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1.
JAMA Netw Open ; 7(9): e2435431, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39320890

RESUMEN

Importance: Previous studies have identified mutations in SARS-CoV-2 strains that confer resistance to nirmatrelvir, yet how often this resistance arises and its association with posttreatment virologic rebound is not well understood. Objective: To examine the prevalence of emergent antiviral resistance after nirmatrelvir treatment and its association with virologic rebound. Design, Setting, and Participants: This cohort study enrolled outpatient adults with acute COVID-19 infection from May 2021 to October 2023. Participants were divided into those who received antiviral therapy and those who did not. The study was conducted at a multicenter health care system in Boston, Massachusetts. Exposure: Treatment regimen, including none, nirmatrelvir, and remdesivir. Main Outcomes and Measures: The primary outcome was emergent SARS-CoV-2 antiviral resistance, defined as the detection of antiviral resistance mutations, which were not present at baseline, were previously associated with decreased antiviral efficacy, and emerged during or after completion of a participant's treatment. Next-generation sequencing was used to detect low frequency mutations down to 1% of the total viral population. Results: Overall, 156 participants (114 female [73.1%]; median [IQR] age, 56 [38-69] years) were included. Compared with 63 untreated individuals, the 79 who received nirmatrelvir were older and more commonly immunosuppressed. After sequencing viral RNA from participants' anterior nasal swabs, nirmatrelvir resistance mutations were detected in 9 individuals who received nirmatrelvir (11.4%) compared with 2 of those who did not (3.2%) (P = .09). Among the individuals treated with nirmatrelvir, those who were immunosuppressed had the highest frequency of resistance emergence (5 of 22 [22.7%]), significantly greater than untreated individuals (2 of 63 [3.1%]) (P = .01). Similar rates of nirmatrelvir resistance were found in those who had virologic rebound (3 of 23 [13.0%]) vs those who did not (6 of 56 [10.7%]) (P = .86). Most of these mutations (10 of 11 [90.9%]) were detected at low frequencies (<20% of viral population) and reverted to the wild type at subsequent time points. Emerging remdesivir resistance mutations were only detected in immunosuppressed individuals (2 of 14 [14.3%]) but were similarly low frequency and transient. Global Initiative on Sharing All Influenza Data analysis showed no evidence of increased nirmatrelvir resistance in the United States after the authorization of nirmatrelvir. Conclusions and Relevance: In this cohort study of 156 participants, treatment-emergent nirmatrelvir resistance mutations were commonly detected, especially in individuals who were immunosuppressed. However, these mutations were generally present at low frequencies and were transient in nature, suggesting a low risk for the spread of nirmatrelvir resistance in the community with the current variants and drug usage patterns.


Asunto(s)
Adenosina Monofosfato , Alanina , Antivirales , Tratamiento Farmacológico de COVID-19 , Farmacorresistencia Viral , SARS-CoV-2 , Humanos , Femenino , Masculino , Antivirales/uso terapéutico , Farmacorresistencia Viral/genética , Persona de Mediana Edad , Alanina/análogos & derivados , Alanina/uso terapéutico , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Adulto , Mutación , COVID-19/epidemiología , Anciano , Estudios de Cohortes
2.
Case Rep Otolaryngol ; 2024: 6400515, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39161628

RESUMEN

Pleomorphic adenoma is a benign tumor of the salivary glands. It develops preferentially in the parotid gland. The authors report a localization of a pleomorphic adenoma on the palate and discuss the value of CT scan in therapeutic strategy.

3.
Viruses ; 16(7)2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-39066182

RESUMEN

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.


