Helena Keico Sato

Serious adverse events associated with yellow fever 17DD vaccine in Brazil: a report of two cases.

BACKGROUND The yellow fever vaccine is regarded as one of the safest attenuated virus vaccines, with few side-effects or adverse events. We report the occurrence of two fatal cases of haemorrhagic fever associated with yellow fever 17DD substrain vaccine in Brazil. METHODS We obtained epidemiological, serological, virological, pathological, immunocytochemical, and molecular biological data on the two cases to determine the cause of the illnesses. FINDINGS The first case, in a 5-year-old white girl, was characterised by sudden onset of fever accompanied by headache, malaise, and vomiting 3 days after receiving yellow fever and measles-mumps-rubella vaccines. Afterwards she decompensated with icterus and haemorrhagic signs and died after a 5-day illness. The second patient-a 22-year-old black woman-developed a sore throat and fever accompanied by headache, myalgia, nausea, and vomiting 4 days after yellow fever vaccination. She then developed icterus, renal failure, and haemorrhagic diathesis, and died after 6 days of illness. Yellow fever virus was recovered in suckling mice and C6/36 cells from blood in both cases, as well as from fragments of liver, spleen, skin, and heart from the first case and from these and other viscera fragments in case 2. RNA of yellow fever virus was identical to that previously described for 17D genomic sequences. IgM ELISA tests for yellow fever virus were negative in case 1 and positive in case 2; similar tests for dengue, hantaviruses, arenaviruses, Leptospira, and hepatitis viruses A-D were negative. Tissue injuries from both patients were typical of wild-type yellow fever. INTERPRETATION These serious and hitherto unknown complications of yellow fever vaccination are extremely rare, but the safety of yellow fever 17DD vaccine needs to be reviewed. Host factors, probably idiosyncratic reactions, might have had a substantial contributed to the unexpected outcome.

Recent immunization against measles does not interfere with the sero-response to yellow fever vaccine

In order to determine whether previous measles vaccination interferes with the sero-response to yellow fever vaccine, 294 children at nine months of age were randomly assigned to immunization with yellow fever vaccine at different time intervals after measles vaccination. The seroconversion rate (SCR) and the log10 geometric mean titer (GMT) for 17 DD yellow fever vaccine at different intervals after Schwarz measles vaccination were: 1-6 days: SCR = 44/57 = 77%; GMT = 4.57; 7-13 days: SCR = 36/53 = 68%; GMT = 4.46; 14-21 days: SCR = 55/65 = 85%; GMT = 4.46; 22-27 days: SCR = 41/54 = 76%; GMT = 4.41 and >28 days: SCR = 52/65 = 80%; GMT = 4.24 (p > 0.05). We conclude that recent immunization against measles does not interfere with the sero-response to yellow fever vaccine.

Effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae among children in São Paulo, Brazil

In March 2010, Brazil introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in the routine infant immunization program using a 4-dose schedule and catch-up for children <23months. We investigated PCV10 effect on nasopharyngeal carriage with vaccine-type Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi) among children in São Paulo city. Cross-sectional surveys were conducted in 2010 (baseline) and 2013 (post-PCV10). Healthy PCV-naïve children aged 12-23months were recruited from primary health centers during immunization campaigns. Nasopharyngeal swabs were collected and tested for Hi; for Spn, all baseline and a stratified random sample of 400 post-PCV10 swabs were tested. We compared vaccine-type Spn and NTHi carriage prevalence pre-/post-PCV10, and used logistic regression to estimate PCV10 effectiveness (1-adjusted odds ratio×100%). Overall 501 children were included in the baseline and 1167 in the post-PCV10 survey (including 400 tested for Spn). Spn was detected in 40.3% of children at baseline and 48.8% post-PCV10; PCV10 serotypes were found in 19.8% and 1.8% respectively, representing a decline of 90.9% (p<0.0001). Carriage of vaccine-related serotypes increased (10.8-21.0%, p<0.0001), driven primarily by a rise in serotype 6C (1.8-11.2%, p<0.0001); carriage of serotypes 6A and 19A did not significantly change. PCV10 effectiveness (4 doses) against vaccine-type carriage was 97.3% (95% confidence interval 88.7-99.3). NTHi prevalence increased from 26.0% (130/501) to 43.6% (509/1167, p<0.0001); PCV10 vaccination seemed significantly associated with NTHi carriage, even after adjusting for other known risk factors. Carriage with PCV10 serotypes among toddlers declined dramatically following PCV10 introduction in São Paulo, Brazil. No protection of PCV10 against NTHi was observed. Our findings contribute to a growing body of evidence of PCV10 impact on vaccine-type carriage and highlight the importance of PCV10 as a tool to reduce the burden of pneumococcal disease in Brazil and globally.

