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Clinical and epidemiologic characterization of WU polyomavirus infection, St. Louis, Missouri.

WU polyomavirus is a recently described polyomavirus found in patients with respiratory infections. Of 2,637 respiratory samples tested in St. Louis, Missouri, 2.7% were positive for WU polyomavirus by PCR, and 71% were coinfected with other respiratory viruses. Persistent human infection with WU polyomavirus is described.

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An initial report described the identification of WU polyomavirus in 6 (0.7%) of 890 respiratory tract samples collected in St. Louis, Missouri, USA, and in 37 (3.0%) of 1,245 respiratory tract specimens tested from Brisbane, Queensland, Australia (1). The goal of our study was to extend these initial findings by determining the prevalence of WU polyomavirus in a larger patient cohort in St. Louis.

The Study

We tested 2,637 nasopharyngeal swabs or nasal washes (from patients 1 day to 88 years of age) submitted to the virology laboratory at St. Louis Children's Hospital for routine respiratory virus detection from July 2003 through June 2004. Of these samples, 2,263 were from children [greater than or equal to] 4 years of age (including 419 newborns) and 374 were from children >4 years of age. The specimens were extracted with the automated Roche MagNA Pure LC extractor and MagNA Pure LC Total Nucleic Acid Isolation Kit (Roche Diagnostics, Indianapolis, IN, USA).

For real-time PCR, amplification primers WU-TAB02-F 5'-TGTTGCATCCATTTGTTACATTCAT-3' and WUTAB03-R 5'-GAAAGAACTGTTAGACAAATATATAGGCCTTA-3' and the minor groove binder probe WU-TAB04-pro 5'-6FAMATGTCAGCAAATTCMGBNFQ-3' were used with a commercially available universal TaqMan real-time PCR master mix and AB1 7500 Real-Time Thermocycler (Applied Biosystems, Foster City, CA, USA). All WU polyomavirus--positive specimens were screened for 17 additional viruses (influenza A and B; RSV A and B; PIV 1-4; human metapneumovirus; adenovirus subgroups B, C, and E; rhinovirus; and coronaviruses OC43, 229E, and NL63) by using the EraGen MultiCode-PLx respiratory virus panel as described previously (1).

Each clinical specimen was assigned a code. Collection of clinical data was approved by the Washington University Human Research Protection Office. Pertinent demographic, historical, and clinical information, when available, was collected by using a standard collection form. Statistical significance was determined by using 2-tailed Fisher exact [chi square] tests with Epi Info software version 3.4 (Centers for Disease Control and Prevention, Atlanta, GA, USA)

Seventy (2.7%) of the 2,637 tested specimens were positive for WU polyomavirus; 71% of the positive samples were also positive for [greater than or equal to] 1 other respiratory virus. Of the 70 positive samples, 5 were omitted from analysis because of chart unavailability. The remaining 65 samples were collected from 60 individual patients (5 specimens were serial samples associated with distinct clinical syndromes in 2 immunocompromised patients).

Of the 60 WU-positive patients, 31 (52%) were female. The ethnic breakdown was as follows: 50% African-American, 47% Caucasian, 3% other. Positive specimens were noted for patients 1 day to 15 years of age (online Appendix Table, available from www.cdc.gov/EID/content/13/12/1936-appT.htm). The highest and lowest rates of infection are displayed in the Figure, panel A.

Patients positive for WU polyomavirus were detected throughout the year. A small peak was observed in July 2003, and a second small peak was observed in April and May 2004 (Figure, panel B). WU polyomavirus was the only virus detected in a 1-day-old full-term infant delivered by cesarean section who had been transferred to St. Louis Children's Hospital with respiratory distress requiring intubation. He was afebrile with lung opacities on chest radiograph. Patent ductus arteriosus and pulmonary hypertension were eventually diagnosed.

The 3 oldest patients positive for WU polyomavirus in this cohort were immunosuppressed. They included a 12-year-old with Evans syndrome and a 15-year-old with severe combined immunodeficiency syndrome (both post-bone marrow transplant) and a 14-year-old with end-stage renal disease and asthma.

The most common clinical findings in the patients with WU polyomavirus are listed in the Table. The most frequent diagnoses were pneumonia (31%) (although 40% had positive bacterial cultures), bronchiolitis (25%), and upper respiratory tract infections (15%). We also compared all the measured parameters from the patients who were infected with WU alone to the patients who were co-infected with other viruses. In most cases, no statistically significant differences occurred between the co-infected and WU polyomavirus--only patients, except that more co-infected patients than WU polyomavirus--only patients had rhinorrhea (23/47 vs. 2/18; p = 0.005) and upper respiratory tract symptoms (30/47 vs. 6/18; p = 0.049). In addition, significantly more children with co-infection than with only WU polyomavirus had prior daycare exposure (18/45 vs. 1/15; p = 0.02).

[FIGURE A OMITTED]

The cohort of 2,637 samples included several sets of sequential samples taken from the same patient during the course of prolonged illness. In 2 patients, sequential samples obtained over a span of 6 8 weeks were positive for WU polyomavirus. The first patient was a 4-year-old girl with hemophagocytic lymphohistiocytosis, who had 4 distinct respiratory specimens that tested positive during a 2-month period. Her first positive specimen was obtained while she was asymptomatic during admission for a bone marrow transplant in September 2003. A second sample was obtained during a clinic visit for nasal congestion and cough in November 2003. Her third sample (also positive for coronavirus OC43) was obtained during an admission 5 days later for pneumonia. Finally, a fourth sample (negative for the previously detected coronavirus OC43) was taken 7 days later during the same admission after an episode of apnea.

