London School of Hygiene and Tropical Medicine

The Strongyloides genus of parasitic nematodes have a fascinating life cycle and biology, but are also important pathogens of people and a World Health Organization-defined neglected tropical disease. Here, a community of Strongyloides researchers have posed thirteen major questions about Strongyloides biology and infection that sets a Strongyloides research agenda for the future. This article is part of the Theo Murphy meeting issue ‘Strongyloides: omics to worm-free populations’.

Background Tuberculous meningitis (TBM) mortality averages at 27% but may reach 70% in HIV co-infection. High MRC severity grade, lower cerebrospinal fluid (CSF) white blood cell count (WBC) count, low weight, low CD4 and low plasma sodium were linked to mortality in Vietnam. Prognostic factors in African adults with HIV-associated TBM are unknown. We sought to determine the baseline factors predictive of death in HIV-positive Ugandan adults with TBM. Methods We prospectively enrolled patients who received TBM treatment and were classified as definite, probable or possible TBM by the uniform case definition from January 2019 to March 2023 in two National Referral Hospitals in Uganda. Participants received standard quadruple TB and corticosteroid therapy. We assessed association between baseline clinical and CSF characteristics (WBC< 5, 5-100, >100 cells/µl), antiretroviral therapy (ART) status and 14-day mortality. Results In 261 participants, median age was 36 years, 46% were women, median CD4 count was 74 cells/µl. 27% had definite, 39% probable, and 34% possible TBM. 142 (54%) had baseline CSF WBC < 5, 50 (19%) had 5-100, and 69 (27%) had >100 cells/µl. Overall, 14-day mortality was 25.9%. Mortality was 73.6% in participants with CSF WBC count < 5, 7.5% in 5-100, and 18.9% in >100 cells/µl, p=0.0012. Factors associated with 14-day mortality were MRC severity grade, CSF WBC, CSF opening pressure (OP), CSF protein and glucose, CD4 count. ART status did not influence survival. The hazard of 14-day mortality was 4 times as high for those with CSF WBC < 5 cells/µl as for those with >100 cells/ µl (95%CI 1.47-11.5, P=0.004). However, on adjustment for Glasgow Coma Scale (GCS), CSF OP, glucose, and CD4 count the association was less significant (aHR, 2.93, 0.82-10.4, P=0.13). Conclusion 14-day mortality varied significantly by baseline CSF WBC group, being extremely high (73.6%) in those with a paucity of CSF inflammation (WBC < 5 cells/µl). Those with intermediate inflammation (CSF WBC 5-100 cells/µl) had lowest mortality in-line with the damage response framework parabola. The association with acellular CSF and mortality was ameliorated by adjustment for CD4 count. CSF inflammation is at predictor of mortality in HIV-associated TBM and CSF WBC-directed corticosteroid therapy needs further exploration. Disclosures All Authors: No reported disclosures

