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2.
Infect Genet Evol ; 78: 104129, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31786339

RESUMO

Chikungunya virus (CHIKV), a positive-sense, single-stranded RNA virus in the family Togaviridae, is transmitted by Aedes mosquitoes. Of three known CHIKV genotypes, the Asian genotype was introduced into the Caribbean islands and rapidly spread throughout Central and South Americas. We previously found patients with symptoms compatible with chikungunya fever in 2014-2015 in Aruba, a Caribbean island of 180 km2. We here describe the full genome sequences of eight CHIKV strains isolated from patient sera of the Aruban outbreak. Phylogenetic analysis revealed that two closely related but distinct lineages of Asian-genotype CHIKV circulated simultaneously during the epidemic in 2014-2015. These results suggested that CHIKV was introduced into Aruba more than once in a short period, reflecting the importance of Aruba as a travel hub within the region.

3.
Trends Microbiol ; 28(4): 276-292, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31864844

RESUMO

Infections with arthropod-borne viruses are increasing globally as a result of climate and demographic changes, global dispersion of insect vectors, and increased air travel. The similar symptomatology of arboviral diseases and the cocirculation of different arboviruses in Africa, Asia, and South America complicate diagnosis. Despite the high sensitivity and specificity of molecular diagnostic tests, their utility is limited to the short viremic phase of arbovirus infections, and therefore the diagnosis of infection is frequently missed in clinical practice. Conversely, the duration of antibody responses provides a wider window of opportunity, making diagnosis more dependent on IgM/IgG detection. This review discusses the issues underlying the low specificity of antibody-detection assays, and addresses the challenges and strategies for discovering more specific biomarkers to enable a more accurate diagnosis.

4.
Glob Health Action ; 12(1): 1666566, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31640505

RESUMO

Zika Preparedness Latin American Network (ZikaPLAN) is a research consortium funded by the European Commission to address the research gaps in combating Zika and to establish a sustainable network with research capacity building in the Americas. Here we present a report on ZikaPLAN`s mid-term achievements since its initiation in October 2016 to June 2019, illustrating the research objectives of the 15 work packages ranging from virology, diagnostics, entomology and vector control, modelling to clinical cohort studies in pregnant women and neonates, as well as studies on the neurological complications of Zika infections in adolescents and adults. For example, the Neuroviruses Emerging in the Americas Study (NEAS) has set up more than 10 clinical sites in Colombia. Through the Butantan Phase 3 dengue vaccine trial, we have access to samples of 17,000 subjects in 14 different geographic locations in Brazil. To address the lack of access to clinical samples for diagnostic evaluation, ZikaPLAN set up a network of quality sites with access to well-characterized clinical specimens and capacity for independent evaluations. The International Committee for Congenital Anomaly Surveillance Tools was formed with global representation from regional networks conducting birth defects surveillance. We have collated a comprehensive inventory of resources and tools for birth defects surveillance, and developed an App for low resource regions facilitating the coding and description of all major externally visible congenital anomalies including congenital Zika syndrome. Research Capacity Network (REDe) is a shared and open resource centre where researchers and health workers can access tools, resources and support, enabling better and more research in the region. Addressing the gap in research capacity in LMICs is pivotal in ensuring broad-based systems to be prepared for the next outbreak. Our shared and open research space through REDe will be used to maximize the transfer of research into practice by summarizing the research output and by hosting the tools, resources, guidance and recommendations generated by these studies. Leveraging on the research from this consortium, we are working towards a research preparedness network.