Carriage Rate and Effects of Vaccination after Outbreaks of Serogroup C Meningococcal Disease, Brazil, 2010

Polysaccharide vaccine did not affect carriage nor interrupt transmission of an epidemic strain.

Impact of rotavirus vaccination on diarrhea-related hospitalizations in São Paulo State, Brazil

INTRODUCTION Following introduction of routine infant rotavirus vaccination, severe diarrhea hospitalization rates declined among children aged <5 years throughout Brazil. Ensuring equity of rotavirus vaccine impact is important in countries that self-finance immunization programs. The objective of this study was to examine rotavirus vaccine impact on diarrhea admission rates among children aged <5 years in Brazils public health system, according to area-based measures of human development in the state of São Paulo, Brazil. METHODS Ecological analysis of public health system hospitalization rates for acute gastroenteritis among children aged <5 years in the state of São Paulo, Brazil, according to five categories of municipal development based on a modified Human Development Index for municipalities. Acute gastroenteritis hospitalization rates among children aged <5 years after national rotavirus vaccine introduction (2008-2011) were compared to rates in pre-vaccine years (2000-2005) to calculate percent decline in rates (1-rate ratio) and 95% confidence intervals (CI) for each municipal development category. Direct hospitalization costs during the two periods were compared. RESULTS Annual rates declined by 40% (95% CI, 39-42%) from 631 diarrhea hospitalizations per 100,000 person years pre-rotavirus vaccination to 377 per 100,000 post-vaccination among children aged <5 years and 50% (95% CI, 48-52%) from 1009 to 505 per 100,000 among infants. Highest rates were observed in least developed municipalities. Significant declines of 26-52% among children <5 years and 41-63% among infants were observed in all categories of municipal development. Lower diarrhea hospitalization rates resulted in annual savings of approximately 2 million USD for the state of São Paulo. Savings in direct hospitalization costs benefitted municipalities in all five categories. CONCLUSION The introduction of rotavirus vaccination was associated with substantial reductions of diarrhea-related admissions at all levels of municipal development in São Paulo State, Brazil.

Eventos adversos pós-vacina contra a difteria, coqueluche e tétano e fatores associados à sua gravidade

OBJETIVO: Avaliar os eventos adversos pos-vacina contra a difteria, coqueluche e tetano (EAPV-DPT) e os fatores associados a sua gravidade. METODOS: Estudo transversal com componente descritivo e analitico, abrangendo os eventos adversos pos-vacina DPT notificados no Estado de Sao Paulo, de 1984 a 2001, entre criancas menores de sete anos de idade. A definicao de caso foi a adotada pela vigilância de EAPV-DPT; os dados obtidos foram originados da vigilância passiva desses eventos. No calculo das taxas, o numerador foram os EAPV e o denominador o numero de doses aplicadas. A associacao entre a gravidade dos EAPV-DPT e as exposicoes de interesse foi investigada pelas estimativas nao ajustadas e ajustadas da odds ratio, com os respectivos intervalos de 95% de confianca, usando regressao logistica nao condicional. RESULTADOS: Identificaram-se 10.059 EAPV-DPT relativos a 6.266 criancas, apresentando um ou mais EAPV, 29,5% foram internadas e em 68,2% houve contra-indicacao das doses subsequentes de DPT. Cerca de 75% dos eventos ocorreram nas primeiras seis horas apos a aplicacao da vacina. Os eventos mais frequentes foram: febre<39,5°C, reacao local, evento hipotonico hiporresponsivo e convulsao. Mostraram-se independentemente associadas a gravidade: intervalo inferior a uma hora entre a aplicacao da vacina e o evento (OR=2,1), primeira dose aplicada (OR=5,8), antecedentes neurologicos pessoais (OR=2,2) e familiares (OR=5,3). CONCLUSOES: A vigilância passiva de EAPV mostrou-se util no monitoramento da seguranca da vacina DPT, descrevendo as caracteristicas e a magnitude desses eventos, assim como permitiu identificar possiveis fatores associados as formas graves.

Rubella Vaccination of Unknowingly Pregnant Women: The São Paulo Experience, 2001

BACKGROUND Rubella vaccination is contraindicated during pregnancy. During mass immunization of women of childbearing age against rubella, women unknowingly pregnant may be vaccinated. To evaluate the effects of rubella vaccination during pregnancy, the Brazilian state of São Paulo conducted a follow-up study of pregnant women vaccinated during a rubella campaign in 2001. METHODS Women vaccinated during pregnancy were reported to a national surveillance system. In the state of São Paulo, follow-up of vaccinated women included household interviews. Serum samples from vaccinated women were tested for antirubella antibodies to classify susceptibility to rubella infection. Children born to susceptible mothers were tested for evidence of congenital rubella infection and evaluated for signs of congenital rubella syndrome. RESULTS The São Paulo State Health Department received 6473 notifications of women vaccinated during pregnancy. Serology performed for 5580 women identified 811 (15%) that were previously susceptible. Incidence of spontaneous abortion or stillbirth among previously susceptible vaccinated women was similar to women with prior immunity. Twenty-seven (4.7%) of 580 newborns tested had evidence of congenital rubella infection; none had congenital rubella syndrome. CONCLUSIONS Mass rubella vaccination of women of childbearing age was not associated with adverse birth outcomes or congenital rubella syndrome among children born to women vaccinated during pregnancy.

