Treatment of COVID-19-associated ARDS with umbilical cord-derived mesenchymal stromal cells in the STROMA-CoV-2 multicenter randomized double-blind trial: long-term safety, respiratory function, and quality of life.

BACKGROUND: The STROMA-CoV-2 study was a French phase 2b, multicenter, double-blind, randomized, placebo-controlled clinical trial that did not identify a significant efficacy of umbilical cord-derived mesenchymal stromal cells in patients with SARS-CoV-2-induced acute respiratory distress syndrome. Safety on day 28 was found to be good. The aim of our extended study was to assess the 6- and 12-month safety of UC-MSCs administration in the STROMA-CoV-2 cohort. METHODS: A detailed multi-domain assessment was conducted at 6 and 12 months following hospital discharge focusing on adverse events, lung computed tomography-scan, pulmonary and muscular functional status, and quality of life in the STROMA-CoV-2 cohort including SARS-CoV-2-related early (< 96 h) mild-to-severe acute respiratory distress syndrome. RESULTS: Between April 2020 and October 2020, 47 patients were enrolled, of whom 19 completed a 1-year follow-up. There were no significant differences in any endpoints or adverse effects between the UC-MSCs and placebo groups at the 6- and 12-month assessments. Ground-glass opacities persisted at 1 year in 5 patients (26.3%). Furthermore, diffusing capacity for carbon monoxide remained altered over 1 year, although no patient required oxygen or non-invasive ventilatory support. Quality of life revealed declines in mental, emotional and physical health throughout the follow-up period, and the six-minute walking distance remained slightly impaired at the 1-year patient assessment. CONCLUSIONS: This study suggests a favorable safety profile for the use of intravenous UC-MSCs in the context of the first French wave of SARS-CoV-2-related moderate-to-severe acute respiratory distress syndrome, with no adverse effects observed at 1 year.

Crimean-Congo haemorrhagic fever outbreak in Northern Senegal in 2022: Prevalence of the virus in livestock and ticks, associated risk factors and epidemiological implications.

OBJECTIVE: Crimean-Congo haemorrhagic fever (CCHF) is a severe zoonotic arboviral disease that occurs widely in Eastern and Western Europe, Asia and Africa. The disease is becoming of growing public health importance in Senegal. However, analysis of tick infestation, CCHF virus (CCHFV) circulation extent and risk factors during ongoing outbreak are scarce. A thorough outbreak investigation was carried out during a CCHF outbreak in Podor (Northern Senegal) in August 2022. METHODS: Ticks and blood samples were collected from animals (cattle, goats and sheep) randomly selected from confirmed CCHF human cases houses, neighbourhoods and surrounding villages. Blood samples were tested for CCHFV antibodies using a commercial enzyme-linked immunosorbent assay (ELISA) test. Tick samples were screened for CCHFV RNA by RT-PCR. RESULTS: Overall, tick infestation rate (TIR) and CCHFV seroprevalence of livestock were 52.12% (95% confidence interval (CI): 45.54%-58.64%) and 43.28% (95% CI: 36.33%-50.44%), respectively. The TIRs were 87.7% in cattle, 57.6% in sheep and 20.0% in goats. These rates were significantly associated with location, host species and tick control (p < 0.001) but not with animal age and sex (p > 0.7). CCHFV seroprevalence was 80.4% (95% CI: 67.57%-89.77%) in cattle, 35.4% (95% CI: 25.00%-47.01%) in sheep and 21.2% (95% CI: 12.11%-33.02%) in goats. Age, sex, location, animal host and presence of ticks were significantly associated to the presence of antibodies. The 950 ticks collected included among other species, Hyalomma impeltatum (48.84%) and H. rufipes (10.21%). Five pools of Hyalomma ssp. were found CCHFV RT-PCR positive. These infected ticks included 0.86% (4/464) of H. impeltatum collected on cattle and sheep and 1.03% (1/97) of H. rufipes collected on a sheep. CONCLUSIONS: To our knowledge, this is the first report on the extend of tick infestation and CCHFV infection in livestock during an outbreak in Senegal. The results highlight the risk of human infections and the importance of strengthening vector, animal and human surveillance as well as tick control measures in this area to prevent CCHF infections in humans.

Evaluating the performance of Plasmodium falciparum genetic metrics for inferring National Malaria Control Programme reported incidence in Senegal.

