Terezinha Maria de Paiva

The Dilemma of Influenza Vaccine Recommendations when Applied to the Tropics: The Brazilian Case Examined Under Alternative Scenarios

Since 1999 the World Health Organization issues annually an additional influenza vaccine composition recommendation. This initiative aimed to extend to the Southern Hemisphere (SH) the benefits—previously enjoyed only by the Northern Hemisphere (NH)—of a vaccine recommendation issued as close as possible to the moment just before the onset of the influenza epidemic season. A short time between the issue of the recommendation and vaccine delivery is needed to maximize the chances of correct matching between putative circulating strains and one of the three strains present in the vaccine composition. Here we compare the effectiveness of the SH influenza vaccination adopted in Brazil with hypothetical alternative scenarios defined by different timings of vaccine delivery and/or composition. Scores were based on the temporal overlap between vaccine-induced protection and circulating strains. Viral data were obtained between 1999 and 2007 from constant surveillance and strain characterization in two Brazilian cities: Belém, located at the Equatorial region, and São Paulo, at the limit between the tropical and subtropical regions. Our results show that, among currently feasible options, the best strategy for Brazil would be to adopt the NH composition and timing, as in such case protection would increase from 30% to 65% (p<.01) if past data can be used as a prediction of the future. The influenza season starts in Brazil (and in the equator virtually ends) well before the SH winter, making the current delivery of the SH vaccination in April too late to be effective. Since Brazil encompasses a large area of the Southern Hemisphere, our results point to the possibility of these conclusions being similarly valid for other tropical regions.

Safety of simultaneous pneumococcal and influenza vaccination in elderly patients in Brazil.

The elderly population (≥60 years) in Brazil is currently around 11.5 million (7% of the total Brazilian population of 165 million), but by the year 2025 it is estimated that this figure will have reached 32 million. Because of the high risk of morbidity and mortality associated with respiratory infections in the elderly, the World Health Organization (WHO) now recommends both pneumococcal and influenza vaccination in this age group. However, until recently, pneumococcal and influenza vaccination rates among the elderly population of Brazil have been very low, although it appeared they could increase as a result of collaborative programmes to advance global awareness of the benefits of adult vaccination. In the city of Sao Paulo (population 9 million) in 1996 and 1997, the Aging Research Centre at the Federal University of Sao Paulo held Elderly Vaccination Days in which pneumococcal and influenza vaccines were offered free of charge to elderly patients during autumn (April in the southern hemisphere). This initiative resulted from previous experience with mass media promotion of National Immunisation Days against poliomyelitis, and its success in achieving high vaccination rates against this disease. As part of the Elderly Vaccination Day initiative, we evaluated the safety of simultaneous pneumococcal and influenza vaccination in the elderly population who attended the Aging Research Centre in Sao Paulo during April 1996. This institute provides medical care for some 500 outpatients aged ≥60 years on a regular basis.

Evolutionary pattern of reemerging influenza B/Victoria lineage viruses in São Paulo, Brazil, 1996–2012: Implications for vaccine composition strategy

Since the 1980s, 2 antigenically distinct influenza B lineages have cocirculated in the world: B/Victoria/2/87 (first appeared in the 1980s) and B/Yamagata/16/88 (became predominant in the 1990s). B/Victoria/2/87 isolates were geographically restricted to eastern Asia during 1991–2000. During 2000–2001 and 2001–2002, B/Victoria/2/87 isolates reemerged in North America, Europe, and South America, and then spread globally. During influenza virus surveillance, season 2002, an outbreak of acute respiratory illness, which quickly spread among the population, has been notified by public health authorities living in Araraquara, São Paulo, Brazil. Instituto Adolfo Lutz and Secretariat of Health of São Paulo state teams initiate an investigation towards to describe the pattern of infection in this population temporally and by age and to characterize the strains by virus isolation and hemagglutination inhibition assay. The outbreak lasted approximately 10 weeks; many cases occurred between mid‐August and mid‐September. Children younger than 13 years were the most affected; the elderly were mostly immune to infection. Analysis of the clinical respiratory samples helped in identifying the B/Hong Kong/330/2001 and B/Brisbane/32/2002 subtypes—recent variants of B/Victoria/02/88, a lineage restricted to Southeast Asia until 2001. The Araraquara outbreak confirms the reemergence of the B/Victoria viruses in South America and highlights the importance of monitoring local circulating strains, especially in light of the absence of cross‐protection between antigenically distinct influenza lineages. Based on influenza virus surveillance, public health authorities worldwide should decide whether trivalent vaccines or quadrivalent vaccines (containing both influenza virus B lineages) are to be used in each country. J Med. Virol. 85:1983–1989, 2013.

