RÉSUMÉ
Rift Valley fever (RVF) is a re-emerging vector-borne zoonosis with a high public health and veterinary impact. In West Africa, many lineages were previously detected, but since 2020, lineage H from South Africa has been the main cause of the outbreaks. In this study, clinical samples collected through national surveillance were screened for RVF virus (RVFV) acute infection by RT-PCR and IgM ELISA tests. Sequencing, genome mapping and in vitro phenotypic characterization in mammal cells were performed on RT-PCR positive samples in comparison with other epidemic lineages (G and C). Four RVFV human cases were detected in Senegal and the sequence analyses revealed that the strains belonged to lineage H. The in vitro kinetics and genome mapping showed different replication efficiency profiles for the tested RVFV lineages and non-conservative mutations, which were more common to lineage G or specific to lineage H. Our findings showed the re-emergence of lineage H in Senegal in 2022, its high viral replication efficiency in vitro and support the findings that genetic diversity affects viral replication. This study gives new insights into the biological properties of lineage H and calls for deeper studies to better assess its potential to cause a future threat in Senegal.
Sujet(s)
Génome viral , Phylogenèse , Fièvre de la Vallée du Rift , Virus de la fièvre de la vallée du Rift , Réplication virale , Virus de la fièvre de la vallée du Rift/génétique , Virus de la fièvre de la vallée du Rift/isolement et purification , Virus de la fièvre de la vallée du Rift/classification , Virus de la fièvre de la vallée du Rift/physiologie , Fièvre de la Vallée du Rift/virologie , Fièvre de la Vallée du Rift/épidémiologie , Fièvre de la Vallée du Rift/transmission , Sénégal/épidémiologie , Humains , Animaux , Maladies transmissibles émergentes/virologie , Maladies transmissibles émergentes/épidémiologie , Maladies transmissibles émergentes/médecine vétérinaire , Épidémies de maladies , Afrique de l'Ouest/épidémiologie , Variation génétique , MutationRÉSUMÉ
Dengue virus is becoming a major public health threat worldwide, principally in Africa. From 2016 to 2020, 23 outbreaks were reported in Africa, principally in West Africa. In Senegal, dengue outbreaks have been reported yearly since 2017. Data about the circulating serotypes and their spatial and temporal distribution were limited to outbreaks that occurred between 2017 and 2018. Herein, we describe up-to-date molecular surveillance of circulating DENV serotypes in Senegal between 2019 to 2023 and their temporal and spatial distribution around the country. For this purpose, suspected DENV-positive samples were collected and subjected to dengue detection and serotyping using RT-qPCR methods. Positive samples were used for temporal and spatial mapping. A subset of DENV+ samples were then sequenced and subjected to phylogenetic analysis. Results show a co-circulation of three DENV serotypes with an overall predominance of DENV-3. In terms of abundance, DENV-3 is followed by DENV-1, with scarce cases of DENV-2 from February 2019 to February 2022. Interestingly, data show the extinction of both serotype 1 and serotype 2 and the only circulation of DENV-3 from March 2022 to February 2023. At the genotype level, the analysis shows that sequenced strains belong to same genotype as previously described: Senegalese DENV-1 strains belong to genotype V, DENV-2 strains to the cosmopolitan genotype, and DENV-3 strains to Genotype III. Interestingly, newly obtained DENV 1-3 sequences clustered in different clades within genotypes. This co-circulation of strains belonging to different clades could have an effect on virus epidemiology and transmission dynamics. Overall, our results highlight DENV serotype replacement by DENV-3, accompanied by a wider geographic distribution, in Senegal. These results highlight the importance of virus genomic surveillance and call for further viral fitness studies using both in vitro and in vivo models, as well as in-depth phylogeographic studies to uncover the virus dispersal patterns across the country.