Asunto(s)
Genoma Viral , Filogenia , Fiebre del Valle del Rift , Virus de la Fiebre del Valle del Rift , Replicación Viral , Virus de la Fiebre del Valle del Rift/genética , Virus de la Fiebre del Valle del Rift/aislamiento & purificación , Virus de la Fiebre del Valle del Rift/clasificación , Virus de la Fiebre del Valle del Rift/fisiología , Fiebre del Valle del Rift/virología , Fiebre del Valle del Rift/epidemiología , Fiebre del Valle del Rift/transmisión , Senegal/epidemiología , Humanos , Animales , Enfermedades Transmisibles Emergentes/virología , Enfermedades Transmisibles Emergentes/epidemiología , Enfermedades Transmisibles Emergentes/veterinaria , Brotes de Enfermedades , África Occidental/epidemiología , Variación Genética , Mutación
4.
Medicina (Kaunas) ; 60(7)2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-39064464

RESUMEN

Background and Objectives: Patients with perianal Crohn's (CD) fistula often need repetitive surgeries and none of the established techniques was shown to be superior or preferable. Furthermore, the long-term outcome of fistula Seton drainage is not well described. The aims of this study were to analyze the long-term healing and recurrence rate of CD perianal fistulas in a large patient cohort. Materials and Methods: Database analysis of the Swiss IBD (Inflammatory Bowel Disease) cohort study. Results: 365 perianal fistula patients with 576 surgical interventions and a median follow-up of 7.5 years (0-12.6) were analyzed. 39.7% of patients required more than one procedure. The first surgical interventions were fistulectomies ± mucosal sliding flap (59.2%), Seton drainage (29.6%), fistula plugs or fibrin glue installations (2.5%) and combined procedures (8.8%). Fistulectomy patients required no more surgery in 69%, one additional surgery in 25% and more than one additional surgery in 6%, with closure rates at 7.5 years follow-up of 77.1%, 74.1% and 66.7%, respectively. In patients with Seton drainage as index surgery, 52% required no more surgery, and over 75% achieved fistula closure after 10 years. Conclusions: First-line fistulectomies, when feasible, achieved the highest healing rates, but one-third of patients required additional surgeries, and one-fourth of patients will remain with a fistula at 10 years. Initial Seton drainage and concurrent medical therapy can achieve fistula closure in 75%. However, in 50% of patients, more surgeries are needed, and fistula closure is achieved in only two-thirds of patients.


Asunto(s)
Enfermedad de Crohn , Fístula Rectal , Humanos , Enfermedad de Crohn/cirugía , Enfermedad de Crohn/complicaciones , Masculino , Femenino , Fístula Rectal/cirugía , Fístula Rectal/etiología , Adulto , Resultado del Tratamiento , Persona de Mediana Edad , Estudios de Cohortes , Drenaje/métodos , Suiza , Recurrencia , Anciano
5.
Emerg Infect Dis ; 30(8): 1687-1691, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39043450

RESUMEN

In December 2023, we observed through hospital-based surveillance a severe outbreak of enterovirus D68 infection in pediatric inpatients in Dakar, Senegal. Molecular characterization revealed that subclade B3, the dominant lineage in outbreaks worldwide, was responsible for the outbreak. Enhanced surveillance in inpatient settings, including among patients with neurologic illnesses, is needed.


Asunto(s)
Brotes de Enfermedades , Enterovirus Humano D , Infecciones por Enterovirus , Infecciones del Sistema Respiratorio , Humanos , Senegal/epidemiología , Enterovirus Humano D/genética , Enterovirus Humano D/clasificación , Enterovirus Humano D/aislamiento & purificación , Infecciones por Enterovirus/epidemiología , Infecciones por Enterovirus/virología , Infecciones por Enterovirus/diagnóstico , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Preescolar , Lactante , Niño , Filogenia , Masculino , Femenino , Enfermedad Aguda/epidemiología , Adolescente , Hospitales , Historia del Siglo XXI
6.
Emerg Microbes Infect ; 13(1): 2373308, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38934257

RESUMEN

Chikungunya virus has caused millions of cases worldwide over the past 20 years, with recent outbreaks in Kedougou region in the southeastern Senegal, West Africa. Genomic characterization highlights that an ongoing epidemic in Kedougou in 2023 is not due to an introduction event but caused by the re-emergence of an endemic strain evolving linearly in a sylvatic context.


