Effectiveness of the Fiocruz recombinant ChadOx1-nCoV19 against variants of SARS-CoV-2 in the Municipality of Botucatu-SP.

Introduction: As the COVID-19 pandemic progresses, rapidly emerging variants of concern raise fears that currently licensed vaccines may have reduced effectiveness against these new strains. In the municipality of Botucatu, São Paulo State, Brazil, a mass vaccination campaign using ChadOx1-nCoV19 was initiated on 16th of May 2021, targeting people 18-60 years old. Two vaccine doses were offered 12 weeks apart, with the second delivered on 8th of August, 2021. This setting offered a unique opportunity to assess the effectiveness of two ChadOx1-nCoV19 doses in a real-life setting. Materials and methods: Data on testing, hospitalization, symptoms, demographics, and vaccination were obtained from the Hospital das Clínicas da Faculdade de Medicina de Botucatu. A test-negative study design was employed; whereby the odds of being vaccinated among cases vs controls were calculated to estimate vaccine effectiveness (VE; 1-OR). All individuals aged 18-60 who received a PCR test after the 16th of May and were unvaccinated prior to this date were included in the analysis until the study ended in mid-November 2021. Results: 77,683 citizens of Botucatu aged 18-60 received the first dose, and 74,051 received a second ChadOx1-nCoV19 dose 12 weeks later for a vaccination coverage of 84.2 and 80.2%, respectively. Of 7.958 eligible PCR tests, 2.109 were positive and 5.849 negative. The VE against any symptomatic infection was estimated at 39.2%, 21 days after dose 1, and 74.5%, 14 days after dose 2. There were no COVID-19-related hospitalizations or deaths among the 74,051 fully vaccinated individuals. The VE against severe disease was estimated at 70.8 and 100% after doses 1 and 2, respectively. 90.5% of all lineages sequenced between doses 1 and 2 (16th of May-7th of August) were of the Gamma variant, while 83.0% were of the Delta variant during the second period after dose 2 (8th of August-18th of November). Discussion: This observational study found the effectiveness of ChadOx1-nCoV19 to be 74.5% against COVID-19 disease of any severity, comparable to the efficacy observed in clinical trials (81.3% after dose 2), despite the dominance of the Gamma and Delta VoCs. No COVID-19-related hospitalizations or deaths in fully vaccinated individuals were reported.

Economic Evaluation of Universal Varicella Vaccination in Mexico.

BACKGROUND: Universal varicella vaccination has proven to be cost-effective (CE) in countries where implemented. However, this has not been evaluated for Mexico. METHODS: The yearly disease burden (varicella cases/deaths, outpatient visits, and hospitalizations) was derived from Mexican seroprevalence data adjusted to the 2020 population. The yearly economic burden was calculated by combining disease with Mexican unit cost data from both health care and societal perspectives. Four different vaccination strategies were evaluated: (1) 1 dose of varicella vaccine at 1 year old; (2) 2 doses at 1 and 6 years; (3) 1 dose of varicella vaccine at 1 year, and quadrivalent measles-mumps-rubella-varicella vaccine at 6 years; (4) 2 doses of measles-mumps-rubella-varicella vaccine at 1 and 6 years. We developed an economic model for each vaccination strategy where 20 consecutive birth cohorts were simulated. Vaccination impact (number of avoided cases/deaths) was evaluated for a 20-year follow-up period based on vaccine effectiveness (87% and 97.4% for 1 and 2 doses), and assuming a 95% coverage. We estimated annual costs saved, incremental cost-effectiveness ratio, and costs per life year gained. RESULTS: Avoided cases during the 20-year follow-up with 1, and 2 doses were 20,570,722 and 23,029,751, respectively. Strategies 1 and 2 were found to be cost saving, and strategy 3 to be CE. Strategy 4 was not CE. Strategies 1 and 2 would allow saving annually $53.16 and $34.41 million USD, respectively, to the Mexican society. CONCLUSIONS: Universal varicella vaccination, using 1 dose or 2 doses, would result in a cost-beneficial and CE public health intervention in Mexico.

