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T-cell response plays an important role in SARS-CoV-2 immunogenicity. For people living with HIV (PWH) and solid organ transplant (SOT) recipients there is limited evidence on the reliability of commercially available T-cell tests. We assessed 173 blood samples from 81 participants (62 samples from 35 PWH; 111 samples from 46 SOT recipients [lung and kidney]) with two commercial SARS-CoV-2 Interferon-γ (IFN-γ) release assays (IGRA; SARS-CoV-2 IGRA by Euroimmun, and IGRA SARS-CoV-2 by Roche). The reliability between the tests was judged as low (Cohen's kappa [κ] = 0.20; overall percent agreement [OPA] = 66%). A high proportion of tests were invalid (22% Euroimmun; 8% Roche). When excluding these invalid tests, the agreement was higher (κ = 0.43; OPA = 90%). The low reliability between the two T-cell tests indicates that results should be interpreted with caution in SOT recipients and PWH and that SARS-CoV-2 T-cell tests need to be optimized and further validated for use in vulnerable patient populations.

Background and aims There is no data on hepatitis B virus (HBV) prevalence and treatment eligibility among the general population in Lesotho. We aimed to determine the prevalence of HBV infection in a large-scale cross-sectional survey among the general population in Lesotho, assess determinants of seropositivity, and evaluate treatment eligibility according to the 2024 WHO guidelines.Approach and results We conducted a household-based, cross-sectional survey among participants≥10 years old in 120 randomly sampled village clusters in two districts. From participants screened positive for HBV surface antigen (HBsAg), we collected dried blood spots for HBV DNA measurement and referred the participants to health facilities for clinical assessment and treatment eligibility evaluation.Out of 6709 participants screened, 6705 had a valid HBsAg test result (3509 (52.3%) female, median age 33 years (IQR: 20–53)), which was positive in 78 participants, yielding a prevalence of 1.2% (95% CI: 0.9 to 1.4). Being≥18 years old, male, living in urban areas, living with HIV, consuming tobacco and belonging to higher wealth index quintiles, were associated with increasing odds of HBV infection. Of the 78 participants with HBV infection, 62 (79.5%) linked to care. Among these, 25/62 (40.3%) were also living with HIV and 23/25 (92%) already taking antiretroviral treatment active against HBV. Among the remaining, 10/37 (27.0%) were eligible for antiviral treatment based on HBV DNA, Aspartate aminotransferase to Platelet Ratio Index or alanine aminotransferase levels.Conclusions We observed a low prevalence of HBV infection among Basotho. Treatment eligibility was high mostly due to the presence of HIV co-infection. However, nearly one-third of HBV mono-infected participants were eligible for treatment, suggesting a testing and treatment gap in this population.

ObjectivesTo assess the real-world diagnostic performance of nasal and nasopharyngeal swabs for SD Biosensor STANDARD Q COVID-19 Antigen Rapid Diagnostic Test (Ag-RDT).MethodsIndividuals ≥5 years with COVID-19 compatible symptoms or history of exposure to SARS-CoV-2 presenting at hospitals in Lesotho received two nasopharyngeal and one nasal swab. Ag-RDT from nasal and nasopharyngeal swabs were performed as point-of-care on site, the second nasopharyngeal swab used for polymerase chain reaction (PCR) as the reference standard.ResultsOut of 2198 participants enrolled, 2131 had a valid PCR result (61% female, median age 41 years, 8% children), 84.5% were symptomatic. Overall PCR positivity rate was 5.8%. The sensitivity for nasopharyngeal, nasal, and combined nasal and nasopharyngeal Ag-RDT result was 70.2% (95%CI: 61.3-78.0), 67.3% (57.3-76.3) and 74.4% (65.5-82.0), respectively. The respective specificity was 97.9% (97.1-98.4), 97.9% (97.2-98.5) and 97.5% (96.7-98.2). For both sampling modalities, sensitivity was higher in participants with symptom duration ≤ 3days versus ≤ 7days. Agreement between nasal and nasopharyngeal Ag-RDT was 99.4%.ConclusionsThe STANDARD Q Ag-RDT showed high specificity. Sensitivity was, however, below the WHO recommended minimum requirement of ≥ 80%. The high agreement between nasal and nasopharyngeal sampling suggests that for Ag-RDT nasal sampling is a good alternative to nasopharyngeal sampling.

