Vaccine Reports
Changes in Childhood Pneumonia and Infant Mortality Rates Following Introduction of the 13-valent Pneumococcal Conjugate Vaccine in Nicaragua Sylvia Becker-Dreps, MD, MPH,* Erick Amaya, PhD,† Lan Liu, PhD,‡ Gilberto Moreno, MD, MPH,§ Julio Rocha, RN, MPH,¶ Rafaela Briceño, MD, MPH,§ Jorge Alemán, MD,|| Michael G. Hudgens, PhD,‡ Christopher W. Woods, MD, MPH,** and David J. Weber, MD, MPH†† Background: In 2010, Nicaragua became the first developing nation to add 13-valent pneumococcal conjugate vaccine (PCV-13) to its national immunization schedule, using a “3+0” dosing schedule. We assessed changes in incidence rates of health facility visits for childhood pneumonia and infant mortality after PCV-13 introduction in the Department of León, Nicaragua. Methods: We collected visit diagnoses from all 107 public health facilities in León between 2008 and 2012. We compared rates of pneumonia hospitalizations, ambulatory visits for pneumonia and infant mortality during the prevaccine (2008–2010) and vaccine (2011–2012) periods among different age groups of children using generalized estimating equations, accounting for clustering by municipality. Exposure time was estimated by official municipality population estimates. Results: The adjusted incidence rate ratio for pneumonia hospitalization in the vaccine versus prevaccine period was 0.67 (0.59–0.75) among infants and 0.74 (0.67–0.81) among 1-year olds. The adjusted incidence rate ratio for ambulatory visits for pneumonia was 0.87 (0.75–1.01) among infants, and 0.84 (0.74, 0.95) among 1-year olds. The adjusted incidence rate ratio for infant mortality was 0.67 (0.57–0.80). We also observed lower rates of health facility visits for pneumonia among age groups (2- to 4-year old and 5- to 14-year old) not eligible to receive PCV-13. Conclusions: Within the first 2 years of a PCV-13 immunization program in Nicaragua, we observed lower rates of hospitalizations and ambulatory visits for pneumonia among children of all ages and a lower infant mortality rate. Lower rates of pneumonia among age groups not eligible to receive PCV-13 suggest an indirect effect of the vaccine. Key Words: pneumonia, Streptococcus pneumoniae; 13-valent pneumococcal vaccine, childhood, Nicaragua (Pediatr Infect Dis J 2014;33:637–642)
Accepted for publication December 27, 2013. From the *Department of Family Medicine, University of North Carolina School of Medicine, Chapel Hill, NC; †Department of Microbiology, National Autonomous University of Nicaragua, León, Nicaragua; ‡Department of Biostatistics, UNC Gillings School of Global Public Health, Chapel Hill, NC; §Sistemas Locales de Atención Integral a la Salud, León (SILAIS-León); ¶Hospital Epidemiology, ||Department of Pediatrics, Hospital Escuela Oscar Danilo Rosales Argüello (HEODRA), León, Nicaragua; **Division of Infectious Diseases, Duke U niversity School of Medicine, Durham, NC; and ††Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, NC. Funding was provided by Investigator-initiated Research Program, Pfizer, Inc. Dr. S.B.-D. has received investigator-initiated research grants from Pfizer and Merck, Inc. Dr. C.W.W. has been a consultant for Becton Dickinson, has been an advisor for BioMerieux, and has received a research grant from Novartis Diagnostics. Dr. D.J.W. has been a consultant and speaker for Pfizer and Merck, Inc. The authors have no other funding or conflicts of interest to disclose. Address for correspondence: Sylvia Becker-Dreps, MD, MPH, UNC Department of Family Medicine, 590 Manning Drive, Chapel Hill, NC 27599-7595. E-mail: [email protected]. Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0891-3668/14/3306-0637 DOI: 10.1097/INF.0000000000000269
S
treptococcus pneumoniae is estimated to cause the deaths of 826,000 children in the world each year.1 To reduce the burden of pneumococcal disease, several middle and high-income countries have implemented routine pediatric immunization with pneumococcal conjugate vaccines (PCV) and have experienced reduced rates of community-acquired pneumonia and pneumococcal pneumonia.2–6 As certain nonvaccine pneumococcal serotypes were found to increase in incidence in countries where the vaccine had been introduced, conjugate pneumococcal vaccines with additional serotypes have been developed, such as the 13-valent PCV (PCV-13). Currently, the World Health Organization supports the inclusion of PCV vaccines with additional serotypes to national pediatric immunization schedules worldwide.7 On December 12, 2010, Nicaragua became the first nation eligible for GAVI Alliance support to introduce routine immunization with PCV-13. Nicaraguan infants are offered the vaccine in a “3 + 0” dosing schedule, at 2, 4 and 6 months of age. During the first year of the immunization program, a single catch-up dose was also provided to children aged 12–24 months. While substantial reductions in hospitalizations for pneumococcal disease have been observed in higher income countries following the introduction of pneumococcal immunization programs, less is known about the impact of PCV immunization programs in lower income countries. In these settings, the prevaccine burden of pneumococcal disease and distribution of circulating pneumococcal serotypes are often unknown. Also, the clinical trials of PCVs were primarily conducted in the United States and Europe; there may be differences in the host immune response to the vaccine in developing countries. The goal of this study was to examine changes in pediatric hospitalizations and ambulatory (outpatient) visits for pneumonia before and after introduction of a PCV-13 immunization program in León, Nicaragua. To investigate whether there may have been differences in health care access during the years we studied, we planned to also report on health facility visits for an unrelated diagnosis, diarrhea. A secondary goal included examining changes in all-cause infant mortality before and after PCV-13 introduction.
