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.

Disruption of the Expression of the Placental Clock and Melatonin Genes in Preeclampsia.

Circadian rhythms have been described in numerous tissues of living organisms and are necessary for homeostasis. The understanding of their role in normal and pathological pregnancy is only just emerging. It has been established that clock genes are expressed in the placenta of animals and humans, but the rhythmicity of placenta immune cells is not known. Macrophages from healthy placenta of women at term were isolated and the expression of clock genes BMAL1, CLOCK, PER2, CRY2, and NR1D1 was assessed by qRT-PCR every 4 h over 24 h. Raw data were treated with cosinor analysis to evaluate the significance of the oscillations. Placental macrophages exhibited significant circadian expression of clock genes but one third of placental macrophages lost clock gene rhythmicity; the clock gene oscillations were restored by co-culture with trophoblasts. We wondered if melatonin, a key hormone regulating circadian rhythm, was involved in the oscillations of placental cells. We showed that macrophages and trophoblasts produced melatonin and expressed MT2 receptor. In women who developed preeclampsia during pregnancy, circadian oscillations of placental macrophages were lost and could not be rescued by coculture with trophoblasts from healthy women. Moreover, production and oscillations of melatonin were altered in preeclamptic macrophages. For the first time to our knowledge, this study shows circadian rhythms and melatonin production by placental macrophages. It also shows that preeclampsia is associated with a disruption of the circadian rhythm of placental cells. These results represent a new scientific breakthrough that may contribute to the prevention and treatment of obstetrical pathologies.

The direct cost of dialysis supported by families for patients with chronic renal failure in Ouagadougou (Burkina Faso).

BACKGROUND: Chronic renal failure can lead to dialysis and/or a kidney transplant in the final stage. The number of patients under dialysis has increased considerably in the world and particularly in sub-Saharan Africa. Dialysis is a very expensive care. This is the reason why this study on the costs of dialysis management was initiated in Burkina Faso. The objective of the study is to determine the direct medical and non-medical costs of managing chronic renal failure among dialysis patients in Ouagadougou in 2020. METHODS: An analytical cross-sectional study was conducted. Data were collected in the hemodialysis department of three public university hospitals in Ouagadougou, Burkina Faso. All dialysis patients with chronic renal failure were included in the study. Linear regression was used to investigate the determinants of the direct medical and non-medical cost of hemodialysis. RESULTS: A total of 290 patients participated in this study, including children, adults, and the elderly with extremes of 12 and 82 years. Almost half of the patients (47.5%) had no income. The average monthly total direct cost across all patients was 75842 CFA or US$134.41.The average direct medical cost was 51315 CFA or US$90.94 and the average direct non-medical cost was 24 527 CFA or US$43.47. Most of the patients (45.2%) funded their hemodialysis by their own source. The multivariate analysis showed that the presence of an accompanying person during treatment, residing in a rural area, ambulatory care, use of personal cars, and treatment at the dialysis center of Yalgado Teaching Hospital were associated with higher direct costs. CONCLUSION: The average cost of dialysis services borne by the patient and his family is very high in Burkina Faso, since it is 2.1 times higher than the country's minimum interprofessional wage (34664 CFA or US$61.4). It appears that the precariousness of the means of subsistence increases strongly with the onset of chronic renal failure requiring dialysis. Thus, to alleviate the expenses borne by dialysis patients, it would be important to extend the government subsidy scheme to the cost of drugs and to promote health insurance to ensure equitable care for these patients.

Involving the health sector in the prevention and care of female genital mutilation: results from formative research in Guinea.

