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

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

High-Throughput Compatibility Screening of Materials for SF6-Alternative Insulation.

With the annual global electricity production exceeding 30,000 TWh, the safe transmission of electric power has been heavily relying on SF6, the most potent industrial greenhouse gas. While promising SF6 alternatives have been proposed, their compatibilities with materials used in gas-insulated equipment (GIE) must be thoroughly studied. This is particularly true as the emerging SF6 alternatives generally leverage their relatively higher reactivity to achieve lower global warming potentials (GWPs). Here, a high-throughput compatibility screening of common GIE materials was conducted with a representative SF6 alternative, namely, C4F7N (2,3,3,3-tetrafluoro-2-(trifluoromethyl)propanenitrile)/CO2 gas mixtures. In this screening, the insulation performance of C4F7N/CO2 gas mixtures, as an indicator of the C4F7N/materials compatibility level, was periodically monitored during the thermal aging with tens of materials from SF6-insulated GIE, including desiccants/adsorbents, rubber, plastics, composites, ceramics, metals, etc. The identification of incompatible materials and the follow-up mechanism studies suggested that the acidity of materials represents the primary cause for C4F7N/materials incompatibility when C4F7N/CO2 gas mixtures are used as a drop-in replacement solution for existing SF6-insulated apparatuses. Mitigation strategies tackling the acidity of materials were then proposed and validated. Additionally, the amphoteric characteristics of C4F7N were briefly discussed. This work provides insight into the materials incompatibility of SF6 alternatives, along with validated mitigation strategies, for the selection and design of materials used in future eco-friendly GIE.

Factors associated with contraceptive use among adolescents in three regions of Senegal.

The study aimed to evaluate the use of contraception by adolescents aged 10 to 19 years in three municipalities of Senegal, as well as the associated factors. The study was conducted in 2022 and used a cross-sectional approach. The sample size was 940 participants. Sampling was done using a multistage stratified random sampling method. The chi-square test and logistic regression using R software version 4.2.1 were used to analyze the data. Only 2.2% of adolescents had ever used a contraceptive method. Adolescents aged 15 to 19 years, those residing in Kolda, married adolescents, and those who were aware of family planning were more likely to use family planning methods. We conclude that policymakers in Senegal should implement policies and programmes for improving the reproductive health needs of adolescents in Senegal.

L'étude consistait à évaluer l'utilisation de la contraception par les adolescentes âgées de 10 à 19 ans dans trois communes du Sénégal, ainsi que les facteurs qui y sont associés. L'étude menée en 2022 a utilisé l'approche transversale. La taille de l'échantillon était de 940 participants. L'échantillonnage a été réalisé en utilisant une méthode de sondage aléatoire stratifié à plusieurs degrés. Le test de chi-carré et la régression logistique au moyen du logiciel R version 4.2.1 ont été utilisé pour analyser les données. Seulement 2,2% des adolescentes avaient utilisé une méthode contraceptive. Les adolescentes âgées de 15 à 19 ans, celles qui résident à Kolda, les adolescentes mariées étaient plus nombreuses et celles qui ont été sensibilisée à la planification familiale étaient plus nombreuses que les autres à utiliser les méthodes de planification familiale. Ainsi, il est nécessaire que les autorités améliorent la mise en œuvre des programmes axés sur les besoins de santé reproductive des adolescentes au Sénégal.

Analysis of care for adolescent victims of gender-based violence in Senegal: a qualitative study.

In Senegal, many adolescent victims of gender-based violence (GBV) do not receive care. The aim of this study was to analyse the care circuit for adolescent victims of GBV, taking gender differences into account. This was a qualitative case study. A thematic analysis of the data was carried out using Nvivo 12 software. The study showed that society attached less importance to the rape of boys. The study also showed that the main attitude of adolescents to GBV was silence, encouraged by under-reporting. The structural barriers to providing care were the insensitivity of health and judicial structures towards adolescents, as well as geographical and financial obstacles. In conclusion, it is important for policies to tackle these structural barriers in order to promote a system of care suited to cases of GBV among adolescents.

