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Background: Data on the national-level impact of pneumococcal conjugate vaccine (PCV) introduction on mortality are lacking from Africa. PCV was introduced in South Africa in 2009. We estimated the impact of PCV introduction on all-cause pneumonia mortality in South Africa, while controlling for changes in mortality due to other interventions., Methods and Findings: We used national death registration data in South Africa from 1999 to 2016 to assess the impact of PCV introduction on all-cause pneumonia mortality in all ages, with the exclusion of infants aged <1 month. We created a composite (synthetic) control using Bayesian variable selection of nondiarrheal, nonpneumonia, and nonpneumococcal deaths to estimate the number of expected all-cause pneumonia deaths in the absence of PCV introduction post 2009. We compared all-cause pneumonia deaths from the death registry to the expected deaths in 2012 to 2016. We also estimated the number of prevented deaths during 2009 to 2016. Of the 9,324,638 deaths reported in South Africa from 1999 to 2016, 12·6% were pneumonia-related. Compared to number of deaths expected, we estimated a 33% (95% credible interval (CrI) 26% to 43%), 23% (95%CrI 17% to 29%), 25% (95%CrI 19% to 32%), and 23% (95%CrI 11% to 32%) reduction in pneumonia mortality in children aged 1 to 11 months, 1 to 4 years, 5 to 7 years, and 8 to 18 years in 2012 to 2016, respectively. In total, an estimated 18,422 (95%CrI 12,388 to 26,978) pneumonia-related deaths were prevented from 2009 to 2016 in children aged <19 years. No declines were estimated observed among adults following PCV introduction. This study was mainly limited by coding errors in original data that could have led to a lower impact estimate, and unmeasured factors could also have confounded estimates., Conclusions: This study found that the introduction of PCV was associated with substantial reduction in all-cause pneumonia deaths in children aged 1 month to <19 years. The model predicted an effect of PCV in age groups who were eligible for vaccination (1 months to 4 years), and an indirect effect in those too old (8 to 18 years) to be vaccinated. These findings support sustaining pneumococcal vaccination to reduce pneumonia-related mortality in children., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AvG received research funding from Pfizer and Sanofi unrelated to this project. DMW is PI on a research grant from Pfizer Yale and has received consulting fees from Pfizer, Merck, GSK, and Affinivax. CC has received grant funding from Sanofi Pasteur, US Centers for Disease Control and Prevention and Programme for Applied Technologies in Health awarded to the institute. She has had travel costs reimbursed by Parexel. JK, ST, and KS report no conflicts of interest.

Background: HIV-infected children are at a higher risk of Invasive Pneumococcal Disease (IPD) and its mortality, even in the era of antiretroviral therapy. Therefore, an effective vaccination strategy would be beneficial. To investigate the effectiveness of Pneumococcal Conjugate Vaccination (PCV) against IPD among HIV-Infected and HIV-Uninfected Children through a systematic review and meta-analysis., Methods: Observational studies and randomized trials on 7 years old or older children were searched in the Cochrane Library, Web of Science core collection, Embase, Medline/PubMed, and Google Scholar. Critical appraisal was done using the Cochrane risk of bias tool and the Newcastle-Ottawa quality assessment form. Effectiveness and efficacy of at least one dose of PCV was investigated among children with and without HIV considering subgroups of pneumococcal serotypes. We meta-analyzed the effect sizes using random-effects modeling., Results: Efficacy of PCV was estimated as 45.0% (31.2, 56.1) and 52.6% (25.7, 69.8) among HIV-infected and HIV-uninfected children, respectively. Effectiveness of PCV among HIV-infected children as - 6.2% (- 67.6, 32.7) was significantly lower than HIV-uninfected children 65.1% (47.3, 76.9). Effectiveness of PCV among HIV-infected children for IPDs caused by vaccine serotypes was estimated as 7.7(- 66.7, 48.9), and for IPDs caused by non-vaccine serotypes was estimated as - 402.8(- 1856, - 29.2)., Conclusion: Unlike the evidence on the efficacy of PCV against IPD among both of HIV-infected and HIV-uninfected children, its effectiveness against IPD among HIV-infected children is much less limited., Review Registration: The study protocol was registered at PROSPERO (registration ID: CRD42018108187).

Streptococcus pneumoniae is the most frequent pathogen in community-acquired pneumonia and also causes invasive diseases like bacteremia and meningitis. Young children and elderly are especially at risk for pneumococcal diseases and are, therefore, eligible for pneumococcal vaccination in most countries. This reviews provides an overview of the current epidemiology of pneumococcal infections, history and evidence of available pneumococcal polysaccharide and conjugate vaccines, and current recommendations., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Following the introduction of 7- and 13-pneumococcal conjugate vaccines (PCVs) in Israel, we demonstrated that within Streptococcus pneumoniae (Sp) positive middle ear cultures, obtained from young children with severe acute otitis media (AOM) episodes, there were more penicillin-susceptible and less multi-drug resistant Sp isolates in PCV immunized children., (Copyright © 2015. Published by Elsevier B.V.)

