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      Invasive pneumococcal disease in children with cancer: Incidence density, risk factors and isolated serotypes

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          Abstract

          Background

          Pediatric oncology patients (POP) have a high risk of infections due to impaired immunity. Invasive pneumococcal disease (IPD) is an important cause of severe infection in these patients and it is associated with high mortality. This study aimed to evaluate the incidence and risk factors associated with IPD at a Pediatric Oncology Center in Brazil.

          Methods

          This was a retrospective case-control study. All IPD cases in children with cancer from 2005 through 2016 were reviewed. Each case of IPD was matched with two controls from a cohort of patients matched for year of IPD, age and disease in order to assess risk factors. The incidence density was calculated as the number of IPD per 100,000 patients-year.

          Results

          A total of 51 episodes of IPD in 49 patients was identified. All pneumococci were isolated from blood cultures. The median age was five years and 67% were male; mortality rate was 7.8%. The IPD incidence density rate in POP was 311.21 per 100,000 patients-year, significantly higher than the rate in the general pediatric population. Severe neutropenia was the only risk factor associated with IPD, after multivariate conditional logistic regression analysis.

          Conclusion

          Although pneumococcal disease decreased after the introduction of 10-valent pneumococcal vaccine in the Brazilian national immunization schedule in 2010, there was no decrease in the IPD incidence rate in our cohort. A higher coverage rate of pneumococcal vaccination in children in the general population might be necessary to reduce the incidence rate in this high-risk population.

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          Most cited references36

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          Streptococcus pneumoniae: transmission, colonization and invasion

          Streptococcus pneumoniae as a complex relationship with its obligate human host. On the one hand, the pneumococci are highly adapted commensals, and their main reservoir on the mucosal surface of the upper airways of carriers enables transmission. On the other hand, they can cause severe disease when bacterial and host factors allow them to invade essentially sterile sites, such as the middle ear spaces, lungs, bloodstream and meninges. Transmission, colonization and invasion depend on the remarkable ability of S. pneumoniae to evade or take advantage of the host inflammatory and immune responses. The different stages of pneumococcal carriage and disease have been investigated in detail in animal models and, more recently, in experimental human infection. Furthermore, widespread vaccination and the resulting immune pressure have shed light on pneumococcal population dynamics and pathogenesis. Here, we review the mechanistic insights provided by these studies on the multiple and varied interactions of the pneumococcus and its host.
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            Serotype replacement in disease after pneumococcal vaccination.

            Vaccination with heptavalent pneumococcal conjugate vaccine (PCV7) has significantly reduced the burden of pneumococcal disease and has had an important public health benefit. Because this vaccine targets only seven of the more than 92 pneumococcal serotypes, concerns have been raised that non-vaccine serotypes (NVTs) could increase in prevalence and reduce the benefits of vaccination. Indeed, among asymptomatic carriers, the prevalence of NVTs has increased substantially, and consequently, there has been little or no net change in the bacterial carriage prevalence. In many populations, pneumococcal disease caused by NVT has increased, but in most cases this increase has been less than the increase in NVT carriage. We review the evidence for serotype replacement in carriage and disease, and address the surveillance biases that might affect these findings. We then discuss possible reasons for the discrepancy between near-complete replacement in carriage and partial replacement for disease, including differences in invasiveness between vaccine serotypes. We contend that the magnitude of serotype replacement in disease can be attributed, in part, to a combination of lower invasiveness of the replacing serotypes, biases in the pre-vaccine carriage data (unmasking), and biases in the disease surveillance systems that could underestimate the true amount of replacement. We conclude by discussing the future potential for serotype replacement in disease and the need for continuing surveillance. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              Guideline for the Management of Fever and Neutropenia in Children With Cancer and Hematopoietic Stem-Cell Transplantation Recipients: 2017 Update.

              Purpose To update a clinical practice guideline (CPG) for the empirical management of fever and neutropenia (FN) in children with cancer and hematopoietic stem-cell transplantation recipients. Methods The International Pediatric Fever and Neutropenia Guideline Panel is a multidisciplinary and multinational group of experts in pediatric oncology and infectious diseases that includes a patient advocate. For questions of risk stratification and evaluation, we updated systematic reviews of observational studies. For questions of therapy, we conducted a systematic review of randomized trials of any intervention applied for the empirical management of pediatric FN. The Grading of Recommendation Assessment, Development and Evaluation approach was used to make strong or weak recommendations and to classify levels of evidence as high, moderate, low, or very low. Results Recommendations related to initial presentation, ongoing management, and empirical antifungal therapy of pediatric FN were reviewed; the most substantial changes were related to empirical antifungal therapy. Key differences from our 2012 FN CPG included the listing of a fourth-generation cephalosporin for empirical therapy in high-risk FN, refinement of risk stratification to define patients with high-risk invasive fungal disease (IFD), changes in recommended biomarkers and radiologic investigations for the evaluation of IFD in prolonged FN, and a weak recommendation to withhold empirical antifungal therapy in IFD low-risk patients with prolonged FN. Conclusion Changes to the updated FN CPG recommendations will likely influence the care of pediatric patients with cancer and those undergoing hematopoietic stem-cell transplantation. Future work should focus on closing research gaps and on identifying ways to facilitate implementation and adaptation.
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                Author and article information

                Contributors
                Journal
                Braz J Infect Dis
                Braz J Infect Dis
                The Brazilian Journal of Infectious Diseases
                Elsevier
                1413-8670
                1678-4391
                23 October 2020
                Nov-Dec 2020
                23 October 2020
                : 24
                : 6
                : 489-496
                Affiliations
                [a ]Universidade Federal de São Paulo, Departamento de Pediatria, São Paulo, SP, Brazil
                [b ]Universidade Federal de São Paulo, Departamento de Medicina, Divisão de Doenças Infecciosas, São Paulo, SP, Brazil
                Author notes
                [* ] Corresponding author. m.isabelmp@ 123456gmail.com
                Article
                S1413-8670(20)30143-4
                10.1016/j.bjid.2020.09.003
                9392108
                33164827
                305a8fc8-e2e8-4e21-a19e-629b75abbf5a
                © 2020 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 14 May 2020
                : 18 September 2020
                Categories
                Original Article

                invasive pneumococcal disease,pneumococcal vaccines,pediatric cancer

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