BACKGROUND: Despite efforts to reduce the burden of female genital mutilation (FGM) in Guinea, the practice remains prevalent, and health care providers are increasingly being implicated in its medicalization. This formative study was conducted to understand the factors that facilitate or impede the health sector in providing FGM prevention and care services to inform the development of health sector-based interventions. METHODS: Between April and May 2018, a mixed methods formative study was carried out using a rapid assessment methodology in three regions of Guinea-Faranah, Labe and Conakry. A structured questionnaire was completed by one hundred and fifty health care providers of different cadres and 37 semi-structured interviews were conducted with health care providers, women seeking services at public health clinics and key stakeholders, including health systems managers, heads of professional associations and schools of nursing, midwifery, and medicine as well as representatives of the Ministry of Health. Eleven focus group discussions were conducted with female and male community members. RESULTS: This study revealed health systems factors, attitudinal factors held by health care providers, and other factors, that may not only promote FGM medicalization but also impede a comprehensive health sector response. Our findings confirm that there is currently no standardized pre-service training on how to assess, document and manage complications of FGM nor are there interventions to promote the prevention of the practice within the health sector. This research also demonstrates the deeply held beliefs of health care providers and community members that perpetuate this practice, and which need to be addressed as part of a health sector approach to FGM prevention. CONCLUSION: As integral members of FGM practicing communities, health care providers understand community beliefs and norms, making them potential change agents. The health sector can support them by incorporating FGM content into their clinical training, ensuring accountability to legal and policy standards, and promoting FGM abandonment as part of a multi-sectoral approach. The findings from this formative research have informed the development of a health sector intervention that is being field tested as part of a multi-country implementation research study in Guinea, Kenya, and Somalia.

Despite the implementation of various interventions to prevent female genital mutilation (FGM), it is still widely practiced in Guinea, and health care providers are increasingly being implicated in the practice. We conducted research in three regions of Guinea, namely, Faranah, Labe and Conakry, to understand factors that might be addressed to strengthen the role of the health sector in prevention and care of women and girls who have undergone FGM. Our findings highlight the need to strengthen the capacity of health care providers to be able to identify cases of FGM and manage complications. The study also highlights the importance of engaging health care providers in efforts to prevent FGM, which will require that any trainings include an opportunity to discuss their own values and beliefs around FGM so that they are better equipped to communicate with their clients and patients in a sensitive and non-judgmental manner, whether during consultation visits or community health outreach activities. The results of this research have informed the development of a health system strengthening intervention package for the prevention and care of FGM, which is being tested in Kenya, Somalia, and Guinea.

RadA, a Key Gene of the Circadian Rhythm of Escherichia coli.

Circadian rhythms are present in almost all living organisms, and their activity relies on molecular clocks. In prokaryotes, a functional molecular clock has been defined only in cyanobacteria. Here, we investigated the presence of circadian rhythms in non-cyanobacterial prokaryotes. The bioinformatic approach was used to identify a homologue of KaiC (circadian gene in cyanobacteria) in Escherichia coli. Then, strains of E. coli (wild type and mutants) were grown on blood agar, and sampling was made every 3 h for 24 h at constant conditions. Gene expression was determined by qRT-PCR, and the rhythmicity was analyzed using the Cosinor model. We identified RadA as a KaiC homologue in E. coli. Expression of radA showed a circadian rhythm persisting at least 3 days, with a peak in the morning. The circadian expression of other E. coli genes was also observed. Gene circadian oscillations were lost in radA mutants of E. coli. This study provides evidence of molecular clock gene expression in E. coli with a circadian rhythm. Such a finding paves the way for new perspectives in antibacterial treatment.

Stakeholders' perceptions on improving women's health after obstetric fistula repair: results from a qualitative study in Guinea.

The holistic care of obstetric fistula remains a significant public health concern in developing countries. Improving women's outcomes after repair requires perspectives on post-surgical period within which women have to fulfil their social roles and expectations, mainly becoming pregnant, cooking, resuming farming activities or sexual intercourse. Our objective was to explore stakeholders' perceptions of women's health and well-being after fistula repair, and their perspectives on strategies for improving their quality of life in Guinea. A qualitative study involving representatives from the Ministry of Health, regional, district and hospital managers, representatives of NGOs and funding bodies, local leaders, women who underwent fistula surgery and their relatives (husbands, family members), health providers and community health workers at different levels was conducted. Thematic analysis was performed using NVivo software. Overall, 41 in-depth interviews and seven focus group discussions were conducted with 83 various stakeholders. Unanimously, respondents perceived women treated for obstetric fistula are "diminished" and "vulnerable". This "vulnerability" encompasses physical, socio-emotional and economic dimensions. The high risk of maternal and neonatal complications such as fistula recurrence, abortion or stillbirth in these women was mentioned. Stakeholders emphasized the need for a multidisciplinary approach to improve women's health after repair. Social support, economic empowerment and medical follow-up were identified as key components to mitigate women's vulnerability for successful post-repair reintegration. The programmatic level in Guinea should consider women's health after fistula repair a vital component of the holistic fistula care.

