Predictor Variables in the Spread of Chagas Disease in Rural Areas.

Over a hundred years ago after the discovery of Chagas disease (CD) in Brazil, the World Health Organization estimates a number of 6 to 7 million people infected by Trypanosoma cruzi worldwide. Therefore, the goal of this work was to identify variables related to the spread of infection by T. cruzi in humans living in rural areas, seeking predictor variables. A systematic review of the literature has been conducted, with a search in the Scopus platform, using the search string "Chagas disease" and "rural", resulting in 85 valid and analyzed scientific studies (1977 and 2022). Twenty-seven predictor variables have been acquired, and 19 of them have been grouped, such as: socioeconomic and educational, housing, environmental, sanitary, and cultural; and 8 variables related to T. cruzi seropositive individuals. The predictor variables yielded significant results (p-value < 0.05) in 59.5% of the cases (195/328), with a median of 66.7%. In other words, studies relating to 50% of the 27 variables showed significance equal to or greater than 66.7% of the time. The independent variables with the highest proportion of significant data (p-value < 0.05) were Education (87.6%), Intradomicile building (70%), Domestic animals (69.6%), and Triatomines (69.2%) in the households. Some variables reached 100%; however, few articles were found, indicating the need for further research, especially for Sanitation and Culture. It has been concluded that, in the several contexts found, the social vulnerability and lack of information led the individual to living in environments where inhabitability is inadequate, to perform limited work activity and develop habits and behaviors which impair them in an environmental insalubrity situation, favorable to the access of vectors and pathogens of anthropozoonoses such as CD.

Distinct anti-NP, anti-RBD and anti-Spike antibody profiles discriminate death from survival in COVID-19.

Introduction: Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces rapid production of IgM, IgA, and IgG antibodies directed to multiple viral antigens that may have impact diverse clinical outcomes. Methods: We evaluated IgM, IgA, and IgG antibodies directed to the nucleocapsid (NP), IgA and IgG to the Spike protein and to the receptor-binding domain (RBD), and the presence of neutralizing antibodies (nAb), in a cohort of unvaccinated SARS-CoV-2 infected individuals, in the first 30 days of post-symptom onset (PSO) (T1). Results: This study included 193 coronavirus disease 2019 (COVID-19) participants classified as mild, moderate, severe, critical, and fatal and 27 uninfected controls. In T1, we identified differential antibody profiles associated with distinct clinical presentation. The mild group presented lower levels of anti-NP IgG, and IgA (vs moderate and severe), anti-NP IgM (vs severe, critical and fatal), anti-Spike IgA (vs severe and fatal), and anti-RBD IgG (vs severe). The moderate group presented higher levels of anti-RBD IgA, comparing with severe group. The severe group presented higher levels of anti-NP IgA (vs mild and fatal) and anti-RBD IgG (vs mild and moderate). The fatal group presented higher levels of anti-NP IgM and anti-Spike IgA (vs mild), but lower levels of anti-NP IgA (vs severe). The levels of nAb was lower just in mild group compared to severe, critical, and fatal groups, moreover, no difference was observed among the more severe groups. In addition, we studied 82 convalescent individuals, between 31 days to 6 months (T2) or more than 6 months (T3), PSO, those: 12 mild, 26 moderate, and 46 severe plus critical. The longitudinal analyzes, for the severe plus critical group showed lower levels of anti-NP IgG, IgA and IgM, anti-Spike IgA in relation T3. The follow-up in the fatal group, reveals that the levels of anti-spike IgG increased, while anti-NP IgM levels was decreased along the time in severe/critical and fatal as well as anti-NP IgG and IgA in several/critical groups. Discussion: In summary, the anti-NP IgA and IgG lower levels and the higher levels of anti-RBD and anti-Spike IgA in fatal compared to survival group of individuals admitted to the intensive care unit (ICU). Collectively, our data discriminate death from survival, suggesting that anti-RBD IgA and anti-Spike IgA may play some deleterious effect, in contrast with the potentially protective effect of anti-NP IgA and IgG in the survival group.

