RESUMO
BACKGROUND: Early pregnancy Zika virus (ZIKV) infection is associated with major brain damage in fetuses, leading to microcephaly in 0.6-5.0% of cases, but the underlying mechanisms remain largely unknown. METHODS: To understand the kinetics of ZIKV infection during fetal development in a nonhuman primate model, four cynomolgus macaque fetuses were exposed in utero through echo-guided intramuscular inoculation with 103 PFU of ZIKV at 70-80 days of gestation, 2 controls were mock inoculated. Clinical, immuno-virological and ultrasound imaging follow-ups of the mother/fetus pairs were performed until autopsy after cesarean section 1 or 2 months after exposure (n = 3 per group). RESULTS: ZIKV was transmitted from the fetus to the mother and then replicate in the peripheral blood of the mother from week 1 to 4 postexposure. Infected fetal brains tended to be smaller than those of controls, but not the femur lengths. High level of viral RNA ws found after the first month in brain tissues and placenta. Thereafter, there was partial control of the virus in the fetus, resulting in a decreased number of infected tissue sections and a decreased viral load. Immune cellular and humoral responses were effectively induced. CONCLUSIONS: ZIKV infection during the second trimester of gestation induces short-term brain injury, and although viral genomes persist in tissues, most of the virus is cleared before delivery.
Assuntos
Encéfalo , Modelos Animais de Doenças , Feto , Complicações Infecciosas na Gravidez , Carga Viral , Infecção por Zika virus , Zika virus , Animais , Feminino , Gravidez , Infecção por Zika virus/virologia , Feto/virologia , Complicações Infecciosas na Gravidez/virologia , Encéfalo/virologia , Macaca fascicularis/virologia , RNA Viral , Placenta/virologia , Transmissão Vertical de Doenças InfecciosasRESUMO
During 2019-2020, a chikungunya outbreak occurred in Djibouti City, Djibouti, while dengue virus and malaria parasites were cocirculating. We used blotting paper to detect arbovirus emergence and confirm that it is a robust method for detecting and monitoring arbovirus outbreaks remotely.
Assuntos
Arbovírus , Febre de Chikungunya , Vírus Chikungunya , Vírus da Dengue , Dengue , Infecção por Zika virus , Humanos , Febre de Chikungunya/epidemiologia , Vírus Chikungunya/genética , Djibuti/epidemiologia , Surtos de Doenças , Dengue/epidemiologia , Infecção por Zika virus/epidemiologiaRESUMO
We investigated a COVID-19 outbreak at a fire station in Marseille, France. Confirmed cases were defined as individuals with positive SARS-CoV-2 reverse transcription (RT)-PCR and/or neutralising antibodies. All 85 firefighters at work during the outbreak period were included after questioning and sampled for RT-PCR and viral neutralisation assay. Twenty-three firefighters were confirmed positive, 19 of them were symptomatic, and four asymptomatic cases were confirmed by virus neutralisation. A total of 22 firefighters had specific neutralising antibodies against SARS-CoV-2. Neutralising antibodies were found in four asymptomatic and 18 symptomatic cases. Eleven symptomatic cases had high titres (≥ 1:80). The earliest detection of neutralising antibodies was 7 days after symptom onset, and 80% had neutralising antibodies 15 days after onset. One viral culture was positive 13 days after onset. The attack rate was 27%. We identified two introductions of the virus in this outbreak, through a presymptomatic and a paucisymptomatic case. Asymptomatic cases were not the source of a third generation of cases, although they worked without wearing a mask, indicating that asymptomatic cases did not play a significant role in this outbreak. Management and strategy based on early research of clinical signs associated with self-quarantine was effective.
Assuntos
COVID-19 , Bombeiros , Surtos de Doenças , França/epidemiologia , Humanos , SARS-CoV-2RESUMO
We compared the performance of SARS-CoV-2 neutralising antibody testing between 12 European laboratories involved in convalescent plasma trials. Raw titres differed almost 100-fold differences between laboratories when blind-testing 15 plasma samples. Calibration of titres in relation to the reference reagent and standard curve obtained by testing a dilution series reduced the inter-laboratory variability ca 10-fold. The harmonisation of neutralising antibody quantification is a vital step towards determining the protective and therapeutic levels of neutralising antibodies.
Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/terapia , Europa (Continente) , Humanos , Imunização Passiva , Soroterapia para COVID-19RESUMO
BACKGROUND: Passive therapy with convalescent plasma (CP) could be an effective and safe treatment option in COVID-19 patients. Neutralizing antibodies present in CP generated in response to SARS-CoV-2 infection and directed against the receptor-binding domain of the spike protein are considered to play a major role in the viral clearance. CP infusion may also contribute to the modulation of the immune response through its immunomodulatory effect. We describe for the first time the effectiveness of a CP collection protocol from repeated donations in young patients. MATERIALS AND METHODS: We enrolled health service workers who experienced mild to moderate COVID-19 and from whom several donations have been collected. No minimal severity threshold and no biological cure criteria were required. Donors could return to a second plasma donation 14 days after the first donation. A minimal neutralizing antibody titer of 1:40 was considered for clinical use. RESULTS: Eighty-eight donors were included (median age 35 [28-48] years, 41 women), and 149 plasma products were collected. COVID-19 were mainly WHO stage 2 infections (96%). Among the 88 first donations, 76% had neutralizing antibody titers higher than or equal to 1:40. Eighty-eight percent of donors who came for a second donation had a neutralizing antibody titer of 1:40. Median durations were 15 (15-19) and 38 (33-46) days from the first to the second donation and from recovery to the second donation, respectively. Sixty-nine percent of donors who came for a third donation had a neutralizing antibody titer of 1:40. Median durations were 16 (13-37) and 54 (49-61) days from the second to the third donation and from recovery to the third donation, respectively. No significant difference was observed between the IgG ratio and the age of the donors or the time between recovery and donation. The average IgG ratio did not significantly vary between donations. When focused on repeated blood donors, no significant differences were observed either. CONCLUSION: The recruitment of young patients with a mild to moderate CO-VID-19 course is an efficient possibility to collect CP with a satisfactory level of neutralizing antibodies. Repeated donations are a well-tolerated and effective way of CP collection.
RESUMO
BACKGROUND: Persistence of Zika virus (ZIKV) ribonucleic acid (RNA) in semen is common after infection. METHODS: We designed a reverse-transcription polymerase chain reaction assay that targets antisense ZIKV RNA (asRNA) to assess ZIKV replication competence in ZIKV RNA-positive semen samples. RESULTS: We detected ZIKV asRNA in semen of 9 of 19 men (47.4%) diagnosed with ZIKV infection. All asRNA-positive samples had high ZIKV loads (cycle threshold values <26) and were obtained within 21 days of symptom onset. CONCLUSIONS: The sensitivity of the asRNA assay for detection of ZIKV replication was higher than that of conventional virus isolation methods (47.4% vs 21.1%, P = .032).
Assuntos
RNA Antissenso/análise , RNA Viral/análise , Sêmen/virologia , Replicação Viral , Infecção por Zika virus/virologia , Zika virus/fisiologia , Humanos , Masculino , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Zika virus/genética , Zika virus/isolamento & purificaçãoRESUMO
In a matched case-control study where 24 cases developed Guillain-Barré syndrome (GBS) during the 2014 chikungunya outbreak in the French West Indies and 72 controls were blood donors during the same period, chikungunya infection was a risk factor for GBS (odds ratio, 8.3; 95% confidence interval, 2.3-29.7; P = .001).
Assuntos
Febre de Chikungunya , Síndrome de Guillain-Barré , Infecção por Zika virus , Estudos de Casos e Controles , Febre de Chikungunya/complicações , Febre de Chikungunya/epidemiologia , Síndrome de Guillain-Barré/epidemiologia , Síndrome de Guillain-Barré/etiologia , Humanos , Fatores de RiscoRESUMO
We investigated a case of dengue virus type 1 infection acquired in Benin. Phylogenetic analysis revealed the strain belongs to genotype V but clusters with Asian, rather than with known African, strains. Our finding suggests the introduction of Asian dengue virus in West Africa.
