Cuauhtémoc Ruiz Matus

Intussusception Risk and Health Benefits of Rotavirus Vaccination in Mexico and Brazil

BACKGROUND Because postlicensure surveillance determined that a previous rotavirus vaccine, RotaShield, caused intussusception in 1 of every 10,000 recipients, we assessed the association of the new monovalent rotavirus vaccine (RV1) with intussusception after routine immunization of infants in Mexico and Brazil. METHODS We used case-series and case-control methods to assess the association between RV1 and intussusception. Infants with intussusception were identified through active surveillance at 69 hospitals (16 in Mexico and 53 in Brazil), and age-matched infants from the same neighborhood were enrolled as controls. Vaccination dates were verified by a review of vaccination cards or clinic records. RESULTS We enrolled 615 case patients (285 in Mexico and 330 in Brazil) and 2050 controls. An increased risk of intussusception 1 to 7 days after the first dose of RV1 was identified among infants in Mexico with the use of both the case-series method (incidence ratio, 5.3; 95% confidence interval [CI], 3.0 to 9.3) and the case-control method (odds ratio, 5.8; 95% CI, 2.6 to 13.0). No significant risk was found after the first dose among infants in Brazil, but an increased risk, albeit smaller than that seen after the first dose in Mexico--an increase by a factor of 1.9 to 2.6 - was seen 1 to 7 days after the second dose. A combined annual excess of 96 cases of intussusception in Mexico (approximately 1 per 51,000 infants) and in Brazil (approximately 1 per 68,000 infants) and of 5 deaths due to intussusception was attributable to RV1. However, RV1 prevented approximately 80,000 hospitalizations and 1300 deaths from diarrhea each year in these two countries. CONCLUSIONS RV1 was associated with a short-term risk of intussusception in approximately 1 of every 51,000 to 68,000 vaccinated infants. The absolute number of deaths and hospitalizations averted because of vaccination far exceeded the number of intussusception cases that may have been associated with vaccination. (Funded in part by the GAVI Alliance and the U.S. Department of Health and Human Services.).

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.

Strengthening the technical capacity at country-level to make informed policy decisions on new vaccine introduction: Lessons learned by PAHO's ProVac Initiative

Rotavirus, pneumococcal conjugate and HPV vaccines have the potential to make substantial gains in health, specifically in reducing child mortality and improving womens health. Decisions regarding new vaccine introduction should be grounded in a broad evidence base that reflects national conditions. In this paper, we describe the Pan American Health Organization ProVac Initiatives experience in strengthening national decision making regarding new vaccine introduction through five sets of activities: (1) strengthening infrastructure for decision making; (2) developing tools for economic analyses and providing training to national multidisciplinary teams; (3) collecting data, conducting analysis, and gathering a framework of evidence; (4) advocating for evidence-based decisions; and (5) effectively planning for new vaccine introduction when evidence supports it. Key lessons learned regarding the role of multidisciplinary country teams, provision of direct technical support, development of tools, and provision of distance and in-person training are highlighted.

Elimination of Rubella and Congenital Rubella Syndrome in the Americas

In 2003, the Pan American Health Organization (PAHO) adopted a resolution calling for rubella and congenital rubella syndrome (CRS) elimination in the Americas by the year 2010. To accomplish this goal, PAHO advanced a rubella and CRS elimination strategy including introduction of rubella-containing vaccines into routine vaccination programs accompanied by high immunization coverage, interruption of rubella transmission through mass vaccination of adolescents and adults, and strengthened surveillance for rubella and CRS. The rubella elimination strategies were aligned with the successful measles elimination strategies. By the end of 2009, all countries routinely vaccinated children against rubella, an estimated 450 million people had been vaccinated against measles and rubella in supplementary immunization activities, and rubella transmission had been interrupted. This article describes how the region eliminated rubella and CRS.

