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Associations between herpes zoster vaccination and herpes zoster with dementia risk in APOE‐e4 carriers and non‐carriers
Get PDFBackground: Recent studies have reported a reduced risk of dementia in herpes zoster vaccine (HZ‐Vx) recipients. However, none evaluated whether genetic factors influence this potentially protective effect. We used the UK Biobank (UKB) and FinnGen (FG) cohorts to investigate associations between HZ‐Vx or herpes zoster (HZ; shingles) and dementia risk by APOE‐e4 carrier status.
Method: This study used structured data from 1990‐2022 (UKB)/2023 (FG). Exposed adults (HZ‐Vx/HZ) were matched (1:5) by age, sex, and APOE‐e4 status (≥1 allele vs. 0) to unexposed adults. Observation started 12‐months post‐exposure. We measured associations between each exposure and incident all‐cause dementia (dementia), vascular dementia (VaD) or Alzheimer's disease (AD) by Cox regressions in age‐exposure‐specific cohorts: 1) HZ‐Vx in 65‐74‐year‐olds; 2) HZ in 45‐64‐year‐olds; and 3) HZ in 65‐74‐year‐olds. Hazard ratios (HRs) are reported overall and by APOE‐e4 status.
Result: HZ‐Vx was associated with a reduced risk of dementia (HR=0.68 [95% confidence interval: 0.59‐0.77]) and AD (HR=0.69 [0.57‐0.84]) in UKB. Associations in APOE‐e4 non‐carriers and carriers were: dementia HR=0.59 [0.48‐0.73] and HR=0.75 [0.63‐0.90]; AD: HR=0.64 [0.47‐0.88] and HR=0.73 [0.57‐0.92], respectively. HZ in 45‐64‐year‐olds was associated with increased risk of dementia (UKB: HR=1.21 [1.04‐1.42]; FG: HR=1.55 [1.31‐1.82]) and VaD (UKB: HR=1.46 [1.07‐1.97]; FG: HR=1.78 [1.28‐2.46]). HZ in 45‐64‐year‐olds was associated with dementia (HR=1.43 [1.14,1.79]) and AD (HR=1.59 [1.10‐2.29]) in APOE‐e4 non‐carriers only in UKB (Figure); in FG, the associations were observed in both non‐carriers (HR=1.61 [1.31‐1.97]) and carriers (HR=1.45 [1.11‐1.90]) for dementia. HZ in 65‐74‐year‐olds was not associated with any outcome.
Conclusion: Our findings support previous research indicating a reduced risk of dementia among HZ‐Vx recipients. We uniquely showed the potential effect in both APOE‐e4 carriers and non‐carriers. Conversely, we observed an increased risk of dementia in individuals with a recorded HZ diagnosis in the younger age group. Further research is required to understand the role of HZ as a potential risk factor for dementia
Circulation of Salmonella spp. between humans, animals and the environment in animal-owning households in Malawi.
Get PDFDiverse salmonellae have the potential to cause disease and may be carried asymptomatically within the intestine of many vertebrate species. The relative contribution of human, animal, and environmental hosts to the transmission of Salmonella is unknown within and between households in low-income settings, especially where humans and animals may live in close contact and sanitary infrastructure is often inadequate. Between November 2018 and December 2019, we isolated Salmonella spp. from thirty households in urban and rural locations in Malawi, sampling at three time points from the stool of humans, animals, and their household environment. Using whole genome sequencing and fine-resolution bioinformatic and phylogenetic analyses we found evidence of sharing of Salmonella species and strains between humans, animals and the environment, both within and between households. The intricate web of interconnected salmonellae within this ecosystem underscores the importance of adopting a multi-faceted 'One Health' strategy when considering control of Salmonella in low-intensity agricultural systems
Self-Efficacy and One-Year HIV Outcomes for Hospitalized People with HIV in Tanzania: A Mediation Analysis of the Daraja Clinical Trial.
