RESUMO
In 2023, dengue virus serotype 2 (DENV2) affected most French overseas territories. In the French Caribbean Islands, viral circulation continues with > 30,000 suspected infections by March 2024. Genome sequence analysis reveals that the epidemic lineage in the French Caribbean islands has also become established in French Guiana but not Réunion. It has moreover seeded autochthonous circulation events in mainland France. To guide prevention of further inter-territorial spread and DENV introduction in non-endemic settings, continued molecular surveillance and mosquito control are essential.
Assuntos
Epidemias , Humanos , Guiana Francesa/epidemiologia , Epidemiologia Molecular , Índias Ocidentais/epidemiologia , França/epidemiologiaRESUMO
BACKGROUND: The risk of congenital neurologic defects related to Zika virus (ZIKV) infection has ranged from 6 to 42% in various reports. The aim of this study was to estimate this risk among pregnant women with symptomatic ZIKV infection in French territories in the Americas. METHODS: From March 2016 through November 2016, we enrolled in this prospective cohort study pregnant women with symptomatic ZIKV infection that was confirmed by polymerase-chain-reaction (PCR) assay. The analysis included all data collected up to April 27, 2017, the date of the last delivery in the cohort. RESULTS: Among the 555 fetuses and infants in the 546 pregnancies included in the analysis, 28 (5.0%) were not carried to term or were stillborn, and 527 were born alive. Neurologic and ocular defects possibly associated with ZIKV infection were seen in 39 fetuses and infants (7.0%; 95% confidence interval, 5.0 to 9.5); of these, 10 were not carried to term because of termination of pregnancy for medical reasons, 1 was stillborn, and 28 were live-born. Microcephaly (defined as head circumference more than 2 SD below the mean for sex and gestational age) was detected in 32 fetuses and infants (5.8%), of whom 9 (1.6%) had severe microcephaly (more than 3 SD below the mean). Neurologic and ocular defects were more common when ZIKV infection occurred during the first trimester (24 of 189 fetuses and infants [12.7%]) than when it occurred during the second trimester (9 of 252 [3.6%]) or third trimester (6 of 114 [5.3%]) (P=0.001). CONCLUSIONS: Among pregnant women with symptomatic, PCR-confirmed ZIKV infection, birth defects possibly associated with ZIKV infection were present in 7% of fetuses and infants. Defects occurred more frequently in fetuses and infants whose mothers had been infected early in pregnancy. Longer-term follow-up of infants is required to assess any manifestations not detected at birth. (Funded by the French Ministry of Health and others; ClinicalTrials.gov number, NCT02916732 .).
Assuntos
Anormalidades Congênitas/epidemiologia , Microcefalia/epidemiologia , Complicações Infecciosas na Gravidez , Resultado da Gravidez/epidemiologia , Infecção por Zika virus/complicações , Adolescente , Adulto , Líquido Amniótico/virologia , Transtornos Cromossômicos/epidemiologia , Estudos de Coortes , Feminino , Doenças Fetais/epidemiologia , Guiana Francesa/epidemiologia , Guadalupe/epidemiologia , Humanos , Recém-Nascido , Martinica/epidemiologia , Pessoa de Meia-Idade , Gravidez , Trimestres da Gravidez , Adulto Jovem , Zika virus/isolamento & purificação , Infecção por Zika virus/epidemiologiaRESUMO
OBJECTIVE: To analyze, describe, and quantify the collaborations and scientific output of the two university teaching hospitals of Martinique and Guadeloupe, at the regional, national, and international level. METHODS: A bibliometrics analysis was performed from the international databases Web of Science and PubMed, for the period from 1989 to 2018, inclusive (30 years). Three types of bibliometric indicators were used, namely quantitative indicators, performance indicators, and organization-specific indicators. Affiliations of the first and last authors were identified from PubMed. RESULTS: Between 1989 and 2018, a total of 1 522 indexed articles were published with at least one author affiliated to either the University Hospital of Martinique (n = 827) or the University Hospital of Guadeloupe (n = 685). The majority of articles were in category Q1 (35.8% for Martinique and 35.2% for Guadeloupe). In Martinique, over the last 30 years, the three main research areas have been clinical neurology, ophthalmology, and surgery, together representing 28.7% of all research areas, with the highest number of articles published in the field of clinical neurology (n = 81). In the University Hospital of Guadeloupe, the area of hematology was largely represented, with 79 articles published. For both hospitals, the first and last authors of the articles published were mainly from mainland France. CONCLUSIONS: This quantitative analysis shows the development of medical and scientific research in Martinique and Guadeloupe over the last three decades, as well as the extent of their collaborative partnerships at the national and international levels.