Streptococcus pneumoniae inflicts a huge disease burden as the leading cause of community-acquired pneumonia and meningitis. Soon after mainstream antibiotic usage, multiresistant pneumococcal clones emerged and disseminated worldwide. Resistant clones are generated through adaptation to antibiotic pressures imposed while naturally residing within the human upper respiratory tract. Here, a huge array of related commensal streptococcal strains transfers core genomic and accessory resistance determinants to the highly transformable pneumococcus. β-Lactam resistance is the hallmark of pneumococcal adaptability, requiring multiple independent recombination events that are traceable to nonpneumococcal origins and stably perpetuated in multiresistant clonal complexes. Pneumococcal strains with elevated MICs of β-lactams are most often resistant to additional antibiotics. Basic underlying mechanisms of most pneumococcal resistances have been identified, although new insights that increase our understanding are continually provided. Although all pneumococcal infections can be successfully treated with antibiotics, the available choices are limited for some strains. Invasive pneumococcal disease data compiled during 1998 to 2013 through the population-based Active Bacterial Core surveillance program (U.S. population base of 30,600,000) demonstrate that targeting prevalent capsular serotypes with conjugate vaccines (7-valent and 13-valent vaccines implemented in 2000 and 2010, respectively) is extremely effective in reducing resistant infections. Nonetheless, resistant non-vaccine-serotype clones continue to emerge and expand., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Pneumococcal infections remain a major public health issue in aging people. The recent publication of the CAPITA trial evaluating the efficacy of 13-valent pneumococcal conjugate vaccine (PCV13, Prevenar 13®) in elderly subjects has brought several countries including Belgium to modify their vaccinal recommendations. These new developments have motivated us to write this brief review about the burden of pneumococcal disease, the mechanism of action of conjugate vaccines, the clinical efficacy of PCV13 with a special emphasis on CAPITA data. The questions of herd protection and serotype substitution are also introduced as well as a summary of the more recent guidelines.

Background: The use of molecular diagnostic techniques for the evaluation of the impact of pneumococcal conjugate vaccines (PCVs) has not been documented. We aimed to evaluate the impact of PCVs on invasive pneumococcal disease (IPD) using polymerase chain reaction (PCR)-based techniques and compare with results obtained from culture-based methods., Methods: We implemented two independent surveillance programs for IPD among individuals hospitalized at one large surveillance site in Soweto, South Africa during 2009-2012: (i) PCR-based (targeting the lytA gene) syndromic pneumonia surveillance; and (ii) culture-based laboratory surveillance. Positive samples were serotyped. The molecular serotyping assay included targets for 42 serotypes including all serotypes/serogroups included in the 7-valent (PCV-7) and 13-valent (PCV-13) PCV. The Quellung reaction was used for serotyping of culture-positive cases. We calculated the change in rates of IPD (lytA- or culture-positive) among HIV-uninfected children aged <2 years from the year of PCV-7 introduction (2009) to the post-vaccine years (2011 or 2012)., Results: During the study period there were 607 lytA-positive and 1,197 culture-positive cases that were serotyped. Samples with lytA cycle threshold (Ct)-values ≥35 (30.2 %; 123/407) were significantly less likely to have a serotype/serogroup detected for serotypes included in the molecular serotyping assay than those with Ct-values <35 (78.0 %; 156/200) (p < 0.001). From 2009 to 2012 rates of PCV-7 serotypes/serogroups decreased -63.8 % (95 % CI: -79.3 % to -39.1 %) among lytA-positive cases and -91.7 % (95 % CI: -98.8 % to -73.6 %) among culture-positive cases. Rates of lytA-positive non-vaccine serotypes/serogroups also significantly decreased (-71.7 %; 95 % CI: -81.1 % to -58.5 %) over the same period. Such decline was not observed among the culture-positive non-vaccine serotypes (1.2 %; 95 % CI: -96.7 % to 58.4 %)., Conclusions: Significant downward trends in IPD PCV-7 serotype-associated rates were observed among patients tested by PCR or culture methods; however trends of non-vaccine serotypes/serogroups differed between the two groups. Misclassifications of serotypes/serogroups, affecting the use of non-vaccine serotypes as a control group, may have occurred due to the low performance of the serotyping assay among lytA-positive cases with high Ct-values. Until PCR methods improve further, culture methods should continue to be used to monitor the effects of PCV vaccination programs on IPD incidence.

Reduction of drug-resistant Streptococcus pneumoniae (DRSP) by pneumococcal conjugate vaccines (PCVs) has recently become a reality. We now know that (1) most clinically significant DRSP strains belong to seven serotypes (6A, 6B, 9V, 14, 19A, 19F, 23F), (2) five (6B, 9V, 14, 19F, 23F) of the seven are constituents of heptavalent PCV (PCV7), and (3) the remaining two serotypes (6A, 19A) are immunologically related to serotypes in PCV7, but only 6A has been reduced by PCV7. Furthermore, PCVs can also reduce DRSP in unvaccinated individuals (herd immunity). PCVs lead to a reduction in antibiotic use, which is also potentially helpful to contain DRSP. Although a reduction in disease caused by most penicillin-resistant strains has been reported, reductions in intermediately penicillin-resistant strains has not been shown to the same degree, because of increased intermediate resistance among non-PCV7 serotypes. Serotype 19A, which is both antibiotic resistant and a common cause of disease, is not affected by PCV7, and is now increasing worldwide, including in countries without PCV7. Continued exposure of non-PCV7 serotypes to antibiotic pressure may reduce the overall impact of PCVs on DRSP. Further strategies include expansion of PCV serotype coverage, development of protein-based vaccines, and further limitation of antibiotic use.