Risk of adverse pregnancy and infant outcomes associated with prenatal Zika virus infection: a post-epidemic cohort in Central-West Brazil.

This study aimed to estimate the risks of adverse infant outcomes in the first year of life related to prenatal Zika virus (ZIKV) exposure. A prospective cohort of pregnant women with rash was recruited in Central-West Brazil in a post-epidemic period (January 2017 to April 2019). We evaluated participants' medical histories and performed ZIKV diagnostic testing using molecular (reverse transcription polymerase chain reaction [RT-PCR]) and serologic (immunoglobulin [Ig]M and plaque reduction neutralization tests [PRNT90]) assays. The ZIKV-positive group included both RT-PCR-confirmed cases as well as IgM and/or PRNT90-positive probable cases. Children were evaluated at birth and in the first 12 months of life. Transfontanellar ultrasound, central nervous system computed tomography, eye fundoscopy and retinography were performed. We estimated the absolute risk and 95% confidence interval (95% CI) of adverse infant outcomes among confirmed prenatally ZIKV-exposed children. Among 81 pregnant women with rash, 43 (53.1%) were ZIKV infected. The absolute risk of microcephaly among offspring of ZIKV-infected pregnant women was 7.0% (95% CI: 1.5-19.1), including the two cases of microcephaly detected prenatally and one detected postnatally. In total, 54.5% (95% CI: 39.8-68.7) of children in the ZIKV-exposed group had at least one ophthalmic abnormality, with the most frequent abnormalities being focal pigmentary mottling and chorioretinal atrophy or scarring. Our findings reinforce the importance of long-term monitoring of prenatally ZIKV-exposed children born apparently asymptomatic for Congenital Zika Syndrome.

Dengue, chikungunya, and Zika virus infections in Latin America and the Caribbean: a systematic review.

Objectives: To characterize the distribution profile of dengue, chikungunya, and Zika virus infections in Latin America and the Caribbean and to identify possible factors associated with the risk of dissemination and severity of these arboviruses. Methods: The protocol of this review was registered on the PROSPERO platform. Searches were carried out in the following databases: Virtual Health Library, MEDLINE/PubMed, and Embase. The search terms were: Zika virus, Zika virus infection, dengue, dengue virus, chikungunya virus, chikungunya fever, epidemiology, observational study, Latin America, and Caribbean region. Studies that addressed the distribution of these arboviruses and the risk factors associated with dengue, Zika virus disease, and chikungunya, published between January 2000 and August 2020 in English, Portuguese, and Spanish, were included. Results: Of 95 studies included, 70 identified risk factors, clinical manifestations, and outcomes for arbovirus infections and 25 described complications and/or deaths. The highest frequency of confirmed cases was for dengue. Brazil reported most cases of the three arboviruses in the period analyzed. Environmental and socioeconomic factors facilitated the proliferation and adaptation of vectors, and host-related factors were reported to aggravate dengue. Most deaths were due to chikungunya, Zika virus disease caused most neurological alterations, and dengue resulted in greater morbidity leading to more frequent hospitalization. Conclusions: The review provides a broad view of the three arboviruses and the intrinsic aspects of infections, and highlights the factors that influence the spread of these viruses in the populations studied.

Dengue, chikungunya, and Zika virus infections in Latin America and the Caribbean: a systematic review

[ABSTRACT]. Objectives. To characterize the distribution profile of dengue, chikungunya, and Zika virus infections in Latin America and the Caribbean and to identify possible factors associated with the risk of dissemination and severity of these arboviruses. Methods. The protocol of this review was registered on the PROSPERO platform. Searches were carried out in the following databases: Virtual Health Library, MEDLINE/PubMed, and Embase. The search terms were: Zika virus, Zika virus infection, dengue, dengue virus, chikungunya virus, chikungunya fever, epidemiology, observational study, Latin America, and Caribbean region. Studies that addressed the distribution of these arboviruses and the risk factors associated with dengue, Zika virus disease, and chikungunya, published between January 2000 and August 2020 in English, Portuguese, and Spanish, were included. Results. Of 95 studies included, 70 identified risk factors, clinical manifestations, and outcomes for arbovirus infections and 25 described complications and/or deaths. The highest frequency of confirmed cases was for dengue. Brazil reported most cases of the three arboviruses in the period analyzed. Environmental and socio- economic factors facilitated the proliferation and adaptation of vectors, and host-related factors were reported to aggravate dengue. Most deaths were due to chikungunya, Zika virus disease caused most neurological alterations, and dengue resulted in greater morbidity leading to more frequent hospitalization. Conclusions. The review provides a broad view of the three arboviruses and the intrinsic aspects of infections, and highlights the factors that influence the spread of these viruses in the populations studied.

