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Factors associated with non-adherence to clinic visits among patients with severe mental illness enrolled in the SMILE study in Uganda.
Get PDFBACKGROUND: Non-adherence to clinic visits among patients with severe mental illness (SMI) presents challenges to patient management, treatment outcomes, and research in resource-limited settings. This study investigated the factors associated with non-adherence to clinic visits in Uganda, using appointment attendance as a proxy for clinic adherence. METHODS: This cohort study took place at Butabika National Referral Mental Hospital and Masaka Regional Referral Hospital from January to March 2018. A total of 1,201 participants with confirmed diagnoses of SMI were systematically sampled from over 3,000 outpatients. Data on socio-demographic, psychosocial, psychiatric, and behavioural factors were collected, with adherence defined as attending scheduled visits at 3, 6, 9, and 12 months post-enrolment. Descriptive statistics, bivariate, and multivariate logistic regression analyses were employed to identify significant predictors of non-adherence. RESULTS: The overall prevalence of non-adherence to clinic visits was 20% (95% CI: 17.8 − 22.3%), with males showing higher rates (22.9%) compared to females (17.6%). Factors significantly associated with increased non-adherence included younger age, being treated at Butabika National Referral Mental Hospital, and alcohol use. Conversely, higher social support was linked to improved adherence. Among psychiatric variables, patients with major depressive disorder and severe psychiatric symptoms were more likely to miss appointments. CONCLUSIONS: The study highlights the multifaceted nature of non-adherence in patients with SMI, emphasizing the need for targeted interventions addressing socio-demographic, psychosocial, and clinical factors. Enhancing social support, managing psychiatric symptoms, and reducing substance use are critical strategies for improving adherence rates, which could, in turn, lead to better health outcomes and resource optimization in mental health services. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12888-025-07121-7
Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) predicts mortality in patients with febrile illness in southern Mozambique.
Get PDFBACKGROUND: Fever is a leading reason for seeking healthcare globally. Early in the course of febrile illness, it is challenging to identify patients at risk of severe and fatal infections. Quantifying biomarkers of immune and endothelial activation may facilitate patient triage. METHODS: We prospectively enrolled children ≥2 months and adults with fever visiting two Mozambican hospitals from December 2018 to February 2021. Standard clinical and laboratory parameters, including lactate levels, were assessed at presentation. Plasma levels of Angpt-2, CHI3L1, CRP, IL-6, IL-8, PCT, sFlt-1, sTNFR1, sTREM-1, and suPAR at presentation were retrospectively quantified. Clinical outcomes were evaluated up to 28 days. We assessed the prognostic performance of biomarkers for 28-day mortality and explored their association with other adverse outcomes. RESULTS: This study includes 1955 participants, with 93 deaths occurring within 28 days. We show that all biomarker levels are elevated in inpatients compared to outpatients and are associated with 28-day mortality (all p < 0.001). sTREM-1 is the best biomarker predicting 28-day mortality with an AUROC of 0.82 (95% CI: 0.78-0.86), superior to that of PCT (p < 0.001), CRP (p < 0.001), and lactate (p = 0.0033). Its prognostic performance is consistent across age and sex, but is reduced in HIV-positive individuals (AUROC = 0.73, 95% CI: 0.66-0.80). Adding sTREM-1 improves the discrimination of clinical severity scores for 28-day mortality. Among discharged inpatients, sTREM-1 is positively correlated with duration of hospitalisation (p < 0.001). Among outpatients, sTREM-1 levels are higher in those seeking further care (p = 0.0022) or subsequently hospitalised (p = 0.012). CONCLUSIONS: sTREM-1 is a promising biomarker for risk stratification of all-age, all-cause febrile illnesses in resource-limited settings
Tissue-specific T cell profiles in Mycobacterium tuberculosis uninfected IGRA negative and positive individuals
Get PDFIntroduction
Interferon-gamma release assays (IGRAs), such as the T-SPOT.TB and QuantiFERON-TB Gold, are commonly used to detect immune responses to Mycobacterium tuberculosis (M.tb) and identify latent TB infection. However, their role in reflecting immune dynamics within tissues, especially in the absence of active disease, remains unclear.
