Transfusion-associated Hepatitis E, France.To the Editor: Hepatitis E virus (HEV HEV
hepatitis E virus
hemagglutinating encephalomyelitis virus of pigs. ) is a leading cause of acute and fulminant ful·mi·nant
Occurring suddenly, rapidly, and with great severity or intensity, usually of pain.
ful hepatitis in developing countries (1). In industrialized in·dus·tri·al·ize
v. in·dus·tri·al·ized, in·dus·tri·al·iz·ing, in·dus·tri·al·iz·es
1. To develop industry in (a country or society, for example).
2. countries, HEV seroprevalence rates of 0.4%-3% are common, and evidence is mounting that autochthonous autochthonous /au·toch·tho·nous/ (aw-tok´thah-nus)
1. originating in the same area in which it is found.
2. denoting a tissue graft to a new site on the same individual. transmission might account for a substantial proportion of infections (1-3). Whereas fecal-oral HEV transmission is preponderant pre·pon·der·ant
Having superior weight, force, importance, or influence. See Synonyms at dominant.
pre·ponder·ant·ly adv. in developing countries, other routes have been demonstrated in industrialized countries, among them consumption of pork or boar meat (1,4). Parenteral transmission was first suggested but not demonstrated (5,6). Because viruses cannot be fully inactivated inactivated
rendered inactive; the activity is destroyed.
treated so that they are no longer able to produce evidence of growth or damaging effect on tissue. in blood products, HEV recently emerged as a transfusion-transmitted pathogen, with 6 reported cases, including 3 in which comparative analysis of HEV sequences from blood donor and recipient was performed (7). We describe what is, to our knowledge, the first case in France and the first case worldwide involving a child as blood recipient.
A 7-year-old boy was examined in June 2006; he had erythematous-papulous skin and an increased level of alanine aminotransferase (ALT, 796 IU/L) of 1 week's duration. From October 2005 to May 2006, he had received several courses of combined chemotherapy for a rhabdoid tumor in his kidney. Therapy included carboplatin, cyclophosphamide cyclophosphamide /cy·clo·phos·pha·mide/ (-fos´fah-mid) a cytotoxic alkylating agent of the nitrogen mustard group; used as an antineoplastic, as an immunosuppressant to prevent transplant rejection, and to treat some diseases , etoposide, adriamycin, and vincristine vincristine /vin·cris·tine/ (vin-kris´ten) an antineoplastic vinca alkaloid; used as the sulfate salt in the treatment of various neoplasms, including Hodgkin's disease, acute lymphocytic leukemia, non-Hodgkin's lymphoma, Kaposi's , and, because of the chemotherapy's hematotoxicity, the patient required 22 transfusions of concentrated erythrocytes or platelets. Peak levels of ALT and bilirubin Bilirubin
The predominant orange pigment of bile. It is the major metabolic breakdown product of heme, the prosthetic group of hemoglobin in red blood cells, and other chromoproteins such as myoglobin, cytochrome, and catalase. were reached 4 weeks after onset of hepatitis (2,001 IU/L and 49 [micro]mol/L, respectively), and ALT levels returned to normal range (8-45 IU/L) 6 weeks later. During a follow-up examination, the boy's prothrombin prothrombin
Carbohydrate-protein compound in plasma essential to coagulation. In response to bleeding, a complex series of clotting-factor interactions leads to its conversion by thromboplastin to thrombin, which transforms fibrinogen in plasma into fibrin. index remained >80%, and clinical signs mostly consisted of clinical jaundice. HEV diagnosis was established by detection in serum of HEV antibodies (EIAgen Kits, Adaltis Development Inc., Laval, Quebec, Canada) and HEV RNA RNA: see nucleic acid.
in full ribonucleic acid
One of the two main types of nucleic acid (the other being DNA), which functions in cellular protein synthesis in all living cells and replaces DNA as the carrier of genetic with in-house assays. Other infectious or noninfectious causes of acute hepatitis were excluded. HEV immunoglobulin M (IgM) was weakly positive in June 2006 (optical density ratio = 1.6), then strongly positive the next month (ratio = 10.8); IgG remained negative. HEV RNA was detected from serum samples collected in June 2006 by an in-house real-time PCR PCR polymerase chain reaction.
polymerase chain reaction
Polymerase chain reaction (PCR) that targeted the open reading frame 2 region of the HEV genome. Sequences of primers/ probe are as follows: HevMrsRT fwd: 5'-AATTRATTTCGTCGGCY GG-3'; HevMrsRTRev: 5'- ACW GTCGGCTCGCCATTG-3'; HevMrsFam: 5'-FAM-ACTCYCGC CASGTYGTCTCA-TAMRA-3'.
