Pneumococcal conjugate vaccine - A health priority

Department of Paediatric Pulmonology and School of Child and Adolescent Health, Red Cross War Memorial Children's Hospital and University of Cape Town.
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde (Impact Factor: 1.63). 07/2008; 98(6):463-7.
Source: PubMed


Pneumonia is a major cause of childhood mortality and morbidity. Streptococcus pneumoniae is the most important bacterial pathogen causing pneumonia in children. The HIV epidemic has increased the burden and severity of childhood pneumococcal pneumonia and invasive disease fortyfold. Pneumococcal conjugate vaccine (PCV) is a highly effective intervention to reduce invasive pneumococcal disease and pneumonia. Studies evaluating a 9-valent PCV in South Africa and The Gambia reported a 72 - 77% reduction in vaccine-serotype-specific invasive disease in vaccinated children. As many of the pneumococcal serotypes associated with antibiotic resistance are included in PCV, vaccination has also been associated with a reduction in antimicrobial-resistant invasive disease. PCV may also reduce childhood mortality, especially in places with limited access to health care, as shown in Gambian study in which PCV reduced childhood mortality by 16%. In addition to the direct effects of PCV, there is a substantial reduction in disease burden through indirect protection of non-vaccinated populations. PCV is immunogenic in HIV-infected children and provides protection against invasive disease or pneumonia in a substantial number of children. Although the efficacy of PCV for prevention of invasive disease or pneumonia is lower in HIV-infected compared to -uninfected children, the overall burden of disease prevented is much greater in HIV-infected children because of the higher burden of pneumococcal disease in these children. Consequently, vaccine-preventable invasive disease is almost 60 times higher in HIV-infected compared to -uninfected children, while the reduction in pneumonia in HIV-infected children is 15 times greater. However, the long-term efficacy of PCV wanes in HIV-infected children who are not taking antiretroviral therapy, and booster doses are probably indicated. Although there is concern about the potential for replacement disease due to non-vaccine serotypes, a substantial and sustained reduction in invasive disease has occurred overall in populations with widespread childhood immunisation. Routine childhood immunisation is now the standard of care in most developed countries. However, PCV is much less accessible to children in developing countries due to cost and availability. Cost-effectiveness analysis indicates that use of PCV is potentially highly cost-effective, at tiered pricing, even in very low-income countries. Widespread availability and vaccination with PCV is urgently needed for all children under 2 years of age in South Africa. In addition, the use of PCV for all HIV-infected children under 9 years should be prioritised.