5.
PLoS Negl Trop Dis ; 13(9): e0007047, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31487279

RESUMO

BACKGROUND: Pathogens causing acute fever, with the exception of malaria, remain largely unidentified in sub-Saharan Africa, given the local unavailability of diagnostic tests and the broad differential diagnosis. METHODOLOGY: We conducted a cross-sectional study including outpatient acute undifferentiated fever in both children and adults, between November 2015 and June 2016 in Kinshasa, Democratic Republic of Congo. Serological and molecular diagnostic tests for selected arboviral infections were performed on blood, including PCR, NS1-RDT, ELISA and IFA for acute, and ELISA and IFA for past infections. RESULTS: Investigation among 342 patients, aged 2 to 68 years (mean age of 21 years), with acute undifferentiated fever (having no clear focus of infection) revealed 19 (8.1%) acute dengue-caused by DENV-1 and/or DENV-2 -and 2 (0.9%) acute chikungunya infections. Furthermore, 30.2% and 26.4% of participants had been infected in the past with dengue and chikungunya, respectively. We found no evidence of acute Zika nor yellow fever virus infections. 45.3% of patients tested positive on malaria Rapid Diagnostic Test, 87.7% received antimalarial treatment and 64.3% received antibacterial treatment. DISCUSSION: Chikungunya outbreaks have been reported in the study area in the past, so the high seroprevalence is not surprising. However, scarce evidence exists on dengue transmission in Kinshasa and based on our data, circulation is more important than previously reported. Furthermore, our study shows that the prescription of antibiotics, both antibacterial and antimalarial drugs, is rampant. Studies like this one, elucidating the causes of acute fever, may lead to a more considerate and rigorous use of antibiotics. This will not only stem the ever-increasing problem of antimicrobial resistance, but will-ultimately and hopefully-improve the clinical care of outpatients in low-resource settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT02656862.


Assuntos
Febre de Chikungunya/diagnóstico , Dengue/diagnóstico , Febre/diagnóstico , Adolescente , Adulto , Idoso , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/virologia , Vírus Chikungunya/genética , Vírus Chikungunya/isolamento & purificação , Vírus Chikungunya/fisiologia , Criança , Pré-Escolar , Estudos Transversais , República Democrática do Congo/epidemiologia , Dengue/epidemiologia , Dengue/virologia , Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Vírus da Dengue/fisiologia , Feminino , Febre/epidemiologia , Febre/virologia , Humanos , Malária/diagnóstico , Malária/epidemiologia , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais/estatística & dados numéricos , Adulto Jovem
6.
Vaccines (Basel) ; 7(3)2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31450775

RESUMO

To combat emerging infectious diseases like Zika virus (ZIKV), synthetic messenger RNAs (mRNAs) encoding viral antigens are very attractive as they allow a rapid, generic, and flexible production of vaccines. In this work, we engineered a self-replicating mRNA (sr-mRNA) vaccine encoding the pre-membrane and envelope (prM-E) glycoproteins of ZIKV. Intradermal electroporation of as few as 1 µg of this mRNA-based ZIKV vaccine induced potent humoral and cellular immune responses in BALB/c and especially IFNAR1-/- C57BL/6 mice, resulting in a complete protection of the latter mice against ZIKV infection. In wild-type C57BL/6 mice, the vaccine resulted in very low seroconversion rates and antibody titers. The potency of the vaccine was inversely related to the dose of mRNA used in wild-type BALB/c or C57BL/6 mice, as robust type I interferon (IFN) response was determined in a reporter mice model (IFN-ß+/Δß-luc). We further investigated the inability of the sr-prM-E-mRNA ZIKV vaccine to raise antibodies in wild-type C57BL/6 mice and found indications that type I IFNs elicited by this naked sr-mRNA vaccine might directly impede the induction of a robust humoral response. Therefore, we assume that the efficacy of sr-mRNA vaccines after intradermal electroporation might be increased by strategies that temper their inherent innate immunogenicity.

7.
Int J STD AIDS ; 30(5): 486-495, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30999835

RESUMO

In this study, we assessed if the superimposition of incident sexually transmitted infections (STIs) on HIV phylogenetic analyses could reveal possible sexual behaviour misclassifications in our HIV-infected population. HIV-1 sequences collected between 1997 and 2014 from 1169 individuals attending a HIV clinic in Antwerp, Belgium were analysed to infer a partial HIV transmission network. Individual demographic, clinical and laboratory data collected during routine HIV follow-up were used to compare clustered and non-clustered individuals using logistic regression analyses. In total, 438 (37.5%) individuals were identified in 136 clusters, including 76 transmission pairs and 60 clusters consisting of three or more individuals. Individuals in a cluster were more likely to have a history of syphilis, Chlamydia and/or gonorrhoea (P < 0.05); however, when analyses were stratified by HIV transmission risk groups (heterosexual and men who have sex with men [MSM]), this association only remained significant for heterosexuals with syphilis (P = 0.001). Under closer scrutiny, this association was driven by six heterosexual men who were located in six almost exclusively MSM clusters. A parsimonious conclusion is that these six individuals were potentially misclassified as heterosexual. Improving the accuracy of sexual behaviour reporting could improve care.