[RESUMEN]. Objetivos. Caracterizar el perfil de distribución de infecciones por dengue, chikungunya y el virus de Zika en América Latina y el Caribe, y determinar posibles factores relacionados con el riesgo de propagación y gravedad de estas arbovirosis. Métodos. Se registró el protocolo de esta revisión en la plataforma PROSPERO. Se realizaron búsquedas en las siguientes bases de datos: Virtual Health Library, MEDLINE/PubMed y Embase. Los términos de búsqueda fueron: “zika virus” [virus del Zika], “zika virus infection” [infección por el virus del Zika], “dengue”, “den- gue virus” [virus del dengue], “chikungunya virus” [virus del chikunguña], “chikungunya fever” [fiebre de chikunguña], “epidemiology” [epidemiología], “observational study” [estudio observacional], “Latin America” [América Latina] y “Caribbean región” [Caribe]. Se incluyeron estudios que abordaban la distribución de estas arbovirosis y los factores de riesgo asociados con el dengue, la enfermedad por el virus del Zika y el chikunguña, publicados entre enero del 2000 y agosto del 2020 en español, inglés y portugués. Resultados. De los 95 estudios incluidos, 70 establecieron factores de riesgo, manifestaciones clínicas y resultados de las infecciones por arbovirus y 25 describieron complicaciones o muertes. La mayor frecuen- cia de casos confirmados fue del dengue. Brasil notificó la mayoría de los casos de infección por los tres arbovirus en el período analizado. Los factores ambientales y socioeconómicos facilitaron la proliferación y adaptación de los vectores, y se notificó que los factores relacionados con el huésped agravaban el dengue. El chikunguña causó la mayor parte de las muertes, la enfermedad por el virus del Zika causó la mayor parte de las alteraciones neurológicas y el dengue fue responsable de una mayor morbilidad, lo que llevó a una hospitalización más frecuente. Conclusiones. Esta revisión ofrece un panorama de las tres arbovirosis y de los aspectos intrínsecos de las infecciones, y pone de relieve los factores que influyen en la propagación de estos virus en las poblaciones estudiadas.

[RESUMO]. Objetivos. Descrever a distribuição das arboviroses causadas pelo vírus da dengue, zika e chikungunya na América Latina e no Caribe e identificar possíveis fatores associados ao potencial de disseminação e à grav- idade dessas infecções. Métodos. O protocolo desta revisão sistemática foi registado na plataforma PROSPERO. Foram realizadas buscas nas bases de dados Biblioteca Virtual em Saúde, MEDLINE/PubMed e Embase. Os termos de busca foram: vírus zika, infecção pelo vírus zika, dengue, vírus da dengue, vírus chikungunya, febre chikungunya, epidemiologia, estudo observacional, América Latina e região do Caribe. Foram selecionados estudos publicados em inglês, português e espanhol, entre janeiro de 2000 e agosto de 2020, que tratavam da dis- tribuição desses arbovírus e de fatores de risco associados à dengue, à infecção pelo vírus zika e à febre chikungunya. Resultados. Dos 95 estudos selecionados, 70 descreveram fatores de risco, manifestações clínicas e des- fechos das arboviroses e 25 destacaram as complicações e/ou mortes. Houve uma maior taxa de casos confirmados de dengue. O Brasil foi o país onde se registrou a maioria dos casos dessas três arboviroses no período analisado. Fatores ambientais e socioeconômicos facilitaram a proliferação e a adaptação dos vetores dos arbovírus e fatores próprios do hospedeiro são determinantes na gravidade da dengue. As mortes ocorreram principalmente nos casos de febre chikungunya, as manifestações neurológicas foram mais comuns na infecção pelo vírus zika e a dengue resultou em maior morbidade e internação hospitalar. Conclusões. Esta revisão sistemática oferece um panorama destas três arboviroses e de suas peculiari- dades destacando os fatores que influenciam a disseminação destes arbovírus nas populações estudadas.