The Americas: Paving the Road Toward Global Measles Eradication

BACKGROUND The Region of the Americas set a goal of interrupting endemic measles virus transmission by the end of 2000. This decision was primarily based on rapid decreases in measles disease burden in pioneering countries that implemented Pan American Health Organization-recommended vaccination and surveillance strategies. Review of these strategies may inform measles elimination efforts in other regions. METHODS Results from the implementation of the measles elimination strategy in the Americas were compiled and analyzed over a 30-year period, which was divided into 4 phases: the early years of the Expanded Program on Immunization (1980-1986); the start-up phase for elimination (1987-1994); the elimination phase (1995-2002); and the postelimination phase (2003-2010). Factors that contributed to elimination and the challenges confronted during the postelimination phase are discussed. RESULTS An analysis of vaccination strategies over time highlights the transition from monovalent measles vaccine to the incorporation of measles-mumps-rubella vaccine administered in the routine program. Regional vaccination coverage increased during the period 1987-2010, sustained at ≥90% since 1998. Measles elimination efforts led to the implementation of 157 national vaccination campaigns, vaccinating a total of 440 million persons. Endemic measles virus transmission was interrupted in 2002. After elimination, measles importations and associated outbreaks occurred. Measles incidence has remained at <1 case per 1 million population since 2002. CONCLUSIONS The success of measles elimination strategies in the Americas suggests that global measles eradication is attainable.

Sentinel Hospital Surveillance for Rotavirus in Latin American and Caribbean Countries

The burden of rotavirus disease in the Latin American region has been poorly understood despite the promise of effective vaccines. We describe here the implementation and results of a rotavirus surveillance network in the Latin American and Caribbean region. From 2005 through 2007, stool specimens and epidemiologic information were gathered from children <5 years of age who were hospitalized for acute diarrhea (3 looser-than-normal stools within <24 h) lasting <14 days with use of a standardized generic protocol. Stool samples were tested for rotavirus, and a proportion of detected strains were typed. The proportion of samples positive for rotavirus was applied to World Health Organization diarrhea-related mortality estimates to calculate rotavirus-associated mortality. In 2007, the network comprised 54 sites in 11 countries. During 2006-2007, specimens were collected from 19,817 children; 8141 of these specimens were positive for rotavirus. The median percentage of positive specimens in the country was 31.5% (range, 24%-47%). The risk of death from rotavirus diarrhea by age 5 years was 1 of 2874. Strong rotavirus winter seasonality was apparent, even in tropical Central America. Globally common strains (P[8] G1, P[8] G9, and P[4] G2) accounted for >75% of strains, although unusual strains, including G12, were detected at low levels. As rotavirus vaccines continue to be introduced in Latin America, maintenance of surveillance will provide robust pre-introduction data and a platform for estimating vaccine effectiveness and other measures of impact.

Rubella Vaccination of Unknowingly Pregnant Women During Mass Campaigns for Rubella and Congenital Rubella Syndrome Elimination, The Americas 2001–2008

BACKGROUND Due to the significant teratogenicity of rubella virus and the use of a live-attentuated vaccine, pregnancy is a contraindication of receipt of rubella vaccine (RCV). Data collected from several countries that have observed susceptible women who had received RCV during pregnancy documented that no infant with congenital rubella syndrome (CRS) has been born, so the risk is theoretical. As part of the regional initiative to eliminate rubella and CRS in the Americas, one of the key strategies was the vaccination of women of childbearing age. The implementation of mass vaccination campaigns targeting women of childbearing age in Argentina, Brazil, Costa Rica, Ecuador, El Salvador, and Paraguay provided an opportunity to further increase the body of knowledge on the safety of rubella vaccine if an unknowingly pregnant woman is vaccinated in early pregnancy. METHODS Using a standard protocol, women who were unknowingly pregnant or become pregnant ≤ 30 days after receiving RCV were evaluated to determine immunity status (eg, susceptible, immune, and unknown) at the time of vaccination. Susceptible pregnant women were observed to determine the outcome of the pregnancy. For pregnancies that resulted in live births, serum samples were obtained from the newborn for rubella immunoglobulin (Ig) M antibody testing. If the newborns serum sample was IgM positive, the infant was evaluated for manifestations of CRS. RESULTS During the period 2001-2008, 48748253 women of childbearing age were vaccinated in the region of the Americas, 39542253 (81%) of whom were vaccinated in the 6 selected countries. Of these women, 30139 (0.07%) were pregnant or became pregnant ≤1 month after receiving vaccine and were followed up. On the basis of serological evaluation, 2894 (10%) women were classified as susceptible at the time of vaccination; of their pregnancies, 1980 (90%) resulted in a live birth. Sera from 70 (3.5%) of these infants were rubella IgM antibody positive, but none of the infants had features of CRS as a result of rubella vaccination. The maximum theoretical risk for CRS following rubella vaccination of susceptible pregnant women was 0.2%. Conclusions. The results of these studies from 6 select countries provides additional evidence showing an absence of risk of CRS associated with administering rubella vaccine shortly before or during pregnancy.