Get PDFExamining the causal pathways through which the Daraja intervention led to sustained improvement in HIV outcomes, including retention in HIV care, ART adherence, and viral load suppression, could highlight critical mechanisms for improving post-hospital outcomes in people with HIV. This pre-specified analysis of the Daraja trial assessed five mediators identified from the Gelberg-Andersen model (self-efficacy, social support, perceived need for HIV services, perceived stigma, and traditional HIV beliefs) and two additional potential mediators, depression and alcohol use. Mediators were quantified pre- and post-intervention. A causal mediation analysis framework was used to construct independent single mediator models for each hypothesized mediator to understand their effect on HIV-related outcomes. Our intervention-mediator analysis demonstrated that the Daraja intervention improved self-efficacy (1.34 (95% CI (0.2, 2.48)) but no effect on other factors in the Gelberg-Andersen model. In our mediator-outcome analysis, improvements in self-efficacy, social support, and traditional HIV beliefs were associated with higher retention in care at 12 months. Results were similar for other HIV outcomes. Self-efficacy was associated with all three HIV outcomes, according to the intervention-mediator effect, mediator-outcome effect, average causal mediation effect, and average total effect. For these outcomes, 37-42% of the intervention effect was mediated by self-efficacy. Self-efficacy was an important mediator of the effect of the Daraja intervention in promoting retention in HIV care, improving ART adherence and reducing HIV viral load. Targeting self-efficacy appears to be critical for enabling hospitalized people with HIV to make the difficult transition from hospital to primary HIV care and live a healthy life with HIV. Clinical Trial Number ClinicalTrials.gov Identifier NCT03858998
No guts, no glory: IL-26 in host-microbiota interactions.
Get PDFThe gastrointestinal tract is composed of epithelial cells, immune cells and microbiota that interact dynamically to preserve homoeostasis. In this issue of The EMBO Journal, Salloum et al, (2025) exploit zebrafish models to show that bactericidal activity of interleukin-26 (IL-26), a poorly understood cytokine produced by innate lymphoid cells (ILCs), controls microbiota composition and gut epithelial homoeostasis
Experiences of stigma and discrimination among people experiencing homelessness: a cross-sectional pilot survey in South London, UK.
Get PDFOBJECTIVES: To understand experiences of stigma and discrimination among adults who are homeless across multiple care and support system contexts.
DESIGN: Cross-sectional survey embedded within an ethnographic case study.
SETTING: South London, UK, 2024.
PARTICIPANTS: Convenience sample of 74 people experiencing homelessness, aged over 18 years.
RESULTS: Participants most commonly reported unfair treatment in public settings (85%), legal settings (72%), housing and homelessness services (68%) and health settings (65%). These experiences were attributed to a range of factors and identities, with homelessness the most commonly cited; people commonly linked unfair experiences to multiple identities. People with more comorbidities reported experiencing unfair treatment across more system settings, including and beyond health systems.
CONCLUSIONS: Unfair treatment was reported across multiple care and support systems with greater ill-health associated with more unfair treatment. Future larger-scale surveys should measure the extent of stigma and discrimination across the population
Unaided reading speed in pseudophakic patients after emmetropic monofocal intraocular lens implantation.
Get PDFAIM: This study aimed to assess the reading speed and font size in pseudophakic eyes following implantation of a spherically neutral monofocal intraocular lens (IOL) aimed at an emmetropic refractive outcome.
METHODS: This was a prospective, single-eye study on patients undergoing routine cataract surgery with a spherically neutral monofocal IOL and expected to achieve 20/40 or better-unaided vision. Eyes with surgical complications or co-existing ocular pathology were excluded. At 3-9 months post-surgery, manifest refraction, uncorrected and best-corrected distance (UCDVA and BCDVA), and uncorrected near (UCNVA) LogMAR acuity, spherical equivalent (SEQ) were assessed. Uniocular unaided reading speed and smallest print size were assessed using the Salzburg Reading Desk (SRD) at 40 cm.
RESULTS: Median UCDVA, BCDVA, UCNVA, and SEQ of 301 patients (301 eyes) with age of 75 years (IQR:70 to 82) were 0.14 LogMAR (IQR = 0.02-0.24), 0 LogMAR (IQR = -0.08 to 0.02), and 0 D (IQR = -0.13 D to -0.07), respectively. The unaided reading speed was 100-150 wpm in 42.8% (129 patients), followed by 151-200 wpm in 26.1% (78 patients). The median unaided reading speed with SRD was 130 wpm (IQR: 101.50 to 165.50). 30.9% (93 patients) read 0.4 to 0.5 LogMAR, followed by 10.8% (33 patients) for 0.3 to 0.4 LogMAR and 7.4% (22 patients) for 0.2 to 0.3 LogMAR. The median smallest font size was 0.48 LogMAR (0.40 to 0.61 LogMAR).