MATERIALS AND METHODS Setting Nicaragua is a low-middle income country in Central America with a per capita gross domestic product of US$1020.8 This study was conducted in the Department of León in western Nicaragua. León is home to Nicaragua’s second largest city, the Municipality of León (2012 population: 193,598), 5 peri-urban municipalities and 4 rural municipalities, for a total population of 396,969 in 2012. The climate is tropical with distinct dry and rainy seasons; an annual peak in pneumonia cases occurs during the rainy season, July to October.9 Among the 56 typeable S. pneumoniae isolates from Nicaraguan children submitted to the SIREVA II surveillance network between 2000 and 2010, 71% had serotypes that are included in PCV-13.10
The Pediatric Infectious Disease Journal • Volume 33, Number 6, June 2014
www.pidj.com | 637
Becker-Dreps et al
The Pediatric Infectious Disease Journal • Volume 33, Number 6, June 2014
The National Immunization Program offered routine influenza immunization for children
Changes in Childhood Pneumonia and Infant Mortality Rates Following Introduction of the 13-valent Pneumococcal Conjugate Vaccine in Nicaragua Sylvia Becker-Dreps, MD, MPH,* Erick Amaya, PhD,† Lan Liu, PhD,‡ Gilberto Moreno, MD, MPH,§ Julio Rocha, RN, MPH,¶ Rafaela Briceño, MD, MPH,§ Jorge Alemán, MD,|| Michael G. Hudgens, PhD,‡ Christopher W. Woods, MD, MPH,** and David J. Weber, MD, MPH†† Background: In 2010, Nicaragua became the first developing nation to add 13-valent pneumococcal conjugate vaccine (PCV-13) to its national immunization schedule, using a “3+0” dosing schedule. We assessed changes in incidence rates of health facility visits for childhood pneumonia and infant mortality after PCV-13 introduction in the Department of León, Nicaragua. Methods: We collected visit diagnoses from all 107 public health facilities in León between 2008 and 2012. We compared rates of pneumonia hospitalizations, ambulatory visits for pneumonia and infant mortality during the prevaccine (2008–2010) and vaccine (2011–2012) periods among different age groups of children using generalized estimating equations, accounting for clustering by municipality. Exposure time was estimated by official municipality population estimates. Results: The adjusted incidence rate ratio for pneumonia hospitalization in the vaccine versus prevaccine period was 0.67 (0.59–0.75) among infants and 0.74 (0.67–0.81) among 1-year olds. The adjusted incidence rate ratio for ambulatory visits for pneumonia was 0.87 (0.75–1.01) among infants, and 0.84 (0.74, 0.95) among 1-year olds. The adjusted incidence rate ratio for infant mortality was 0.67 (0.57–0.80). We also observed lower rates of health facility visits for pneumonia among age groups (2- to 4-year old and 5- to 14-year old) not eligible to receive PCV-13. Conclusions: Within the first 2 years of a PCV-13 immunization program in Nicaragua, we observed lower rates of hospitalizations and ambulatory visits for pneumonia among children of all ages and a lower infant mortality rate. Lower rates of pneumonia among age groups not eligible to receive PCV-13 suggest an indirect effect of the vaccine. Key Words: pneumonia, Streptococcus pneumoniae; 13-valent pneumococcal vaccine, childhood, Nicaragua (Pediatr Infect Dis J 2014;33:637–642)
Accepted for publication December 27, 2013. From the *Department of Family Medicine, University of North Carolina School of Medicine, Chapel Hill, NC; †Department of Microbiology, National Autonomous University of Nicaragua, León, Nicaragua; ‡Department of Biostatistics, UNC Gillings School of Global Public Health, Chapel Hill, NC; §Sistemas Locales de Atención Integral a la Salud, León (SILAIS-León); ¶Hospital Epidemiology, ||Department of Pediatrics, Hospital Escuela Oscar Danilo Rosales Argüello (HEODRA), León, Nicaragua; **Division of Infectious Diseases, Duke U niversity School of Medicine, Durham, NC; and ††Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, NC. Funding was provided by Investigator-initiated Research Program, Pfizer, Inc. Dr. S.B.