Dengue, chikungunya, and Zika virus infections in Latin America and the Caribbean: a systematic review / Infecciones por dengue, chikungunya y el virus de Zika en América Latina y el Caribe: revisión sistemática / Dengue, zika e chikungunya na América Latina e no Caribe: revisão sistemática

ABSTRACT Objectives. To characterize the distribution profile of dengue, chikungunya, and Zika virus infections in Latin America and the Caribbean and to identify possible factors associated with the risk of dissemination and severity of these arboviruses. Methods. The protocol of this review was registered on the PROSPERO platform. Searches were carried out in the following databases: Virtual Health Library, MEDLINE/PubMed, and Embase. The search terms were: Zika virus, Zika virus infection, dengue, dengue virus, chikungunya virus, chikungunya fever, epidemiology, observational study, Latin America, and Caribbean region. Studies that addressed the distribution of these arboviruses and the risk factors associated with dengue, Zika virus disease, and chikungunya, published between January 2000 and August 2020 in English, Portuguese, and Spanish, were included. Results. Of 95 studies included, 70 identified risk factors, clinical manifestations, and outcomes for arbovirus infections and 25 described complications and/or deaths. The highest frequency of confirmed cases was for dengue. Brazil reported most cases of the three arboviruses in the period analyzed. Environmental and socioeconomic factors facilitated the proliferation and adaptation of vectors, and host-related factors were reported to aggravate dengue. Most deaths were due to chikungunya, Zika virus disease caused most neurological alterations, and dengue resulted in greater morbidity leading to more frequent hospitalization. Conclusions. The review provides a broad view of the three arboviruses and the intrinsic aspects of infections, and highlights the factors that influence the spread of these viruses in the populations studied.

RESUMEN Objetivos. Caracterizar el perfil de distribución de infecciones por dengue, chikungunya y el virus de Zika en América Latina y el Caribe, y determinar posibles factores relacionados con el riesgo de propagación y gravedad de estas arbovirosis. Métodos. Se registró el protocolo de esta revisión en la plataforma PROSPERO. Se realizaron búsquedas en las siguientes bases de datos: Virtual Health Library, MEDLINE/PubMed y Embase. Los términos de búsqueda fueron: "zika virus" [virus del Zika], "zika virus infection" [infección por el virus del Zika], "dengue", "dengue virus" [virus del dengue], "chikungunya virus" [virus del chikunguña], "chikungunya fever" [fiebre de chikunguña], "epidemiology" [epidemiología], "observational study" [estudio observacional], "Latin America" [América Latina] y "Caribbean región" [Caribe]. Se incluyeron estudios que abordaban la distribución de estas arbovirosis y los factores de riesgo asociados con el dengue, la enfermedad por el virus del Zika y el chikunguña, publicados entre enero del 2000 y agosto del 2020 en español, inglés y portugués. Resultados. De los 95 estudios incluidos, 70 establecieron factores de riesgo, manifestaciones clínicas y resultados de las infecciones por arbovirus y 25 describieron complicaciones o muertes. La mayor frecuencia de casos confirmados fue del dengue. Brasil notificó la mayoría de los casos de infección por los tres arbovirus en el período analizado. Los factores ambientales y socioeconómicos facilitaron la proliferación y adaptación de los vectores, y se notificó que los factores relacionados con el huésped agravaban el dengue. El chikunguña causó la mayor parte de las muertes, la enfermedad por el virus del Zika causó la mayor parte de las alteraciones neurológicas y el dengue fue responsable de una mayor morbilidad, lo que llevó a una hospitalización más frecuente. Conclusiones. Esta revisión ofrece un panorama de las tres arbovirosis y de los aspectos intrínsecos de las infecciones, y pone de relieve los factores que influyen en la propagación de estos virus en las poblaciones estudiadas.