BACKGROUND: Genetic surveillance of the Plasmodium falciparum parasite shows great promise for helping National Malaria Control Programmes (NMCPs) assess parasite transmission. Genetic metrics such as the frequency of polygenomic (multiple strain) infections, genetic clones, and the complexity of infection (COI, number of strains per infection) are correlated with transmission intensity. However, despite these correlations, it is unclear whether genetic metrics alone are sufficient to estimate clinical incidence. METHODS: This study examined parasites from 3147 clinical infections sampled between the years 2012-2020 through passive case detection (PCD) across 16 clinic sites spread throughout Senegal. Samples were genotyped with a 24 single nucleotide polymorphism (SNP) molecular barcode that detects parasite strains, distinguishes polygenomic (multiple strain) from monogenomic (single strain) infections, and identifies clonal infections. To determine whether genetic signals can predict incidence, a series of Poisson generalized linear mixed-effects models were constructed to predict the incidence level at each clinical site from a set of genetic metrics designed to measure parasite clonality, superinfection, and co-transmission rates. RESULTS: Model-predicted incidence was compared with the reported standard incidence data determined by the NMCP for each clinic and found that parasite genetic metrics generally correlated with reported incidence, with departures from expected values at very low annual incidence (< 10/1000/annual [‰]). CONCLUSIONS: When transmission is greater than 10 cases per 1000 annual parasite incidence (annual incidence > 10‰), parasite genetics can be used to accurately infer incidence and is consistent with superinfection-based hypotheses of malaria transmission. When transmission was < 10‰, many of the correlations between parasite genetics and incidence were reversed, which may reflect the disproportionate impact of importation and focal transmission on parasite genetics when local transmission levels are low.

Quality assessment of malaria microscopic diagnosis at the Aristide Le Dantec University Hospital of Dakar, Senegal, in 2020.

BACKGROUND: Following WHO guidelines, microscopy is the gold standard for malaria diagnosis in endemic countries. The Parasitology-Mycology laboratory (LPM) is the National Reference Laboratory and is currently undergoing ISO 15189 accreditation. In this context, we assessed the performance of the laboratory by confirming the reliability and the accuracy of results obtained in accordance with the requirements of the ISO 15189 standards. This study aimed to verify the method of microscopic diagnosis of malaria at the LPM, in the Aristide Le Dantec hospital (HALD) in Dakar, Senegal. METHODS: This is a validation/verification study conducted from June to August 2020. Twenty (20) microscopic slides of thick/thin blood smear with known parasite densities (PD) selected from the Cheick Anta Diop University malaria slide bank in Dakar were used for this assessment. Six (6) were used to assess microscopists' ability to determine PD and fourteen (14) slides were used for detection (positive vs negative) and identification of parasites. Four (4) LPM-HALD microscopists read and recorded their results on prepared sheets. Data analysis was done with Microsoft Excel 2010 software. RESULTS: A minimum threshold of 50% concordance was used for comparison. Of the twenty (20) slides read, 100% concordance was obtained on eight (8) detection (positive vs negative) slides. Four (4) out of the six (6) parasite density evaluation slides obtained a concordance of less than 50%. Thirteen (13) out of the fourteen (14) identification slides obtained a concordance greater than 50%. Only one (1) identification slide obtained zero agreement from the microscopists. For species identification a concordance greater than 80% was noted and the microscopists obtained scores between 0.20 and 0.4 on a scale of 0 to 1 for parasite density reading. The microscopists obtained 100% precision, sensitivity, specificity and both negative and positive predictive values. CONCLUSION: This work demonstrated that the microscopic method of malaria diagnosis used in the LPM/HALD is in accordance with the requirements of WHO and ISO 15189. Further training of microscopists may be needed to maintain competency.

PASQUALE - A long-term partnership to improve hand hygiene and capacity building in infection prevention and control in the Faranah region of Guinea.

Across the globe, hand hygiene (HH) is promoted to fight the spread of healthcare associated infections. Despite multiple ongoing HH campaigns and projects, the healthcare associated infection rates remain high especially in low- and middle-income countries. In the narrative overview presented here, we aim to share objectives, framework, successes and challenges of our long-term partnership in Guinea to offer guidance for other projects aiming to sustainably improve HH.

Perspectives and experiences of healthcare providers on the response to the COVID-19 pandemic in three maternal and neonatal referral hospitals in Guinea in 2020: a qualitative study.