Assuntos
Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Heterossexualidade/estatística & dados numéricos , Homossexualidade Masculina/estatística & dados numéricos , Filogenia , Adulto , Bélgica/epidemiologia , Análise por Conglomerados , Feminino , Genótipo , Infecções por HIV/epidemiologia , HIV-1/isolamento & purificação , Humanos , Incidência , Masculino , Estudos Retrospectivos , Análise de Sequência de DNA , Comportamento Sexual/estatística & dados numéricos , Doenças Sexualmente Transmissíveis/epidemiologia , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética
9.
Eur J Clin Microbiol Infect Dis ; 38(4): 771-778, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30680570

RESUMO

Diagnosing a patient with Zika infection is not always straightforward. Here, we aim to describe our data collected from December 2015 to December 2017 and discuss the implemented algorithm and diagnostic challenges we encountered. At the National Reference Center for Arboviruses at the Institute of Tropical Medicine, Antwerp, Belgium (ITM), a commercial Zika virus (ZIKV) enzyme-linked immunosorbent assay (ELISA) detecting immunoglobulin (Ig) M and IgG, a commercial ZIKV immunofluorescence assay (IFA) detecting IgM, and an in-house Zika virus neutralization test (VNT) were implemented. For molecular detection of ZIKV, an in-house and a commercial real-time RT-PCR were applied. An algorithm, adapted from the European Centre for Disease Control and Prevention (ECDC), was implemented. Between December 2015 and December 2017, we tested 6417 patients for ZIKV. Of those, according to ECDC criteria, 127 (2.0%) were classified as a confirmed Zika infection of which 39 by RT-PCR (0.6%), 15 (0.2%) as a probable Zika infection, 73 (1.1%) as undefined, and 65 (1.0%) as false positive reactions. Main challenges were the brief window for detection of IgM, cross-reactivity of antibodies with other flaviviruses and malaria, and low VNT titers in the acute phase. In RT-PCR negative samples, classification of ZIKV infection as recent or past proved difficult, when IgM was negative. The majority of patients could be classified according to ECDC criteria, though 1.1% of patients remained "undefined" and 1.0% were ELISA false positive reactions. Complementary IFA IgM was of added value to increase IgM detection rates. Improved serological assays and more longitudinal data on antibody kinetics are needed.


Assuntos
Algoritmos , Técnicas de Laboratório Clínico/normas , Infecção por Zika virus/diagnóstico , Zika virus/isolamento & purificação , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Técnicas de Laboratório Clínico/métodos , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Reações Falso-Positivas , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Testes de Neutralização , Gravidez , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Adulto Jovem , Zika virus/genética
10.
Global health action ; 12(1): 1666566, 2019.
Artigo | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: but-ib17261

RESUMO

Zika Preparedness Latin American Network (ZikaPLAN) is a research consortium funded by the European Commission to address the research gaps in combating Zika and to establish a sustainable network with research capacity building in the Americas. Here we present a report on ZikaPLAN's mid-term achievements since its initiation in October 2016 to June 2019, illustrating the research objectives of the 15 work packages ranging from virology, diagnostics, entomology and vector control, modelling to clinical cohort studies in pregnant women and neonates, as well as studies on the neurological complications of Zika infections in adolescents and adults. For example, the Neuroviruses Emerging in the Americas Study (NEAS) has set up more than 10 clinical sites in Colombia. Through the Butantan Phase 3 dengue vaccine trial, we have access to samples of 17,000 subjects in 14 different geographic locations in Brazil. To address the lack of access to clinical samples for diagnostic evaluation, ZikaPLAN set up a network of quality sites with access to well-characterized clinical specimens and capacity for independent evaluations. The International Committee for Congenital Anomaly Surveillance Tools was formed with global representation from regional networks conducting birth defects surveillance. We have collated a comprehensive inventory of resources and tools for birth defects surveillance, and developed an App for low resource regions facilitating the coding and description of all major externally visible congenital anomalies including congenital Zika syndrome. Research Capacity Network (REDe) is a shared and open resource centre where researchers and health workers can access tools, resources and support, enabling better and more research in the region. Addressing the gap in research capacity in LMICs is pivotal in ensuring broad-based systems to be prepared for the next outbreak. Our shared and open research space through REDe will be used to maximize the transfer of research into practice by summarizing the research output and by hosting the tools, resources, guidance and recommendations generated by these studies. Leveraging on the research from this consortium, we are working towards a research preparedness network.

