Search

Antibody features vary with tuberculosis (TB) disease state. Whether clinical variables, such as age or sex, influence associations between Mycobacterium tuberculosis-specific antibody responses and disease state is not well explored. Here we profiled Mycobacterium tuberculosis-specific antibody responses in 140 TB-exposed South African individuals from the Adolescent Cohort Study. We identified distinct response features in individuals progressing to active TB from non-progressing, matched controls. A multivariate antibody score differentially associated with progression (SeroScore) identified progressors up to 2 years before TB diagnosis, earlier than that achieved with the RISK6 transcriptional signature of progression. We validated these antibody response features in the Grand Challenges 6-74 cohort. Both the SeroScore and RISK6 correlated better with risk of TB progression in adolescents compared with adults, and in males compared with females. This suggests that age and sex are important, underappreciated modifiers of antibody responses associated with TB progression., (© 2024. The Author(s).)

Introduction: Progress related to sexual, reproductive, maternal, newborn, child and adolescent health (SRMNCAH) has stalled. COVID-19, conflict and climate change threaten to reverse decades of progress and to ensure the health and well-being of vulnerable populations in humanitarian and fragile settings (HFS) going forward, there is a need for tailored guidance for women, children and adolescents (WCA). This review seeks to map and appraise current resources on SRMNCAH in HFS., Methods: In line with the updated Joanna Briggs Institute guidance and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews framework, a manual literature review was conducted of global and regional guidance published between January 2008 and May 2023 from members of the Global Health Cluster, the Global Nutrition Cluster and the Inter-Agency Working Group on Reproductive Health in Crises. A content analysis was conducted. Scores were then calculated according to the Appraisal of Guidelines for Research and Evaluation II scoring tool and subsequently categorised as high quality or low quality., Results: A total of 730 documents were identified. Of these, 141 met the selection criteria and were analysed. Available guidance for delivering SRMNCH services exists, which can inform policy and programming for the general population and WCA. Important gaps related to beneficiaries, health services and health system strengthening strategies were identified., Conclusion: The review revealed there is evidence-based guidance available to support interventions targeting WCA in HFS, including: pregnant and lactating women, women of reproductive age, adolescents, newborns, small vulnerable newborns, stillbirths, refugees and internally displaced persons and WCA with disabilities. However, gaps related to beneficiaries, health services and health system strengthening strategies must be addressed in updated guidance that is created, disseminated and monitored in a standardised way that is mindful of the need to respond rapidly in HFS., Competing Interests: Competing interests: None declared., (© World Health Organization 2024. Licensee BMJ.)

Background: Active and protracted conflict settings demonstrate the need to prioritise the peace through health agenda. This can be achieved by reorienting attention toward gender diverse leadership and more effective governance within health systems. This approach may enable women to have a greater voice in the decision-making of health and social interventions, thereby enabling the community led and context specific knowledge required to address the root causes of persistent inequalities and inequities in systems and societies., Methods: We conducted a qualitative study, which included semi-structured interviews with 25 key informants, two focus group discussions and one workshop with humanitarian workers in local and international non-governmental organisations (NGOs), United Nations (UN) agencies, health practitioners, and academics, from Sub-Saharan Africa, Middle East and North Africa (MENA), and Latin America. Findings were then applied to the peacebuilding pyramid designed by John Paul Lederach which provides a practical framework for mediation and conflict resolution in several conflict-affected settings. The purpose of the framework was to propose an adapted conceptualisation of leadership to include women's leadership in the health system and be more applicable in protracted conflict settings., Results: Five interrelated themes emerged. First, perceptions of terms such as gender equality, equity, mainstreaming, and leadership varied across participants and contexts. Second, armed conflict is both a barrier and an enabler for advancing women's leadership in health systems. Third, health systems themselves are critical in advancing the nexus between women's leadership, health systems and peacebuilding. Fourth, across all contexts we found strong evidence of an instrumental relationship between women's leadership in health systems in conflict-affected settings and peacebuilding. Lastly, the role of donors emerged as a critical obstacle to advance women's leadership., Conclusion: Continuing to empower women against social, cultural, and institutional barriers is crucial, as the emerging correlation between women's leadership, health systems, and peacebuilding is essential for long-term stability, the right to health, and health system responsiveness., (© 2023. The Author(s).)