Background Hospital-onset (HO) carbapenem-resistant Enterobacterales (CRE) infections are increasing; recently, the Centers for Disease Control and Prevention (CDC) reported a 35% increase during the COVID-19 pandemic. We evaluated the impact of HO CRE blood stream infections (BSI) on outcomes compared to community-onset (CO) CRE BSI. Methods Patients prospectively enrolled in CRACKLE-2 from 56 hospitals in 10 countries between April 30, 2016 to November 30, 2019 with a qualifying CRE bloodstream culture were eligible. Infections were defined per CDC guidelines as CO when the culture was obtained immediately prior to admission or through the first three days of hospitalization, and HO when the culture was obtained on or after the fourth day of admission. Categorical variables were tested using a chi-square test; continuous variable distributions were compared using Wilcoxon rank sum and Kruskal Wallis tests, as appropriate. The primary outcome was desirability of outcome ranking (DOOR) 30 days after index culture. Difference in 30-day mortality was calculated with 95% confidence intervals (CI). Results Among 891 patients with CRE BSI (Table 1), 65% of BSIs were hospital-onset (582/891). Compared to those with CO CRE, patients with HO CRE were younger (median 60 [Q1 42, Q3 70] years vs 65 [52, 74]; p< 0.001), had lower Charlson comorbidity score (median 2 [1, 4] versus 3 [1, 5]; p=0.002), and more often had Pitt bacteremia sore ≥4, indicative of critical illness, (47% versus 32%; p=< 0.001). ICU admission prior to first culture was associated with HO BSI (68% versus 42%, p< 0.001). Distribution of DOOR outcome at 30 days is shown in Figure 1. The probability of a better DOOR outcome in a randomly selected patient with CO BSI compared to a patient with HO BSI is 60.6% (95% CI: 56.8-64.3%). Mortality at 30-days was 11.6% higher in HO BSI than CO BSI (95% CI: 5.7, 17.6%, p=0.0003). A Kaplan-Meier curve of all-cause 30-day mortality is in Figure 2Figure 1:Distribution of Desirability of Outcome Ranking (DOOR) Categories by Infection Onset Desirability of outcome ranking at 30-days. Events evaluated included 1) deleterious effects, including absence of clinical response, prolonged hospitalization (>30 days following first positive culture), or readmission within 30 days; 2) any adverse events including renal failure or C. difficile infection; and 3) mortality at 30 days. Two subjects (1 in hospital onset group and 1 in community onset group) missing 30-day DOOR due to missing disposition information are not included in the figure.Figure 2:30-day Survival Plot by Infection Onset Two subjects (1 in hospital onset group and 1 in community onset group) are excluded from the figure due to missing mortality outcome information. One subject in the hospital onset group died on day 30 and is still considered at risk in the figure. Conclusion HO CRE BSIs are associated with worse outcomes than CO CRE BSIs; this unique population warrants special attention. As CRE often contain mobile genetic elements that facilitate horizontal transfer, close monitoring of HO CRE rates and optimizing hospital infection prevention methods are critical to prevent added morbidity and mortality. Disclosures Yohei Doi, MD, PHD, bioMerieux: Advisor/Consultant|FujiFilm: Advisor/Consultant|Gilead: Advisor/Consultant|Gilead: Honoraria|GSK: Advisor/Consultant|Meiji Seika Pharma: Advisor/Consultant|Moderna: Advisor/Consultant|Moderna: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Shionogi: Honoraria Michael J. Satlin, MD, AbbVie: IDMC member|Biomerieux: Grant/Research Support|Merck: Grant/Research Support|SNIPRBiome: Grant/Research Support Vance G. Fowler, MD, MHS, Amphliphi Biosciences, Integrated Biotherapeutics; C3J, Armata, Valanbio; Akagera, Aridis, Roche, Astra Zeneca: Advisor/Consultant|Genentech, Regeneron, Deep Blue, Basilea, Janssen;: Grant/Research Support|Infectious Diseases Society of America: Honoraria|MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck; Medical Biosurfaces; Locus; Affinergy; Contrafect; Karius;: Grant/Research Support|Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny,: Advisor/Consultant|Sepsis diagnostic: Patent pending|UpToDate: Royalties|Valanbio and ArcBio: Stock Options David van Duin, MD, PhD, Entasis: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Union: Advisor/Consultant|Utility: Advisor/Consultant