Au Sénégal, de nombreux adolescents victimes de violences basées sur le genre ne sont pas pris en charge. L'objectif de cette étude est d'analyser le circuit de prise en charge des adolescent(es) victimes de VBG en tenant compte des différences de genre. Il s'agissait d'une étude qualitative de type étude de cas. Une analyse thématique des données avait été faite avec le logiciel Nvivo 12. L'étude a montré que la société accordait peu d'importance aux viols des garçons. L'étude a également montré que la principale attitude des adolescents face aux VBG était le silence, favorisant la sous-dénonciation. Les barrières structurelles à la prise en charge étaient l'insensibilité des structures sanitaires et judiciaires envers les adolescents, ainsi que les obstacles géographiques et financières. En conclusion, il est important que les politiques s'attaquent à ces barrières structurelles pour promouvoir un système de prise en charge adapté aux cas de VBG chez les adolescents.

Knowledge and practice of health workers on sexual and reproductive health and rights and gender-based violence: Evidence from three municipalities in Senegal.

Adolescents in low- and middle-income countries face numerous developmental, sexual and reproductive health (SRHR) challenges, including exposure to multidimensional violence. Dealing with gender-based violence (GBV) is of great importance and health personnel are key players. The objective of this work was to study the knowledge and practices of health personnel on SRHR and gender-based violence in Guédiawaye, Kaolack and Kolda communities in Senegal. A descriptive and analytical cross-sectional study was conducted, which consisted of health professionals (general practitioners and specialists, nurses, and midwives) and community health workers (community relays, bajenu gox, matrons). All health facilities in the three communities were included. Data analysis consisted of univariate analysis and logistic regression modeling to investigate the factors associated with the knowledge and practice of health personnels. An alpha risk of 5% was taken. A total of 78 health professionals and 128 community actors were included in the study. More than half of the health personnel (56.3%) had good knowledge of policies, standards and protocols relating to sexual and reproductive health services for women (adolescents) and about 60% on conventions and laws. The level of knowledge was good among 51% of respondents and good practices among 54.9%. The factors associated with good knowledge were the municipality in which the profession was practiced, and the effects of training received in the social construction of gender. The factors associated with the practices were knowledge of policies, standards and protocols through training, training received in the provision of family planning services, and in medico-psychosocial management of cases of sexual violence. We conclude that the knowledge of stakeholders (health professionals and community health workers) about sexual and reproductive health and gender-based violence is important for better service provision and good management of cases of gender based violence.

Les adolescents des pays à revenu faible et moyen (PRFM) sont confrontés à de nombreux défis en matière de développement, de santé sexuelle et reproductive (SSR), notamment l'exposition à une violence multidimensionnelle. La prise en charge des violences de genre est d'une grande importance et le personnel de santé en constituent des acteurs clés. L'objectif de ce travail était d'étudier les connaissances et les pratiques du personnel de santé sur la santé sexuelle et reproductive (SSR) et les violences basées sur le genre dans les communes de Guédiawaye, Kaolack et Kolda au Sénégal. Une étude transversale descriptive et analytique a été menée. La population était constituée des professionnels de santé (médecins généralistes et spécialistes, infirmiers, sages-femmes) et des agents de santé communautaires (relais communautaires, bajénu gox, matrones). L'ensemble des structures de santé des trois communes ont été inclus avec un choix raisonné des cibles. Une analyse univariée une modélisation par une régression logistique a été effectuée pour rechercher les facteurs associés à la connaissance et la pratique du personnel de santé. Un risque alpha de 5% a été pris. Au total 78 professionnels de santé et 128 acteurs communautaires ont été inclus dans cette étude. Plus de la moitié du personnel de santé (56,3%) avaient une bonne connaissance des politiques, normes et protocoles (PNP) des services de santé sexuelle et reproductive des femmes (adolescentes) et environ 60% sur les conventions et Lois. Le niveau de connaissance était bon chez 51% des enquêtés et les pratiques bonnes chez 54,9%. Les facteurs associés à la bonne connaissance étaient la commune d'exercice de la profession, le fait de bénéficier d'une formation en construction sociale du genre. Les facteurs associés aux pratiques étaient la connaissance des PNP à travers la formation, les formations reçues en offre de services PF et contraception d'urgence, en prise en charge médico-psychosociale des cas de violences sexuelles. En conclusion, la connaissance des acteurs (professionnels de santé, agents de sante communautaires) sur la santé sexuelle et reproductive et les violences basées sur le genre est importante pour une meilleure offre de service et une bonne prise en charge des cas de violences. (Afr J Reprod Health 2024; 28 [8s]: 163-175).