Methods
Post-mortem tissues, including lung, lymph nodes, spleen, and bronchoalveolar lavage, were collected from apparently healthy, HIV-negative road traffic accident victims. M.tb infection was ruled out using liquid MGIT culture, while M.tb exposure history was assessed with the TSPOT.TB assay. T and B cell phenotyping was performed using a 29-color flow cytometry panel, with data analyzed in FlowJo and GraphPad Prism.
Results
Of the 52 individuals recruited, 48% were IGRA-positive (TSPOT+). Using a 29-color flow cytometry panel, we analyzed T and B cell populations across various tissues. We observed similar overall frequencies of CD3, CD4, CD8, and CD19 cells, as well as memory T and B cell subsets defined by CCR7/CD45RA and IgD/CD27 between TSPOT+ and TSPOT individuals. Notably, in the lungs, TSPOT+ individuals exhibited a higher frequency of CD4+ tissue-resident memory (TRM) T cells, along with increased expression of KLRG1, a marker of terminal differentiation, on mature CD4+CD27 T cells. This phenotype was specific to CD4 T cells in the lungs, highlighting the known role of CD4 T cells in TB immunity and their localization to the primary site of infection.
Discussion
Our findings suggest that IGRA positivity, while indicating immune memory, may also be associated with highly differentiated CD4 T cells in tissue-specific compartments, particularly in the lungs. These localized immune changes raise important questions about the long-term effects of chronic immune engagement following repeated M.tb exposure in endemic settings. Further research is needed to assess the clinical implications of these findings, including their impact on susceptibility to future infections or disease progression
Hybrid, vaccine-induced and natural immunity against SARS-CoV-2 in traditional food markets in Bolivia (2020-2022): A cross-sectional analysis of a serological survey.
Get PDFBACKGROUND: In low-and middle-income countries, market vendors played a crucial role in food security during the coronavirus pandemic. High numbers of contacts, combined with social, political and health system upheaval in Bolivia, meant they were highly exposed to SARS-CoV-2 infections. METHODS: Demographic, clinical and serological data were collected at survey rounds between 2020 and 2022 from a cohort of market vendors in two purposively selected markets where the community and researchers co-promoted health and safety. We used these longitudinal data to examine SARS-CoV-2 anti-spike antibody levels between those vaccinated with and without previous infection and those unvaccinated. The association between antibody levels, and vaccine status, socio-demographic and health information was assessed using linear regression. FINDINGS: A total of 213 market vendors had repeated serological sampling in July, and November 2021, and again in May 2022. In November 2020, 105 (49.3 %) of this cohort had participated in a pre-vaccination municipal serological survey. Seroprevalence then was 45·7 % (95 %CI 36·3-55·4). By November 2021, 67·8 % of the full cohort had one vaccination and seroprevalence was 83·6 %. We showed IgG levels in those seropositive were higher in participants with evidence of vaccination and prior infection compared to those unvaccinated. By May 2022, the majority of participants developed antibodies against SARS-CoV-2, and these differences were attenuated. INTERPRETATION: A substantial proportion of vendors were susceptible to SARS-CoV-2 in late 2020 when, nationally, excess mortality was high. Our analyses suggested a combination of natural infection and vaccination provided better protective antibody levels than natural infection alone at the peak of the pandemic. Future pandemic planning requires timely targeted serological surveys to understand pandemic dynamics and support prompt interventions. In addition, communication with organized communities can inform effectiveness of pandemic mitigation strategies including improved vaccination uptake. Timely quantitative IgG level monitoring can also inform waning immunity. FUNDING: This study was supported by the Medical Research Council and a National Institutes for Health and Care Research (NIHR) Global Effort on COVID-19 (GECO) Health Research award 2020 [MR/V028561/1]
Building trust during crises by engaging with existing distrust.
