Lucia Helena de Oliveira

Effectiveness of ten-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in Brazil: a matched case-control study

BACKGROUND In March 2010, Brazil introduced the ten-valent pneumococcal conjugate vaccine (PCV10), which was licensed based on non-inferiority of immunological correlates of protection compared with the seven-valent vaccine. The schedule comprised three primary doses at ages 2 months, 4 months, and 6 months, and a booster dose at age 12 months. A single catch-up dose was offered for children aged 12-23 months at the time of introduction. We assessed PCV10 effectiveness against invasive pneumococcal disease in Brazilian children. METHODS Invasive pneumococcal disease, defined as isolation of Streptococcus pneumoniae from blood, cerebrospinal fluid, or another normally sterile site, was identified in children age-eligible for at least one PCV10 dose through laboratory-based and hospital-based surveillance in ten states in Brazil from March 1, 2010, until Dec 31, 2012. We aimed to identify four age-matched and neighbourhood-matched controls for each case. We used conditional logistic regression and calculated PCV10 effectiveness as (1-adjusted matched odds ratio) × 100% for vaccine-type and vaccine-related serotypes (ie, in the same serogroup as a vaccine serotype). FINDINGS In 316 cases (median age 13·2 months, range 2·6-53·1) and 1219 controls (13·3 months, 2·6-53·1), the adjusted effectiveness of an age-appropriate PCV10 schedule was 83·8% (95% CI 65·9-92·3) against vaccine serotypes, and 77·9% (41·0-91·7) against vaccine-related serotypes. Serotype-specific effectiveness was shown for the two most common vaccine serotypes-14 (87·7%, 60·8-96·1) and 6B (82·8%, 23·8-96·1)-and serotype 19A (82·2%, 10·7-96·4), a serotype related to vaccine serotype 19F. A single catch-up dose in children aged 12-23 months was effective against vaccine-type disease (68·0%, 17·6-87·6). No significant effectiveness was shown against non-vaccine serotypes for age-appropriate or catch-up schedules. INTERPRETATION In the routine immunisation programme in Brazil, PCV10 prevents invasive disease caused by vaccine serotypes. PCV10 might provide cross-protection against some vaccine-related serotypes. FUNDING Brazilian Ministry of Health, Pan-American Health Organization, and US Centers for Disease Control and Prevention.

Association between pentavalent rotavirus vaccine and severe rotavirus diarrhea among children in Nicaragua.

CONTEXT Pentavalent rotavirus vaccine (RV5), a live, oral attenuated vaccine, prevented 98% of severe rotavirus diarrhea in a trial conducted mainly in Finland and the United States. Nicaragua introduced RV5 in 2006, providing the first opportunity to assess the association between vaccination and rotavirus disease in a developing country. OBJECTIVE To assess the association between RV5 vaccination and subsequent rotavirus diarrhea requiring overnight admission or intravenous hydration. DESIGN, SETTING, AND PARTICIPANTS Case-control evaluation in 4 hospitals in Nicaragua from June 2007 to June 2008. Cases were children age-eligible to receive RV5 who were admitted or required intravenous hydration for laboratory-confirmed rotavirus diarrhea. For each case (n = 285), 1 to 3 neighborhood (n = 840) and hospital (n = 690) controls were selected. MAIN OUTCOME MEASURES Primary outcome was the association of RV5 and rotavirus diarrhea requiring overnight admission or intravenous hydration in the emergency department. Secondary analysis further classified disease as severe and very severe. We computed the matched odds ratio of vaccination in cases vs controls. Vaccine effectiveness was estimated using the formula 1 - matched odds ratio x 100%. RESULTS Of the 285 rotavirus cases, 265 (93%) required hospitalization; 251 (88%) received intravenous hydration. A single rotavirus strain (G2P[4]) was identified in 88% of the cases. Among cases and controls, respectively, 18% and 12% were unvaccinated, 12% and 15% received 1 dose of RV5, 15% and 17% received 2 doses, and 55% and 57% received 3 doses. Vaccination with 3 doses was associated with a lower risk of rotavirus diarrhea requiring overnight admission or intravenous hydration (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.36-0.82). Of the 285 rotavirus cases, 191 (67%) were severe and 54 (19%) were very severe. A progressively lower risk of severe (OR, 0.42; 95% CI, 0.26-0.70) and very severe rotavirus diarrhea (OR, 0.23; 95% CI, 0.08-0.61) was observed after RV5 vaccination. Thus, effectiveness of 3 doses of RV5 against rotavirus disease requiring admission or treatment with intravenous hydration was 46% (95% CI, 18%-64%); against severe rotavirus diarrhea, 58% (95% CI, 30%-74%); and against very severe rotavirus diarrhea, 77% (95% CI, 39%-92%). CONCLUSION Vaccination with RV5 was associated with a lower risk of severe rotavirus diarrhea in children younger than 2 years in Nicaragua but to a lesser extent than that seen in clinical trials in industrialized countries.

