PLoS One. 2014 Nov 6;9(11):e112337. doi: 10.1371/journal.pone.0112337.

Effect of pneumococcal conjugate vaccination in Uruguay, a middle-income country.


García Gabarrot G1, López Vega M1, Pérez Giffoni G1, Hernández S1, Cardinal P2, Félix V1, Gabastou JM3, Camou T1; Uruguayan SIREVA II Group.
  • 1Departamento de Laboratorios, Ministerio de Salud Pública, Montevideo, Uruguay.
  • 2Unidad de Terapia Intensiva, CASMU-IAMPP, Montevideo, Uruguay.
  • 3Area of Technology and Health Services Delivery, Pan American Health Organization, Washington, D. C., United States of America.



BACKGROUND: In 2008, a 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the routine childhood immunization program in Uruguay, with a 2+1 schedule. In 2010, PCV13 replaced PCV7, and the same 2+1 schedule was used. The effect of these pneumococcal vaccines on the incidence of invasive pneumococcal infections (IPD) and on serotype distribution was analyzed retrospectively, based on passive national laboratory surveillance.

METHODS: Data from 1,887 IPD isolates from 5 years before and 5 years after PCV7 introduction (7 before and 3 after PCV13 introduction) was examined to assess the incidence rate per 100,000 age-specific population of all IPD, PCV7-serotypes, and PCV13-serotypes associated IPD among children < 2 years and 2 to 4 years old, and patients ≥ 5 years old. Trends of frequency for each serotype were also analyzed.

RESULTS: Comparison of pre-vaccination (2003-2007) and post-vaccination (2008-2012) periods showed a significant decrease in IPD incidence among children < 2 years old (IR 68.7 to IR 29.6, p<0.001) and children 2 to 4 years (p < 0.04). IPD caused by serotypes in PCV7 was reduced by 95.6% and IPD caused by 6 serotypes added in PCV13 was reduced by 83.9% in children <5 years old. Indirect effects of both conjugate vaccines were observed among patients ≥ 5 years old one year after the introduction of each vaccine, in 2010 for PCV7 and in 2012 for PCV13. Nevertheless, for reasons that still need to be explained, perhaps due to ascertainment bias, total IPD in this group increased after 2007. In 2012, the relative frequency of vaccine serotypes among vaccinated and unvaccinated population declined, except for serotype 3. Non vaccine serotypes with increasing frequency were identified, in rank order: 12F, 8, 24F, 22F, 24A, 15C, 9N, 10A and 33.

CONCLUSION: Consecutive immunization with PCV7 and PCV13 has significantly reduced IPD in children < 5 years of age in Uruguay.

PMID: 25375647



Invasive pneumococcal diseases (IPD), such as bacteremic pneumonia and meningitis, are one of the most important causes of severe disease and death among children less than 5 years old and among adults over 60 years old.

The strategy to fight these infections has been the formulation of conjugate vaccines which include the most frequent capsular serotypes of Streptococcus pneumoniae causing infection around the world. In 2000, a seven-valent conjugate vaccine (PCV7) was introduced in USA and other developed countries. In 2010, new conjugate vaccines with extended formulations, useful even for those countries with diverse serotype distribution, became available: PCV10 and PCV13 with the same serotypes in PCV7 plus 3 and 6 additional serotypes respectively.


Figure 1. Uruguay in South America

Our country, Uruguay (Figure 1), was the first country in South America to introduce routine vaccination against Haemophilus influenzae type b into the national immunization program. Thus, the introduction of PCV7 was promptly considered but not implemented because the percentage of pneumococcal invasive disease caused by the seven serotypes included in the available vaccine reached only 49% of isolates from Uruguayan children under 5 years of age [1]. In 2008, National Health authorities decided to introduce PCV7 anyway, with the understanding that it would be replaced shortly after, by one of the extended-formulation vaccines, which in our case was PCV13. Vaccines coverage has always reached >90% and catch-up was offered to older children on both occasions.

