Suchitra Rao

Seroepidemiology of human polyomaviruses.

In addition to the previously characterized viruses BK and JC, three new human polyomaviruses (Pys) have been recently identified: KIV, WUV, and Merkel Cell Py (MCV). Using an ELISA employing recombinant VP1 capsid proteins, we have determined the seroprevalence of KIV, WUV, and MCV, along with BKV and JCV, and the monkey viruses SV40 and LPV. Soluble VP1 proteins were used to assess crossreactivity between viruses. We found the seroprevalence (+/− 1%) in healthy adult blood donors (1501) was SV40 (9%), BKV (82%), JCV (39%), LPV (15%), KIV (55%), WUV (69%), MCV strain 350 (25%), and MCV strain 339 (42%). Competition assays detected no sero-crossreactivity between the VP1 proteins of LPV or MCV or between WUV and KIV. There was considerable sero-crossreactivity between SV40 and BKV, and to a lesser extent, between SV40 and JCV VP1 proteins. After correcting for crossreactivity, the SV40 seroprevalence was ∼2%. The seroprevalence in children under 21 years of age (n = 721) for all Pys was similar to that of the adult population, suggesting that primary exposure to these viruses likely occurs in childhood.

WU and KI polyomavirus infections in pediatric hematology/oncology patients with acute respiratory tract illness.

Abstract Background WU and KI polyomaviruses (PyV) were discovered in 2007 in respiratory tract samples in adults and children. Other polyomaviruses (BKPyV and JCPyV) have been associated with illness in immunocompromised patients, and some studies suggest a higher prevalence of WUPyV and KIPyV in this population. Objective To determine whether a higher prevalence or viral load for WUPyV and KIPyV exists in immunocompromised children compared with immunocompetent children. Study design We measured the prevalence and viral load of WU and KI PyV by quantitative real-time PCR of viral DNA in respiratory tract specimens from pediatric hematology/oncology patients and immunocompetent controls with acute respiratory illnesses. Results The prevalence of WUPyV in the immunocompromised population was 5/161 (3%) versus 14/295 (5%) in the control population (P =0.5), and 9/161 (5.6%) versus 7/295 (2.3%) respectively for KIPyV (P =0.13). The mean viral load (in copies per cell or mL of sample) for KIPyV, was higher in the immunocompromised group compared to the control group (P =0.019), but was not statistically different for WUPyV. A higher prevalence was seen in the hematopoietic stem cell transplant recipients compared with other immunocompromised patients (6/26 versus 3/43, P =0.054). Viral persistence was demonstrated only in 1/25 (4%) of sequential samples for KIPyV, and no persistence was seen for WUPyV. Conclusions A higher prevalence of WUPyV or KIPyV in the immunocompromised population compared with the immunocompetent group was not demonstrated. Higher viral loads for KIPyV in the immunocompromised group may suggest an increased pathogenic potential in this population.

Intravenous acyclovir and renal dysfunction in children: a matched case control study.

OBJECTIVES A cluster of children receiving intravenous (IV) acyclovir for meningoencephalitis developed acute renal failure in April-May 2008, which prompted a retrospective case-control study to determine the rate of and risk factors for acute nephrotoxicity during IV acyclovir treatment in children. STUDY DESIGN The percentage decrease in glomerular filtration rate in children receiving IV acyclovir who had ≥ 1 creatinine measurement after acyclovir initiation from October 2006 to January 2009 was classified as renal risk, injury, or failure according to modified Pediatric Risk Injury, Failure, Loss, End-Stage Renal Disease criteria. Univariate and multivariate matched analyses were conducted to identify risk factors contributing to nephrotoxicity. RESULTS In the selected study group, renal dysfunction was seen in 131 of 373 (35%) treatment courses studied: 81 of 373 (22%) risk, 36 of 373 (9.7%) injury, and 14 of 373 (3.8%) failure. Most renal dysfunction occurred within 48 hours of the initiation of acyclovir. Renal function returned to the normal range but not to baseline in most cases during the follow-up period. Risk factors for renal dysfunction included acyclovir dose >15 mg/kg (OR 3.81, 95% CI 1.55-9.37) for risk; cumulative exposure greater than calculated cumulative exposure based on 500 mg/m(2)/dose (OR 6.00, 95% CI 1.95-18.46) for injury; and age >8 years (OR 21.5, 95% CI 2.2, >1000) and ceftriaxone coadministration (OR 19.3, 95% CI 1.8, >1000) for failure. CONCLUSIONS Nephrotoxicity associated with IV acyclovir is common and necessitates renal function monitoring. Risk factors include greater dose, older age, and concomitant ceftriaxone administration. Outside the neonatal period, renal dysfunction may be minimized by dosing IV acyclovir below thresholds associated with nephrotoxicity (ie, ≤ 500 mg/m(2)/dose or ≤ 15 mg/kg/dose), particularly in older patients.