BACKGROUND: The COVID-19 pandemic has adversely affected access to essential healthcare services. This study aimed to explore healthcare providers' perceptions and experiences of the response to the COVID-19 pandemic in three referral maternal and neonatal hospitals in Guinea. METHODS: We conducted a longitudinal qualitative study between June and December 2020 in two maternities and one neonatology referral ward in Conakry and Mamou. Participants were purposively recruited to capture diversity of professional cadres, seniority, and gender. Four rounds of in-depth interviews (46 in-depth interviews with 18 respondents) were conducted in each study site, using a semi-structured interview guide that was iteratively adapted. We used both deductive and inductive approaches and an iterative process for content analysis. RESULTS: We identified four themes and related sub-themes presented according to whether they were common or specific to the study sites, namely: 1) coping strategies & care reorganization, which include reducing staffing levels, maintaining essential healthcare services, suspension of staff daily meetings, insertion of a new information system for providers, and co-management with COVID-19 treatment center for caesarean section cases among women who tested positive for COVID-19; 2) healthcare providers' behavior adaptations during the response, including infection prevention and control measures on the wards and how COVID-19-related information influenced providers' daily work; 3) difficulties encountered by providers, in particular unavailability of personal protective equipment (PPE), lack of financial motivation, and difficulties reducing crowding in the wards; 4) providers perceptions of healthcare service use, for instance their fear during COVID-19 response and perceived increase in severity of complications received and COVID-19 cases among providers and parents of newborns. CONCLUSION: This study provides insights needed to be considered to improve the preparedness and response of healthcare facilities and care providers to future health emergencies in similar contexts.

The Medication Quantification Scale 4.0: An Updated Index Based on Prescribers' Perceptions of the Risk Associated With Chronic Pain Medications.

To quantify risks associated with drug utilization in the real world for the treatment of chronic pain (CP), an index called the Medication Quantification Scale (MQS) was developed in 1992 in the United States and last updated in 2003. This study aimed to update, adapt to the contemporary Canadian context, and validate a revised version of the MQS (the MQS-4.0). Step 1: An expert committee adapted the MQS to the Canadian clinical practice context. Step 2: An update of risk weights given to medication subclasses was achieved using a prescriber survey (weights were derived from median 0-10 scores given to each subclass). Step 3: Construct validity of the MQS-4.0 was assessed after applying risk weights to the medication use profile of persons living with CP covered by public drug insurance plan. Thirty-six medication subclasses were included in the MQS-4.0. A total of 207 prescribers (physicians, pharmacists, and nurse practitioners) participated in the perception survey; 10.63% identified as pain specialists. When risk weights were applied to prescription claims (n = 9,122), the MQS-4.0 score was associated (P < .05) with the MQS-III score and variables associated with polypharmacy (eg, Charlson Comorbidity Index, number of prescribers or health care visits). This study provides an updated index intended for adult populations based on prescribers' perceptions of the risk associated with CP medications that can be useful for clinical practice and research among persons living with CP in Canada. It will, however, be relevant to verify whether similar risk weights are obtained in future pain specialist surveys. PERSPECTIVE: The MQS-4.0 is an update of the MQS used for quantifying the risk associated with the use of analgesics/coanalgesics. Adequate psychometrics properties were found.

Effect of anti-Ebola virus monoclonal antibodies on endogenous antibody production in survivors of Ebola virus disease in the Democratic Republic of the Congo: an observational cohort study.