Decline in Diarrhea Mortality and Admissions after Routine Childhood Rotavirus Immunization in Brazil: A Time-Series Analysis

A time series analysis by Manish Patel and colleagues shows that the introduction of rotavirus vaccination in Brazil is associated with reduced diarrhea-related deaths and hospital admissions in children under 5 years of age.

Effectiveness of rotavirus vaccination against childhood diarrhoea in El Salvador: case-control study

Objective To evaluate the effectiveness of a monovalent rotavirus vaccine against severe rotavirus disease and to assess its impact on diarrhoea in children aged less than 2 years after national introduction in El Salvador, a low-middle income country in Central America. Design Matched case-control study. Setting Seven hospitals in cities across El Salvador, January 2007 to June 2009. Participants 323 children aged less than 2 years admitted with laboratory confirmed rotavirus diarrhoea and 969 healthy controls matched for age and neighbourhood. Main outcome measure Effectiveness of rotavirus vaccination ((1–adjusted odds ratio of vaccination)×100) against rotavirus diarrhoea requiring hospital admission. Results Cases and controls were similar for breast feeding, premature birth, maternal education, and socioeconomic variables. G1P[8] strains were identified in 92% of rotavirus cases. Effectiveness of two doses of vaccination against diarrhoea requiring hospital admission was 76% (95% confidence interval 64% to 84%). Protection was significantly lower (P=0.046) among children aged 12 months or more (59%, 27% to 77%) compared with children aged 6-11 months (83%, 68% to 91%). One dose of vaccine was 51% (26% to 67%) effective. At the sentinel hospitals, all admissions for diarrhoea among children under 5 declined by 40% in 2008 and by 51% in 2009 from the prevaccine year 2006. Conclusions A monovalent rotavirus vaccine was highly effective against admissions for rotavirus diarrhoea in children aged less than 2 years in El Salvador and substantially reduced the number of such admissions in this low-middle income setting. The impact on disease epidemiology after vaccination, particularly among older children, warrants future attention.

Rotavirus vaccine introduction in the Americas: progress and lessons learned

In Latin America and the Caribbean, rotavirus causes approximately 15,000 deaths, 75,000 hospitalizations, 2 million clinic visits and 10 million cases of rotavirus diarrhea annually. Two safe vaccines are available that are effective in preventing severe illness. To date, seven countries in Latin America (Brazil, Ecuador, El Salvador, Panama, Mexico, Nicaragua and Venezuela) have introduced the vaccine. For successful rotavirus vaccine introduction, the lessons learned re-emphasize the critical need for countries to have precise plans that will ensure technical, programmatic and financial sustainability of vaccine introduction. Of these lessons learned, programmatic feasibility and financial sustainability were particularly challenging for countries that were the first to introduce a rotavirus vaccine.

Global impact of rotavirus vaccines

The WHO has recently recommended the inclusion of rotavirus vaccine in the national immunization programs of all countries. In countries in the Americas, Europe and Australia that have adopted routine childhood immunization against rotavirus, significant reductions in the burden of severe childhood diarrhea have been observed. Besides protecting vaccinated children, disease rates also appear to be reduced in unvaccinated children, suggesting indirect benefits from vaccination (i.e., herd protection). Early clinical trial data from Africa and Asia are promising, and further efforts are needed to optimize the benefits of vaccination in developing countries where vaccines are likely to have their greatest impact.

Reduction of diarrhea-associated hospitalizations among children aged < 5 Years in Panama following the introduction of rotavirus vaccine.

Background: In March 2006, rotavirus vaccine (Rotarix, RV1) was introduced into the Panamanian national immunization program. We assessed the effect of vaccine on diarrhea-associated hospitalizations among young Panamanian children. Methods: We obtained monthly numbers of diarrhea-associated hospitalizations among children aged ≤5 years during 2003 and 2008 from 5 health regions in Panama, representing 53% of the birth cohort. We compared the number of diarrhea-associated hospitalizations during the postvaccine years of 2007 and 2008 with the prevaccine mean numbers 2003–2005 among children <1 year and those 1 to 4 years of age. Administrative data were used to estimate national rotavirus vaccine coverage. Results: During prevaccine years, diarrhea-associated hospitalizations among children <5 years in the 5 regions averaged 4057 annually. After the vaccine introduction, a decrease in diarrhea-associated hospitalizations of 22% (898 fewer) occurred in 2007 and 37% (1502 fewer) in 2008. Greater reductions were observed during January through June, the months presumed to have high rotavirus activity in prevaccine years (33% reduction in 2007 and 58% in 2008, compared with prevaccine mean). Reduction estimates were similar among infants and those aged 1–4 years of age, even though only 25% of the latter group was likely to have received vaccine by early 2008. Estimated coverage with ≥1 dose of rotavirus vaccine among infants increased from 63% at the end of 2006 to 94% at the end of 2008. Conclusions: RV1 appears to have had a substantial impact on diarrhea-associated hospitalizations among young children in Panama.

