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      Nasopharyngeal carriage of Streptococcus pneumoniae among Brazilian children: Interplay with viral co-infection

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          Abstract

          Nasopharyngeal transmission of Streptococcus pneumoniae is a prerequisite for the development of pneumococcal diseases. Previous studies have reported a relationship between respiratory viruses and S. pneumoniae infections. However, there are few studies on this issue among healthy children. This study aimed to examine the relationships between these agents in healthy children from Southern Brazil. This cohort study included 229 nasopharyngeal samples collected from children aged 18–59 months at baseline. S. pneumoniae was detected using bacterial culture, whereas respiratory viruses were identified using quantitative polymerase chain reaction. A questionnaire was used at the time of sample collection and medical records were reviewed 14 days after participant inclusion. The prevalence of pneumococcal carriage was 63.7% (146/229), while respiratory viruses were detected in 49.3% (113/229) of the children. Respiratory viruses were more frequently found among pneumococcal carriers than among non-carriers (54.4% vs. 39.7%, p = 0.033). Additionally, rhinovirus (hRV) was more frequent among the pneumococcal carriers (39% vs. 21.7%, p = 0.012), and the presence of human bocavirus (hBOV) alone was associated with the absence of pneumococcal carriage (2.7% vs. 10.8%, p = 0.016). No differences were found in the frequency of pneumococcal carriage, respiratory virus detection, or the co-occurrence of clinical symptoms and diagnosis in the participants 14 days after specimen collection. Our findings revealed a positive relationship between pneumococcal carriage and respiratory virus detection, particularly for hRV. However, we did not observe a relationship between nasopharyngeal respiratory viruses and pneumococci detection during medical appointments, respiratory symptoms, or diseases. This study was one of the first investigations in Latin America to explore the relationship between respiratory viruses and pneumococcal carriage in a healthy children.

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          Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000–15

          Brian Wahl, Katherine L O'Brien, Adena Greenbaum … (2018)
          Summary Background Pneumococcal conjugate vaccine (PCV) and Haemophilus influenzae type b (Hib) vaccine are now used in most countries. To monitor global and regional progress towards improving child health and to inform national policies for disease prevention and treatment, we prepared global, regional, and national disease burden estimates for these pathogens in children from 2000 to 2015. Methods Using WHO and Maternal and Child Epidemiology Estimation collaboration country-specific estimates of pneumonia and meningitis mortality and pneumonia morbidity from 2000 to 2015, we applied pneumococcal and Hib cause-specific proportions to estimate pathogen-specific deaths and cases. Summary estimates of the proportion of pneumonia deaths and cases attributable to these pathogens were derived from four Hib vaccine and six PCV efficacy and effectiveness study values. The proportion of meningitis deaths due to each pathogen was derived from bacterial meningitis aetiology and adjusted pathogen-specific meningitis case–fatality data. Pneumococcal and Hib meningitis cases were inferred from modelled pathogen-specific meningitis deaths and literature-derived case–fatality estimates. Cases of pneumococcal and Hib syndromes other than pneumonia and meningitis were estimated using the ratio of pathogen-specific non-pneumonia, non-meningitis cases to pathogen-specific meningitis cases from the literature. We accounted for annual HIV infection prevalence, access to care, and vaccine use. Findings We estimated that there were 294 000 pneumococcal deaths (uncertainty range [UR] 192 000–366 000) and 29 500 Hib deaths (18 400–40 700) in HIV-uninfected children aged 1–59 months in 2015. An additional 23 300 deaths (15 300–28 700) associated with pneumococcus and fewer than 1000 deaths associated Hib were estimated to have occurred in children infected with HIV. We estimate that pneumococcal deaths declined by 51% (7–74) and Hib deaths by 90% (78–96) from 2000 to 2015. Most children who died of pneumococcus (81%) and Hib (76%) presented with pneumonia. Less conservative assumptions result in pneumococcccal death estimates that could be as high as 515 000 deaths (302 000–609 000) in 2015. Approximately 50% of all pneumococcal deaths in 2015 occurred in four countries in Africa and Asia: India (68 700 deaths, UR 44 600–86 100), Nigeria (49 000 deaths, 32 400–59 000), the Democratic Republic of the Congo (14 500 deaths, 9300–18 700), and Pakistan (14 400 deaths, 9700–17 000]). India (15 600 deaths, 9800–21 500), Nigeria (3600 deaths, 2200–5100), China (3400 deaths, 2300–4600), and South Sudan (1000 deaths, 600–1400) had the greatest number of Hib deaths in 2015. We estimated 3·7 million episodes (UR 2·7 million–4·3 million) of severe pneumococcus and 340 000 episodes (196 000–669 000) of severe Hib globally in children in 2015. Interpretation The widespread use of Hib vaccine and the recent introduction of PCV in countries with high child mortality is associated with reductions in Hib and pneumococcal cases and deaths. Uncertainties in the burden of pneumococcal disease are largely driven by the fraction of pneumonia deaths attributable to pneumococcus. Progress towards further reducing the global burden of Hib and pneumococcal disease burden will depend on the efforts of a few large countries in Africa and Asia. Funding Bill & Melinda Gates Foundation.
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            Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine.