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OBJECTIVE: To describe the viruses involved, seasonality and coinfection in hospitalised children with suspected bronchiolitis. METHODS: Over the period 1/07/2007 to 31/12/2008, all children hospitalised for bronchiolitis in the paediatric ward were prospectively included, and had respiratory syncytial virus (RSV) screenings. We retrospectively tested all samples for RSVA, RSVB, rhinovirus (RV), human metapneumovirus, parainfluenza 1, 2, 3, 4, influenza A and influenza B. RESULTS: 198 children were tested, and 23% were negative for all viruses. RSVA was predominant in 2008 (64% of all viruses) and RSVB in 2007 (66% of all viruses). RV was frequent during both seasons (24% of all viruses). Flu was not found during the study period. Virus distribution was similar regardless of season or age, and identical to typical patterns in temperate countries. Coinfections were less frequent than in temperate regions because respiratory virus seasons seem to be better separated. The bronchiolitis season started in August and finished in December with a peak in October. CONCLUSION: The specific seasonality of bronchiolitis infection requires palivizumab prophylaxis starting in early July for high-risk infants.
OBJECTIF: Décrire les virus impliqués, la saisonnalité et la coinfection chez les enfants hospitalisés avec une suspicion de bronchiolite. MÉTHODES: Au cours de la période du 01/07/2007 au 31/12/2008, tous les enfants hospitalisés pour bronchiolite dans le service de pédiatrie ont été prospectivement inclus et soumis à un dépistage du virus respiratoire syncytial (VRS). Nous avons testé rétrospectivement tous les échantillons pour RSVA, RSVB, rhinovirus (RV), métapneumovirus humain, Parainfluenza 1, 2, 3, 4, Influenza A, et Influenza B. RÉSULTATS: 198 enfants ont été testés et 23% étaient négatifs pour tous les virus. RSVA était prédominant en 2008 (64% de tous les virus) et RSVB en 2007 (66% de tous les virus). RV était fréquent pendant les deux saisons (24% de tous les virus). La grippe n'a pas été trouvée pendant la période d'étude. La distribution des virus était similaire quelle que soit la saison ou l'âge, et identique aux modèles typiques dans les pays tempérés. Les coinfections étaient moins fréquentes que dans les régions tempérées car les saisons virales respiratoires semblent mieux séparées. La saison des bronchiolites a commencé en août et s'est terminée en décembre avec un pic en octobre. CONCLUSION: La saisonnalité spécifique de l'infection bronchiolite nécessite une prophylaxie au palivizumab débutant en juillet pour les nourrissons à haut risque.
Assuntos
Bronquiolite/epidemiologia , Resfriado Comum/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Vírus Sincicial Respiratório Humano/isolamento & purificação , Rhinovirus/isolamento & purificação , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Bronquiolite/prevenção & controle , Bronquiolite/virologia , Criança , Criança Hospitalizada , Pré-Escolar , Coinfecção , Resfriado Comum/prevenção & controle , Resfriado Comum/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Martinica/epidemiologia , Palivizumab/administração & dosagem , Palivizumab/uso terapêutico , Estudos Prospectivos , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/virologia , Estudos Retrospectivos , Estações do Ano , Clima TropicalRESUMO
Since 2015, Zika virus (ZIKV) has caused large epidemics in the Americas. Households are natural targets for control interventions, but quantification of the contribution of household transmission to overall spread is needed to guide policy. We developed a modeling framework to evaluate this contribution and key epidemic features of the ZIKV epidemic in Martinique in 2015-2016 from the joint analysis of a household transmission study (n = 68 households), a study among symptomatic pregnant women (n = 281), and seroprevalence surveys of blood donors (n = 457). We estimated that the probability of mosquito-mediated within-household transmission (from an infected member to a susceptible one) was 21% (95% credible interval (CrI): 5, 51), and the overall probability of infection from outside the household (i.e., in the community) was 39% (95% CrI: 27, 50). Overall, 50% (95% CrI: 43, 58) of the population was infected, with 22% (95% CrI: 5, 46) of infections acquired in households and 40% (95% CrI: 23, 56) being asymptomatic. The probability of presenting with Zika-like symptoms due to another cause was 16% (95% CrI: 10, 23). This study characterized the contribution of household transmission in ZIKV epidemics, demonstrating the benefits of integrating multiple data sets to gain more insight into epidemic dynamics.
