Multikingdom and functional gut microbiota markers for autism spectrum disorder.

Associations between the gut microbiome and autism spectrum disorder (ASD) have been investigated although most studies have focused on the bacterial component of the microbiome. Whether gut archaea, fungi and viruses, or function of the gut microbiome, is altered in ASD is unclear. Here we performed metagenomic sequencing on faecal samples from 1,627 children (aged 1-13 years, 24.4% female) with or without ASD, with extensive phenotype data. Integrated analyses revealed that 14 archaea, 51 bacteria, 7 fungi, 18 viruses, 27 microbial genes and 12 metabolic pathways were altered in children with ASD. Machine learning using single-kingdom panels showed area under the curve (AUC) of 0.68 to 0.87 in differentiating children with ASD from those that are neurotypical. A panel of 31 multikingdom and functional markers showed a superior diagnostic accuracy with an AUC of 0.91, with comparable performance for males and females. Accuracy of the model was predominantly driven by the biosynthesis pathways of ubiquinol-7 or thiamine diphosphate, which were less abundant in children with ASD. Collectively, our findings highlight the potential application of multikingdom and functional gut microbiota markers as non-invasive diagnostic tools in ASD.

Fecal Microbiota Transplantation for Sleep Disturbance in Postacute COVID-19 Syndrome.

BACKGROUND & AIMS: Postacute COVID-19 syndrome (PACS) is associated with sleep disturbance, but treatment options are limited. The etiology of PACS may be secondary to alterations in the gut microbiome. Here, we report the efficacy of fecal microbiota transplantation (FMT) in alleviating post-COVID insomnia symptoms in a nonrandomized, open-label prospective interventional study. METHODS: Between September 22, 2022, and May 22, 2023, we recruited 60 PACS patients with insomnia defined as Insomnia Severity Index (ISI) ≥8 and assigned them to the FMT group (FMT at weeks 0, 2, 4, and 8; n = 30) or the control group (n = 30). The primary outcome was clinical remission defined by an ISI of <8 at 12 weeks. Secondary outcomes included changes in the Pittsburgh Sleep Quality Index, Generalized Anxiety Disorder-7 scale, Epworth Sleepiness Scale, Multidimensional Fatigue Inventory, blood cortisol and melatonin, and gut microbiome analysis on metagenomic sequencing. RESULTS: At week 12, more patients in the FMT than the control group had insomnia remission (37.9% vs 10.0%; P = .018). The FMT group showed a decrease in ISI score (P < .0001), Pittsburgh Sleep Quality Index (P < .0001), Generalized Anxiety Disorder-7 scale (P = .0019), Epworth Sleepiness Scale (P = .0057), and blood cortisol concentration (P = .035) from baseline to week 12, but there was no significant change in the control group. There was enrichment of bacteria such as Gemmiger formicilis and depletion of microbial pathways producing menaquinol derivatives after FMT. The gut microbiome profile resembled that of the donor in FMT responders but not in nonresponders at week 12. There was no serious adverse event. CONCLUSIONS: This pilot study showed that FMT could be effective and safe in alleviating post-COVID insomnia, and further clinical trials are warranted. CLINICALTRIALS: gov, Number: NCT05556733.

Beyond isotropic repulsion: Classical anisotropic repulsion by inclusion of p orbitals.

Accurate modeling of intermolecular repulsion is an integral component in force field development. Although repulsion can be explicitly calculated by applying the Pauli exclusion principle, this approach is computationally viable only for systems of limited sizes. Instead, it has previously been shown that repulsion can be reformulated in a "classical" picture: the Pauli exclusion principle prohibits electrons from occupying the same state, leading to a depletion of electronic charge between atoms, giving rise to an enhanced nuclear-nuclear electrostatic repulsion. This classical picture is called the isotropic S2/R approximation, where S is the overlap and R is the interatomic distance. This approximation accurately captures the repulsion of isotropic atoms such as noble gas dimers; however, a key deficiency is that it fails to capture the angular dependence of the repulsion of anisotropic molecules. To include directionality, the wave function must at least be a linear combination of s and p orbitals. We derive a new anisotropic S2/R repulsion model through the inclusion of the anisotropic p orbital term in the total wave function. Because repulsion is pairwise and decays rapidly, it can be truncated at a short range, making it amenable for efficient calculation of energy and forces in complex biomolecular systems. We present a parameterization of the S101 dimer database against the ab initio benchmark symmetry-adapted perturbation theory, which yields an rms error of only 0.9 kcal/mol. The importance of the anisotropic term is demonstrated through angular scans of water-water dimers and dimers involving halobenzene. Simulation of liquid water shows that the model can be computed efficiently for realistic system sizes.