            Tamara Pilishvili, Catherine Lexau, Monica M. Farley … (2010)
            Changes in invasive pneumococcal disease (IPD) incidence were evaluated after 7 years of 7-valent pneumococcal conjugate vaccine (PCV7) use in US children. Laboratory-confirmed IPD cases were identified during 1998-2007 by 8 active population-based surveillance sites. We compared overall, age group-specific, syndrome-specific, and serotype group-specific IPD incidence in 2007 with that in 1998-1999 (before PCV7) and assessed potential serotype coverage of new conjugate vaccine formulations. Overall and PCV7-type IPD incidence declined by 45% (from 24.4 to 13.5 cases per 100,000 population) and 94% (from 15.5 to 1.0 cases per 100,000 population), respectively (P< .01 all age groups). The incidence of IPD caused by serotype 19A and other non-PCV7 types increased from 0.8 to 2.7 cases per 100,000 population and from 6.1 to 7.9 cases per 100,000 population, respectively (P< .01 for all age groups). The rates of meningitis and invasive pneumonia caused by non-PCV7 types increased for all age groups (P< .05), whereas the rates of primary bacteremia caused by these serotypes did not change. In 2006-2007, PCV7 types caused 2% of IPD cases, and the 6 additional serotypes included in an investigational 13-valent conjugate vaccine caused 63% of IPD cases among children <5 years-old. Dramatic reductions in IPD after PCV7 introduction in the United States remain evident 7 years later. IPD rates caused by serotype 19A and other non-PCV7 types have increased but remain low relative to decreases in PCV7-type IPD.
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              Streptococcus pneumoniae colonisation: the key to pneumococcal disease.

              D Bogaert, R. de Groot, P. Hermans (2004)
              Streptococcus pneumoniae is an important pathogen causing invasive diseases such as sepsis, meningitis, and pneumonia. The burden of disease is highest in the youngest and oldest sections of the population in both more and less developed countries. The treatment of pneumococcal infections is complicated by the worldwide emergence in pneumococci of resistance to penicillin and other antibiotics. Pneumococcal disease is preceded by asymptomatic colonisation, which is especially high in children. The current seven-valent conjugate vaccine is highly effective against invasive disease caused by the vaccine-type strains. However, vaccine coverage is limited, and replacement by non-vaccine serotypes resulting in disease is a serious threat for the near future. Therefore, the search for new vaccine candidates that elicit protection against a broader range of pneumococcal strains is important. Several surface-associated protein vaccines are currently under investigation. Another important issue is whether the aim should be to prevent pneumococcal disease by eradication of nasopharyngeal colonisation, or to prevent bacterial invasion leaving colonisation relatively unaffected and hence preventing the occurrence of replacement colonisation and disease. To illustrate the importance of pneumococcal colonisation in relation to pneumococcal disease and prevention of disease, we discuss the mechanism and epidemiology of colonisation, the complexity of relations within and between species, and the consequences of the different preventive strategies for pneumococcal colonisation.
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                Author and article information