Background: Almost half of the under-5 deaths occur in the neonatal period and most can be prevented with quality newborn care. The already vulnerable state of newborns is exacerbated in humanitarian settings. This review aims to assess the current evidence of the interventions being provided in these contexts, identify strategies that increase their utilisation and their effects on health outcomes in order to inform involved actors in the field and to guide future research., Methods: Searched for peer-reviewed and grey literature in four databases and in relevant websites, for published studies between 1990 and 15 November 2021. Search terms were related to newborns, humanitarian settings, low-income and middle-income countries and newborn health interventions. Quality assessment using critical appraisal tools appropriate to the study design was conducted. Data were extracted and analysed using a narrative synthesis approach., Results: A total of 35 articles were included in this review, 33 peer-reviewed and 2 grey literature publications. The essential newborn care (ENC) interventions reported varied across the studies and only three used the Newborn Health in Humanitarian Settings: Field Guide as a guideline document. The ENC interventions most commonly reported were thermal care and feeding support whereas delaying of cord clamping and administration of vitamin K were the least. Training of healthcare workers was the most frequent strategy reported to increase utilisation. Community interventions, financial incentives and the provision of supplies and equipment were also reported., Conclusion: There is insufficient evidence documenting the reality of newborn care in humanitarian settings in low-income and middle-income countries. There is a need to improve the reporting of these interventions, including when there are gaps in service provision. More evidence is needed on the strategies used to increase their utilisation and the effect on health outcomes., Prospero Registration Number: CRD42020199639., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: The impacts of COVID-19 are unprecedented globally. The pandemic is reversing decades of progress in maternal, newborn, child health and nutrition (MNCHN), especially fragile and conflict-affected settings (FCAS) whose populations were already facing challenges in accessing basic health and nutrition services. This study aimed to investigate the collateral impact of COVID-19 on funding, services and MNCHN outcomes in FCAS, as well as adaptations used in the field to continue activities., Methods: A scoping review of peer-reviewed and grey literature published between 1st March 2020-31st January 2021 was conducted. We analysed 103 publications using a narrative synthesis approach. 39 remote semi-structured key informant interviews with humanitarian actors and donor staff within 12 FCAS were conducted between October 2020 and February 2021. Thematic analysis was undertaken independently by two researchers on interview transcripts and supporting documents provided by key informants, and triangulated with literature review findings., Results: Funding for MNCHN has been reduced or suspended with increase in cost of continuing the same activities, and diversion of MNCHN funding to COVID-19 activities. Disruption in supply and demand of interventions was reported across different settings which, despite data evidence still being missing, points towards likely increased maternal and child morbidity and mortality. Some positive adaptations including use of technology and decentralisation of services have been reported, however overall adaptation strategies have been insufficient to equitably meet additional challenges posed by the pandemic, and have not been evaluated for their effectiveness., Conclusions: COVID-19 is further exacerbating negative women's and children's health outcomes in FCAS. Increased funding is urgently required to re-establish MNCHN activities which have been deprioritised or halted. Improved planning to sustain routine health services and enable surge planning for emergencies with focus on the community/service users throughout adaptations is vital for improved MNCHN outcomes in FCAS., (© 2022. The Author(s).)

