Proteome-scale characterisation of motif-based interactome rewiring by disease mutations.

Whole genome and exome sequencing are reporting on hundreds of thousands of missense mutations. Taking a pan-disease approach, we explored how mutations in intrinsically disordered regions (IDRs) break or generate protein interactions mediated by short linear motifs. We created a peptide-phage display library tiling ~57,000 peptides from the IDRs of the human proteome overlapping 12,301 single nucleotide variants associated with diverse phenotypes including cancer, metabolic diseases and neurological diseases. By screening 80 human proteins, we identified 366 mutation-modulated interactions, with half of the mutations diminishing binding, and half enhancing binding or creating novel interaction interfaces. The effects of the mutations were confirmed by affinity measurements. In cellular assays, the effects of motif-disruptive mutations were validated, including loss of a nuclear localisation signal in the cell division control protein CDC45 by a mutation associated with Meier-Gorlin syndrome. The study provides insights into how disease-associated mutations may perturb and rewire the motif-based interactome.

Association of symptomatic upper respiratory tract infections with the alteration of the oropharyngeal microbiome in a cohort of school children in Côte d'Ivoire.

Introduction: The oropharyngeal microbiome plays an important role in protection against infectious agents when in balance. Despite use of vaccines and antibiotic therapy to prevent respiratory tract infections, they remain one of the major causes of mortality and morbidity in Low- and middle-income countries. Hence the need to explore other approaches to prevention by identifying microbial biomarkers that could be leveraged to modify the microbiota in order to enhance protection against pathogenic bacteria. The aim of this study was to analyze the oropharyngeal microbiome (OPM) of schoolchildren in Côte d'Ivoire presenting symptoms of upper respiratory tract infections (URTI) for better prevention strategy. Methods: Primary schools' children in Korhogo (n = 37) and Abidjan (n = 39) were followed for six months with monthly oropharyngeal sampling. Clinical diagnostic of URT infection was performed and nucleic acid extracted from oropharyngeal swabs were used for 16S rRNA metagenomic analysis and RT-PCR. Results: The clinical examination of children's throat in Abidjan and Korhogo identified respectively 17 (43.59%) and 15 (40.54%) participants with visible symptoms of URTIs, with 26 episodes of infection in Abidjan and 24 in Korhogo. Carriage of Haemophilus influenzae (12%), Streptococcus pneumoniae (6%) and SARS-CoV-2 (6%) was confirmed by PCR. A significant difference in alpha diversity was found between children colonized by S. pneumoniae and those that were not (p = 0.022). There was also a significant difference in alpha diversity between children colonised with H. influenzae and those who were not (p = 0.017). No significant difference was found for SARS-CoV-2. Sphingomonas, Ralstonia and Rothia were significantly enriched in non-carriers of S. pneumoniae; Actinobacillus was significantly enriched in non-carriers of H. influenzae; Actinobacillus and Porphyromonas were significantly enriched in non-carriers of SARS-CoV-2 (p < 0.001). Discussion: Nearly 40% of children showed clinical symptoms of infection not related to geographical location. The OPM showed an imbalance during H. influenzae and S. pneumoniae carriage. This study provides a baseline understanding of microbiome markers in URTIs in children for future research, to develop targeted interventions aimed at restoring the microbial balance and reducing the symptoms associated with RTIs.

Genomic epidemiology of SARS-CoV-2 in Senegal in 2020-2021.