Ex vivo RSA and pfkelch13 targeted-amplicon deep sequencing reveal parasites susceptibility to artemisinin in Senegal, 2017.

BACKGROUND: Malaria control is highly dependent on the effectiveness of artemisinin-based combination therapy (ACT), the current frontline malaria curative treatment. Unfortunately, the emergence and spread of parasites resistant to artemisinin (ART) derivatives in Southeast Asia and South America, and more recently in Rwanda and Uganda (East Africa), compromise their long-term use in sub-Saharan Africa, where most malaria deaths occur. METHODS: Here, ex vivo susceptibility to dihydroartemisinin (DHA) was evaluated from 38 Plasmodium falciparum isolates collected in 2017 in Thiès (Senegal) expressed in the Ring-stage Survival Assay (RSA). Both major and minor variants were explored in the three conserved-encoding domains of the pfkelch13 gene, the main determinant of ART resistance using a targeted-amplicon deep sequencing (TADS) approach. RESULTS: All samples tested in the ex vivo RSA were found to be susceptible to DHA (parasite survival rate < 1%). The non-synonymous mutations K189T and K248R in pfkelch13 were observed each in one isolate, as major (99%) or minor (5%) variants, respectively. CONCLUSION: The results suggest that ART is still fully effective in the Thiès region of Senegal in 2017. Investigations combining ex vivo RSA and TADS are a useful approach for monitoring ART resistance in Africa.

Genomic investigation of atypical malaria cases in Kanel, northern Senegal.

BACKGROUND: The diagnosis of malaria cases in regions where the malaria burden has decreased significantly and prevalence is very low is more challenging, in part because of reduced clinical presumption of malaria. The appearance of a cluster of malaria cases with atypical symptoms in Mbounguiel, a village in northern Senegal where malaria transmission is low, in September 2018 exemplifies this scenario. The collaboration between the National Malaria Control Programme (NMCP) at the Senegal Ministry of Health and the Laboratory of Parasitology and Mycology at Cheikh Anta Diop University worked together to evaluate this cluster of malaria cases using molecular and serological tools. METHODS: Malaria cases were diagnosed primarily by rapid diagnostic test (RDT), and confirmed by photo-induced electron transfer-polymerase chain reaction (PET-PCR). 24 single nucleotide polymorphisms (SNPs) barcoding was used for Plasmodium falciparum genotyping. Unbiased metagenomic sequencing and Luminex-based multi-pathogen antibody and antigen profiling were used to assess exposure to other pathogens. RESULTS: Nine patients, of 15 suspected cases, were evaluated, and all nine samples were found to be positive for P. falciparum only. The 24 SNPs molecular barcode showed the predominance of polygenomic infections, with identifiable strains being different from one another. All patients tested positive for the P. falciparum antigens. No other pathogenic infection was detected by either the serological panel or metagenomic sequencing. CONCLUSIONS: This work, undertaken locally within Senegal as a collaboration between the NMCP and a research laboratory at University of Cheikh Anta Diop (UCAD) revealed that a cluster of malaria cases were caused by different strains of P. falciparum. The public health response in real time demonstrates the value of local molecular and genomics capacity in affected countries for disease control and elimination.

Molecular epidemiology of Plasmodium falciparum by multiplexed amplicon deep sequencing in Senegal.

