RESUMO
Lymphatic filariasis (LF) is a leading cause of disability due to infectious disease worldwide. The Recife Metropolitan Region (RMR) is the only remaining focus of LF in Brazil, where the parasite Wuchereria bancrofti is transmitted solely by the mosquito Culex quinquefasciatus. This study reports the results of transmission assessment surveys and molecular xenomonitoring in the city of Olinda, RMR, after nearly 15 years (2015-2016) of interventions for LF elimination. Participants were screened for W. bancrofti antigen via immunochromatographic card tests (ICT) in: 1) door-to-door surveys conducted for all children aged 5-7 years from 4 out of 17 intervention areas treated with at least five annual doses of mass drug administration (MDA), and 2) a two-stage cluster sampling survey of residents aged 5 years and older in non-MDA areas. Mosquitoes were collected via handheld aspirators in four MDA areas, differentiated by species, sex, and physiological status, pooled into groups of up to 10 blood-fed, semigravid, and gravid mosquitoes, and screened for W. bancrofti infection by real-time quantitative polymerase chain reaction (RT-qPCR). All 1,170 children from MDA areas and the entire population sample of 990 residents in non-MDA areas were ICT negative. In MDA areas, a total of 3,152 female Cx. quinquefasciatus mosquitoes in 277 households (range, 0-296 mosquitoes per house) were collected via aspiration. RT-qPCR of 233 pools of mosquitos were negative for W. bancrofti RNA; an independent reference laboratory confirmed these results. These results provide evidence that LF transmission has been halted in this setting.
Assuntos
Culex , Culicidae , Filariose Linfática , Criança , Animais , Humanos , Feminino , Filariose Linfática/epidemiologia , Filariose Linfática/prevenção & controle , Filariose Linfática/tratamento farmacológico , Brasil/epidemiologia , Culex/genética , Wuchereria bancroftiRESUMO
It is currently not clear whether humoral immunity to Zika virus (ZIKV) elicited upon natural ZIKV infection is long-lasting. In addition, cross-reactivity of anti-ZIKV antibodies with antigenically related dengue viruses (DENV) may have biological implications in nonnaive individuals who subsequently acquire a heterotypic infection. Cross-reactive humoral immunity between ZIKV and DENV also complicates the interpretation of serological tests to evaluate previous exposure to either virus. Here, we have measured the 2-year decay of ZIKV neutralizing antibodies in people living in a ZIKV/DENV endemic area in Brazil who were identified as having an acute infection (group 1) or past (but recent) infection (group 2) with ZIKV in 2015-16. The titers of neutralizing antibodies to ZIKV decreased 9.1 and 2.3 times in groups 1 and 2, respectively. We also show that the plaque reduction neutralization assay (PRNT) is a reliable method to measure past exposure to ZIKV in coendemic areas.
Assuntos
Vírus da Dengue , Dengue , Infecção por Zika virus , Zika virus , Anticorpos Neutralizantes , Anticorpos Antivirais , Brasil/epidemiologia , Reações Cruzadas , HumanosRESUMO
The diagnostic of arbovirus-related obstetric complications in high-risk pregnancy and childbirth care is challenging, especially in endemic areas. We conducted a prospective study to track active or recent Zika (ZIKV), dengue (DENV), or chikungunya (CHIKV) virus infection among hospitalized pregnant women (PW) with obstetric complications in a hospital at the epicenter of Zika outbreak and ZIKV-related microcephaly in Brazil. Clinical data and blood samples were collected at enrollment and 10 days after the admission of study participants, between October 2018 and May 2019. Further clinical data were extracted from medical records. Samples were screened by molecular and serological tests. Out of 780 participants, 93.1% (95% CI: 91.1-94.7%) presented previous DENV exposure (IgG). ZIKV, CHIKV, and/or DENV laboratory markers of recent or active infection were detected in 130 PW, yielding a prevalence of 16.6% (95% CI: 14.2-19.5%); 9.4% (95% CI: 7.4-11.7%), 7.4% (95% CI: 5.7-9.7%), and 0.38% (95% CI: 0.1-1.2%) of CHIKV, ZIKV, and DENV infections, respectively. Most ZIKV infections were detected by molecular assays (89.6%), while CHIKV infections were detected by serology (95.9%). Our findings highlight the need for arbovirus infections screening in PW with obstetrical complications, potentially associated to these infections in endemic areas regardless of the signs or symptoms suggestive of arboviral disease.