BACKGROUND: The use of specific anti-Ebola virus therapy, especially monoclonal antibodies, has improved survival in patients with Ebola virus disease. We aimed to assess the effect of monoclonal antibodies on anti-Ebola virus antibody responses in survivors of the 2018-20 Ebola outbreak in the Democratic Republic of the Congo. METHODS: In this observational prospective cohort study, participants were enrolled at three Ebola survivor clinics in Beni, Mangina, and Butembo (Democratic Republic of the Congo). Eligible children and adults notified as survivors of Ebola virus disease (ie, who had confirmed Ebola virus disease [RT-PCR positive in blood sample] and were subsequently declared recovered from the virus [RT-PCR negative in blood sample] with a certificate of recovery from Ebola virus disease issued by an Ebola treatment centre) during the 2018-20 Ebola virus disease outbreak were invited to participate in the study. Participants were recruited on discharge from Ebola treatment centres and followed up for 12-18 months depending on recruitment date. Routine follow-up assessments were done at 1, 3, 6, and 12-18 months after inclusion. We collected sociodemographic (age, sex, visit site), clinical (anti-Ebola virus drugs), and laboratory data (RT-PCR and Ct values). The primary outcome was the antibody concentrations against Ebola virus glycoprotein, nucleoprotein, and 40-kDa viral protein antigens over time assessed in all participants. Antibody concentrations were measured by the multiplex immunoassay, and the association between anti-Ebola virus antibody levels and the relevant exposures, such as anti-Ebola virus disease drugs (ansuvimab, REGN-EB3, ZMapp, or remdesivir), was assessed using both linear and logistic mixed regression models. This study is registered at ClinicalTrials.gov, NCT04409405. FINDINGS: Between April 16, 2020, and Oct 18, 2021, 1168 survivors were invited to participate in the Les Vainqueurs d'Ebola cohort study. 787 survivors were included in the study, of whom 358 had data available for antibody responses. 85 (24%) of 358 were seronegative for at least two Ebola virus antigens on discharge from the Ebola treatment centre. The antibody response over time fluctuated but a continuous decrease in an overall linear evolution was observed. Quantitative modelling showed a decrease in nucleoprotein, glycoprotein, and VP-40 antibody concentrations over time (p<0·0001) with the fastest decrease observed for glycoprotein. The probability of being seropositive for at least two antigens after 36 months was 53·6% (95% CI 51·6-55·6) for participants who received ansuvimab, 73·5% (71·5-75·5) for participants who received REGN-EB3, 76·8% (74·8-78·8) for participants who received remdesivir, and 78·5% (76·5-80·5) for participants who received ZMapp. INTERPRETATION: Almost a quarter of survivors were seronegative on discharge from the Ebola treatment centre and antibody concentrations decreased rapidly over time. These results indicate that monoclonal antibodies might negatively affect the production of anti-Ebola virus antibodies in survivors of Ebola virus disease which could increase the risk of reinfection or reactivation. FUNDING: The French National Agency for AIDS Research-Emergent Infectious Diseases-The French National Institute of Health and Medical Research, the French National Research Institute for Development, and the European and Developing Countries Clinical Trials Partnership. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Analysis of cardiovascular risk factors: a retrospective epidemiological study in Guinea in 2022.

OBJECTIVE: This study presents a comprehensive descriptive and comparative analysis of a Guinean cohort, focusing on geographical variables and medical histories in relation to family backgrounds and cardiovascular risk scores. The primary goal is to enhance understanding of cardiovascular risk factor distribution within the Guinean population and identify significant correlations among the investigated variables. PATIENTS & METHODS: In this retrospective study, data from 2435 Guinean patients in 2022 were analyzed based on demographic and medical variables. Cardiovascular risk scores were calculated following Guinea's national program guidelines for non-communicable disease prevention and control. Rigorous data collection, including retrospective analyses and screening campaigns, was conducted in collaboration with the Fondation pour le Diabète et les Maladies Non Transmissibles de Conakry. Statistical tests, including one-way ANOVA, Kruskal-Wallis, Pearson Chi², V Cramer, Fisher exact, and Mann-Whitney U, were applied for a comprehensive comparative analysis. RESULTS: Analysis across five cardiovascular risk score levels revealed significant variations in gender, region, and tuberculosis prevalence. Gender differences were notable, with a female predominance in both groups, slightly higher in the 10 % or more risk group. The higher-risk group exhibited a greater proportion of fasting blood glucose measurements. CONCLUSIONS: Effectively assessing and managing hypertension, diabetes, and other pathologies requires considering factors such as geographic area, family history, cardiovascular risk score, and gender for accurate evaluation. These factors influence pathology prevalence and should be considered in individualized prevention and management strategies. The study underscores the importance of tailored measures to enhance disease management and reduce associated risks.

SEROPREVALENCE TO SCHISTOSOMA SOLUBLE EGG ANTIGEN AMONG NOMADIC PASTORALISTS RESIDING IN NORTHERN SENEGAL.

Urinary and intestinal schistosomiasis are endemic in Senegal, with prevalence heterogeneous throughout the country. Because of their way of life, nomadic pastoralists are not typically included in epidemiological surveys, and data on the prevalence of schistosomiasis in Senegalese nomadic populations are largely non-existent. The purpose of this study was to determine the seroprevalence of schistosomiasis in Senegalese nomadic pastoralists. A modified snowball sampling survey was conducted among 1,467 nomadic pastoralists aged 6 mo and older in 5 districts in northern Senegal. Dried blood spots from participants of all ages and data regarding demographics were collected to assess IgG antibody responses against Schistosoma mansoni soluble egg antigen (SEA) using a bead-based multiplex assay. Out of 1,467 study subjects, 1,464 (99.8%) provided IgG serological data that cleared quality assurance. Of the participants with appropriate data, 56.6% were male, the median age was 22 yr, and 31.6% were under 15 yr of age. The overall anti-SEA IgG seroprevalence was 19.1% (95% confidence interval [CI]: 17.1-21.1%) with the highest estimates observed in Dagana (35.9%) and the lowest observed in Podor nomadic groups (3.4%). Antibody responses increased significantly with age except for the oldest age groups (>40 yr of age), which saw lower levels of antibody response compared to younger adults. When controlling for age and location by multivariate regression, the male sex was associated with a 2-fold greater odds of anti-SEA IgG seropositivity (aPOR: 2.0; 95% CI: 1.5-2.7). Serosurveys for anti-SEA IgG among nomadic peoples in northern Senegal found a substantial percentage of individuals with evidence for current or previous Schistosoma spp. infection with the highest levels of exposure in the district adjacent to the Diama dam along the Senegal River. With IgG prevalence increased by age except in the older adults, and the male sex significantly associated with seropositivity, these data point toward sex-associated behavioral practices and human environmental modification as risk factors for Schistosoma exposure.

