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Pregnancy Risk, Infant Surveillance, and Measurement Alliance (PRISMA) Maternal and Newborn Health Study:Protocol for a multisite, prospective, open cohort study of pregnancy and postpartum health outcomes in South Asia and sub-Saharan Africa
Full text linkIntroduction Maternal and child mortality has markedly decreased worldwide over the past few decades. Despite this success, the decline remains unequal across countries and is overall insufficient to meet the Sustainable Development Goals. South Asia and sub-Saharan Africa bear most of the burden of maternal and child morbidity and mortality. Major gaps persist in our understanding of the causes, timing, diagnostic thresholds and risk factors for adverse outcomes in these regions. Addressing these gaps requires new ways to prevent and treat disease, from novel diagnostics to precision public health strategies, all of which rely on high-quality clinical data from diverse populations. The Pregnancy Risk, Infant Surveillance, and Measurement Alliance (PRISMA) Maternal and Newborn Health Study aims to estimate population-level prevalence of morbidities and mortality and to assess biological, clinical and sociodemographic risk among mother-infant pairs in India, Pakistan, Kenya, Ghana and Zambia. Methods and analysis This study is a prospective, open cohort study with a planned recruitment of about 6000 women annually across six research sites in five countries. Participants are pregnant women enrolled less than 20 weeks gestation, as determined by ultrasound, identified through active house-to-house and facility-based surveillance. Robust clinical data will be collected at 12 scheduled study visits during antenatal care, labour and delivery, and through 1 year postpartum. A total of 34 outcomes will be captured. The primary analysis will estimate the burden of adverse outcomes and examine associated risk factors to inform future intervention strategies. Data will also be used to develop normative values for pregnant and postpartum women, as well as predictive models to assess pregnancy risk. Ethics and dissemination PRISMA received institutional and national ethical approvals. Findings will be published in peer-reviewed open-access journals and disseminated at national and international forums to inform clinical guidelines and public health practice.</p
Machine learning-driven identification of serotype-independent pneumococcal vaccine candidates using samples from human infection challenge studies
Full text linkIdentifying conserved, immunogenic proteins that confer protection against Streptococcus pneumoniae (pneumococcus) colonization could enable development of serotype-independent vaccines. In our controlled human infection model, no individual IgG or cytokine/chemokine response correlated significantly with protection against colonization with pneumococcus, suggesting that effective immunity reflects a coordinated, multi-antigen response. To capture these complex patterns, we trained independent Random Forest models on humoral and cellular datasets. The humoral model identified IgG responses to PdB, SP1069, and SP0899 as predictive of protection. The cellular model revealed that MCP-1 responses to SP1069 and SP0899, and IL-17A production in response to SP0648-3, were associated with protection. Elevated baseline IFN-γ, RANTES, and anti-protein IgG levels were linked to reduced colonization density. We highlight SP1069 and SP0899 as potential serotype-independent vaccine candidates and demonstrate the utility of machine learning to identify immune correlates of protection.</p
Hemostatic hellfire: Rhabdophis helleri (Red-necked Keelback) snake venom pathophysiologically activates Factor VII and Factor X through novel uses of the clotting cofactors calcium, phospholipid, and Factor Va
Full text linkRhabdophis helleri envenomations may cause lethal coagulopathy, yet the venom mechanisms are poorly characterized. This study investigated the procoagulant mechanisms of R. helleri venom, with particular focus on coagulation factor activation and cofactor dependencies. We demonstrate that R. helleri venom potently activates Factor VII (FVII) and Factor X (FX) in a highly cofactor-dependent manner. FVII activation was minimal with venom alone but increased dramatically with the addition of the cofactor protein Factor V (FV) and reached maximal activity with the addition of the cofactor Factor Va (FVa). In addition to using endogenous thrombin produced FVa, the itself is able to convert FV into a useable FVa product. Similarly, FX activation was greatly amplified in the presence of FV or FVa, and showed similar cofactor dependence and the ability to use venom-activated FVa. Under comparable FV or FVa cofactor conditions, FX was activated at substantially lower magnitude than Factor VII, suggesting that Factor VII is the primary pathophysiological target. Systematic calcium