Background The WHO recently set out priority fungal pathogens of global importance which were previously neglected in terms of awareness & funding(1). Accurate diagnosis of fungal infection is a challenge & mortality remains high(2) as expertise and dedicated mycology services are lacking globally. Our centre provides one of the UK’s first complex fungal infection clinics, established in 2019. We sought to describe the patients attending this clinic, as a step towards understanding the landscape of clinical mycology in the UK. Methods Electronic health record systems were searched for all patients attending our clinic over 4 years from 01/04/19-01/04/23. Patients referred for consideration of a fungal diagnosis were included in the analysis. Invasive fungal infections (IFIs) were classified as per EORTC/MSGERC guidance.(3) Results 80/407 patients attending our clinic were referred for consideration of a fungal diagnosis. 31 (39%) were male. Median age was 53 (IQR 38-62). Most referrals (59/80; 74%) were received from within our institution. 41 (51%) had a fungal diagnosis confirmed prior to review. 28 were treated for invasive fungal infections (IFIs), 9 for chronic mycoses (including 5 chronic pulmonary aspergillosis & 2 mycetoma), 28 for superficial mycoses (20 recurrent mucocutaneous infections & 8 onychomycoses) & 15 had no evidence of fungal infection. Of the IFI: 16 were proven; 8 probable; 2 possible IFI & 2 did not meet diagnostic criteria. 7 IFI were caused by Aspergillus, 8 by Cryptococcus & 2 each by Coccidiodes, Candida & Histoplasma. The IFIs mainly affected the upper & lower respiratory tract (17/28). 20/80 (25%) were immunosuppressed (commonest causes: diabetes; HIV; steroids; malignancy & chemotherapy). On average (median), patients visited clinic 4 times (IQR 2-7) & received 2 different antifungal drugs (IQR 1-3). The most common side-effects prompting a change in therapy were visual changes, rash & diarrhoea. Conclusion Our data illustrate the need for dedicated follow-up for patients with complex fungal infections. With several new antifungal drugs currently undergoing clinical trials, complexity in therapeutic decision-making will only increase.(4) Establishing centralised complex fungal infection clinics helps to build diagnostic & clinical capacity in mycology. Disclosures Hamish Houston, BA MBBCh, Gilead Sciences: Grant/Research Support Neil RH Stone, MD PhD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Pfizer: Honoraria|Shionogi: Honoraria

Intimate partner violence (IPV) is a highly prevalent public health challenge and human rights violation. Sociological theories address social structures to understand prevalence and dynamics of IPV against women. This systematic review aims (1) to identify, describe, categorize, and synthesize sociological theories that account for predictors of IPV against women, and (2) to compare and contrast sociological theories of predictors of IPV against women. Following a structured search of nine electronic databases, members of the review team screened title/abstract and full texts against inclusion and exclusion criteria, to identify studies that engaged with theory/ies of predictors of IPV. Review team members extracted data according to a data extraction template developed for the review. Results are presented using a narrative synthesis approach. Following review of 108 included articles, included articles were grouped into sub-theories. The sub-theories provide differing, yet overlapping, accounts of predictors of male perpetration of IPV and women’s experience of IPV. Sociological theories primarily engage with exo- and macro-system levels of the social-ecological framework, yet some also address structural influences on individual behaviors. This systematic review fills a gap in theoretical syntheses of sociological theories of predictors of male-perpetrated IPV against women and also provides critical analysis of how these theories overlap and intersect. While sociological theories may not be able to fully explain all aspects of dynamics of male-perpetrated IPV against women, this overview indicates that there are several compelling components of sociological theory that hold explanatory power for comprehending how, where, and why IPV occurs.

Purpose The COVID-19 pandemic and lockdown restrictions introduced personal and relationship stressors that potentially increased the risk of intimate partner violence (IPV) for some. We estimated the population prevalence and correlates of fearing a partner in the first year of the pandemic in Britain. Method We used data from Natsal-COVID Wave 2—a web-panel survey undertaken one year after the initial British lockdown from 23 March 2020. Quotas and weighting were used to achieve a quasi-representative sample of the general population. Participants were asked about fearing a partner, which is a simple and valid screening tool to identify IPV experiences. Results In our sample (unweighted n = 6302, aged 18–59), 9.0% of women and 8.7% of men reported fearing a partner in the first year of the pandemic. Women (73.3%) were more likely than men (49.9%) to indicate that fearing a partner made them feel anxious or depressed; men were more likely to report increased substance use (30.8% vs. 18.4%) and affected work/studies (30.0% vs. 20.0%). For both women and men, fearing a partner during the first year of the pandemic was associated with established health and wellbeing outcomes like anxiety/depression, alcohol use, accessing sexual/reproductive health services, and relationship dissolution as well as feeling that the “pandemic made things worse” across various life domains. Conclusions Population-level estimates of IPV during the COVID-19 pandemic highlight harmful experiences that occurred alongside other wide-ranging hardships, and the associations presented identify key populations with potential ongoing need. We make recommendations for primary, secondary, and tertiary prevention of IPV.