Monocytes and Macrophages, Targets of Severe Acute Respiratory Syndrome Coronavirus 2: The Clue for Coronavirus Disease 2019 Immunoparalysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) clinical expression is pleiomorphic, severity is related to age and comorbidities such as diabetes and hypertension, and pathophysiology involves aberrant immune activation and lymphopenia. We wondered if the myeloid compartment was affected during COVID-19 and if monocytes and macrophages could be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Monocytes and monocyte-derived macrophages (MDMs) from COVID-19 patients and controls were infected with SARS-CoV-2 and extensively investigated with immunofluorescence, viral RNA extraction and quantification, and total RNA extraction followed by reverse-transcription quantitative polymerase chain reaction using specific primers, supernatant cytokines (interleukins 6, 10, and 1ß; interferon-ß; transforming growth factor-ß1, and tumor necrosis factor-α), and flow cytometry. The effect of M1- vs M2-type or no polarization prior to infection was assessed. RESULTS: SARS-CoV-2 efficiently infected monocytes and MDMs, but their infection is abortive. Infection was associated with immunoregulatory cytokines secretion and the induction of a macrophagic specific transcriptional program characterized by the upregulation of M2-type molecules. In vitro polarization did not account for permissivity to SARS-CoV-2, since M1- and M2-type MDMs were similarly infected. In COVID-19 patients, monocytes exhibited lower counts affecting all subsets, decreased expression of HLA-DR, and increased expression of CD163, irrespective of severity. CONCLUSIONS: SARS-CoV-2 drives monocytes and macrophages to induce host immunoparalysis for the benefit of COVID-19 progression.SARS-CoV-2 infection of macrophages induces a specific M2 transcriptional program. In Covid-19 patients, monocyte subsets were decreased associated with up-expression of the immunoregulatory molecule CD163 suggesting that SARS-CoV-2 drives immune system for the benefit of Covid-19 disease progression.

Daytime variation in SARS-CoV-2 infection and cytokine production.

S. Ray and A. Reddy recently anticipated the implication of circadian rhythm in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of the coronavirus disease (Covid-19). In addition to its key role in the regulation of biological functions, the circadian rhythm has been suggested as a regulator of viral infections. Specifically, the time of day of infection was found critical for illness progression, as has been reported for influenza, respiratory syncytial and parainfluenza type 3 viruses. We analyzed circadian rhythm implication in SARS-CoV-2 virus infection of isolated human monocytes, key actor cells in Covid-19 disease, from healthy subjects. The circadian gene expression of BMAL1 and CLOCK genes was investigated with q-RTPCR. Monocytes were infected with SARS-CoV-2 virus strain and viral infection was investigated by One-Step qRT-PCR and immunofluorescence. Interleukin (IL)-6, IL-1ß and IL-10 levels were also measured in supernatants of infected monocytes. Using Cosinor analysis, we showed that BMAL1 and CLOCK transcripts exhibited circadian rhythm in monocytes with an acrophase and a bathyphase at Circadian Time (CT)6 and CT17. After 48 h, the amount of SARS-CoV-2 virus increased in the monocyte infected at CT6 compared to CT17. The high virus amount at CT6 was associated with significant increased release in IL-6, IL-1ß and IL-10 compared to CT17. Our results suggest that time day of SARS-CoV-2 infection affects viral infection and host immune response. They support consideration of circadian rhythm in SARS-CoV-2 disease progression and we propose circadian rhythm as a novel target for managing viral progression.

Effectiveness of the World Health Organization Safe Childbirth Checklist (WHO-SCC) in preventing poor childbirth outcomes: a study protocol for a matched-pair cluster randomized control trial.