INTRODUCTION: In Senegal, molecular diagnosis was widely used for the detection and management of COVID-19 patients. However, genomic surveillance was very limited in the public sector. This study aimed to share the experience of a Senegalese public sector laboratory in response to the COVID-19 pandemic, and to describe the distribution of variants circulating in 2020 and 2021. METHODOLOGY: From July 2020 to December 2021, SARS-CoV-2 qRT-PCR was performed on nasopharyngeal samples from travelers and symptomatic patients at the Bacteriology and Virology Laboratory (LBV) of the Aristide le Dantec University Teaching Hospital. Samples with a cycle threshold (Ct) ≤ 30 were selected for whole-genome sequencing (WGS) using the Nanopore technology. In-house scripts were developed to study the spatial and temporal distribution of SARS-CoV-2 variants in Senegal, using our sequences and those retrieved from the GISAID database. RESULTS: Of 8,207 patients or travelers screened for SARS-CoV-2, 970 (11.8%) were positive and 386 had a Ct ≤ 30. WGS was performed on 133 samples. Concomitantly with high-quality sequences deposited in the GISAID database covering nine cities in Senegal in 2020 and 2021 (n = 1,539), we observed a high circulation of the 20A (B.1, B.1.416 and B.1.620) and 20B (B.1.1.420) lineages in 2020, while most of the samples belonged to Delta variants (AY34 and AY.34.1, 22%) in 2021. CONCLUSIONS: Despite its late involvement, COVID-19 diagnosis was routinely performed in LBV, but genomic characterization remained challenging. The genomic diversity of SARS-CoV-2 strains in Senegal reflected that observed worldwide during the first waves of the pandemic.

Gossypiboma migration into the bladder.

Gossypiboma is a dreaded complication following mainly abdomino-pelvic surgeries. The clinical presentation varies widely and is strongly associated with two factors: localization of the textiloma and type of the tissue reaction. Intravesical gossypiboma migration is rare and usually presents as recurrent urinary tract infections. We report a case of gossypiboma migration into the bladder that was treated by endoscopic extraction. The purpose of this report is to remind the importance of the prevention which must be the challenge rather than the treatment modalities.

Nirsevimab and Hospitalization for RSV Bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis, resulting in 3 million hospitalizations each year worldwide. Nirsevimab is a monoclonal antibody against RSV that has an extended half-life. Its postlicensure real-world effectiveness against RSV-associated bronchiolitis is unclear. METHODS: We conducted a prospective, multicenter, matched case-control study to analyze the effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis in infants younger than 12 months of age. Case patients were infants younger than 12 months of age who were hospitalized for RSV-associated bronchiolitis between October 15 and December 10, 2023. Control patients were infants with clinical visits to the same hospitals for conditions unrelated to RSV infection. Case patients were matched to control patients in a 2:1 ratio on the basis of age, date of hospital visit, and study center. We calculated the effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis (primary outcome) by means of a multivariate conditional logistic-regression model with adjustment for confounders. Several sensitivity analyses were performed. RESULTS: The study included 1035 infants, of whom 690 were case patients (median age, 3.1 months; interquartile range, 1.8 to 5.3) and 345 were matched control patients (median age, 3.4 months; interquartile range, 1.6 to 5.6). Overall, 60 case patients (8.7%) and 97 control patients (28.1%) had received nirsevimab previously. The estimated adjusted effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis was 83.0% (95% confidence interval [CI], 73.4 to 89.2). Sensitivity analyses gave results similar to those of the primary analysis. The effectiveness of nirsevimab therapy against RSV-associated bronchiolitis resulting in critical care was 69.6% (95% CI, 42.9 to 83.8) (27 of 193 case patients [14.0%] vs. 47 of 146 matched control patients [32.2%]) and against RSV-associated bronchiolitis resulting in ventilatory support was 67.2% (95% CI, 38.6 to 82.5) (27 of 189 case patients [14.3%] vs. 46 of 151 matched control patients [30.5%]). CONCLUSIONS: In a real-world setting, nirsevimab therapy was effective in reducing the risk of hospitalized RSV-associated bronchiolitis. (Funded by the National Agency for AIDS Research-Emerging Infectious Disease and others; ENVIE ClinicalTrials.gov number, NCT06030505.).

Comparison of the outcomes of first metatarsophalangeal joint arthrodesis by locking plate and compression screw in patients with severe hallux valgus or hallux valgus revision.