Background Cladribine is an immunotherapy for people with multiple sclerosis (pwMS). Whilst many pwMS do not require retreatment after completing a standard dosing schedule, disease activity resumes in others. Aims To investigate whether baseline characteristics, including degree of lymphocyte reduction, and total or weight-adjusted drug dose, were associated with re-emerging disease activity. Methods Demographics, clinical, laboratory and magnetic resonance imaging data of pwMS who received two courses of cladribine were extracted from the health record. To assess associations of predictor variables with time to new disease activity, a series of Cox proportional hazards models were fitted. Results Of our total cohort (n=264) 236 pwMS received two courses of cladribine. Median follow-up was 3.5 years (IQR:2.9,4.3) from the last administration. Re-emerging disease activity occurred in 57/236 (24%). Twenty-two/236 received a third course of cladribine 37 months (median;IQR:31.7,42.1), and 22/236 other immunotherapies 19 months (13.0,30.2) after their second course of cladribine, respectively. Thirteen/236 were yet to receive immunotherapy. Hazard models indicated association between re-emerging disease activity and (i) baseline MRI activity (ii) dose of cladribine administered at the second course. Conclusions Re-emerging disease activity was associated with high baseline MRI activity and low dose second treatment course.

Background Rapid diagnostic testing may support improved treatment of COVID patients. Understanding COVID testing and care pathways is important for assessing the impact and cost-effectiveness of testing in the real world, yet there is limited information on these pathways in low-and-middle income countries (LMICs). We therefore undertook an expert consultation to better understand testing policies and practices, clinical screening, the profile of patients seeking testing or care, linkage to care after testing, treatment, lessons learnt and expected changes in 2023. Methods We organized a qualitative consultation with ten experts from seven LMICs (India, Indonesia, Malawi, Nigeria, Peru, South Africa, and Zimbabwe) identified through purposive sampling. We conducted structured interviews during six regional consultations, and undertook a thematic analysis of responses. Results Participants reported that, after initial efforts to scale-up testing, the policy priority given to COVID testing has declined. Comorbidities putting patients at heightened risk (e.g., diabetes) mainly relied on self-identification. The decision to test following clinical screening was highly context-/location-specific, often dictated by local epidemiology and test availability. When rapid diagnostic tests were available, public sector healthcare providers tended to rely on them for diagnosis (alongside PCR for Asian/Latin American participants), while private sector providers predominantly used polymerase chain reaction (PCR) tests. Positive test results were generally taken at ‘face value’ by clinicians, although negative tests with a high index of suspicion may be confirmed with PCR. However, even with a positive result, patients were not always linked to care in a timely manner because of reluctance to receiving care or delays in returning to care centres upon clinical deterioration. Countries often lacked multiple components of the range of therapeutics advised in WHO guidelines: notably so for oral antivirals designed for high-risk mild patients. Severely ill patients mostly received corticosteroids and, in higher-resourced settings, tocilizumab. Conclusions Testing does not always prompt enhanced care, due to reluctance on the part of patients and limited therapeutic availability within clinical settings. Any analysis of the impact or cost-effectiveness of testing policies post pandemic needs to either consider investment in optimal treatment pathways or constrain estimates of benefits based on actual practice.

