Hermann G. Schatzmayr

An outbreak of dengue virus at Rio de Janeiro - 1986

Dengue virus type 1 has been isolated in Aedes albopictus cell strain, from sera of patients living in the Nova Iguaçu county, by Rio de Janeiro. The clinical picture was characterized by fever, headache, retrobulbar pain, backache, pains in the muscles and the joints and prostration. Studies in paired sera confirmed the presence of recent infection by dengue virus type 1. The outbreak reached adjacent areas, including Rio de Janeiro city (May, 1986).

Dengue virus type 3 in Rio de Janeiro, Brazil

Dengue virus type 3 was isolated for the first time in the country as an indigenous case from a 40 year-old woman presenting signs and symptoms of a classical dengue fever in the municipality of Nova Iguaçu, State of Rio de Janeiro. This serotype has been associated with dengue haemorrhagic epidemics and the information could be used to implement appropriate prevention and control measures. Virological surveillance was essential in order to detected this new serotype.

Evaluation of an IgG enzyme-linked immunosorbent assay for dengue diagnosis

BACKGROUND The hemagglutination inhibition (HI) test has been one of the standards, with the IgM antibody capture ELISA (MAC-ELISA), for the diagnosis of dengue virus infections. The spread of dengue throughout the world and the increasing number of cases to be tested makes an ELISA-format test for IgG antibodies to replace the HI test highly desirable. OBJECTIVES Evaluate the use of the IgG-ELISA as a substitute for the HI test in dengue diagnosis. STUDY DESIGN Paired serum samples defined as being from primary or secondary dengue virus infections by HI, were tested by an ELISA that detects IgG antibodies. The correlations of titers and serologic interpretations between these two tests were examined. RESULTS The IgG-ELISA showed a low correlation with the HI in primary infections, and a higher correlation in secondary infections because of the influence of IgM antibodies in the HI test. Nevertheless, IgG ELISA titers could be reliably associated with primary or secondary infections when analyzed by days after onset of symptoms, and can be used to characterize the immune response after flavivirus infections. CONCLUSION The combination of the IgM and IgG ELISAs may be used to serologically diagnose dengue virus infections, since the IgG ELISA can substitute for the HI test in characterizing the immune response to dengue virus infections.

Dengue Virus Type 3, Brazil, 2002

An explosive epidemic of DENV-3 in 2002 was the most severe dengue epidemic reported in Brazil since dengue viruses were introduced.

Comparison of three commercially available dengue NS1 antigen capture assays for acute diagnosis of dengue in Brazil.

Background Dengue is associated with explosive urban epidemics and has become a major public health problem in many tropical developing countries, including Brazil. The laboratory diagnosis of dengue can be carried out using several approaches, however sensitive and specific assays useful to diagnose in the early stage of fever are desirable. The flavivirus non-structural protein NS1, a highly conserved and secreted glycoprotein, is a candidate protein for rapid diagnosis of dengue in endemic countries. Methodology/Principal Findings We aimed to evaluate the potential use of 3 commercial kits in a panel of 450 serum samples for early diagnosis of dengue in Brazil. The PanBio Early ELISA (PanBio Diagnostics) showed a sensitivity of 72.3% (159/220) and a specificity of 100%, while the sensitivity of the Platelia™ NS1 assay (Biorad Laboratories) was 83.6% (184/220). However, the highest sensitivity (89.6%; 197/220) was obtained by using the NS1 Ag Strip (Biorad Laboratories). A lower sensitivity was observed in DENV-3 cases by all 3 kits. Serum positive by virus isolation were more often positive than cases positive by RT-PCR by all three assays and a higher detection rate was observed during the first four days after the onset of the symptoms. The presence or absence of IgM showed no influence in the confirmation by the pan-E Early ELISA (P = 0,6159). However, a higher confirmation by both Platelia™ NS1 (Biorad) and Dengue NS1 Ag Strip (Biorad) in the absence of IgM was statistically significant (P<0,0001 and P = 0,0008, respectively). Only the Platelia™ NS1 test showed a higher sensitivity in confirming primary infections than secondary ones. Conclusions/Significance The results indicate that commercial kits of dengue NS1 antigen are useful for the laboratory diagnosis of acute primary and secondary dengue. It can be used in combination with the MAC-ELISA for case detection and as screening test to complement viral isolation.

