Christine C. Robinson

Genotype Prevalence and Risk Factors for Severe Clinical Adenovirus Infection, United States 2004-2006

BACKGROUNDnRecently, epidemiological and clinical data have revealed important changes with regard to clinical adenovirus infection, including alterations in antigenic presentation, geographical distribution, and virulence of the virus.nnnMETHODSnIn an effort to better understand the epidemiology of clinical adenovirus infection in the United States, we adopted a new molecular adenovirus typing technique to study clinical adenovirus isolates collected from 22 medical facilities over a 25-month period during 2004-2006. A hexon gene sequence typing method was used to characterize 2237 clinical adenovirus-positive specimens, comparing their sequences with those of the 51 currently recognized prototype human adenovirus strains. In a blinded comparison, this method performed well and was much faster than the classic serologic typing method.nnnRESULTSnAmong civilians, the most prevalent adenovirus types were types 3 (prevalence, 34.6%), 2 (24.3%), 1 (17.7%), and 5 (5.3%). Among military trainees, the most prevalent types were types 4 (prevalence, 92.8%), 3 (2.6%), and 21 (2.4%).nnnCONCLUSIONSnFor both populations, we observed a statistically significant increasing trend of adenovirus type 21 detection over time. Among adenovirus isolates recovered from specimens from civilians, 50% were associated with hospitalization, 19.6% with a chronic disease condition, 11% with a bone marrow or solid organ transplantation, 7.4% with intensive care unit stay, and 4.2% with a cancer diagnosis. Multivariable risk factor modeling for adenovirus disease severity found that age <7 years (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4-7.4), chronic disease (OR, 3.6; 95% CI, 2.6-5.1), recent transplantation (OR, 2.7; 95% CI, 1.3-5.2), and adenovirus type 5 (OR, 2.7; 95% CI, 1.5-4.7) or type 21 infection (OR, 7.6; 95% CI, 2.6-22.3) increased the risk of severe disease.

Clinical and In Vitro Evaluation of Cidofovir for Treatment of Adenovirus Infection in Pediatric Hematopoietic Stem Cell Transplant Recipients

Post-hematopoietic stem cell transplantation (HSCT) adenovirus infections were identified in 31 of 204 consecutive pediatric HSCT patients, 18 of whom had severe manifestations of infection. Cidofovir treatment led to clinical improvement in 8 of 10 patients with severe infection and to virologic clearance in 9 patients. In vitro susceptibility to cidofovir was demonstrated in 12 clinical adenovirus isolates. Cidofovir is a promising treatment option for this population.

Multiplex MassTag-PCR for respiratory pathogens in pediatric nasopharyngeal washes negative by conventional diagnostic testing shows a high prevalence of viruses belonging to a newly recognized rhinovirus clade

n Abstractn n Backgroundn Respiratory infections are the most common infectious diseases in humans worldwide and are a leading cause of death in children less than 5 years of age.n n n Objectivesn Identify candidate pathogens in pediatric patients with unexplained respiratory disease.n n n Study designn Forty-four nasopharyngeal washes collected during the 2004–2005 winter season from pediatric patients with respiratory illnesses that tested negative for 7 common respiratory pathogens by culture and direct immunofluorescence assays were analyzed by MassTag-PCR. To distinguish human enteroviruses (HEV) and rhinoviruses (HRV), samples positive for picornaviruses were further characterized by sequence analysis.n n n Resultsn Candidate pathogens were detected by MassTag PCR in 27 of the 44 (61%) specimens that previously were rated negative. Sixteen of these 27 specimens (59%) contained picornaviruses; of these 9 (57%) contained RNA of a recently discovered clade of rhinoviruses. Bocaviruses were detected in three patients by RT-PCR.n n n Conclusionsn Our study confirms that multiplex MassTag-PCR enhances the detection of pathogens in clinical specimens, and shows that previously unrecognized rhinoviruses, that potentially form a species HRV-C, may cause a significant amount of pediatric respiratory disease.n n