Background Though the laryngeal cancer only has 1% of the total cancer cases and related deaths, it is a type of head and neck cancers with the highest prevalence. This study aims to investigate the epidemiological trend of laryngeal cancer with updated data on the global distribution of the disease burden. Materials and Methods The incidence and mortality rate of laryngeal cancer was extracted from GLOBOCAN (2020), Cancer Incidence in Five Continents series I-X, WHO mortality database , the Nordic Cancer Registries , and the Surveillance, Epidemiology, and End Results Program. The Global Health data exchanges for the prevalence of its associated risk factors. A Joinpoint regression analysis was used to calculate Average Annual Percentage Change (AAPC). Results The age-standardised rate (ASR) of laryngeal cancer incidence and mortality were 2.0 and 1.0 per 100,000 worldwide. The Caribbean (ASR = 4.0) and Central and Eastern Europe (ASR = 3.6) had the highest incidence and mortality rate. Incidence and risk factors associated with laryngeal cancer included tobacco usage, alcohol consumption, poor diet, obesity, diabetes, hypertension, and lipid disorders. There was an overall decreasing trend in incidence, especially for males, but an increasing incidence was observed in female populations and younger subjects. Conclusions As overall global trends of laryngeal cancer have been decreasing, especially for the male population, this could possibly be attributed to reduced tobacco use and alcohol consumption. Decrease in mortality may be due to improved diagnostic methods and accessibility to treatment, yet disparity in trend remains potentially because of differences in the level of access to surgical care. Disparities in temporal trends across countries may require further research and exploration to determine other underlying factors influencing this.

Background Retinopathy of prematurity (ROP) is a leading cause of blindness in children and an ROP epidemic is predicted this decade in sub-Saharan Africa. With the increasing survival rate of preterm babies in Uganda, and no data on ROP prevalence, there is a need to assess the burden of ROP to inform preventive strategies and targeted screening. Methods We conducted a two-center cross-sectional study of preterm (< 37 weeks gestational age) infants from the neonatal units of Kawempe National Referral Hospital (KNRH) and Mulago Specialised Women and Neonatal Hospital (MSWNH) from August 2022 to October 2022. An ophthalmologist examined all participants using an indirect ophthalmoscope with a + 20D convex lens and captured digital images using a Volk iNview™ Fundus Camera. The collected data were entered into Epidata 4.2 and exported to Stata 14.0 for analysis. Results 331 preterm infants enrolled in this study. The oxygen received was unblended. The mean gestational age was 30.4 ± 2.7 weeks, and the mean birth weight was 1597 ± 509 g. 18/101 (17.8%) were found to have any ROP amongst the preterm infants recruited from MSWNH, 1/230 (0.4%) from KNRH [95% CI] had any stage of ROP (i.e. stage 5). Of these, 8 (42.1%) had stage 2 ROP. Infants with a birth weight below 1500 g were 10 times more likely to have ROP than those among infants with a birth weight more than 1500 g [AOR: 10.07 (2.71–37.44)]. Infants who were not fed exclusively on breast milk had higher odds of having ROP than those exclusively fed on breast milk [AOR: 7.82(1.92–31.82)]. Conclusion 6% of preterm infants born in two tertiary hospitals in Uganda were found to have ROP. Lack of exclusive feeding on breast milk and birth weight of less than 1500 g were strong predictors of ROP. The higher prevalence of ROP in MSWNH calls for cautious use of oxygen among preterms. We recommend targeted ROP screening for those at risk.

Background In September, 2014, Médecins Sans Frontières (MSF) called for militarised assistance in response to the rapidly escalating West Africa Ebola Epidemic. Soon after, the United Kingdom deployed its military to Sierra Leone, which (among other contributions) helped to support the establishment of novel and military-led Ebola Virus Disease (Ebola) response centres throughout the country. To examine these civil-military structures and their effects, 110 semi-structured interviews with civilian and military Ebola Response Workers (ERWs) were conducted and analysed using neo-Durkheimian theory. Results The hierarchical Ebola response centres were found to be spaces of ‘conflict attenuation’ for their use of ‘rule-bound niches’, ‘neutral zones’, ‘co-dependence’, and ‘hybridity’, thereby not only easing civil-military relationships (CMRel), but also increasing the efficiency of their application to Ebola response interventions. Furthermore, the hierarchical response centres were also found to be inclusive spaces that further increased efficiency through the decentralisation and localisation of these interventions and daily decision making, albeit for mostly privileged groups and in limited ways. Conclusions This demonstrates how hierarchy and localisation can (and perhaps should) go hand-in-hand during future public health emergency responses as a strategy for more robustly including typically marginalised local actors, while also improving necessary efficiency—in other words, an ‘inclusive hierarchical coordination’ that is both operationally viable and an ethical imperative.

