogenicity objective is to assess non-inferiority of the typhoid IgG response compared with a licensed Vi-PS control.

The study has received ethical approval from the Berkshire Research Ethics Committee (24/SC/0309) and regulatory approval from the UK Medicines and Healthcare products Regulatory Agency. Results will be disseminated via peer-reviewed publications and scientific meetings.

ISRCTN65855590.

To evaluate the performance of Ghana’s environmental surveillance (ES) system for poliovirus (PV) detection from 2018 to 2022 using standardised indicators developed by the WHO and the US Centers for Disease Control and Prevention.

A retrospective performance evaluation using 10 key indicators benchmarked against global targets for PV surveillance.

Seven regions across Ghana, participating in the national ES programme implemented under the Global Polio Eradication Initiative.

Wastewater sampling was conducted at designated ES sites, supported by field collection teams and laboratory personnel responsible for sample acquisition, processing and reporting of PV detection results.

Detection rates of PV and non-polio enteroviruses (NPEVs), timeliness of sample collection and reporting, data quality and system stability.

A total of 738 wastewater samples were collected. The system demonstrated high sensitivity, detecting circulating vaccine-derived PV type 2 in 51 (6.9%) of samples, Sabin PV types 1 and 3 in 61 (9.5%) and 114 (17.8%), respectively, and NPEVs in 491 (66.5%) of samples. Over 80% of samples met the recommended 21-day collection-to-reporting time frame. Data quality exceeded the ≥80% threshold, and workflows remained stable throughout the evaluation period.

Ghana’s ES system for PV was found to be flexible, stable and effective in generating high-quality data for early detection and public health response. These findings underscore the system’s critical role in supporting polio eradication efforts and highlight its potential as a model for surveillance in similar settings.

To characterise long-term trajectory of recovery in individuals with long covid.

Prospective cohort.

Single-centre, specialist post-COVID service (London, UK).

Individuals aged ≥18 years with long covid (hospitalised and non-hospitalised) from April 2020 to March 2024.

Routine, prospectively collected data on symptoms, quality of life (including Fatigue Assessment Scale (FAS) and EuroQol 5 Dimensions (EQ-5D), return to work status and healthcare utilisation (investigations, outpatient and emergency attendances). The primary outcome was recovery by self-reported >75% of ‘best health’ (EQ-5D Visual Analogue Scale) and was assessed using Cox proportional hazards regression models over 4 years. Linked National Health Service England registry data provided secondary care healthcare utilisation and expenditure.

We included 3590 individuals (63.3% female, 73.5% non-hospitalised, median age 50.0 years, 71.9% with ≥2 doses of COVID-19 vaccination), who were followed up for a median of 136 (0–346) days since first assessment and 502 (251–825) days since symptom onset. At first assessment, 33.2% of employed individuals were unable to work. Dominant symptoms were fatigue (78.7%), breathlessness (68.1%) and brain fog (53.5%). 33.4% of individuals recovered to >75% of best health prior to clinic discharge (recovery occurred median 202 (94–468) days from symptom onset). Vaccinated individuals were more likely to recover faster (pre: HR 2.93 (2.00–4.28) and post: HR 1.34 (1.05–1.71) COVID-19 infection), whereas recovery hazard was inversely associated with FAS (HR 0.37 (0.33–0.42)), myalgia (HR 0.59 (0.45–0.76)) and dysautonomic symptoms (HR 0.46 (0.34–0.62)). There was high secondary care healthcare utilisation (both emergency and outpatient care). Annual inpatient and outpatient expenditure was significantly lower in hospitalised individuals while under the service. When compared with the prereferral period, emergency department attendances were reduced in non-hospitalised patients with long covid, but outpatient costs increased.

In the largest long covid cohort from a single specialist post-COVID service to date, only one-third of individuals under follow-up achieved satisfactory recovery. Fatigue severity and COVID-19 vaccination at presentation, even after initial COVID-19 infection, was associated with long covid recovery. Ongoing service provision for this and other post-viral conditions is necessary to support care, progress treatment options and provide capacity for future pandemic preparedness. Research and clinical services should emphasise these factors as the strongest predictors of non-recovery.

To identify the factors influencing the choice of private healthcare facilities among individuals experiencing tuberculosis (TB) symptoms.

Cross-sectional study.