Increased Activity of Coxsackievirus B1 Strains Associated with Severe Disease among Young Infants in the United States, 2007—2008

BACKGROUNDnEnterovirus infections are very common and typically cause mild illness, although neonates are at higher risk for severe illness. In 2007, the Centers for Disease Control and Prevention (CDC) received multiple reports of severe neonatal illness and death associated with coxsackievirus B1 (CVB1), a less common enterovirus serotype not previously associated with death in surveillance reports to the CDC.nnnMETHODSnThis report includes clinical, epidemiologic, and virologic data from cases of severe neonatal illness associated with CVB1 reported during the period from 2007 through 2008 to the National Enterovirus Surveillance System (NESS), a voluntary, passive surveillance system. Also included are data on additional cases reported to the CDC outside of the NESS. Virus isolates or original specimens obtained from patients from 25 states were referred to the CDC picornavirus laboratory for molecular typing or characterization.nnnRESULTSnDuring 2007-2008, the NESS received 1079 reports of enterovirus infection. CVB1 accounted for 176 (23%) of 775 reported cases with known serotype, making it the most commonly reported serotype for the first time ever in the NESS. Six neonatal deaths due to CVB1 infection were also reported to the CDC during that time. Phylogenetic analysis of the 2007 and 2008 CVB1 strains indicated that the increase in cases resulted from widespread circulation of a single genetic lineage that had been present in the United States since at least 2001.nnnCONCLUSIONSnHealthcare providers and public health departments should be vigilant to the possibility of continuing CVB1-associated neonatal illness, and testing and continued reporting of enterovirus infections should be encouraged.

Acyclovir-resistant neonatal herpes simplex virus infection of the larynx

A 10-day-old infant with stridor was found to have herpes simplex virus type 2 infection of the larynx. The infants poor clinical response to both acyclovir and foscarnet prompted extensive clinical and virologic evaluations, which revealed acyclovir-resistant herpes simplex virus.

Enterovirus D68 Infection in Children with Acute Flaccid Myelitis, Colorado, USA, 2014

Odds of this viral infection in the nasopharynx were 10 times greater for children with this condition than for controls.

Outbreak of Mycoplasma pneumoniae-Associated Stevens-Johnson Syndrome.

BACKGROUND: Stevens-Johnson syndrome (SJS) is an uncommon, sporadic disease and outbreaks are rare. In November 2013, an outbreak of SJS was identified at Children’s Hospital Colorado. METHODS: Outbreak cases were children aged 5–21 with a discharge diagnosis of SJS admitted from September 1 to November 30, 2013. Medical charts were reviewed using standardized data collection forms. Respiratory specimens were tested for viruses and Mycoplasma pneumoniae (Mp) by polymerase chain reaction (PCR). We conducted a separate 4-year retrospective case-control study comparing hospitalized SJS cases with and without evidence of Mp infection. RESULTS: During the outbreak, 8 children met SJS criteria. Median age was 11.5 years (range 8–16 years); 5 (63%) were boys and 5 (63%) were Mp-PCR–positive. Of the 5 PCR-positive children, none had preceding medication exposure, and all had radiographic pneumonia. All outbreak Mp isolates were macrolide susceptible. The retrospective case-control analysis showed that Mp-associated SJS episodes (n = 17) were more likely to have pneumonia (odds ratio [OR] 10.0, confidence interval [CI] 1.3–5.1), preceding respiratory symptoms (OR 30.0, CI 1.6–72.6), an erythrocyte sedimentation rate ≥35 mg/dL (OR 22.8, CI 2.1–244.9), and ≤3 affected skin sites (OR 4.5, CI 1.2–17.4) than non–Mp-associated SJS episodes (n = 23). CONCLUSIONS: We report the largest outbreak of SJS in children, which was also predominately associated with Mp infection. Mp-associated SJS was associated with a distinct clinical presentation that included less extensive skin disease, an elevated erythrocyte sedimentation rate, and evidence of a preceding respiratory infection.

