Cristina Pedreira

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.

Duration of protection of pentavalent rotavirus vaccination in Nicaragua.

OBJECTIVE: To evaluate the duration of protection of pentavaent rotavirus vaccine (RV5) against rotavirus hospitalizations in Nicaragua, a developing country in Central America. METHODS: We conducted a case-control study at 4 hospitals from 2007 through 2010, including 1016 children hospitalized with laboratory-confirmed rotavirus diarrhea, 4930 controls with nonrotavirus diarrhea (ie, “test-negative”), and 5627 controls without diarrhea. All cases and controls were aged ≥6 months and born after August 2006. Outcomes included odds of antecedent vaccination between case-patients and controls, and effectiveness of vaccination (1 – adjusted odds ratio [OR] × 100). Duration of protection was assessed by comparing effectiveness among children aged <1 year compared with ≥1 year. RESULTS: Indicators of socioeconomic conditions and nonrotavirus vaccination (oral polio vaccine and diphtheria/tetanus/pertussis/hepatitis A/hepatitis B) for test-negative controls were more comparable to the rotavirus case-patients than nondiarrhea controls. RV5 vaccination was associated with a significantly lower risk of rotavirus hospitalization by using test-negative controls (OR: 0.55; 95% confidence interval [CI]: 0.41–0.74) and nondiarrhea controls (OR: 0.30; 95% CI: 0.22–0.40). Risk of rotavirus hospitalization was twofold lower among RV5 vaccinated children aged <1 year (OR: 0.36; 95% CI: 0.22–0.57) compared with RV5 vaccinated children aged ≥1 year (OR: 0.70; 95% CI: 0.47–1.05). CONCLUSIONS: RV5 provided good protection against severe rotavirus disease in Nicaragua during the first year of life, when most severe and fatal rotavirus disease in developing countries occurs. However, the decline in protection with age warrants monitoring of disease among older children and consideration of a booster dose evaluation at the end of infancy.

Uptake of Rotavirus Vaccine and National Trends of Acute Gastroenteritis among Children in Nicaragua

BACKGROUND In October 2006, a new rotavirus vaccine was introduced in Nicaragua and was available free to all age-eligible children. We assessed vaccine uptake and trends in acute gastroenteritis (AGE) to assess vaccine impact. METHODS We analyzed national data from the period 2001-2007 on the total number of AGE episodes and on RotaTeq vaccine dose administration during 2006-2007. RESULTS After the introduction of RotaTeq, 1-dose vaccine coverage rates rapidly increased to 80% among age-eligible children. During the 2007 rotavirus season, when combined 2- and 3-dose vaccine coverage among children aged 0-11 months was approximately 26%, the total number of AGE episodes among children aged 0-11 months decreased by 23%, compared with a decrease of 6% among unvaccinated children aged 12-59 months. Furthermore, a 12% decrease in the number of all-cause hospitalizations for AGE was noted among children aged 0-11 months, whereas a approximately 5% increase was observed among children aged 12-59 months. CONCLUSIONS The high rate of vaccination among age-eligible children soon after vaccine introduction in Nicaragua indicates an efficient immunization program. However, in the age group at risk of rotavirus disease, vaccine coverage during the 2007 rotavirus season had yet to reach a level sufficient for making firm conclusions about vaccine impact. Epidemiologic studies to evaluate vaccine effectiveness and ongoing surveillance as vaccine uptake increases will allow a better assessment of vaccine impact.

Rotavirus disease burden, Nicaragua 2001–2005: defining the potential impact of a rotavirus vaccination program

BACKGROUND In October 2006, a rotavirus vaccine was introduced in Nicaragua for routine immunization of all children. We document the baseline diarrheal disease burden in Nicaragua prior to the vaccine program to facilitate future studies to measure vaccine impact. METHODS We analyzed national data for 2001-2005 on total acute gastroenteritis healthcare visits, hospitalizations, and mortality in Nicaraguan children aged <5 years. RESULTS Prior to vaccine introduction, by age 5 years, one in four Nicaraguan children required an outpatient consultation, one in 34 were hospitalized, and one in 2487 died from rotavirus-associated diarrhea, representing approximately 41,122 outpatient visits, 4460 hospitalizations, and 60 deaths per year that are preventable through vaccination. Almost half of the total acute gastroenteritis burden was in children <1 year of age. Two distinct seasonal peaks were noted in acute gastroenteritis hospitalizations and deaths. CONCLUSIONS Existing data sources on all-cause acute gastroenteritis could be useful for establishing diarrhea disease burden and monitoring trends after vaccine introduction. Blunting of winter season peaks in rates of diarrhea, particularly among children aged <1-2 years, would be a useful indicator of impact from rotavirus vaccination.

Effectiveness of Pentavalent Rotavirus Vaccine Against a Diverse Range of Circulating Strains in Nicaragua

BACKGROUND Because >60 rotavirus strains have been reported worldwide, concerns exist about strain replacement after the introduction of rotavirus vaccines, particularly in developing countries with diverse strains and lower efficacy. METHODS We used the case-control design in 4 hospitals in Nicaragua to assess strain-specific vaccine effectiveness (VE) of a pentavalent rotavirus vaccine (RotaTeq) against rotavirus diarrhea. Cases were identified through prospective strain surveillance with reverse transcription-polymerase chain reaction for 3 years among children hospitalized for diarrhea, and controls were children negative for rotavirus. RESULTS We enrolled 1178 case-patients, 1082 (92%) with G and P typing, and 4927 controls. A different strain predominated each year with increasing age of the vaccine-eligible cohort during the study period: G2P[4] in 2008 (97%; mean age, 11.9 months), G1P[8] in 2009 (55%; mean age, 17.0 months), and G3P[8] in 2010 (78%; mean age, 17.3 months). Overall VE was 45% (95% confidence interval, 25%-59%). Regardless of the strain, VE estimates were 12%-79% lower among children aged ≥12 months relative to those 6-11 months of age. The lower VE for G3P[8] was related to the higher mean age of cases (17.3 months) compared with the G2P[4] strains (11.9 months), with a significant trend (R(2)= 0.819;P< .001) of declining effectiveness with increasing mean age of the cases. CONCLUSIONS Introduction of RotaTeq did not result in sustained emergence of any particular strain in Nicaragua. Variation in strain-specific effectiveness was due to an age-related decline in effectiveness rather than differences in protection against the observed strains.

Systematization of the Introduction of IPV and Switch from tOPV to bOPV in the Americas

Abstract The synchronized introduction of the inactivated polio vaccine (IPV) and the switch from trivalent oral polio vaccine (tOPV) to bivalent oral polio vaccine (bOPV) has constituted an effort without precedents, and with astonishing results. Within the established time frame, all countries in our region managed to carry out the decision, planning, and introduction of this vaccine and subsequent switch to their national immunization schedules. The purpose of this article is to systematize the process of IPV introduction and switch in Latin America and the Caribbean, which constitutes an important piece in the documentation of the polio legacy in the Americas. Regional level as well as country perspectives and viewpoints are described. Analyzing and summarizing the lessons learned from the introduction of IPV and the switch from tOPV to bOPV can be useful for the introduction of new vaccines in the Pan American Health Organization (PAHO) region and in other regions of the world, and to help our own region successfully carry out another synchronized vaccine introduction in the future, if necessary.