Effectiveness of monovalent rotavirus vaccine in Bolivia: case-control study

Objective To evaluate the effectiveness of two doses of a monovalent rotavirus vaccine (RV1) against hospital admission for rotavirus in Bolivia. Design Case-control study. Setting Six hospitals in Bolivia, between March 2010 and June 2011. Participants 400 hospital admissions for rotavirus, 1200 non-diarrhea hospital controls, and 718 rotavirus negative hospital controls. Main outcome measures Odds of antecedent vaccination between case patients and controls; effectiveness of vaccination ((1–adjusted odds ratio)×100), adjusted for age and other confounders; and stratified effectiveness by dose, disease severity, age group, and serotype. Results In comparison with non-diarrhea controls, case patients were more likely to be male and attend day care but less likely to have chronic underlying illness, higher level maternal education, and telephones and computers in their home. Rotavirus negative controls were somewhat more similar to case patients but also were more likely to be male and attend day care and less likely to have higher level maternal education and computers in their homes. The adjusted effectiveness of RV1 against hospital admission for rotavirus was 69% (95% confidence interval 54% to 79%) with rotavirus negative controls and 77% (65% to 84%) with non-diarrhea controls. The effectiveness of one dose of RV1 was 36% and 56%, respectively. With both control groups, protection was sustained through two years of life, with similar efficacy against hospital admission among children under 1 year (64% and 77%) and over 1 year of age (72% and 76%). RV1 provided significant protection against diverse serotypes, partially and fully heterotypic to the G1P[8] vaccine. Effectiveness using the two control groups was 80% and 85% against G9P[8], 74% and 93%% against G3P[8], 59% and 69% against G2P[4], and 80% and 87% against G9P[6] strains. Conclusion The monovalent rotavirus vaccine conferred high protection against hospital admission for diarrhea due to rotavirus in Bolivian children. Protection was sustained through two years of life against diverse serotypes different from the vaccine strain.

Confirmation of Rubella within 4 Days of Rash Onset: Comparison of Rubella Virus RNA Detection in Oral Fluid with Immunoglobulin M Detection in Serum or Oral Fluid

ABSTRACT Rubella virus infection is typically diagnosed by the identification of rubella virus-specific immunoglobulin M (IgM) antibodies in serum, but approximately 50% of serum samples from rubella cases collected on the day of rash onset are negative for rubella virus-specific IgM. The ability to detect IgM in sera and oral fluids was compared with the ability to detect rubella virus RNA in oral fluids by reverse transcription-PCR (RT-PCR) by using paired samples taken within the first 4 days after rash onset from suspected rubella cases during an outbreak in Perú. Sera were tested for IgM by both indirect and capture enzyme immunoassays (EIAs), and oral fluids were tested for IgM by a capture EIA. Tests for IgM in serum were more sensitive for the confirmation of rubella than the test for IgM in oral fluid during the 4 days after rash onset. RT-PCR confirmed more suspected cases than serum IgM tests on days 1 and 2 after rash onset. The methods confirmed approximately the same number of cases on days 3 and 4 after rash onset. However, a few cases were detected by serum IgM tests but not by RT-PCR even on the day of rash onset. Nine RT-PCR-positive oral fluid specimens were shown to contain rubella virus sequences of genotype 1C. In summary, RT-PCR testing of oral fluid confirmed more rubella cases than IgM testing of either serum or oral fluid samples collected in the first 2 days after rash onset; the maximum number of confirmations of rubella cases was obtained by combining RT-PCR and serology testing.

Progress in the introduction of the rotavirus vaccine in Latin America and the Caribbean: four years of accumulated experience.

Background: Two effective and safe rotavirus vaccines became available in 2006 and have been recommended for use in all countries by the World Health Organization. This article provides an update on the use of rotavirus vaccine in Latin American and Caribbean (LAC) countries. Methods: Data reported by LAC countries to the Pan American Health Organization (PAHO) were reviewed. Results: As of May 2010, 14 LAC countries and 1 territory have introduced the rotavirus vaccine into their national expanded program on immunization (EPI). Reported coverage levels for rotavirus vaccine are lower than those for other EPI vaccines recommended at the same age. A total of 15 LAC countries are part of the PAHOs LAC rotavirus surveillance network; 12 of them are using the vaccine. LAC countries are conducting several studies on rotavirus vaccine effectiveness, cost-effectiveness, and monitoring safety. Also, LAC countries are generating lessons learned on the public health implications of introducing a new vaccine into the EPI. Nine countries and the Cayman Islands pay for the entire cost of the vaccine using government funds. All but 2 countries purchase their rotavirus vaccine through PAHOs Revolving Fund. Conclusions: Rotavirus vaccine introduction in LAC has been faster than for other new vaccines, but coverage levels need to increase to maximize the effect of the intervention. Rotavirus surveillance needs to expand and be strengthened to better assess the effect of vaccine use. LAC countries will continue to provide useful data to monitor rotavirus trends and vaccine effect.