Streptococcus pneumoniae-associated Hemolytic Uremic Syndrome Among Children in North America

Ritu Banerjee, MD, PhD; Adam L. Hersh, MD, PhD; Jason Newland, MD; Susan E. Beekmann, RN, MPH; Philip M. Polgreen, MD, MPH; Jeffrey Bender, MD; Jana Shaw, MD, MPH; Lawrence Copelovitch, MD; Bernard S. Kaplan, MB BCH; Samir S. Shah, MD

Disclosures

Pediatr Infect Dis J. 2011;30(9):736-739. 

In This Article

Abstract and Introduction

Abstract

Background: To better characterize Streptococcus pneumoniae-associated hemolytic-uremic syndrome (SP-HUS), we report the largest series of SP-HUS among children in North America.
Methods: We surveyed pediatric members of the Emerging Infections Network to identify SP-HUS cases. Respondents contributed clinical and laboratory features of these pediatric cases.
Results: A total of 37 cases occurring between 1997 and 2009 were submitted. Of them, 33 cases (89%) were culture-confirmed and 4 (11%) were diagnosed clinically. The median patient age was 2 years, and 28 (76%) patients had completed their heptavalent pneumococcal conjugate vaccination (PCV7) series. Most patients presented with pneumonia (84%) and bacteremia (78%), whereas other clinical manifestations such as pericardial effusion (14%) and meningitis (11%) were less common. Of 29 patients, with bacteremia 6 (21%) had S. pneumoniae concurrently isolated from cerebrospinal fluid or pleural fluid. Severe illness was common with 35 (95%) patients requiring admission to the intensive care unit, over half requiring mechanical ventilation and chest tube placement or videoassisted thoracoscopic surgery, and 27 (73%) requiring dialysis during hospitalization. Among 30 patients with follow-up of 6 months, 7 (23%) remained dialysis dependent, 3 (10%) had undergone renal transplantation, 4 (13%) had neurologic sequelae, and 1 (3%) died. Among 24 serotyped isolates, 96% were non-PCV7 serotypes, most commonly 19A (50%), 92% are included in PCV13, and 10% were penicillin nonsusceptible (minimal inhibitory concentration >2 μg/mL).
Conclusions: North American children with SP-HUS had severe clinical manifestations and significant morbidity. In this series, nearly all cases were caused by serotypes that are not in PCV7 but are included in PCV13.

Introduction

Nondiarrheal hemolytic uremic syndrome (HUS) is defined as microangiopathic hemolytic anemia, thrombocytopenia, and renal failure in the absence of diarrheal illness or infection with Shiga-toxin expressing Escherichia coli (STEC). Nondiarrheal HUS occurs following infection with a variety of pathogens[1] or exposure to certain medications, and in individuals with complement dysregulation.[2]

Streptococcus pneumoniae (SP) is the most common infectious cause of nondiarrheal HUS.[3–7]S. pneumoniae-associated HUS is a severe disease, usually associated with complicated pneumonia and empyema.[4,8] Patients with SP-HUS have more morbidity and mortality than other forms of invasive pneumococcal disease or diarrhea-associated HUS,[6,9–11] although most studies describing SP-HUS are single center case series with limited clinical and microbiologic data.

Few studies have examined the clinical and molecular epidemiology of SP-HUS following licensure of the heptavalent pneumococcal conjugate vaccine (PCV7).[7,12,13] The overall decline in invasive pneumococcal disease rates in the post-PCV7 era was accompanied by an increase in invasive disease due to nonvaccine S. pneumoniae serotypes, most commonly 19A.[14–16] Furthermore, while the hospitalization rates for childhood pneumonia have decreased following widespread vaccination, the incidence of hospitalizations for pneumonia complicated by empyema has increased,[17] most dramatically in children younger than 4 years.[18,19]

The incidence of SP-HUS is likely underestimated due to the lack of awareness of this disease among physicians, and to the overlap in symptoms between SP-HUS and disseminated intravascular coagulopathy from S. pneumoniae sepsis. To further increase awareness and understanding of this rare and severe disease, the objective of this study was to report the clinical and laboratory features for the largest series, to date, of culture-confirmed SP-HUS among children in North America.

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