INTRODUCTION: Arthrodesis of the first metatarsophalangeal joint (MTP1) is indicated for hallux rigidus, septic arthritis, severe hallux valgus (HV) or HV revision. Few studies have compared the functional and radiographic outcomes between indications. The goal of this study was to compare the results of MTP1 arthrodesis in patients with severe HV or HV revision at 6 months postoperative. The hypothesis was that there are no differences in the fusion rate, functional scores and radiological correction between the two groups. MATERIALS AND METHODS: This was a retrospective, observational, single-center study conducted between January 1, 2018 and July 31, 2021. The inclusion criteria were patients treated for severe HV or HV revision by MTP1 arthrodesis with a compression screw and locking plate who were at least 18 years of age. The exclusion criteria were a history of septic arthritis of MTP1 without prior HV surgery, primary hallux rigidus, rheumatoid arthritis, incomplete medical record. The functional outcomes consisted of the Foot Function Index (FFi-f) and the European Foot and Ankle Society (EFAS) score. Radiographs were made to evaluate preoperative and postoperative deformity, the correction and the fusion rate. These outcomes were compared between two groups: severe HV and HV revision. RESULTS: An analysis was done of 58 cases of MTP1 arthrodesis: 45 severe HV and 13 HV revisions. The mean patient age was 66 years, and the mean follow-up was 15.7 months. There were no significant differences between the two groups in the postoperative functional scores: EFAS (p = 0.85) and FFI-f (p = 0.14). At the final review, there were no significant differences between the two groups in the foot angle measurements (hallux valgus angle, p = 0.08 and intermetatarsal angle, p = 0.15) and fusion rate (p = 0.89) with a 93% fusion rate in patients with severe HV and 92% in patients with HV revision. CONCLUSION: Given the good radiographic and functional outcomes, MTP1 arthrodesis by locking plate and compression screw is indicated as a first line surgical treatment for patients with severe HV or for patients undergoing HV revision. There is no evidence of a significant difference in the functional scores, fusion rate and radiographic correction between these two indications. LEVEL OF PROOF: IV; retrospective case series.

The feasibility, acceptability, appropriateness and impact of implementing person-centered communication for prevention of female genital mutilation in antenatal care settings in Guinea, Kenya and Somalia.

BACKGROUND: There is limited evidence on how to engage health workers as advocates in preventing female genital mutilation (FGM). This study assesses the feasibility, acceptability, appropriateness and impact of a person-centered communication (PCC) approach for FGM prevention among antenatal care (ANC) providers in Guinea, Kenya and Somalia. METHODS: Between August 2020 and September 2021, a cluster randomised trial was conducted in 180 ANC clinics in three countries testing an intervention on PCC for FGM prevention. A process evaluation was embedded, comprising in-depth interviews (IDIs) with 18 ANC providers and 18 ANC clients. A qualitative thematic analysis was conducted, guided by themes identified a priori and/or that emerged from the data. RESULTS: ANC providers and clients agreed that the ANC context was a feasible, acceptable and appropriate entry point for FGM prevention counselling. ANC clients were satisfied with how FGM-related information was communicated by providers and viewed them as trusted and effective communicators. Respondents suggested training reinforcement, targeting other cadres of health workers and applying this approach at different service delivery points in health facilities and in the community to increase sustainability and impact. CONCLUSION: These findings can inform the scale up this FGM prevention approach in high prevalence countries.

Mixed influence of COVID-19 on primary maternal and child health services in sub-Saharan Africa: a scoping review.