11.
PLoS One ; 13(12): e0208851, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30557365

RESUMO

In response to the aggressive global spread of the mosquito-borne chikungunya virus (CHIKV), an accurate and accessible diagnostic tool is of high importance. CHIKV, an arthritogenic alphavirus, comprises three genotypes: East/Central/South African (ECSA), West African (WA), and Asian. A previous rapid immunochromatographic (IC) test detecting CHIKV E1 protein showed promising performance for detection of the ECSA genotype. Unfortunately, this kit exhibited lower capacity for detection of the Asian genotype, currently in circulation in the Americas, reflecting the low avidity of one of the monoclonal antibodies (mAbs) in this IC kit for the E1 protein of the Asian-genotype because of a variant amino acid sequence. To address this shortcoming, we set out to generate a new panel of broad-spectrum mouse anti-CHIKV mAbs using hybridoma technology. We report here the successful generation of mouse anti-CHIKV mAbs targeting CHIKV E1 and capsid proteins. These mAbs possessed broad reactivity to all three CHIKV genotypes, while most of the mAbs lacked cross-reactivity towards Sindbis, dengue, and Zika viruses. Two of the mAbs also lacked cross-reactivity towards other alphaviruses, including O'nyong-nyong, Ross River, Mayaro, Western Equine Encephalitis, Eastern Equine Encephalitis, and Venezuelan Equine Encephalitis viruses. In addition, another two mAbs cross-reacted weakly only with most closely related O'nyong-nyong virus. Effective diagnosis is one of the keys to disease control but to date, no antibody-based rapid IC platform for CHIKV is commercially available. Thus, the application of the mAbs characterized here in the rapid diagnostic IC kit for CHIKV detection is expected to be of great value for clinical diagnosis and surveillance purposes.


Assuntos
Anticorpos Monoclonais , Febre de Chikungunya/diagnóstico , Vírus Chikungunya/imunologia , Proteínas Virais/imunologia , Animais , Testes Diagnósticos de Rotina , Camundongos
14.
PLoS One ; 13(4): e0196630, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29709007

RESUMO

BACKGROUND: Chikungunya virus (CHIKV) emerged in Aruba for the first time in 2014. We studied the clinical presentation of acute CHIKV infection and the contribution of serologic and molecular assays to its diagnosis. In a cohort of confirmed CHIKV cases, we analysed the frequency, duration and predictors of post-chikungunya chronic polyarthralgia (pCHIK-CPA), defined as joint pains lasting longer than 6 weeks or longer than 1 year. METHODOLOGY: Patient sera obtained within 10 days of symptom onset were tested for CHIKV, using an indirect immunofluorescence test for the detection of CHIKV-specific Immunoglobulin M (IgM) and post-hoc, by reverse-transcription polymerase chain reaction (RT-PCR). CHIKV was isolated from selected samples and genotyped. For confirmed CHIKV cases, clinical data from chart review were complemented by a Telephone survey, conducted 18-24 months after diagnosis. When joint pain was reported, the duration, presence of inflammatory signs, type and number of joints affected, were recorded. Joint involvement was scored according to the 2010 'American College of Rheumatology/ European League Against Rheumatism' criteria for seronegative rheumatoid arthritis (ACR-score). Risk factors for pCHIK-CPA were identified by logistic regression. PRINCIPAL FINDINGS: Acute CHIKV infection was diagnosed in 269 of 498 sera, by detection of IgM (n = 105), by RT-PCR (n = 59), or by both methods (n = 105). Asian genotype was confirmed in 7 samples. Clinical data were complete for 171 of 248 (69.0%) patients, aged 15 years or older (median 49.4 [35.0-59.6]). The female-to-male ratio was 2.2. The main acute symptoms were arthralgia (94%), fever (85%), myalgia (85%), headache (73%) and rash (63%). In patients with arthralgia (n = 160), pCHIK-CPA longer than 6 weeks was reported by 44% and longer than 1 year by 26% of cases. Inflammatory signs, stiffness, edema and redness were frequent (71%, 39% and 21%, respectively). Joints involved were knees (66%), ankles (50%), fingers (52%), feet (46%), shoulders (36%), elbows (34%), wrists (35%), hips (31%), toes (28.1%) and spine (28.1%). Independent predictors of pCHIK-CPA longer than 1 year were female gender (OR 5.9, 95%-CI [2.1-19.6]); high ACR-score (7.4, [2.7-23.3]), and detection of CHIKV-RNA in serum beyond 7 days of symptom onset (6.4, [1.4-34.1]. CONCLUSIONS: We identified 269 CHIKV patients after the first outbreak of Asian genotype CHIKV in Aruba in 2014-2015. RT-PCR yielded 59 (28%) additional CHIKV diagnoses compared to IgM antibody detection alone. Arthralgia, fever and skin rash were the dominant acute phase symptoms. pCHIK-CPA longer than 1 year affected 26% of cases and was predicted by female gender, high ACR-score and CHIKV-RNA detection beyond 7 days of symptom onset.