Asunto(s)
Fiebre Chikungunya , Virus Chikungunya , Brotes de Enfermedades , Genoma Viral , Filogenia , Senegal/epidemiología , Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/virología , Humanos , Virus Chikungunya/genética , Virus Chikungunya/clasificación , Virus Chikungunya/aislamiento & purificación , Genómica , Enfermedades Transmisibles Emergentes/epidemiología , Enfermedades Transmisibles Emergentes/virología , Animales
7.
Ann Cardiol Angeiol (Paris) ; 73(3): 101762, 2024 Jun.
Artículo en Francés | MEDLINE | ID: mdl-38733860

RESUMEN

INTRODUCTION: An electrocardiogram (ECG), combined with a well-conducted clinical examination, is more effective than the clinical examination alone in detecting underlying cardiac pathologies in athletes. The aim of this study was to evaluate the use of ECGs by physicians who are members of the Guinean Association of Sports Physicians, during the non-contraindication visit for competitive sports between the ages of 12 and 35. METHODOLOGY: We conducted a web-survey from July 15 to August 15, 2023. A survey form was created on "Google Docs" and pre-tested. It was then broadcast on all the communication networks used by these doctors. The data were secured using "Google Drive" software. Analyses were performed using SPSS version 20 software. RESULTS: Of the 51 included, 74.51% said they had received at least one training session on ECG interpretation for athletes. All of them either requested or performed an ECG at least once in a while, as part of the check-up for non-contraindication to competitive sport. The ECG was systematic, according to 72.55% of doctors. Three quarters referred to a sports cardiologist in the event of an abnormal ECG, 66.67% to a cardiology resident and 58.82% to a cardiologist. In the absence of an ECG, the presence of functional signs on exertion, the notion of a family history of cardiovascular disease and the presence of at least two cardiovascular risk factors were the main reasons for seeking an opinion. CONCLUSION: A resting ECG is carried out almost systematically by doctors who are members of the Guinean Association of Sports Doctors, as part of the check-up for non-contraindication to practising sport.


Asunto(s)
Electrocardiografía , Medicina Deportiva , Deportes , Humanos , Adulto , Adolescente , Adulto Joven , Masculino , Femenino , Niño , Pautas de la Práctica en Medicina/estadística & datos numéricos , Encuestas y Cuestionarios
8.
Zoonoses Public Health ; 71(6): 696-707, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38627964

RESUMEN

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.


Asunto(s)
Brotes de Enfermedades , Enfermedades de las Cabras , Cabras , Virus de la Fiebre Hemorrágica de Crimea-Congo , Fiebre Hemorrágica de Crimea , Ganado , Enfermedades de las Ovejas , Garrapatas , Animales , Fiebre Hemorrágica de Crimea/epidemiología , Senegal/epidemiología , Virus de la Fiebre Hemorrágica de Crimea-Congo/aislamiento & purificación , Virus de la Fiebre Hemorrágica de Crimea-Congo/inmunología , Brotes de Enfermedades/veterinaria , Factores de Riesgo , Humanos , Ovinos , Garrapatas/virología , Enfermedades de las Ovejas/epidemiología , Enfermedades de las Ovejas/virología , Enfermedades de las Cabras/epidemiología , Enfermedades de las Cabras/virología , Bovinos , Ganado/virología , Masculino , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/virología , Femenino , Estudios Seroepidemiológicos , Infestaciones por Garrapatas/epidemiología , Infestaciones por Garrapatas/veterinaria , Prevalencia , Zoonosis/epidemiología , Anticuerpos Antivirales/sangre
9.
Emerg Infect Dis ; 30(4): 770-774, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38526209

RESUMEN

In 2020, a sylvatic dengue virus serotype 2 infection outbreak resulted in 59 confirmed dengue cases in Kedougou, Senegal, suggesting those strains might not require adaptation to reemerge into urban transmission cycles. Large-scale genomic surveillance and updated molecular diagnostic tools are needed to effectively prevent dengue virus infections in Senegal.