RÉSUMÉ
This work addresses the problem of supervised classification for highly correlated high-dimensional data describing non-independent observations to identify SNPs related to a phenotype. We use a general penalized linear mixed model with a single random effect that performs simultaneous SNP selection and population structure adjustment in high-dimensional prediction models. Specifically, the model simultaneously selects variables and estimates their effects, taking into account correlations between individuals. Single nucleotide polymorphisms (SNPs) are a type of genetic variation and each SNP represents a difference in a single DNA building block, namely a nucleotide. Previous research has shown that SNPs can be used to identify the correct source population of an individual and can act in isolation or simultaneously to impact a phenotype. In this regard, the study of the contribution of genetics in infectious disease phenotypes is of great importance. In this study, we used uncorrelated variables from the construction of blocks of correlated variables done in a previous work to describe the most related observations of the dataset. The model was trained with 90% of the observations and tested with the remaining 10%. The best model obtained with the generalized information criterion (GIC) identified the SNP named rs2493311 located on the first chromosome of the gene called PRDM16 ((PR/SET domain 16)) as the most decisive factor in malaria attacks.
RÉSUMÉ
During the COVID-19 pandemic in Senegal, contact tracing was done to identify transmission clusters, their analysis allowed to understand their dynamics and evolution. In this study, we used information from the surveillance data and phone interviews to construct, represent and analyze COVID-19 transmission clusters from March 2, 2020, to May 31, 2021. In total, 114,040 samples were tested and 2153 transmission clusters identified. A maximum of 7 generations of secondary infections were noted. Clusters had an average of 29.58 members and 7.63 infected among them; their average duration was 27.95 days. Most of the clusters (77.3%) are concentrated in Dakar, capital city of Senegal. The 29 cases identified as super-spreaders, i.e., the indexes that had the most positive contacts, showed few symptoms or were asymptomatic. Deepest transmission clusters are those with the highest percentage of asymptomatic members. The correlation between proportion of asymptomatic and degree of transmission clusters showed that asymptomatic strongly contributed to the continuity of transmission within clusters. During this pandemic, all the efforts towards epidemiological investigations, active case-contact detection, allowed to identify in a short delay growing clusters and help response teams to mitigate the spread of the disease.
Sujet(s)
COVID-19 , SARS-CoV-2 , Humains , COVID-19/épidémiologie , Traçage des contacts , Pandémies , Sénégal/épidémiologieRÉSUMÉ
In Senegal, the burden of dengue is increasing and expanding. As case management and traditional diagnostic techniques can be difficult to implement, rapid diagnostic tests (RDTs) deployed at point of care are ideal for investigating active outbreaks. The aim of this study was to evaluate the diagnostic performance of the Dengue NS1 and Dengue IgM/IgG RDTs on the serum/plasma samples in a laboratory setting and in the field. During laboratory evaluation, performance of the NS1 RDT was assessed using NS1 ELISA as the gold standard. Sensitivity and specificity were 88% [75-95%] and 100% [97-100%], respectively. Performance of the IgM/IG RDT was assessed using the IgM Antibody Capture (MAC) ELISA, indirect IgG, and PRNT as gold standards. The IgM and IgG test lines respectively displayed sensitivities of 94% [83-99%] and 70% [59-79%] and specificities of 91% [84-95%] and 91% [79-98%]. In the field, the Dengue NS1 RDT sensitivity and specificity was 82% [60-95%] and 75% [53-90%], respectively. The IgM and IgG test lines displayed sensitivities of 86% [42-100%] and 78% [64-88%], specificities of 85% [76-92%] and 55% [36-73%], respectively. These results demonstrate that RDTs are ideal for use in a context of high prevalence or outbreak setting and can be implemented in the absence of a confirmatory test for acute and convalescent patients.