Dengue viruses in Brazil, 1986-2006

A total of 4,243,049 dengue cases have been reported in Brazil between 1981 and 2006, including 5,817 cases of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) and a total of 338 fatal cases. Although all Brazilian regions have been affected, the Northeast and Southeast regions have registered the highest number of notifications. DENV-1 and DENV-4 were isolated for the first time in the Amazon region of Brazil in 1981 and 1982. The disease became a nationwide public health problem following outbreaks of DENV-1 and DENV-2 in the state of Rio de Janeiro in 1986 and 1990, respectively. The introduction of DENV-3 in 2000, also in the state of Rio de Janeiro, led to a severe epidemic with 288 245 reported dengue cases, including 91 deaths. Virus strains that were typed during the 2002 epidemic show that DENV-3 has displaced other dengue virus serotypes and entered new areas, a finding that warrants closer evaluation. Unusual clinical symptoms, including central nervous system involvement, have been observed in dengue patients in at least three regions of the country.

Phylogeography and evolutionary history of dengue virus type 3

In this study, we revisited the phylogeography of the three of major DENV-3 genotypes and estimated its rate of evolution, based on the analysis of the envelope (E) gene of 200 strains isolated from 31 different countries around the world over a time period of 50 years (1956-2006). Our phylogenetic analysis revealed a geographical subdivision of DENV-3 population in several country-specific clades. Migration patterns of the main DENV-3 genotypes showed that genotype I was mainly circumspect to the maritime portion of Southeast-Asia and South Pacific, genotype II stayed within continental areas in South-East Asia, while genotype III spread across Asia, East Africa and into the Americas. No evidence for rampant co-circulation of distinct genotypes in a single locality was found, suggesting that some factors, other than geographic proximity, may limit the continual dispersion and reintroduction of new DENV-3 variants. Estimates of the evolutionary rate revealed no significant differences among major DENV-3 genotypes. The mean evolutionary rate of DENV-3 in areas with long-term endemic transmissions (i.e., Indonesia and Thailand) was similar to that observed in the Americas, which have been experiencing a more recent dengue spread. We estimated the origin of DENV-3 virus around 1890, and the emergence of current diversity of main DENV-3 genotypes between the middle 1960s and the middle 1970s, coinciding with human population growth, urbanization, and massive human movement, and with the description of the first cases of DENV-3 hemorrhagic fever in Asia.

Dengue in the State of Rio de Janeiro, Brazil, 1986-1998

This paper presents epidemiological, laboratory, and clinical data on 12 years of dengue virus activity in the State of Rio de Janeiro from the time the disease was first confirmed virologically in April 1986 through April 1998. DEN-1 and DEN-2 viruses are the serotypes circulating in the state and were responsible for the epidemics reported during the last 12 years. The results published here show both the impact of dengue virus infections on the population and laboratory advances that have improved dengue diagnosis.

Prevalence of infection with hepatitis delta virus (HDV) among carriers of hepatitis B surface antigen in Amazonas State, Brazil

Serum samples were non-randomly obtained from apparently healthy inhabitants of 5 villages in the Amazonas State, Brazil. Sera were tested by enzyme immunoassay for the presence of hepatitis B surface antigen (HBsAg) and, if this was found, for antibody to hepatitis delta virus (HDV). Of 574 people tested, 96 (16.7%) were reactive for HBsAg and 33 of these (34.4%) for anti-HDV. The results were analysed according to sex, age and history of jaundice and showed a high prevalence of hepatitis B virus (HBV) and HDV infections in these asymptomatic persons, mainly in young people. The rates of prevalence observed in Amazonas for both HBV and HDV are perhaps among the highest in the world, demonstrating that these viruses are endemic in this region of Brazil.

Virological study of a dengue type 1 epidemic at Rio de Janeiro

A dengue outbreak started in March, 1986 in Rio de Janeiro and spread very rapidly to other parts of the country. The great majority of cases presented classical dengue fever but there was one fatal case, confirmed by virus isolation. Dengue type 1 strains were isolated from patients and vectors (Aedes aegypti) in the area by cultivation in A. albopictus C6/36 cell line. The cytopathic effect (CPE) was studied by electron microscopy. An IgM capture test (MAC-ELISA) was applied with clear and reproducible results for diagnosis and evaluation of virus circulation; IgM antibodies appeared soon after start of clinical disease, and persisted for about 90 days in most patients. The test was type-specific in about 50% of the patients but high levels of heterologous response for type 3 were observed. An overall isolation rate of 46.8% (813 virus strains out of 1734 specimens) was recorded. The IgM test increased the number of confirmed cases to 58.2% (1479 out of 2451 suspected cases). The importance of laboratory diagnosis in all regions where the vectors are present is emphasized.