Asunto(s)
Virus del Dengue , Dengue , Humanos , Virus del Dengue/genética , Senegal/epidemiología , Serogrupo , Ambiente , Dengue/epidemiología
10.
Viruses ; 16(2)2024 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-38400090

RESUMEN

Crimean-Congo hemorrhagic fever (CCHF), the most widespread tick-borne viral human infection, poses a threat to global health. In this study, clinical samples collected through national surveillance systems were screened for acute CCHF virus (CCHFV) infection using RT-PCR and for exposure using ELISA. For any CCHF-positive sample, livestock and tick samples were also collected in the neighborhood of the confirmed case and tested using ELISA and RT-PCR, respectively. Genome sequencing and phylogenetic analyses were also performed on samples with positive RT-PCR results. In Eastern Senegal, two human cases and one Hyalomma tick positive for CCHF were identified and a seroprevalence in livestock ranging from 9.33% to 45.26% was detected. Phylogenetic analyses revealed that the human strain belonged to genotype I based on the available L segment. However, the tick strain showed a reassortant profile, with the L and M segments belonging to genotype I and the S segment belonging to genotype III. Our data also showed that our strains clustered with strains isolated in different countries, including Mauritania. Therefore, our findings confirmed the high genetic variability inside the CCHF genotypes and their introduction to Senegal from other countries. They also indicate an increasing CCHF threat in Senegal and emphasize the need to reinforce surveillance using a one-health approach.


Asunto(s)
Virus de la Fiebre Hemorrágica de Crimea-Congo , Fiebre Hemorrágica de Crimea , Garrapatas , Animales , Humanos , Virus de la Fiebre Hemorrágica de Crimea-Congo/genética , Fiebre Hemorrágica de Crimea/epidemiología , Filogenia , Estudios Seroepidemiológicos , Senegal/epidemiología , Ganado
11.
Trop Med Infect Dis ; 9(2)2024 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-38393121

RESUMEN

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.

12.
Urolithiasis ; 52(1): 26, 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38216696

RESUMEN

Our aim was to determine the current trend of endourology in the management of upper urinary tract calculi in Africa reference centres. We conducted an online multiple-choice questionnaire survey involving 46 centres from 27 countries using a structured well-designed Google Form (®) questionnaire. The questionnaires were distributed to the head of service through their emails. The questions collected demographic data about the centre, the epidemiology of urolithiasis, diagnostic means and management of upper urolithiasis, especially access to endourology procedures and their practices. Descriptive analyses were performed. The participation rate was 77.9%. Urinary lithiasis was one of the three main pathologies encountered in 42/46 centres. 33 centres had easy access to CT scanners and 34 had operating theatres equipped with endo-urological surgery equipment. Of these 34 centres, 30 perform endourology for the management of upper urinary tract stones. Rigid ureteroscopy is the main technique used by the centres. It is the only endourology technique used for stone management by 12 centres (40%). 7/30 (23.3%) have the option of performing rigid ureteroscopy, flexible ureteroscopy and percutaneous nephrolithotomy. The frequency of procedures varies widely, with 43.3% rarely performing endourological surgery. Seventeen centres have their operating theatre equipped with a fluoroscope and 6/42 centres have extracorporeal lithotripsy. Open surgery is still used in 29/42 centres (69.1%). Laparoscopy is available in 50% of centres, but none reported performing laparoscopic lithotomy. In Africa, urinary lithiasis plays an important role in the activities of referral centres. Modern management techniques are used to varying degrees (not all centres have them) and with very variable frequency. Open surgery is still widely performed as a management. Rigid ureteroscopy is the main endourological technique. It is essential to develop the practice of modern urology in Africa, mainly endourology.