Escherichia coli commonly inhabits the gut of humans and animals as part of their microbiota. Though mostly innocuous, some strains have virulence markers that make them pathogenic. This paper presents results of a cross-sectional epidemiological study examining prevalence of diarrheagenic E . coli (DEC) pathotypes in stool samples of asymptomatic healthy children (n = 540) in Dagoretti South subcounty, Nairobi, Kenya. E . coli was cultured and pathotyped using PCR to target specific virulence markers associated with Shiga-toxin, enteropathogenic, enterotoxigenic, enteroaggregative, entero-invasive and diffusely adherent E . coli . Overall prevalence of DEC pathotypes was 20.9% (113/540) with enteropathogenic E . coli being the most prevalent (34.1%), followed by enteroaggregative E . coli (23.5%) and Shiga-toxin producing E . coli (22.0%) among positive samples. We found evidence of co-infection with multiple pathotypes in 15% of the positive samples. Our models indicated that at the household level, carriage of DEC pathotypes in children was associated with age group [12–18 months] (OR 1.78; 95%CI 1.03–3.07; p = 0.04), eating matoke (mashed bananas) (OR 2.32; 95%CI 1.44–3.73; p = 0.001) and pulses/legumes (OR 1.74; 95%CI 1.01–2.99; p = 0.046) while livestock ownership or contact showed no significant association with DEC carriage (p>0.05). Our findings revealed significant prevalence of pathogenic DEC circulating among presumptive healthy children in the community. Since there has been no previous evidence of an association between any food type and DEC carriage, unhygienic handling, and preparation of matoke and pulses/legumes could be the reason for significant association with DEC carriage. Children 12–18 months old are more prone to DEC infections due to exploration and hand-to-mouth behavior. A detailed understanding is required on what proportion of positive cases developed severe symptomatology as well as fatal outcomes. The co-infection of pathotypes in the rapidly urbanizing environment needs to be investigated for hybrid or hetero-pathotype circulation that have been implicated in previous infection outbreaks.

Malaria and schistosomiasis are two major parasitic vector-borne diseases that are a particular threat to young children in Sub-Saharan Africa. In the present study, we investigated factors that are associated with malaria, schistosomiasis, and co-infection among school-aged children, using an explanatory sequential mixed-methods approach. A cross-sectional study was conducted in January 2022 in Misungwi, Tanzania, that sampled 1,122 children aged 5 to 14 years old for malaria and schistosomiasis infection. Mixed-effect logistic regression models were used to assess the association between infection prevalence or seroprevalence, and environmental determinants that create favorable conditions for vectors and parasites and social determinants that relate to disease exposure. Community mapping combined with direct field observations were conducted in August 2022 in three selected villages from the cross-sectional study to understand specific water use behaviors and to identify potential malaria mosquito larval breeding sites and freshwater snail habitat. The prevalence of malaria, seroprevalence of schistosomiasis, and co-infection in this study were 40.4%, 94.3%, and 38.1%, respectively. Individual-level factors emerged as the primary determinants driving the association with infection, with age (every one-year increase in age) and sex (boys vs girls) being statistically and positively associated with malaria, schistosomiasis, and co-infection ( P <0.05 for all). Community maps identified many unimproved water sources in all three villages that were used by humans, cattle, or both. We found that children primarily fetched water, and that unprotected wells were dedicated for drinking water whereas ponds were dedicated for other domestic uses and cattle. Although not identified in the community maps, we found hand pumps in all three villages were not in use because of unpleasant taste and high cost. This study improves our understanding of individual, social and environmental factors that are associated with malaria, schistosomiasis, and co-infection, which can inform potential entry points for integrated disease prevention and control.