Assuntos
Vírus da Dengue , Dengue , África Ocidental , Benin/epidemiologia , Dengue/diagnóstico , Dengue/epidemiologia , Vírus da Dengue/genética , França/epidemiologia , Humanos , FilogeniaRESUMO
The kinetics of arthropod-borne virus (arbovirus) transmission by their vectors have long been recognized as a powerful determinant of arbovirus epidemiology. The time interval between virus acquisition and transmission by the vector, termed extrinsic incubation period (EIP), combines with vector mortality rate and vector competence to determine the proportion of infected vectors that eventually become infectious. However, the dynamic nature of this process, and the amount of natural variation in transmission kinetics among arbovirus strains, are poorly documented empirically and are rarely considered in epidemiological models. Here, we combine newly generated empirical measurements in vivo and outbreak simulations in silico to assess the epidemiological significance of genetic variation in dengue virus (DENV) transmission kinetics by Aedes aegypti mosquitoes. We found significant variation in the dynamics of systemic mosquito infection, a proxy for EIP, among eight field-derived DENV isolates representing the worldwide diversity of recently circulating type 1 strains. Using a stochastic agent-based model to compute time-dependent individual transmission probabilities, we predict that the observed variation in systemic mosquito infection kinetics may drive significant differences in the probability of dengue outbreak and the number of human infections. Our results demonstrate that infection dynamics in mosquitoes vary among wild-type DENV isolates and that this variation potentially affects the risk and magnitude of dengue outbreaks. Our quantitative assessment of DENV genetic variation in transmission kinetics contributes to improve our understanding of heterogeneities in arbovirus epidemiological dynamics.
Assuntos
Culicidae/virologia , Vírus da Dengue/genética , Dengue/genética , Dengue/transmissão , Mosquitos Vetores/virologia , Animais , Variação GenéticaRESUMO
BACKGROUND: Yellow fever vaccine exists for over 80 years and is considered to be relatively safe. However, in rare cases it can produce serious neurotropic and viscerotropic complications. We report a case of a patient who presented both viscerotropic and neurological manifestations after yellow fever vaccination. CASE PRESENTATION: We describe the case of a 37 years old man who developed after the yellow fever vaccination a yellow fever vaccine-associated viscerotropic disease followed by acute uveitis. Prolonged detection of yellow fever RNA in blood and urine was consistent with yellow fever vaccine-associated adverse event. The final outcome was good, although with persistent fatigue over a few months. CONCLUSIONS: Even if the yellow fever vaccine is relatively safe, physicians should be aware of its possible serious adverse effects.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Uveíte/induzido quimicamente , Vacinação/efeitos adversos , Vacina contra Febre Amarela/efeitos adversos , Doença Aguda , Adulto , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/sangue , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/urina , Fadiga/induzido quimicamente , Humanos , Masculino , RNA Viral/sangue , RNA Viral/urinaRESUMO
Rift Valley Fever (RVF) is an emerging zoonotic arbovirus with a complex cycle of transmission that makes difficult the prediction of its expansion. Recent outbreaks outside Africa have led to rediscover the human disease but it remains poorly known. The wide spectrum of acute and delayed manifestations with potential unfavorable outcome much complicate the management of suspected cases and prediction of morbidity and mortality during an outbreak. We reviewed literature data on bio-clinical characteristics and treatments of RVF human illness. We identified gaps in the field and provided a practical algorithm to assist clinicians in the cases assessment, determination of setting of care and prolonged follow-up.
Assuntos
Surtos de Doenças , Monitoramento Epidemiológico , Fidelidade a Diretrizes , Febre do Vale de Rift , Animais , Vetores Artrópodes/virologia , Bunyaviridae/isolamento & purificação , Bunyaviridae/patogenicidade , Doenças Transmissíveis Emergentes/virologia , Humanos , Gado/virologia , Febre do Vale de Rift/diagnóstico , Febre do Vale de Rift/patologia , Febre do Vale de Rift/terapia , Febre do Vale de Rift/transmissão , Zoonoses/virologiaRESUMO
Three autochthonous cases of tick-borne encephalitis (TBE) acquired in rural areas of France where Lyme borreliosis, but not TBE, is endemic highlight the emergence of TBE in new areas. For patients with neurologic involvement who have been in regions where Ixodes ticks circulate, clinicians should test for TBE virus and other tickborne viruses.
