This systematic review of Spn19A data in children under 6 years old, from studies conducted in LAC over a period of 20 years shows that Spn19A remains a less common agent of IPD than other serotypes (3.8%), ranking 9th in the twenty most prevalent serotypes
. The percentage of isolates accounted by Spn19A differed between countries, being the 10th most frequently reported from Colombia, the 6th from Mexico and 4th from Venezuela (Additional file
3a and Additional file
11). This information provides a complete overview of the role of Spn19A for pneumococcal disease facilitating the decision process for those countries considering to introduce PCV, but also will allow evaluation of potential variations in the prevalence of Spn19A and other serotypes, as reported previously in studies following introduction of PCV7
Our analysis of the literature identified the serotypes accounting for 85.4% of IPD in the region, serotype 14 being the most common (28.7%). However, the percentage of isolates accounted for by each of these serotypes varied from country to country, in agreement with JohnsonÂ´s observation in her recent global serotype paper
The scope of our search strategy allowed us to retrieve comprehensive lists of peer-reviewed publications. Two of our authors being members of the SIREVA team, we were able to identify the vast majority of relevant publications in non-indexed journals and obtain personal communications with SIREVA coordinators
. Additionally, information retrieved from over a 20 year period evaluated secular trends and the periodicity of serotypes described in the literature
A strength of our analysis is that the percentage of IPD Spn19A isolates reported in the non SIREVA data that we reviewed (7 reports, 1990–2008) was not significantly different from that for the SIREVA data (3.8%).
Regarding time period of Spn19A prevalence, a significant increase, from 3.3% to 4.6%, was noted only in Argentina and Colombia between 1994–1999 and 2006–2009 before any universal vaccine intervention could have had an impact. However, Spn19A stability was observed in Brazil, Chile, Dominican Republic and Mexico. Similar increases in the percentage of isolates accounted for Spn19A, even prior to the introduction of PCV7, have been reported in Europe
, South Korea
, Southern Israel
 and Taiwan
, likely reflecting selection pressure from antibiotic use.
On the other hand, in the USA the observed increasing prevalence of PRSP and MDR Spn19A has been suggested to be due to a rapid expansion of the Spn19A clonal complex CC320, to more than one new clone introduced or to successful clones associated with other serotypes that have undergone a recombinational switch to Spn19A
In the LAC region only one study, describing PFGE patterns of Spn19A isolates, and conducted in Colombia
, reported Spn19A MDR isolates in IPD; two were found related to the clone Colombia23F-ST338, one to the clone Spain23F-ST81, and 6 were not related to the clones studied. A possible explanation of these findings may be that a successful clone, such as Spain23F, underwent a recombinational switch to Spn19A.
No differences could be established between age groups for the prevalence of Spn19A as an IPD agent. In contrast, serotypes 1 and 5 were more frequent in children 2–5 years old and serotypes 6B and 14 were more frequent in <2 year olds than in the other age groups in the LAC region (See Additional file
Our analysis suggests that Spn19A causing IPD in LAC is more frequently an agent of non-meningitis disease (4.5% of cases), in particular pneumonia than of meningitis (2.9%) (See Additional file
PNSP in invasive Spn19A isolates has been reported in LAC since 1993
. A study conducted in 2010, using the new CLSI breakpoints for penicillin
, showed that resistant Spn19A isolates are circulating in the region, more frequently as agents of meningitis (MIC ≥ 0.125 μg/ml) than for of non-meningitis (MIC ≥ 4.0 μg/ml). However, the finding of a prevalence of 3.2% for Spn19A with MIC ≥ 8.0 μg/ml among non-meningitis cases, recovered in Mexico, Colombia and Venezuela is of great concern, as it follows reports of 7.7% of cases being attributed to serotype 19F. Molecular surveillance data will reveal their role as agents of pneumococcal disease
Despite the fact that S. pneumoniae causes 30–60% of AOM cases worldwide
, only three papers and one abstract were found and analyzed; overall, 2.4% of these were attributed to Spn19A. As AOM continues to be an important childhood infection and given that the etiology might change from VT to non-PCV7 strains once pneumococcal vaccines are widely implemented
, it is important to conduct AOM etiology studies in the region. S. pneumoniae may be subject to serotype replacement phenomena and attention to antibiotic resistant NVT otopathogens as well as non typable Haemophilus influenzae is required