Sujet(s)
Virus de la dengue , Dengue , Humains , Dengue/diagnostic , Dengue/épidémiologie , Tests de diagnostic rapide , Sénégal/épidémiologie , Sensibilité et spécificité , Immunoglobuline M , Test ELISA/méthodes , Immunoglobuline G , Anticorps antiviraux , Protéines virales non structuralesRÉSUMÉ
Profiling of the antibody responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) proteins in African populations is scarce. Here, we performed a detailed IgM and IgG epitope mapping study against 487 peptides covering SARS-CoV-2 wild-type structural proteins. A panel of 41 pre-pandemic and 82 COVID-19 RT-PCR confirmed sera from Madagascar and Senegal were used. We found that the main 36 immunodominant linear epitopes identified were (i) similar in both countries, (ii) distributed mainly in the Spike and the Nucleocapsid proteins, (iii) located outside the RBD and NTD regions where most of the reported SARS-CoV-2 variant mutations occur, and (iv) identical to those reported in European, North American, and Asian studies. Within the severe group, antibody levels were inversely correlated with the viral load. This first antibody epitope mapping study performed in patients from two African countries may be helpful to guide rational peptide-based diagnostic assays or vaccine development.
Sujet(s)
COVID-19 , SARS-CoV-2 , Humains , SARS-CoV-2/génétique , Cartographie épitopique , Anticorps antiviraux , Épitopes immunodominants , SénégalRÉSUMÉ
Globally, 390 million people are at risk of dengue infection and over the past 50 years, the virus incidence increased thirty-fold. In Senegal, an unprecedented occurrence of outbreaks and sporadic cases have been noticed since 2017. In October 2018, an outbreak of Dengue virus 2 (DENV-2) was reported in the north of Senegal affecting multiple areas including Saint-Louis, Richard Toll, and Rosso which are located at the border with Mauritania. Of these 173 blood specimen samples collected from patients, 27 were positive for dengue by quantitative reverse transcription PCR (qRT-PCR), and eight were serologically confirmed to be positive for DENV immunoglobulin M (IgM). Serotyping using qRT-PCR reveals that isolates were positive for DENV-2. A subset of DENV-2 positive samples was selected and subjected to whole-genome sequencing followed by phylogenetic analysis. Analysis of six nearly complete genome sequences revealed that the isolates belong to the cosmopolitan genotype and are closely related to the Mauritanian strains detected between 2017 and 2018 and those detected in many West African countries such as Burkina Faso or Cote d'Ivoire. Our results suggest a transboundary circulation of the DENV-2 cosmopolitan genotype between Senegal and Mauritania and call for a need for coordinated surveillance of arboviruses between these two countries. Interestingly, a high level of homology between West African isolates highlights endemicity and calls for the set-up of subregional viral genomic surveillance which will lead to a better understanding of viral dynamics, transmission, and spread across Africa.
Sujet(s)
Virus de la dengue , Dengue , Humains , Dengue/épidémiologie , Sénégal/épidémiologie , Phylogenèse , Épidémies de maladies , Génotype , Burkina , SérogroupeRÉSUMÉ
The genus Flavivirus in the Flaviridae contains arthropod born viruses associated with high public health burdens like Zika, Dengue or Yellow fever. Saboya virus (SABV) is an understudied flavivirus grouping in the same genetic sub-group as Yellow Fever Virus (YFV) together with Sepik virus (SEPV) and Wesselbron virus (WSLV). Flavivirus infections are characterized by non-specific clinical presentations resulting in a high risk of misdiagnosis. SABV virus has been shown to circulate in the Sahelian zone and in central Africa. To study this virus we a qRT-PCR system based on TaqMan chemistry was developed to allow rapid and specific detection of SABV. The SABV assay was evaluated on available SABV isolates and others flaviviruses (DENV, ZIKV, YFV, WNV, KEDV). The system reliably detected all used SABV strains without cross amplification of other flaviviruses. In term of sensitivity the SABV assay detect up to 40.25 copies of SABV standard DNA molecule per ul. This system can be easily added to the available panel of arboviruses detection assays as a reliable tool to study virus prevalence in human, vertebrate and insect-vector samples.