and phospholipid requirement analysis revealed extremely high levels of dependence upon both cofactors. This is the first time for any venom that such a high level of phospholipid dependence has been noted. These results represent the first documentation of Factor Va-dependent zymogen activation in a non-front-fanged species, indicating convergent evolution of this mechanism across Natricidae, Elapidae, and Viperidae snake families. The determination of the biochemistry underpinning the rapid plasma clotting induced by the venom provides mechanistic insight into the consumption coagulopathy observed clinically in human envenomations and the stroke-inducing effect in prey. These toxicological findings advance understanding of rear-fanged snake venom evolution and inform development of treatment strategies for this understudied but medically important species.</p
Sub-optimal menstrual materials and vaginal microbiome disruption in women relying on sex for livelihood
No full textBackground: Sub-optimal menstrual materials (MM), such as using cloths, cotton balls, or tissues, can adversely affect the vaginal microbiome (VMB). Women who rely on sex for economic livelihood often use sub-optimal materials to conceal menstruation and avoid loss of income. We hypothesized that among women who rely on sex for economic livelihood, those using sub-optimal MM would be more likely to have non-optimal VMB than those with adequate MM.Methods: This cross-sectional analysis used baseline data from women participating in a trial assessing the impact of reusable menstrual discs on the VMB, Bacterial vaginosis (BV), and sexually transmitted infections (STIs). Data on sociodemographics, menstrual materials, and sexual practices were collected via interviewer-administered survey. Clinician-collected vaginal samples were tested for BV, STI, and VMB. VMB was assessed via 16S rRNA gene amplicon sequencing. A suite of statistical approaches identified factors associated with sub-optimal MM (use of cotton balls, tissue, or cloth) and VMB composition. Results: 407 women were enrolled February through October 2023, with median age 27 years, 24.7% were HIV-positive, 42.2% had BV, and 21.9% had STI (composite of chlamydia, gonorrhea, trichomoniasis). Vaginal community state type (CST) was primarily diverse (CST-IV; 63.5%), or Lactobacillus iners dominated (CST-III; 28.1%), while CST-I (L. crispatus dominated) was uncommon (7.9%). Sub-optimal MM was reported by 42.0% of participants and in multivariable modeling, was more common among women with indicators of economic strain. In multivariable analyses, alpha diversity was higher with sub-optimal MM and indicators of economic strain. Sub-optimal MM was associated with CST-IV in crude analyses but was attenuated and non-significant when adjusted for age, educational attainment, amount paid at last sexual encounter, number of sex partners, and HSV-2. Non-targeted machine learning algorithms identified non-optimal VMB taxa with greater relative abundance among women with sub-optimal MM.Discussion: Sub-optimal menstrual materials were used commonly and associated with non-optimal VMB composition. Reusable menstrual discs that may be worn during sex may address the economic factors driving sub-optimal MM that are associated with non-optimal VMB.<br/
Operationalising people-centred community-led self-help groups to improve mental health and wellbeing for people with skin-neglected tropical diseases : a case study from Kasai, DRC
No full textIntroduction: People affected by skin-neglected tropical diseases (NTDs) may experience stigma and discrimination due to visible physical impairments, negatively affecting their mental health, wellbeing, and quality of life. To address these challenges, our partnership used a community-based participatory research (CBPR) approach to co-develop, test, and evaluate a community-led intervention that included self-help groups. In this article, we critically evaluate the intervention implementation process, to provide clear implementation considerations when operationalising self-help groups for NTDs, a missing component of the evidence base. Method: Photovoice activities with self-help group members and leaders explored the experience of peer-support amongst people affected by skin NTDs. Additional data included reports from self-help group meetings and reflective sessions, in-depth interviews with group members, and key-informant interviews with stakeholders. Data were analysed using framework analysis using NVivo 12. Results: Five interrelated elements were identified as central to people-centred community-led self-help groups for people affected by skin NTDs in Kasai, DRC: 1) relevant and actionable needs-based activities; 2) a shared purpose amongst group members; 3) inclusivity and equity in roles, responsibilities, and benefits; 4) committed leadership; and 5) continuous capacity strengthening and support from research and implementing partners. Conclusion: This is one of the first studies presenting insights from people affected by skin NTDs on how community-led self-help groups can be operationalised in a people-centred way. The findings highlight key implementation considerations that may inform the design and delivery of self-help group interventions in low-resource settings, potentially supporting sustainability and user-led engagement.</p
