Sueli Guerreiro Rodrigues

Zika virus in the Americas: Early epidemiological and genetic findings

Zika virus genomes from Brazil The Zika virus outbreak is a major cause for concern in Brazil, where it has been linked with increased reports of otherwise rare birth defects and neuropathology. In a phylogenetic analysis, Faria et al. infer a single introduction of Zika to the Americas and estimated the introduction date to be about May to December 2013—some 12 months earlier than the virus was reported. This timing correlates with major events in the Brazilian cultural calendar associated with increased traveler numbers from areas where Zika virus has been circulating. A correlation was also observed between incidences of microcephaly and week 17 of pregnancy. Science, this issue p. 345 Virus sequencing indicates that Zika arrived in Brazil during the middle of 2013, coincident with a surge in air travelers. Brazil has experienced an unprecedented epidemic of Zika virus (ZIKV), with ~30,000 cases reported to date. ZIKV was first detected in Brazil in May 2015, and cases of microcephaly potentially associated with ZIKV infection were identified in November 2015. We performed next-generation sequencing to generate seven Brazilian ZIKV genomes sampled from four self-limited cases, one blood donor, one fatal adult case, and one newborn with microcephaly and congenital malformations. Results of phylogenetic and molecular clock analyses show a single introduction of ZIKV into the Americas, which we estimated to have occurred between May and December 2013, more than 12 months before the detection of ZIKV in Brazil. The estimated date of origin coincides with an increase in air passengers to Brazil from ZIKV-endemic areas, as well as with reported outbreaks in the Pacific Islands. ZIKV genomes from Brazil are phylogenetically interspersed with those from other South American and Caribbean countries. Mapping mutations onto existing structural models revealed the context of viral amino acid changes present in the outbreak lineage; however, no shared amino acid changes were found among the three currently available virus genomes from microcephaly cases. Municipality-level incidence data indicate that reports of suspected microcephaly in Brazil best correlate with ZIKV incidence around week 17 of pregnancy, although this correlation does not demonstrate causation. Our genetic description and analysis of ZIKV isolates in Brazil provide a baseline for future studies of the evolution and molecular epidemiology of this emerging virus in the Americas.

Evaluation of an Enzyme Immunoassay for Detection of Dengue Virus NS1 Antigen in Human Serum

ABSTRACT We evaluated a one-step sandwich-format microplate enzyme immunoassay for detecting dengue virus NS1 antigen (Ag) in human serum by use of Platelia Dengue NS1 Ag kits (Bio-Rad Laboratories, Marnes La Coquette, France). We collected 299 serum samples from patients with dengue disease and 50 serum samples from patients not infected with dengue virus. For the 239 serum samples from patients with acute infections testing positive by reverse transcription-PCR and/or virus isolation for one of the four dengue virus serotypes, the sensitivity of the Platelia Dengue NS1 Ag kit was 88.7% (95% confidence interval, 84.0% to 92.4%). None of the serum samples from patients not infected with dengue virus tested positive with the Platelia Dengue NS1 Ag kit. A diagnostic strategy combining the Platelia Dengue NS1 Ag test for acute-phase sera and immunoglobulin M capture enzyme-linked immunosorbent assay for early-convalescent-phase sera increased sensitivity only from 88.7% to 91.9%. Thus, NS1 antigen detection with the Platelia Dengue NS1 Ag kit could be used for first-line testing for acute dengue virus infection in clinical diagnostic laboratories.