Sujet(s)
Virus de la dengue , Flavivirus , Fièvre jaune , Infection par le virus Zika , Virus Zika , Humains , Flavivirus/génétique , Fièvre jaune/diagnostic , Réaction de polymérisation en chaine en temps réel , Virus de la fièvre jaune/génétiqueRÉSUMÉ
Dengue virus (DENV) was detected in Senegal in 1979 for the first time. Since 2017, unprecedented frequent outbreaks of DENV were noticed yearly. In this context, epidemiological and molecular evolution data are paramount to decipher the virus diffusion route. In the current study, we focused on a dengue outbreak which occurred in Senegal in 2018 in the context of a large religious gathering with 263 confirmed DENV cases out of 832 collected samples, including 25 life-threatening cases and 2 deaths. It was characterized by a co-circulation of dengue serotypes 1 and 3. Phylogenetic analysis based on the E gene revealed that the main detected serotype in Touba was DENV-3 and belonged to Genotype III. Bayesian phylogeographic analysis was performed and suggested one viral introduction around 2017.07 (95% HPD = 2016.61-2017.57) followed by cryptic circulation before the identification of the first case on 1 October 2018. DENV-3 strains are phylogenetically related, with strong phylogenetic links between strains retrieved from Burkina Faso and other West African countries. These phylogenetic data substantiate epidemiological data of the origin of DENV-3 and its spread between African countries and subsequent diffusion after religious mass events. The study also highlighted the usefulness of a mobile laboratory during the outbreak response, allowing rapid diagnosis and resulting in improved patient management.
Sujet(s)
Virus de la dengue , Dengue , Humains , Dengue/épidémiologie , Virus de la dengue/génétique , Sérogroupe , Phylogenèse , Sénégal/épidémiologie , Théorème de Bayes , Épidémies de maladies , Génotype , BurkinaRÉSUMÉ
BACKGROUND: The novel coronavirus disease 2019 (COVID-19) pandemic has spread from China to the rest of the world. Africa seems less impacted with lower number of cases and deaths than other continents. Senegal recorded its first case on March 2, 2020. We present here data collected from March 2 to October 31, 2020 in Senegal. METHODS: Socio-demographic, epidemiological, clinical and virological information were collected on suspected cases. To determine factors associated with diagnosed infection, symptomatic disease and death, multivariable binary logistic regression and log binomial models were used. Epidemiological parameters such as the reproduction number and growth rate were estimated. RESULTS: 67,608 suspected cases were tested by the IPD laboratories (13,031 positive and 54,577 negative). All age categories were associated with SARS-CoV-2 infection, but also patients having diabetes or hypertension or other cardiovascular diseases. With diagnosed infection, patients over 65 years and those with hypertension and cardiovascular disease and diabetes were highly associated with death. Patients with co-morbidities were associated with symptomatic disease, but only the under 15 years were not associated with. Among infected, 27.67% were asymptomatic (40.9% when contacts were systematically tested; 12.11% when only symptomatic or high-risk contacts were tested). Less than 15 years-old were mostly asymptomatic (63.2%). Dakar accounted for 81.4% of confirmed cases. The estimated mean serial interval was 5.57 (± 5.14) days. The average reproduction number was estimated at 1.161 (95%CI: 1.159-1.162), the growth rate was 0.031 (95%CI: 0.028-0.034) per day. CONCLUSIONS: Our findings indicated that factors associated with symptomatic COVID-19 and death are advanced age (over 65 years-old) and comorbidities such as diabetes and hypertension and cardiovascular disease.
Sujet(s)
COVID-19 , Maladies cardiovasculaires , Diabète , Hypertension artérielle , Adolescent , Sujet âgé , COVID-19/épidémiologie , Diabète/épidémiologie , Humains , Hypertension artérielle/épidémiologie , Pandémies , SARS-CoV-2 , Sénégal/épidémiologieRÉSUMÉ
To assess the genetic diversity of circulating dengue virus 2 (DENV-2) in Senegal, we analyzed nine newly generated complete genomes of strains isolated during the 2018 outbreaks and 06 sequences obtained in 2018 and 2019 from Thiès and Rosso, respectively. Phylogenetic analyses revealed that Senegalese strains belonged to the cosmopolitan genotype of DENV-2, but we observed intragenotype variability leading to a divergence in two clades associated with specific geographic distribution. We report two DENV-2 variants belonging to two distinct clades. Isolates from the "Northern clade" (n = 8) harbored three nonsynonymous mutations (V1183M, R1405K, P2266T) located respectively on NS2A, NS2B, and NS4A, while isolates from the "Western clade" (n = 7) had two nonsynonymous mutations (V1185E, V3214E) located respectively in the NS2A and NS5 genes. These findings call for phylogeographic analysis to investigate routes of introductions, dispersal patterns, and in-depth in vitro and functional study to elucidate the impact of observed mutations on viral fitness, spread, epidemiology, and pathology.
