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The International Study on COVID-19 Vaccines to Assess Immunogenicity, Reactogenicity, and Efficacy is an observational study to assess the immunogenicity of COVID-19 vaccines used in Democratic Republic of Congo, Guinea, Indonesia, Liberia, Mali, Mexico, and Mongolia. The study, which has enrolled 5,401 adults, is prospectively following participants for approximately two years. This study is important as it has enrolled participants from resource-limited settings that have largely been excluded from COVID-19 research studies during the pandemic. There are significant challenges to mounting a study during an international health emergency, especially in resource-limited settings. Here we focus on challenges and hurdles encountered during the planning and implementation of the study with regard to study logistics, national vaccine policies, pandemic-induced and supply chain constraints, and cultural beliefs. We also highlight the successful mitigation of these challenges through the team's proactive thinking, collaborative approach, and innovative solutions. This study serves as an example of how established programs in resource-limited settings can be leveraged to contribute to biomedical research during a pandemic response. Lessons learned from this study can be applied to other studies mounted to respond rapidly during a global health crisis and will contribute to capacity for stronger pandemic preparedness in the future when there is a crucial need for urgent response and data collection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Introduction: Maternal mortality remains very high in Sub-Saharan African countries and the risk is higher among adolescent girls. Maternal mortality occurs in these settings mainly around the time of childbirth and the first 24 hours after birth. Therefore, skilled attendance in an enabling environment is essential to reduce the occurrence of adverse outcomes for both women and their children. This study aims to analyze the determinants of facility childbirth among adolescents and young women in Guinea., Methods: We used the Guinea Demographic and Health Survey (DHS) conducted in 2018. All females who were adolescents (15-19) or young women (20-24 years) at the time of their most recent live birth in the five years before the survey were included. We examined the use of health facilities for childbirth and its determinants selected through the Andersen health-seeking model using descriptive analysis and multilevel multivariable logistic regression. All descriptive and analytical estimated were produced by adjusting for the survey sampling using the svy option, including adjustment for clustering, stratification and unequal probability of selection and non-response (individual sample weights). The subpopulation option was also used to account for the variance of estimations., Results: Overall, 58% of adolescents and 57% of young women gave birth in a health facility. Young women were more likely to have used private sector facilities compared to adolescents (p<0.001). Factors significantly associated with a facility birth in multivariable regression included: secondary or higher educational level (aOR = 1.86; 95%CI:1.24-2.78) compared to no formal education; receipt of 1-3 antenatal visits (aOR = 9.33; 95%CI: 5.07-17.16) and 4+ visits (aOR = 16.67; 95%CI: 8.82-31.48) compared to none; living in urban (aOR = 2.50; 95%CI: 1.57-3,98) compared to rural areas. Women from poorest households had lower odds of facility-based childbirth. There was substantial variation in the likelihood of birth in a health facility by region, with highest odds in N'Zérékoré and lowest in Labé., Conclusion: The percentage of births in health facilities among adolescents and young women in Guinea was 58%. This remains suboptimal regarding the challenges associated maternal mortality and morbidity issues in Guinea. Socio-economic characteristics, region of residence and antenatal care use were the main determinants of its use. Efforts to improve maternal health among this group should target care discontinuation between antenatal care and childbirth (primarily by removing financial barriers) and increasing the demand for facility-based childbirth services in communities, while paying attention to the quality and respectful nature of healthcare services provided there., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Grovogui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Febrile illnesses constitute a major clinical challenge in tropical settings. We aimed to assess the frequency, presentation and management of febrile illness at two health facilities in Forécariah, Guinea, with a focus on appropriateness of antibiotic prescription., Materials and Methods: This was a retrospective study conducted in patient files in a health center and a district hospital. Proportions of antibiotic prescription were determined by age group and syndromes as well as appropriateness of antibiotic prescription using the WHO model list (2019)., Results: From 2014 to 2020, 23,583 of 62,185 (38.0%) visits were related to febrile illness. Most patients with fever were female (56.1%) and evaluated at the health center (81.0%). Gastrointestinal (40.6%) and respiratory syndromes (36.8%), and undifferentiated fever (30.0%) were the most common presentations. Malaria was confirmed in 61.3% of the cohort. Overall, the rate of antibiotic prescription was high (14,834/23,583, 62.9%), mostly among patients aged <5 years (5,285/7,566, 69.9%), those with respiratory (7,577/8,684, 87.3%) and gastrointestinal (6,324/9,585, 66.0%) syndromes. Moreover, 7,432/14,465 (51.4%) patients with malaria were also prescribed an antibiotic. Penicillin (42.0%), cotrimoxazole (26.3%) and quinolones (18.7%) were the most frequently prescribed antibiotics. Overall, appropriateness of antibiotic prescription was low (38.3%), and even more so in patients with respiratory (29.1%) and gastrointestinal (25.8%) syndromes., Conclusions: Febrile illness is a major cause of consultation in rural Guinea. Rate of antibiotic prescription was high, even in confirmed malaria and was often considered inappropriate. There is a pressing need to investigate the etiological spectrum and improve the diagnostic approach of febrile illness in Guinea., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2022 Kourouma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In response to the COVID-19 pandemic, COVID-19 vaccines have been developed, and the World Health Oraganization (WHO) has granted emergency use listing to multiple vaccines. Studies of vaccine immunogenicity data from implementing COVID-19 vaccines by national immunization programs in single studies spanning multiple countries and continents are limited but critically needed to answer public health questions on vaccines, such as comparing immune responses to different vaccines and among different populations., Competing Interests: The authors have declared that no competing interests exist.