BACKGROUND: Women delivering in health facilities in sub-Saharan Africa and their newborns do not always receive proven interventions needed to prevent and/or adequately manage severe complications. The gaps in quality of care are increasingly pointed out as major contributing factor to the high and slow declining perinatal mortality rates. The World Health Organization Safe Childbirth Checklist (WHO-SCC), as a quality improvement strategy, targets low cost and easy to perform interventions and suits well with the context of limited resource settings. In this matched-pair cluster randomized controlled trial, we assess the effectiveness of the WHO-SCC in improving healthcare providers' adherence to best practices and ultimately improving childbirth outcomes. METHODS: This is a multi-country study. In each country we will carry out a matched-pair cluster randomized controlled trial whereby four pairs of regional hospitals will be randomized on a 1:1 basis to either the intervention or control group. A context specific WHO-SCC will be implemented in the intervention facilities along with trainings of healthcare providers on best childbirth practices and ongoing supportive supervisions. The standard of care will prevail in the control group. The primary outcome is a summary composite metric that combine the following poor childbirth outcomes: stillbirths, maternal deaths, early neonatal deaths, severe postpartum hemorrhage, maternal infections, early neonatal infections, prolonged obstructed labor, severe pre-eclampsia, uterine rupture in the health facility, eclampsia and maternal near miss. The occurrence of these outcomes will be ascertained in a sample of 2530 childbirth events in each country using data extraction. A secondary outcome of interest is the adherence of healthcare providers to evidence best practices. This will be measured through direct observations of a sample of 620 childbirth events in each country. DISCUSSION: Our study has the potential to provide strong evidence on the effectiveness of the WHO-SCC, a low cost and easy to implement intervention that can be easily scaled up if found effective. TRIAL REGISTRATION: The trial was registered in the Pan-African Clinical Trials Registry on 21st January 2020 under the following number: PACTR202001484669907. https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=9662.

Learning Ordinal Embedding from Sets.

Ordinal embedding is the task of computing a meaningful multidimensional representation of objects, for which only qualitative constraints on their distance functions are known. In particular, we consider comparisons of the form "Which object from the pair (j,k) is more similar to object i?". In this paper, we generalize this framework to the case where the ordinal constraints are not given at the level of individual points, but at the level of sets, and propose a distributional triplet embedding approach in a scalable learning framework. We show that the query complexity of our approach is on par with the single-item approach. Without having access to features of the items to be embedded, we show the applicability of our model on toy datasets for the task of reconstruction and demonstrate the validity of the obtained embeddings in experiments on synthetic and real-world datasets.

A Granulocytic Signature Identifies COVID-19 and Its Severity.

BACKGROUND: An unbiased approach to SARS-CoV-2-induced immune dysregulation has not been undertaken so far. We aimed to identify previously unreported immune markers able to discriminate COVID-19 patients from healthy controls and to predict mild and severe disease. METHODS: An observational, prospective, multicentric study was conducted in patients with confirmed mild/moderate (n = 7) and severe (n = 19) COVID-19. Immunophenotyping of whole-blood leukocytes was performed in patients upon hospital ward or intensive care unit admission and in healthy controls (n = 25). Clinically relevant associations were identified through unsupervised analysis. RESULTS: Granulocytic (neutrophil, eosinophil, and basophil) markers were enriched during COVID-19 and discriminated between patients with mild and severe disease. Increased counts of CD15+CD16+ neutrophils, decreased granulocytic expression of integrin CD11b, and Th2-related CRTH2 downregulation in eosinophils and basophils established a COVID-19 signature. Severity was associated with emergence of PD-L1 checkpoint expression in basophils and eosinophils. This granulocytic signature was accompanied by monocyte and lymphocyte immunoparalysis. Correlation with validated clinical scores supported pathophysiological relevance. CONCLUSIONS: Phenotypic markers of circulating granulocytes are strong discriminators between infected and uninfected individuals as well as between severity stages. COVID-19 alters the frequency and functional phenotypes of granulocyte subsets with emergence of CRTH2 as a disease biomarker.

Accuracy of syndromic management in targeting vaginal and cervical infections among symptomatic women of reproductive age attending primary care clinics in Dakar, Senegal.