Modelling spatiotemporal variation in under-five malaria risk in Ghana in 2016-2021.

BACKGROUND: Ghana is among the top 10 highest malaria burden countries, with about 20,000 children dying annually, 25% of which were under five years. This study aimed to produce interactive web-based disease spatial maps and identify the high-burden malaria districts in Ghana. METHODS: The study used 2016-2021 data extracted from the routine health service nationally representative and comprehensive District Health Information Management System II (DHIMS2) implemented by the Ghana Health Service. Bayesian geospatial modelling and interactive web-based spatial disease mapping methods were employed to quantify spatial variations and clustering in malaria risk across 260 districts. For each district, the study simultaneously mapped the observed malaria counts, district name, standardized incidence rate, and predicted relative risk and their associated standard errors using interactive web-based visualization methods. RESULTS: A total of 32,659,240 malaria cases were reported among children < 5 years from 2016 to 2021. For every 10% increase in the number of children, malaria risk increased by 0.039 (log-mean 0.95, 95% credible interval = - 13.82-15.73) and for every 10% increase in the number of males, malaria risk decreased by 0.075, albeit not statistically significant (log-mean - 1.82, 95% credible interval = - 16.59-12.95). The study found substantial spatial and temporal differences in malaria risk across the 260 districts. The predicted national relative risk was 1.25 (95% credible interval = 1.23, 1.27). The malaria risk is relatively the same over the entire year. However, a slightly higher relative risk was recorded in 2019 while in 2021, residing in Keta, Abuakwa South, Jomoro, Ahafo Ano South East, Tain, Nanumba North, and Tatale Sanguli districts was associated with the highest malaria risk ranging from a relative risk of 3.00 to 4.83. The district-level spatial patterns of malaria risks changed over time. CONCLUSION: This study identified high malaria risk districts in Ghana where urgent and targeted control efforts are required. Noticeable changes were also observed in malaria risk for certain districts over some periods in the study. The findings provide an effective, actionable tool to arm policymakers and programme managers in their efforts to reduce malaria risk and its associated morbidity and mortality in line with the Sustainable Development Goals (SDG) 3.2 for limited public health resource settings, where universal intervention across all districts is practically impossible.

The gut microbiome associates with phenotypic manifestations of post-acute COVID-19 syndrome.

The mechanisms underlying the many phenotypic manifestations of post-acute COVID-19 syndrome (PACS) are poorly understood. Herein, we characterized the gut microbiome in heterogeneous cohorts of subjects with PACS and developed a multi-label machine learning model for using the microbiome to predict specific symptoms. Our processed data covered 585 bacterial species and 500 microbial pathways, explaining 12.7% of the inter-individual variability in PACS. Three gut-microbiome-based enterotypes were identified in subjects with PACS and associated with different phenotypic manifestations. The trained model showed an accuracy of 0.89 in predicting individual symptoms of PACS in the test set and maintained a sensitivity of 86% and a specificity of 82% in predicting upcoming symptoms in an independent longitudinal cohort of subjects before they developed PACS. This study demonstrates that the gut microbiome is associated with phenotypic manifestations of PACS, which has potential clinical utility for the prediction and diagnosis of PACS.

Association between concurrence of multiple risk factors and under-5 mortality: a pooled analysis of data from Demographic and Health Survey in 61 low-and-middle-income countries.