BACKGROUND: Molecular epidemiology can provide important information regarding the genetic diversity and transmission of Plasmodium falciparum, which can assist in designing and monitoring elimination efforts. However, malaria molecular epidemiology including understanding the genetic diversity of the parasite and performing molecular surveillance of transmission has been poorly documented in Senegal. Next Generation Sequencing (NGS) offers a practical, fast and high-throughput approach to understand malaria population genetics. This study aims to unravel the population structure of P. falciparum and to estimate the allelic diversity, multiplicity of infection (MOI), and evolutionary patterns of the malaria parasite using the NGS platform. METHODS: Multiplex amplicon deep sequencing of merozoite surface protein 1 (PfMSP1) and merozoite surface protein 2 (PfMSP2) in fifty-three P. falciparum isolates from two epidemiologically different areas in the South and North of Senegal, was carried out. RESULTS: A total of 76 Pfmsp1 and 116 Pfmsp2 clones were identified and 135 different alleles were found, 56 and 79 belonged to the pfmsp1 and pfmsp2 genes, respectively. K1 and IC3D7 allelic families were most predominant in both sites. The local haplotype diversity (Hd) and nucleotide diversity (π) were higher in the South than in the North for both genes. For pfmsp1, a high positive Tajima's D (TD) value was observed in the South (D = 2.0453) while negative TD value was recorded in the North (D = - 1.46045) and F-Statistic (Fst) was 0.19505. For pfmsp2, non-directional selection was found with a highly positive TD test in both areas and Fst was 0.02111. The mean MOI for both genes was 3.07 and 1.76 for the South and the North, respectively, with a statistically significant difference between areas (p = 0.001). CONCLUSION: This study revealed a high genetic diversity of pfmsp1 and pfmsp2 genes and low genetic differentiation in P. falciparum population in Senegal. The MOI means were significantly different between the Southern and Northern areas. Findings also showed that multiplexed amplicon deep sequencing is a useful technique to investigate genetic diversity and molecular epidemiology of P. falciparum infections.

Amplicon deep sequencing of kelch13 in Plasmodium falciparum isolates from Senegal.

BACKGROUND: In 2006, the Senegalese National Malaria Control Programme recommended artemisinin-based combination therapy (ACT) with artemether-lumefantrine as the first-line treatment for uncomplicated Plasmodium falciparum malaria. To date, multiple mutations associated with artemisinin delayed parasite clearance have been described in Southeast Asia in the Pfk13 gene, such as Y493H, R539T, I543T and C580Y. Even though ACT remains clinically and parasitologically efficacious in Senegal, the spread of resistance is possible as shown by the earlier emergence of resistance to chloroquine in Southeast Asia that subsequently spread to Africa. Therefore, surveillance of artemisinin resistance in malaria endemic regions is crucial and requires the implementation of sensitive tools, such as next-generation sequencing (NGS) which can detect novel mutations at low frequency. METHODS: Here, an amplicon sequencing approach was used to identify mutations in the Pfk13 gene in eighty-one P. falciparum isolates collected from three different regions of Senegal. RESULTS: In total, 10 SNPs around the propeller domain were identified; one synonymous SNP and nine non-synonymous SNPs, and two insertions. Three of these SNPs (T478T, A578S and V637I) were located in the propeller domain. A578S, is the most frequent mutation observed in Africa, but has not previously been reported in Senegal. A previous study has suggested that A578S could disrupt the function of the Pfk13 propeller region. CONCLUSION: As the genetic basis of possible artemisinin resistance may be distinct in Africa and Southeast Asia, further studies are necessary to assess the new SNPs reported in this study.

Safety and Immunogenicity of a Heterologous Prime-Boost Ebola Virus Vaccine Regimen in Healthy Adults in the United Kingdom and Senegal.