Assuntos
Febre de Chikungunya/epidemiologia , Vírus Chikungunya , Infecção Hospitalar/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Infecção por Zika virus/epidemiologia , Zika virus , Adolescente , Adulto , Brasil/epidemiologia , Infecção Hospitalar/virologia , Suscetibilidade a Doenças , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Gravidez , Complicações Infecciosas na Gravidez/virologia , Estudos Prospectivos , Vigilância em Saúde Pública , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Zika virus (ZIKV) is a mosquito-borne virus that is also transmitted sexually; however, the epidemiological relevance of ZIKV sexual transmission in endemic regions is unclear. METHODS: We performed a household-based serosurvey in Northeast Brazil to evaluate the differential exposure to ZIKV and chikungunya virus (CHIKV) among households. Individuals who participated in our previous arboviral disease cohort (indexes) were recontacted and enrolled, and their household members were newly enrolled. RESULTS: The relative risk of sexual partners being ZIKV-seropositive when living with a ZIKV-seropositive index participant was significantly higher, whereas this was not observed among nonsexual partners of the index. For CHIKV, both sexual and nonsexual partner household members living with a CHIKV-seropositive index had a significantly higher risk of being seropositive. In the nonindex-based dyadic and generalized linear mixed model analyses, the odds of sexual dyads having a concordant ZIKV plaque reduction neutralization test result was significantly higher. We have also analyzed retrospective clinical data according to the participants' exposure to ZIKV and CHIKV. CONCLUSIONS: Our data suggest that ZIKV sexual transmission may be a key factor for the high ZIKV seroprevalence among households in endemic areas and raises important questions about differential disease from the 2 modes of transmission.
Assuntos
Parceiros Sexuais , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/transmissão , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Brasil/epidemiologia , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/transmissão , Vírus Chikungunya/imunologia , Criança , Pré-Escolar , Características da Família , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Estudos Soroepidemiológicos , Comportamento Sexual , Doenças Virais Sexualmente Transmissíveis/transmissão , Adulto Jovem , Zika virus/imunologiaRESUMO
Zika virus (ZIKV) infection during pregnancy is associated with microcephaly, a congenital malformation resulting from neuroinflammation and direct effects of virus replication on the developing central nervous system (CNS). However, the exact changes in the affected CNS remain unknown. Here, we show by transcriptome analysis (at 48 h post-infection) and multiplex immune profiling that human induced-neuroprogenitor stem cells (hiNPCs) respond to ZIKV infection with a strong induction of type-I interferons (IFNs) and several type-I IFNs stimulated genes (ISGs), notably cytokines and the pro-apoptotic chemokines CXCL9 and CXCL10. By comparing the inflammatory profile induced by a ZIKV Brazilian strain with an ancestral strain isolated from Cambodia in 2010, we observed that the response magnitude differs among them. Compared to ZIKV/Cambodia, the experimental infection of hiNPCs with ZIKV/Brazil resulted in a diminished induction of ISGs and lower induction of several cytokines (IFN-α, IL-1α/ß, IL-6, IL-8, and IL-15), consequently favoring virus replication. From ZIKV-confirmed infant microcephaly cases, we detected a similar profile characterized by the presence of IFN-α, CXCL10, and CXCL9 in cerebrospinal fluid (CSF) samples collected after birth, evidencing a sustained CNS inflammation. Altogether, our data suggest that the CNS may be directly affected due to an unbalanced and chronic local inflammatory response, elicited by ZIKV infection, which contributes to damage to the fetal brain.