Background: Exposure to multiple risk factors is prevalent in low-and middle-income countries (LMICs), challenging one-directional strategies to address preventable under-5 mortality (U5M). This study aims to assess the associations between concurrence of multiple risk factors and U5M in LMICs. Methods: We extracted data from the Demographic and Health Surveys conducted between 2010 and 2021 across 61 LMICs. Our primary outcome was U5M, defined as deaths from birth to 59 months. Binary logistic regression model was applied to ascertain the association between U5M and a total of 20 critical risk factors. Upon identifying the risk factors demonstrating the strongest associations, we investigated the simultaneous presence of multiple risk factors in each individual and assessed their combined effects on U5M with logistic regression models. Findings: Of the 604,372 under-5 children, 18,166 (3.0%) died at the time of the survey. Unsatisfied family planning needs was the strongest risk factor for U5M (odds ratio [OR]: 2.0, 95% confidence interval [CI]: 1.9-2.1), followed by short birth interval (<18 months; OR: 2.0, 95% CI: 1.9-2.1), small birth size (OR: 2.0, 95% CI: 1.8-2.1), never breastfed or delayed breastfeeding (OR: 2.0, 95% CI: 1.9-2.0), and low maternal education (OR: 1.6, 95% CI: 1.4-1.8). 66.7% (66.6%-66.8%) of the children had 2 or more leading risk factors simultaneously. Simultaneous presence of multiple leading risk factors was significantly associated with elevated risk of U5M and children presenting with all 5 leading risk factors exhibited an exceedingly high risk of U5M (OR: 5.2, 95% CI: 4.3-6.3); a dose-response relationship between the number of risk factors and U5M was also observed-with the increment of numbers of leading risk factors, the U5M showed an increasing trend (p-trend < 0.001). Interpretation: Exposure to multiple risk factors is very common in LMICs and underscores the necessity of developing multisectoral and integrated approaches to accelerate progress in reducing U5M in line with the SDG 3.2. Funding: This research is funded by Research Fund, Vanke School of Public Health, Tsinghua University.

A scoping review of the literature on the application and usefulness of the Problem Management Plus (PM+) intervention around the world.

BACKGROUND: Given the high rates of common mental disorders and limited resources, task-shifting psychosocial interventions are needed to provide adequate care. One such intervention developed by the World Health Organization is Problem Management Plus (PM+). AIMS: This review maps the evidence regarding the extent of application and usefulness of the PM+ intervention, i.e. adaptability, feasibility, effectiveness and scalability, since it was introduced in 2016. METHOD: We conducted a scoping review of seven literature databases and grey literature from January 2015 to February 2024, to identify peer-reviewed and grey literature on PM+ around the world. RESULTS: Out of 6739 potential records, 42 met the inclusion criteria. About 60% of the included studies were from low- and middle-income countries. Findings from pilot/feasibility trials demonstrated that PM+ is feasible, acceptable and safe. Results from definitive randomised controlled trials at short-term follow-up also suggested that PM+ is effective, with overall moderate-to-large effect sizes, in improving symptoms of common mental health problems. Although PM+ was more effective in reducing symptoms of common mental disorders, it was found to be costlier compared to usual care in the only study that evaluated its cost-effectiveness. CONCLUSIONS: Our findings indicate that PM+, in its individual and group formats, can be adapted and effectively delivered by trained helpers to target a wide range of common mental health concerns. More effectiveness and implementation evidence is required to understand the long-term impact of PM+, its cost-effectiveness and scalability, and moderators of treatment outcomes such as gender and delivery formats.

Accuracy of and preferences for blood-based versus oral-fluid-based HIV self-testing in Malawi: a cross-sectional study.