Asunto(s)
Cálculos Renales , Litotricia , Cálculos Urinarios , Sistema Urinario , Urolitiasis , Humanos , Cálculos Renales/cirugía , Ureteroscopía , Urolitiasis/cirugía , Litotricia/métodos , Encuestas y Cuestionarios , Resultado del Tratamiento
13.
Sci Transl Med ; 16(731): eadk1599, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38266109

RESUMEN

Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but the immune defects that predispose an individual to persistent coronavirus disease 2019 (COVID-19) remain incompletely understood. In this study, we performed detailed viro-immunologic analyses of a prospective cohort of participants with COVID-19. The median times to nasal viral RNA and culture clearance in individuals with severe immunosuppression due to hematologic malignancy or transplant (S-HT) were 72 and 40 days, respectively, both of which were significantly longer than clearance rates in individuals with severe immunosuppression due to autoimmunity or B cell deficiency (S-A), individuals with nonsevere immunodeficiency, and nonimmunocompromised groups (P < 0.01). Participants who were severely immunocompromised had greater SARS-CoV-2 evolution and a higher risk of developing resistance against therapeutic monoclonal antibodies. Both S-HT and S-A participants had diminished SARS-CoV-2-specific humoral responses, whereas only the S-HT group had reduced T cell-mediated responses. This highlights the varied risk of persistent COVID-19 across distinct immunosuppressive conditions and suggests that suppression of both B and T cell responses results in the highest contributing risk of persistent infection.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Estudios Prospectivos , Cinética , Terapia de Inmunosupresión
14.
Am J Primatol ; 86(2): e23578, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37985945

RESUMEN

Precise estimates of population dynamics and social grouping patterns are required for effective conservation of wild animal populations. It is difficult to obtain such information on non-human great apes as they have slow reproductive rates. To gain a better understanding of demography in these populations, previous research has typically involved habituation\, a process that requires years. Here, we collected data continuously over year-long periods to monitor an unhabituated population of critically endangered Western chimpanzees (Pan troglodytes verus) in the Moyen Bafing National Park, Guinea. We used two arrays of 100 camera traps that were placed opportunistically in two distinct 100 km2 sites, named Bakoun and Koukoutamba. We identified 227 individuals in Bakoun and 207 in Koukoutamba through their unique facial features. Our camera trap data make clear that these individuals belong to six and seven closed groups, respectively. Six of those groups were near-completely sampled with an average minimum size of 46.8 individuals (range: 37-58), and a mean adult sex ratio of 1.32 (range: 0.93-2.10). We described the demographic composition of these groups and use Bayesian social network analysis to understand population structure. The network analyses suggested that the social bonds within the two populations were structured by sex homophily, with male chimpanzees being more or equally likely to be observed together than other adult associations. Through estimation of minimum convex polygons, we described the minimum home range for those groups. Compared to other chimpanzee groups living in a similar environment (mosaic savanna-forest), the Moyen Bafing region seems to host a high-density of chimpanzees with small home ranges for their group size. Our research highlights the potential of camera traps for studying the demographic composition of chimpanzee populations with high resolution and obtaining crucial information on several groups in a time-efficient and cost-effective way.


Asunto(s)
Fenómenos de Retorno al Lugar Habitual , Pan troglodytes , Humanos , Masculino , Animales , Guinea , Parques Recreativos , Teorema de Bayes , Dinámica Poblacional , Estructura Social
15.
Ann Intern Med ; 176(12): 1577-1585, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37956428