RESUMO Objetivos. Descrever a distribuição das arboviroses causadas pelo vírus da dengue, zika e chikungunya na América Latina e no Caribe e identificar possíveis fatores associados ao potencial de disseminação e à gravidade dessas infecções. Métodos. O protocolo desta revisão sistemática foi registado na plataforma PROSPERO. Foram realizadas buscas nas bases de dados Biblioteca Virtual em Saúde, MEDLINE/PubMed e Embase. Os termos de busca foram: vírus zika, infecção pelo vírus zika, dengue, vírus da dengue, vírus chikungunya, febre chikungunya, epidemiologia, estudo observacional, América Latina e região do Caribe. Foram selecionados estudos publicados em inglês, português e espanhol, entre janeiro de 2000 e agosto de 2020, que tratavam da distribuição desses arbovírus e de fatores de risco associados à dengue, à infecção pelo vírus zika e à febre chikungunya. Resultados. Dos 95 estudos selecionados, 70 descreveram fatores de risco, manifestações clínicas e desfechos das arboviroses e 25 destacaram as complicações e/ou mortes. Houve uma maior taxa de casos confirmados de dengue. O Brasil foi o país onde se registrou a maioria dos casos dessas três arboviroses no período analisado. Fatores ambientais e socioeconômicos facilitaram a proliferação e a adaptação dos vetores dos arbovírus e fatores próprios do hospedeiro são determinantes na gravidade da dengue. As mortes ocorreram principalmente nos casos de febre chikungunya, as manifestações neurológicas foram mais comuns na infecção pelo vírus zika e a dengue resultou em maior morbidade e internação hospitalar. Conclusões. Esta revisão sistemática oferece um panorama destas três arboviroses e de suas peculiaridades destacando os fatores que influenciam a disseminação destes arbovírus nas populações estudadas.

Six Cases of Zika/Dengue Coinfection in a Brazilian Cohort, 2015-2019.

Brazil is one of the countries which has been most affected by dengue epidemics. This scenario became more challenging with the emergence of Zika virus after 2014. The cocirculation of dengue and Zika viruses makes their diagnosis and treatment a challenge for health professionals, especially due to their similar clinical outcomes. From 2015 to 2019, we followed a cohort of 2017 participants in Goiania, Goias, Central Brazil. Febrile cases were monitored weekly, and after identification of fever, the physician performed a home visit for clinical evaluation and collection of blood/urine for diagnosis of acute dengue/Zika infection in suspected cases. Dengue acute infection was investigated by NS1 antigen and real time RT-PCR and seroconversion of anti-dengue IgM. ZIKV infection was confirmed by real time RT-PCR. Six cases of Zika/dengue coinfection among participants were reported. The clinical outcomes were suggestive for both DENV and ZIKV infection. No coinfected patient had neurological clinical manifestation, warning signs or need for hospitalization. A continuous specific laboratory confirmation for both dengue and Zika viruses should be enforced as part of the surveillance systems even in the presence of very suggestive cases of dengue fever, minimizing the risk of a late detection of ZIKV circulation.

Detection of Rocio Virus SPH 34675 during Dengue Epidemics, Brazil, 2011-2013.

Recent seroprevalence studies in animals detected Rocio virus in regions of Brazil, indicating risk for re-emergence of this pathogen. We identified Rocio virus RNA in samples from 2 human patients for whom dengue fever was clinically suspected but ruled out by laboratory findings. Testing for infrequent flavivirus infections should expedite diagnoses.

Dengue-specific serotype related to clinical severity during the 2012/2013 epidemic in centre of Brazil.