BACKGROUND: HIV self-testing (HIVST) can use either oral-fluid or blood-based tests. Studies have shown strong preferences for self-testing compared to facility-based services. Despite availability of low-cost blood-based HIVST options, to date, HIVST implementation in sub-Saharan Africa has largely been oral-fluid-based. We investigated whether users preferred blood-based (i.e. using blood sample derived from a finger prick) or oral fluid-based HIVST in rural and urban Malawi. METHODS: At clinics providing HIV testing services (n = 2 urban; n = 2 rural), participants completed a semi-structured questionnaire capturing sociodemographic data before choosing to test using oral-fluid-based HVST, blood-based HIVST or provider-delivered testing. They also completed a self-administered questionnaire afterwards, followed by a confirmatory test using the national algorithm then appropriate referral. We used simple and multivariable logistic regression to identify factors associated with preference for oral-fluid or blood-based HIVST. RESULTS: July to October 2018, N = 691 participants enrolled in this study. Given the choice, 98.4% (680/691) selected HIVST over provider-delivered testing. Of 680 opting for HIVST, 416 (61.2%) chose oral-fluid-based HIVST, 264 (38.8%) chose blood-based HIVST and 99.1% (674/680) reported their results appropriately. Self-testers who opted for blood-based HIVST were more likely to be male (50.3% men vs. 29.6% women, p < 0.001), attending an urban facility (43% urban vs. 34.6% rural, p = 0.025) and regular salary-earners (49.5% regular vs. 36.8% non-regular, p = 0.012). After adjustment, only sex was found to be associated with choice of self-test (adjusted OR 0.43 (95%CI: 0.3-0.61); p-value < 0.001). Among 264 reporting blood-based HIVST results, 11 (4.2%) were HIV-positive. Blood-based HIVST had sensitivity of 100% (95% CI: 71.5-100%) and specificity of 99.6% (95% CI: 97.6-100%), with 20 (7.6%) invalid results. Among 416 reporting oral-fluid-based HIVST results 18 (4.3%) were HIV-positive. Oral-fluid-based HIVST had sensitivity of 88.9% (95% CI: 65.3-98.6%) and specificity of 98.7% (95% CI: 97.1-99.6%), with no invalid results. CONCLUSIONS: Offering both blood-based and oral-fluid-based HIVST resulted in high uptake when compared directly with provider-delivered testing. Both types of self-testing achieved high accuracy among users provided with a pre-test demonstration beforehand. Policymakers and donors need to adequately plan and budget for the sensitisation and support needed to optimise the introduction of new quality-assured blood-based HIVST products.

A multilevel analysis of the predictors of health facility delivery in Ghana: Evidence from the 2014 Demographic and Health Survey.

Health facility delivery has the potential to improve birth and general health outcomes for both newborns and mothers. Regrettably, not all mothers, especially in low-and-middle income countries like Ghana deliver at health facilities, and mostly under unhygienic conditions. Using data from the 2014 Ghana Demographic and Health Survey, we fitted both weighted single-level and random intercept multilevel binary logistic regression models to analyse predictors of a health facility delivery among mothers aged 15-49 years and to quantify unobserved household and community differences in the likelihood of health facility delivery. We analysed data on 4202 mothers residing in 3936 households and 427 communities. Of the 4202 mothers who delivered, 3031 (75.3%-weighted and 72.1%-unweighted) delivered at the health facility. Substantial unobserved household only (Median Odds Ratio (MOR) = 5.1) and household conditional on community (MOR = 4.7) level differences in the likelihood of health facility delivery were found. Mothers aged 25-34 (aOR = 1.4, 95%CI: 1.0-2.1) and 35-44 (aOR = 2.9, 95%CI: 1.7-4.8), mothers with at least a secondary education (aOR = 2.7, 95%CI: 1.7-4.1), with health insurance coverage (aOR = 1.6, 95%CI: 1.2-2.2) and from richer/richest households (aOR = 8.3, 95%CI: 3.6-19.1) and with piped water (aOR = 1.5, 95%CI: 1.1-2.1) had increased odds of health facility delivery. Mothers residing in rural areas (aOR = 0.3, 95%CI: 0.2-0.5) and with no religion (aOR = 0.5, 95%CI: 0.3-1.0) and traditional religion (aOR = 0.2, 95%CI: 0.1-0.6), who reported not wanting to go to health facilities alone as a big problem (aOR = 0.5, 95%CI: 0.3-0.8) and having a parity of 2 (aOR = 0.4, 95%CI: 0.3-0.7), 3 (aOR = 0.3, 95%CI: 0.2-0.6) and ≥4 (aOR = 0.3, 95%CI: 0.1-0.5) had reduced odds of health facility delivery. Our predictive model showed outstanding predictive power of 96%. The study highlights the need for improved healthcare seeking behaviours, maternal education and household wealth, and bridge the urban-rural gaps to improve maternal and newborn health outcomes.

Accurate surgical posterior tibial slope alteration can be achieved in total knee arthroplasty regardless of surgeon skill level or local soft tissue thickness-A retrospective radiograph-based study.