Assuntos
Surtos de Doenças , Transmissão de Doença Infecciosa , Características da Família , Infecção por Zika virus/transmissão , Aedes/virologia , Animais , Feminino , Humanos , Masculino , Martinica/epidemiologia , Mosquitos Vetores/virologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Fatores de Risco , Infecção por Zika virus/epidemiologiaRESUMO
OBJECTIVE: To investigate whether the long-term survival in elderly patients with prior Chikungunya virus infection (CVI) is associated with the clinical form presented in the acute phase, as defined by the WHO classification. METHODS: Retrospective cohort study performed in Martinique University Hospitals. Patients who attended the emergency department for suspected CVI, and who had a positive biological diagnosis of CVI by reverse transcription-polymerase chain reaction on a plasma sample between 10 January and 31 December 2014 were eligible for inclusion. Time-to-death was the primary outcome. The independent relationship between clinical forms and time-to-death was analysed using a Cox model. RESULTS: In total, 268 patients were included. Mean age was 80 ± 8 years, 53% were women. Median length of follow-up was 28 months (range: 0-39). During follow-up, 53 (19.8%) patients died. Median survival time was 13.2 months (range: 0-33.6). At the end of follow-up, death rates were 4.6% for acute clinical cases, 19.0% for atypical cases, 19.2% for severe acute cases and 23.5% for unclassifiable cases. By multivariable analysis, the clinical form of CVI at admission was found to be independently associated with long-term survival (atypical form: HR = 2.38; 95% CI = 2.15-2.62; severe acute form: HR = 2.40; 95% CI = 2.17-2.64; unclassifiable form: HR = 2.28; 95% CI = 2.06-2.51). CONCLUSION: The clinical form at presentation with CVI has a significant impact on long-term survival. Management of CVI patients should be tailored according to their clinical form at admission.
OBJECTIF: Etudier si la survie à long terme chez les patients âgés avec une infection antérieure par le virus du chikungunya (IVC) est associée à la forme clinique présente dans la phase aiguë, telle que définie par la classification de l'OMS. MÉTHODES: Etude de cohorte rétrospective réalisée dans les hôpitaux universitaires de la Martinique. Les patients qui se présentaient au service des urgences en cas de suspicion d'IVC et qui avaient un diagnostic biologique positif d'ICV par la PCR à transcription inverse sur un échantillon plasmatique entre le 10 janvier et le 31 décembre 2014 étaient éligibles à l'inclusion. Le temps jusqu'au décès était le résultat principal. La relation indépendante entre les formes cliniques et le temps jusqu'au décès a été analysée à l'aide d'un modèle de Cox. RÉSULTATS: Au total, 268 patients ont été inclus. L'âge moyen était de 80 ± 8 ans, 53% étaient des femmes. La durée médiane du suivi était de 28 mois (intervalle: 0 à 39 ans). Au cours du suivi, 53 patients (19,8%) sont décédés. La durée médiane de survie était de 13,2 mois (intervalle: 0 à 33,6). A la fin du suivi, les taux de décès étaient de 4,6% pour les cas cliniques aigus, 19,0% pour les cas atypiques, 19,2% pour les cas aigus sévères et 23,5% pour les cas non classifiables. L'analyse multivariée a révélé que la forme clinique de l'IVC à l'admission était indépendamment associée à la survie à long terme (forme atypique: HR = 2,38; IC95%: 2,15-2,62; forme aiguë sévère: HR = 2,40; IC95%: 2,17-2,64; forme inclassable: HR = 2,28; IC95%: 2,06-2,51). CONCLUSION: La forme clinique lors de la présentation avec IVC a un impact significatif sur la survie à long terme. La prise en charge des patients atteints d'ICV devrait être adaptée à la forme clinique lors de l'admission.