Information about serotype distribution was available as a result of laboratory-based surveillance established at the national level since 1994, when we and other 5 Latin American countries were encouraged by Pan American Health Organization to start a regional network, SIREVA, aimed to monitor the distribution of serotypes among pneumococcal invasive isolates [2, 3]. The SIREVA II network includes now almost all Latin American and Caribbean countries.

One of the advantages to be one of the smallest countries in South America, with 3.3 million inhabitants, was the possibility to organize a not-mandatory national laboratory surveillance that became enough robust to collect a number of pneumococcal invasive isolates which represent the true incidence. We also believed that our national network would be able to detect the effect of consecutive immunization with PCV7 and PCV13, both among vaccinated and unvaccinated population.

Our main questions were: Can we see a decline in the total number of IPD cases and vaccine-related disease among vaccinated children? Can we observe an indirect or “herd” effect among non-vaccinated population? Is IPD caused by non-vaccine serotypes increasing in these populations and is this increase of the same or different magnitude as the decline of vaccine-related disease? Are there any emerging serotypes? And the most important…Is our surveillance accurate and reflect real changes after vaccination or were there changes in reporting protocols or procedures that introduced a bias in our results?

We decided to include the results of 5 years before and 5 years after PCV 7 introduction (2003-2007 and 2008-2012) and to analyze incidence rates for 5 different age groups. The total number of pneumococcal isolates from children <5 years decreased by half during the post-vaccination period (Figure 2), and this was the result of the decline in IPD caused by vaccine serotypes. We did not detect statistical significant increase in IPD caused by non-vaccine serotypes among vaccinated children.

In contrast, we observed an important increase of the total number of pneumococcal isolates from adults immediately after PCV7 introduction, but we think it might be caused, at least partially, by increased compliance with surveillance, facing the potential usefulness of the conjugate vaccines to prevent IPD among the elderly. During the next years of the study (2009-2012), the incidence of IPD remained more or less unchanged among adults 15-59 years and >60 years old. A decline of vaccine serotypes or “herd” effect among non-vaccinees was observed for both PCV7 and PCV13 two years after each vaccine introduction (Figure 3). Nevertheless a net benefit could not be recorded during that period because IPD caused by non-vaccine serotypes increased to the same magnitude as the decline caused by vaccine serotypes.

Emerging non-vaccine serotypes, for instance 12F and 24F, were already detected IPD serotypes which increased their frequencies both within vaccinated and unvaccinated population. It remains to demonstrate the epidemiologic importance of these findings.

According to international recommendations, all these trends need to be monitoring in the future to evaluate long-term effects and consider novel strategies [4].


Figure 2. Invasive S. pneumoniae isolates collected during National Laboratory Surveillance.




Figure 3. Introduction of pneumococcal conjugate vaccines in Uruguay




  1. Camou T, Palacio R, Di Fabio JL, Hortal M (2003) Invasive pneumococcal diseases in Uruguayan children: comparison between serotype distribution and conjugate vaccine formulations. Vaccine 21: 2093-2096.
  2. Di Fabio JL, Castaneda E, Agudelo CI, De La Hoz F, Hortal M, et al. (2001) Evolution of Streptococcus pneumoniae serotypes and penicillin susceptibility in Latin America, Sireva-Vigia Group, 1993 to 1999. PAHO Sireva-Vigia Study Group. Pan American Health Organization. Pediatr Infect Dis J 20: 959-967.
  3. Castaneda E, Agudelo CI, Regueira M, Corso A, Brandileone MC, et al. (2009) Laboratory-based surveillance of Streptococcus pneumoniae invasive disease in children in 10 Latin American countries: a SIREVA II project, 2000-2005. Pediatr Infect Dis J 28: e265-270.
  4. World Health Organization (2012) Pneumococcal vaccines: WHO position paper 2012. 129-144. p.



Teresa Camou, PhD

Head of Microbiology

Departamento de Laboratorios

Ministerio de Salud Pública, Uruguay



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