Guinea, like many other African countries, has been facing an unprecedented COVID-19 outbreak, since March 2020. In April 2020, Guinean National agency for health security recorded 1351 confirmed cases of COVID-19, including 313 recoveries and 07 deaths. To address this health crisis, some drastic measures were implemented to prevent the spread of COVID-19. Those measures might potentially cause some psychological problems among Guineans. Thus, we conducted this study to assess the psychosocial impacts of COVID-19 in the Guinean population. We carried out an online cross-sectional survey among internet users in Guinea. A free e-survey platform was used, and questionnaires were sent to internet users. The study ran from May 1 through May 10 2020. Participation in the study was voluntary. Data collection was based on sociodemographic information and self-reported questionnaires: Impact of Event Scale-Revised (IES-R) for stress evaluation, Penn state worry questionnaire (PSWQ), and an adapted Social Psychological Measurements of COVID-19. A total of 280 participants took part in the study; responses from 5 participants were deleted because of incompleteness. The average age of participants was 28.9 [95% CI: 28.1;29.6]. Most of participants were male 65.5% [95% CI: 59.5%;71.1%]. Unemployed participants stood for 48.7% [95% CI: 42.7%;54.8%]. IES-R scale for stress evaluation yielded the following findings: 19.6% (mild), 5.23% (moderate) and 9.15% (severe); 82.8% and 17.2% of participants had respectively reported low and moderate worry. No significant statistical association was found between sociodemographic variables and traumatic events (IES-R and PSWQ). However, 82% of our participants had to cope with the negative impacts of COVID-19. Although there were few cases of traumatic events, negative impacts of COVID-19 on study participants deserve to be underlined. So, further investigations are necessary to identify and disentangle specific psychosocial problems in different Guinean socio-cultural contexts., Competing Interests: The authors have declared that no competing interests exist.

During the large Ebola outbreak that affected West Africa in 2014 and 2015, studies were launched to evaluate potential treatments for the disease. A clinical trial to evaluate the effectiveness of the antiviral drug favipiravir was conducted in Guinea. This paper describes the main challenges of the implementation of the trial in the Ebola treatment center of Guéckédou. Following the principles of the Good Clinical Research Practices, we explored the aspects of the community's communication and engagement, ethical conduct, trial protocol compliance, informed consent of participants, ongoing benefit/risk assessment, record keeping, confidentiality of patients and study data, and roles and responsibilities of the actors involved. We concluded that several challenges have to be addressed to successfully implement a clinical trial during an international medical emergency but that the potential for collaboration between research teams and humanitarian organizations needs to be highlighted.

