Autochthonous Infections with Hepatitis E Virus Genotype 4, France

Philippe Colson

, Pauline Romanet, Valérie Moal, Patrick Borentain, Raj Purgus, Alban Benezech, Anne Motte, and René Gérolami

Author affiliations: Institut Hospitalo-Universitaire Méditerranée Infection, Marseille, France (P. Colson, P. Romanet, A. Motte); Aix-Marseille Université, Marseille (P. Colson); Hôpital Conception, Marseille (V. Moal, R. Purgus); and Centre Hospitalo-Universitaire Conception, Marseille (P. Borentain, A. Benezech, R. Gérolami)

Abstract

During January–March 2011, diagnoses of hepatitis E virus (HEV) infection increased in Marseille University hospitals in southeastern France. HEV genotype 4, which is described almost exclusively in Asia, was recovered from 2 persons who ate uncooked pork liver sausage. Genetic sequences were 96.7% identical to those recently described in swine in Europe.

In industrialized countries, most cases of hepatitis E virus (HEV) infection in humans are autochthonous (1). Pigs are a major reservoir of HEV, and transmission of virus to humans who ate raw or undercooked pork has been reported (1–3). In France, >300 cases of HEV infection are reported annually (3); most infections are autochthonous and occur in southern France, where the prevalence of anti-HEV IgG is higher than in northern France (3–5). Almost all cases of autochthonous HEV infection reported in Europe have involved genotype 3 strains (1–6).
Beginning February 21, 2011, a biosurveillance program (EPIMIC) (7) detected an increase in the number of HEV infections diagnosed at Marseille University hospitals in southeastern France. During February 21–March 28, the weekly number of serum samples that were tested and found positive for HEV was above the elected critical threshold (Technical Appendix Figure 1

[PDF - 419 KB - 4 pages]).

The Cases

In Marseille during January–March 2011, a total of 11 cases of HEV infection were confirmed by anti-HEV IgM testing and detection of HEV RNA in serum samples. EIAgen assays (Adaltis Italia, Casalecchio di Reno, Italy) were used to detect anti-HEV IgM and IgG. Additional anti-HEV IgM testing was performed by using the Assure HEV IgM Rapid Test (MP Biomedicals, Illkirch, France) and the recomLine HEV IgG/IgM test (Mikrogen Diagnostik, Neuried, Germany). HEV RNA was detected by using a real-time reverse transcription PCR targeting open reading frame (ORF) 2 (2).
The mean age of the case-patients was 57 years (±11 years). Of the 11 case-patients, 10 were male and 3 were kidney transplant recipients (Table 1, Table 2). HEV infection was clinically asymptomatic in all transplant recipients; the infection was diagnosed after routine posttransplant laboratory tests showed elevated levels of liver enzymes. Longitudinal testing indicated chronic HEV infection in 1 case-patient (no. 5), and an 80-year-old case-patient died 9 weeks after disease onset.
HEV 5′-ORF2 RNA was recovered from the serum of 8 case-patients. Phylogenetic analysis (2) showed that 4 patients each had HEV genotype 3c or 3f (Technical Appendix Figure 2

[PDF - 419 KB - 4 pages]). Sequences from 2 unrelated case-patients (nos. 7, 8) showed 99.8% identity; for other pairwise comparisons, maximal identity was 93.4% (mean 83.6%).