Background & Aims: In Wilson disease (WD), copper accumulates in the liver and other tissues because of mutations in the ATP7B copper transporter gene. Early and effective anticopper treatment is crucial. However, routine diagnostic methods based on clinical findings, copper metabolism tests, liver biopsies and DNA analyses do not always provide a conclusive diagnosis. The aim was to evaluate radioactive copper incorporation as a diagnostic test., Methods: We included cases with a diagnosis of WD supported by radiocopper testing and later, when available, confirmed by DNA analysis. Incorporation of 64 Cu was measured at 2, 24 and 48 hours following intravenous injection. Diagnostic accuracy (area under the receiver operating characteristic curve [AUC]), sensitivity, specificity and predictive value were assessed for 24 hours/2 hours and 48 hours/2 hours 64 Cu ratios and compared with serum measurements of ceruloplasmin, copper, non-ceruloplasmin-bound copper and urinary 24-hours copper excretion., Results: Patients having two pathogenic ATP7B mutations (homozygotes/compound heterozygotes) (n = 74) had significantly lower 24 hours/2 hours and 48 hours/2 hours 64 Cu ratios than heterozygote controls (n = 21) (mean 0.14 and 0.12 vs 0.49 and 0.63, respectively; both P < .001). Of note, 24 hours/2 hours and 48 hours/2 hours 64 Cu ratios had excellent diagnostic accuracy, with AUCs approaching 1, and only 24-hours urinary copper excretion displayed similar positive features. Other copper metabolism tests studied had lower accuracy, specificity and sensitivity., Conclusions: The radioactive copper test had excellent diagnostic accuracy and may be useful in the evaluation of new therapies aimed at restoring ATP7B function., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Unlabelled: The aim of this study was to assess two factors influencing the amount of oxidized LDL-paraoxonase 1 (PON1) activity and the level of anti-oxidized LDL antibodies (anti-ox LDL) in a large group of elderly individuals in Poland. The effects of cognitive status, hypertension and metabolic syndrome and of selected serum lipids and inflammation indicators on PON1 activity and anti-ox LDL level were also examined. The investigated population consisted of 3154 individuals aged 65 and more - participants of the population-based PolSenior project. PON1 arylesterase activity was determined spectrophotometrically, anti-ox-LDL antibodies using ELISA method. PON1 activity significantly decreased with advancing age, was lower in males than in females and decreased in persons with impaired cognition. Individuals with hypertension and high lipid levels showed higher PON1 activity. Lower PON1 activity was related to higher level of inflammation indicators - hsCRP and IL-6. The significant association of PON1 activity with age, HDL-C, LDL-C, sex and IL-6 was confirmed in multivariate analysis. Anti-ox LDL antibodies level was significantly higher in the two oldest subgroups of males. It was significantly lower in males than in females. It was decreased in persons with higher serum triglycerides. No relationship of anti-ox LDL level with cognition, hypertension, metabolic syndrome, inflammation indicators and serum lipid levels was observed. In some persons very high levels of anti-ox LDL were stated, most frequently in the oldest persons, particularly in men., Conclusion: Both investigated antioxidant factors - PON1 activity and anti-ox LDL level, could play an important role in aging., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Paraoxonase 1 (PON1) activity and metabolic syndrome traits were evaluated in 169 demented patients (81 recognized as AD, 32 as VaD, 56 as MD) and in 64 control individuals. Paraoxonase activity was determined spectrophotometrically using phenyloacetate as substrate. Metabolic syndrome was recognized according to AHA/NHLBI criteria. In the whole group with dementia significant positive correlation between PON1 activity/HDL cholesterol ratio (i.e. HDL corrected PON1 activity) and insulin level as well as HOMA IR index, was observed. The multivariate analysis showed that the PON1/HDL-C ratio was also significantly positively associated with the presence of metabolic syndrome (with insulin resistance as a major underlying trait) both in dementia and in control group. High insulin level and HOMA-IR are considered to be the traits of insulin resistance. It has however to be taken into account that they both could also depend on insulin production and release which, as was recently stated in cell experiments, are enhanced by PON1. The observed positive correlation suggests an advantageous role of the enzyme in metabolic syndrome influence on dementia development., (Copyright © 2012 Elsevier B.V. All rights reserved.)