Journal of Infectious Diseases & Therapy
Open Access

There are clinical studies on Streptococcal Infection (SI) among hospitalized children, but only a few provide any postmortem correlation. Similarly, there is limited published autopsy data available on fatal pediatric SI. In our autopsy-based study we analyzed the clinical and the pathological features of pediatric deaths due to SI [1]. Our cohort included 38 Coroner-warranted and next-kin-consented autopsied cases between 1997 and 2019. Neonates, under the age of 28 days, and children with pre-existing factors, which would have predisposed for SI, were excluded from the study [1].

The largest number of SI deaths was due to Streptococcus pneumoniae (SPn) (45%), followed by Streptococcus pyogenes (SPy) (37%) [1]. Indeed, SPn and SPy are the two most commonly reported Streptococcus species associated with invasive infection in children. Streptococcus agalactiae (SAg) usually causes severe disease in neonates and this age group was excluded from the study. However, there were three deaths in our cohort attributed to SAg infection: two infants and one 23 month-old child [1].

SPn causes more infections under the age of 5 years, especially in those younger than SPn typically causes bacteraemia and meningitis in children under 2 years of age, whereas pneumonia is more prevalent in the older age group [2]. The majority of SPy infections occurs in school-aged children, between 5-17 years of age, and SPy most frequently causes acute pharyngotonsillitis and cutaneous infections [3]. Our data align with this age-related prevalence. Most deaths occurred in children over 2 years of age with similar number of deaths in both SPy and SPn groups. Under the age of 24 months, more deaths were due to SPn infection [1].

Children are at increased risk for SIs for many reasons. They have high incidences of nasopharyngeal colonization, their immune system is relatively immature and they are more frequently exposure to bacteria in daycare centres and schools [4]. Moreover, early signs and symptoms of invasive SI are often non-specific, such as fever, irritability, rhinitis and decreased appetite, and making early diagnosis challenging.

Our data showed that almost all children (92%) had prodromal symptoms or signs of an illness prior to death. Most of them (79%) had a history of being unwell for at least a day, and 34% were seen by a doctor in the days prior to their terminal presentation. Fever (80%) was the most common clinical sign, followed by gastrointestinal and respiratory symptoms (60% and 51%, respectively). These included vomiting, diarrhoea, nausea, abdominal pain, difficulty drinking, feeding, cough, shortness of breath, tachypnoea, wheezing, grunting, chest pain, sore throat and runny nose. Skin rash was more documented in the setting of SPy infection [1].

Another interesting finding our study demonstrated was that the terminal events were generally very brief. 89% of decedents had a rapid terminal course, including 13% were found unresponsive at home, 21% had witnessed collapse at home or en route to the hospital in an ambulance, and 55% died within 24 hours of hospital admission. 11% survived beyond 1-day post-admission and died later [1]. In a study from England, analysing SPn infection related pediatric deaths, it was found that 13.3% died at home, 5.5% en route to hospital, and 16.7% in the emergency department. 64% died later in the hospital, though, there was no specification on the length of hospital admission [5,6].

Our study showed that majority (64%) of death was attributed to sepsis, which was more frequent in the SPy group (71%) than in the SPn group (48%). All SAg infection related deaths were due to sepsis. In half of the septic deaths, source of infection was demonstrated at postmortem examination. These included pneumonia, meningitis, lung abscess, ruptured appendicitis, neck abscess and purulent peritonitis. Non-septic deaths (37%) were due to localized organ inflammation and resultant organ failure, for example necrotizing pneumonia, purulent meningitis, and diffuse purulent peritonitis. Pneumonia was present in a similar number of cases in both SPn and SPy groups. All meningitis-associated deaths were caused by SPn infection [1].

Recommendations on post mortem microbiology sampling in cases which are clinically suspicious of sepsis include heart blood and spleen, with additional sampling of lung, liver and kidney to be able to confirm presence of the same pathogen at multiple sites [7,9]. Middle ears should always be examined in children with swab culturing as this may be a primary site of infection in cases of meningitis. To optimize interpretation of any positive culture results, histological examination of the area sampled for culture is advised i.e., vital inflammatory response seen on histology would corroborate that an isolated organism in the culture is pathologically significant. This relates not only to internal organs but to any abnormal skin lesions, as skin is the most common portal of entry in invasive SPy infection [3,10,11].