Pain Medications Used by Persons Living With Fibromyalgia: A Comparison Between the Profile of a Quebec Sample and Clinical Practice Guidelines.

Background: Pharmacological management of fibromyalgia is complex. Chronic pain management is characterized by off-label prescribing and use, multimorbidity, and polypharmacy. Aims: This study aimed to describe pain medications use and perceived risk among people living with fibromyalgia and compare this use to evidence-based recommendations. Methods: Directive telephone interviews were conducted with 63 individuals self-reporting a diagnosis of fibromyalgia (Quebec, Canada). The questionnaire addressed specific questions about their pain and pharmacological treatments currently used for pain management (prescribed and over-the-counter). Collected data were compared to the Canadian Fibromyalgia Clinical Practice Guidelines and to evidence reports published by recognized organizations. Results: Despite a lack of robust scientific evidence to support opioids use to manage pain in fibromyalgia, 33% of our sample reported using them. Nonsteroidal anti-inflammatory drugs were used by 54.0% of participants, although this medication is not recommended due to lack of efficacy. Tramadol, which is recommended, was used by 23.8% of participants. Among the medications strongly recommended, anticonvulsants were used by 36.5%, serotonin norepinephrine reuptake inhibitor antidepressants by 55.6%, and tricyclic antidepressants by 22.2%. Cannabinoids (17.5%) and medical cannabis (34.9%) use were also reported. For all of these medication subclasses, no differences were found between participants not reporting (n = 35) or reporting (n = 28) more than one pain diagnosis (P < 0.05). Medication subclasses considered most at risk of adverse effects by participants were the least used. Conclusions: Results reveal discordance between evidence-based recommendations and medications use, which highlights the complexity of pharmacological treatment of fibromyalgia.

Contexte: La prise en charge pharmacologique de la fibromyalgie est complexe. La prise en charge de la douleur chronique est caractérisée par la prescription et l'utilisation non conforme de médicaments, la multimorbidité et la polypharmacothérapie.Objectifs: Cette étude visait à décrire l'utilisation de médicaments contre la douleur et le risque perçu chez les personnes atteintes de fibromyalgie, et à comparer cette utilisation aux recommandations fondées sur des données probantes.Méthodes: Des entretiens téléphoniques directifs ont été menés auprès de 63 personnes ayant déclaré avoir reçu un diagnostic de fibromyalgie (Québec, Canada). Le questionnaire abordait des questions précises sur leur douleur et les traitements pharmacologiques actuellement utilisés pour la prise en charge de leur douleur (prescrits et vendus sans ordonnance). Les données recueillies ont été comparées aux Lignes directrices canadiennes sur la fibromyalgie et aux rapports de données probantes publiés par des organisations reconnues.Résultats: Malgré l'absence de données probantes robustes à l'appui de l'utilisation des opioïdes pour la prise en charge la douleur chez les personnes atteintes de fibromyalgie, 33 % de notre échantillon a déclaré les utiliser. Les anti-inflammatoires nonstéroïdiens étaient pour leur part utilisés par 54,0 % des participants, bien que ce médicament ne soit pas recommandé en raison d'un manque d'efficacité. Le tramadol, recommandé, était utilisé par 23,8 % des participants. Parmi les médicaments fortement recommandés, les anticonvulsivants étaient utilisés par 36,5 % desparticipants, les antidépresseurs inhibiteurs de la recapture de la sérotonine et de la noradrénaline par 55,6 % des participants, et les antidépresseurs tricycliques par 22,2 % d'entre eux. La consommation de cannabinoïdes (17,5 %) et de cannabis médical (34,9 %) ont également été signalées. Pour toutes ces sous-classes de médicaments, aucune différence n'a été trouvée entre les participants ne signalant pas (n = 35) ou signalant (n = 28) plus d'un diagnostic de douleur (P < 0,05). Les sous-classes de médicaments considérées par les participants comme les plus à risque d'effets indésirables étaient les moins utilisées.Conclusions: Les résultats révèlent une discordance entre les recommandations fondées sur des données probantes et l'utilisation de médicaments, ce qui met en évidence la complexité du traitement pharmacologique de la fibromyalgie.