Emergence and potential for spread of Chikungunya virus in Brazil

BackgroundIn December 2013, an outbreak of Chikungunya virus (CHIKV) caused by the Asian genotype was notified in the Caribbean. The outbreak has since spread to 38 regions in the Americas. By September 2014, the first autochthonous CHIKV infections were confirmed in Oiapoque, North Brazil, and in Feira de Santana, Northeast Brazil.MethodsWe compiled epidemiological and clinical data on suspected CHIKV cases in Brazil and polymerase-chain-reaction-based diagnostic was conducted on 68 serum samples from patients with symptom onset between April and September 2014. Two imported and four autochthonous cases were selected for virus propagation, RNA isolation, full-length genome sequencing, and phylogenetic analysis. We then followed CDC/PAHO guidelines to estimate the risk of establishment of CHIKV in Brazilian municipalities.ResultsWe detected 41 CHIKV importations and 27 autochthonous cases in Brazil. Epidemiological and phylogenetic analyses indicated local transmission of the Asian CHIKV genotype in Oiapoque. Unexpectedly, we also discovered that the ECSA genotype is circulating in Feira de Santana. The presumed index case of the ECSA genotype was an individual who had recently returned from Angola and developed symptoms in Feira de Santana. We estimate that, if CHIKV becomes established in Brazil, transmission could occur in 94% of municipalities in the country and provide maps of the risk of importation of each strain of CHIKV in Brazil.ConclusionsThe etiological strains associated with the early-phase CHIKV outbreaks in Brazil belong to the Asian and ECSA genotypes. Continued surveillance and vector mitigation strategies are needed to reduce the future public health impact of CHIKV in the Americas.

Inadequate management of natural ecosystem in the Brazilian Amazon region results in the emergence and reemergence of arboviruses

A total of 187 different species of arboviruses and other viruses in vertebrates were identified at the Evandro Chagas Institute (IEC) from 1954 to 1998, among more than 10,000 arbovirus strains isolated from humans, hematophagous insects, and wild and sentinel vertebrates. Despite intensive studies in the Brazilian Amazon region, especially in Pará State, very little is known about most of these viruses, except for information on date, time, source, and method of isolation, as well as their capacity to infect laboratory animals. This paper reviews ecological and epidemiological data and analyzes the impact of vector and host population changes on various viruses as a result of profound changes in the natural environment. Deforestation, mining, dam and highway construction, human colonization, and urbanization were the main manmade environmental changes associated with the emergence and/or reemergence of relevant arboviruses, including some known pathogens for humans.

Epidemia de dengue em Fortaleza, Ceará: inquérito soro-epidemiológico aleatório

OBJETIVO: Seguindo-se a epidemia de dengue (DEN), em 1994, em Fortaleza, Ceara, causada pelo sorotipo 2 (DEN-2), realizou-se inquerito soro-epidemiologico aleatorio para avaliar e dimensionar o impacto da mesma e a prevalencia do dengue por distrito sanitario. METODO: Foi aplicado questionario contendo informacoes gerais, condicoes socio-economicas, informacoes sobre o quadro clinico e tempo de doenca. A amostra foi calculada para estimar uma prevalencia de 20%, com erro relativo de 10%, e intervalo de confianca de 95% (erro a de 5%). O sorteio e as analises foram realizadas por meio de computador usando programas apropriados. RESULTADOS E CONCLUSOES: Foram colhidas 1.341 amostras de soro de 9 distritos sanitarios, testadas por inibicao da hemaglutinacao, sendo classificadas como negativas e positivas (respostas primaria - RP e secundaria - RS). Foram reativas 588 (44%) amostras, sendo 93 (7%) RP e 495 (37%) RS. A prevalencia global em Fortaleza variou de 21% a 71%. Houve 41% (243/588) de infeccoes assintomaticas (IA) e 59% (346/588) sintomaticas (IS). Nao houve diferenca da prevalencia quanto ao sexo, faixa etaria e escolaridade, ao contrario da condicao socioeconomica que apresentou diferencas estatisticamente significantes (p < 0,001). Ocorreram mais IA (p<0,001) e IS (p<0,0001) em casos de RS que RP, com significância estatistica em ambos os sexos. Os sintomas mais prevalentes no casos confirmados foram febre, cefaleia, mialgias, exantema, mal estar geral, tontura e artralgias, sendo que prurido, dor ocular, exantema e gengivorragia foram estatisticamente significantes (p<0,005). Tontura e artralgias foram mais associados com RS que com RP, havendo diferencas estatisticas (p <0,05).OBJECTIVE A seroepidemiological random survey was carried out in Fortaleza city, State of Ceará, Brazil, following an epidemic of dengue virus type 2 (DEN 2), with the purpose of evaluating the frequency of clinical manifestations (signs and symptoms) and the prevalence of dengue infection. METHOD A questionnaire calling for information on address, sex, age, clinical, epidemiological and economic status was applied to the population, followed by venupuncture collection of 5-10 ml of blood for testing by hemagglutination-inhibition (HI). The sample was calculated to obtain a prevalence of 20% with relative risk of 10% and confidence interval of 95%. All information obtained was analyzed by computer using Epi Info 5.0, Lotus 123, Excel 5.0, and Stata software. RESULTS AND CONCLUSIONS A total of 1,341 serum samples were obtained from nine Health Districts (SD) and tested by hemagglutination inhibition. Of these, 589 (44%) were positive and 752 (56%) negative. Of the positive results, 93 primary responses (PR) (7%) to DEN-2 and 496 secondary responses (SR) (37%) were observed. The global prevalence in the SD ranged from 21% to 71%. There were 41% (243/589) asymptomatic infections and 59% (346/589) symptomatic infections. Data analysis showed no difference in frequency by sex, age, on schooling, although a highly statistically significant difference was found as between the different social classes, the infection most commonly observed being among people of better social status. The stratification of positive cases showed greater prevalence of AI (p < 0.001) and SI (p < 0.0001) in both sexes, among people with SR rather than PR. The most prevalent symptoms were fever, headache, muscle pains, rash, dizziness, and joint pains. Moreover, itching, retro-bulbar pain, rash, and gingival bleeding, showed statistically significant differences. On the other hand, dizziness and joint pains were more associated in the patients with SR than PR, and statistically significant differences were also observed.