PURPOSE: To retrospectively report on the impact of local soft tissue thickness and surgeon skill level on the accuracy of surgical posterior tibial slope (PTS) alteration achieved in patients undergoing total knee arthroplasty (TKA) utilising lateral knee radiographs. METHODS: Pre- and postoperative radiographs of 82 patients undergoing primary TKA using conventional mechanical alignment technique were measured by two observers and subjected to quality criteria for accurate measurement of the PTS. All patients underwent a standardised surgical approach for PTS alteration: cruciate-retaining (CR) cases with preoperative PTS ≤ 10° were set for reconstruction of the preoperative PTS. Cases indicated for posterior-stabilised (PS) design and/or with a preoperative PTS > 10° were set for 3° of postoperative PTS. Pretibial subcutaneous fat (PSF) and surgeon skill level were analysed for their predictive quality regarding the accuracy of surgical PTS alteration achieved. RESULTS: The overall mean postoperative PTS was significantly lower than the preoperative values (6.2°, SD 2.7 vs. 7.7°, SD 3.2; p = 0.002103). Neither local soft tissue thickness, namely PSF, nor surgeon skill level was found to be a predictor of the accuracy of surgical PTS alteration achieved. Among cases set for PTS reconstruction, 25.9% and 42.6% achieved a postoperative PTS within ±1° and ±2° of preoperative values, respectively. In patients with a PTS > 10° or those indicated for PS design, slope reduction was achieved with a mean postoperative PTS of 6.5°. Furthermore, 14.3% and 32.1% of cases were within ±1° and ±2° of 3, respectively. CONCLUSION: This study demonstrates that accurate surgical alteration of the PTS is possible in TKA regardless of local knee soft tissue thickness or surgeon skill level. This proves the clinical feasibility of both targeted reduction as well as reconstruction of the PTS in TKA. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Cytotoxic ent-abietane diterpenoids, banyangmbolides A-E, from the leaves of Suregada occidentalis.

The chemical investigation of a leaf extract from a herbarium specimen of Suregada occidentalis collected in Banyang Mbo Wildlife Sanctuary, Southwest Region, Cameroon, yielded five undescribed ent-abietane diterpenoids, banyangmbolides A-E, (1-5), and four known diterpenoids, gelomulides A (6), B (7), D (8) and O (9). The structures of the isolated compounds were determined using NMR, IR, ECD and HRESIMS. Compounds 5, 7 and 8, showed 48-55% inhibition at 200 µM against FM-55-M1 human melanoma cells.

A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Post-acute COVID-19 syndrome (PACS) affects over 65 million individuals worldwide but treatment options are scarce. We aimed to assess a synbiotic preparation (SIM01) for the alleviation of PACS symptoms. METHODS: In this randomised, double-blind, placebo-controlled trial at a tertiary referral centre in Hong Kong, patients with PACS according to the US Centers for Disease Control and Prevention criteria were randomly assigned (1:1) by random permuted blocks to receive SIM01 (10 billion colony-forming units in sachets twice daily) or placebo orally for 6 months. Inclusion criterion was the presence of at least one of 14 PACS symptoms for 4 weeks or more after confirmed SARS-CoV-2 infection, including fatigue, memory loss, difficulty in concentration, insomnia, mood disturbance, hair loss, shortness of breath, coughing, inability to exercise, chest pain, muscle pain, joint pain, gastrointestinal upset, or general unwellness. Individuals were excluded if they were immunocompromised, were pregnant or breastfeeding, were unable to receive oral fluids, or if they had received gastrointestinal surgery in the 30 days before randomisation. Participants, care providers, and investigators were masked to group assignment. The primary outcome was alleviation of PACS symptoms by 6 months, assessed by an interviewer-administered 14-item questionnaire in the intention-to-treat population. Forward stepwise multivariable logistical regression was performed to identify predictors of symptom alleviation. The trial is registered with ClinicalTrials.gov, NCT04950803. FINDINGS: Between June 25, 2021, and Aug 12, 2022, 463 patients were randomly assigned to receive SIM01 (n=232) or placebo (n=231). At 6 months, significantly higher proportions of the SIM01 group had alleviation of fatigue (OR 2·273, 95% CI 1·520-3·397, p=0·0001), memory loss (1·967, 1·271-3·044, p=0·0024), difficulty in concentration (2·644, 1·687-4·143, p<0·0001), gastrointestinal upset (1·995, 1·304-3·051, p=0·0014), and general unwellness (2·360, 1·428-3·900, p=0·0008) compared with the placebo group. Adverse event rates were similar between groups during treatment (SIM01 22 [10%] of 232 vs placebo 25 [11%] of 231; p=0·63). Treatment with SIM01, infection with omicron variants, vaccination before COVID-19, and mild acute COVID-19, were predictors of symptom alleviation (p<0·0036). INTERPRETATION: Treatment with SIM01 alleviates multiple symptoms of PACS. Our findings have implications on the management of PACS through gut microbiome modulation. Further studies are warranted to explore the beneficial effects of SIM01 in other chronic or post-infection conditions. FUNDING: Health and Medical Research Fund of Hong Kong, Hui Hoy and Chow Sin Lan Charity Fund, and InnoHK of the HKSAR Government. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Geostatistical modelling of child undernutrition in developing countries using remote-sensed data: evidence from Bangladesh and Ghana demographic and health surveys.