Assuntos
Febre de Chikungunya/mortalidade , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Região do Caribe/epidemiologia , Feminino , Humanos , Masculino , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Análise de SobrevidaRESUMO
BACKGROUND: Cervical cancer prevention using cervical cytology is insufficiently sensitive, a significant proportion of HPV-infected women having normal cytology. The objective of the present study was to try to identify factors associated with abnormal cytology in HPV-infected women living in remote areas of French Guiana. METHODS: A study was conducted in women aged 20-65 years having HPV infections confirmed by HPV DNA detection using the GREINER-BIO-ONE kit. In addition to HPV testing, cytology was performed and classified as normal or abnormal. Demographic and life history variables, and infecting genotypes were compared between the normal and abnormal cytology groups. RESULTS: None of the demographic and life history variables were associated with cytology results. HPV genotype 53 was significantly associated with absence of cytological abnormalities whereas HPV 52, 58, 16 and perhaps 33 and 66 were independently associated with a greater risk of cytological abnormalities. When grouping HPV genotypes in different species, only species 9 (HPV 16, 31, 33, 35, 52, 58, 67) was significantly associated with abnormal cytology AOR = 5.1 (95% CI = 2.3-11.2), P < 0.001. CONCLUSIONS: It was not possible to predict which HPV-infected women will have cytological abnormalities or notfrom anamnesis. In this study HPV 53 seemed more benign than other HPV genotypes. On the contrary, species n°9, containing 5 of the genotypes contained in the nonavalent HPV vaccine, was significantly associated with more cytological abnormalities. HPV testing and vaccination with the nonavalent vaccine should be implemented in these remote parts of French Guiana.
Assuntos
Citodiagnóstico/estatística & dados numéricos , DNA Viral/análise , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Idoso , Feminino , Guiana Francesa , Genótipo , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus , Valor Preditivo dos Testes , População Rural , Neoplasias do Colo do Útero/virologia , Adulto JovemRESUMO
BACKGROUND: Guillain-Barré syndrome (GBS) has been reported to be associated with Zika virus (ZIKV) infection in case reports and retrospective studies, mostly on the basis of serological tests, with the problematic cross-reacting antibodies of the Flavivirus genus. Some GBS cases do not exhibit a high level of diagnostic certainty. This prospective study aimed to describe the clinical profiles and the frequency of GBS associated with ZIKV during the ZIKV outbreak in Martinique in 2016. METHODS: We recorded prospective data from GBS meeting levels 1 or 2 of diagnostic certainty for the Brighton Collaboration, with proof of recent ZIKV infection and negative screening for etiologies of GBS. RESULTS: Of the sample of 34 patients with suspected GBS during the outbreak, 30 had a proven presence of GBS, and 23 had a recent ZIKV infection. The estimated GBS incidence rate ratio (2016 vs 2006-2015) was 4.52 (95% confidence interval, 2.80-7.64; P = .0001). Recent ZIKV infection was confirmed by urine reverse-transcription polymerase chain reaction (RT-PCR) analysis in 17 cases and by serology in 6 cases. Patients, 65% of whom were male, had a median age of 61 years (interquartile range, 56-71 years) and experienced severe GBS. Electrophysiological tests were consistent with the primary demyelinating form of the disease. CONCLUSIONS: ZIKV infection is usually benign, when symptomatic, but in countries at risk of ZIKV epidemics, adequate intensive care bed capacity is required for management of severe GBS cases. Arbovirus RNA detection by RT-PCR should be part of the management of GBS cases.
Assuntos
Surtos de Doenças/estatística & dados numéricos , Síndrome de Guillain-Barré , Infecção por Zika virus , Zika virus , Idoso , Feminino , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/etiologia , Humanos , Masculino , Martinica/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Infecção por Zika virus/complicações , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologiaRESUMO
BACKGROUND: In French Guiana, cervical cancer is the second most frequent cancer in females. The objective of the present study was to describe the prevalence of HPV infections in women with normal cervical cytology living in the remote villages of French Guiana. METHODS: Before the study, the study team communicated in the remote villages on the importance of screening. All women from the target population were offered to participate. They signed informed consent during inclusion and then had a concomitant HPV-test and cervical smear. Only women with normal cytology and a good quality smear were analyzed. The detection of HPV-DNA was performed using the GREINER-BIO-ONE kit. RESULTS: Overall, 27.2% of women with normal cervical cytology had a positive HPV-test. There was a U-shaped evolution of prevalence with women over 50 years having the highest HPV prevalence, followed by the 20 to 29 years group. The most prevalent HPV genotypes were HPV 53(3.52%), 68(3.33%), 52(2.59%), 31(2.22%) and 16 (1.85%). The proportion of HPV 16 among HPV-infected women was 6.8%. CONCLUSIONS: HPV prevalence in cytologically normal women was very high. The most prevalent genotypes were very different from what is usually described in the world, and notably in South America.