Assuntos
Sistema Nervoso Central/imunologia , Células-Tronco Pluripotentes Induzidas/citologia , Microcefalia/imunologia , Células-Tronco Neurais/citologia , Zika virus/imunologia , Brasil , Camboja , Células Cultivadas , Sistema Nervoso Central/patologia , Sistema Nervoso Central/virologia , Quimiocina CXCL10/líquido cefalorraquidiano , Quimiocina CXCL10/imunologia , Quimiocina CXCL9/líquido cefalorraquidiano , Quimiocina CXCL9/imunologia , Citocinas/análise , Feminino , Perfilação da Expressão Gênica , Humanos , Lactente , Inflamação/imunologia , Inflamação/patologia , Interferon-alfa/líquido cefalorraquidiano , Interferon-alfa/imunologia , Interferon beta/imunologia , Masculino , Microcefalia/patologia , Gravidez , Complicações Infecciosas na Gravidez/virologia , Replicação Viral/imunologia , Infecção por Zika virus/imunologiaRESUMO
Laboratory confirmation of Zika virus (ZIKV) infection during pregnancy is challenging due to cross-reactivity with dengue virus (DENV) and limited knowledge about the kinetics of anti-Zika antibody responses during pregnancy. We described ZIKV and DENV serological markers and the maternal-fetal transfer of antibodies among mothers and neonates after the ZIKV microcephaly outbreak in Northeast Brazil (2016). We included 89 microcephaly cases and 173 neonate controls at time of birth and their mothers. Microcephaly cases were defined as newborns with a particular head circumference (2 SD below the mean). Two controls without microcephaly were matched by the expected date of delivery and area of residence. We tested maternal serum for recent (ZIKV genome, IgM and IgG3 anti-NS1) and previous (ZIKV and DENV neutralizing antibodies [NAbs]) markers of infection. Multiple markers of recent or previous ZIKV and DENV infection in mothers were analyzed using principal component analysis (PCA). At delivery, 5.6% of microcephaly case mothers and 1.7% of control mothers were positive for ZIKV IgM. Positivity for ZIKV IgG3 anti-NS1 was 8.0% for case mothers and 3.5% for control mothers. ZIKV NAbs was slightly higher among mothers of cases (69.6%) than that of mothers of controls (57.2%; p = 0.054). DENV exposure was detected in 85.8% of all mothers. PCA discriminated two distinct components related to recent or previous ZIKV infection and DENV exposure. ZIKV NAbs were higher in newborns than in their corresponding mothers (p<0.001). We detected a high frequency of ZIKV exposure among mothers after the first wave of the ZIKV outbreak in Northeast Brazil. However, we found low sensitivity of the serological markers to recent infection (IgM and IgG3 anti-NS1) in perinatal samples of mothers of microcephaly cases. Since the neutralization test cannot precisely determine the time of infection, testing for ZIKV immune status should be performed as early as possible and throughout pregnancy to monitor acute Zika infection in endemic areas.
Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Dengue/diagnóstico , Microcefalia/epidemiologia , Microcefalia/etiologia , Complicações Infecciosas na Gravidez/diagnóstico , Infecção por Zika virus/diagnóstico , Adolescente , Adulto , Brasil/epidemiologia , Estudos de Casos e Controles , Dengue/epidemiologia , Vírus da Dengue/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Recém-Nascido , Masculino , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Adulto Jovem , Zika virus/imunologia , Infecção por Zika virus/complicações , Infecção por Zika virus/epidemiologiaRESUMO
The clinical outcomes associated with Zika virus (ZIKV) in the Americas have been well documented, but other aspects of the pandemic, such as attack rates and risk factors, are poorly understood. We prospectively followed a cohort of 1453 urban residents in Salvador, Brazil, and, using an assay that measured immunoglobulin G3 (IgG3) responses against ZIKV NS1 antigen, we estimated that 73% of individuals were infected during the 2015 outbreak. Attack rates were spatially heterogeneous, varying by a factor of 3 within a community spanning 0.17 square kilometers. Preexisting high antibody titers to dengue virus were associated with reduced risk of ZIKV infection and symptoms. The landscape of ZIKV immunity that now exists may affect the risk for future transmission.