Objectives :To determine how muscle strength, power, mass, and density ( i.e . quality) differ between children living with HIV (CWH) and those uninfected, and whether antiretroviral therapy (ART) regime is associated with muscle quality. Design :A cross-sectional study in Harare, Zimbabwe. Methods :The study recruited CWH aged 8–16years, taking ART for ≥2years, from HIV clinics, and HIV-uninfected children from local schools. Muscle outcomes comprised grip strength measured by hand-held Jamar dynamometer, lower-limb power measured by standing long-jump distance, lean mass measured by dual-energy X-ray absorptiometry, and muscle density (reflecting intramuscular fat) by peripheral quantitative computed tomography. Linear regression calculated adjusted mean differences (aMD) by HIV status. Results :Overall, 303 CWH and 306 without HIV, had mean(SD) age 12.5(2.5) years, BMI 17.5(2.8), with 50% female. Height and fat mass were lower in CWH, mean differences(SE) 7.4(1.1)cm and 2.7(0.4)kgs, respectively. Male CWH had lower grip strength (aMD 2.5[1.1,3.9]kg, P < 0.001), long-jump distance (7.1[1.8,12.5]cm, P = 0.006), muscle density (0.58[0.12,1.05]mg/cm ³ , P = 0.018, but not lean mass 0.06[-1.08,1.21]kg, P = 0.891) versus boys without HIV; differences were consistent but smaller in females. Mediation analysis suggested the negative effect of HIV on jumping power in males was partially mediated by muscle density ( P = 0.032). CWH taking tenofovir disoproxil fumarate (TDF) had lower muscle density (0.56[0.00,1.13]mg/cm ³ , P = 0.049) independent of fat mass, than CWH on other ART. Conclusions :Perinatally-acquired HIV is associated, particularly in males, with reduced upper and lower-limb muscle function, not mass. Intra-muscular fat (poorer muscle quality) partially explained reductions in lower-limb function. TDF is a novel risk factor for impaired muscle quality.

Introduction Clinical staging models in psychiatry assert that there are earlier, less severe or more malleable forms of illness that are distinguishable from later, more chronic forms of illness, and that these stages may have different prognostic and treatment implications. Previous reviews on clinical staging in eating disorders (EDs) suggest a staging heuristic could be useful for anorexia nervosa, but less research is available on how this applies to other EDs. An up-to-date review is required to synthesise new and heterogenous avenues of research. This scoping review aims to explore the extent and types of evidence in relation to illness staging for EDs and how these concepts are associated with treatment response and outcomes. Methods and analysis This protocol was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol extension for Scoping Reviews checklist and the Joanna Briggs Institute Reviewer’s Manual. We will consider any documents providing evidence for clinical staging such as those which describe full or partial staging models, for all EDs, across various domains of assessment and functioning. Participants will include clinical or non-clinical population samples with full-syndrome EDs or disordered eating behaviour. PubMed, PsycINFO, MEDLINE and Web of Science databases will be systematically searched for relevant literature. Two authors will export documents and screen titles, abstracts and full texts. Data will be extracted into a charting form drafted by the authors. A narrative summary of the documents will be conducted in line with the study aims. Finally, clinical and research recommendations will be outlined. Ethics and dissemination Ethical approval will not be required to synthesise published and unpublished literature. The study will be published in a peer-reviewed journal and shared at conferences, via social media, and in other communications.

The current Marburg virus (MARV) outbreak in Tanzania served as a stark reminder of the ongoing threat posed by emerging infectious diseases and the urgent need for global health security. The Tanzanian Ministry of Health (MoH) officially declared the outbreak on March 21, 2023. Eight cases in all, five of which included fatalities, have been reported in the country at present. The virus is a member of the Filoviridae family closely related to the widely known Ebola virus. Similar to other filoviruses, MARV causes acute and lethal hemorrhagic fever in both human and nonhuman primates with high case fatality rates ranging from 24% to 90%. The outbreak has highlighted the need for improved disease surveillance and response systems, as well as increased funding for research into emerging infectious diseases. The Tanzanian MoH has deployed a response team to investigate and monitor the transmission in the Kagera Region. The team works closely in collaboration with other organizations, such as the World Health Organization and the Africa Centre for Disease Control and Prevention, to ensure the effective control of the situation. Although there is no vaccine or treatment approved for Marburg virus disease (MVD), supportive management improves survival. Existing infection prevention and control protocols for Ebola and other viral hemorrhagic fevers such as isolation and use of appropriate personal protective equipment can be used to prevent transmission of MVD. The global community must work together to strengthen health systems, enhance research efforts, and build resilient and responsive health systems to prevent future outbreaks of this kind. In this article, we have analyzed the MVD outbreak in Tanzania, specifically in the Bukoba district of the Kagera Region, and provided recommendations for the management of the current outbreak and future outbreaks.