BACKGROUND: The 2014 West African outbreak of Ebola virus disease highlighted the urgent need to develop an effective Ebola vaccine. METHODS: We undertook 2 phase 1 studies assessing safety and immunogenicity of the viral vector modified vaccinia Ankara virus vectored Ebola Zaire vaccine (MVA-EBO-Z), manufactured rapidly on a new duck cell line either alone or in a heterologous prime-boost regimen with recombinant chimpanzee adenovirus type 3 vectored Ebola Zaire vaccine (ChAd3-EBO-Z) followed by MVA-EBO-Z. Adult volunteers in the United Kingdom (n = 38) and Senegal (n = 40) were vaccinated and an accelerated 1-week prime-boost regimen was assessed in Senegal. Safety was assessed by active and passive collection of local and systemic adverse events. RESULTS: The standard and accelerated heterologous prime-boost regimens were well-tolerated and elicited potent cellular and humoral immunogenicity in the United Kingdom and Senegal, but vaccine-induced antibody responses were significantly lower in Senegal. Cellular immune responses measured by flow cytometry were significantly greater in African vaccinees receiving ChAd3 and MVA vaccines in the same rather than the contralateral limb. CONCLUSIONS: MVA biomanufactured on an immortalized duck cell line shows potential for very large-scale manufacturing with lower cost of goods. This first trial of MVA-EBO-Z in humans encourages further testing in phase 2 studies, with the 1-week prime-boost interval regimen appearing to be particularly suitable for outbreak control. CLINICAL TRIALS REGISTRATION: NCT02451891; NCT02485912.

Ex vivo susceptibility and genotyping of Plasmodium falciparum isolates from Pikine, Senegal.

BACKGROUND: The monitoring of Plasmodium falciparum sensitivity to anti-malarial drugs is a necessity for effective case management of malaria. This species is characterized by a strong resistance to anti-malarial drugs. In Senegal, the first cases of chloroquine resistance were reported in the Dakar region in 1988 with nearly 7% population prevalence, reaching 47% by 1990. It is in this context that sulfadoxine-pyrimethamine temporarily replaced chloroquine as first line treatment in 2003, pending the introduction of artemisinin-based combination therapy in 2006. The purpose of this study is to assess the ex vivo sensitivity to different anti-malarial drugs of the P. falciparum population from Pikine. METHODS: Fifty-four samples were collected from patients with non-complicated malaria and aged between 2 and 20 years in the Deggo health centre in Pikine in 2014. An assay in which parasites are stained with 4', 6-di-amidino-2-phenylindole (DAPI), was used to study the ex vivo sensitivity of isolates to chloroquine, amodiaquine, piperaquine, pyrimethamine, and dihydroartemisinin. High resolution melting was used for genotyping of pfdhps, pfdhfr, pfmdr1, and pfcrt genes. RESULTS: The mean IC50s of chloroquine, amodiaquine, piperaquine, dihydroartemisinin, and pyrimethamine were, respectively, 39.44, 54.02, 15.28, 2.23, and 64.70 nM. Resistance mutations in pfdhfr gene, in codon 437 of pfdhps gene, and an absence of mutation at position 540 of pfdhps were observed. Mutations in codons K76T of pfcrt and N86Y of pfmdr1 were observed at 51 and 11% population prevalence, respectively. A relationship was found between the K76T and N86Y mutations and ex vivo resistance to chloroquine. CONCLUSION: An increase in sensitivity of isolates to chloroquine was observed. A high sensitivity to dihydroartemisinin was observed; whereas, a decrease in sensitivity to pyrimethamine was observed in the parasite population from Pikine.

High resolution melting: a useful field-deployable method to measure dhfr and dhps drug resistance in both highly and lowly endemic Plasmodium populations.