Introduction: The COVID-19 pandemic profoundly affected the provision of and demand for routine health services in the world. The objective of this scoping review was to synthesize the influence of the COVID-19 pandemic on primary maternal and child health (MCH) services in sub-Saharan Africa. Methods: The studies searched original studies reporting on the influence of the COVID-19 pandemic on primary MCH services. Four scientific databases (Pubmed, AJOL, CAIRN, CINAHL) and one gray literature database (Google Scholar) were used for this search. We also searched through the snowball citation approach and study reference lists. Results: The influence of the COVID-19 pandemic on primary MCH services has been mixed in sub-Saharan Africa. Attendance at some health centers declined for antenatal care, deliveries, immunization, and pneumonia cases. Other health centers did not experience a significant influence of the pandemic on some of these services. In fact, antenatal care increased in a number of health centers. MCH service indicators which declined during COVID-19 were linked on the demand side to regulatory measures against COVID-19, the perceived unavailability of resources for routine services, the perceived negative attitude of staff in these facilities, the perceived transmission risk in primary health care facilities and the perceived anticipated stigma. On the supply side, factors included the lack of equipment in primary facilities, the lack of guidelines for providing care in the pandemic context, the regulatory measures against COVID-19 taken in these facilities, and the lack of motivation of providers working in these facilities. Conclusion: This study recommends prioritizing the improvement of infection prevention measures in primary health care facilities for resilience of MCH indicators to epidemic crises. Improvement efforts should be tailored to the disparities in preventive measures between health centers. The identification of best practices from more resilient health centers could better guide these efforts.

Prevalence and factors associated with unskilled childbirth attendance in Guinea: Analysis of the 2018 Demographic and Health Survey.

This study aimed to analyze the prevalence and factors associated with the unassisted delivery by qualified health personnel in the Republic of Guinea, based on data from the 2018 demographic and health survey. Multivariate logistic regression was used to identify the associated factors. The prevalence of unassisted delivery was 40.8%; it was 38.4% in rural areas and 2.3% in urban areas. Factors associated with this type of delivery included the performance of no ANC (ORa = 6.19 IC95%: [4.86 - 7.87], p<0.001) and those who had performed one to three ANC (ORa =1.75 IC95%: [1.49 - 2.05], p<0.001) the perception of the distance to the health institution as a problem (ORa =1.28 IC95%: [1.10 - 1.48], p<0.001), belonging to the poor wealth index (ORa = 2.77 IC 95%: [2.19 - 3.50], p<0.001) and average (ORa = 2.01 IC95%: [1.57 - 2.57], p<0.001), the fact of residing in the region of Faranah (ORa = 2.24 IC95%: [1.37 - 3.65], p<0.001) and rural areas (ORa = 4.15 IC95%: [3.10 - 5.56], p<0.001). Strengthening community awareness, making functional ambulances available to rural health centers and making prenatal care inputs available in health institutions would help to reduce the scale of unassisted deliveries in the Republic of Guinea.

Cette étude visait à analyser la prévalence et les facteurs associés à l'accouchement non assisté par un personnel de santé qualifié en Guinée, partant des données de l'enquête démographique et de santé de 2018. La régression logistique multivariée a servi à identifier les facteurs associés. La fréquence de l'accouchement non assisté était de 40.8% ; elle était de 38.4% en milieu rural et 2.3% en milieu urbain. Les facteurs associés à ce type d'accouchement comprenaient la réalisation d'aucune CPN (ORa =6.19 IC95% : [4.86 - 7.87], p<0.001) et celles qui avaient réalisées une à trois CPN (ORa =1.75 IC95% : [1.49 - 2.05], p<0.001) la perception de la distance pour la structure de santé comme un problème (ORa =1.28 IC95% : [1.10 - 1.48], p<0.001), l'appartenance à l'indice de richesse pauvre (ORa =2.77 IC95% : [2.19 - 3.50], p<0.001) et moyenne (ORa =2.01 IC 95% : [1.57 - 2.57], p<0.001), le fait de résider dans la région de Faranah (ORa =2.24 IC95% : [1.37 - 3.65], p<0.001) et rurale (ORa =4,15 IC 95% : [3,10 - 5,56], p<0,001). Le renforcement de la sensibilisation communautaire, la mise d'ambulances fonctionnelles à la disposition des centres de santé ruraux et rendre disponible les intrants de soins prénatals dans les structures sanitaires contribueraient serte à réduire l'ampleur des accouchements non assistés en Guinée.