CONCLUSION: This study establishes the baseline data of reading speed and font size with monofocal IOL, which can be used by further studies on extended depth-of-focus or multifocal IOLs for comparison
Access to eye health services among older people with disabilities in Karamoja, Uganda: a qualitative exploration of successful care seeking.
Get PDFBACKGROUND: Older people with disabilities frequently have high healthcare needs, but little is known about how they access health services or effective strategies to improve their access. The aim of this study was to explore journeys to access eye health services of older people with diverse disabilities in two districts in Karamoja, Uganda, and to identify the resources they drew on to access care. This study provides evidence about how older people with diverse disabilities in Uganda access eye health services and provides insights into how access can be expanded across this group.
METHODS: We used a positive deviance approach focussed on successful care seekers to identify strategies that may help improve access among this group. We purposively selected 20 older men and women with different disabilities from two districts of Karamoja, who had successfully accessed eye care services. We generated data through in-depth interviews and analysed it using Levesque's conceptual framework of access to health care to situate and describe the findings.
RESULTS: Participants narrated their eye health seeking journeys and described a wide range of factors that supported and hindered them across different domains described in the Levesque framework. For example, people's ability to perceive their eye healthcare need could be hindered by the similarity of symptoms with their existing disability, or by understanding them as a normal part of aging. Some individuals were known to healthcare workers because of their disability and were visited regularly to check on their well-being and provide information about services. People with children, spouses and other close social connections got information and advice about eye health that was not available to individuals who were socially isolated due to mobility issues or disability-related stigma.
CONCLUSIONS: Older people with disabilities in Karamoja face a range of disability-specific challenges in their abilities to perceive, seek, reach and engage with health care. This study adds useful context to the population-based survey conducted in Karamoja in 2023 and demonstrates how the positive deviance approach can be helpful in identifying strategies to improve access where little or no evidence currently exists
Hypertension prevalence and coverage and intellectual disability: a systematic review and meta-analysis.
No full textBACKGROUND: People with intellectual disabilities (ID) frequently experience poorer health and lower treatment coverage compared to those without ID, yet differences in hypertension prevalence and treatment coverage remain unclear. OBJECTIVE: To estimate the pooled prevalence ratio (PR) of hypertension and hypertension treatment coverage comparing adults with and without ID. METHODS: We searched MEDLINE, Embase, PsychINFO, Global Health and Global Index Medicus on June 6, 2024. We included observational and intervention studies that estimated the prevalence of hypertension and/or treatment coverage. The risk of bias was assessed using the Newcastle-Ottawa Scale tool. We undertook a random-effects meta-analysis to estimate the pooled PR with 95 % confidence intervals (CI). Sources of heterogeneity were explored through sensitivity and subgroup analyses, and meta-regression. RESULTS: 21 studies from 10 countries across three regions were included. The pooled PR were 0.71 (95 % CI: 0.47-1.05) for hypertension and 0.61 (95 % CI: 0.47-0.81) for hypertension treatment coverage. Only one study adjusted for age; most reported unadjusted estimates, making them prone to confounding. 14 studies were rated as high risk of bias. Subgroup analysis and meta-regression revealed variability in the methods used to diagnose ID, with sample size emerging as the primary source of variability in the effect estimates. CONCLUSIONS: This systematic review showed that adults with ID have a similar prevalence of hypertension, but lower hypertension treatment coverage compared to those without disabilities. However, these results should be interpreted with caution due to the lack of adjustment for confounding in the association and variability in the diagnosis of ID
Leishmaniasis in the United Kingdom: Experience of a national multidisciplinary team meeting in a non-endemic setting.
Get PDFINTRODUCTION: Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania. Disease phenotypes are heterogenous, and diagnosis is frequently delayed. Treatment is often challenging, and international guidelines recommend consultation with experts. The UK Leishmaniasis Multidisciplinary Team (UKLMDT) meeting provides an accessible online forum for clinicians to discuss cases of leishmaniasis, facilitating access to expertise and enabling local care for patients where possible.
METHODS: Three years of UKLMDT discussions, from its inception in November 2021 to October 2024, were reviewed using electronic patient records. An anonymous feedback questionnaire was sent to referrers. Data regarding treatment outcomes for patients discussed up to June 2024 were gathered using a separate questionnaire completed by their responsible clinician.