The Emergence of Zoonotic Onchocerca lupi Infection in the United States – A Case-Series

This case-series describes the 6 human infections with Onchocerca lupi, a parasite known to infect cats and dogs, that have been identified in the United States since 2013. Unlike cases reported outside the country, the American patients have not had subconjunctival nodules but have manifested more invasive disease (eg, spinal, orbital, and subdermal nodules). Diagnosis remains challenging in the absence of a serologic test. Treatment should be guided by what is done for Onchocerca volvulus as there are no data for O. lupi. Available evidence suggests that there may be transmission in southwestern United States, but the risk of transmission to humans is not known. Research is needed to better define the burden of disease in the United States and develop appropriately-targeted prevention strategies.

Intravenous Versus Oral Antibiotics for Postdischarge Treatment of Complicated Pneumonia.

BACKGROUND AND OBJECTIVES: Postdischarge treatment of complicated pneumonia includes antibiotics administered intravenously via a peripherally inserted central venous catheter (PICC) or orally. Antibiotics administered via PICC, although effective, may result in serious complications. We compared the effectiveness and treatment-related complications of postdischarge antibiotics delivered by these 2 routes. METHODS: This multicenter retrospective cohort study included children ≥2 months and <18 years discharged with complicated pneumonia between 2009 and 2012. The main exposure was the route of postdischarge antibiotic administration, classified as PICC or oral. The primary outcome was treatment failure. Secondary outcomes included PICC complications, adverse drug reactions, other related revisits, and a composite of all 4 outcomes, termed “all related revisits.” RESULTS: Among 2123 children, 281 (13.2%) received antibiotics via PICC. Treatment failure rates were 3.2% among PICC and 2.6% among oral antibiotic recipients and were not significantly different between the groups in across-hospital-matched analysis (matched odds ratio [OR], 1.26; 95% confidence interval [CI], 0.54 to 2.94). PICC complications occurred in 7.1%. Adverse drug reactions occurred in 0.6% of children; PICC antibiotic recipients had greater odds of adverse drug reaction in across hospital matched analysis (matched OR, 19.1; 95% CI, 4.2 to 87.3). The high rate of PICC complications and differences in adverse drug reactions contributed to higher odds of the composite outcome of all related revisits among PICC antibiotic recipients (matched OR, 4.71; 95% CI, 2.97 to 7.46). CONCLUSIONS: Treatment failure rates between PICC and oral antibiotics did not differ. Children with complicated pneumonia should preferentially receive oral antibiotics at discharge when effective oral options are available.

WU and KI polyomavirus infections in Filipino children with lower respiratory tract disease

BACKGROUND WU and KI are human polyomaviruses initially detected in the respiratory tract, whose clinical significance remains uncertain. OBJECTIVES To determine the epidemiology, viral load and clinical characteristics of WU and KI polyomaviruses. STUDY DESIGN We tested respiratory specimens collected during a randomized, placebo-controlled pneumococcal conjugate vaccine trial and related epidemiological study in the Philippines. We analyzed 1077 nasal washes from patients aged 6 weeks to 5 years who developed lower respiratory tract illness using quantitative real-time PCR for WU and KI. We collected data regarding presenting symptoms, signs, radiographic findings, laboratory data and coinfection. RESULTS The prevalence and co-infection rates for WU were 5.3% and 74% respectively and 4.2% and 84% respectively for KI. Higher KI viral loads were observed in patients with severe or very severe pneumonia, those presenting with chest indrawing, hypoxia without wheeze, convulsions, and with KI monoinfection compared with co-infection. There was no significant association between viral load and clinical presentation for WU. CONCLUSIONS These findings suggest a potential pathogenic role for KI, and that there is an association between KI viral load and illness severity.

Enterovirus D68 in Critically Ill Children: A Comparison With Pandemic H1N1 Influenza.

