Neurosyphilis in 2025

PURPOSE OF REVIEW: Syphilis continues to be a major global health problem. In recent years epidemics of syphilis have also been reported in many high-income countries. In this review, we aim to highlight varied presentations, including recent guidelines on diagnosis and treatment, including in people with HIV (PWH). RECENT FINDINGS: Neurosyphilis is increasingly being diagnosed and presentations are varied in both the immunocompetent and immunocompromised host. An appropriate history, examination and diagnostic work-up is central to identification of neurosyphilis and to enable appropriate treatment. Clear criteria for indication and interpretation of results from lumbar punctures, neuroimaging and treatment protocols have been outlined by the British association for sexual health and HIV (BASHH) in 2024. SUMMARY: The increase in overall cases of syphilis has been accompanied by increases in the number of cases with neurological involvement. The presentation of neurosyphilis is variable and may occur early or late in the disease course. It is important to be aware of the varied presentations, diagnostic and treatment criteria to limit the late sequelae of disease and address the global health challenge it poses and measures being taken to help reduce this global burden

Prevalence and Causes of Blindness and Vision Impairment in the State of Qatar: Results of a Population-Based Cross-Sectional Study.

INTRODUCTION: This study is a population-based investigation into the prevalence and causes of blindness and vision impairment (VI) among people aged 50 years and older living in the State of Qatar. METHODS: A Rapid Assessment of Avoidable Blindness (RAAB) methodology, applied from May 2022 to June 2023, utilized stratified two-stage cluster random sampling to select 5,060 persons aged 50 years and older resident in Qatar from 145 communities chosen by probability proportional to size. Communities were stratified by Qatari and non-Qatari nationality. Participants were examined by ophthalmologists in primary health centers. Data collection was through the RAAB7 Android application and supervised by a trainer using secure, encrypted cloud storage. RESULTS: Of the 3,206 participants examined, 14 (0.4%) had blindness and 10 (0.3%) had severe VI. Compared to a previous RAAB study in 2009, the prevalence of blindness (presenting visual acuity [VA] <3/60) decreased from 1.28% to 0.4% (95% confidence interval (CI): 0.2-0.7%). The age-sex-adjusted prevalence of all VI (presenting VA <6/12-NPL) was 9.7% (95% CI: 8.3-11.1), higher among females 12.6% (95% CI: 10.5-14.6), and Qataris 16.7% (95% CI: 14.4-19.1), compared to males 7.6% (95% CI: 6.3-9.0), and non-Qataris 6.3% (95% CI: 5.1-7.5). The principal causes of blindness included diabetic retinopathy (DR) (33.3%), cataract (20%), glaucoma (13%), and other posterior segment diseases (13%). All VI was mainly attributed to uncorrected refractive errors at 58% and cataract at 17%, with the former being more common among non-Qataris and cataract more prevalent among Qataris. CONCLUSION: Our findings show a low prevalence of VI compared with many countries that have published VI data. VI was mainly caused by DR, cataract, and uncorrected refractive error. Further reduction in vision loss can be achieved with early detection and improved access using innovation and technology

Evidence quality and uncertainties considered in appraisal documents of drugs for rare diseases in England and Germany: a data extraction protocol.

INTRODUCTION: Rare disease treatments (RDTs) promise considerable patient benefit but the evidence to demonstrate their value in health technology assessment (HTA) is often limited. HTA outcomes for RDTs vary across countries and there are differences in how uncertainty is dealt with by HTA agencies. Yet, there is limited comparative research assessing how different HTA agencies consider issues affecting evidence quality and uncertainty in RDT appraisals. This protocol describes a systematic and consistent approach for data extraction from RDT appraisal documents produced to inform decisions by HTA agencies. By documenting data extraction rules transparently, we ensure reproducibility and reliability of analyses of the extracted data. METHODS AND ANALYSIS: We will select RDT appraisals issued by the National Institute for Health and Care Excellence (NICE) in England and the Federal Joint Committee (GBA) in Germany, using predefined inclusion criteria. We will extract data from appraisal documents in accordance with the rules set out in this protocol. We will analyse the extracted data to investigate how issues affecting evidence quality and uncertainty as documented in appraisals are considered, highlighting the similarities and differences between countries and identifying factors that are associated with HTA outcomes. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of the London School of Hygiene & Tropical Medicine (reference number 29156). Study results will be submitted for publication in peer-reviewed journals

PrEP Uptake and Utilisation Among Adolescent Girls and Young Women in Sub-Saharan Africa: A Scoping Review.

