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Epidemiologic and Molecular Investigation of Outbreaks of Hepatitis C Virus Infection on a Pediatric Oncology Service

Anders Widell, MD, PhD; Bertil Christensson, MD, PhD; Thomas Wiebe, MD, PhD; Claes Schalén, MD, PhD; Hans Bertil Hansson, MD; Tobias Allander, MD, PhD; and Mats A.A. Persson, MD, PhD
[+] Article and Author Information

From University Hospital and the Regional Center for Communicable Disease Control, Malmö, Sweden; University Hospital, Lund, Sweden; and Karolinska Hospital, Stockholm, Sweden.


Ann Intern Med. 1999;130(2):130-134. doi:10.7326/0003-4819-130-2-199901190-00007
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Background: Despite screening of blood donors, hepatitis C virus (HCV) infection can occur in patients who receive multiple transfusions.

Objective: To clarify mechanisms of nosocomial transmission of HCV.

Design: Epidemiologic and molecular analyses of hepatitis C outbreaks.

Setting: Pediatric oncology ward.

Patients: Children with cancer.

Measurements: Epidemiologic analysis, HCV RNA detection, genotyping, and hypervariable region 1 (HVR1) sequencing.

Results: Ten cases of infection with acute HCV genotype 3a occurred between 1990 and 1993. Sequencing of HVR1 revealed three related strains. Despite an overhaul of hygiene procedures, a patient infected with genotype 1b generated nine subsequent infected patients in 1994. Several patients had high virus titers and strongly delayed anti-HCV antibody responses. All had permanent intravenous catheters. Multidose vials used for flushing or treatment had probably been contaminated during periods of overlapping treatment.

Conclusions: Contamination of multidose vials was the most likely mode of HCV transmission; therefore, use of such vials should be restricted. Rigorous adherence to hygiene routines remains essential to preventing transmission of bloodborne infections.

Figures

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Figure 1.
Top.HCVBottom.

Treatment periods at the pediatric oncology department during the outbreak of hepatitis C virus ( ) genotype 3a. Patients are grouped and designated according to strain similarity (A-3a, B-3a, C-3a, D-3a, and E-3; F-3a and G-3a; H-3a, I-3a, and J-3a). The horizontal width of the boxes indicates time spent in the inpatient ward; circles indicate 1-day treatments in the outpatient ward. White and black symbols represent periods during which available serum samples were HCV negative and HCV positive, respectively. Gray symbols denote periods during which no serum was available and viremia status was therefore unknown. Sequences of hypervariable region 1 (shown in bold type) and flanking regions of the HCV isolates detected during the genotype 3a outbreak. The isolates designated X-3a and Y-3a represent sequences obtained from genotype 3a transmitted at the adult hematology ward; patient X-3a was the adult index case, and patient Y-3a was the secondary case.

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Grahic Jump Location
Figure 2.
Top.HCVMEq/mLBottom.

Treatment periods at the pediatric oncology department during the outbreak of hepatitis C virus ( ) genotype 1b. The horizontal width of the boxes indicates time spent in the inpatient ward; circles indicate 1-day treatments at the outpatient ward. White and black symbols represent periods during which available serum samples were HCV negative and HCV positive, respectively. Gray symbols denote periods when no serum was available and viremia status was therefore unknown. The viral titers at certain points in time are indicated and expressed as millions of genomic equivalents per milliliter of plasma or serum ( ). All serologic specimens selected for quantification had been stored under optimal conditions, and none of these specimens tested negative by branched-DNA technique. Sequences of hypervariable region 1 (shown in bold type) and flanking regions of the HCV isolates detected during the genotype 1b outbreak. Data are lacking for patient N-1b (who seroconverted to antibody to HCV); the single viremic serum sample was exhausted, which made it impossible to amplify and sequence hypervariable region 1. Four isolates from a previously described outbreak (4) of nosocomially transmitted hepatitis C genotype 1b are shown for comparison; two of these isolates (Sthlm A and E) were related in that outbreak, and two others (Sthlm P and Q) were highly divergent.

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