Use of the Minimum Spanning Tree Model for Molecular Epidemiological Investigation of a Nosocomial Outbreak of Hepatitis C Virus Infection

Abstract

The minimum spanning tree (MST) model was applied to identify the history of transmission of hepatitis C virus (HCV) infection in an outbreak involving five children attending a pediatric oncology-hematology outpatient ward between 1992 and 2000. We collected blood samples from all children attending since 1992, all household contacts, and one health care worker positive for antibody to HCV (anti-HCV). HCV RNA detection was performed with these samples and with smears of routinely collected bone marrow samples. For all isolates, we performed sequence analysis and phylogenetic tree analysis of hypervariable region 1 of the E2 gene. The MST model was applied to clinical-epidemiological and molecular data. No additional cases were detected. All children, but not the health care worker, showed genotype 3a. On six occasions, all but one child had shared the medication room with another patient who later seroconverted. HCV RNA detection in bone marrow smears revealed, in some cases, a delay of several months in anti-HCV responses. Sequence analysis and phylogenetic tree analysis revealed a high identity among the isolates. The MST model applied to molecular data, together with the clinical-epidemiological data, allowed us to identify the source of the outbreak and the most probable patient-to-patient chain of transmission. The management of central venous catheters was suspected to be the probable route of transmission. In conclusion, the MST model, supported by an exhaustive clinical-epidemiological investigation, appears to be a useful tool in tracing the history of transmission in outbreaks of HCV infection.Since the introduction of blood donor screening through antibody testing, the risk of acquiring infection with hepatitis C virus (HCV) through the transfusion of blood or blood products has dramatically decreased in industrialized countries (8,28,34). Nonetheless, the nosocomial transmission of HCV continues to occur (21). Several recent studies provided evidence of patient-to-patient transmission in most of the cases of nosocomial transmission (2, 5, 6, 9, 13, 15-17, 19, 20, 29, 36), although some studies also reported transmission from health care workers to patients and vice versa (10,26,32).In recent years, the use of molecular biology techniques has proven to be a powerful tool in the epidemiological investigation of HCV infection in health care facilities and other settings (2,4,6,9,10,13,15,16,19,20,24,30,32). In particular, phylogenetic tree analysis has often been used to identify the original source of infection. However, this technique does not allow a detailed history of transmission to be traced or the modes of transmission to be identified, except in cases of provider-to-patient transmission.In an attempt to more completely describe nosocomial outbreaks of HCV infection, we adopted a parsimonious theoretical approach, referred to as the minimum spanning tree (MST) model (see Appendix). The MST approach, a concept of the graph theory, represents one of the most common problems of combinatorial optim...

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