RESUMEN

BACKGROUND: Data are conflicting regarding an association between treatment of acute COVID-19 with nirmatrelvir-ritonavir (N-R) and virologic rebound (VR). OBJECTIVE: To compare the frequency of VR in patients with and without N-R treatment for acute COVID-19. DESIGN: Observational cohort study. SETTING: Multicenter health care system in Boston, Massachusetts. PARTICIPANTS: Ambulatory adults with acute COVID-19 with and without use of N-R. INTERVENTION: Receipt of 5 days of N-R treatment versus no COVID-19 therapy. MEASUREMENTS: The primary outcome was VR, defined as either a positive SARS-CoV-2 viral culture result after a prior negative result or 2 consecutive viral loads above 4.0 log10 copies/mL that were also at least 1.0 log10 copies/mL higher than a prior viral load below 4.0 log10 copies/mL. RESULTS: Compared with untreated persons (n = 55), those taking N-R (n = 72) were older, received more COVID-19 vaccinations, and more commonly had immunosuppression. Fifteen participants (20.8%) taking N-R had VR versus 1 (1.8%) who was untreated (absolute difference, 19.0 percentage points [95% CI, 9.0 to 29.0 percentage points]; P = 0.001). All persons with VR had a positive viral culture result after a prior negative result. In multivariable models, only N-R use was associated with VR (adjusted odds ratio, 10.02 [CI, 1.13 to 88.74]; P = 0.038). Virologic rebound was more common among those who started therapy within 2 days of symptom onset (26.3%) than among those who started 2 or more days after symptom onset (0%) (P = 0.030). Among participants receiving N-R, those who had VR had prolonged shedding of replication-competent virus compared with those who did not have VR (median, 14 vs. 3 days). Eight of 16 participants (50% [CI, 25% to 75%]) with VR also reported symptom rebound; 2 were completely asymptomatic. No post-VR resistance mutations were detected. LIMITATIONS: Observational study design with differences between the treated and untreated groups; positive viral culture result was used as a surrogate marker for risk for ongoing viral transmission. CONCLUSION: Virologic rebound occurred in approximately 1 in 5 people taking N-R, often without symptom rebound, and was associated with shedding of replication-competent virus. PRIMARY FUNDING SOURCE: National Institutes of Health.


Asunto(s)
COVID-19 , SARS-CoV-2 , Adulto , Humanos , Ritonavir/uso terapéutico , Tratamiento Farmacológico de COVID-19
16.
Sci Rep ; 13(1): 20404, 2023 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-37990112

RESUMEN

In 2022, many regions around the world experienced a severe respiratory syncytial virus (RSV) epidemic with an earlier-than-usual start and increased numbers of paediatric patients in emergency departments. Here we carried out this study to describe the epidemiology and genetic characteristics of RSV infection in patients hospitalized with severe acute respiratory infections in 2022. Samples were tested for RSV by multiplex real time reverse transcription polymerase chain reaction. Subsequently, a subset of RSV positive samples was selected for NGS sequencing. RSV was detected in 16.04%, among which RSV-A was confirmed in 7.5% and RSV-B in 76.7%. RSV infection were more identified in infants aged ≤ 11 months (83.3%) and a shift in the circulation pattern was observed, with highest incidences between September-November. Phylogenetic analyses revealed that all RSV-A strains belonged to GA2.3.5 genotype and all RSV-B strains to GB5.0.5a genotype. Three putative N-glycosylation sites at amino acid positions 103, 135, 237 were predicted among RSV-A strains, while four N-linked glycosylation sites at positions 81, 86, 231 and 294 were identified in RSV-B strains. Globally, our findings reveal an exclusive co-circulation of two genetic lineages of RSV within the pediatric population in Senegal, especially in infants aged ≤ 11 months.


Asunto(s)
Neumonía , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio , Lactante , Humanos , Niño , Estaciones del Año , Filogenia , Senegal , Vigilancia de Guardia , Virus Sincitial Respiratorio Humano/genética , Genotipo , Infecciones del Sistema Respiratorio/epidemiología
17.
Vaccines (Basel) ; 11(10)2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37896941

RESUMEN

Dengue fever is the most prevalent arboviral disease worldwide. Dengue virus (DENV), the etiological agent, is known to have been circulating in Senegal since 1970, though for a long time, virus epidemiology was restricted to the circulation of sylvatic DENV-2 in south-eastern Senegal (the Kedougou region). In 2009 a major shift was noticed with the first urban epidemic, which occurred in the Dakar region and was caused by DENV-3. Following the notification by Senegal, many other West African countries reported DENV-3 epidemics. Despite these notifications, there are scarce studies and data about the genetic diversity and molecular evolution of DENV-3 in West Africa. Using nanopore sequencing, phylogenetic, and phylogeographic approaches on historic strains and 36 newly sequenced strains, we studied the molecular evolution of DENV-3 in Senegal between 2009 and 2022. We then assessed the impact of the observed genetic diversity on the efficacy of preventive countermeasures and vaccination by mapping amino acid changes against vaccine strains. The results showed that the DENV-3 strains circulating in Senegal belong to genotype III, similarly to strains from other West African countries, while belonging to different clades. Phylogeographic analysis based on nearly complete genomes revealed three independent introduction events from Asia and Burkina Faso. Comparison of the amino acids in the CprM-E regions of genomes from the Senegalese strains against the vaccine strains revealed the presence of 22 substitutions (7 within the PrM and 15 within the E gene) when compared to CYD-3, while 23 changes were observed when compared to TV003 (6 within the PrM and 17 within the E gene). Within the E gene, most of the changes compared to the vaccine strains were located in the ED-III domain, which is known to be crucial in neutralizing antibody production. Altogether, these data give up-to-date insight into DENV-3 genomic evolution in Senegal which needs to be taken into account in future vaccination strategies. Additionally, they highlight the importance of the genomic epidemiology of emerging pathogens in Africa and call for the implementation of a pan-African network for genomic surveillance of dengue virus.