Genomic Reference Resource for African Cattle: Genome Sequences and High-Density Array Variants.

The diversity in genome resources is fundamental to designing genomic strategies for local breed improvement and utilisation. These resources also support gene discovery and enhance our understanding of the mechanisms of resilience with applications beyond local breeds. Here, we report the genome sequences of 555 cattle (208 of which comprise new data) and high-density (HD) array genotyping of 1,082 samples (537 new samples) from indigenous African cattle populations. The new sequences have an average genome coverage of ~30X, three times higher than the average (~10X) of the over 300 sequences already in the public domain. Following variant quality checks, we identified approximately 32.3 million sequence variants and 661,943 HD autosomal variants mapped to the Bos taurus reference genome (ARS-UCD1.2). The new datasets were generated as part of the Centre for Tropical Livestock Genetics and Health (CTLGH) Genomic Reference Resource for African Cattle (GRRFAC) initiative, which aspires to facilitate the generation of this livestock resource and hopes for its utilisation for complete indigenous breed characterisation and sustainable global livestock improvement.

Mucocutaneous Manifestations in Patients with Dengue Fever: From the EPIDENGUE Cohort on Reunion Island.

Nearly 4 billion people live in a dengue risk area worldwide. The prevalence of dengue-related mucocutaneous manifestations and their association with severe dengue differ across studies. The aim of the study was to describe the characteristics of patients with dengue-related mucocutaneous manifestations and to investigate those were associated with severe dengue. A retrospective study was conducted in 2019 among patients with a positive RT-PCR for dengue at the University Hospital of Reunion, which has been experiencing a re-emergence of dengue since 2018. Of 847 patients with confirmed dengue, 283 (33.4%) developed mucocutaneous manifestations. Only manifestations of dehydration such as glossitis, dysgeusia, or conjunctivitis were associated with severe dengue, unlike pruritus and rash, in bivariate analysis but not in multivariate analysis. The rash and pruritus of dengue appear to be accompanied by a pronounced flu-like syndrome in younger people without comorbidity or severity, although careful examination of mucous membranes would better identify signs of dehydration and thus cases likely to worsen.

Morbidity and Mortality Associated with COVID-19 and Acute Chest Syndrome in Sickle Cell Disease Patients.

SUMMARYCOVID-19 infection has emerged as a comorbidity that can significantly increase morbidity and mortality in sickle cell patients with ACS (acute thoracic/chest syndrome). The aim of our study was to assess COVID-19-related morbidity and mortality in sickle cell patients with ACS. This was a retrospective, descriptive study of patient records followed over a 36-month period from January 2020 to December 2022. The study was conducted at the national blood transfusion center in Dakar. The sex ratio (M/F) was 0.82. The median age was 26 (17-39) years. The most represented age group was between 21 and 30 years. Factors associated with death were: at baseline, SS genotype, presence of comorbidities (asthma, chronic obstructive pulmonary disease, viral hepatitis B, ischemic heart disease), osteonecrosis of the femoral head, and use of NSAIDs (non-steroidal anti-inflammatory drugs) at diagnosis of COVID-19; at the diagnosis of ACS associated with COVID-19, respiratory distress, hypoxia (Sa02 < 92%), creatininemia >18.5 mg/l, CRP >192 mg/l, lymphopenia; the therapeutic modalities associated with death were: transfusion of RBCs (packed red blood cells) and curative anticoagulation. This study shows that patients with comorbidities and/or chronic complications of sickle cell disease can develop severe forms of ACS associated with COVID 19, leading to death. Other factors linked to death, notably diagnostic and therapeutic, were also identified in the course of this study.

A cyclic lipopeptide from Fusarium graminearum targets plant membranes to promote virulence.