Infection screen should also include virology testing as viral infection, such as Varicella and Influenza viruses have been identified as risk factors for SI [12-14]. In our study two children had a history of viral infection (chickenpox and Influenza A virus) shortly before death.

Autopsy examination continues to be a source of valuable information, which enhances our understanding of fatal pediatric infectious deaths. It helps to identify specific infective organisms, and their portals of entry, through internal organ/tissue sampling, not readily accessible in the living.

Though, multivalent pneumococcal conjugate vaccines (PCV-7 and PCV-13) and improved antimicrobial treatment have decreased the number of invasive SPn infections, non-vaccine preventable serotypes are demonstrated to be responsible for a more recent increase in invasive pneumococcal diseases [15,16]. Currently, there is no licensed vaccine against SPy. Therefore, additional molecular serotyping and/or genotyping of the bacteria in autopsy samples to identify more virulent Streptococcal strains associated with a high risk for sudden death would be of great value in future vaccine development.

1. Nagy A, Reyes JA, Chiasson DA (2022) Fatal pediatric streptococcal infection: A clinico - pathological study. Pediatr Dev Pathol. 25:409-418.
2. Gangoiti I, Valle JR, Sota M, Martinez-Indart L, Benito J, et al. (2018) Characteristics of children with microbiologically confirmed invasive bacterial infections in the emergency department. Eur J Emerg Med 25:274-280.
3. Avire NJ, Whiley H, Ross K (2021) A review of Streptococcus pyogenes: Public health risk factors, prevention and control. Pathogens 10: 248.
4. Efstratiou A, Lamagni T (2021) Epidemiology of Streptococcus pyogenes. In: Ferretti JJ, Stevens DL, Fischetti VA (eds), Streptococcus pyogenes: Basic biology to clinical manifestations. University of Oklahoma Health Sciences Center, Oklahoma, USA.
5. Bogaert D, De Groot R, Hermans PMW (2004) Streptococcus pneumoniae colonisation: The key to pneumococcal disease. Lancet Infect Dis 4:144-154.
6. Oligbu G, Collins S, Sheppard CL, Fry NK, Slack M, et al. (2017) Childhood deaths attributable to invasive pneumococcal disease in England and Wales, 2006–2014. Clin Infect Dis 65:308-314.
7. Fatal pediatric streptococcal infection: A clinico - pathological study
8. Boeddha NP, Schlapbach LJ, Driessen GJ, Herberg JA, Rivero-Calle I, et al. (2019) Mortality and morbidity in community-acquired sepsis in European pediatric intensive care units: a prospective cohort study from the European Childhood Life-threatening Infectious Disease Study (EUCLIDS). Crit Care 22:143.
9. Tsokos M (2006) Pathology of Sepsis. In: Rutty GN (ed), Essentials of autopsy practice. Springer, London, UK. pp:39-85.
10. Kimberlin DW, Long SS, Brady MT, Jackson MA (2015) Red book 2015: Report of the committee on infectious diseases. American Academy of Pediatrics, Illinois, USA.
11. Thompson KM, Sterkel AK, McBride JA, Corliss RF (2018) The shock of strep: Rapid deaths due to group a streptococcus. Acad Forensic Pathol 8:136-149.
12. Fernández-Rodríguez A, Burton JL, Andreoletti L, Alberola J, Fornes P, et al. (2019) Post-mortem microbiology in sudden death: Sampling protocols proposed in different clinical settings. Clin Microbiol Infect 25:570-579.
13. Patel RA, Helen J Binns HJ, Shulman ST (2004) Reduction in pediatric hospitalizations for varicella-related invasive group a streptococcal infections in the varicella vaccine era. J Pediatr 144:68-74.
14. Herrera AL, Huber VC, Chaussee MS (2016) The association between invasive group A streptococcal diseases and viral respiratory tract infections. Front Microbiol 7:342.
15. Levy C, Ouldali N, Caeymaex L, Angoulvant F, Varon E, et al. (2019) Diversity of serotype replacement after Pneumococcal conjugate vaccine implementation in europe. J Pediatr 213:252.e3-253.e3.
16. Wijayasri S, Hillier K, Lim GH, Harris TM, Wilson SE, et al. (2019) The shifting epidemiology and serotype distribution of invasive pneumococcal disease in Ontario, Canada, 2007-2017. PLoS One 14:e0226353.