Adverse events following yellow fever immunization: Report and analysis of 67 neurological cases in Brazil

Neurological adverse events following administration of the 17DD substrain of yellow fever vaccine (YEL-AND) in the Brazilian population are described and analyzed. Based on information obtained from the National Immunization Program through passive surveillance or intensified passive surveillance, from 2007 to 2012, descriptive analysis, national and regional rates of YFV associated neurotropic, neurological autoimmune disease, and reporting rate ratios with their respective 95% confidence intervals were calculated for first time vaccinees stratified on age and year. Sixty-seven neurological cases were found, with the highest rate of neurological adverse events in the age group from 5 to 9 years (2.66 per 100,000 vaccine doses in Rio Grande do Sul state, and 0.83 per 100,000 doses in national analysis). Two cases had a combination of neurotropic and autoimmune features. This is the largest sample of YEL-AND already analyzed. Rates are similar to other recent studies, but on this study the age group from 5 to 9 years of age had the highest risk. As neurological adverse events have in general a good prognosis, they should not contraindicate the use of yellow fever vaccine in face of risk of infection by yellow fever virus.

Varicella vaccines and measles, mumps, rubella, and varicella vaccine.

OBJECTIVES To present an up-to-date review of studies investigating the efficacy, adverse events and vaccination regimens of the varicella vaccine and the new presentation combined with the vaccine for measles, mumps and rubella. SOURCES OF DATA Bibliographic review of the MEDLINE and LILACS databases covering the period 1999 to 2006. SUMMARY OF THE FINDINGS The varicella vaccine protects 70 to 90% of immunized children against any form of varicella zoster infection, but the efficacy against severe forms is higher (95 to 98%). This is a well-tolerated vaccine that causes few reactions. Since the vaccine was licensed, there have been three confirmed cases of transmission of the vaccine virus by domestic contacts to previously healthy people, who went on to develop mild disease. Despite evidence that the protection offered by this vaccine can wane over a number of years, it is not yet possible to state that a second dose is warranted, bearing in mind exposure to wild virus. After universal vaccination the chances of natural stimulation should drop and it is very probable that booster doses will become necessary. A measles, mumps, rubella, and varicella vaccine has recently been licensed that combines vaccines for measles, mumps, rubella and varicella in a single product with high rates of seroconversion. CONCLUSIONS The Brazilian Society of Pediatrics recommends the varicella vaccine for children from 1 year on. We hope that the measles, mumps, rubella, and varicella vaccine will soon be available in Brazil, since combined vaccines facilitate wider vaccination coverage.

Influenza B Outbreak on a Cruise Ship off the São Paulo Coast, Brazil

BACKGROUND In February 2012, crew and passengers of a cruise ship sailing off the coast of São Paulo, Brazil, were hospitalized for acute respiratory illness (ARI). A field investigation was performed to identify the disease involved and factors associated. METHODS Information on passengers and crew with ARI was obtained from the medical records of hospitalized individuals. Active case finding was performed onboard the ship. ARI was defined as the presence of one nonspecific symptom (fever, chills, myalgia, arthralgia, headache, or malaise) and one respiratory symptom (cough, nasal congestion, sore throat, or dyspnea). A case-control study was conducted among the crew. The cases were crew members with symptoms of influenza-like illness (ILI) (fever and one of the following symptoms: cough, sore throat, and dyspnea) in February 2012. The controls were asymptomatic crew members. RESULTS The study identified 104 ARI cases: 54 (51.9%) crew members and 50 (49.1%) passengers. Among 11 ARI hospitalized cases, 6 had influenza B virus isolated in nasopharyngeal swab. One mortality among these patients was caused by postinfluenza Staphylococcus aureus pneumonia. The crew members housed in the two lower decks and those belonging to the 18- to 32-year-old age group were more likely to develop ILI [odds ratio (OR) = 2.39, 95% confidence interval (CI) 1.09-5.25 and OR = 3.72, CI 1.25-11.16, respectively]. CONCLUSIONS In February 2012, an influenza B outbreak occurred onboard a cruise ship. Among crew members, ILI was associated with lower cabin location and younger age group. This was the first influenza outbreak detected by Brazilian public health authorities in a vessel cruising in South American waters.