Malaria surveillance reveals parasite relatedness, signatures of selection, and correlates of transmission across Senegal.

We here analyze data from the first year of an ongoing nationwide program of genetic surveillance of Plasmodium falciparum parasites in Senegal. The analysis is based on 1097 samples collected at health facilities during passive malaria case detection in 2019; it provides a baseline for analyzing parasite genetic metrics as they vary over time and geographic space. The study's goal was to identify genetic metrics that were informative about transmission intensity and other aspects of transmission dynamics, focusing on measures of genetic relatedness between parasites. We found the best genetic proxy for local malaria incidence to be the proportion of polygenomic infections (those with multiple genetically distinct parasites), although this relationship broke down at low incidence. The proportion of related parasites was less correlated with incidence while local genetic diversity was uninformative. The type of relatedness could discriminate local transmission patterns: two nearby areas had similarly high fractions of relatives, but one was dominated by clones and the other by outcrossed relatives. Throughout Senegal, 58% of related parasites belonged to a single network of relatives, within which parasites were enriched for shared haplotypes at known and suspected drug resistance loci and at one novel locus, reflective of ongoing selection pressure.

Evaluating the performance of Plasmodium falciparum genetics for inferring National Malaria Control Program reported incidence in Senegal.

Genetic surveillance of the Plasmodium falciparum parasite shows great promise for helping National Malaria Control Programs (NMCPs) assess parasite transmission. Genetic metrics such as the frequency of polygenomic (multiple strain) infections, genetic clones, and the complexity of infection (COI, number of strains per infection) are correlated with transmission intensity. However, despite these correlations, it is unclear whether genetic metrics alone are sufficient to estimate clinical incidence. Here, we examined parasites from 3,147 clinical infections sampled between the years 2012-2020 through passive case detection (PCD) across 16 clinic sites spread throughout Senegal. Samples were genotyped with a 24 single nucleotide polymorphism (SNP) molecular barcode that detects parasite strains, distinguishes polygenomic (multiple strain) from monogenomic (single strain) infections, and identifies clonal infections. To determine whether genetic signals can predict incidence, we constructed a series of Poisson generalized linear mixed-effects models to predict the incidence level at each clinical site from a set of genetic metrics designed to measure parasite clonality, superinfection, and co-transmission rates. We compared the model-predicted incidence with the reported standard incidence data determined by the NMCP for each clinic and found that parasite genetic metrics generally correlated with reported incidence, with departures from expected values at very low annual incidence (<10/1000/annual [‰]). When transmission is greater than 10 cases per 1000 annual parasite incidence (annual incidence >10 ‰), parasite genetics can be used to accurately infer incidence and is consistent with superinfection-based hypotheses of malaria transmission. When transmission was <10 ‰, we found that many of the correlations between parasite genetics and incidence were reversed, which we hypothesize reflects the disproportionate impact of importation and focal transmission on parasite genetics when local transmission levels are low.

Obstetric referrals, complications and health outcomes in maternity wards of large hospitals during the COVID-19 pandemic: a mixed methods study of six hospitals in Guinea, Nigeria, Uganda and Tanzania.

OBJECTIVES: The COVID-19 pandemic affected provision and use of maternal health services. This study describes changes in obstetric complications, referrals, stillbirths and maternal deaths during the first year of the pandemic and elucidates pathways to these changes. DESIGN: Prospective observational mixed-methods study, combining monthly routine data (March 2019-February 2021) and qualitative data from prospective semi-structured interviews. Data were analysed separately, triangulated during synthesis and presented along three country-specific pandemic periods: first wave, slow period and second wave. SETTING: Six referral maternities in four sub-Saharan African countries: Guinea, Nigeria, Tanzania and Uganda. PARTICIPANTS: 22 skilled health personnel (SHP) working in the maternity wards of various cadres and seniority levels. RESULTS: Percentages of obstetric complications were constant in four of the six hospitals. The percentage of obstetric referrals received was stable in Guinea and increased at various times in other hospitals. SHP reported unpredictability in the number of referrals due to changing referral networks. All six hospitals registered a slight increase in stillbirths during the study period, the highest increase (by 30%-40%) was observed in Uganda. Four hospitals registered increases in facility maternal mortality ratio; the highest increase was in Guinea (by 158%), which had a relatively mild COVID-19 epidemic. These increases were not due to mortality among women with COVID-19. The main pathways leading to these trends were delayed care utilisation and disruptions in accessing care, including sub-optimal referral linkages and health service closures. CONCLUSIONS: Maternal and perinatal survival was negatively affected in referral hospitals in sub-Saharan Africa during COVID-19. Routine data systems in referral hospitals must be fully used as they hold potential in informing adaptations of maternal care services. If combined with information on women's and care providers' needs, this can contribute to ensuring continuation of essential care provision during emergency.