IntroductionTo sustainably provide good quality care to increasing numbers of people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in resource-limited settings, care delivery must shift from a "one-size-fits-all" approach to differentiated service delivery models. Such models should reallocate resources from PLHIV who are doing well to groups of PLHIV who may need more attention, such as those with treatment failure. The VIral load Triggered ART care Lesotho (VITAL) trial assesses a viral load (VL)-, participant's preference-informed, electronic health (eHealth)-supported, automated differentiated service delivery model (VITAL model). With VITAL, we aim to assess if the VITAL model is at least non-inferior to the standard of care in the proportion of participants engaged in care with viral suppression at 24 months follow-up and if it is cost-saving.MethodsThe VITAL trial is a pragmatic, multicenter, cluster-randomized, non-blinded, non-inferiority trial with 1:1 allocation conducted at 18 nurse-led, rural health facilities in two districts of northern Lesotho, enrolling adult PLHIV taking ART. In intervention clinics, providers are trained to implement the VITAL model and are guided by a clinical decision support tool, the VITALapp. VITAL differentiates care according to VL results, clinical characteristics, sub-population and participants' and health care providers' preferences.Expected outcomesEvidence on the effect of differentiated service delivery for PLHIV on treatment outcomes is still limited. This pragmatic cluster-randomized trial will assess if the VITAL model is at least non-inferior to the standard of care and if it is cost saving.Trial registrationThe study has been registered with clinicaltrials.gov (Registration number NCT04527874; August 27, 2020).

Introduction Lopinavir/ritonavir (LPV/r) has been proposed as repurposed drugs for pre-exposure and postexposure prophylaxis as well as therapy of COVID-19. Coronavirus postexposure prophylaxis (COPEP) trial aims at assessing their efficacy as postexposure ring-prophylaxis among adults exposed to SARS-CoV-2.Methods and analysis COPEP is a two-arm open-label cluster-randomised trial conducted in three cantons of Switzerland. Asymptomatic contacts (≥16 years) of individuals diagnosed with COVID-19 will be randomised (2:1) to either LPV/r (400 mg/100 mg two times per day) for 5 days, or a standard of care arm (no treatment). Asymptomatic individuals may be either SARS-CoV-2 positive or negative. Contacts living in the single household will form a cluster and will be randomised into the same arm. All participants will be followed-up for 21 days and undergo daily monitoring for COVID-19 symptoms. The primary endpoint is 21-day incidence of laboratory-confirmed COVID-19 with ≥1 compatible symptom, analysed in an intention-to-treat (ITT) analysis. The secondary endpoints include the 21-day incidence of COVID-19 as well as SARS-CoV-2 infection in a modified ITT analysis, excluding participants who had a positive SARS-CoV-2 RT-PCR from oropharyngeal swab and/or a positive SARS-CoV-2 IgG serology at baseline. Assuming a 21-day incidence for COVID-19 of 20% among contacts without postexposure chemoprophylaxis, to detect a relative risk reduction of 60% (ie, translating in an absolute reduction from 20% to 8%), with a power of 80%, an alpha of 5%. Accounting for design effect of cluster design of circa 1.1, we plan to enrol 200 participants to the LPV/r arm and 100 to the standard of care arm, 300 participants in total.Ethics and dissemination Ethics approval has been granted by the Commission Cantonale d’Ethique de la Recherche, Ethikkommission Nordwest- und Zentralschweiz and Comitato Etico Cantonale (ref 2020-00864) and Swissmedic (2020DR3056). Results from this trial will be disseminated via journal articles and presentations at national and international conferences.Trial registration number Clinicaltrials.gov Registry (NCT04364022); Swiss National Clinical Trial Portal Registry (SNCTP 000003732).Registered report identifier CCER 2020-0864.

Abstract Background Depression and alcohol use disorder have been shown to be associated with poor adherence to antiretroviral therapy (ART). Studies examining their association with viral suppression in rural Africa are, however, scarce. Methods This study reports prevalence of depressive symptoms and alcohol use disorder, and their potential association with adherence and viral suppression in adult patients on ART in ten clinics in rural Lesotho, Southern Africa. Results Among 1,388 adult patients (69 % women), 80.7 % were alcohol abstinent, 6.3 % were hazardous drinkers (men: 10.7 %, women: 4.4 %, p