The second patient was a 16-month-old child with biliary atresia admitted for a liver transplant in September 2003. He had 3 positive samples during a 6-week period. An initial sample taken on admission was negative for WU polyomavirus. Six weeks after transplant, fever and shortness of breath requiring intubation developed. A sample taken then was positive for both WU polyomavirus and adenovirus. Four weeks later, worsening shortness of breath and fever developed. His blood cultures were now also positive for Klebsiella and Enterobacter spp., and his third respiratory sample demonstrated both WU polyomavirus and rhinovims. Two weeks later, fever, hypoxia, and increasing secretions developed, with his fourth sample positive only for WU polyomavirus. Followup samples obtained 3 months later for each patient indicated clearance of WU virus.

Conclusions

Patients infected with WU polyomavirus in this cohort were primarily hospitalized with pneumonia, bronchiolitis, and upper respiratory tract infections. One new observation is that multiple respiratory specimens sampled from the same patient over 6-8 weeks were positive for WU polyomavirus, which suggests that WU polyomavirus may persistently infect humans. Both patients were immunocompromised, although they were able to clear infections with other viruses (coronavirus OC43, rhinovirus, adenovirus), which suggests that the continued detection of WU polyomavirus was not due to a completely incapacitated immune system. Sequence analysis of a 250-bp fragment of the VP2 gene of WU polyomavirus amplified from multiple samples from the 2 patients showed no sequence polymorphisms between the initial and later samples (data not shown). As some sequence variation has previously been reported in this locus (1), these data are consistent with the model of persistent infection. The detection of WU polyomavirus in the respiratory secretions of a 1-day-old infant suggests that vertical transmission of WU polyomavirus from mother to fetus may occur, although further studies are needed to verify this suggestion.

In conclusion, WU polyomavirus was detected in 2.7% of patients with respiratory tract infections. A high percentage of coinfection with other respiratory viruses was detected, complicating interpretation of the clinical findings. However, WU polyomavirus was the sole virus detected in 20 specimens from patients with respiratory illness, which suggests that it may be a respiratory pathogen. Finally, the observed persistence of this virus suggests analogy to BK and JC viruses in this regard (2).

Acknowledgment

We thank Monique Gaudreault-Keener for technical assistance.

This work was supported in part by National Institutes of Health grant U54 M057160 to the Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases.

All experiments described in this manuscript were performed at Washington University, St. Louis, MO, USA.

Dr Le is an infectious diseases fellow at Washington University in St. Louis. Her research focuses on characterization of novel human viruses.

References

(1.) Gaynor AM, Nissen MD, Whiley DM, Mackay IM, Lambert SB, Wu G, et al. Identification of a novel polyomavirus from patients with acute respiratory tract infections. PLoS Pathog. 2007 May 4;3(5): e64.

(2.) Chesters PM, Heritage J, McCance DJ. Persistence of DNA sequences of BK virus and JC virus in normal human tissues and in diseases tissues. J Infect Dis. 1983;147:676-84.

Address for correspondence: David Wang, Washington University School of Medicine, Campus Box 8230, 660 S Euclid Ave, St. Louis, MO 63110 USA; email: davewang@borcim.wustl.edu

Binh-Minh Le, * Lee M. Demertzis, * Guang Wu, * Robert J. Tibbets, * Richard Buller, * Max Q. Arens, * Anne M. Gaynor, * Gregory A. Storch, * and David Wang *

* Washington University School of Medicine, St. Louis, Missouri, USA
Table. Clinical parameters in episodes of WU polyomavirus
infection

Symptoms and physical examination findings (n = 65) %

Symptoms
 Cough 57
 Upper respiratory tract symptoms 55
 Rhonchi/crackles/coarse breath sounds 46
 Shortness of breath or increased work of breathing 42
 Wheezing 40
 Rhinorrhea 38
 Retractions 37
 Decreased oral intake 34
 Vomiting 32
 Diarrhea 18
 Stridor 6
 Rash 6
 Apnea 5

Signs
 Tachypnea * (n =57) 79
 Hypoxia ([dagger]) (n = 55) 47
 Fever ([double dagger]) (n = 63) 41
 Bandemia (n = 42) 40
 Leukocytosis ([section]) (n = 42) 31
 Leukopenia ([paragraph]) n = 42) 10

Radiographic or computed tomographic findings (n = 50)
 Infiltrate or consolidation 72
 Hyperinflation 14
 Peribronchial cuffing 12
 Effusions 6

Treatment
 Antimicrobial agents (n = 65) 58
 Bronchodilators (n = 65) 38
 Steroids (n = 65) 37
 Oxygen (n = 65) 25
 Intubation (n = 63) 11
 Intensive care (n = 63) 19

Risk factors
 Daycare 32
 Sick contacts 25

Medical history
 Asthma (n = 60) 37

* Defined per National Institutes of Health clinical center guidelines.

([dagger]) Sa[O.sub.2] [less than or equal to] 95% or Pa[O.sub.2] >80%.

([double dagger]) Temperature [greater than or equal to] 38[degrees]C.

([section]) Leukocyte count >15,000/[mm.sup.3].

([paragraph]) Leukocyte count <4,000/[mm.sup.3].
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Article Details
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Title Annotation:DISPATCHES
Author:Le, Binh-Minh; Demertzis, Lee M.; Wu, Guang; Tibbets, Robert J.; Buller, Richard; Arens, Max Q.; Gay
Publication:Emerging Infectious Diseases
Geographic Code:1USA
Date:Dec 1, 2007
Words:1676
Previous Article:Enhanced Subtyping scheme for Salmonella Enteritidis.
Next Article:WU polyomavirus in children, Canada.
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