Quantifying venom in African snakes: Insights into protein content, yield and body size associations
No full textSnake venoms are complex mixtures primarily composed of toxic proteins used during prey capture and defence. There is limited knowledge concerning the protein concentration of snake venom and the biases of different protein determination methods. Here, we assess the ability of the Qubit protein assay, bicinchoninic acid (BCA) assay, Bradford assay and NanoDrop spectrometry (A280 with a mass extinction coefficient of one) to accurately quantify protein concentrations of toxins isolated from venom, including three-finger toxins and phospholipase A2. The Bradford assays severely underestimated three-finger toxin concentrations and NanoDrop spectrometry overestimated phospholipase A2 concentrations, whilst the BCA assay was the most accurate. Venom from six major African venomous snake genera was also assessed: coral cobras (Aspidelaps spp.); mambas (Dendroaspis spp.); cobras (Naja spp.); bush vipers (Atheris sp.); adders (Bitis spp.); and saw-scaled vipers (Echis sp.). Protein concentration results were inconsistent between methods. Protein concentrations were found to be lowest for Bitis spp. venom and highest for Naja spp. venom and did not vary between species of the same genus. However, in general, Elapidae species had venoms with significantly higher protein concentrations than Viperidae species. Moreover, there was greater variability between Elapidae species. We also determined wet venom yields and used this to provide a tentative estimate of the total protein quantity that may be injected during a snake bite. We found snake weight and length influenced wet venom yield for the Atheris squamigera but not for Bitis arietans and Echis romani. Our results aim to improve our understanding of the physical properties of snake venom
Deinfibulation for improving obstetric, neonatal, gynecologic, and sexual health outcomes in women and girls with type III female genital mutilation: A systematic review and meta-analysis
No full textBackground: Type III female genital mutilation (FGM) is corrected by the scar tissue removal of the vaginal opening, known as deinfibulation. Objectives: To determine the current evidence on whether deinfibulation leads to improved obstetric, neonatal, gynecologic, and sexual health outcomes. Search Strategy: The following databases were searched from inception to May 18, 2023: CINAHL Plus (EBSCOhost), MEDLINE (Ovid), PsycINFO (EBSCOhost), SCOPUS, and Web of Science. Selection Criteria: Two review authors independently screened the titles and abstracts, extracted data, and performed the risk of bias assessment. Data Collection and Analysis: Meta-analysis was conducted with RevMan, and the quality of evidence was assessed using the GRADE approach. Main Results: Eight studies with serious risk of bias involving 3166 women were included. Very low-certainty evidence indicates that deinfibulation for women with type III FGM reduced the odds of an emergency cesarean birth (odds ratio [OR] 0.16, 95% confidence interval [CI] 0.06–0.42) and genital tract lacerations (OR 0.48, 95% CI 0.29–0.79) when compared to women with type III FGM without deinfibulation. Reduced odds of an emergency cesarean birth apply when compared to women without FGM (OR 0.59, 95% CI 0.37–0.93). Antepartum deinfibulation, compared to intrapartum deinfibulation, may lead to a reduction in the duration of labor, with little or no difference in the risk of prolonged labor (low-certainty evidence). Antepartum deinfibulation may increase the likelihood of postpartum hemorrhage and cesarean births in pregnant women with type III FGM (low-certainty evidence). We found no studies for inclusion on gynecologic, urologic, and sexual health outcomes for this update. Conclusions: The evidence of deinfibulation for women with type III FGM is available only for obstetrics outcomes. Larger observational studies in settings where type III FGM is predominantly practiced are required to improve the certainty of the evidence in these findings.</p
Medical oxygen and respiratory support requirements for patients hospitalised with COVID-19 in 23 low-income and middle-income countries: a prospective, observational cohort study