Microbial plant pathogens deploy amphipathic cyclic lipopeptides to reduce surface tension in their environment. While plants can detect these molecules to activate cellular stress responses, the role of these lipopeptides or associated host responses in pathogenesis are not fully clear. The gramillin cyclic lipopeptide is produced by the Fusarium graminearum fungus and is a virulence factor and toxin in maize. Here, we show that gramillin promotes virulence and necrosis in both monocots and dicots by disrupting ion balance across membranes. Gramillin is a cation-conducting ionophore and causes plasma membrane depolarization. This disruption triggers cellular signaling, including a burst of reactive oxygen species (ROS), transcriptional reprogramming, and callose production. Gramillin-induced ROS depends on expression of host ILK1 and RBOHD genes, which promote fungal induction of virulence genes during infection and host susceptibility. We conclude that gramillin's ionophore activity targets plant membranes to coordinate attack by the F. graminearum fungus.

Protective role of macrophages from maternal-fetal interface in unvaccinated coronavirus disease 2019 pregnant women.

Pregnant women represent a high-risk population for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. The presence of SARS-CoV-2 has been reported in placenta from infected pregnant women, but whether the virus influences placenta immune response remains unclear. We investigated the properties of maternal-fetal interface macrophages (MFMs) in a cohort of unvaccinated women who contracted coronavirus disease 2019 (COVID-19) during their pregnancy. We reported an infiltration of CD163+ macrophages in placenta from COVID-19 women 19 whereas lymphoid compartment was not affected. Isolated MFMs exhibited nonpolarized activated signature (NOS2, IDO1, IFNG, TNF, TGFB) mainly in women infected during the second trimester of pregnancy. COVID-19 during pregnancy primed MFM to produce type I and III interferon response to SARS-CoV-2 (Wuhan and δ strains), that were unable to elicit this in MFMs from healthy pregnant women. COVID-19 also primed SARS-CoV-2 internalization by MFM in an angiotensin-converting enzyme 2-dependent manner. Activation and recall responses of MFMs were influenced by fetal sex. Collectively, these findings support a role for MFMs in the local immune response to SARS-CoV-2 infection, provide a basis for protective placental immunity in COVID-19, and highlight the interest of vaccination in pregnant women.

Two decades of molecular surveillance in Senegal reveal rapid changes in known drug resistance mutations over time.

BACKGROUND: Drug resistance in Plasmodium falciparum is a major threat to malaria control efforts. Pathogen genomic surveillance could be invaluable for monitoring current and emerging parasite drug resistance. METHODS: Data from two decades (2000-2020) of continuous molecular surveillance of P. falciparum parasites from Senegal were retrospectively examined to assess historical changes in malaria drug resistance mutations. Several known drug resistance markers and their surrounding haplotypes were profiled using a combination of single nucleotide polymorphism (SNP) molecular surveillance and whole genome sequence based population genomics. RESULTS: This dataset was used to track temporal changes in drug resistance markers whose timing correspond to historically significant events such as the withdrawal of chloroquine (CQ) and the introduction of sulfadoxine-pyrimethamine (SP) in 2003. Changes in the mutation frequency at Pfcrt K76T and Pfdhps A437G coinciding with the 2014 introduction of seasonal malaria chemoprevention (SMC) in Senegal were observed. In 2014, the frequency of Pfcrt K76T increased while the frequency of Pfdhps A437G declined. Haplotype-based analyses of Pfcrt K76T showed that this rapid increase was due to a recent selective sweep that started after 2014. DISCUSSION (CONCLUSION): The rapid increase in Pfcrt K76T is troubling and could be a sign of emerging amodiaquine (AQ) resistance in Senegal. Emerging AQ resistance may threaten the future clinical efficacy of artesunate-amodiaquine (ASAQ) and AQ-dependent SMC chemoprevention. These results highlight the potential of molecular surveillance for detecting rapid changes in parasite populations and stress the need to monitor the effectiveness of AQ as a partner drug for artemisinin-based combination therapy (ACT) and for chemoprevention.