Objective: In 2014, the Unites States experienced an outbreak of enterovirus D68 associated with severe respiratory illness. The clinical characteristics associated with severe illness from enterovirus D68 during this outbreak compared with those associated with the 2009 H1N1 influenza virus outbreak are unknown. Design and Setting: In this retrospective cohort study, we characterized the clinical features of children with enterovirus D68 admitted to the PICU between August 1, 2014, and November 1, 2014, and compared them with critically ill children infected with H1N1 influenza during the pandemic admitted between May 1, 2009, and January 31, 2010. Patients: PICU patients. Interventions: None. Measurements and Main Results: Ninety-seven severely ill children with enterovirus D68 infections were compared with 68 children infected with H1N1 influenza during the 2009 pandemic. Children with enterovirus D68 were more likely to have asthma (62% vs 23%; p < 0.001) and present with reactive airway disease exacerbations, with greater receipt of albuterol (94% vs 49%) and steroids (89% vs 40%; p < 0.0001 for both). Although more children with enterovirus D68 were admitted to the ICU compared with those with H1N1 influenza, they had a shorter hospital length of stay (4 vs 7 d; p < 0.0001), with lower intubation rates (7% vs 44%), vasopressor use (3% vs 32%), acute respiratory distress syndrome (3% vs 24%), shock (0% vs 16%), and death (0% vs 12%; p < 0.05 for all). Compared with children with other enteroviruses and rhinoviruses, children with enterovirus D68 were more likely to have a history of asthma (64% vs 45%) or multiple prior wheezing episodes (54% vs 34%; p < 0.01 for both). Conclusions: Critically ill children with enterovirus D68 were more likely to present with reactive airway disease exacerbations, whereas children with H1N1 influenza were more likely to present with pneumonia. Compared with the pandemic H1N1 influenza outbreak, the enterovirus D68 outbreak resulted in more children requiring admission to the ICU, but was associated with less severe outcomes.

Eosinophilic meningitis in a previously healthy 13-year-old child.

A previously healthy 13-year-old male developed acute onset of a bi-temporal headache. The headache persisted, and two weeks later, he was diagnosed with sinusitis and was given amoxicillin. On illness day 17, he experienced worsening headache, slurred speech, transient left facial droop, right hand numbness, and dizziness. At a local emergency department (ED), magnetic resonance imaging (MRI) of the brain showed no significant abnormalities, though images were obscured by artifact from his orthodontic hardware. He was discharged without a specific diagnosis after his neurologic symptoms had resolved. On illness day 19, the patient had return of hand tingling and slurred speech and presented to the Children’s Hospital Colorado ED. He was diagnosed with an atypical migraine and was treated with ketorolac, diphenhydramine, and prochlorperazine. His symptoms improved, and he was discharged. On illness day 20, the patient experienced severe right eye pain and recurrence of his headache. He returned to his local ED and was hospitalized after minimal clinical improvement with treatment for migraine. At that time, his Romberg sign was abnormal, he was ataxic, and he had diplopia. On illness day 22, he underwent a lumbar puncture (LP) because of concern of pseudotumor cerebri. The cerebral spinal fluid (CSF) showed white blood cell count (WBC) of 763/mm3 (with a differential of 80% lymphocytes, 15% monocytes, and 5% eosinophils), red blood cell count (RBC) of 2/mm3, protein of 49 mg/dL, and glucose of 54 mg/dL. Intravenous acyclovir was started but was discontinued when polymerase chain reaction assay (PCR) of the CSF for herpes simplex virus returned negative. Bacterial and fungal cultures of the CSF were negative. He was discharged home after a three-day hospitalization. Over the next several weeks, he remained stable but continued to have intermittent headaches and ongoing diplopia. Then, forty-seven days after initial onset of illness, the patient developed severe right eye pain and photophobia and returned to the local ED. Repeat LP showed an opening pressure of 44 cm H20, WBC of 347/mm3 (with a differential of 53% lymphocytes, 26% monocytes, 21% eosinophils), RBC of 3/mm3, protein of 127 of mg/dL, and glucose of 35 mg/dL. He was subsequently transferred to Children’s Hospital Colorado. On admission, the patient was afebrile and had normal vital signs. Physical examination showed papilledema with splinter hemorrhages, left esotropia with subjective diplopia, and no signs of meningismus. Complete blood count (CBC) showed WBC of 9,100/mm3 (with differential of 44% neutrophils, 33% lymphocytes, 11% monocytes, 12% eosinophils), hemoglobin of 16.1 g/dL, hematocrit of 47.1%, and platelet count of 320,000/mm3. Repeat lumbar puncture on day 50 of illness showed an opening pressure of 34–35 cm H20, WBC of 273/mm3 (with a differential of 46% lymphocytes, 46% eosinophils, 5% monocytes, 3% macrophages), RBC of 32/mm3, protein of 107 mg/dL, and glucose of 38 mg/dL. A brain MRI, performed after removal of the patient’s braces, was normal. Additional blood testing was negative, including: EBV PCR, Bartonella henselae IgG/IgM, Bartonella quintana IgG/IgM, Blastomyces antibody, Coccidioides IgG/IgM, Histoplasma antibody, HIV 1/2 antibodies, Cryptococcus antigen, Toxocara antibody, and Toxoplasma IgG/IgM. CSF acid-fast bacillus stain, cryptococcal antigen, and mycobacterial, fungal, aerobic and anaerobic cultures were also negative. Upon further questioning, the patient reported that he and his family had traveled to their vacation home in Kauai, Hawaii for the two weeks directly preceding the onset of symptoms. They had not stopped on any other Hawaiian island. During the trip, the family had found a dead rat in their hot tub, though the patient had not been in it. They had consumed organic lettuce from a local vendor and fresh produce from their herb garden. The patient denied exposure to seafood, mollusks or other exotic cuisine. The family had stopped in Los Angeles on their return trip home but had not ventured outside of the city. The patient denied any other travel, animal contact, or known insect bites. The patient’s exposure history prompted additional testing of the CSF, which confirmed the etiology of his eosinophilic meningitis.