Nasopharyngeal carriage has been confirmed with greater values reported for children less than 5 years old. From the papers analyzed, Spn19A ranked the 6th most frequently reported serotype for healthy children (4.1%), jointly with Non-Typable. There were a high number of serotypes with ability for colonizing the nasopharynx, with serotype 19 F the most frequently identified (See Additional file
Nasopharyngeal serotypes described in Latin America from 1994 to 2008 are very similar to those described by Huang in 2001 (pre vaccine data) for generally healthy children in 16 Massachusetts communities. Spn19A represented 4.2% of 143 isolates; PNSP was described for 77% of the NVT, in particular for serotypes 6A, 19A and 9A
Studies conducted since the introduction of PCV7 vaccination have shown decreases in colonization with pneumococcal VT shortly after immunization as well as longer-term changes in colonization patterns. Huang
 reported a decrease in the carriage of VT from 36% to 3% seven years after mass introduction of PCV7, whereas NVT carriage increased from 15% to 29%. The common colonizing serotypes in 2007 included 19A (16%) (Baseline data 6.0%), 6A (12%), 15B/C (11%), 35B (9%) and 11A (8%), a clear reflection of the replacement phenomenon. Additionally, the more frequent colonizing serotypes have greater resistance to penicillin. Nasopharyngeal surveillance appears to be a reliable system for measuring vaccination impact in terms of a decrease in VT types and will help to elucidate the emergence of NVT following PCV introduction.
Incidence rates reported by Lagos
 for IPD caused by Spn19A ranged from 0.4 to 2.2 cases x 100,000 between 1994 and 2007, suggesting a seasonal pattern for this serotype. Similar variations have been shown for other serotypes in the LAC region, such as 1 and 5
 and may explain changes during time periods in the SIREVA data presented in this review. This should be considered when interpreting data post introduction of pneumococcal vaccines in this region. In contrast, the incidence of other serotypes such as 14 has shown small variations
PCVs have been introduced recently in several countries in LAC, but currently, there are no data published about their impact in reducing IPD. Consequently, little is known about the replacement phenomenon with Spn19A, which has been well described previously
. Available data provide only an estimation of hypothetical impact (supplement 10). The same calculation for the recent SIREVA data
 showed a major impact of PCV10 and PCV13 vaccination, in particular related to the inclusion of serotypes 1 and 5. In fact, after 2009, countries in the region have incorporated different PCV into their expanded program of immunization following individual assessment for their epidemiology (PCV7/13: Costa Rica, Uruguay, Mexico and PCV-10: Brazil, Colombia, Ecuador and Chile). Following the results of this review, indicating the low prevalence of Spn19A in most of the countries, it is necessary to report any subsequent change in the distribution of this serotype in those countries who have introduced one of the available PCV. Particularly, trying to explain any increase or decrease in the Spn19A prevalence comparing the statistics prior to universal vaccination and possible factors that could explain this, such as vaccine coverage, antibiotic use and immune response based on the vaccine formulation.
The results of our systematic review have a number of limitations. The source of primary data, either from SIREVA or from independent research teams, could introduce selection bias, potentially promoting the selection of more severe forms of the disease. However, it is important to highlight that more severe disease will have the largest impact from a burden of disease or a public health perspective. Information on disease severity caused by Spn19A in this region was limited; this is also the case for data collected for other serotypes, given that similar surveillance activities are employed in the different countries. As this limitation is not restricted to a specific serotype, it should not bias our conclusions. It was not possible to analyze temporal changes in serotype frequency, except from a very broad perspective. The small amount of data available on burden of disease and on the possible effects of mass vaccination highlights the need for more research in this area.
Incidence of IPD in this region ranges from 3.0 to 206.8 cases per 100,000. Overall 9 serotypes are responsible for 80% of IPD and 30% are due to serotype 14; Spn19A remains relatively uncommon as an agent of IPD, with the exception of Mexico and Venezuela. Data on noninvasive disease and nasopharyngeal carriage, although not as robust, show the same low prevalence.