Cluster randomised trial of a health system strengthening approach applying person-centred communication for the prevention of female genital mutilation in Guinea, Kenya and Somalia.

INTRODUCTION: There is limited evidence on effective health systems interventions for preventing female genital mutilation (FGM). This study tested a two-level intervention package at primary care applying person-centred communication (PCC) for FGM prevention. METHODS: A cluster randomised trial was conducted in 2020-2021 in 180 antenatal care (ANC) clinics in Guinea, Kenya and Somalia. At baseline, all clinics received guidance and materials on FGM prevention and care; at month 3, ANC providers at intervention sites received PCC training. Data were collected from clinic managers, ANC providers and clients at baseline, month 3 and month 6 on primary outcomes, including delivery of PCC counselling, utilisation of level one materials, health facility preparedness for FGM prevention and care services and secondary outcomes related to clients' and providers' knowledge and attitudes. Data were analysed using multilevel and single-level logistic regression models. RESULTS: Providers in the intervention arm were more likely to deliver PCC for FGM prevention compared with those in the control arm, including inquiring about clients' FGM status (adjusted OR (AOR): 8.9, 95% CI: 6.9 to 11.5; p<0.001) and FGM-related beliefs (AOR: 9.7, 95% CI: 7.5 to 12.5; p<0.001) and discussing why (AOR: 9.2, 95% CI: 7.1 to 11.9; p<0.001) or how (AOR: 7.7, 95% CI: 6.0 to 9.9; p<0.001) FGM should be prevented. They were more confident in their FGM-related knowledge (AOR: 7.0, 95% CI: 1.5 to 32.3; p=0.012) and communication skills (AOR: 1.8; 95% CI: 1.0 to 3.2; p=0.035). Intervention clients were less supportive of FGM (AOR: 5.4, 95% CI: 2.4 to 12.4; p<0.001) and had lower intentions of having their daughters undergo FGM (AOR: 0.3, 95% CI: 0.1 to 0.7; p=0.004) or seeking medicalised FGM (AOR: 0.2, 95% CI: 0.1 to 0.5; p<0.001) compared with those in the control arm. CONCLUSION: This is the first study to provide evidence of an effective FGM prevention intervention that can be delivered in primary care settings in high-prevalence countries. TRIAL REGISTRATION AND DATE: PACTR201906696419769 (3 June 2019).

Relationship Between LDL-Cholesterol, Small and Dense LDL Particles, and mRNA Expression in a Cohort of African Americans.

Understanding the characteristics and behavior of LDL particles provides insights into the atherogenic risk of high levels of LDL cholesterol (LDL-C) in hypercholesterolemia. Studying LDL particles helps identify specific LDL subtypes (e.g., small and dense LDL particles, sdLDL) that may be atherogenic and, consequently, potential targets for therapeutics. This study cohort consists of African Americans (AAs), a population disproportionately affected by hypercholesterolemia, thereby accentuating the importance of the investigation.Differential expression (DE) analysis was undertaken utilizing a dataset comprising 17,947 protein-coding mRNAs from the whole-blood transcriptomes of 416 samples to identify mRNAs associated with LDL-C and sdLDL. Subsequently, mediation analyses were used to investigate the mediating role of sdLDL particles on the relationship between LDL-C and mRNA expression. Finally, pathway enrichment analysis was conducted to identify pathways involving mRNAs whose relationship with LDL-C is mediated by sdLDL.DE analysis revealed 1048 and 284 mRNA transcripts differentially expressed by LDL-C and sdLDL, respectively. Mediation analysis revealed that the associations between LDL-C and 33 mRNAs were mediated by sdLDL. Pathway analysis showed the 33 mRNAs are involved in pathways associated with immune system, inflammatory response, metabolism, and cardiovascular disease (CVD) risk.Our study provides valuable insights into the complex interplay between LDL-C, sdLDL and mRNA expression in a large sample of AAs. The results underscore the importance of incorporating sdLDL measurement alongside LDL-C levels to improve the accuracy of managing hypercholesterolemia and effectively stratify the risk of CVD. This is essential as differences in sdLDL modulate atherogenic properties at the transcriptome level.