The data for this study were obtained from a cross-sectional population-based TB prevalence survey conducted in 33 districts of Tamil Nadu, a state in southern India, between February 2021 to July 2022.

130 932 individuals, 15 years and above, residents of the selected cluster for the past 1 month, were included. Hospitalised patients, sick/morbid individuals and the institutional population were excluded.

Of 143 005 eligible individuals, 130 932 (91.6%) participated. Among them, 9540 individuals were found to have at least one TB symptom. Of these symptomatic individuals, 2678 sought healthcare, with 62.7% in the public facilities and 37.3% in private facilities. Factors associated with seeking care in the private healthcare facilities included working in organised sector (aOR: 1.3; 95% CI 1.0 to 1.7; p

Conversely, individual with symptom of weight loss (aOR: 0.4; 95% CI 00.3 to 00.6; p25 years (aOR: 0.6; 95% CI 0.4 to 0.9; p

The study highlights the distinct factors that could affect healthcare seeking for TB symptoms in the public and private healthcare settings for TB and the need for tailored interventions and customised healthcare policies to address such gaps and distinctions in care seeking.

Treatment failure remains a major challenge in tuberculosis (TB) management. Rapid and objective assessment of treatment response is essential, as existing tools have limited accuracy and slow turnaround times. The PATHFAST TB LAM Ag assay (PATHFAST-LAM), an automated chemiluminescent enzyme immunoassay, was developed to quantify lipoarabinomannan (LAM) in sputum within 1 hour. Previous studies have shown a strong correlation between sputum LAM concentration and culture-based bacterial load. However, its clinical utility for predicting poor outcomes during treatment has not been prospectively evaluated.

We will conduct a prospective longitudinal study enrolling newly diagnosed, bacteriologically confirmed patients with pulmonary TB at Rhodes Chest Clinic and Mbagathi County Referral Hospital in Nairobi, Kenya. We will follow participants throughout the 6-month treatment course, attempting to collect sputum weekly during weeks 1–4, biweekly during weeks 5–12 and monthly during months 3–6. We will measure LAM concentrations at these time points using the PATHFAST-LAM assay. The primary outcome is to assess whether changes in sputum LAM concentration during the intensive phase (baseline to week 4 and/or week 8) predict a composite poor outcome, defined as positive sputum culture at month 6, treatment failure, death during treatment or relapse within 3 months after treatment completion. The primary endpoint is the area under the curve from the receiver operating characteristic analysis, representing the predictive performance of changes in sputum LAM concentration for the composite poor outcome. We will identify the optimal cut-off value for LAM change and estimate sensitivity and specificity with 95% CIs using 2x2 tables. We will apply an adaptive design that allows sample-size re-estimation after interim analysis.

The study was approved by the Kenya Medical Research Institute (KEMRI/SERU/CRDR/124/5241) and Nagasaki University (250619327). Findings will be disseminated through peer-reviewed publications and scientific meetings.

NCT07157904.

Understanding the epidemiological shifts of respiratory syncytial virus (RSV) is essential to inform public health interventions, particularly given its increased burden on healthcare systems post-COVID-19 pandemic. This study aimed to examine age-specific trends and seasonal variations in RSV incidence, considering the recent introduction of a newborn RSV immunisation programme in Ireland.

A surveillance time series study analysing routinely collected RSV notification data.

National-level weekly RSV notifications collected by the Health Service Executive-Health Protection Surveillance Centre in Ireland from 2012 to 2024.

Infants (

Annual trends in RSV epidemiology with special reference to the pre- and post-COVID-19 winter surges, and the time lag in age-related transmission to peak incidence among the various age groups. Data were analysed to evaluate incidence rates, peak timing, age-related transmission trends and lag times before and after the COVID-19 pandemic.

The study examined the increasing incidence of RSV post-COVID-19 and a significant shift toward earlier RSV peaks in recent years (2021/2022, 2022/2023 and 2023/2024 seasons) in Ireland, with the onset and peak of the season nearly 2 months earlier than in pre-COVID-19 pandemic seasons (p

This analysis highlights an early seasonal onset and intensified RSV burden among infants in recent winters (2021/2022, 2022/2023 and 2023/2024 seasons). Quantifying the time lag for the community-level RSV transmission from infants and young children to older adults will offer insights to optimise RSV intervention strategies as a ‘life-course approach’ to alleviate healthcare system pressures during peak seasons.