Assuntos
Vírus da Encefalite Transmitidos por Carrapatos , Encefalite Transmitida por Carrapatos/epidemiologia , Idoso , Animais , Criança , Encefalite Transmitida por Carrapatos/diagnóstico , Feminino , França/epidemiologia , Humanos , Ixodes/virologia , Masculino , Testes Sorológicos/métodosRESUMO
The incidence of arbovirus infections has increased dramatically in recent decades, affecting hundreds of millions of people each year. The Togaviridae family includes the chikungunya virus (CHIKV), which is typically transmitted by Aedes mosquitoes and causes a wide range of symptoms from flu-like fever to severe arthralgia. Although conventional diagnostic tests can provide early diagnosis of CHIKV infections, access to these tests is often limited in developing countries. Consequently, there is an urgent need to develop efficient, affordable, simple, rapid, and robust diagnostic tools that can be used in point-of-care settings. Early diagnosis is crucial to improve patient management and to reduce the risk of complications. A glass-fiber laser-cut microfluidic device (paper-based analytical device [PAD]) was designed and evaluated in a proof of principle context, for the analysis of 30 µL of patient serum. Biological raw materials used for the functionalization of the PAD were first screened by MAC-ELISA (IgM capture enzyme-linked immunosorbent assay) for CHIKV Immunoglobulin M (IgM) capture and then evaluated on the PAD using various human samples. Compared with viral lysate traditionally used for chikungunya (CHIK) serology, CHIKV pseudo-particles (PPs) have proven to be powerful antigens for specific IgM capture. The PAD was able to detect CHIKV IgM in human sera in less than 10 minutes. Results obtained in patient sera showed a sensitivity of 70.6% and a specificity of around 98%. The PAD showed few cross-reactions with other tropical viral diseases. The PAD could help health workers in the early diagnosis of tropical diseases such as CHIK, which require specific management protocols in at-risk populations.
Assuntos
Anticorpos Antivirais/isolamento & purificação , Febre de Chikungunya/diagnóstico , Imunoglobulina M/isolamento & purificação , Microfluídica/instrumentação , Papel , Adulto , Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , Febre de Chikungunya/imunologia , Vírus Chikungunya , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina M/sangue , Lasers , Masculino , Microfluídica/métodos , Sensibilidade e Especificidade , Vírion/imunologiaRESUMO
On 16 September 2016, the World Health Organization confirmed a Rift Valley fever (RVF) outbreak in Niger. Epidemiological surveillance was reinforced among the French Armed Forces deployed in Niger and bordering countries: Chad, Mali and Burkina Faso. On 26 October, a probable case of RVF was reported in a service member sampled in Mali 3 weeks earlier. At the time the result was reported, the patient was on vacation on Martinique. An epidemiological investigation was conducted to confirm this case and identify other cases. Finally, the case was not confirmed, but three suspected cases of RVF were confirmed using serological and molecular testing. RVF viral RNA was detectable in whole blood for 57 and 67 days after onset of symptoms for two cases, although it was absent from plasma and serum. At the time of diagnosis, these cases had already returned from Mali to Europe. The infectivity of other arboviruses in whole blood has already been highlighted. That RVF virus has been detected in whole blood that long after the onset of symptoms (67 days) raises the question of its potential prolonged infectivity. Because of exposure to tropical infectious diseases during deployment, military populations could import emerging pathogens to Europe.
Assuntos
Febre/etiologia , Febre do Vale de Rift/diagnóstico , Vírus da Febre do Vale do Rift/isolamento & purificação , Adulto , Animais , Anticorpos Antivirais/sangue , Estudos Transversais , Culex/virologia , Surtos de Doenças , Europa (Continente)/epidemiologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Mali/epidemiologia , Militares , RNA Viral/sangue , RNA Viral/genética , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Febre do Vale de Rift/sangue , Febre do Vale de Rift/epidemiologia , Febre do Vale de Rift/transmissão , Vírus da Febre do Vale do Rift/genética , Vigilância de Evento Sentinela , Estudos Soroepidemiológicos , ZoonosesRESUMO
On 1 October 2019, a locally-acquired Zika virus disease case was laboratory confirmed in Hyères, Var department. Active case finding identified two additional locally-acquired cases living within 90 m, with symptom onset 8 days before the index case. Extensive patient interviews did not yield information supporting transmission through sexual contact or substances of human origin. Vector-borne transmission by local Aedes albopictus mosquitoes is the most likely mode of transmission. Here we describe the public health response.
Assuntos
Aedes/virologia , Mosquitos Vetores/virologia , Saliva/virologia , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/transmissão , Zika virus/isolamento & purificação , Animais , França , Humanos , Controle de Mosquitos/métodos , Infecção por Zika virus/virologiaRESUMO
Infection with Usutu virus (USUV) has been recently associated with neurologic disorders, such as encephalitis or meningoencephalitis, in humans. These findings indicate that USUV is a potential health threat. We report an acute human infection with USUV in France putatively associated with a clinical diagnosis of idiopathic facial paralysis.