Assuntos
Anticorpos Antivirais/sangue , Reações Cruzadas , Dengue/imunologia , Proteínas não Estruturais Virais/imunologia , Infecção por Zika virus/imunologia , Adolescente , Adulto , Número Básico de Reprodução , Brasil , Criança , Surtos de Doenças , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Estudos Prospectivos , Estudos Soroepidemiológicos , População Urbana , Adulto Jovem , Zika virusRESUMO
INTRODUCTION: Molecular xenomonitoring (MX)-pathogen detection in the mosquito rather than human-is a promising tool for lymphatic filariasis (LF) surveillance. In the Recife Metropolitan Region (RMR), the last LF focus in Brazil, Culex quinquefasciatus mosquitoes have been implicated in transmitting Wuchereria bancrofti parasites. This paper presents findings on the ideal mosquito collection method, mosquito dispersion, W. bancrofti infection in mosquitoes and W. bancrofti antigen in humans to aid MX development. METHODS: Experiments occurred within two densely populated urban areas of Olinda, RMR, in July and August 2015. U.S. Centers for Disease Control and Prevention (CDC) light traps were compared to battery-powered aspirators as collection methods, and mosquito dispersion was measured by mosquito mark release recapture (MMRR). Female Cx. quinquefasciatus were tested by PCR for W. bancrofti infection, and study area residents were screened by rapid tests for W. bancrofti antigen. RESULTS: Aspirators caught 2.6 times more total Cx. quinquefasciatus, including 38 times more blood-fed and 5 times more gravid stages, than CDC light traps. They also collected 123 times more Aedes aegypti. Of the 9,644 marked mosquitoes released, only ten (0.01%) were recaptured, nine of which were < 50m (34.8m median, 85.4m maximum) from the release point. Of 9,169 unmarked mosquitoes captured in the MMR, 38.3% were unfed, 48.8% blood-fed, 5.5% semi-gravid, and 7.3% gravid. PCR on 182 pools (1,556 mosquitoes) found no evidence of W. bancrofti infection in Cx. quinquefasciatus. Rapid tests on 110 of 111 eligible residents were all negative for W. bancrofti antigen. CONCLUSIONS: Aspirators were more effective than CDC light traps at capturing Ae. aegypti and all but unfed stages of Cx. quinquefasciatus. Female Cx. quinquefasciatus traveled short (< 86m) distances in this urban area. Lack of evidence for W. bancrofti infection in mosquitoes and antigen in humans in these fine-scale studies does not indicate that LF transmission has ceased in the RMR. A MX surveillance system should consider vector-specific collection methods, mosquito dispersion, and spatial scale but also local context, environmental factors such as sanitation, and host factors such as infection prevalence and treatment history.
Assuntos
Aedes/parasitologia , Antígenos de Protozoários/sangue , Culex/parasitologia , Filariose Linfática/epidemiologia , Entomologia/métodos , Monitoramento Epidemiológico , Wuchereria bancrofti/isolamento & purificação , Adulto , Aedes/crescimento & desenvolvimento , Idoso , Idoso de 80 Anos ou mais , Animais , Brasil/epidemiologia , Estudos Cross-Over , Culex/crescimento & desenvolvimento , Transmissão de Doença Infecciosa , Feminino , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prevalência , População Urbana , Wuchereria bancrofti/genéticaRESUMO
BACKGROUND: Zika virus (ZIKV) is a recently emerged arbovirus, which infection during pregnancy is associated with a series of congenital malformations, collectively denominated Congenital Zika Syndrome (CZS). Following infection, ZIKV RNA has a median duration period of 10 days in plasma and up to 6 months in semen in immunocompetent adult individuals. Moreover, ZIKV is able to replicate and persist in fetal brains and placentas, consequently, infection is associated with pregnancy loss, albeit the pathogenic mechanisms are still unknown. CASE PRESENTATION: Here we report a CZS case of an infant born during the ZIKV outbreak in northeast Brazil, the child presented recurrent episodes of seizures with prolonged presence of ZIKV RNA on the central nervous system (CNS) and blood. ZIKV RNA was identified and partially sequenced from a sample of cerebrospinal fluid (CSF) obtained from the infant with 6 months of life, and later from another sample after the infant completed 17 months of life. Commonly congenital infections were discarded based on STORCH (syphilis, toxoplasmosis, rubella, cytomegalovirus and herpes simplex virus) negative laboratory results. Presence of specific ZIKV antibodies on both mother and children confirmed the association of severe microcephaly and ZIKV infection, diagnosed after birth. CONCLUSIONS: Altogether, our data raise the possibility that CZS cases may result in prolonged viral presence, these findings could be useful for therapy and diagnostic recommendations.