Please see Additional file 1 for translations of the abstract into the five official working languages of the United Nations. BACKGROUND: Currently, in Brazil, there is a co-circulation of the four dengue (DENV-1 to DENV-4) serotypes. This study aimed to assess whether different serotypes and antibody response patterns were associated with the severity of the disease during a dengue outbreak, which occurred in 2012/2013 in centre of Brazil. METHODS: We conducted a prospective study with 452 patients with laboratory confirmed dengue in central Brazil, from January 2012 to July 2013. The clinical outcome was the severity of cases: dengue, dengue with warning signs, and severe dengue. The patients were evaluated at three different moments. Blood sampling for laboratory testing and confirmatory tests for dengue infection were performed. We performed a multinomial analysis considering the three categories of the dependent variable, as outlined above. The odds ratios (ORs) were calculated. A multinomial logistic regression model was applied for variables with a P-value <0.20. Statistical analysis was performed with STATA 12.0 software. RESULTS: Four hundred fifty-two patients (452/632, 71.5%) were diagnosed with dengue. The dengue virus (DENV) serotypes were identified in 243 cases. DENV-4 was detected in 135 patients (55.6%), DENV-1 in 91 (37.4%), DENV-3 in 13 (5.3%), and DENV-2 in 4 (1.6%). Patients with the DENV-1 serotype were more prone to present with several clinical and laboratory features as compared with DENV-4 patients, including spontaneous bleeding (P = 0.03), intense abdominal pain (P = 0.004), neurological symptoms (P = 0.09), and thrombocytopenia (P = 0.01). Secondary infection was more predominant among DENV-4 cases (80.0%) compared with DENV-1 cases (62.3%) (P = 0.03). The univariate analysis showed that females (OR = 2.12; 95% CI: 1.44-3.13; P < 0.01) had a higher risk of having dengue with warning signs. The multinomial analysis showed that severe dengue cases with secondary infection had an adjusted OR of 2.80 (95% CI: 0.78-10.00; P = 0.113) as compared with dengue fever with primary infection when adjusted for age and sex. CONCLUSION: The current data show that 5.8% of patients recruited for treatment in healthcare centres and hospitals during the study period had severe dengue. DENV-4 was the predominant serotype, followed by DENV-1, in a large outbreak of dengue in central Brazil. Our findings contribute to the understanding of clinical differences and immune status related to the serotypes DENV-1 and DENV-4 in central of Brazil.

Neurological manifestations of dengue in Central Brazil.

INTRODUCTION:: The incidence of dengue has increased throughout the 2000s with a consequent global increase in atypical clinical forms. METHODS:: This study reports a series of cases of neurological dengue out of 498 confirmed cases of laboratory dengue in Goiânia, Brazil. Cases were confirmed based on viral RNA detection via polymerase chain reaction or IgM antibody capture. RESULTS:: Neurological symptoms occurred in 5.6% of cases, including paresthesia (3.8%), encephalitis (2%), encephalopathy (1%), seizure (0.8%), meningoencephalitis (0.4%), and paresis (0.4%). DENV-3 was the predominant circulating serotype (93%). CONCLUSIONS:: We reported dengue cases with neurological manifestations in endemic area.

Neurological manifestations of dengue in Central Brazil

Abstract INTRODUCTION: The incidence of dengue has increased throughout the 2000s with a consequent global increase in atypical clinical forms. METHODS: This study reports a series of cases of neurological dengue out of 498 confirmed cases of laboratory dengue in Goiânia, Brazil. Cases were confirmed based on viral RNA detection via polymerase chain reaction or IgM antibody capture. RESULTS: Neurological symptoms occurred in 5.6% of cases, including paresthesia (3.8%), encephalitis (2%), encephalopathy (1%), seizure (0.8%), meningoencephalitis (0.4%), and paresis (0.4%). DENV-3 was the predominant circulating serotype (93%). CONCLUSIONS: We reported dengue cases with neurological manifestations in endemic area.

High frequency of pre-existing neutralizing antibody responses in patients with dengue during an outbreak in Central Brazil.