Long-Term Outcomes and Risk Factors Associated With Acute Encephalitis in Children

Background Factors associated with poor outcomes of children with encephalitis are not well known. We sought to determine whether electroencephalography (EEG) findings, magnetic resonance imaging (MRI) abnormalities, or the presence of seizures at presentation were associated with poor outcomes. Methods A retrospective review of patients aged 0 to 21 years who met criteria for a diagnosis of encephalitis admitted between 2000 and 2010 was conducted. Parents of eligible children were contacted and completed 2 questionnaires that assessed current physical and emotional quality of life and neurological deficits at least 1 year after discharge. Results During the study period, we identified 142 patients with an International Classification of Diseases 9th Revision diagnosis of meningitis, meningoencephalitis, or encephalitis. Of these patients, 114 met criteria for a diagnosis of encephalitis, and 76 of these patients (representing 77 hospitalizations) had complete data available. Forty-nine (64%) patients were available for follow-up. Patients admitted to the intensive care unit were more likely to have abnormal EEG results (P = .001). The presence of seizures on admission was associated with ongoing seizure disorder at follow-up. One or more years after hospitalization, 78% of the patients had persistent symptoms, including 35% with seizures. Four (5%) of the patients died. Abnormal MRI findings and the number of abnormal findings on initial presentation were associated with lower quality-of-life scores. Conclusions Encephalitis leads to significant morbidity and death, and incomplete recovery is achieved in the majority of hospitalized patients. Abnormal EEG results were found more frequently in critically ill children, patients with abnormal MRI results had lower quality-of-life scores on follow-up, and the presence of seizures on admission was associated with ongoing seizure disorder and lower physical quality-of-life scores.

A comparison of H1N1 influenza among pediatric inpatients in the pandemic and post pandemic era.

BACKGROUND The novel influenza A H1N1 (A[H1N1]pdm09) strain emerged in 2009, contributing to significant morbidity and mortality. It is not known whether illness associated with A(H1N1) pdm09 in the post-pandemic era exhibits a similar disease profile. OBJECTIVE The objectives of this study were to compare the burden of disease of A(H1N1) pdm09 influenza from the 2009 pandemic year to the post-pandemic years (2010-2014), and to explore potential reasons for any differences. STUDY DESIGN We conducted a retrospective cohort study of inpatients admitted to Childrens Hospital Colorado with a positive respiratory specimen for influenza from May-December, 2009 and December, 2010-April, 2014. Univariate and multivariate analyses were conducted to compare the demographics and clinical characteristics of patients with H1N1 during the two periods. RESULTS There were 388 inpatients with influenza A(H1N1) pdm09 in 2009, and 117 during the post-pandemic years. Ninety-four percent of all H1N1 during the post-pandemic era was observed during the 2013-2014 influenza season. Patients with A(H1N1) pdm09 during the post-pandemic year were less likely to have an underlying medical condition (P<0.01). Patients admitted to the ICU during the post-pandemic year had a lower median age (5 vs 8 years, P=0.01) and a lower proportion of patients were intubated, had mental status changes, and ARDS compared with the pandemic years, (P<0.01 for all), with decreased mortality (P=0.02). CONCLUSION Patients with influenza A(H1N1) pdm09 during the post-pandemic years appeared to have less severe disease than patients with A(H1N1) pdm09 during the pandemic year. The reasons for this difference are likely multifactorial.