Assuntos
Microcefalia/virologia , Infecção por Zika virus/congênito , Infecção por Zika virus/complicações , Adulto , Brasil , Epilepsia/etiologia , Epilepsia/patologia , Epilepsia/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Microcefalia/patologia , Gravidez , Complicações Infecciosas na Gravidez/virologia , RNA Viral/isolamento & purificação , Índice de Gravidade de Doença , Zika virus/genética , Zika virus/isolamento & purificação , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/patologiaRESUMO
Dengue virus (DENV) infections elicit antibody responses to the non-structural protein 1 (NS1) that are associated with protection against disease. However, the antibody isotypes and subclasses involved, and their kinetics have not been extensively studied. We characterized the antibody responses to DENV NS1 by enzyme-linked immunosorbent assay (ELISA) in a longitudinal cohort of 266 confirmed dengue cases in Recife, Northeast Brazil. Samples were collected during the febrile phase and up to over 3 years after onset of symptoms. The antibodies investigated [IgA, IgM, total IgG (all subclasses measured together) and each subclass (IgG2, IgG3 and IgG4) measured separately] had distinct kinetic profiles following primary or secondary DENV infections. Of interest, most of these antibodies were consistently detected greater than 6 months after onset of symptoms, except for IgG3. Anti-dengue NS1-specific IgG was consistently detected from the acute phase to beyond 3 years after symptom onset. In contrast, anti-dengue NS1-specific IgG3 was detected within the first week, peaked at week 2-3, and disappeared within 4-6 months after onset of symptoms. The mean duration of the IgG3 positive signal was 149 days (ranging from 126 to 172 days). In conclusion, anti-dengue NS1-specific IgG and IgG3 are potential biomarkers of long-term and recent (less than 6 months) DENV infections, respectively.
Assuntos
Anticorpos Antivirais/sangue , Biomarcadores/sangue , Vírus da Dengue/imunologia , Dengue/diagnóstico , Dengue/imunologia , Proteínas não Estruturais Virais/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Several arboviruses, including dengue virus (DENV), Zika virus (ZIKV) and chikungunya virus (CHIKV), transmitted by Aedes mosquitoes, circulate in northeast Brazil. Diseases caused by these viruses are of great public health relevance, however, their epidemiological features in areas where the three viruses co-circulate are scarce. Here, we present analyses of molecular and serological diagnostics in a prospective study of acute febrile patients recruited from May 2015 to May 2016 in Recife, Brazil. METHODS: Two hundred sixty-three acute febrile patients with symptoms suggestive of an arboviral disease who attended an urgent heath care clinic in the Recife Metropolitan Region in northeast Brazil were enrolled. Acute and convalescent blood samples were collected and tested using molecular and serological assays for infection with DENV, ZIKV and CHIKV. RESULTS: Quantitative real-time reverse-transcriptase polymerase chain reactions (qRTPCR) performed on acute phase sera detected no patients positive for DENV, but 26 (9.9%) positive for ZIKV and 132 (50.2%) positive for CHIKV. There were a few suspected and only one confirmed dengue case. Specific serological assays for ZIKV and CHIKV confirmed the qRTPCR data. Analyses of DENV IgM and IgG ELISAs in the context of qRTPCR results suggested high levels of cross reactive antibodies in ZIKV-positive samples. Results from neutralization assays highly corroborated those from qRTPCR and ZIKV ELISA, indicating very few positive DENV cases. ZIKV infections were temporally clustered in the first months of the study and started to decrease concomitantly with an increase in CHIKV infections in August 2015. The proportion of CHIKV infections increased significantly in September 2015 and remained high until the end of the study period, with an average of 84.7% of recruited patients being diagnosed from August 2015 to May 2016. ZIKV infections exhibited a female bias and the cases were spread over the study site, while CHIKV cases had a male bias and were spatially clustered in each month. CONCLUSIONS: In 2015-2016 in the Recife Metropolitan Region, we detected the tail end of a Zika epidemic, which was displaced by a chikungunya epidemic. Few dengue cases were identified despite a high number of official dengue notifications in the area during this period. We show here important epidemiological features of these cases.
Assuntos
Febre de Chikungunya/epidemiologia , Surtos de Doenças , Infecção por Zika virus/epidemiologia , Adolescente , Adulto , Aedes/virologia , Idoso , Animais , Anticorpos Antivirais/sangue , Brasil/epidemiologia , Febre de Chikungunya/diagnóstico , Vírus Chikungunya/genética , Vírus Chikungunya/isolamento & purificação , Criança , Dengue/epidemiologia , Vírus da Dengue/imunologia , Vírus da Dengue/isolamento & purificação , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Saúde Pública , Análise Espaço-Temporal , Adulto Jovem , Zika virus/genética , Zika virus/imunologia , Zika virus/isolamento & purificação , Infecção por Zika virus/diagnósticoRESUMO
Anti-Flavivirus antibodies are highly cross-reactive and may facilitate Zika virus (ZIKV) infection through the antibody-dependent enhancement (ADE) mechanism. We demonstrate that dengue-specific antibodies enhance the infection of a primary Brazilian ZIKV isolate in a FcγRII-expressing K562 cell line. In addition, we demonstrate that serum samples from dengue-immune pregnant women enhanced ZIKV infection. These findings highlight the need for epidemiological studies and animal models to further confirm the role of ADE in the development of congenital and neurological complications associated with ZIKV infections.