Childhood chronic undernutrition, known as stunting, remains a critical public health problem globally. Unfortunately while the global stunting prevalence has been declining over time, as a result of concerted public health efforts, there are areas (notably in sub-Saharan Africa and South Asia) where progress has stagnated. These regions are also resource-poor, and monitoring progress in the fight against chronic undernutrition can be problematic. We propose geostatistical modelling using data from existing demographic surveys supplemented by remote-sensed information to provide improved estimates of childhood stunting, accounting for spatial and non-spatial differences across regions. We use two study areas-Bangladesh and Ghana-and our results, in the form of prevalence maps, identify communities for targeted intervention. For Bangladesh, the maps show that all districts in the south-eastern region are identified to have greater risk of stunting, while in Ghana the greater northern region had the highest prevalence of stunting. In countries like Bangladesh and Ghana with limited resources, these maps can be useful diagnostic tools for health planning, decision making and implementation.

Does mobile renewal make health insurance more responsive to clients? A case study of the National Health Insurance Scheme in Ghana.

BACKGROUND: In 2018, Ghana's National Health Insurance Authority (NHIA) introduced a mobile strategy to enhance re-enrolment and improve client knowledge of their entitlements. This study investigated how Ghana's mobile strategy has influenced the NHIA's responsiveness to clients in terms of patient rights and entitlements, equity and satisfaction with health services. METHODS: We surveyed people (n=1700) in 6 districts who had renewed their insurance in the previous 12 months, using any strategy (mobile or manual). Multiple regression analysis examined correlation between individual characteristics and renewal modality. Policy documents on the mobile programme's design and focus group discussions (n=12) on people's experiences renewing their insurance were analysed thematically. RESULTS: While the mobile platform was designed for mobile National Health Insurance Scheme (NHIS) renewal and to provide information about insurance entitlements, few people surveyed (20%) knew about these informational features. Among those who renewed their NHIS coverage, 58% did so on the mobile renewal platform. Mobile renewal was high among those with tertiary education and those in the higher wealth quintiles. Mobile renewal was considered convenient, but required literacy in English, a phone and a mobile money wallet. For those who lacked some or all of these prerequisites but wanted to use mobile renewal, mobile vendors emerged as valued facilitators. CONCLUSION: The mobile platform has increased the responsiveness of Ghana's NHIS through offering clients a more convenient mechanism to renew their insurance policies. It does not, however, eliminate the one month waiting period for activating the card, does not provide prompts to reassure clients of their renewal and does not empower most clients with information on entitlements. To improve the adoption and use of the mobile renewal strategy, the NHIA should publicise the platform's information-sharing functions and explore formally engaging mobile vendors.

Geospatial Analyses of Recent Household Surveys to Assess Changes in the Distribution of Zero-Dose Children and Their Associated Factors before and during the COVID-19 Pandemic in Nigeria.