OBJECTIVE: To assess the effectiveness of the WHO syndromic algorithm in the management of vaginal discharge among women of reproductive age in Dakar. METHODS: Cross-sectional study of consecutive female patients (aged 18-49 years) presenting with vaginal symptoms at six selected study sites in Dakar; of these, 276 patients were included in the analysis. Vaginal and cervical swab samples were collected and analysed to establish an aetiological diagnosis of any infection. Syndrome-based diagnosis was compared with the laboratory results to evaluate its accuracy based on sensitivity, specificity and positive and negative predictive values. The degree of agreement between the two approaches was assessed using the Cohen's kappa concordance analysis. RESULTS: Overall prevalence of vaginal infections was 56.9% (157/276); 5.4% (15/276) of the patients had cervical infection. Using the syndromic approach, 51% of patients were correctly managed for Trichomonas vaginalis (TV)/Gardnerella vaginalis (GV); 61% for Candida albicans (CA) and 54% for Chlamydia trachomatis (CT)/Neisseria gonorrhoea (NG) infections. Consequently, 31% of patients with TV/GV, 51% with CA and 53% with CT/NG infections would have missed treatment. Further, the kappa value was <0.20, indicating that there was no agreement or only slight agreement between the syndromic approach and laboratory-based diagnosis. CONCLUSION: This study highlights the limitations of the applicability of the WHO syndromic approach in settings with low prevalence of sexually transmitted infections (STIs) and calls for affordable and accurate rapid tests for STIs.

Emergence and clonal transmission of multi-drug-resistant tuberculosis among patients in Chad.

BACKGROUND: Emergence of Multidrug-resistant (MDR) strains constitutes a significant public health problem worldwide. Prevalence of MDR tuberculosis from Chad is unavailable to date. METHODS: We collected samples from consecutive TB patients nationwide in the seven major cities of Chad between 2007 and 2012 to characterize drug resistance and the population structure of circulating Mycobacterium tuberculosis complex (MTBC) strains. We tested drug sensitivity using Line Probe Assays and phenotypic drug susceptibility testing (DST) were used for second line drugs. We genotyped the isolates using spoligotype analysis and MIRU-VNTR. RESULTS: A total of 311 cultures were isolated from 593 patients. The MDR prevalence was 0.9% among new patients and 3.5% among retreatment patients, and no second line drug resistance was identified. The distribution of genotypes suggests a dissemination of MDR strains in the Southern city of Moundou, bordering Cameroon and Central African Republic. CONCLUSION: Emerging MDR isolates pose a public health threat to Southern Chad, with risk to neighboring countries. This study informs public health practitioners, justifying the implementation of continuous surveillance with DST for all retreatment cases as well as contacts of MDR patients, in parallel with provision of adequate 2nd line regimens in the region.

The emerging threat of pre-extensively drug-resistant tuberculosis in West Africa: preparing for large-scale tuberculosis research and drug resistance surveillance.

BACKGROUND: Drug-resistant tuberculosis (TB) is a global public health problem. Adequate management requires baseline drug-resistance prevalence data. In West Africa, due to a poor laboratory infrastructure and inadequate capacity, such data are scarce. Therefore, the true extent of drug-resistant TB was hitherto undetermined. In 2008, a new research network, the West African Network of Excellence for Tuberculosis, AIDS and Malaria (WANETAM), was founded, comprising nine study sites from eight West African countries (Burkina Faso, The Gambia, Ghana, Guinea-Bissau, Mali, Nigeria, Senegal and Togo). The goal was to establish Good Clinical Laboratory Practice (GCLP) principles and build capacity in standardised smear microscopy and mycobacterial culture across partnering laboratories to generate the first comprehensive West African drug-resistance data. METHODS: Following GCLP and laboratory training sessions, TB isolates were collected at sentinel referral sites between 2009-2013 and tested for first- and second-line drug resistance. RESULTS: From the analysis of 974 isolates, an unexpectedly high prevalence of multi-drug-resistant (MDR) strains was found in new (6 %) and retreatment patients (35 %) across all sentinel sites, with the highest prevalence amongst retreatment patients in Bamako, Mali (59 %) and the two Nigerian sites in Ibadan and Lagos (39 % and 66 %). In Lagos, MDR is already spreading actively amongst 32 % of new patients. Pre-extensively drug-resistant (pre-XDR) isolates are present in all sites, with Ghana showing the highest proportion (35 % of MDR). In Ghana and Togo, pre-XDR isolates are circulating amongst new patients. CONCLUSIONS: West African drug-resistance prevalence poses a previously underestimated, yet serious public health threat, and our estimates obtained differ significantly from previous World Health Organisation (WHO) estimates. Therefore, our data are reshaping current concepts and are essential in informing WHO and public health strategists to implement urgently needed surveillance and control interventions in West Africa.

HBV carriage in children born from HIV-seropositive mothers in Senegal: The need of birth-dose HBV vaccination.