Assuntos
Anticorpos Antivirais/sangue , Anticorpos Facilitadores , Vírus da Dengue , Infecção por Zika virus/imunologia , Zika virus/patogenicidade , Anticorpos Antivirais/imunologia , Antivirais/farmacologia , Brasil , Reações Cruzadas , Feminino , Humanos , Células K562 , Gravidez , Receptores de IgG/imunologia , Infecção por Zika virus/sangueRESUMO
BACKGROUND: Maternal-fetal transferred dengue virus (DENV)-specific antibodies have been implicated in the immunopathogenesis of dengue during infancy. METHODS: A prospective birth cohort was established in a dengue-endemic area in the Northeast Region of Brazil. DENV-specific immunoglobulin G (IgG) and DENV-1-4 serotype-specific neutralizing antibody (NAb) levels were assessed in 376 paired maternal and umbilical cord blood samples. The kinetics of enhancing activity by maternally acquired DENV antibodies was determined in serum samples from children enrolled in the cohort. RESULTS: Mothers were mostly immune to DENV-3 alone (53.7%) or combined with DENV-4 (30.6%). Levels of DENV-specific IgG, DENV-3 NAbs, and DENV-4 NAbs were significantly higher in newborns than in their respective mothers. Mothers immune to a single serotype transferred greater levels of DENV-specific IgG (P = .02) and DENV-3 NAbs (P = .04) than mothers immune to multiple DENV serotypes. Maternally acquired DENV-3 NAbs disappeared in >90% of the children by the age of 4 months. The peak enhancing activity was detected by the age of 2 months (P < .0001) and rapidly declined by the age of 4 months (P = .0035). CONCLUSIONS: Unlike Asian infants, the enhancing activity of DENV infection by maternally transferred DENV antibodies occurs at earlier ages in Brazilian children. These findings might explain the low occurrence of severe dengue among infants in our setting.
Assuntos
Anticorpos Bloqueadores/sangue , Anticorpos Antivirais/sangue , Anticorpos Facilitadores , Vírus da Dengue/imunologia , Dengue/imunologia , Exposição Materna , Adolescente , Adulto , Fatores Etários , Anticorpos Neutralizantes/sangue , Brasil , Feminino , Humanos , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Masculino , Gravidez , Estudos Prospectivos , Adulto JovemRESUMO
Dengue cases have increased in younger age groups in Brazil. Maternal anti-dengue antibodies can have a protective effect in the first months of life, but their decline can increase the risk of severe dengue. A prospective birth cohort was established in 2011-2012 in the city of Recife, Pernambuco State, Brazil, to determine the incidence of serotype-specific dengue infection and the kinetics of transferred maternal anti-dengue antibodies in the first years of life. This article describes the design, methods and preliminary results of this cohort study. 354 children underwent clinical and laboratory monitoring for two years, with 15% losses to follow-up. The overall rate of new infections was approximately 10% in the first year of follow-up. Information on the force of serotype-specific dengue infection and the evaluation of transferred maternal antibodies can contribute to understanding dengue etiopathogenesis.
Assuntos
Anticorpos Antivirais/sangue , Vírus da Dengue/imunologia , Dengue/epidemiologia , Doenças Endêmicas , Brasil/epidemiologia , Pré-Escolar , Dengue/imunologia , Ensaio de Imunoadsorção Enzimática , Métodos Epidemiológicos , Feminino , Humanos , Imunidade Materno-Adquirida , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , MasculinoRESUMO
Abstract Dengue cases have increased in younger age groups in Brazil. Maternal anti-dengue antibodies can have a protective effect in the first months of life, but their decline can increase the risk of severe dengue. A prospective birth cohort was established in 2011-2012 in the city of Recife, Pernambuco State, Brazil, to determine the incidence of serotype-specific dengue infection and the kinetics of transferred maternal anti-dengue antibodies in the first years of life. This article describes the design, methods and preliminary results of this cohort study. 354 children underwent clinical and laboratory monitoring for two years, with 15% losses to follow-up. The overall rate of new infections was approximately 10% in the first year of follow-up. Information on the force of serotype-specific dengue infection and the evaluation of transferred maternal antibodies can contribute to understanding dengue etiopathogenesis.