The persistence of geographic inequities in vaccination coverage often evidences the presence of zero-dose and missed communities and their vulnerabilities to vaccine-preventable diseases. These inequities were exacerbated in many places during the coronavirus disease 2019 (COVID-19) pandemic, due to severe disruptions to vaccination services. Understanding changes in zero-dose prevalence and its associated risk factors in the context of the COVID-19 pandemic is, therefore, critical to designing effective strategies to reach vulnerable populations. Using data from nationally representative household surveys conducted before the COVID-19 pandemic, in 2018, and during the pandemic, in 2021, in Nigeria, we fitted Bayesian geostatistical models to map the distribution of three vaccination coverage indicators: receipt of the first dose of diphtheria-tetanus-pertussis-containing vaccine (DTP1), the first dose of measles-containing vaccine (MCV1), and any of the four basic vaccines (bacilli Calmette-Guerin (BCG), oral polio vaccine (OPV0), DTP1, and MCV1), and the corresponding zero-dose estimates independently at a 1 × 1 km resolution and the district level during both time periods. We also explored changes in the factors associated with non-vaccination at the national and regional levels using multilevel logistic regression models. Our results revealed no increases in zero-dose prevalence due to the pandemic at the national level, although considerable increases were observed in a few districts. We found substantial subnational heterogeneities in vaccination coverage and zero-dose prevalence both before and during the pandemic, showing broadly similar patterns in both time periods. Areas with relatively higher zero-dose prevalence occurred mostly in the north and a few places in the south in both time periods. We also found consistent areas of low coverage and high zero-dose prevalence using all three zero-dose indicators, revealing the areas in greatest need. At the national level, risk factors related to socioeconomic/demographic status (e.g., maternal education), maternal access to and utilization of health services, and remoteness were strongly associated with the odds of being zero dose in both time periods, while those related to communication were mostly relevant before the pandemic. These associations were also supported at the regional level, but we additionally identified risk factors specific to zero-dose children in each region; for example, communication and cross-border migration in the northwest. Our findings can help guide tailored strategies to reduce zero-dose prevalence and boost coverage levels in Nigeria.

A new 30-norfriedelane triterpnoid from Caloncoba lophocarpa (Oliv.) Gilg. (Achariaceae).

The chemical investigation of the methanol extract of the roots of Caloncoba lophocarpa (Oliv.) Gilg. exhibited a new 30-norfriedelane triterpenoid, laphocarpanol (1), together with seven known compounds, caloncobalactone (2), friedelin (3), friedelanol (4), asperphernamate (5), stigmasterol (6), sitosterol (7) and sitosterol-3-O-ß-D-glucopyranoside (8). The structures of the compounds were elucidated by extensive spectroscopic and spectrometric analyses (1D and 2D NMR, ESI-MS) and by comparison with previously reported data. All the compounds were tested for their antifungal and antibacterial activities. Compound 1 displayed weak antibacterial effect with MIC value of 62.5 µg/mL against Shigella flexineri. All the isolates were found to be inactive against the tested fungal strains.

Predicted broadly neutralizing antibody (bnAb) resistance and associated envelope characteristics of adults with HIV-1 seroconversion in Botswana.

We used HIV-1C sequences to predict (in silico) resistance to 33 known broadly neutralizing antibodies (bNAbs) and evaluate the different HIV-1 env characteristics that may affect virus neutralization. We analyzed proviral sequences from adults with documented HIV-1 seroconversion (N=140) in Botswana (2013-2018). HIV-1 env sequences were used to predict bnAb resistance using bNAb-ReP, to determine the number of potential N-linked glycosylation sites (PNGS) and evaluate env variable region characteristics (VC). We also assessed the presence of signature mutations that may affect bnAb sensitivity in vitro. We observe varied results for predicted bnAb resistance among our cohort. 3BNC117 showed high predicted resistance (72%) compared to intermediate levels of resistance to VRC01 (57%). We predict low resistance to PGDM100 and 10-1074 and no resistance to 4E10. No difference was observed in the frequency of PNGS by bNAb susceptibility patterns except for higher number of PNGs in V3 bnAb resistant strains. Associations of VC were observed for V1, V4 and V5 loop length and net charge. We also observed few mutations that have been reported to confer bnAb resistance in vitro. Our results support use of sequence data and machine learning tools to predict the best bnAbs to use within populations.