BACKGROUND: This study aims to identify dengue neutralizing antibody response in patients with dengue from a well-characterized cohort during an outbreak in central Brazil, 2012-2013. METHODS: We analyzed paired samples from 40 patients with severe dengue and 20 patients with dengue. Eligibility criteria were: IgM, NS1Ag and/or RT-PCR positivity and positive IgG result. Plaque reduction neutralization test (PRNT50) from DENV-1 to DENV-4 was performed to identify serotype-specific NAbs response. An infecting serotype was defined as ≥4-fold increase in DENV NAbs in paired samples. Monotypic response was classified as PRNT50 ≥ 1/20 to only one DENV serotype, and multitypic response was considered to be PRNT50 ≥ 1/20 to two or more serotypes simultaneously. RESULTS: Patients were mainly adults. Virological dengue infection was confirmed by RT-PCR: DENV-4(n = 14) and DENV-1(n = 10). Forty-four out of 60(73.3 %) patients had NAbs to DENV-4, DENV-1(68.3 %), DENV-2(68.3 %) and DENV-3(61.6 %) respectively. Fifteen percent of the cases presented monotypic response, whereas 85 % had multitypic response. DENV-4 infected-patients presented the greatest difference in PRNT50 titers compared with other serotypes. Pre-existing DENV NAbs was not correlated with disease severity. This was the first time that DENV-4 was implicated in an epidemic in the region. CONCLUSION: Our data indicates high exposure of multiple DENV serotypes in all age groups in the pre-dengue vaccine era and also previous to Zika virus introduction in Brazil.

Prevalence and incidence of dengue virus and antibody placental transfer during late pregnancy in central Brazil.

BACKGROUND: Maternal dengue antibodies are considered to play a significant role in dengue pathogenesis among infants. Determining the transplacental specific antibody transfer is invaluable for establishing the optimal vaccination age among infants in endemic regions. METHODS: We conducted a cross-sectional study among pairs of maternal and corresponding umbilical cord blood samples in public hospitals. The prevalence and incidence of dengue infection were determined in 505 pairs of pregnant women and neonates during a large outbreak (2009-2010) in central Brazil. The women were interviewed at late pregnancy to assess current or past symptoms of dengue. All parturients and their neonates were screened using Dengue IgG Indirect ELISA (Panbio) to assess previous dengue exposure. A semi-quantitative measurement of the IgG antibody expressed by the index ratio was calculated using optical density (OD) values according to the manufacturer's instructions. The studied population of parturients and their offspring was also screened for recent dengue infection by the Dengue IgM-capture ELISA (Panbio). Those participants with history of fever and two or more symptoms of dengue at least 10 days before the delivery were also tested for the dengue NS1 antigen using the Dengue Early ELISA (Panbio) and RT-PCR. RESULTS: The mean maternal age was 25.8 (SD = 6.4), and 83.6% of deliveries were between 37 and 41 weeks. Approximately half of the 505 women and neonates were IgG-seropositive, yielding 99.3% co-positive mother-child frequency of antibody transfer (Kappa = 0.96). The incidence of dengue infection was 2.8% (95% CI 1.4-4.4%) among the women considering 14 IgM-positive results and one DENV2 detected by RT-PCR. The dengue NS1 antigen was undetectable in the matched pairs. CONCLUSION: This study provides critical data on the prevalence of transplacental transferred maternal-infant anti-dengue antibodies and incidence of infection. The design of future vaccine trials should consider diverse regional epidemiological scenarios.

Dengue and dengue hemorrhagic fever among adults: clinical outcomes related to viremia, serotypes, and antibody response.

