Ana Maria Sardinha Afonso

Identification of Primary and Secondary Measles Vaccine Failures by Measurement of Immunoglobulin G Avidity in Measles Cases during the 1997 São Paulo Epidemic

ABSTRACT Despite almost universal use of measles vaccines in recent decades, epidemics of the disease continue to occur. Understanding the role of primary vaccine failure (failure to seroconvert after vaccination) and secondary vaccine failures (waning immunity after seroconversion) in measles epidemics is important for the evaluation of measles control programs in developing countries. After a measles epidemic in São Paulo, Brazil, 159 cases previously confirmed by detection of specific immunoglobulin M (IgM) antibodies were tested for IgG avidity, and a secondary immune response, defined by an IgG avidity index of at least 30%, was established in 30 of 159 (18.9%) patients. Among the 159 patients, 107 (67.3%) had not been vaccinated and 52 (32.7%) had received one or more doses of measles vaccine. Of the 107 unvaccinated patients, 104 (97.2%) showed a primary immune response, defined as an IgG avidity index of less than 30%. Among the 52 patients with documented vaccination, 25 (48.1%) showed a primary immune response and 27 (51.9%) showed a secondary immune response, thereby constituting a secondary vaccine failure. Primary vaccine failure was observed in 13 of 13 patients vaccinated prior to 1 year of age and in 43.5 and 12.5%, respectively, of patients receiving one or two doses after their first birthdays. These results provide evidence that measurement of IgG avidity can be used to distinguish between primary and secondary vaccine failures in vaccinated patients with measles; the method can also be a useful tool for the evaluation of measles control programs.

Etiologies of Rash and Fever Illnesses in Campinas, Brazil

BACKGROUND Few population-based studies of infectious etiologies of fever-rash illnesses have been conducted. This study reports on enhanced febrile-rash illness surveillance in Campinas, Brazil, a setting of low measles and rubella virus transmission. METHODS Cases of febrile-rash illnesses in individuals aged <40 years that occurred during the period 1 May 2003-30 May 2004 were reported. Blood samples were collected for laboratory diagnostic confirmation, which included testing for adenovirus, dengue virus, Epstein-Barr virus (EBV), enterovirus, human herpes virus 6 (HHV6), measles virus, parvovirus-B19, Rickettsia rickettsii, rubella virus, and group A streptococci (GAS) infections. Notification rates were compared with the prestudy period. RESULTS A total of 1248 cases were notified, of which 519 (42%) had laboratory diagnosis. Of these, HHV-6 (312 cases), EBV (66 cases), parvovirus (30 cases), rubella virus (30 cases), and GAS (30 cases) were the most frequent causes of infection. Only 10 rubella cases met the rubella clinical case definition currently in use. Notification rates were higher during the study than in the prestudy period (181 vs 52.3 cases per 100,000 population aged <40 years). CONCLUSIONS Stimulating a passive surveillance system enhanced its sensitivity and resulted in additional rubella cases detected. In settings with rubella elimination goals, rubella testing may be considered for all cases of febrile-rash illness, regardless of suspected clinical diagnosis.

Rubella encephalitis in a young adult male: isolation and genotype analysis

Rubella virus (RV) is the etiologic agent of a mild exanthematous disease associated with low-grade fever, lymphadenopathy, and a short-lived morbilliform rash [1, 2]. The complications of rubella are arthritis, thrombocytopenia, thyroiditis, and encephalitis, with the latter occurring in approximately 1 in 6,000 cases [3]. The severity is encephalitis as a complication of rubella is highly variable, and there is an overall mortality rate of 20%. Viral encephalitis refers to an acute inflammatory process of the brain parenchyma due to direct viral infection. The clinical presentation of viral encephalitis is non-specific and includes fever, varying degrees of alteration in sensorium with or without focal neurological deficits and/or seizures, all of which may be due as well to a variety of other infective and noninfective causes. A diagnosis of viral encephalitis can be achieved either by demonstrating the presence of viral nucleic acid or antibody in the cerebrospinal fluid (CSF) or by isolating the virus from CSF or brain tissue. However, even under optimal conditions, 30–60% of patients with clinically suspected viral encephalitis remain undiagnosed. We report here a case of encephalitis in a young man from whom it was possible to isolate RV from the CSF and peripheral blood mononuclear cells (PBMC). Case presentation

Investigation of measles IgM-seropositive cases of febrile rash illnesses in the absence of documented measles virus transmission, State of São Paulo, Brazil, 2000-2004

INTRODUCTION To review measles IgM-positive cases of febrile rash illnesses in the State of São Paulo, Brazil, over the five-year period following interruption of measles virus transmission. METHODS We reviewed 463 measles IgM-positive cases of febrile rash illness in the State of São Paulo, from 2000 to 2004. Individuals vaccinated against measles < or = 56 days prior to specimen collection were considered to be exposed to the vaccine. Serum from the acute and convalescent phases was tested for evidence of measles, rubella, parvovirus B19 and human herpes virus-6 infection. In the absence of seroconversion to measles immunoglobulin-G, measles IgM-positive cases were considered false positives in individuals with evidence of other viral infections. RESULTS Among the 463 individuals with febrile rash illness who tested positive for measles IgM antibodies during the period, 297 (64%) were classified as exposed to the vaccine. Among the 166 cases that were not exposed to the vaccine, 109 (66%) were considered false positives based on the absence of seroconversion, among which 21 (13%) had evidence of rubella virus infection, 49 (30%) parvovirus B19 and 28 (17%) human herpes virus-6 infection. CONCLUSIONS Following the interruption of measles virus transmission, thorough investigation of measles IgM-positive cases is required, especially among cases not exposed to the vaccine. Laboratory testing for etiologies of febrile rash illness aids interpretation of these cases.