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Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adulto , Idoso , Colo do Útero/citologia , Estudos Transversais , DNA Viral/genética , Feminino , Guiana Francesa/epidemiologia , Humanos , Pessoa de Meia-Idade , Teste de Papanicolaou , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/prevenção & controle , Prevalência , Inquéritos e Questionários , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/prevenção & controle , Serviços de Saúde da Mulher , Adulto JovemRESUMO
We report two cases of encephalopathy (one with seizures, one with electroencephalogram changes) in patients with Zika virus infection. The cases occurred on Martinique in February 2016, during the Zika virus outbreak. Awareness of the various neurological complications of Zika virus infection is needed for patients living in areas affected by Zika virus infections or for travellers to these areas.
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Líquido Cefalorraquidiano/virologia , Encefalite Viral/líquido cefalorraquidiano , Encefalite Viral/virologia , Infecção por Zika virus/líquido cefalorraquidiano , Infecção por Zika virus/virologia , Zika virus/isolamento & purificação , Idoso , Feminino , Humanos , Masculino , Martinica/epidemiologia , Vigilância da População , Adulto JovemRESUMO
We report two cases of Guillain-Barré syndrome who had concomitant Zika virus viruria. This viruria persisted for longer than 15 days after symptom onset. The cases occurred on Martinique in January 2016, at the beginning of the Zika virus outbreak. Awareness of this possible neurological complication of ZikV infection is needed.
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Síndrome de Guillain-Barré/virologia , Urina/virologia , Infecção por Zika virus/complicações , Zika virus/isolamento & purificação , Ensaio de Imunoadsorção Enzimática , Feminino , Síndrome de Guillain-Barré/complicações , Humanos , Masculino , Martinica , Pessoa de Meia-Idade , RNA Viral/sangue , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem , Zika virus/genética , Infecção por Zika virus/diagnósticoRESUMO
Following of the emergence of Zika virus in Brazil in 2015, an epidemiological surveillance system was quickly implemented in the French overseas Territories of America (FTA) according to previous experience with dengue and chikungunya and has detected first cases of Zika. General practitioners and medical microbiologists were invited to report all clinically suspected cases of Zika, laboratory investigations were systematically conducted (RT-PCR). On 18 December, the first autochthonous case of Zika virus infection was confirmed by RT-PCR on French Guiana and Martinique, indicating introduction of Zika virus in FTA. The viral circulation of Zika virus was then also confirmed on Guadeloupe and Saint-Martin. We report here early findings on 203 confirmed cases of Zika virus infection identified by RT-PCR or seroneutralisation on Martinique Island between 24 November 2015 and 20 January 2016. All cases were investigated. Common clinical signs were observed (maculopapular rash, arthralgia, fever, myalgia and conjunctival hyperaemia) among these patients, but the rash, the foundation of our case definition, may be absent in a significant proportion of patients (16%). These results are important for the implementation of a suspected case definition, the main tool for epidemiological surveillance, in territories that may be affected by ZIKV emergence, including Europe.
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Doenças Transmissíveis Emergentes/epidemiologia , Surtos de Doenças , Vigilância da População , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia , Zika virus/isolamento & purificação , Humanos , Martinica/epidemiologia , RNA Viral/genética , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Zika virus/genética , Infecção por Zika virus/transmissãoRESUMO
To identify factors associated with disease severity, we examined 102 patients with quantitative PCR-confirmed leptospirosis in Martinique during 2010-2013. Associated factors were hypotension, chest auscultation abnormalities, icterus, oligo/anuria, thrombocytopenia, prothrombin time <68%, high levels of leptospiremia, and infection with L. interrogans serovar Icterohaemorrhagiae/Copenhageni.