Adolescent girls and young women (AGYW) in sub-Saharan Africa (SSA) are disproportionately affected by HIV. Despite the effectiveness of oral pre-exposure prophylaxis (PrEP) in preventing HIV, uptake and effective utilisation among AGYW remain suboptimal. This scoping review maps research on PrEP delivery outside clinical trials to AGYW in SSA. Quantitative and qualitative data were extracted from 58 studies on the facilitators and barriers to PrEP uptake and utilisation (including initiation, persistence, and adherence), and recommendations for effective PrEP delivery from AGYW and PrEP providers. Only studies on oral PrEP met the inclusion criteria. Facilitators of effective PrEP utilisation included social support with strong familial and peer networks positively influencing PrEP adherence and persistence. Healthcare provider interactions were pivotal in promoting PrEP uptake through dissemination of accurate information and ongoing support. Studies reported consistent barriers to PrEP uptake and utilisation including anticipated or experienced stigma, pill burden, and side effects. Addressing identified barriers and leveraging facilitators can enhance future effectiveness for PrEP delivery. There is a lack of strategies to support AGYW in long-term persistence and engagement with PrEP services. Our findings emphasise the urgent need for people-centred and localised, context-specific strategies to improve PrEP delivery among AGYW in SSA. Effective PrEP delivery strategies should include differentiated service delivery models, innovative approaches such as digital health, and integration with existing services such as antenatal care for pregnant and breastfeeding AGYW. More data is needed for PrEP delivery among AGYW across the region, including other PrEP modalities as they roll out

Association of sitting time with cardiovascular events among manual and non-manual workers: a prospective cohort study (PURE-China).

BACKGROUND: Prolonged sitting time is associated with an increased risk of cardiovascular disease (CVD) in the general population. However, it is unclear how these risks differ across occupational groups. This study aimed to investigate the association between sitting time and CVD in manual and non-manual workers among Chinese adults. METHODS: This population-based cohort study recruited 47,931 participants aged 35 to 70 years from 115 communities across 12 provinces in China between 2005 and 2009. Daily sitting time was measured using the International Physical Activity Questionnaire (IPAQ). The main outcome was a major CVD event (defined as cardiovascular death, myocardial infarction, stroke, or heart failure). Information on each participant's occupation was collected using standardized questionnaires and categorized into manual and non-manual occupations according to the Italian National Institute of Statistics 2001 (ISTAT-2001) occupational classification standard. Cox frailty models were used to examine the associations. RESULTS: Of 43,256 in the final sample (excluding those with CVD at baseline and missing data), 25,252 (58.4%) were women, and the mean (± SD, Standard Deviation) age was 50.6 ± 9.5 years. During a median follow-up of 11.9 (IQR, Interquartile Range: 9.5-12.6) years, 3,408 major CVD events (899 myocardial infarctions, 2,400 strokes, 240 incident heart failure, and 764 cardiovascular deaths) were documented. Compared with the reference group (< 4 h per day of sitting), the risk of major CVD events was positively associated with increasing sitting time among manual workers (HR, 1.20; 95% CI, 1.05-1.37 for 6-8 h per day; HR, 1.43; 95% CI, 1.12-1.82 for ≥ 8 h per day), while the risk among non-manual workers was greater for those reporting daily sitting times of more than 8 h (HR, 1.86; 95% CI, 1.18-2.95). Similar trends were observed when CVD mortality and incidence were analysed separately. CONCLUSIONS: Longer daily sitting time was associated with an increased risk of major CVD in both manual and non-manual occupational groups, and the risk was especially high among non-manual workers. Our findings highlight the importance of including measures to reduce sedentary behaviour within a comprehensive strategy to reduce the burden of cardiovascular disease in China

Understanding experiences of neglected tropical diseases of the skin: a mixed-methods study to inform intervention development in Ethiopia.