18.
Microorganisms ; 11(8)2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37630521

RESUMEN

We conducted an active influenza surveillance in the single pig slaughterhouse in Dakar to investigate the epidemiology and genetic characteristics of influenza A viruses (IAVs) and to provide serologic evidence of avian influenza virus (AIV) infection in pigs at interfaces with human populations in Senegal. Nasal swab and blood samples were collected on a weekly basis from the same animal immediately after slaughter. Influenza A viruses were diagnosed using RT-qPCR and a subset of positive samples for H3 and H1 subtypes were selected for full genome amplification and NGS sequencing. Serum samples were tested by HI assay for the detection of antibodies recognizing four AIVs, including H9N2, H5N1, H7N7 and H5N2. Between September 2018 and December 2019, 1691 swine nasal swabs were collected and tested. Influenza A virus was detected in 30.7% (520/1691), and A/H1N1pdm09 virus was the most commonly identified subtype with 38.07% (198/520), followed by A/H1N2 (16.3%) and A/H3N2 (5.2%). Year-round influenza activity was noted in pigs, with the highest incidence between June and September. Phylogenetic analyses revealed that the IAVs were closely related to human IAV strains belonging to A/H1N1pdm09 and seasonal H3N2 lineages. Genetic analysis revealed that Senegalese strains possessed several key amino acid changes, including D204 and N241D in the receptor binding site, S31N in the M2 gene and P560S in the PA protein. Serological analyses revealed that 83.5% (95%CI = 81.6-85.3) of the 1636 sera tested were positive for the presence of antibodies against either H9N2, H5N1, H7N7 or H5N2. Influenza H7N7 (54.3%) and H9N2 (53.6%) were the dominant avian subtypes detected in Senegalese pigs. Given the co-circulation of multiple subtypes of influenza viruses among Senegalese pigs, the potential exists for the emergence of new hybrid viruses of unpredictable zoonotic and pandemic potential in the future.

19.
medRxiv ; 2023 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-37577493

RESUMEN

Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged SARS-CoV-2 infection, but the immune defects that predispose to persistent COVID-19 remain incompletely understood. In this study, we performed detailed viro-immunologic analyses of a prospective cohort of participants with COVID-19. The median time to nasal viral RNA and culture clearance in the severe hematologic malignancy/transplant group (S-HT) were 72 and 40 days, respectively, which were significantly longer than clearance rates in the severe autoimmune/B-cell deficient (S-A), non-severe, and non-immunocompromised groups (P<0.001). Participants who were severely immunocompromised had greater SARS-CoV-2 evolution and a higher risk of developing antiviral treatment resistance. Both S-HT and S-A participants had diminished SARS-CoV-2-specific humoral, while only the S-HT group had reduced T cell-mediated responses. This highlights the varied risk of persistent COVID-19 across immunosuppressive conditions and suggests that suppression of both B and T cell responses results in the highest contributing risk of persistent infection.

20.
Emerg Infect Dis ; 29(9): 1808-1817, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37610149

RESUMEN

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.


Asunto(s)
COVID-19 , Gripe Humana , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Senegal/epidemiología , Gripe Humana/epidemiología , Pandemias
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