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Surtos de Doenças , Leptospirose/epidemiologia , Adulto , Animais , Doenças do Cão/epidemiologia , Doenças do Cão/genética , Doenças do Cão/patologia , Cães , Feminino , Humanos , Leptospirose/sangue , Leptospirose/genética , Masculino , Martinica/epidemiologia , Pessoa de Meia-Idade , Zoonoses/epidemiologiaRESUMO
UNLABELLED: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that promotes neuronal proliferation, survival, and plasticity. These effects occur through autocrine and paracrine signaling events initiated by interactions between secreted BDNF and its high-affinity receptor, TrkB. A BDNF/TrkB autocrine/paracrine signaling loop has additionally been implicated in augmenting the survival of cells representing several human cancers and is associated with poor patient prognosis. Adult T-cell leukemia (ATL) is a fatal malignancy caused by infection with the complex retrovirus human T-cell leukemia virus type 1 (HTLV-1). In this study, we found that the HTLV-1-encoded protein HBZ activates expression of BDNF, and consistent with this effect, BDNF expression is elevated in HTLV-1-infected T-cell lines compared to uninfected T cells. Expression of TrkB is also higher in HTLV-1-infected T-cell lines than in uninfected T cells. Furthermore, levels of both BDNF and TrkB mRNAs are elevated in peripheral blood mononuclear cells (PBMCs) from ATL patients, and ATL patient sera contain higher concentrations of BDNF than sera from noninfected individuals. Finally, chemical inhibition of TrkB signaling increases apoptosis in HTLV-1-infected T cells and reduces phosphorylation of glycogen synthase kinase 3ß (GSK-3ß), a downstream target in the signaling pathway. These results suggest that HBZ contributes to an active BDNF/TrkB autocrine/paracrine signaling loop in HTLV-1-infected T cells that enhances the survival of these cells. IMPORTANCE: Infection with human T-cell leukemia virus type 1 (HTLV-1) can cause a rare form of leukemia designated adult T-cell leukemia (ATL). Because ATL patients are unresponsive to chemotherapy, this malignancy is fatal. As a retrovirus, HTLV-1 integrates its genome into a host cell chromosome in order to utilize host factors for replication and expression of viral proteins. However, in infected cells from ATL patients, the viral genome is frequently modified to block expression of all but a single viral protein. This protein, known as HBZ, is therefore believed to modulate cellular pathways necessary for the leukemic state and the chemotherapeutic resistance of the cell. Here we provide evidence to support this hypothesis. We found that HBZ promotes a BDNF/TrkB autocrine/paracrine signaling pathway that is known to enhance the survival and chemotherapeutic resistance of other types of cancer cells. It is possible that inhibition of this pathway may improve treatments for ATL.
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Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Transformação Celular Viral , Interações Hospedeiro-Patógeno , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Glicoproteínas de Membrana/metabolismo , Proteínas Tirosina Quinases/metabolismo , Linfócitos T/virologia , Proteínas Virais/metabolismo , Sobrevivência Celular , Humanos , Receptor trkB , Proteínas dos Retroviridae , Linfócitos T/fisiologiaRESUMO
BACKGROUND: Dengue is the most frequent arthropod-borne viral disease worldwide. Because dengue manifestations are similar to those of many other febrile syndromes, the availability of dengue-specific laboratory tests is useful for the differential diagnosis. Timely and accurate diagnosis of dengue virus (DENV) infection is important for appropriate management of complications, pathophysiological studies, epidemiological investigations and optimization of vector-control measures. Several "in-house" reverse transcriptase-polymerase chain reaction (RT-PCR) methods have been developed to detect, type and/or quantify DENV. Standardized dengue RT-PCR kits with internal controls have been recently introduced, but need clinical evaluation. We assessed the performances of 4 commercial DENV real-time RT-PCR kits. FINDINGS: The 4 kits were evaluated using a panel of 162 samples positive with an existing in-place hemi-nested RT-PCR used for routine DENV-infection diagnosis in patients with acute-febrile disease. The panel included 46 DENV-1, 37 DENV-2, 33 DENV-3, and 46 DENV-4. Also, 70 negative serum specimens were used to determine specificity. Geno-Sen's Dengue 1-4 Real-Time RT-PCR kit was the only assay to provide quantification using standards, but lacked sensitivity for DENV-4 detection. The SimplexaTM Dengue RT-PCR assay, with 151 (93.2% [95% confidence interval, 89.3-97.1]) positive samples, had significantly higher sensitivity than the other 3 kits; in a complementary evaluation of 111 consecutive patients' samples, its performance and genotyping agreed with the hemi-nested gold-standard assay. CONCLUSIONS: The SimplexaTM Dengue RT-PCR's good performance to detect and genotype DENV1-4 requires further evaluation in multicenter and prospective studies, particularly in settings of clinical diagnosis during dengue outbreaks.