Get PDFIt has often been argued that trust cannot be built during crises. While this line of thinking recognizes the importance of building trust before or after crises, it negates the possibility of building trust during a crisis. This paper offers two scenarios to argue for the possibilities of building trust during crises by engaging with existing distrust, with special reference to examples during the COVID-19 pandemic. The first considers distrust towards vaccines and public health interventions among Black Americans that was addressed through interventions that partnered with trusted third parties during the COVID-19 pandemic. The second discusses the Indian transgender community where trust networks built between public health organizations and activists groups was mobilized to engage with existing distrust during the COVID-19 pandemic. Despite the success of these interventions, this perspective paper ends by clarifying that engaging with distrust does not have to result in achieving public health goals with a brief considerations of two cases: the polio vaccine boycott in Nigeria (2003) and medical populism in the United States during the COVID-19 pandemic. These examples highlight that if existing distrust toward the medical system is not addressed, then space is created during crises-periods for distrust to be mobilized in ways that compromise public health goals
Challenges and opportunities of artificial intelligence in African health space.
Get PDFThe application of artificial intelligence (AI) to healthcare in Africa has the potential to transform productivity, diagnosis, disease surveillance, and resource allocation by improving accuracy and efficiency. However, to fully realize its benefits, it is necessary to consider issues concerning data privacy, equity, infrastructure integration, and ethical policy development. The use of these tools may improve the detection of diseases, the distribution of resources, and the continuity of care. The use of AI allows for the development of policies that are tailored to address health disparities based on evidence. While AI may increase accessibility and affordability through telehealth, remote monitoring, and cost reductions, significant barriers remain. Ethical guidelines are needed to ensure AI decisions align with medical standards and patient autonomy. Strict privacy and security controls are crucial to protecting sensitive health data. This article evaluates the current and potential roles of AI in the African health sector. It identifies opportunities to address challenges through tailored interventions and an AI framework to simulate policy impacts
The effect of centralising novel cell therapies for solid cancers - a health systems planning model for Europe.
Get PDFBACKGROUND: Integrating cell therapies for solid cancers requires centralising services to ensure high quality and poses unique challenges for all healthcare systems. In this national population-based study, we modelled the effect of different centralisation scenarios in the English NHS on travel times, equity and hospital capacity as an archetype to inform European planning. METHODS: We identified 10,050 patients treated with systemic therapy for metastatic colorectal cancer in 139 NHS hospitals between 2016 and 2018. Seven hypothetical scenarios A-G centralised cell therapy services to between 15 and 51 centres. For example to A) 51 comprehensive cancer centres; or D) 15 CAR-T centres. For each scenario reallocation of patients to the designated specialist centre was based on patient preferences using conditional logistic regression models; travel times were calculated using a geographic information system; multivariable linear regression models estimated the variation in travel burden across demographic characteristics. KEY FINDINGS: For each centralisation scenario there was a 3 times increase in predicted travel time. Centralising services to comprehensive cancer centres (scenario A) had the smallest impact on travel time (additional 40.9 min); 72 % of patients remained within 1 h of specialist services. Centralisation to existing CAR-T centres (scenario D) resulted in 44 % of patients not having access to a facility within 1 h. For 5 scenarios additional travel burden disproportionately affected low socioeconomic groups. CONCLUSIONS: Localisation of solid cancer cell therapy services in Europe requires a balance between access, equity, and clinical safety. This modelling approach can be used in all European health systems, to understand the pre-implementation impact of centralisation to inform optimum service design and mitigations
Impact of increasing CD4 count threshold eligibility for antiretroviral therapy initiation on advanced HIV disease and tuberculosis prevalence and incidence in South Africa: an interrupted time series analysis.