                Contributors
                Kauana Pizzutti:
                ORCID: https://orcid.org/0000-0002-3652-5517
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ValidationRole: VisualizationRole: Writing – original draft
                Juliana Comerlato: Role: ConceptualizationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Daniele Vargas de Oliveira: Role: InvestigationRole: MethodologyRole: SupervisionRole: Validation
                Amanda Robaina: Role: Data curationRole: InvestigationRole: MethodologyRole: ValidationRole: Visualization
                Mariana Preussler Mott: Role: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: ValidationRole: Visualization
                Pedro Uriel Pedrotti Vieira: Role: Data curationRole: MethodologyRole: ValidationRole: Visualization
                Tiago Fetzner: Role: Data curationRole: InvestigationRole: MethodologyRole: Visualization
                Gabriela Rosa da Cunha: Role: Data curationRole: InvestigationRole: MethodologyRole: Visualization
                Muriel Primon de Barros: Role: Data curationRole: InvestigationRole: MethodologyRole: Visualization
                Jaqueline Verardo:
                ORCID: https://orcid.org/0000-0002-9470-5137
                Role: Data curationRole: MethodologyRole: SoftwareRole: ValidationRole: Visualization
                Neide Maria Bruscato: Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: Visualization
                João Carlos Batista Santana: Role: Data curationRole: Formal analysisRole: ResourcesRole: SupervisionRole: VisualizationRole: Writing – review & editing
                Roberta Rigo Dalla Corte: Role: ConceptualizationRole: ResourcesRole: SupervisionRole: Visualization
                Emilio Hideyuki Moriguchi: Role: ConceptualizationRole: Formal analysisRole: Project administrationRole: ResourcesRole: Supervision
                Vlademir Vicente Cantarelli: Role: ConceptualizationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: Visualization
                Cícero Armídio Gomes Dias: Role: Data curationRole: Formal analysisRole: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: VisualizationRole: Writing – original draft
                Jairam Meena: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS One
                Journal ID (publisher-id): plos
                Title: PLOS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 2 January 2025
                Publication date Collection: 2025
                Volume: 20
                Issue: 1
                Electronic Location Identifier: e0316444
                Affiliations
                [1 ] Federal University of Health Sciences of Porto Alegre, Porto Alegre, RS, Brazil
                [2 ] Hospital Moinhos de Vento, Porto Alegre, RS, Brazil
                [3 ] Moriguchi Institute, Veranópolis, RS, Brazil
                [4 ] Community Hospital São Peregrino Lazziozi, Veranópolis, RS, Brazil
                [5 ] Hospital of Health Clinic of Porto Alegre, Porto Alegre, RS, Brazil
                Indian Institute of Technology BHU Varanasi, INDIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-3652-5517
                https://orcid.org/0000-0002-9470-5137
                Article
                Publisher ID: PONE-D-23-41647
                DOI: 10.1371/journal.pone.0316444
                PMC ID: 11694996
                PubMed ID: 39746082
                SO-VID: 6f07e152-47cc-43ff-a316-c6fc5b6cf095
                Copyright © © 2025 Pizzutti et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 19 December 2023
                Date accepted : 11 December 2024
                Page count
                Figures: 1, Tables: 4, Pages: 15
                Funding
                The author(s) received no specific funding for this work.
                Categories
                Subject: Research Article
                Subject: Biology and Life Sciences
                Subject: Organisms
                Subject: Bacteria
                Subject: Streptococcus
                Subject: Pneumococcus
                Subject: Biology and Life Sciences
                Subject: Microbiology
                Subject: Medical Microbiology
                Subject: Microbial Pathogens
                Subject: Bacterial Pathogens
                Subject: Streptococcus
                Subject: Pneumococcus
                Subject: Medicine and Health Sciences
                Subject: Pathology and Laboratory Medicine
                Subject: Pathogens
                Subject: Microbial Pathogens
                Subject: Bacterial Pathogens
                Subject: Streptococcus
                Subject: Pneumococcus
                Subject: People and places
                Subject: Geographical locations
                Subject: South America
                Subject: Brazil
                Subject: Medicine and Health Sciences
                Subject: Medical Conditions
                Subject: Infectious Diseases
                Subject: Respiratory Infections
                Subject: Medicine and Health Sciences
                Subject: Medical Conditions
                Subject: Respiratory Disorders
                Subject: Respiratory Infections
                Subject: Medicine and Health Sciences
                Subject: Pulmonology
                Subject: Respiratory Disorders
                Subject: Respiratory Infections
                Subject: Medicine and Health Sciences
                Subject: Pediatrics
                Subject: Child Health
                Subject: Medicine and Health Sciences
                Subject: Public and Occupational Health
                Subject: Child Health
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Neck
                Subject: Throat
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Neck
                Subject: Throat
                Subject: People and Places
                Subject: Population Groupings
                Subject: Age Groups
                Subject: Children
                Subject: People and Places
                Subject: Population Groupings
                Subject: Families
                Subject: Children
                Subject: Medicine and Health Sciences
                Subject: Pulmonology
                Subject: Pneumonia
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Physiological Processes
                Subject: Respiration
                Subject: Aquatic Respiration
                Custom metadata
                Data Availability All relevant data are within the manuscript and its Supporting Information files

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