Hepatitis B is a major public health problem in Senegal, a country with high prevalence and a transmission occurring mainly during infancy. Only, one 6-8 weeks vaccination campaign was initiated in 2005 and it was part of the expanded program of immunization. The aim of this study was to determine the prevalence of HBsAg in children born from HIV-seropositive mothers by using dried blood specimens. Specimens were collected between July 2007 and November 2012 from children aged 2-48 weeks in Dakar and decentralized sites working on HIV mother-to-child transmission prevention. HBsAg detection was performed using Architect HBsAg Qualitative II kit (Abbott Diagnostics, Ireland) and for all reactive samples confirmation was done using Architect HBsAg Qualitative II Confirmatory kit (Abbott Diagnostics, Ireland). Nine hundred thirty samples were collected throughout the country with 66% out of Dakar, the capital city. The median age was 20 weeks and 88% of children were less than 1 year of age with a sex ratio of 1.27 in favor of boys. HBsAg was detected in 28 cases giving a global prevalence of 3%. According to age, HBsAg prevalences were 5.1% for children less than 6 weeks, 4.1% and 4.6%, respectively, for those aged 12-18 weeks and 18-24 weeks of age. The HIV prevalence was 2.6% with no HIV/HBV co-infection. This study showed a high rate of HBV infection in children under 24 months, highlighting the need to promote birth-dose HBV vaccination as recommended by WHO.

Prevalence of hepatitis B markers in Senegalese HIV-1-infected patients.

The study aimed to estimate the prevalence of Hepatitis B virus (HBV) infection and to describe the HBV virological profiles among Senegalese HIV-1-infected patients. We conducted a retrospective study between 2006 and 2010 among Senegalese HIV-1-infected patients from the antiretroviral therapy cohort. Samples were screened using Determine(®) HBsAg or MONOLISA(®) POC test. The HBsAg positivity status was confirmed by Architect(®) HBsAg. Detection of HBeAg, anti-HBe Ab, and HBV DNA load were done for the HBsAg-positive samples. Then, Anti-HBcAb was tested for the HBsAg-negative samples. Microsoft Excel was used for data collection and statistical analyses were performed using Epi info 3.5.1. Overall, 466 HIV-infected patients were enrolled including 271 women (58.4%), and 193 men (41.6%) with a median age of 39 years (19-74 years). The global prevalence of HIV/HBV coinfection (HBsAg positive) was 8.8% (41/466). For HBsAg positives samples, the prevalence of HBeAg and the anti-HBeAb were, respectively, 24.4 and 69.2% and the median of HBV DNA viral load, for 27 HBsAg-positive samples, was 3.75 log10 copies/ml. The virological profiles were the following: 7, 15, and 5 patients infected, respectively, by a replicative virus, an inactive virus and a probably mutant virus. For HBsAg-negative samples, 83 out of 109 were positive for anti-HBcAb. This study showed a significant decrease of the prevalence of HBV/HIV coinfection between 2004 and 2014 (P = 0.003), which highlighted the performance of the Senegalese HBV vaccine program. However, implementing a systematic quantification of HBV DNA viral load could improve the monitoring of HBV-infected patient.

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.

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).

Cis-regulatory elements driving motor neuron-restricted viral payload expression within the mammalian spinal cord.

Spinal motor neuron (MN) dysfunction is the cause of a number of clinically significant movement disorders. Despite the recent approval of gene therapeutics targeting these MN-related disorders, there are no viral delivery mechanisms that achieve MN-restricted transgene expression. In this study, chromatin accessibility profiling of genetically defined mouse MNs was used to identify candidate cis-regulatory elements (CREs) capable of driving MN-selective gene expression. Subsequent testing of these candidates identified two CREs that confer MN-selective gene expression in the spinal cord as well as reduced off-target expression in dorsal root ganglia. Within one of these candidate elements, we identified a compact core transcription factor (TF)-binding region that drives MN-selective gene expression. Finally, we demonstrate that selective spinal cord expression of this mouse CRE is preserved in non-human primates. These findings suggest that the generation of cell-type-selective viral reagents, in which cell-type-selective CREs drive restricted gene expression, will be valuable research tools in mice and other mammalian species, with potentially significant therapeutic value in humans.