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Vírus da Dengue/isolamento & purificação , Dengue/diagnóstico , Kit de Reagentes para Diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Dengue/virologia , Humanos , Sensibilidade e Especificidade , Proteínas Virais/isolamento & purificaçãoRESUMO
Objectives: Human T-lymphotropic virus 1 infection is endemic in the French Antilles, French Guiana, and sub-Saharan Africa, the origin of many immigrants currently living in France. There are no national screening recommendations outside of the regulatory obligations concerning donations of blood, tissue, gametes, or milk to a lactarium. This study aimed to investigate the screening and diagnostic practices for this infection in France. Methods: Serological statistics for regulatory, antenatal, sexually transmitted infections (for CeGIDDs (Centre Gratuit d'Information, de Dépistage et de Diagnostic des Infections Sexuellement Transmissibles), which are public sexual health clinics), accidental exposure to blood screenings, and diagnosis since January 1, 2018 were collected from 23 hospital laboratories (two in the French Antilles, 21 in mainland France) associated with 55 hospitals and 22 maternity units. Results: A total absence of antenatal screening was reported by 75% of the laboratories associated with maternity units in mainland France. All the laboratories in mainland France reported an absence of screening in the accidental exposure to blood context, as did all the laboratories in mainland France associated with a CeGIDD in the context of sexually transmitted infection screening. Conversely, screening in accordance with the existing regulations was generally systematically carried out. The most frequently reported diagnostic contexts were hematology and neurology. Conclusions: This study reveals an underscreening of human T-lymphotropic virus 1 in the hospital laboratories of mainland France.
RESUMO
Ten Hepatitis B virus (HBV) genotypes, as well as numerous subgenotypes, have been described in well-characterized ethnogeographical populations. Martinique has been at a crossroads between Africa, Europe, India and the Americas because of the slave trade (17th-19th centuries), followed by an important immigration of Indian and West African workers. In this work, we aimed to study the molecular epidemiology of HBV infection in Martinique according to this unique settlement pattern. To that end, blood samples from 86 consecutive HBV-infected patients from the main hospitals of the island, were retrospectively analysed. Direct sequencing of the pre-S1 or pre-C-C region or complete genome sequencing, followed by phylogenetic analyses were performed. HBV genotypes were: HBV/A1 (68.6â%), HBV/A2 (10.5â%), HBV/D, mainly HBV/D3 and HBV/D4 (8.1â%), HBV/F (3.5â%), and also HBV/E (2.3â%), two strains isolated from two West-African patients. Moreover, 74â% of the HBeAg-negative strains harboured classical pre-C-C mutations, and most HBV/A1 strains also containing specific mutations. Finally, various patterns of deletion mutants in pre-S and pre-C-C regions were found. In conclusion, our findings point to historical and migration-related issues in HBV-genotype distribution suggesting that HBV/A1, but not HBV/E, was imported from Africa during the slave trade, and further supporting the hypothesis that HBV/E has emerged recently in West Africa (<150 years). Potential origins of 'European' HBV/A2 and HBV/D3, 'Amerindian' HBV/F, and HBV/D4 strains are also discussed. Such HBV genetic diversity, beyond its epidemiological interest, may have a clinical impact on the natural history of HBV infection in Martinique.
Assuntos
Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Hepatite B/epidemiologia , Hepatite B/virologia , Adolescente , Adulto , África/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Indígena Americano ou Nativo do Alasca , América/epidemiologia , Criança , Europa (Continente)/epidemiologia , Feminino , Genoma Viral , Genótipo , Hepatite B/etnologia , Humanos , Masculino , Martinica/epidemiologia , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação , Filogenia , Estudos Retrospectivos , Carga Viral , Adulto JovemRESUMO
Infection with the human T-cell leukemia virus type 1 (HTLV-1) results in a variety of diseases including adult T-cell leukemia (ATL), a fatal malignancy characterized by the uncontrolled proliferation of virally infected CD4(+) T cells. The HTLV-1 basic leucine zipper factor (HBZ) is believed to contribute to development and maintenance of ATL. Unlike the other HTLV-1 genes, the hbz gene is encoded on the complementary strand of the provirus and therefore is not under direct control of the promoter within the 5' long terminal repeat (LTR) of the provirus. This promoter can undergo inactivating genetic or epigenetic changes during the course of ATL that eliminates expression of all viral genes except that of hbz. In contrast, repressive modifications are not known to occur on the hbz promoter located in the 3' LTR, and hbz expression has been consistently detected in all ATL patient samples. Although Sp1 regulates basal transcription from the HBZ promoter, other factors that activate transcription remain undefined. In this study, we used a proviral reporter construct deleted of the 5' LTR to show that HBZ upregulates its own expression through cooperation with JunD. Activation of antisense transcription was apparent in serum-deprived cells in which the level of JunD was elevated, and elimination of JunD expression by gene knockout or shRNA-mediated knockdown abrogated this effect. Activation through HBZ and JunD additionally required Sp1 binding at the hbz promoter. These data favor a model in which JunD is recruited to the promoter through Sp1, where it heterodimerizes with HBZ thereby enhancing its activity. Separately, hbz gene expression led to an increase in JunD abundance, and this effect correlated with emergence of features of transformed cells in immortalized fibroblasts. Overall, our results suggest that JunD represents a novel therapeutic target for the treatment of ATL.
Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Regulação Viral da Expressão Gênica , Vírus Linfotrópico T Tipo 1 Humano/genética , Leucemia-Linfoma de Células T do Adulto/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , RNA Antissenso/genética , Sequências Repetidas Terminais , Proteínas Virais/metabolismo , Animais , Fatores de Transcrição de Zíper de Leucina Básica/genética , Linhagem Celular , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Humanos , Leucemia-Linfoma de Células T do Adulto/genética , Leucemia-Linfoma de Células T do Adulto/virologia , Camundongos , Ligação Proteica , Proteínas Proto-Oncogênicas c-jun/genética , RNA Antissenso/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , Regulação para Cima , Proteínas Virais/genéticaRESUMO
A determinant of human T-lymphotropic virus-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) development is the HTLV-1-infected cell burden. Viral proteins Tax and HBZ, encoded by the sense and antisense strands of the pX region, respectively, play key roles in HTLV-1 persistence. Tax drives CD4(+)-T cell clonal expansion and is the immunodominant viral antigen recognized by the immune response. Valproate (2-n-propylpentanoic acid, VPA), a histone deacetylase inhibitor, was thought to trigger Tax expression, thereby exposing the latent HTLV-1 reservoir to immune destruction. We evaluated the impact of VPA on Tax, Gag, and HBZ expressions in cultured lymphocytes from HTLV-1 asymptomatic carriers and HAM/TSP patients. Approximately one-fifth of provirus-positive CD4(+) T cells spontaneously became Tax-positive, but this fraction rose to two-thirds of Tax-positive-infected cells when cultured with VPA. Valproate enhanced Gag-p19 release. Tax- and Gag-mRNA levels peaked spontaneously, before declining concomitantly to HBZ-mRNA increase. VPA enhanced and prolonged Tax-mRNA expression, whereas it blocked HBZ expression. Our findings suggest that, in addition to modulating Tax expression, another mechanism involving HBZ repression might determine the outcome of VPA treatment on HTLV-1-infected-cell proliferation and survival.
Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/biossíntese , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Produtos do Gene tax/biossíntese , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Ácido Valproico/farmacologia , Proteínas Virais/biossíntese , Elementos Antissenso (Genética)/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Doenças Assintomáticas , Fatores de Transcrição de Zíper de Leucina Básica/genética , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/virologia , Genes gag , Genes pX , Histona Acetiltransferases/antagonistas & inibidores , Humanos , Linfócitos/efeitos dos fármacos , Linfócitos/virologia , Paraparesia Espástica Tropical , Provírus/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Viral/biossíntese , RNA Viral/genética , Proteínas dos Retroviridae , Proteínas Virais/genética , Produtos do Gene gag do Vírus da Imunodeficiência Humana/biossínteseRESUMO
HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease of the central nervous system induced by human T-lymphotropic virus type 1. As a potential therapeutic approach, we previously suggested reducing the proviral load by modulating lysine deacetylase activity using valproic acid (VPA) and exposing virus-positive cells to the host immune response. We conducted a single-center, 2-year, open-label trial, with 19 HAM/TSP volunteers treated with oral VPA. Proviral load, CD38/HLA-DR expression, and CD8(+) lysis efficiency were not significantly affected by VPA. Mean scores of HAM/TSP disability did not differ between baseline and final visit. Walking Time Test increased significantly (> 20%) in 3 patients and was in keeping with minor VPA side effects (drowsiness and tremor). Walking Time Test improved rapidly after VPA discontinuation. We conclude that long-term treatment with VPA is safe in HAM/TSP.