Assuntos
Blefaroptose/etiologia , Paralisia Facial/etiologia , Infecções por Flavivirus/epidemiologia , Infecções por Flavivirus/virologia , Flavivirus/isolamento & purificação , Corticosteroides/uso terapêutico , Adulto , Antivirais/uso terapêutico , Flavivirus/genética , Infecções por Flavivirus/complicações , Infecções por Flavivirus/tratamento farmacológico , França/epidemiologia , Humanos , Masculino , Filogenia , RNA Viral/isolamento & purificação , Valaciclovir/uso terapêuticoRESUMO
BackgroundClusters of dengue cases have recently become more frequent in areas of southern France colonised by the vector mosquito Aedes albopictus. In July 2015, a 2-month outbreak of dengue virus serotype 1 (DENV-1) was reported in Nîmes. Aim: We conducted a serosurvey in the affected area at the end of the vector activity period to determine the true extent of dengue transmission. Methods: We collected capillary blood from consenting household members, and information on their medical and travel histories, and exposure to mosquito bites. Recent infections were identified using IgM and IgG anti-DENV ELISA, followed, when positive, by plaque reduction neutralisation tests on serum against DENV 1-4 and West Nile virus. The prevalence estimator was calibrated on reference demographic data. We quantified the spatial clustering of dengue cases within the affected community and inferred the transmission tree. Results: The study participation rate was 39% (564/1,431). Three of 564 participants tested positive for DENV-1 infection (after marginal calibration, 0.41%; 95% confidence interval: 0.00-0.84). The spatial analysis showed that cases were clustered at the household level. Most participants perceived the presence of mosquitos as abundant (83%) and reported frequent mosquito bites (57%). We incidentally identified six past West Nile virus infections (0.9%; 95% CI: 0.2-1.6). Conclusion: This serosurvey confirms the potential for arboviral diseases to cause outbreaks - albeit limited for now - in France and Europe.
Assuntos
Aedes/virologia , Vírus da Dengue/isolamento & purificação , Dengue/diagnóstico , Surtos de Doenças , Mosquitos Vetores , Animais , Dengue/epidemiologia , Vírus da Dengue/classificação , Vírus da Dengue/genética , Surtos de Doenças/estatística & dados numéricos , Feminino , França/epidemiologia , Humanos , Masculino , Prevalência , Estudos Soroepidemiológicos , Análise EspacialRESUMO
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
Zika virus (ZIKV) infections are a significant public health concern. A strong capability for ZIKV detection is an absolute requirement for adequate preparedness and response strategies and individual patient care. The objective of this study was to assess and improve the capability of European expert laboratories for molecular testing for ZIKV through an external quality assessment (EQA) scheme. Laboratories were provided a panel of 12 samples which included negative samples, samples containing African- or Asian-lineage ZIKV at various concentrations (103 to 109 copies/ml), and samples containing dengue virus, yellow fever virus, or chikungunya virus. The results were analyzed on the basis of the outcomes of testing for the samples and the extraction and detection method used. Samples with a ZIKV RNA status scored correctly by >50% of the laboratories were designated the core sample. A total of 85 panel outcomes were submitted by 50 laboratories in 31 countries. The results designated all samples as core samples. Thirty-three percent (28/85) of the panel outcomes identified all samples. Analysis at the laboratory level showed that only 40% of the laboratories (20/50), representing 45% of the countries, scored sufficiently; i.e., they had at least one test operational that scored all core samples correctly. There is a need for improvement of the molecular detection of ZIKV in 60% of the participating laboratories. While the specificity of the tests was more robust, the results of the EQA showed large variation in test sensitivity. Improvements should focus on both nucleic acid extraction and ZIKV detection methods.
Assuntos
Laboratórios , Ensaio de Proficiência Laboratorial , Infecção por Zika virus/diagnóstico , Zika virus/isolamento & purificação , Europa (Continente) , Humanos , Sensibilidade e EspecificidadeRESUMO
A woman with controlled HIV infection developed in late August 2016 a pruritic rash with fever and conjunctival hyperaemia after a trip to the French Caribbean islands. On day 3 after symptom onset, Zika virus RNA was detected in plasma, urine and vaginal samples with respective viral loads of 3.8, 6.1 and 5.3 log copies/mL. Notably, we demonstrated the presence of infectious Zika virus particles in the vaginal samples by isolation in cell culture.