BACKGROUND: The WHO and Ethiopia's Ministry of Health have developed strategies to expand and integrate services for co-endemic neglected tropical diseases (NTDs) which manifest in the skin. To inform these strategies, we aimed to understand the social, economic and health system context of skin NTD care in Kalu woreda, Amhara region, Ethiopia, where cutaneous leishmaniasis (CL) and leprosy are endemic. METHODS: Between October 2020 and May 2022, we surveyed and reviewed records of 41 primary healthcare facilities and explored common disease experiences in focus group discussions (n=40) and interviews with people affected by leprosy (n=37) and CL (n=33), health workers (n=23), kebele authorities and opinion leaders (n=33) and traditional healers (n=7). Opportunities for integrated skin NTD service provision were explored through policy document review, interviews with health officials (n=25), and stakeholder meetings. RESULTS: Availability of diagnostic supplies and health worker competence to provide skin care was very limited across primary healthcare facilities, particularly for CL. People with leprosy commonly sought care from healthcare facilities, while people with CL administered self-care or sought help from traditional healers. Travel and costs of care at specialised facilities outside the district inhibited timely care-seeking for both diseases. Transmission discourses shaped different understandings of who was affected by leprosy and CL and expectations of behaviour during and after treatment. Many policy actors felt that existing supply chain interventions, decentralised treatment approaches and community engagement initiatives for leprosy could also benefit CL, but others also warned against increasing care-seeking unless CL treatment could be provided on a scale commensurate with the large burden they perceived. CONCLUSION: Our findings demonstrate significant gaps in the provision of care for skin NTDs within primary healthcare, very different health-seeking patterns for leprosy and CL, and a need to develop new models of care, especially for CL

Joint modelling of longitudinal data: a scoping review of methodology and applications for non-time to event data.

BACKGROUND: Joint models are powerful statistical models that allow us to define a joint likelihood for quantifying the association between two or more outcomes. Joint modelling has been shown to reduce bias in parameter estimates, increase the efficiency of statistical inference by incorporating the correlation between measurements, and allow borrowing of information in cases where data is missing for variables of interest. Most joint modelling methods and applications involve time-to-event data. There is less awareness about the amount of literature available for joint models of non-time-to-event data. Therefore, this review's main objective is to summarise the current state of joint modelling of non-time-to-event longitudinal data. METHODS: We conducted a search in PubMed, Embase, Medline, Scopus, and Web of Science following the PRISMA-ScR guidelines for articles published up to 28 January 2024. Studies were included if they focused on joint modelling of non-time-to-event longitudinal data and published in English. Exclusions were made for time-to-event articles, conference abstracts, book chapters, and studies without full text. We extracted information on statistical methods, association structure, estimation methods, software, etc. RESULTS: We identified 4,681 studies from the search. After removing 2,769 duplicates, 1,912 were reviewed by title and abstract, and 190 underwent full-text review. Ultimately, 74 studies met inclusion criteria and spanned from 2001 to 2024, with the majority (64 studies; 86%) published between 2014 and 2024. Most joint models were based on a frequentist approach (48 studies; 65%) and applied a linear mixed-effects model. The random effect was the most commonly applied association structure for linking two sub-models (63 studies; 85%). Estimation of model parameters was commonly done using Markov Chain Monte Carlo with Gibbs sampler algorithm (10 studies; 38%) for the Bayesian approach, whereas maximum likelihood was the most common (33 studies; 68.75%) for the frequentist approach. Most studies used R statistical software (33 studies; 40%) for analysis. CONCLUSION: A wide range of methods for joint-modelling non-time-to-event longitudinal data exist and have been applied to various areas. An exponential increase in the application of joint modelling of non-time-to-event longitudinal data has been observed in the last decade. There is an opportunity to leverage potential benefits of joint modelling for non-time-to-event longitudinal data for reducing bias in parameter estimates, increasing efficiency of statistical inference by incorporating the correlation between measurements, and allowing borrowing of information in cases with missing data

Blood Transfusions for Chronic Malaria Anemia in Prisoners of War on the Thai-Burma Railway 1943-1945.