Resurgence of measles virus in São Paulo, Brazil.

The epidemic that occurred in SP in 1997 showed the circulation of the D6 group. After this period there was a decrease in the individuals susceptible to it. Due to good strategies for the close observation of measles virus, the circulation of indigenous cases was not registered for the mentioned period. However, in 2001, 2002 and 2005, cases of an imported virus belonging to the group D5 was registered.

Rubella virus genotype 1G and echovirus 9 as etiologic agents of exanthematous diseases in Brazil: insights from phylogenetic analysis

Abstract The aim of the present study was to identify the rubella virus (RV) and enterovirus (EV) genotypes detected during the Epidemiological Surveillance on Exanthematic Febrile Diseases (VIGIFEX) study and to perform phylogenetic analysis. Ten RV- and four EV-positive oropharyngeal samples isolated from cell culture were subjected to RT-PCR and sequencing. Genotype 1G and echovirus 9 (E-9) was identified in RV- and EV-positive samples, respectively. The RV 1G genotype has been persisting in Brazil since 2000-2001. No evidence of E-9 being involved in exanthematic illness in Brazil has been reported previously. Differential laboratory diagnosis is essential for management of rash and fever disease.

Genetic diversity of measles virus--resurgence of new genotype D8 in São Paulo, Brazil.

Measles virus (MV) has been under control in Brazil because of the high coverage rates of immunization. Emphasized by the measles control global program at the Pan American Health Organization, with the use of several strategies of vaccination programs to reduce the number of circulating chains of transmission of the virus, these programs have successfully decreased the incidence of measles on a global scale. However, measles outbreaks still occasionally occur in areas with high vaccine coverage as a result of imported transmission.

Molecular analysis of rubella virus in travelers suspected of measles infection in São Paulo, Brazil

OBJECTIVE To identify measles virus genotypes in three cases of travelers suspected of measles infection. METHODS Samples (blood and urine) were collected for serology, virus isolation, and genotyping. Sera were analyzed for IgM antibodies against measles virus and rubella virus by enzyme-linked immunosorbent assay (ELISA) (Siemens - Marburg, Germany). Clinical samples (lymphocytes and urine) were inoculated into Statens Serum Institute rabbit corneal epithelial cell line- ATCC CL 60 (SIRC) and Vero Slam cells. RNA was extracted from clinical samples and cell culture was inoculated and processed by polymerase chain reaction (PCR) with oligonucleotides specific for measles virus (MV) and rubella virus (RV). RESULTS All patients showed IgM negative serology for MV and positive IgM for RV. RV belonging to genotypes 1B, 1C, and 1E were isolated from patients who came from Finland, Peru, and Germany, respectively. Genotype 1B has been found in Europe and on the East Coast of South America; 1C has been found in Peru and the West Coast of South America, and 1E, first identified in 1997, now appears to have worldwide distribution. CONCLUSION Information about RV and MV genotypes circulating in São Paulo is essential for the control of measles, rubella, and congenital rubella syndrome (CRS) in Brazil.

Genotype 1 of human parvovirus B19 in clinical cases.

Introduction: Virus surveillance strategies and genetic characterization of human parvovirus B19 (B19V) are important tools for regional and global control of viral outbreak. In São Paulo, Brazil, we performed a study of B19V by monitoring the spread of this virus, which is an infectious agent and could be mistakenly reported as a rash and other types of infection. Method: Serum samples were subjected to enzyme immunoassay, real time polymerase chain reaction, and sequencing. Results: From the 462 patients with suspected cases of exanthematic infections, the results of the 164 serum samples were positive for B19V immunoglobulin M. Among these cases, there were 38 patients with erythema infections and B19-associated with other infections such as encephalitis, hydrops fetalis, chronic anemia, hematological malignancies. These samples were sequenced and identified as genotype 1. Conclusion: This study showed patients with infections caused by B19V and sequencing genotype 1. Continuous monitoring is necessary to detect all known genotypes, and the emergence of new genotypes of these viruses for case management in public health control activities.

MOLECULAR EPIDEMIOLOGY OF A MEASLES VIRUS IN SAO PAULO, BRAZIL: AN IMPORTED CASE

Brazil follows the recommendations of the World Health Organization concerning the use of several strategies of measles vaccination programs and has succeeded in reducing transmission of the wild-type viruses. Sao Paulo State follows the same pattern; however, there was circulation of an imported case of virus in 2001 and 2005, which was shown to belong to the D5 group and in 2011 to the D4 group. In 2012 there were no reports of confirmed measles cases.