To date there are no approved antiviral drugs for the treatment of Ebola virus disease (EVD). Based on our in vitro evidence of antiviral activity of interferon (IFN)-ß activity against Ebola virus, we conducted a single arm clinical study in Guinea to evaluate the safety and therapeutic efficacy of IFN β-1a treatment for EVD. Nine individuals infected with Ebola virus were treated with IFN β-1a and compared retrospectively with a matched cohort of 21 infected patients receiving standardized supportive care only during the same time period at the same treatment unit. Cognizant of the limitations of having treated only 9 individuals with EVD, the data collected are cautiously considered. When compared to supportive care only, IFN β-1a treatment seemed to facilitate viral clearance from the blood and appeared associated with earlier resolution of disease symptoms. Survival, calculated from the date of consent for those in the trial and date of admission from those in the control cohort, to the date of death, was 19% for those receiving supportive care only, compared to 67% for those receiving supportive care plus IFN β-1a. Given the differences in baseline blood viremia between the control cohort and the IFN-treated cohort, an additional 17 controls were included for a subset analysis, from other treatment units in Guinea, matched with the IFN-treated patients based on age and baseline blood viremia. Subset analyses using this expanded control cohort suggests that patients without IFN β-1a treatment were ~ 1.5-1.9 fold more likely to die than those treated. Viewed altogether the results suggest a rationale for further clinical evaluation of IFN β-1a.

Background: Ebola virus disease (EVD) is a highly lethal condition for which no specific treatment has proven efficacy. In September 2014, while the Ebola outbreak was at its peak, the World Health Organization released a short list of drugs suitable for EVD research. Favipiravir, an antiviral developed for the treatment of severe influenza, was one of these. In late 2014, the conditions for starting a randomized Ebola trial were not fulfilled for two reasons. One was the perception that, given the high number of patients presenting simultaneously and the very high mortality rate of the disease, it was ethically unacceptable to allocate patients from within the same family or village to receive or not receive an experimental drug, using a randomization process impossible to understand by very sick patients. The other was that, in the context of rumors and distrust of Ebola treatment centers, using a randomized design at the outset might lead even more patients to refuse to seek care. Therefore, we chose to conduct a multicenter non-randomized trial, in which all patients would receive favipiravir along with standardized care. The objectives of the trial were to test the feasibility and acceptability of an emergency trial in the context of a large Ebola outbreak, and to collect data on the safety and effectiveness of favipiravir in reducing mortality and viral load in patients with EVD. The trial was not aimed at directly informing future guidelines on Ebola treatment but at quickly gathering standardized preliminary data to optimize the design of future studies., Methods and Findings: Inclusion criteria were positive Ebola virus reverse transcription PCR (RT-PCR) test, age ≥ 1 y, weight ≥ 10 kg, ability to take oral drugs, and informed consent. All participants received oral favipiravir (day 0: 6,000 mg; day 1 to day 9: 2,400 mg/d). Semi-quantitative Ebola virus RT-PCR (results expressed in "cycle threshold" [Ct]) and biochemistry tests were performed at day 0, day 2, day 4, end of symptoms, day 14, and day 30. Frozen samples were shipped to a reference biosafety level 4 laboratory for RNA viral load measurement using a quantitative reference technique (genome copies/milliliter). Outcomes were mortality, viral load evolution, and adverse events. The analysis was stratified by age and Ct value. A "target value" of mortality was defined a priori for each stratum, to guide the interpretation of interim and final analysis. Between 17 December 2014 and 8 April 2015, 126 patients were included, of whom 111 were analyzed (adults and adolescents, ≥13 y, n = 99; young children, ≤6 y, n = 12). Here we present the results obtained in the 99 adults and adolescents. Of these, 55 had a baseline Ct value ≥ 20 (Group A Ct ≥ 20), and 44 had a baseline Ct value < 20 (Group A Ct < 20). Ct values and RNA viral loads were well correlated, with Ct = 20 corresponding to RNA viral load = 7.7 log10 genome copies/ml. Mortality was 20% (95% CI 11.6%-32.4%) in Group A Ct ≥ 20 and 91% (95% CI 78.8%-91.1%) in Group A Ct < 20. Both mortality 95% CIs included the predefined target value (30% and 85%, respectively). Baseline serum creatinine was ≥110 μmol/l in 48% of patients in Group A Ct ≥ 20 (≥300 μmol/l in 14%) and in 90% of patients in Group A Ct < 20 (≥300 μmol/l in 44%). In Group A Ct ≥ 20, 17% of patients with baseline creatinine ≥110 μmol/l died, versus 97% in Group A Ct < 20. In patients who survived, the mean decrease in viral load was 0.33 log10 copies/ml per day of follow-up. RNA viral load values and mortality were not significantly different between adults starting favipiravir within <72 h of symptoms compared to others. Favipiravir was well tolerated., Conclusions: In