Resumo Casos de dengue têm aumentado em grupos etários mais jovens no Brasil. Anticorpos antidengue maternos podem exercer efeito protetor nos primeiros meses de vida, mas seu declínio pode aumentar o risco de dengue grave. Uma coorte de nascimento prospectiva foi estabelecida na cidade do Recife, Pernambuco, Brasil, entre 2011-2012, para determinar a incidência de infecção sorotipo-específica do dengue e cinética dos anticorpos antidengue materno-transferidos nos primeiros anos de vida. Este artigo descreve o desenho, os métodos e resultados preliminares deste estudo de coorte. Trezentas e cinquenta e quatro crianças foram acompanhadas clínico e laboratorialmente por dois anos, com 15% de perdas de seguimento. A taxa global de novas infecções foi de aproximadamente 10% na coorte de crianças no primeiro ano de seguimento. Informações sobre a força de infecção sorotipo-específica do dengue nos primeiros anos de vida, bem como a avaliação da cinética de anticorpos materno-transferidos poderão contribuir para a compreensão da etiopatogenia da doença.
Resumen Los casos de dengue han aumentado en los grupos de edad más jóvenes en Brasil. Los anticuerpos antidengue maternos pueden ejercer un efecto protector en los primeros meses de vida, pero su decremento puede aumentar el riesgo de dengue grave. Una cohorte de nacimientos prospectiva se estableció en la ciudad de Recife, Pernambuco, Brasil, entre 2011-2012, para determinar la incidencia de infección serotipo-específica de dengue y la cinética de los anticuerpos antidengue materno-transferidos durante los primeros años de vida. Este artículo describe el diseño, los métodos y resultados preliminares de este estudio de cohorte. 354 niños fueron acompañados clínicamente y en laboratorio durante dos años, con un 15% de pérdidas en el seguimiento. La tasa global de nuevas infecciones fue de aproximadamente un 10% en la cohorte de niños durante el primer año de seguimiento. La información sobre la fuerza de infección serotipo-específica del dengue en los primeros años de vida, así como la evaluación de la cinética de los anticuerpos materno-transferidos, podrá contribuir a la comprensión de la etiopatogenia de la enfermedad.
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Doenças Endêmicas , Dengue/epidemiologia , Vírus da Dengue/imunologia , Anticorpos Antivirais/sangue , Brasil/epidemiologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Ensaio de Imunoadsorção Enzimática , Métodos Epidemiológicos , Dengue/imunologia , Imunidade Materno-AdquiridaRESUMO
BACKGROUND: Dengue affects nearly 400 million people annually worldwide and considered one of the most serious health threats in tropical and subtropical countries. OBJECTIVE: To analyze the occurrence of dengue infection among the parturient who have formed the baseline of an ongoing birth cohort study in the city of Recife, Northeast of Brazil. STUDY DESIGN: From March 2011 to May 2012, we recruited 417 parturients with low-risk pregnancies at maternity ward who agreed to a follow-up of their babies. Dengue infection was accessed through DENV RT-PCR and anti-dengue antibodies (IgM and IgG). The prevalence of IgG antibodies in the parturients and their concepts were determined. The concordance among the pairs was tested using Kappa. The association of recent infection (IgM and/or DENV RT-PCR positive) with the maternal characteristics and clinical features of the neonates was analyzed through logistic regression. RESULTS: The prevalence of IgG antibodies in the maternal and cord blood samples was 95.1% (95% CI: 92.6-96.9%) and 95.8% (95% CI: 93.4-97.5%), respectively, with high agreement between maternal-cord pairs (Kappa=0.93). The prevalence of recent infection was 10.6% (95% CI: 7.9-14.2%) in the parturients. Reported fever during pregnancy was associated to recent infection (p=0.023). CONCLUSION: The data draw attention for the high frequency of anti-dengue antibodies in the women studied and for the high occurrence of infection during pregnancy in this region of Brazil. There is a need for further studies to better characterize dengue infection in pregnant women.