Sequence analysis of the 2009 pandemic influenza A H1N1 virus haemagglutinin gene from 2009-2010 Brazilian clinical samples

In this paper, we analysed the haemagglutinin (HA) gene identified by polymerase chain reaction from 90 influenza A H1N1 virus strains that circulated in Brazil from April 2009-June 2010. A World Health Organization sequencing protocol allowed us to identify amino acid mutations in the HA protein at positions S220T (71%), D239G/N/S (20%), Y247H (4.5%), E252K (3.3%), M274V (2.2%), Q310H (26.7%) and E391K (12%). A fatal outcome was associated with the D239G mutation (p < 0.0001). Brazilian HA genetic diversity, in comparison to a reference strain from California, highlights the role of influenza virus surveillance for study of viral evolution, in addition to monitoring the spread of the virus worldwide.

Occurrence of influenza B/Hong Kong-Like strains in Brazil, during 2002

Through the influenza virus surveillance from January to October 2002, influenza B/Hong Kong-like strains circulating in the Southeast and Centre East regions of Brazil have been demonstrated. This strain is a variant from B/Victoria/02/88 whose since 1991 and until recently have been isolated relatively infrequently and have been limited to South-Eastern Asia. A total of 510 respiratory secretions were collected from patients 0 to 60 years of age, with acute respiratory illness, living in the Southeast and Centre East regions of Brazil, of which 86 (17.13%) were positive for influenza virus. Among them 12 (13.95%) were characterized as B/Hong Kong/330/2001; 3 (3.49%) as B/Hong Kong/1351/2002 a variant from B/Hong Kong/330/2001; 1 (1.16%) as B/Sichuan/379/99; 1 (1.16%) as B/Shizuoka/5/2001, until now. The percentages of cases notified during the surveillance period were 34.88%, 15.12%, 15.12%, 4.65%, 15.12%, 13.95%, in the age groups of 0-4, 5-10, 11-15, 16-20, 21-30, 31-50, respectively. The highest proportion of isolates was observed among children younger than 4 years but serious morbidity and mortality has not been observed among people older than 65 years, although B influenza virus component for vaccination campaign 2002 was B/Sichuan/379/99 strain. This was probably due to the elderly protection acquired against B/Victoria/02/88. In addition, in influenza A/Panama/2007/99-like (H3N2) strains 22 (25.58%) were also detected, but influenza A(H1N1) has not been detected yet.

Shift in the timing of respiratory syncytial virus circulation in a subtropical megalopolis: Implications for immunoprophylaxis

Respiratory syncytial virus (RSV) is the most common cause of severe respiratory infections worldwide, and an important cause of childhood bronchiolitis, pneumonia, and mortality. Although prevention of RSV infection by immunoprophylaxis with palivizumab has proved effective, a precise understanding of the timing of RSV outbreaks is necessary to ensure that infants are protected when RSV is circulating. In this study a consistent shift in the seasonal patterns of RSV circulation in southeast Brazil (São Paulo) is reported based on the analysis of 15 years of viral surveillance. Surveillance was conducted from 1996 to 2010 and involved the collection of samples from children with symptoms of acute respiratory infection. Putative changes in school terms, in the proportion of RSV genotypes infecting children and in the seasonal dynamics of several climatic parameters during the period were also investigated. The results revealed a progression in the timing of RSV seasons, with a shift in the onset and peak of RSV epidemics from 2007 onwards. Although lower rainfall and temperatures were associated with the onset of outbreaks, there was no evidence of changes in climate, school terms or in the relative proportion of genotypes in the period analyzed. These findings have direct implications for improving the prophylactic use of palivizumab, and stress the importance of fine tuning prophylaxis with recent surveillance data. In the case of São Paulo, palivizumab prophylaxis should be initiated earlier than suggested currently. Similar adjustments may be necessary in other regions. J. Med. Virol. 84:1825–1830, 2012.