The burden of norovirus disease in children: a multi-country study in Chile, Brazil, Thailand and the Philippines.

BACKGROUND: Noroviruses (NoVs) cause acute gastroenteritis (AGE) worldwide, affecting children in particular. We aimed to estimate the burden of disease due to NoV among children aged <6 years in Brazil, Chile, Philippines and Thailand. METHODS: This was a prospective, hospital-based, observational study. Children were recruited over one year between 2014 and 2017. Four cohorts were analysed: community-acquired AGE outpatients and inpatients, nosocomial AGE inpatients, and asymptomatic outpatients. We collected demographic and clinical data, and a stool sample that was tested for NoV. Positive samples were tested for Rotavirus (RV) and NoV-genotyped. Disease severity was assessed by the Vesikari and modified Vesikari scores. Prevalence and incidence of NoV-AGE were estimated by cohort and country. RESULTS: 1637 participants yielded valid laboratory results. The proportion of NoV-positive cases was 23.8% (95% CI 20.8-27.2) in the outpatient cohort, 17.9% (15.0-21.3) in the hospital cohort, 21.4% (12.7-33.8) in the nosocomial cohort and 9.6% (6.9-13.2) in the asymptomatic cohort. Genotype GII.4 was predominant (58%). Less than 4% samples had RV coinfection. In general, NoV-positive subjects had more severe presentations than NoV-negative subjects. CONCLUSIONS: NoV caused AGE with substantial burden throughout the studied settings, with higher relative frequency in Brazil where RV vaccination coverage is high.

Background rates of disease in Latin American children from a rotavirus vaccine study.

BACKGROUND: Knowledge of background rates of adverse events is crucial to assess vaccine safety concerns. We used data from a rotavirus vaccine study (Ruiz-Palacios et al., NEJM, 2006) including 63,225 infants from 11 Latin American countries to investigate reporting rates of serious adverse events (SAEs) among these infants, and describe rates by country, gender, age, and season. METHODS: For this randomized, double-blind, placebo-controlled, phase 3 trial, investigators from Argentina, Brazil, Chile, Colombia, Dominican Republic, Honduras, Mexico, Nicaragua, Panama, Peru, and Venezuela recruited 6-to-13-week-old healthy infants. The infants received 2 oral doses of vaccine or placebo. The study population was followed 100 d for the assessment of adverse events. SAEs were captured by an active surveillance system. RESULTS: Strong differences in event rates could be observed between countries (min. 48.1/10,000 person-years in Dominican Republic/Peru; max. 296.2/10,000 person-years in Brazil) and between genders: gastroenteritis, pneumonia, bronchiolitis and bronchitis occurred significantly more frequently in males. In addition, infections and infestations, and most disorders, including immune system and cardiac disorders, were more frequent at earlier ages. Finally, looking at seasonality we noted higher rates of SAEs in the second half of the year in all countries except Mexico. DISCUSSION: Significant differences in reporting rates of SAEs between countries, gender and calendar months illustrate the importance of knowing the local epidemiology when interpreting SAEs. Data from clinical trials can be used to better understand background rates of diseases that may be perceived as potential adverse events following immunization.

Postmarketing surveillance of intussusception following mass introduction of the attenuated human rotavirus vaccine in Mexico.