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Available from: Shabir A Madhi, Mar 17, 2014
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    • "In addition, earlier studies have demonstrated that strains from persons with HIV infection are more often antimicrobial resistant than strains from non-infected persons [20] [31]. Although the efficacy of PCV may be lower among HIV-infected children [32] [33], the substantial increased risk of disease in this population means that the potential overall burden of disease prevented may be greater for HIV-infected than uninfected children [34] [35]. In our analysis, disease among HIV-infected children was more likely caused by PCV-7 or PCV-13 serotypes than among HIV-uninfected children, and introduction of any of the vaccine formulations will be useful for prevention of disease, including antimicrobial-resistant pneumococcal disease, in this population [27]. "
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    ABSTRACT: Introduction: Dynamics of pneumococcal disease incidence and serotype distribution prior to introduction of pneumococcal conjugate vaccines (PCV) will assist in understanding effects of the vaccine over time and will be important in choosing the optimal PCV formulation. Methods: We conducted active, laboratory-based, national surveillance for invasive pneumococcal disease (IPD) through the Group for Enteric, Respiratory and Meningeal Disease Surveillance in South Africa (GERMS-SA) from 2003 through 2008. Over 130 laboratories report to this system. Pneumococci were serotyped using Quellung and isolates screened for resistance by disk diffusion; minimum inhibitory concentrations were determined on potentially resistant isolates. We used univariate and multivariable multinomial regression models to assess differences between serotypes. Results: GERMS-SA identified 8674 cases among children <5 years. Overall, 58% (3849/6668), 65% (4314/6668), and 85% (5669/6668) of cases and 61% (455/751), 64% (482/751), 82% (616/751) of deaths were due to serotypes included in 7-valent PCV, 10-valent PCV and 13-valent PCV, respectively. Serotypes 6A and 19A accounted for 16% (527/3252) of penicillin non-susceptible disease. In 2008, reported incidence of IPD was 6-fold higher in children <1 compared to children 1-4 years of age: 87 per 100,000 population and 14/100,000, respectively. The relative risk of IPD was 21-fold (95% CI, 19-24) and 34-fold (29-41) greater in HIV-infected compared to HIV-uninfected children in the <1 year and 1-4-year-old age groups respectively. On multivariable analysis serotypes 6B (relative risk ratio (RRR) 0.7; confidence interval (CI) 0.5-0.9), 18C (RRR 0.3; CI 0.1-0.5), 1 (RRR 0.2; CI 0.1-0.4) and 8 (RRR 0.2; CI 0.1-0.4) were significantly less common in HIV-infected individuals than serotype 14. Conclusions: All vaccine formulations have the potential to prevent most cases and deaths from IPD in children in South Africa. Vaccines with protection against 19A would be advantageous in South Africa.
    Full-text · Article · May 2013 · Vaccine
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    • "In this study, PCV-7 serotypes were isolated in 66% of invasive pneumococcal disease (IPD) in the b5- year age group. This is similar to what has been reported from developed countries such as Spain, as well as from developing countries such as The Gambia and South Africa (Perez-Trallero et al., 2009; Cutts et al., 2005; Zar et al., 2008). The introduction of the PCV-7 vaccine will likely lead to a significant reduction of IPD especially in our region with its high burden of HIV. "
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    ABSTRACT: A description of invasive Streptococcus pneumoniae isolates over a 5-year period from blood culture and cerebrospinal fluid culture follows, in Pretoria South Africa January 2005 through December 2009. Isolates were identified using standard microbiological techniques, serotyped, and a MIC determined for penicillin and cefotaxime. A total of 177 isolates were included in the analysis. Eighty percent of patients in the 18- to 45-year age group tested positive for HIV. In children <5 years of age, 66% (n = 49) of serotypes were those present in the heptavalent pneumococcal conjugate vaccine (PCV-7). Fifty-nine percent (n = 29) were from PCV-7 serotypes in the <1-year-old age group. An additional peak of invasive disease was also seen in the 18- to 45-year age group. Only 1 of 177 isolates had resistance to penicillin (MIC ≥2 μg/mL); none was resistant to cefotaxime. The introduction of the PCV-7 vaccine in South Africa will decrease invasive pneumococcal disease caused by vaccine serotypes.
    Full-text · Article · Sep 2011 · Diagnostic microbiology and infectious disease
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    ABSTRACT: While remarkable gains in health have been achieved since the mid-20th century, these have been unequally distributed, and mortality and morbidity burdens in some regions remain enormous. Of the almost 10 million children under 5 years of age who died in 2006, only 100 000 died in industrialised countries, while 4.8 million died in sub-Saharan Africa.1 In deciding whether to finance an intervention, policy makers commonly weigh the expected population health gains against its costs. Most vaccinations included in national immunisation schedules are inexpensive2 and health gains to costs are very favourable compared with other health interventions. Newer vaccinations, such as those with pneumococcal conjugate vaccine (PCV) or rotavirus vaccine, are also effective in averting child mortality and morbidity but are expensive relative to those commonly included in national immunisation schedules. Policy makers may therefore decide that – at current prices – the comparison of health gains with costs does not justify the free public provision of these vaccinations. The authors of this paper argue that in addition to the health benefits of vaccinations, their effects on education and income3 and benefits for unvaccinated community members are considerable and should be included in calculations to establish their value.
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