MOLECULAR CHARACTERIZATION OF INFLUENZA B VIRUS OUTBREAK ON A CRUISE SHIP IN BRAZIL 2012

In February 2012, an outbreak of respiratory illness occurred on the cruise ship MSC Armonia in Brazil. A 31-year-old female crew member was hospitalized with respiratory failure and subsequently died. To study the etiology of the respiratory illness, tissue taken at necropsy from the deceased woman and respiratory specimens from thirteen passengers and crew members with respiratory symptoms were analyzed. Influenza real-time RT-PCR assays were performed, and the full-length hemagglutinin (HA) gene of influenza-positive samples was sequenced. Influenza B virus was detected in samples from seven of the individuals, suggesting that it was the cause of this respiratory illness outbreak. The sequence analysis of the HA gene indicated that the virus was closely related to the B/Brisbane/60/2008-like virus, Victoria lineage, a virus contained in the 2011-12 influenza vaccine for the Southern Hemisphere. Since the recommended composition of the influenza vaccine for use during the 2013 season changed, an intensive surveillance of viruses circulating worldwide is crucial. Molecular analysis is an important tool to characterize the pathogen responsible for an outbreak such as this. In addition, laboratory disease surveillance contributes to the control measures for vaccine-preventable influenza.

Diagnóstico de conjuntivite adenoviral pelo RPS Adenodetector

OBJETIVO: Avaliar a utilizacao do RPS Adenodetector®, como metodo diagnostico de pacientes com quadro clinico de conjuntivite adenoviral. METODOS: Analise de serie de casos consecutivos de pacientes com diagnostico clinico de ceratoconjuntivite adenoviral submetidos comparativamente ao teste RPS Adenodetector® e a raspado conjuntival para cultura de virus. RESULTADOS: Dos 11 pacientes avaliados, 10 pacientes apresentavam acometimento unilateral. Em relacao ao tempo de inicio dos sintomas no momento da colheita, 5 (45,5%) pacientes apresentavam dois dias de historia, 5 (45,5%) apresentavam tres dias e 1 (9,1%) apresentava 7 dias. A cultura para adenovirus foi positiva em 8 pacientes (73%) e o RPS Adenodetector® foi positivo em 9 pacientes (82%). Oito pacientes apresentaram o teste rapido e cultura positiva. Um paciente apresentou teste RPS Adenodetector® positivo com cultura negativa. Os dois pacientes com teste RPS Adenodetector® negativo apresentaram cultura negativa. O RPS Adenodetector® mostrou sensibilidade de 100% e especificidade de 67% adotando-se a cultura de virus como exame padrao-ouro para o diagnostico de conjuntivite adenoviral. CONCLUSAO: O RPS Adenodetector® foi util para o diagnostico de conjuntivite adenoviral e pode auxiliar na orientacao do paciente quanto ao contagio e disseminacao da doenca.

Coxsackie B2 virus fatal meningoencephalitis in a student

OBJECTIVE: To present the case of a girl who was previously healthy but had fatal evolution due to Coxsackie B2 viral meningoencephalitis.METHODS: The authors describe the case of a female child with fatal meningoencephalitis caused by Coxsackie B2 virus and present a review of the literature (Medline and Lilacs).RESULTS: The girl was eight years old when she presented meningoencephalitis with bad evolution, leading to death on the 32nd day of internation. The exams showed positive serologic reaction to Coxsackie B2. The virus taken from two stool samples was isolated. The CRF exam showed an increase four times higher on Coxsackie B2 titulation.CONCLUSION: The death of healthy patients with enteroviral encephalitis, as described here, is rarely dealt with in the medical literature, perhaps because of lack of clinic suspicion. This case tries to drive attention to the importance of an early etiologic diagnosis in the meningoencephalities and the search for specific etiological treatment.

Comparative study of adenoviruses with monoclonal antibodies

The obtainment of monoclonal antibodies for adenovirus species 4(Ad4) is described. The specificities of selected monoclonal antibodies were determined by means of viral neutralization test in cell culture, immunofluorescence and Enzyme-Linked Immunosorbent Assay (ELISA), in the presence of the following species of human adenovirus: 1, 2, 5 (subgenus C), 4 (subgenus E), 7 and 16 (subgenus B) and 9 (subgenus D). Two monoclonal antibodies species specific to adenovirus 4 (1CIII and 3DIII) and one monoclonal antibody that cross reacted with adenovirus species 4 and 7 (2HIII) were obtained.