BACKGROUND: Emergence and spread of drug resistance to every anti-malarial used to date, creates an urgent need for development of sensitive, specific and field-deployable molecular tools for detection and surveillance of validated drug resistance markers. Such tools would allow early detection of mutations in resistance loci. The aim of this study was to compare common population signatures and drug resistance marker frequencies between two populations with different levels of malaria endemicity and history of anti-malarial drug use: Tanzania and Sénégal. This was accomplished by implementing a high resolution melting assay to study molecular markers of drug resistance as compared to polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) methodology. METHODS: Fifty blood samples were collected each from a lowly malaria endemic site (Sénégal), and a highly malaria endemic site (Tanzania) from patients presenting with uncomplicated Plasmodium falciparum malaria at clinic. Data representing the DHFR were derived using both PCR-RFLP and HRM assay; while genotyping data representing the DHPS were evaluated in Senegal and Tanzania using HRM. Msp genotyping analysis was used to characterize the multiplicity of infection in both countries. RESULTS: A high prevalence of samples harbouring mutant DHFR alleles was observed in both population using both genotyping techniques. HRM was better able to detect mixed alleles compared to PCR/RFLP for DHFR codon 51 in Tanzania; and only HRM was able to detect mixed infections from Senegal. A high prevalence of mutant alleles in DHFR (codons 51, 59, 108) and DHPS (codon 437) were found among samples from Sénégal while no mutations were observed at DHPS codons 540 and 581, from both countries. Overall, the frequency of samples harbouring either a single DHFR mutation (S108N) or double mutation in DHFR (C59R/S108N) was greater in Sénégal compared to Tanzania. CONCLUSION: Here the results demonstrate that HRM is a rapid, sensitive, and field-deployable alternative technique to PCR-RFLP genotyping that is useful in populations harbouring more than one parasite genome (polygenomic infections). In this study, a high levels of resistance polymorphisms was observed in both dhfr and dhps, among samples from Tanzania and Sénégal. A routine monitoring by molecular markers can be a way to detect emergence of resistance involving a change in the treatment policy.

Selection of N86F184D1246 haplotype of Pfmrd1 gene by artemether-lumefantrine drug pressure on Plasmodium falciparum populations in Senegal.

BACKGROUND: The use of artemisinin as a monotherapy resulted in the emergence of artemisinin resistance in 2005 in Southeast Asia. Monitoring of artemisinin combination therapy (ACT) is critical in order to detect and prevent the spread of resistance in endemic areas. Ex vivo studies and genotyping of molecular markers of resistance can be used as part of this routine monitoring strategy. One gene that has been associated in some ACT partner drug resistance is the Plasmodium falciparum multidrug resistance protein 1 (pfmdr1) gene. The purpose of this study was to assess the drug susceptibility of P. falciparum populations from Thiès, Senegal by ex vivo assay and typing molecular markers of resistance to drug components of ACT currently used for treatment. METHODS: The ex vivo susceptibility of 170 P. falciparum isolates to chloroquine, amodiaquine, lumefantrine, artesunate, and artemether was determined using the DAPI ex vivo assay. The high resolution melting technique was used to genotype the pfmdr1 gene at codons 86, 184 and 1246. RESULTS: A significant decrease in IC50 values was observed between 2012 and 2013: from 13.84 to 6.484 for amodiaquine, 173.4 to 113.2 for lumefantrine, and 39.72 to 18.29 for chloroquine, respectively. Increase of the wild haplotype NYD and the decrease of the mutant haplotype NFD (79 and 62.26 %) was also observed. A correlation was observed between the wild type allele Y184 in pfmdr1 and higher IC50 for all drugs, except amodiaquine. CONCLUSION: This study has shown an increase in sensitivity over the span of two transmission seasons, marked by an increase in the WT alleles at pfmdr1. Continuous the monitoring of the ACT used for treatment of uncomplicated malaria will be helpful.

Factors associated with diabetes knowledge, attitudes and practices among people aged 18 and over in the commune of Niakhene in Senegal.