Epidemiology and Clinical Presentation of Parainfluenza Type 4 in Children: A 3-Year Comparative Study to Parainfluenza Types 1–3

Abstract Background.u2003Human parainfluenza viruses (HPIVs) are among the most common causes of respiratory tract infections in children. Little is known about the epidemiology and clinical presentation of HPIV type 4. Methods.u2003A retrospective chart review and comparison of patients positive for HPIV types 1–4 by multiplex polymerase chain reaction between 2009 and 2012 at Childrens Hospital Colorado was performed. Patients who had only direct fluorescent antibody testing performed or concurrent viral infections were excluded. Results.u2003Of 11 533 samples, 752 (6.5%) were positive for HPIV. After exclusion criteria, 316 samples were included in the study. HPIV-4 had year-round prevalence with biennial peaks in odd-numbered years. HPIV-4 and HPIV-3 had similar clinical presentations. 50.8% and 51.5% of patients with HPIV-3–4 had hypoxia compared to 20.3% and 33.3% of patients with HPIV-1–2 (P < .01). HPIV-1 (23.6%) and HPIV-2 (24.2%) were more associated with stridor than HPIV-3 (6.6%) and HPIV-4 (0%) (P < .01). No patients with HPIV-4 had croup. Patients with HPIV-4 had similar lengths of stay and mortality as those with HPIV-1–3. Conclusions.u2003This is the first large-scale analysis of HPIV-4 clinical and epidemiologic features. HPIV-4 was most similar to HPIV-3 in clinical presentation. HPIV-4 had year-round prevalence with peaks in the autumn of odd-numbered years. HPIV-4 is a common respiratory pathogen capable of causing significant morbidity in children.

Potential clinical impact of the film array meningitis encephalitis panel in children with suspected central nervous system infections

The FilmArray Meningitis Encephalitis Panel, a multiplex PCR for testing of cerebrospinal fluid, was compared to conventional diagnostic methods in children with suspected central nervous system infections. The panel had comparable diagnostic yield (96% agreement) and improved time-to-diagnosis by 10.3 hours with potential for more judicious antimicrobial use, particularly acyclovir.

Viral gastroenteritis in children in Colorado 2006-2009.

Acute gastroenteritis accounts for a significant burden of medically attended illness in children under the age of five. For this study, four multiplex reverse transcription PCR assays were used to determine the incidence of adenovirus, astrovirus, coronavirus, norovirus GI and GII, rotavirus, and sapovirus in stool samples submitted for viral electron microscopy (EM) to the Childrens Hospital Colorado. Of 1105 stool samples available, viral RNA/DNA was detected in 247 (26.2%) of 941 pediatric samples (median ageu2009=u20092.97 years, 54% male) with 28 (3.0%) positive for more than one virus. Adenovirus, astrovirus, norovirus GI, norovirus GII, rotavirus, and sapovirus were detected in 95 (10.0%), 33 (3.5%), 8 (0.9%), 90 (9.6%), 49 (5.2%), and 2 (0.2%) of the pediatric samples, respectively. No coronaviruses were identified. Sequencing of norovirus positive samples indicated an outbreak of norovirus strain GII.4 in 2006 with evidence of numerous circulating strains. Multiple samples from the same immunocompromised patients demonstrated symptomatic shedding of norovirus for up to 32 weeks and astrovirus for 12 weeks. RT‐PCR detected 99 of 111 (89%) adenovirus‐positive samples versus 12 (11%) by EM, and 186 of 192 (97%) sapovirus/astrovirus/norovirus‐positive samples versus 21 (11%) by EM. Noroviruses and adenoviruses are common causes of gastroenteritis in children. Immunocompromised patients can be infected with multiple viruses and shed viruses in their stools for prolonged periods. This data support the superiority of RT‐PCR compared to EM for diagnosis of viral gastroenteritis. J. Med. Virol. 87:931–939, 2015.