Multilevel modelling of neonatal mortality in Ghana: Does household and community levels matter?

Background: Neonatal mortality accounts for an increasing share of under-five deaths, and they are declining at a slower rate than postnatal deaths. Apparently, neonatal mortality is increasingly becoming a major public health problem in Ghana and the world over. The current study sought to analyze neonatal mortality as a function of predictor variables and to estimate and understand unobserved household and community-level residual effects on neonatal mortality to provide data driven evidence to shape informed policies and interventions aimed at reducing the neonatal mortality burden. Methods: The current study extracted three-level complex data on 5884 children born in the five years preceding the 2014 Ghana Demographic and Health Survey. A two-level and three-level multilevel logistic models were applied to estimate unobserved household and community-level variations in neonatal mortality in the presence of set of predictor variables. Sampling weights were incorporated in both the descriptive and inferential analysis since the data used emanated from a complex survey. Model fit statistics such as AIC scores for a weighted two-level and three-level random intercept logistic models were compared. The model with the lowest AIC score was considered the most preferred model. Results: The household-level random intercept model suggested that the odds of neonatal mortality was higher among multiple births [OR = 3.15 (95% CI: 1.17, 8.50)], babies born to mothers who received prenatal care from non-skilled worker [OR = 5.88 (95% CI: 2.90, 11.91)], babies delivered through caesarian section [OR = 2.47 (95% CI: 1.06, 5.79)], a household with 1-4 members [OR = 10.23 (95% CI: 4.17, 25.50)], a short preceding birth interval (<24 months) [OR = 3.05 (95% CI: 1.18, 7.88)], and preceding birth interval between 24 and 47 months [OR = 2.88 (95% CI: 1.41, 5.91)]. Substantial unobserved household-level residual variations in neonatal mortality were observed. Conclusion: The findings of the current study provide an actionable information to be used by government and other stakeholders in the health sector to renew commitment to reduce neonatal mortality to an acceptable level. There is the need to intensify maternal health education by health providers to encourage pregnant women to visit antenatal clinics at least four times so they could benefit substantially from ANC services.

A qualitative inquiry of experiences of HIV-related stigma and its effects among people living with HIV on treatment in rural Kilifi, Kenya.

Background: The pervasiveness of HIV-related stigma and discrimination, and its consequences on HIV prevention and treatment, have been well documented. However, little is known about the lived experiences of HIV-related stigma and its effects among the general adult population living with HIV in rural African settings. This study set out to explore this knowledge gap. Methods: From April to June 2018, we conducted in-depth interviews with a convenience sample of 40 adults living with HIV aged 18-58 years in Kilifi, Kenya. A semi-structured interview guide was used to explore experiences of HIV-related stigma and its impact on these adults. A framework approach was used to analyze the data using NVIVO 11 software. Results: Participants reported experiences of HIV-related stigma in its various forms (anticipated, perceived, internalised, and enacted), as well as its effects on HIV treatment and social and personal spheres. The internalisation of stigma caused by enacted stigma impacted care-seeking behavior resulting in worse overall health. Anxiety and depression characterized by suicidal ideation were the results of internalised stigma. Anticipated stigma prompted HIV medication concealment, care-seeking in remote healthcare facilities, and care avoidance. Fewer social interactions and marital conflicts resulted from perceived stigma. Overall, HIV-related stigma resulted in partial and non-disclosure of HIV seropositivity and medication non-adherence. At a personal level, mental health issues and diminished sexual or marital prospects (for the unmarried) were reported. Conclusion: Despite high awareness of HIV and AIDS among the general population in Kenya, adults living with HIV in rural Kilifi still experience different forms of HIV-related stigma (including self-stigma) that result in a raft of social, personal, and HIV-treatment-related consequences. Our findings underscore the urgent need to reevaluate and adopt more effective strategies for implementing HIV-related anti-stigma programs at the community level. Addressing individual-level stigma will require the design of targeted interventions. To improve the lives of adults living with HIV in Kilifi, the effects of HIV-related stigma, particularly on HIV treatment, must be addressed.