Abstract Background Cervical cancer is the fourth most common cancer in women worldwide, and women with human immunodeficiency virus (HIV) are particularly at risk of developing it. Regular screening effectively prevents morbidity and mortality. This mixed-methods study quantitatively assessed cervical cancer screening uptake and qualitatively explored the process of undergoing cervical cancer screening to understand possible reasons for delayed screening among women with HIV in Lesotho. Methods Between October 2020 and March 2022, the Viral load Triggered ART care in Lesotho (VITAL) trial enrolled women aged 18 years and older with HIV who were taking antiretroviral therapy (ART). Cervical cancer screening delay was defined as reporting a screening that occurred more than two years ago or never having been screened. Cervical cancer screening uptake and the association between screening delay and sociodemographic variables were assessed using a multivariable mixed-effects logistic regression model accounting for clustering at clinic level. In-depth interviews were conducted with 16 women to obtain information on awareness, perceptions, and barriers to cervical cancer screening and were analyzed using thematic analysis. Results Quantitative data were available for 3790 women. Among them, cervical cancer screening was delayed in 1814 (47.9%), including 1533 (40.5%) who were never screened. Compared to women aged 25 to 39 years, women aged 18 to 24 years (adjusted odds ratio (aOR) 2.8; 95% confidence interval (CI) 2.1–3.7), women aged 40 to 59 years (aOR 1.3; CI 1.1–1.6), and women older than 60 years (aOR 3.9; CI 3.0-5.1) were at higher risk of screening delay. Furthermore, time on ART below 6 months (aOR 1.6; CI 1.1–2.3) compared to above 6 months was associated with screening delay. Qualitative data identified limited awareness of cervical cancer risks and screening guidelines, misconceptions and fears created by the influence of other women’s narratives, and low internal motivation as the main barriers to screening uptake. Conclusions Cervical cancer screening delay was common. Limited personal awareness and motivation as well as the negative influence of other women were the primary internal barriers to cervical cancer screening. Awareness and screening campaigns in Lesotho should consider these factors. Trial registration clinicaltrials.gov, NCT04527874, August 27, 2020.

Abstract Background The World Health Organization’s (WHO) Mental Health Gap Action Programme (mhGAP) is a validated intervention that can be provided by non-specialised healthcare workers to individuals with unhealthy alcohol use. However, it typically requires several in-person sessions at a health facility, which may limit its feasibility and effectiveness in remote settings. This trial compares mhGAP-Standard, a 4 to 6 in-person session intervention, to mhGAP-Remote, a 1 in-person session intervention followed by 8 week of short message service (SMS) in Lesotho. We hypothesise that mhGAP-Remote is superior to mhGAP-Standard in reducing alcohol use (as detailed by the primary and secondary outcomes below). Methods This is a two-arm randomised open-label multicentre superiority trial. Participants allocated to mhGAP-Standard receive 4 in-person sessions using motivational interviewing, identifying triggers, and alternative behaviours, with the option of two additional booster sessions. Participants in the mhGAP-Remote arm receive 1 in-person session covering the same content, followed by standardised SMSs over 8 weeks that reinforce intervention content. Non-specialist providers deliver the intervention and receive weekly supervision. Adults (N planned = 248) attending participating health facilities for any reason and who meet criteria for unhealthy alcohol use based on the Alcohol Use Disorders Identification Test ([AUDIT] score ≥ 6 for women, ≥ 8 for men) are individually randomised to the two arms (1:1 allocation, stratified by participant sex and age (≥ 50 vs

Summary: In people with HIV-1 (PWH), Mycobacterium tuberculosis (MTB) infection poses a significant threat. While active tuberculosis (TB) accelerates immunodeficiency, the interaction between MTB and HIV-1 during asymptomatic phases remains unclear. Analysis of peripheral blood mononuclear cells (PBMC) transcriptomic profiles in PWH, with and without controlled viral loads, revealed distinct clustering in MTB-infected individuals. Functional annotation identified alterations in IL-6, TNF, and KRAS pathways. Notably, MTB-related genes displayed an inverse correlation with HIV-1 viremia, at both individual and signature score levels. These findings suggest that MTB infection in PWH induces a shift in immune system activation, inversely related to HIV-1 viral load. These results may explain the observed enhanced antiretroviral control in MTB-infected PWH. This study highlights the complex interplay between MTB and HIV-1, emphasizing the importance of understanding their interaction for managing co-infections in this population.

Summary: Infection prevention and control (IPC) research has focused on the hospital setting, neglecting the rapidly expanding home healthcare (HHC) sector. Current infection prevention recommendations do not reflect the challenges specific to the HHC setting.This scoping review considered any original studies reporting on barriers or facilitators to infection prevention practices in the context of HHC. Study characteristics were mapped, and a descriptive content analysis was performed. Based on the findings we propose a framework of eight HHC setting characteristics relevant to infection prevention implementation.33 studies fulfilled the eligibility criteria. A majority of studies addressed sharps injury or blood and body fluid exposure prevention (N=15) and the majority were conducted in the United States (N=23). Study methodologies employed were surveys (N=18), qualitative (N=11), direct observation (N=7), and one interventional study. The HHC setting characteristics relevant to infection prevention implementation were: the care process in the patient's immediate environment; the need to bring equipment and materials into the home; the provision and financing of equipment and materials; the use of patient space and facilities; the unique position of and the expectations towards HHC providers; working alone with little support; the intermittent nature of care; the attitudes of HHC providers formed by their work circumstances.Interventional studies generating higher-quality evidence for implementation are lacking. Furthermore, implementation of aseptic technique and the decontamination and reprocessing of equipment are poorly studied in the HHC setting and deserve more research interest. The proposed framework may guide future research and implementation work.