Shifting Patterns of Influenza Circulation during the COVID-19 Pandemic, Senegal.

Historically low levels of seasonal influenza circulation were reported during the first years of the COVID-19 pandemic and were mainly attributed to implementation of nonpharmaceutical interventions. In tropical regions, influenza's seasonality differs largely, and data on this topic are scarce. We analyzed data from Senegal's sentinel syndromic surveillance network before and after the start of the COVID-19 pandemic to assess changes in influenza circulation. We found that influenza shows year-round circulation in Senegal and has 2 distinct epidemic peaks: during January-March and during the rainy season in August-October. During 2021-2022, the expected January-March influenza peak completely disappeared, corresponding to periods of active SARS-CoV-2 circulation. We noted an unexpected influenza epidemic peak during May-July 2022. The observed reciprocal circulation of SARS-CoV-2 and influenza suggests that factors such as viral interference might be at play and should be further investigated in tropical settings.

FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trial.

BACKGROUND: Vascular leakage is a major feature of acute respiratory distress syndrome (ARDS). We aimed to evaluate the efficacy of FX06, a drug under development that stabilizes interendothelial cell junctions, at reducing vascular leakage during SARS-CoV-2-induced ARDS. METHODS: This multicenter, double-blinded, randomized trial included adults with COVID-19-associated ARDS who had received invasive mechanical ventilation for < 5 days and were randomized to receive either intravenous FX06 (400 mg/d, for 5 days) or its vehicle as placebo. The primary endpoint was the lowering-from day 1 to day 7-of the transpulmonary thermodilution-derived extravascular lung-water index (EVLWi). RESULTS: Twenty-five patients were randomized to receive FX06 and 24 the placebo. Although EVLWi was elevated at baseline (median [IQR] 15.6 mL/kg [13.5; 18.5]), its declines from day 1 to day 7 were comparable for FX06 recipients and controls (respectively, - 1.9 [- 3.3; - 0.5] vs. - 0.8 [- 5.5; - 1.1] mL/kg; estimated effect - 0.8 [- 3.1; + 2.4], p = 0.51). Cardiac indexes, pulmonary vascular permeability indexes, and fluid balances were also comparable, as were PaO2/FiO2 ratios and durations of mechanical ventilation. Adverse event rates were similar for the 2 groups, although more FX06 recipients developed ventilator-associated pneumonia (16/25 (64%) vs. 6/24 (24%), p = 0.009). CONCLUSIONS: In this unique-dosing-regimen study, FX06 did not lower SARS-CoV-2-induced pulmonary vascular leakage. Future investigations will need to evaluate its efficacy at earlier times during the disease or using other regimens. Trial registration NCT04618042. Registered 5 November 2020.

Retention and Predictors of Attrition Among People Living With HIV on Antiretroviral Therapy in Guinea: A 13-Year Historical Cohort Study in Nine Large-Volume Sites.

Objectives: The objective of this study was to estimate the retention rate of patients in an ART program and identify the predictors of attrition. Methods: This was a historical cohort study of HIV patients who started ART between September 2007 and April 2020, and were followed up on for at least 6 months in nine large-volume sites. Kaplan Meier techniques were used to estimate cumulative retention and attrition probabilities. Cox proportional hazards models were used to identify predictors of attrition. Results: The cumulative probability of retention at 12 and 24 months was 76.2% and 70.2%, respectively. The attrition rate after a median follow-up time of 3.1 years was 35.2%, or an incidence of 11.4 per 100 person-years. Having initiated ART between 2012 and 2015; unmarried status; having initiated ART with CD4 count <100 cells/µL; and having initiated ART at an advanced clinical stage were factors significantly associated with attrition. Conclusion: The retention rate in our study is much lower than the proposed national target (90%). Studies to understand the reasons for loss to follow-up are needed.