Allied prisoners of war (POWs) working on the Imperial Japanese Army's railroad from Thailand to Burma during 1943-1945 devised a blood transfusion service to rescue severely ill fellow prisoners who were otherwise unlikely to survive the war. Extant transfusion records (1,251 recipients, 1,189 donors) in ledger books held by the United Kingdom National Archives at Kew were accessed and analyzed. Survival to the end of the war in 1945 was determined from Commonwealth War Graves Commission records. The records examined indicate that freshly donated whole blood was manually defibrinated and transfused after crossmatches based on POW medic sera. Overall survival to the end of the war was 74% in recipients and 88% in donors. Postwar survival rates were significantly higher for transfusion recipients with malaria (89.3%) than for other diagnoses: 52.6% for malnutrition, 59.3% for dysentery, 67.2% for skin ulcers, and 75.4% for other causes (odds ratio: 3.97; 95% CI: 2.79-5.28; P <0.0001). By 1945, the vast majority of blood transfusions were given for severe anemia caused by chronic relapsing vivax malaria. Although the POW situation was admittedly extreme, our data provide evidence that blood transfusions to treat severe anemia were associated with higher survival among patients with Plasmodium vivax infection than among those with other morbidities

"Ashamed of being seen in an HIV clinic": a qualitative analysis of barriers to engaging in HIV care from the perspectives of patients and healthcare workers in the Daraja clinical trial.

BACKGROUND: There is high post-hospital discharge mortality among persons with HIV who are hospitalized, and post-hospital survival is strongly associated with early HIV clinic linkage, clinic attendance, and antiretroviral therapy adherence. The Daraja intervention, a context-tailored case management strategy implemented and tested through a randomized trial in Tanzania, was associated with improved HIV clinic linkage, retention, and ART initiation and adherence. METHODS: We conducted in-depth interviews (IDIs) in a sub-sample of 40 study participants (20 control and 20 intervention) 12 months after enrollment into the trial to gain an in-depth understanding of the barriers to HIV care engagement and the perceived mechanisms through which the Daraja intervention impacted these barriers. We also conducted IDIs with 20 health care providers. We used a thematic analysis approach to generate themes following the Gelberg-Andersen behavioral model for vulnerable population domains. RESULTS: Perceived stigma, coupled with the mistrust of healthcare providers, underemployment or lack of reliable income, unreliable transport, and a lack of social support, were identified as key barriers to HIV clinic attendance and ART adherence. Perceived stigma complicated not only linking to and attending an HIV clinic but also decision-making regarding the choice of the clinic's location. The Daraja intervention was reported to help normalise HIV diagnosis, plug the social support gap, increase patients' self-efficacy and their capacity of participants to navigate the HIV clinic during HIV clinic linkage. CONCLUSION: These qualitative research results identified several important barriers to engaging in HIV care and provide insights into the mechanisms through which the Daraja intervention operated to affect the perceived stigma, social support, self-efficacy, and increased capacity of participants to navigate the HIV clinic during HIV clinic linkage. DARAJA TRIAL REGISTRATION: ClinicalTrials.gov, NCT03858998. Registered on 01 March 2019

"Butterflies in a jar": How girls and young women conceptualise wellbeing in conflict-affected Myanmar

Since the 2021 coup in Myanmar, the country has been driven into further social, political and economic turmoil. The United Nations estimates that 18.6 million people need humanitarian support. Among those most affected are adolescent girls aged 10–19 years who, as adolescents and young women, face unique risks to their health and wellbeing and require tailored interventions to promote their health and wellbeing both now and in the future. Supporting adolescent girls and young women during conflict means addressing their increased risk of gender-based violence, forced marriage, disrupted education, and access to health services. There is limited evidence on the effects of Myanmar's current political situation on adolescent girls and young women, and even less on what can be done to support their health and wellbeing during this period of protracted instability. In this qualitative study, we used the capabilities approach to conceptualise wellbeing from the perspectives of adolescent girls and young women in Myanmar. Collaborating with four young female peer-researchers, we conducted 12 participatory focus group discussions with 73 girls from Yangon, Sagaing and Mandalay. Our findings identified key themes of wellbeing that were prioritised by our study population: education, agency, hope and happiness, which were being undermined by gender inequality and the ongoing conflict. This study highlights the benefits of the capabilities approach in identifying the complex wellbeing needs of adolescent girls and young women in crisis settings as a basis for programme design and implementation