Genetic divergence and dispersal of yellow fever virus, Brazil.

Examining viral isolates collected over 66 years shows divergence into clades and potential dispersal by human migration.

Isolations of yellow fever virus from Haemagogus leucocelaenus in Rio Grande do Sul State, Brazil

Following howling monkey (Alouatta caraya) deaths and yellow fever (YF) antigen detection by immunohistochemistry in the liver sample of a dead monkey in April and May 2001 in the municipalities of Garruchos and Santo Antônio das Missões, Rio Grande do Sul State, Brazil, epidemiological field investigations were initiated. Two strains of YF virus were isolated in suckling mice from 23 Haemagogus (Conopostegus) leucocelaenus Dyar & Shannon mosquitoes collected from the study sites. The YF virus was isolated from this species in the 1930s in Brazil and in the 1940s in Colombia. No human cases were reported during the current epizootic outbreak. The YF virus isolation and the absence of Hg. (Haemagogus) janthinomys Dyar from the area suggest that Hg. leucocelaenus may be a secondary YF vector and play an important role in the epidemiology of this disease in the Southern Cone.

Phylogeography of dengue virus serotype 4, Brazil, 2010-2011.

Multiple origins indicate this serotype was introduced in several episodes.

Mayaro Fever Virus, Brazilian Amazon

In February 2008, a Mayaro fever virus (MAYV) outbreak occurred in a settlement in Santa Barbara municipality, northern Brazil. Patients had rash, fever, and severe arthralgia lasting up to 7 days. Immunoglobulin M against MAYV was detected by ELISA in 36 persons; 3 MAYV isolates sequenced were characterized as genotype D.

Genetic ancestry and income are associated with dengue hemorrhagic fever in a highly admixed population

To test whether African ancestry is protective for severe dengue, we genotyped 49 hospitalized cases of dengue hemorrhagic fever (DHF) as well as 293 neighborhood cases of dengue fever and 294 asymptomatic controls in Salvador, Bahia, Brazil. Ancestry-informative markers and 282 unlinked SNPs not associated with the clinical presentation of dengue were used to estimate ancestry. After controlling for income, both self-defined Afro-Brazilian ethnicity and African ancestry were protective for DHF (P=0.02, OR=0.28 and P=0.02, OR=0.13, respectively). Income or an index of income indicators, however, was also independently associated with the diagnosis of DHF.