Simultaneous seroprevalence of Toxoplasma gondii and rubella virus infections in pregnant women in Dakar (Senegal).

Context: Toxoplasma gondii and rubella virus are microorganisms that can cause intrauterine infections and congenital anomalies in the fetus. Data regarding the simultaneous seroprevalence of these infections are not available in Senegal. Aims: This study aimed to determine for the first time the simultaneous seroprevalence of toxoplasmosis and rubella among pregnant women in Dakar. Materials and Methods: In this retrospective study, anti-Toxoplasma and anti-rubella antibodies were analyzed in the serum samples obtained from pregnant women receiving prenatal care at Military Hospital of Ouakam between 2016 and 2021 using a chemiluminescent microparticle immunoassay for the quantitative determination of immunoglobulin G (IgG) and IgM antibodies to Toxoplasma gondii and rubella in human serum. Results: Overall, data from 2589 women were analyzed. The median age was 29 years (interquartile range: 23.14-34.86). Serum IgG and IgM were positive for T. gondii with 35.84% and 1.66%, respectively. Rubella seroprevalence was 87.14% and 0.35%, respectively, for IgG and IgM. Seroprevalence of toxoplasmosis increases significantly with age and study period. For rubella infection, the highest seroprevalence rates were noted in the youngest age group and at the end of the study period. Conclusions: Data from this first-time study regarding simultaneous seroprevalence of toxoplasmosis and rubella among pregnant women in Senegal indicate a continuing high risk of congenital toxoplasmosis and congenital rubella syndrome in Dakar. Further studies are needed to fully assess the efficacy of rubella vaccination in women of childbearing age.

Characteristics and Prescribing Patterns of Clinicians Waivered to Prescribe Buprenorphine for Opioid Use Disorder Before and After Release of New Practice Guidelines.

Importance: In April 2021, the US Department of Health and Human Services (HHS) released practice guidelines exempting educational requirements to obtain a Drug Addiction Treatment Act (DATA) waiver to treat up to 30 patients with opioid use disorder with buprenorphine. Objective: To compare demographic and practice characteristics of clinicians who received traditional DATA waivers before and after release of the education-exempted HHS practice guidelines and those who were approved under the guidelines. Design, Setting, and Participants: This survey study was conducted electronically from February 1 to March 1, 2022. Eligible survey recipients were US clinicians who obtained an initial DATA waiver between April 2020 and November 2021. Exposure: DATA waiver approval pathway. Main Outcome and Measures: The outcomes were clinician demographic and practice characteristics, buprenorphine prescribing barriers, and strategies to treat patients with opioid use disorder, measured using χ2 tests and z tests to assess for differences among the waivered groups. Results: Of 23 218 eligible clinicians, 4519 (19.5%) responded to the survey. This analysis was limited to 2736 respondents with a 30-patient limit at the time of survey administration who identified their DATA waiver approval pathway. Among these respondents, 1365 (49.9%; female, 831 [61.9%]; male, 512 [38.1%]) received their DATA waiver prior to the education-exempted practice guidelines (prior DATA waiver), 550 (20.1%; female, 343 [63.4%]; male, 198 [36.6%]) received their waiver after guidelines were released but met education requirements (concurrent DATA waiver), and 821 (30.0%; female, 396 [49.2%]; male, 409 [50.8%]) received the waiver under the education-exempted guidelines (practice guidelines). Among practice guidelines clinicians, 500 (60.9%) reported that traditional DATA waiver educational requirements were a reason for not previously obtaining a waiver. Demographic and practice characteristics differed by waiver approval type. Across all groups, a large minority had not prescribed buprenorphine since obtaining a waiver (prior DATA waiver, 483 [35.7%]; concurrent DATA waiver, 226 [41.2%]; practice guidelines, 359 [44.3%]; P < .001). Clinicians who prescribed buprenorphine in the past 6 months reported treating few patients in an average month: 27 practice guidelines clinicians (6.0%) prescribed to 0 patients and 338 (75.1%) to 1 to 4 patients compared with 16 (2.2%) and 435 (59.9%) for prior and 11 (3.6%) and 166 (55.0%) for concurrent DATA waiver clinicians, respectively (P < .001). Across waiver types, clinicians reported multiple challenges to buprenorphine prescribing. Conclusions and Relevance: In this survey of DATA-waivered clinicians, clinician- and systems-level challenges that limit buprenorphine prescribing were observed, even among clinicians approved under the education-exempted guidelines pathway. The findings suggest that as implementation of legislation removing the DATA waiver begins, addressing these barriers could be essential to increasing buprenorphine access.