Sujet(s)
Virus de la dengue , Dengue , Dengue/épidémiologie , Génotype , Humains , Phylogenèse , Phylogéographie , Sénégal/épidémiologieRÉSUMÉ
BACKGROUND: Dengue fever is a mosquito born disease associated with self-limited to life threatening illness. First detected in Senegal in the nineteenth century, and despite its growing incidence this last decade, significant knowledge gaps exist in our knowledge of genetic diversity of circulating strains. This study highlights the circulating serotypes and genotypes between January 2017 and December 2018 and their spatial and temporal distribution throughout all regions of Senegal. METHODS: We used 56 dengue virus (DENV) strains for the analysis collected from 11 sampling areas: 39 from all regions of Senegal, and 17 isolates from Thiès, a particular area of the country. Two real time RT-qPCR systems were used to confirm dengue infection and corresponding serotypes. For molecular characterization, CprM gene was sequenced and submitted to phylogenetic analysis for serotypes and genotypes assignment. RESULTS: Three dengue virus serotypes (DENV-1-3) were detected by all used methods. DENV-3 was detected in 50% (28/56) of the isolates, followed by DENV-1 and DENV-2, each representing 25% (14/56) of the isolates. DENV-3 belongs to genotype III, DENV-1 to genotype V and DENV-2 to Cosmopolitan genotype. Serotype 3 was detected in 7 sampling locations and a co-circulation of different serotypes was observed in Thiès, Fatick and Richard-toll. CONCLUSIONS: These results emphasize the need of continuous DENV surveillance in Senegal to detect DENV cases, to define circulating serotypes/genotypes and to prevent the spread and the occurrence of severe cases.
Sujet(s)
Virus de la dengue/génétique , Dengue/épidémiologie , Dengue/diagnostic , Virus de la dengue/isolement et purification , Humains , Phylogenèse , Surveillance de la santé publique , Sénégal/épidémiologie , Sérogroupe , Analyse spatialeRÉSUMÉ
As of today, little data is available on COVID-19 in African countries, where the case management relied mainly on a treatment by association between hydroxychloroquine (HCQ) and azithromycin (AZM). This study aimed to understand the main clinical outcomes of COVID-19 hospitalized patients in Senegal from March to October 20202. We described the clinical characteristics of patients and analysed clinical status (alive and discharged versus hospitalized or died) at 15 days after Isolation and Treatment Centres (ITC) admission among adult patients who received HCQ plus AZM and those who did not receive this combination. A total of 926 patients were included in this analysis. Six hundred seventy-four (674) (72.8%) patients received a combination of HCQ and AZM. Results showed that the proportion of patient discharge at D15 was significantly higher for patients receiving HCQ plus AZM (OR: 1.63, IC 95% (1.09-2.43)). Factors associated with a lower proportion of patients discharged alive were: age ≥ 60 years (OR: 0.55, IC 95% (0.36-0.83)), having of at least one pre-existing disorder (OR: 0.61, IC 95% (0.42-0.90)), and a high clinical risk at admission following NEWS score (OR: 0.49, IC 95% (0.28-0.83)). Few side effects were reported including 2 cases of cardiac rhythmic disorders in the HCQ and AZM group versus 13 in without HCQ + AZM. An improvement of clinical status at 15 days was found for patients exposed to HCQ plus AZM combination.