the context of an outbreak at its peak, with crowded care centers, randomizing patients to receive either standard care or standard care plus an experimental drug was not felt to be appropriate. We did a non-randomized trial. This trial reaches nuanced conclusions. On the one hand, we do not conclude on the efficacy of the drug, and our conclusions on tolerance, although encouraging, are not as firm as they could have been if we had used randomization. On the other hand, we learned about how to quickly set up and run an Ebola trial, in close relationship with the community and non-governmental organizations; we integrated research into care so that it improved care; and we generated knowledge on EVD that is useful to further research. Our data illustrate the frequency of renal dysfunction and the powerful prognostic value of low Ct values. They suggest that drug trials in EVD should systematically stratify analyses by baseline Ct value, as a surrogate of viral load. They also suggest that favipiravir monotherapy merits further study in patients with medium to high viremia, but not in those with very high viremia., Trial Registration: ClinicalTrials.gov NCT02329054., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: SB, XdL, HR, and SG received a grant from St Luke International University (Tokyo, Japan) to perform research on favipiravir in non-human primates. YY declared board membership for AbbVie, BMS, Gilead, MSD, Roche, Johnson&Johnson, ViiV Healthcare, Pfizer, and consultancy for AbbVie, BMS, Gilead, MSD, Roche, Johnson&Johnson, ViiV Healthcare, and Pfizer. OP worked for Fab'entech biotechnology from 1st April to 13th November 2015. Between January 2014 and now, SC received a grant from the CHU de Québec research center, which had no relationship with the trial described in the paper. All other authors declared no conflict of interest.

Introduction: In 2010, the Ministry of Health (MoH) of Guinea introduced a free emergency obstetric care policy in all the public health facilities of the country. This included antenatal checks, normal delivery and Caesarean section., Objective: This study aims at assessing the changes in coverage of obstetric care according to the Unmet Obstetric Need concept before (2008) and after (2012) the implementation of the free emergency obstetric care policy in a rural health district in Guinea., Methods: We carried out a descriptive cross-sectional study involving the retrospective review of routine programme data during the period April to June 2014., Results: No statistical difference was observed in women's sociodemographic characteristics and indications (absolute maternal indications versus non-absolute maternal indications) before and after the implementation of the policy. Compared to referrals from health centers of patients, direct admissions at hospital significantly increased from 49% to 66% between 2008 and 2012 (p = 0.001). In rural areas, this increase concerned all maternal complications regardless of their severity, while in urban areas it mainly affected very severe complications. Compared to 2008, there were significantly more Major Obstetric Interventions for Maternal Absolute Indications in 2012 (p < 0.001). Maternal deaths decreased between 2008 and 2012 from 1.5% to 1.1% while neonatal death increased from 12% in 2008 to 15% in 2012., Conclusion: The implementation of the free obstetric care policy led to a significant decrease in unmet obstetric need between 2008 and 2012 in the health district of Kissidougou. However, more research is needed to allow comparisons with other health districts in the country and to analyse the trends.

Activation of proteolytic cell death pathways may circumvent drug resistance in deadly protozoan parasites such as Plasmodium falciparum and Leishmania. To this end, it is important to define the cell death pathway(s) in parasites and thus characterize proteases such as metacaspases (MCA), which have been reported to induce cell death in plants and Leishmania parasites. We, therefore, investigated whether the cell death function of MCA is conserved in different protozoan parasite species such as Plasmodium falciparum and Leishmania major, focusing on the substrate specificity and functional role in cell survival as compared to Saccharomyces cerevisae. Our results show that, similarly to Leishmania, Plasmodium MCA exhibits a calcium-dependent, arginine-specific protease activity and its expression in yeast induced growth inhibition as well as an 82% increase in cell death under oxidative stress, a situation encountered by parasites during the host or when exposed to drugs such as artemisins. Furthermore, we show that MCA cell death pathways in both Plasmodium and Leishmania, involve a z-VAD-fmk inhibitable protease. Our data provide evidence that MCA from both Leishmania and Plasmodium falciparum is able to induce cell death in stress conditions, where it specifically activates a downstream enzyme as part of a cell death pathway. This enzymatic activity is also induced by the antimalarial drug chloroquine in erythrocytic stages of Plasmodium falciparum. Interestingly, we found that blocking parasite cell death influences their drug sensitivity, a result which could be used to create therapeutic strategies that by-pass drug resistance mechanisms by acting directly on the innate pathways of protozoan cell death.