More than 422 million people worldwide have diabetes in 2016, and 1.6 million deaths are attributed to diabetes each year. Knowledge of preventive measures would enable the adjustment of preventive policies. Hence this study on knowledge and practices in rural Senegal. This was a cross-sectional, descriptive and analytical survey of subjects aged at least 18 and living in the commune of Niakhene, carried out in October 2020. A systematic random sample, stratified by sex and age group, was used. The questionnaire was based on the STEPS 2015 tool and a review of the literature. In addition to personal characteristics, the questionnaire was used to measure knowledge of symptoms, complications, risk factors, attitude to the disease and screening practices. Descriptive and analytical analyses were performed using R 4.0.2 software. A total of 300 subjects were surveyed. The average age was 35.3 years (+/-16.9), and 52.3% were women. Knowledge (62.7%) was associated with higher education (ORaj2.46{1.16-3.44}), awareness by healthcare staff (ORaj2.88{1.60-5.34}), and a family history of diabetes (ORaj3.09{1.06-11.3}). The positive attitude (53%) was associated with male sex (ORaj1.98{2.07-7.52}), awareness via audio-visual information sources (ORaj3.87{2.07-7.52}), community awareness (ORaj 3.87{2.07-7.52}), existence of a family history of hypertension and knowledge of diabetes (ORaj3.34{2.5-7.69}). Screening was carried out in 34.3% of patients. The associated risk factors were male sex (ORaj 1.95{1.12-3.34}), higher education (ORaj2.49{1.12-559}) and positive attitudes to diabetes (ORaj1.83{1.04-3.26}). One of the most effective interventions against this disease is the adoption of preventive measures which involve early detection and strengthening communication for more effective prevention.

Perceptions, facilitators and barriers to the implementation of interpersonal group therapy to treat depression among people living with HIV in Senegal: a qualitative study.

Background: Depression is highly prevalent in people living with HIV (PLWH) but remains under treated in Sub-Saharan Africa. In this context, we conducted the first study of Group Interpersonal Therapy (IPT) to treat depression in PLWH in Senegal. We assessed the perceptions and experiences of patients and group facilitators, as well as barriers to implementation. Methods: This study was conducted at the Fann National University Hospital Center in Dakar, the urban capital of Senegal. Qualitative data were collected during the implementation phase (February to June 2020 and then from January to February 2021), with a 6-month pause due to the COVID-19 pandemic. Twenty-five patients and three group facilitators were individually interviewed by a socio-anthropologist. Qualitative data were analyzed thematically. Results: Group IPT was perceived as successful and beneficial by patients and facilitators. Patients reported positive experiences with group IPT and sustained outcomes. Beyond improving depressive symptoms, patients reported improvements in their social and professional lives, and the development of skills to prevent relapse. Group facilitators noted the benefits of therapy for their patients and for their professional skills, reporting greater clinical competence and improved supportive skills. Challenges to intervention implementation included confidentiality and patient privacy concerns, healthcare accessibility issues, and time demands. Conclusion: In this first qualitative study of group IPT for depression in PLWH in Senegal, participants described both positive experiences with the intervention and challenges to its implementation. Future studies, conducted in suburban and rural communities outside of Dakar, would further inform the implementation of IPT in Senegal.

Investigating the etiologies of non-malarial febrile illness in Senegal using metagenomic sequencing.

The worldwide decline in malaria incidence is revealing the extensive burden of non-malarial febrile illness (NMFI), which remains poorly understood and difficult to diagnose. To characterize NMFI in Senegal, we collected venous blood and clinical metadata in a cross-sectional study of febrile patients and healthy controls in a low malaria burden area. Using 16S and untargeted sequencing, we detected viral, bacterial, or eukaryotic pathogens in 23% (38/163) of NMFI cases. Bacteria were the most common, with relapsing fever Borrelia and spotted fever Rickettsia found in 15.5% and 3.8% of cases, respectively. Four viral pathogens were found in a total of 7 febrile cases (3.5%). Sequencing also detected undiagnosed Plasmodium, including one putative P. ovale infection. We developed a logistic regression model that can distinguish Borrelia from NMFIs with similar presentation based on symptoms and vital signs (F1 score: 0.823). These results highlight the challenge and importance of improved diagnostics, especially for Borrelia, to support diagnosis and surveillance.

Two mosquito salivary antigens demonstrate promise as biomarkers of recent exposure to P. falciparum infected mosquito bites.