Challenges to building capacity for evidence-based new vaccine policy in developing countries.

There are many challenges to ensuring that people in developing countries have equitable access to new vaccines. Two of the most important are having the capacity to make evidence-based new vaccine policy decisions in developing countries, and then when appropriate actually distributing those new vaccines to those who will most benefit from them. Based on our review of the Pan American Health Organizations ProVac Initiative in the Americas, we found that when national governments in developing countries develop the expertise to make the best technical decisions about immunization programs; take responsibility for helping to pay for and distribute vaccines; and are supported by strong partnerships with international organizations, they succeed in saving more lives more quickly.

Descriptive analysis of immunization policy decision making in the Americas

OBJECTIVES Reducing and eliminating vaccine-preventable diseases requires evidence-based and informed policy decision making. Critical to determining the functionality of the decision-making process for introduction of a new vaccine is understanding the role of the national immunization technical advisory group (ITAG) in each country. The aim of this study is to document the current situation of national level immunization policy decision making for use in the Pan American Health Organization (PAHO) ProVac Initiative. METHODS A structured 66-variable questionnaire developed by the World Health Organization (WHO) in collaboration with the University of Ottawa was distributed to all WHO regions; it was composed of dichotomous, multiple-choice, and open-ended questions. Questionnaires were e-mailed or faxed to the six WHO regional offices and the offices distributed them to all member states. This paper analyzes surveys from the Americas as part of PAHOs ProVac Initiative. RESULTS Twenty-nine countries of the Americas answered the survey. They conveyed that immunization policy making needed to be improved and further supported by organizations such as PAHO. Areas of improvement ranged from organization and technical support to strengthening capacity and infrastructure to improved coordination among stakeholders. This survey also highlighted a variety of ITAG processes that need further investigation. CONCLUSION This survey supports the efforts of PAHOs ProVac Initiative to disseminate knowledge and best practices for an immunization policy decision-making framework through the development of clear definitions and guidelines. By highlighting each problem noted in this study, ProVac will assist countries in Latin America and the Caribbean to build national capacity for making evidence-based decisions about introduction of new vaccines.

Impact of pneumococcal conjugate vaccine in children morbidity and mortality in Peru: Time series analyses

Streptococcus pneumoniae is the leading cause of bacterial pneumonia, meningitis and sepsis in children worldwide. Despite available evidence on pneumococcal conjugate vaccine (PCV) impact on pneumonia hospitalizations in children, studies demonstrating PCV impact in morbidity and mortality in middle-income countries are still scarce. Given the disease burden, PCV7 was introduced in Peru in 2009, and then switched to PCV10 in late 2011. National public healthcare system provides care for 60% of the population, and national hospitalization, outpatient and mortality data are available. We thus aimed to assess the effects of routine PCV vaccination on pneumonia hospitalization and mortality, and acute otitis media (AOM) and all cause pneumonia outpatient visits in children under one year of age in Peru. We conducted a segmented time-series analysis using outcome-specific regression models. Study period was from January 2006 to December 2012. Data sources included the National information systems for hospitalization, mortality, outpatient visits, and RENACE, the national database of aggregated weekly notifications of pneumonia and other acute respiratory diseases (both hospitalized and non-hospitalized). Study outcomes included community acquired pneumonia outpatient visits, hospitalizations and deaths (ICD10 codes J12-J18); and AOM outpatient visits (H65-H67). Monthly age- and sex-specific admission, outpatient visit, and mortality rates per 100,000 children aged <1year, as well as weekly rates for pneumonia and AOM recorded in RENACE were estimated. After PCV introduction, we observed significant vaccine impact in morbidity and mortality in children aged <1year. Vaccine effectiveness was 26.2% (95% CI 16.9-34.4) for AOM visits, 35% (95% CI 8.6-53.8) for mortality due to pneumonia, and 20.6% (95% CI 10.6-29.5) for weekly cases of pneumonia hospitalization and outpatient visits notified to RENACE. We used secondary data sources which are usually developed for other non-epidemiologic purposes. Despite some data limitations, our results clearly demonstrate the overall benefit of PCV vaccination in Peru.