-D. has received investigator-initiated research grants from Pfizer and Merck, Inc. Dr. C.W.W. has been a consultant for Becton Dickinson, has been an advisor for BioMerieux, and has received a research grant from Novartis Diagnostics. Dr. D.J.W. has been a consultant and speaker for Pfizer and Merck, Inc. The authors have no other funding or conflicts of interest to disclose. Address for correspondence: Sylvia Becker-Dreps, MD, MPH, UNC Department of Family Medicine, 590 Manning Drive, Chapel Hill, NC 27599-7595. E-mail: [email protected]. Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0891-3668/14/3306-0637 DOI: 10.1097/INF.0000000000000269
S
treptococcus pneumoniae is estimated to cause the deaths of 826,000 children in the world each year.1 To reduce the burden of pneumococcal disease, several middle and high-income countries have implemented routine pediatric immunization with pneumococcal conjugate vaccines (PCV) and have experienced reduced rates of community-acquired pneumonia and pneumococcal pneumonia.2–6 As certain nonvaccine pneumococcal serotypes were found to increase in incidence in countries where the vaccine had been introduced, conjugate pneumococcal vaccines with additional serotypes have been developed, such as the 13-valent PCV (PCV-13). Currently, the World Health Organization supports the inclusion of PCV vaccines with additional serotypes to national pediatric immunization schedules worldwide.7 On December 12, 2010, Nicaragua became the first nation eligible for GAVI Alliance support to introduce routine immunization with PCV-13. Nicaraguan infants are offered the vaccine in a “3 + 0” dosing schedule, at 2, 4 and 6 months of age. During the first year of the immunization program, a single catch-up dose was also provided to children aged 12–24 months. While substantial reductions in hospitalizations for pneumococcal disease have been observed in higher income countries following the introduction of pneumococcal immunization programs, less is known about the impact of PCV immunization programs in lower income countries. In these settings, the prevaccine burden of pneumococcal disease and distribution of circulating pneumococcal serotypes are often unknown. Also, the clinical trials of PCVs were primarily conducted in the United States and Europe; there may be differences in the host immune response to the vaccine in developing countries. The goal of this study was to examine changes in pediatric hospitalizations and ambulatory (outpatient) visits for pneumonia before and after introduction of a PCV-13 immunization program in León, Nicaragua. To investigate whether there may have been differences in health care access during the years we studied, we planned to also report on health facility visits for an unrelated diagnosis, diarrhea. A secondary goal included examining changes in all-cause infant mortality before and after PCV-13 introduction.
MATERIALS AND METHODS Setting Nicaragua is a low-middle income country in Central America with a per capita gross domestic product of US$1020.8 This study was conducted in the Department of León in western Nicaragua. León is home to Nicaragua’s second largest city, the Municipality of León (2012 population: 193,598), 5 peri-urban municipalities and 4 rural municipalities, for a total population of 396,969 in 2012. The climate is tropical with distinct dry and rainy seasons; an annual peak in pneumonia cases occurs during the rainy season, July to October.9 Among the 56 typeable S. pneumoniae isolates from Nicaraguan children submitted to the SIREVA II surveillance network between 2000 and 2010, 71% had serotypes that are included in PCV-13.10
The Pediatric Infectious Disease Journal • Volume 33, Number 6, June 2014
www.pidj.com | 637
Becker-Dreps et al
The Pediatric Infectious Disease Journal • Volume 33, Number 6, June 2014
The National Immunization Program offered routine influenza immunization for children