RESULTS: The UKLMDT contributed to 139 patient discussions involving 80 patients over in total over the study period. Just over half of individuals (45/80; 56.2 %) had cutaneous leishmaniasis, a quarter had visceral leishmaniasis (20/80; 25 %) and a tenth had mucosal leishmaniasis (8/80; 10 %). Seven patients (8.8 %) were found not to have leishmaniasis. In total, 24/80 (30 %) of patients were immunocompromised, but only in four cases (5 %) was HIV the cause of immunosuppression. All visceral leishmaniasis cases were acquired in Europe, and the majority acquired their disease in Spain. Leishmania donovani complex was the commonest causative agent overall, including in visceral and mucosal disease, whereas Leishmania Viannia subgenus was commonest in cutaneous leishmaniasis. Patients with mucosal or visceral leishmaniasis were more frequently immunosuppressed than those with cutaneous leishmaniasis. Outcomes and feedback on the UKLMDT were generally positive.
DISCUSSION: The experience of the UKLMDT specialist forum provides insight into leishmaniasis in the UK, a non-endemic setting. Key findings include that southern Europe is the primary destination where UK-based leishmaniasis is acquired, and that Leishmania donovani complex (most likely Leishmania infantum) in immunosuppressed hosts is an important cause of mucosal leishmaniasis in Europe. The UKLMDT offers equitable access to expertise for a rare disease in the UK, as well as serving as a model for national provision of multidisciplinary advice for other rare diseases
Human papillomavirus, sexually transmitted infections, and antimicrobial resistance in West Africa: Estimating population burden and understanding exposures to accelerate vaccine impact and drive new interventions: The PHASE survey protocol.
Get PDFHuman papillomavirus (HPV) infection is a primary cause of preventable deaths from cervical cancer, a condition of profound inequality with approximately 90% of deaths occurring in low- and middle-income countries, particularly in sub-Saharan Africa. In May 2018, the WHO Director-General declared a Joint Global Commitment to Cervical Cancer Elimination, highlighting the critical role of HPV vaccines in achieving this goal. However, there is a lack of systemically collected data on HPV prevalence in The Gambia, and impact data from high-income countries may not be reliably extrapolated to West African settings due to geographical variation in HPV types and distinct behavioural, biological, and sociodemographic exposures. The Gambia introduced a two-dose HPV vaccination schedule in 2019, but coverage has been very low, interrupted mainly by the COVID-19 pandemic. This presents a key opportunity to generate vital baseline data on HPV prevalence in the population before potential scale-up of vaccination efforts. The PHASE survey, a multi-stage cluster survey, aims to establish the baseline, population prevalence estimates of high-risk and low-risk, vaccine-type and non-vaccine-type HPV infection in 15- to 49-year-old females in The Gambia by measuring urinary HPV-DNA. The survey will also quantify the effects of various exposures on HPV prevalence, including sexual behaviour, the presence of other sexually-transmitted infections (STIs) - Neisseria gonorrhoea (NG), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV), Mycoplasma genitalium (MG), syphilis, as well as blood borne viruses, human immunodeficiency virus (HIV), hepatitis B and hepatitis C; obstetric history, socio-demographic characteristics, and cervical cancer screening and/or treatment. Additionally, the study will provide important antimicrobial resistance (AMR) data for NG and MG in sub-Saharan Africa, a region poorly represented in global surveillance programs. This data is needed to guide regional treatment guidelines and advocate for new solutions, including gonococcal vaccines. The AMR data are expected to immediately influence recommendations regarding the appropriate choice of antibiotics for syndromic STI management in West Africa and hence to address an important driver of AMR in the sub-region. Leveraging on the Medical Research Council Unit The Gambia funded Health Demographic Surveillance system (HDSS) as its sampling frame, the survey will utilize validated diagnostic assays and culturally sensitive data collection methods, to ensure both scientific rigor and local relevance. Tools such as Audio Computer-Assisted Self-Interviewing (ACASI) technology, developed in consultation with local community advisory boards, are included to reduce social desirability bias in reporting sexual behaviour. This approach aims to maximize both the reliability and cultural appropriateness of the findings. This study directly addresses the critical need for baseline epidemiological data on HPV in a West African setting to accelerate vaccine impact and drive new interventions towards cervical cancer elimination. By understanding other factors that influence HPV (like other STIs, sexual behaviour, etc.), the study aims to ensure that, when the vaccine's impact is measured later, changes in other confounding factors that may impact on HPV prevalence can be accounted for. The study will also establish the population prevalence of the measured STIs and their relationship to common symptoms and other adverse health outcomes related to STIs