BACKGROUND: Mexico initiated mass vaccination with the attenuated human rotavirus vaccine (Rotarix) in 2006. This postlicensure study aimed to assess any potential temporal association between vaccination and intussusception in Mexican infants. METHODS: Prospective, active surveillance for intussusception among infants aged less than 1 year was conducted in 221 hospitals across Mexico from the Mexican Institute of Social Security between January 2008 and October 2010. The temporal association between vaccination and intussusception was assessed by self-controlled case-series analysis. RESULTS: Of the 753 episodes of intussusception reported in 750 infants, 701 were in vaccinated infants (34.5% post-dose 1, 65.5% post-dose 2). The relative incidence of intussusception within 31 days of vaccination was 1.75 (95.5% confidence interval [CI]: 1.24-2.48; P=0.001) post-dose 1 and 1.06 (95.5% CI: 0.75-1.48; P=0.75) post-dose 2. The relative incidence of intussusception within 7 days of vaccination was 6.49 post-dose 1 (95.5% CI: 4.17-10.09; P<0.001) and 1.29 post-dose 2 (95.5% CI: 0.80-2.11; P=0.29). Clustering of intussusception within 7 days of vaccination was observed post-dose 1. An attributable risk of 3 to 4 additional cases of intussusception per 100,000 vaccinated infants was estimated. CONCLUSION: This is the largest surveillance study for intussusception after rotavirus vaccination to date. A temporal increase in the risk for intussusception was seen within 7 days of administration of the first vaccine dose. It is still uncertain whether rotavirus vaccination has any impact on the overall incidence of intussusception. This finding has to be put in perspective with the well-documented substantial benefits of rotavirus vaccination.

Differences in the immune response to hepatitis B and Haemophilus influenzae type b vaccines in Guatemalan infants by ethnic group and nutritional status.

Ladino and native Indian Guatemalan infants developed high rates (96-100%) of protective antibodies after receiving conjugate Haemophilus influenzae type b and hepatitis B vaccines at 2, 4 and 6 months of age. Native Indian infants developed significantly (p<0.01) higher geometric mean anti-PRP (polyribose-ribitol-phosphate) and anti-HBs (anti-hepatitis b surface) antibody concentrations than Ladino infants. Malnourished infants generally responded as well as healthy infants. Unvaccinated native Indian infants had higher rates of developing anti-PRP antibodies than Ladino infants by seven months of age.

Prospective multinational study of pertussis infection in hospitalized infants and their household contacts.

BACKGROUND: Increased incidence of pertussis has been noted among infants too young to be immunized. We studied the disease burden of pertussis in pediatric intensive care units and the source of infection in several Asian, European and Latin American countries. METHODS: The study was conducted in 7 countries from September 2001 to January 2004. Children <1 year of age were enrolled from pediatric intensive care units (PICU) and pediatric wards if they presented with respiratory failure, apnea, bradycardia, or cough accompanied by paroxysms, vomiting, whoop or cyanosis. Household members of pertussis-positive index cases were asked to answer a questionnaire and provide diagnostic specimens. RESULTS: Pertussis was confirmed in 99 infants (12%) of 823 infants included in the analysis: 10 of 90 (11%) in Brazil, 9 of 88 (10%) in Costa Rica, 11 of 145 (8%) in Germany, 13 of 147 (9%) in Singapore, 29 of 67 (43%) in Spain, 2 of 86 (2%) in Taiwan and 25 of 200 (13%) in Uruguay. However, sensitivity analysis indicated that these figures were conservative. The mean (+/- SD) average age of infection was 2.6 +/- 2.2 months. Pertussis was found among 96 of 269 (36%) of household contacts investigated. At least one household contact was identified as the source of infection in 24 of 88 (27%) of the PICU cases and mothers were identified as being the most frequent source of infection. CONCLUSION: Although regional differences exist, severe pertussis represents a considerable global disease burden. Since most infants are infected before vaccination and concomitant protection is completed, household contacts should be targeted for booster vaccination to reduce the pertussis reservoir.

Rotavirus serotype G9 is associated with more-severe disease in Latin America.

The association between rotavirus serotypes and severity is not well established. Analysis of a clinical trial conducted in Latin America points at more-severe disease associated with serotype G9. Thus, demonstration of efficacy against G9 will be an important asset of any rotavirus vaccine to be introduced into a Latin American country or any country where G9 has been shown to be prevalent.