Background: Measuring malaria transmission intensity using the traditional entomological inoculation rate is difficult. Antibody responses to mosquito salivary proteins such as SG6 have previously been used as biomarkers of exposure to Anopheles mosquito bites. Here, we investigate four mosquito salivary proteins as potential biomarkers of human exposure to mosquitoes infected with P. falciparum: mosGILT, SAMSP1, AgSAP, and AgTRIO. Methods: We tested population-level human immune responses in longitudinal and cross-sectional plasma samples from individuals with known P. falciparum infection from low and moderate transmission areas in Senegal using a multiplexed magnetic bead-based assay. Results: AgSAP and AgTRIO were the best indicators of recent exposure to infected mosquitoes. Antibody responses to AgSAP, in a moderate endemic area, and to AgTRIO in both low and moderate endemic areas, were significantly higher than responses in a healthy non-endemic control cohort (p-values = 0.0245, 0.0064, and <0.0001 respectively). No antibody responses significantly differed between the low and moderate transmission area, or between equivalent groups during and outside the malaria transmission seasons. For AgSAP and AgTRIO, reactivity peaked 2-4 weeks after clinical P. falciparum infection and declined 3 months after infection. Discussion: Reactivity to both AgSAP and AgTRIO peaked after infection and did not differ seasonally nor between areas of low and moderate transmission, suggesting reactivity is likely reflective of exposure to infectious mosquitos or recent biting rather than general mosquito exposure. Kinetics suggest reactivity is relatively short-lived. AgSAP and AgTRIO are promising candidates to incorporate into multiplexed assays for serosurveillance of population-level changes in P. falciparum-infected mosquito exposure.

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.

HIV-1 genetic diversity and drug resistance among Senegalese patients in the public health system.

In this study, we investigated the prevalence of human immunodeficiency virus type 1 (HIV-1) drug resistance mutations and genetic variability among Senegalese patients undergoing highly active antiretroviral therapy (ART) in the public health system. We conducted a cross-sectional study of 72 patients with suspected therapeutic failure. HIV-1 genotyping was performed with Viroseq HIV-1 Genotyping System v2.0 or the procedure developed by the ANRS AC11 resistance study group, and a phylogenetic analysis was performed. The median follow-up visit was at 40 (range, 12 to 123) months, and the median viral load was 4.67 (range, 3.13 to 6.94) log(10) copies/ml. The first-line therapeutic regimen was nucleoside reverse transcriptase inhibitors (NRTIs) plus efavirenz (EFV) or NRTIs plus nevirapine (NVP) (54/72 patients; 75%), and the second-line therapy was NRTIs plus a protease inhibitor (PI/r) (18/72; 25%). Fifty-five patients (55/72; 76.39%) had at least one drug resistance mutation. The drug resistance rates were 72.22 and 88.89% for the first-line and second-line ARTs, respectively. In NRTI mutations, thymidine analog mutations (TAMs) were found in 50.79% and the M184V mutation was found in 34.92% of the samples. For non-NRTI resistance, we noted a predominance of the K103N mutation (46.27%). For PI/r, several cases of mutations were found with a predominance of M46I and L76V/F at 24% each. The phylogenetic analysis revealed CRF02_AG as the predominant circulating recombinant form (43/72; 59.72%). We found a high prevalence of resistance mutations and a high rate of TAMs among Senegalese patients in the public health system. These findings emphasize the need to improve virological monitoring in resource-limited settings.

Global stability of reversible enzymatic metabolic chains.

We consider metabolic networks with reversible enzymatic reactions. The model is written as a system of ordinary differential equations, possibly with inputs and outputs. We prove the global stability of the equilibrium (if it exists), using techniques of monotone systems and compartmental matrices. We show that the equilibrium does not always exist. Finally, we consider a metabolic system coupled with a genetic network, and we study the dependence of the metabolic equilibrium (if it exists) with respect to concentrations of enzymes. We give some conclusions concerning the dynamical behavior of coupled genetic/metabolic systems.