Full text linkBackground: The COVID-19 pandemic highlighted a global shortage of, and inequity of access to, medical oxygen. Understanding patient outcomes and the capacities of health facilities to provide respiratory support including oxygen is key to matching need and demand. We report results from a global study including 23 low-income and middle-income countries. Methods: For this prospective, observational cohort study, consecutive patients aged 12 years or older with suspected or confirmed COVID-19 and evidence of respiratory distress were prospectively recruited within 24 h of hospital admission. Hospitals from 23 low-income and middle-income countries were included, representing all WHO regions. Baseline demographic and clinical data were collected, and daily follow-ups were recorded for in-hospital outcomes and respiratory support types. At the facility level, we assessed sources of oxygen and electricity, infrastructural and staffing capacity for critical care provision, and the capabilities of the facility for advanced respiratory support. The primary outcome was 30-day in-hospital mortality. This study was registered on ClinicalTrials.gov (NCT04918875). Findings: Between Jan 24 and Nov 22, 2022, 56 sites took part. Of 53 726 patients screened, 3070 were enrolled. 1814 (61·6%) of 2947 patients had two or more underlying medical conditions and initially received oxygen through nasal cannula or non-rebreather face masks with reservoir. Invasive mechanical ventilation was most frequently used in patients recruited in the Americas (75 [26·4%] of 284 patients) and in the Eastern Mediterranean (90 [18·0%] of 499 patients). The overall mortality was 649 (23·4%) of 2779 patients, varying by region from 53 (10·5%) of 506 patients in South-East Asia to 286 (37·6%) of 760 patients in Africa. Mortality was associated with the maximum level of respiratory support received: from 17 (8·6%) of 198 patients who received no oxygen, 99 (38·4%) of 258 patients for non-rebreather reservoir bags, and 205 (62·9%) of 326 for invasive ventilation. Interpretation: The availability and use of oxygen support options in low-income and middle-income countries are highly variable but appear significantly less in the African region. Mortality might be associated with a lack of access to oxygen, which varied across WHO regions but was highest in Africa. Despite many lessons learned from the COVID-19 pandemic, inequity in access to medical oxygen remains a challenge that WHO and partners must address in the post-pandemic era to avoid preventable deaths. Funding: UNITAID.</p
Evaluating community digital data linkage with or without community data use to increase antenatal care uptake in Western Kenya: protocol for a pragmatic open-label, cluster-randomised controlled superiority trial
Full text linkBackground: Less than 10% of pregnant women in Sub Saharan Africa achieve the World Health Organization recommended eight antenatal care (ANC) contacts for optimal pregnancy management. Robust strategies that involve community outreach programmes, integrated service delivery and continuity of care could help improve ANC uptake and quality. Kenya, as other countries, has promoted use of digital health records at the community and facility levels to improve quality and access to data and promote continuity of care. These records, however, are not always linked and access to data does not guarantee its use to drive quality improvement. C-it-DU-it (pronounced “See it, Do it”) is a two-arm pragmatic cluster-randomised trial set in Homabay County, Kenya. The trial will implement digital linkage of community and facility electronic patient data (control arm) and assess the impact of having quality improvement teams reviewing and acting on the linked data (intervention arm). While several areas are captured in the community health records, we will focus on uptake of ANC services as a lens.Methods: Eighteen healthcare facilities (clusters) will be randomly allocated to either the control or intervention arms at a ratio of 1:1. A data linkage module will be deployed in all clusters, enabling digital referral of pregnant women between the community and health facilities. In each intervention cluster, work improvement teams will be established and trained on reviewing these electronic ANC data, identifying problems, developing and deploying context-specific solutions to these problems and evaluating the impact of their interventions. ANC data will be extracted for 1,440 recruited pregnant women. The primary outcome will be the proportion of pregnant women with at least eight ANC contacts. Secondary outcomes will be ANC uptake before 16 weeks gestation, adverse pregnancy outcomes, uptake of required investigations, medication and skilled birth attendance.Discussion: This trial intends to generate evidence on the benefit of community work improvement teams to review and act on linked digital data to develop and deploy solutions to local problems. This strategy, if successful, will promote antenatal service uptake and quality resulting in improved pregnancy outcomes and progress towards sustainable development goals if appropriately scaled up