Effect of Adding a Six-Week Course of Doxycycline to Intensive Hygiene-Based Care for Improving Lymphedema in a Rural Setting of Mali: A Double-Blind, Randomized Controlled 24-Month Trial.

Lymphedema (LE) is one the most disfiguring chronic manifestations of lymphatic filariasis. Its management relies primarily on limb hygiene and local care. A previous study in Ghana demonstrating a beneficial effect of doxycycline on LE led to the current multicenter trial on the efficacy of doxycycline in filarial LE. A randomized placebo-controlled trial was initiated in two rural health districts in Mali. Patients with LE stages 1-3 were randomized to receive either doxycycline (200 mg/day) or placebo over a 6-week monitored treatment period and were then followed every 6 months for 2 years. Both groups received materials for limb hygiene that was carried out daily for the entire 2-year study. The primary endpoint was lack of progression in LE stage at 24 months. One hundred patients were enrolled in each study arm. The baseline sociodemographic characteristics of each group were largely similar. There was no significant difference at month 24 after treatment initiation in the number of subjects showing progression in LE stage between the two treatment arms (P = 0.5921). Importantly, however, the number of attacks of acute adenolymphangitis (ADLA) was reduced in both arms, but there was no significant difference between the two groups at any follow-up time point (all P >0.23). Doxycycline was well tolerated in those receiving the drug. When added to daily self-administered limb hygiene, a 6-week course of doxycycline (200 mg) was not superior to placebo in increasing the improvement associated with hygiene alone in LE volume, stage, or frequency of ADLA attacks over a 24-month period.

Healthcare workers' knowledge, attitude and practices on infection prevention and control in the context of the COVID-19 pandemic at the Faranah regional hospital and associated healthcare centers, Guinea.

BACKGROUND: In response to the COVID-19 pandemic, WHO launched a strategic preparedness and response plan, outlining public health measures to support countries worldwide. Healthcare workers have an increased risk of becoming infected and their behaviour regarding infection prevention and control (IPC) influences infection dynamics. IPC strategies are important across the globe, but even more in low-resource settings where capacities for testing and treatment are limited. Our study aimed to assess and implement COVID-19 pandemic preparedness and response measures in Faranah, Guinea, primarily focusing on healthcare workers' IPC knowledge, attitude and practice (KAP). METHODS: The study was conducted between April 2020 and April 2021 assessing IPC pandemic preparedness and response measures such as healthcare workers' KAP, alcohol-based handrub (ABHR) consumption and COVID-19 triaging in the Faranah Regional Hospital and two associated healthcare centres. The assessment was accompanied by IPC training and visual workplace reminders and done in pre- and post- phases to evaluate possible impact of these IPC activities. RESULTS: The overall knowledge score in the Faranah Regional Hospital was 32.0 out of 44 at baseline, and did not change in the first, but increased significantly by 3.0 points in the second follow-up. The healthcare workers felt closer proximity to SARS-CoV-2 overtime in addition to higher stress levels in all study sites. There was significant improvement across the observed triaging practices. Hand hygiene compliance showed a significant increase across study sites leading to 80% in Faranah Regional Hospital and 63% in healthcare centers. The average consumption of ABHR per consultation was 3.29 mL with a peak in February 2020 of 23 mL. CONCLUSION: Despite increased stress levels among HCWs, the ongoing IPC partnership well prepared the FRH in terms of triaging processes with a stronger impact on IPC practice than on theoretical knowledge. Throughout the pandemic, global shortages and surges in consumption did not affect the continuous ABHR provision of the FRH. This highlights local ABHR production as a key pandemic preparedness strategy.