Assuntos
Artralgia/virologia , Febre de Chikungunya/complicações , Vírus Chikungunya/genética , Adolescente , Adulto , Anticorpos Antivirais/sangue , Artralgia/complicações , Artralgia/epidemiologia , Aruba , Febre de Chikungunya/epidemiologia , Doença Crônica , Estudos de Coortes , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Genótipo , Humanos , Imunoglobulina G/sangue , Articulações/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
15.
16.
J Virol ; 92(14)2018 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-29695432

RESUMO

Chikungunya virus (CHIKV) is a medically important alphavirus that is transmitted by Aedes aegypti and Aedes albopictus mosquitoes. The viral replicase complex consists of four nonstructural proteins (nsPs) expressed as a polyprotein precursor and encompasses all enzymatic activities required for viral RNA replication. nsPs interact with host components of which most are still poorly understood, especially in mosquitos. A CHIKV trans-replicase system that allows the uncoupling of RNA replication and nsP expression was adapted to mosquito cells and subsequently used for analysis of universal and host-specific effects of 17 different nonstructural polyprotein (ns-polyprotein) mutations. It was found that mutations blocking nsP enzymatic activities as well as insertions of enhanced green fluorescent protein (EGFP) into different nsPs had similar effects on trans-replicase activity regardless of the host (i.e., mammalian or mosquito). Mutations that slow down or accelerate ns-polyprotein processing generally had no effect or reduced trans-replicase activity in mammalian cells, while in mosquito cells most of them increased trans-replicase activity prominently. Increased RNA replication in mosquito cells was counteracted by an antiviral RNA interference (RNAi) response. Substitution of the W258 residue in the membrane binding peptide of nsP1 resulted in a temperature-sensitive defect, in the context of both the trans-replicase and infectious CHIKV. The defect was compensated for by secondary mutations selected during passaging of mutant CHIKV. These findings demonstrate the value of alphavirus trans-replicase systems for studies of viral RNA replication and virus-host interactions.IMPORTANCE Chikungunya virus is an important mosquito-transmitted human pathogen. This virus actively replicates in mosquitoes, but the underlying molecular mechanisms and interactions of viral and host components are poorly understood. This is partly due to the lack of reliable systems for functional analysis of viral nonstructural polyproteins (ns-polyproteins) and nonstructural proteins (nsPs) in mosquito cells. Adaption of a CHIKV trans-replicase system allowed study of the effects of mutations in the ns-polyprotein on RNA replication in cells derived from mammalian and mosquito hosts. We found that a slowdown of ns-polyprotein processing facilitates replication complex formation and/or functioning in mosquito cells and that this process is antagonized by the natural RNAi defense system present in mosquito cells. The mosquito-adapted CHIKV trans-replicase system represents a valuable tool to study alphavirus-mosquito interactions at the molecular level and to develop advanced antiviral strategies.