Background For certain conditions, treatments aim to lessen deterioration over time. A trial outcome could be change in a continuous measure, analysed using a random slopes model with a different slope in each treatment group. A sample size for a trial with a particular schedule of visits (e.g. annually for three years) can be obtained using a two-stage process. First, relevant (co-) variances are estimated from a pre-existing dataset e.g. an observational study conducted in a similar setting. Second, standard formulae are used to calculate sample size. However, the random slopes model assumes linear trajectories with any difference in group means increasing proportionally to follow-up time. The impact of these assumptions failing is unclear. Methods We used simulation to assess the impact of a non-linear trajectory and/or non-proportional treatment effect on the proposed trial’s power. We used four trajectories, both linear and non-linear, and simulated observational studies to calculate sample sizes. Trials of this size were then simulated, with treatment effects proportional or non-proportional to time. Results For a proportional treatment effect and a trial visit schedule matching the observational study, powers are close to nominal even for non-linear trajectories. However, if the schedule does not match the observational study, powers can be above or below nominal levels, with the extent of this depending on parameters such as the residual error variance. For a non-proportional treatment effect, using a random slopes model can lead to powers far from nominal levels. Conclusions If trajectories are suspected to be non-linear, observational data used to inform power calculations should have the same visit schedule as the proposed trial where possible. Additionally, if the treatment effect is expected to be non-proportional, the random slopes model should not be used. A model allowing trajectories to vary freely over time could be used instead, either as a second line analysis method (bearing in mind that power will be lost) or when powering the trial.

Background The low demand for maternal and child health services is a significant factor in Nigeria's high maternal death rate. This paper explores demand and supply-side determinants at the primary healthcare level, highlighting factors affecting provision and utilization. Methods This qualitative study was undertaken in Anambra state, southeast Nigeria. Anambra state was purposively chosen because a maternal and child health programme had just been implemented in the state. The three-delay model was used to analyze supply and demand factors that affect MCH services and improve access to care for pregnant women/mothers and newborns/infants. Result The findings show that there were problems with both the demand and supply aspects of the programme and both were interlinked. For service users, their delays were connected to the constraints on the supply side. On the demand side, the delays include poor conditions of the facilities, the roads to the facilities are inaccessible, and equipment were lacking in the facilities. These delayed the utilisation of facilities. On the supply side, the delays include the absence of security (fence, security guard), poor citing of the facilities, inadequate accommodation, no emergency transport for referrals, and lack of trained staff to man equipment. These delayed the provision of services. Conclusion Our findings show that there were problems with both the demand and supply aspects of the programme, and both were interlinked. For service users, their delays were connected to the constraints on the supply side.

Background and objectives Current dietary habits have substantial negative impacts on the health of people and the planet. This study aimed to develop a novel approach for achieving health-promoting and climate-friendly dietary recommendations for a broad range of consumers. Subjects and methods Hierarchical clustering analysis was combined with linear programming to design nutritionally adequate, health-promoting, climate-friendly and culturally acceptable diets using Swedish national dietary data (n = 1797). Diets were optimised for the average consumption of the total population as well as for the dietary clusters. Results Three dietary clusters were identified. All optimised diets had lower shares of animal-source foods and contained higher amounts of plant-based foods. These dietary shifts reduced climate impacts by up to 53% while leaving much of the diet unchanged. The optimised diets of the three clusters differed from the optimised diet of the total population. All optimised diets differed considerably from the food-group pattern of the EAT-Lancet diet. Conclusions The novel cluster-based optimisation approach was able to generate alternatives that may be more acceptable and realistic for a sustainable diet across different groups in the population.