Get PDFINTRODUCTION: We investigated the impact of increasing CD4 count eligibility for antiretroviral therapy (ART) initiation on advanced HIV disease (AHD) and tuberculosis (TB) prevalence and incidence among people living with HIV (PLHIV) in South Africa. METHODS: We conducted an interrupted time series analysis with de-identified data of PLHIV aged ≥15 years initiating ART between April 2012 and February 2020 at 65 primary healthcare clinics in KwaZulu-Natal, South Africa. Outcomes included monthly proportions of new ART initiators presenting with AHD (CD4 count <200 cells/µL) and TB disease. We created a cohort of monthly ART initiators without TB and evaluated the cumulative incidence of TB within 12 months follow-up. We used segmented binomial regression models to estimate relative risks (RR) of outcomes, allowing for a step and slope change after expanding the ART initiation CD4 count eligibility from <350 to <500 cells/µL in January 2015 and following Universal Test and Treat (UTT) implementation in September 2016. RESULTS: Among 209 984 participants, median age was 32 (range: 26-38), and 141 499 (67.4%) were female. After January 2015, the risk of AHD at initiation decreased in step by 25.0% (RR=0.750, 95% CI 0.688 to 0.812) and further reduced by 26.9% following UTT implementation (RR=0.731, 95% CI 0.681 to 0.781). The risk of TB at initiation also decreased in step by 27.6% after January 2015 (RR=0.724, 95% CI 0.651 to 0.797) and further decreased by 17.4% after UTT implementation (RR=0.826, 95% CI 0.711 to 0.941) but remained stable among initiators with AHD. Among the incidence cohort, we saw a step decrease in the risk of new TB by 31.4% (RR=0.686, 95% CI 0.465 to 0.907) following UTT implementation. Among the incidence cohort with AHD, there was weak evidence of a step decrease in the risk of new TB (RR=0.755, 95% CI 0.489 to 1.021), but the slope decreased by 9.7% per month (RR=0.903, 95% CI 0.872 to 0.934) following UTT implementation. CONCLUSIONS: Our data support the added benefit of decreased TB co-burden with expanded ART access. Early diagnosis and immediate linkage to care should be prioritised among PLHIV
Closing the diagnostic gap in male genital schistosomiasis (MGS): current detection tools and novel strategies.
Get PDFMale genital schistosomiasis (MGS), a gender-specific manifestation of urogenital schistosomiasis and neglected tropical disease, typically results from the entrapment of Schistosoma haematobium eggs within the male genital tract. Across the world, there are no current and accurate estimates of the burden of MGS, due to disease underreporting primarily from diagnostic challenges and a lack of general awareness within the health system. Diagnostic methods for MGS are extremely limited. Conventionally, semen microscopy for Schistosoma ova is used though this technique suffers from low sensitivity and lacks protocol standardization. The introduction of molecular diagnostics, such as polymerase chain reaction (PCR), has partly helped overcome this challenge of low sensitivity, though may not be suitable for use in resource-constrained settings. To address these challenges, in this review, we propose a two-step diagnostic algorithm for MGS in accordance with recent WHO guidelines, consisting of a high sensitivity serological test followed by a high specificity test (microscopy or molecular assay, dependent on setting). Further investigation is required into standardization of sample collection, processing, storage, and analysis in order to identify an evidence-based optimal diagnostic pipeline. New diagnostic tools are needed such as isothermal molecular assays, alongside optimization for semen analysis, which may alleviate barriers to diagnosis and present opportunities for integration with other sexual and reproductive health screening. These areas of future investigation underpin the development of a suitable diagnostic pipeline, as the continued neglect of MGS and its underdiagnosis presents a threat to the goal of elimination of schistosomiasis as a public health problem
Dengue Infections Among Household Contacts of Symptomatic Index Cases: Implications for Community-Based Intervention Studies.
Get PDFBACKGROUND: Dengue is a global health concern, with half of the world's population at risk and no antiviral treatment available. This Phase 0 study investigated dengue infections among household contacts (HHCs) of dengue index cases (ICs) and assessed the feasibility of conducting a Phase 2 trial for a novel antiviral. METHODS: Participants were enrolled in Nha Trang, Vietnam, from April 2022 to February 2023. Dengue ICs were identified within 72 h of fever onset, and their healthy adult HHCs enrolled within 48 h. Blood samples and questionnaires were collected bi-weekly for four weeks, with a follow-up visit on day 40. DENV RT-qPCR, NS1, and anti-DENV IgM/IgG ELISAs were performed. RESULTS: Overall, 130 dengue ICs and 301 HHCs were enrolled, with 91.7% (276/301) completing all follow-up visits. Baseline anti-DENV IgG showed prior dengue infections in 262/301 HHCs (87.0%). Fifty HHCs were excluded from the HHC infection analysis based on evidence of a DENV infection (viral load [VL], NS1, IgM, and IgG results) at enrollment. During follow-up, 2.0% of HHCs (5/251) had DENV infections based on virological parameters (DENV RNA and/or NS1 positivity), and anti-DENV IgG/IgM seroconversion was detected in 7.2% (18/251). CONCLUSIONS: This study demonstrated the operational feasibility of a dengue IC-HHC design for a Phase 2 trial