BACKGROUND: Clinical manifestations of dengue vary in different areas of endemicity and between specific age groups, whereas predictors of outcome have remained controversial. In Brazil, the disease burden predominantly affects adults, with an increasing trend toward progression to dengue hemorrhagic fever (DHF) noted. METHODS: A cohort of adults with confirmed cases of dengue was recruited in central Brazil in 2005. Patients were classified according to the severity of their disease. Associations of antibody responses, viremia levels (as determined by real-time polymerase chain reaction [PCR]), and serotypes (as determined by multiplex PCR) with disease severity were evaluated. RESULTS: Of the 185 symptomatic patients >14 years of age who had a confirmed case of dengue, 26.5% and 23.2% were classified as having intermediate dengue fever (DF)/DHF (defined as internal hemorrhage, plasma leakage, manifested signs of shock, and/or thrombocytopenia [platelet count, < or =50,000 platelets/mm3]) and DHF, respectively. The onset of intermediate DF/DHF and DHF occurred at a late stage of disease, around the period of defervescence. Patients with DHF had abnormal liver enzyme levels, with a >3-fold increase in aspartate aminotransferase level, compared with the range of values considered to be normal. Overall, 65% of patients presented with secondary infections with dengue virus, with such infection occurring in similar proportions of patients in each of the 3 disease category groups. Dengue virus serotype 3 (DV3) was the predominant serotype, and viremia was detected during and after defervescence among patients with DHF or intermediate DF/DHF. CONCLUSIONS: Viremia was detected after defervescence in adult patients classified as having DHF or intermediate DF/DHF. Secondary infection was not a predictor of severe clinical manifestation in adults with infected with the DV3 serotype.

Evaluation of a commercial real-time PCR kit for detection of dengue virus in samples collected during an outbreak in Goiania, Central Brazil, in 2005.

In the past 2 decades, dengue has reemerged in Brazil as a significant public health problem. Clinicians demand a diagnostic test with high sensitivity that is applicable during the early symptomatic phase. We aimed to test two distinct molecular methods on samples from suspected dengue cases during an outbreak in Central Brazil. Acute-phase serum specimens from 254 patients suspected of having dengue were collected during 2005 in the city of Goiânia, Central Brazil. Samples were blindly evaluated by real-time and multiplex PCR in addition to routine immunoglobulin M serology and virus culture. Overall, acute dengue was confirmed by serology, multiplex PCR, or virus isolation for 80% of patients (203/254). Another four patients presented real-time PCR-positive results as the unique marker of dengue. Higher real-time PCR positivity levels and viral loads were observed in the early symptomatic phase of disease (< or =5 days) than after this period. Multiplex and real-time PCR assays presented a high kappa agreement (0.85). According to multiplex PCR, 60 samples harbored dengue virus type 3 (DEN-3), 4 samples harbored DEN-2, and 1 sample displayed a pattern compatible with a double infection with DEN-2 and -3. The dengue virus real-time kit was found to be practical and adjustable for high throughput, to display the best performance in the early symptomatic phase of dengue cases, and to be valuable for confirming dengue diagnosis in a timely manner.

Laboratory surveillance of dengue virus in Central Brazil, 1994-2003.

BACKGROUND: In Brazil, dengue endemic and epidemic patterns indicate an upward trend in incidence and hospitalization in the past decade. OBJECTIVE: To report dengue circulating serotypes from 1994 to 2003 and the role of distinct serotypes on dengue clinical outcomes in Central Brazil. METHODS: Virological surveillance for dengue cases was conducted in the city of Goiania ( approximately 1,200,000 population) from 1994 to 2003. Samples were tested using dengue IgM antibody (MAC-ELISA) and/or virus isolation. Circulating subtypes and genotypes were identified by reverse transcriptase PCR (RT-PCR) and by restricted site-specific PCR (RSS-PCR) patterns in selected samples. RESULTS: Adults (87.4%) were the most affected group and dengue fever accounted for the majority of the cases. Laboratory surveillance identified mainly DEN 1 serotype from 1994 to 2002 shifting to a high circulation of DEN 3 in 2003. The ratio of dengue fever to dengue with complications/DHF remained constant following the introduction of DEN 3. Diagnosis of dengue was confirmed in approximately 50% of the suspected cases enhanced by RT-PCR. RSS-PCR patterns for DEN 1 and DEN 3 corresponded to the circulating subtypes in the country. CONCLUSIONS: The result of virological surveillance did not suggest a major role of infecting DEN 3 serotype in increasing disease severity during its first-year spread in Central Brazil.