Extrapulmonary Coccidioidomycosis Among Children in Central California: A Retrospective Review.

BACKGROUND: The literature on pediatric extrapulmonary coccidioidomycosis is limited. We reviewed the clinical course, diagnostic studies, treatment and outcomes of children with extrapulmonary coccidioidomycosis followed at a tertiary care center in central California. METHODS: Retrospective study of 78 patients ≤21 years old with extrapulmonary coccidioidomycosis diagnosed over 10 years (1/1/07-12/31/16). RESULTS: The median age was 9.7 years (interquartile range, 4.5-14.8). The majority of patients were males (55%), Hispanic (65%) and without comorbid conditions (85%). Over two-thirds (68%) had concurrent pulmonary disease. Organ involvements included bones and joints (33%), mediastinum (19%), central nervous system (19%), cervical lymph nodes (15%), larynx (6%) and skin (5%). Most cases (84%) resolved and/or became stable on maintenance therapy, 14% experienced relapse and/or progressive disease, and 2% were fatal. Children ≥10 years of age tended to have >1 site of involvement (47% vs. 25%, P = 0.06), and more relapsed/progressive/fatal disease (21% vs. 5%, P = 0.06) compared with those <10 years. They also required longer durations of treatment (median, 611 vs. 349 days, P = 0.02). Non-Hispanics were more likely to require >1 drug therapy (85% vs. 70%, P = 0.04) and tended to have Coccidioides complement fixation titers ≥1:32 (89% vs. 72%, P = 0.04) compared with Hispanics. CONCLUSIONS: Extrapulmonary coccidioidomycosis in children can be severe and spread to multiple sites and requires prolonged treatment. Non-Hispanics and those ≥10 years of age are more likely to experience severe disease, suggesting a need for early recognition and intervention in these populations.

Epidemiology of Diarrheal Illness in Pediatric Oncology Patients.

BACKGROUND: Diarrhea is common in children with cancer, but this has not been systematically studied to date. METHODS: Remnant stool samples collected between January 2010 and June 2011 from pediatric oncology patients with diarrhea were tested for bacterial, viral, and parasitic enteropathogens using a combination of standard-of-care (SOC) diagnostic tests, including broad-range, real-time polymerase chain reaction (PCR) assays for adenoviruses, astroviruses, and sapoviruses and 2 commercially available multiplexed PCR assays. Corresponding demographic and clinical data were abstracted from patients' medical records. RESULTS: One hundred fourteen episodes of diarrhea in 93 patients (median age, 3.7 years; range, 0.2-18.8) were included in the study. No patients died, but morbidity was significant. A total of 158 potential pathogens were detected in 114 diarrhea episodes, with >1 organism in one third of these; the most common were Clostridium difficile, noroviruses, adenoviruses, and astroviruses. Clostridium difficile, in combination with norovirus or adenovirus, was most common when >1 pathogen was detected. When both studies were obtained, SOC and broadly multiplexed PCR tests were concordant in 64 episodes (56%). Forty-five pathogens (28%) were identified retrospectively by broadly multiplexed PCR assays only. A total of 19 (13%) were detected by SOC real-time PCR assays but not by either commercially available multiplexed PCR assay. CONCLUSIONS: Most pediatric oncology patients in this study had 1 or more potential infectious causes for their diarrhea. Additional studies are warranted to understand the natural history of gastroenteritis in this patient population. Although broadly multiplexed PCR assays offer some advantages over conventional testing, there may be disadvantages to their use for the diagnosis of infectious gastroenteritis that are unique to pediatric oncology patients.

Comparative Evaluation of Broad-Panel PCR Assays for the Detection of Gastrointestinal Pathogens in Pediatric Oncology Patients.

Broadly multiplexed molecular amplification assays offer an unprecedented ability to diagnose gastrointestinal infection in immunocompromised patients. However, little data are available to compare the performance of such systems in this population. A total of 436 stool samples were collected from 199 predominantly immunocompromised pediatric oncology patients. Remnant samples were tested in parallel with the use of the premarket (investigational use only) versions of two broadly multiplexed PCR assays (BioFire and Luminex), and the results of samples corresponding to the first episode per patient were compared with those from laboratory-developed molecular assays, culture, and antigen detection. Overall performance of the multiplexed systems was comparable, with BioFire and Luminex detecting 94 and 99 positives (P = 0.34), respectively. Stratifying by analyte, BioFire assay detected 51 samples positive for Clostridium difficile, whereas Luminex assay detected 60 (P = 0.01). Biofire and Luminex detected 28 and 38 norovirus-positive samples (P = 0.002), respectively. Astrovirus- and adenovirus-positive samples were detected in higher numbers by in-house PCR than by BioFire; the same was observed for adenovirus with Luminex. Differences observed with other analytes were minimal, did not reach statistical significance, or lacked the numbers needed to detect a difference between systems. Broadly multiplexed PCR offers an effective means of detecting a variety of gastrointestinal pathogens in pediatric oncology patients, with assay performance comparable among the tests examined.