BackgroundCommunity-based care (CBC), where care is delivered outside of the traditional health facility setting, has been proposed to narrow the mental health (MH) and substance use (SU) treatment gap in Africa.ObjectiveThis scoping review aims to comprehensively summarize CBC models addressing adolescent and adult MH (depression, anxiety, trauma, suicidal behavior) and (non-tobacco) SU problems in Africa.MethodsWe searched PsycINFO, Embase, Scopus, CINAHL, and Medline Ovid. Studies and protocols were included if they reported on CBC intervention’s effects on MH or SU symptoms/ diagnoses, acceptability, feasibility, or patient engagement in care, regardless of whether the intervention itself was designed specifically for MH or SU.ResultsAmong 11,477 screened publications, 217 were eligible. Of the unique intervention studies (n = 206), CBC models were classified into the following approaches (non-mutually exclusive): psychotherapeutic (n = 144), social (n = 81), lifestyle/physical health (n = 55), economic (n = 26), and psychopharmacological (n = 2). While quantitative results suggest possible efficacy of CBC models, description of CBC location was often poor. Fewer interventions addressed suicidal behavior (n = 12), the needs of adolescents (n = 49), or used traditional healers or religious figures as providers (n = 3).ConclusionMany CBC models have been tested on MH and SU in Africa and should be critically appraised and meta-analyzed in subsequent reviews, where possible.

BACKGROUND: Long-term symptoms after acute COVID-19 are highly debated. Nevertheless, data on long-term symptoms of COVID-19 in healthcare workers are scarce. METHODS: We assessed frequency and risk factors of persisting symptoms in a retrospective cohort of healthcare workers infected with SARS-CoV-2. RESULTS: Persistent symptoms at 3 and 12 months were reported by 26.5% and 13.5% of participants, respectively. Most commonly reported symptoms were fatigue, impaired sense of taste or smell and general weakness. A history of depression or state of exhaustion, pre-existing lung disease and older age were associated with persisting symptoms. CONCLUSION: Our study shows that a relevant proportion of healthcare workers with mild COVID-19 report persisting symptoms over 3 and 12 months. Although in the majority of cases symptoms are mild, this study highlights the need for further research into causes and therapy.

Abstract Objective Eritrea is the most frequent country of origin among asylum seekers in Switzerland. On their journey through the desert and across the Mediterranean Sea, Eritrea refugees are often exposed to traumatizing experiences. The aim of this study is to assess the mental health status and resilience of Eritrean migrants in Switzerland upon arrival and one-year post-arrival, using standardized mental health screening and resilience assessment tools. Results At baseline, 107 refugees (11.2% female, median age 25) were interviewed: 52 (48.6%) screened positive for Post-Traumatic Stress Disorder (score ≥ 30), 10.3% for anxiety (≥ 10) and 15.0% for depression (≥ 10); 17.8% scored as risk/hazardous drinkers (≥ 8). The majority (94.4%) had a high resilience score (≥ 65). For one-year follow-up, 48 asylum seekers could be reached. In interviews 18 (38%) of these reported imprisonment in a transit country and 28 (58%) that they had witnessed the death of a close person along the migration route. At the one year assessment, rates of risky/hazardous alcohol use remained unchanged, rates of positive PTSD screening tended to be lower (50.0% (24/48) at baseline vs 25.0% (12/48) at follow-up), as were rates of positive screening for anxiety (8.3% vs 4.2%) and depression (14.6 vs 6.3%).

Abstract Objective For the past 10 years, refugees from Eritrea represented the majority of asylum seekers in Switzerland. However, data on their health status remains limited. In this cross-sectional survey followed by a 1-year cohort study, we screened newly arrived Eritrean refugees for cardiovascular risk factors at arrival and 1-year post registration. Results Among 107 participants (88.8% male; median age 25, 9 (9%) had a body mass index ≥ 25 kg/m2, one (1%) had elevated blood pressure, one (1%) had diabetes, 19% smoked and two (2%) had a low density lipoprotein (LDL) cholesterol ≥ 4.1 mmol/l. Among the 48 participants (5 females, 43 males) followed, there were no significant changes in cardiovascular risk profile 1 year post-arrival.