Assuntos
Aedes/virologia , Febre de Chikungunya/virologia , Vírus Chikungunya/patogenicidade , DNA Polimerase Dirigida por DNA/metabolismo , Poliproteínas/metabolismo , Proteínas não Estruturais Virais/metabolismo , Replicação Viral , Animais , Febre de Chikungunya/metabolismo , Replicação do DNA , DNA Polimerase Dirigida por DNA/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Camundongos , Mutação , Poliproteínas/genética , RNA Viral , Proteínas não Estruturais Virais/genética
18.
Sci Rep ; 8(1): 1094, 2018 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-29348674

RESUMO

Chikungunya virus (CHIKV), a mosquito-borne pathogen, consists of three genotypes: East/Central/South African (ECSA), West African (WA), and Asian. Although a current rapid immunochromatographic (IC) test detecting CHIKV E1-antigen showed high sensitivity to ECSA-genotype viruses, it showed poor performance against the Asian-genotype virus that is spreading in the American continents. To understand the basis for the low performance of this IC test against Asian-genotype virus, we re-examined the anti-CHIKV monoclonal antibodies (mAbs) used in the assay for their interaction with E1-antigen of the three CHIKV genotypes. We found that the reactivity of one mAb for Asian-genotype virus was lower than that for ECSA virus. Comparison of E1 amino acid sequences revealed that the ECSA virus used to generate these mAbs possesses glutamic acid (E) at position 350, in contrast to WA and Asian, which possess aspartic acid (D) at this position. Site-directed mutagenesis confirmed that the mutation altered mAb reactivity, since E-to-D substitution at position 350 in ECSA reduced recognition by the mAb, while D-to-E substitution at this position in Asian and WA increased affinity for the mAb. Taken together, these results indicate that residue 350 of the CHIKV 6K-E1 is a key element affecting the performance of this IC assay.


Assuntos
Vírus Chikungunya/genética , Vírus Chikungunya/imunologia , Cromatografia de Afinidade , Códon , Variação Genética , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia , Substituição de Aminoácidos , Animais , Anticorpos Antivirais/imunologia , Antígenos Virais/genética , Antígenos Virais/imunologia , Linhagem Celular , Febre de Chikungunya/diagnóstico , Febre de Chikungunya/imunologia , Febre de Chikungunya/virologia , Vírus Chikungunya/classificação , Cromatografia de Afinidade/métodos , Genótipo , Humanos , Filogenia , Relação Estrutura-Atividade , Células Vero , Proteínas do Envelope Viral/química
19.
Bull World Health Organ ; 95(12): 802-809, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29200521

RESUMO

Objective: To prospectively monitor Zika viral loads in semen from Belgian travellers with confirmed Zika virus infection, who returned from the Americas during the 2016 Zika virus epidemic. Methods: We recruited symptomatic travellers consulting our clinic and we confirmed infection with either reverse-transcriptase (RT) polymerase chain reaction (PCR) assay or virus neutralization test. The participants produced semen samples weekly, either at the clinic or at home. For the initial sample, the laboratory staff did a microscopy analysis if they received the sample within an hour of production. Using RT-PCR, we monitored Zika virus ribonucleic acid (RNA) loads in semen until we obtained two negative results. Findings: We detected Zika virus RNA in nine of 15 participants' semen, one of whom was vasectomized. The median time to loss of RNA detection in semen was 83 days after symptom onset (95% confidence interval, CI: 57-108). The longest duration of viral shedding in semen before obtaining the first negative RT-PCR result was 144 days after symptom onset. All of the 11 participants, for whom we microscopically analysed their semen, had presence of leukocytes, 10 showed haematospermia and six showed oligospermia. These abnormalities occurred irrespective of Zika virus detection in semen. Conclusion: The majority of men in our study had detectable Zika virus RNA in their semen. We recommend that semen from Zika virus-infected men should be analysed with RT-PCR and that health professionals should advise infected men, even if they are vasectomized, about current recommendations for prevention of sexual transmission of the virus.


Assuntos
Doenças Transmissíveis Importadas/virologia , Sêmen/virologia , Viagem , Infecção por Zika virus/diagnóstico , Zika virus/isolamento & purificação , Adulto , Idoso , Américas , Bélgica , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Neutralização , Estudos Prospectivos , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Zika virus/genética , Infecção por Zika virus/virologia
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