Serum samples taken from 12 U of blood products that the child received during the 3-month period before onset of hepatitis were tested for HEV RNA; 1 sample was positive. Concentrated erythrocytes (310 mL) from this positive blood donation were transfused to the child in May 2006, 4 weeks after collection and 6 weeks before acute hepatitis developed. HEV IgG and IgM antibodies were not detected in the blood donation, which indicates that the blood donation occurred during the prodromic pro·drome
n. pl. pro·dromes or pro·dro·ma·ta
An early symptom indicating the onset of an attack or a disease.
[French, from Latin prodromus, precursor, from Greek phase of HEV disease. HEV nucleotide sequences from the blood donor and recipient were identical. Phylogenetic analysis showed that they clustered together and were closely related to genotype 3f, which is prevalent in Europe (Figure ).
The blood donor was a 24-year-old man. He did not travel outside metropolitan France for 8 months before donating blood. Anti-HEV IgG seroconversion was observed on a serum sample collected 24 weeks after blood donation, whereas anti-HEV IgM and serum HEV RNA tested negative. ALT levels were within normal values at the time of blood donation and 24 weeks later. No clinical signs were reported at any time. No other recipient received blood products from this donor.
Our data show that HEV was transmitted from 1 blood donor to the recipient child. On the basis of retrospective HEV RNA detection, 6 other transfusion-transmitted HEV infections, all involving adult blood recipients, have occurred in HEV-hyperendemic and industrialized countries (7). Transfusion-transmitted HEV strains belonged to different genotypes/subtypes that corresponded to those found in the same geographic areas (Figure).
In France, neither HEV antibodies nor HEV RNA are systematically tested in blood donors, and blood donations currently are not tested for ALT. In the absence of systematic HEV RNA testing, HEV diagnosis in blood donations may be hampered by HEV viremia viremia /vi·re·mia/ (vi-re´me-ah) the presence of viruses in the blood.
The presence of viruses in the bloodstream. before clinical onset and anti-HEV seroconversion, the possible short persistence or absence of HEV antibodies, and the high frequency of subclinical infections (1,2,5). On the basis of these data, improved knowledge of HEV epidemiology in the general population and in blood donors is needed in industrialized countries to guide HEV screening policy for blood products.
Another concern of transfusion-transmitted HEV infections is the potential severity of acute hepatitis E. Previously reported cases of contamination through transfusion and our case showed spontaneous recovery. However, although typically self-limited, hepatitis E is potentially life-threatening with mortality rates of 0.2%-4%, reaching 20% in pregnant women (1). Fatal outcome has also been described in children (9). In summary, HEV-contaminated blood donations are a challenge for diagnosis and virus safety of transfusion, including in industrialized countries.
We are indebted to Didier Raoult for his valuable comments and support and also to Dominique Legrand and Sophie Simon for their participation in the transfusion investigation.
Philippe Colson, * ([dagger]) Carole Coze, * Pierre Gallian, ([dagger]) ([double dagger]) Mireille Henry, * ([dagger]) Philippe De Micco, ([dagger]) ([double dagger]) and Catherine Tamalet * ([dagger])
* Centre Hospitalier Regional Universitaire, Timone, Marseille, France; ([dagger]) Universite de la Mediterranee, Marseille, France; and ([double dagger]) Etablissement Francais du Sang Alpes-Mediterranee, Marseille, France
(1.) Worm HC, van der Poel WH, Brandstatter G. Hepatitis E: an overview. Microbes Infect. 2002;4:657-66.
(2.) Peron JM, Mansuy JM, Poirson H, Bureau C, Dupuis E, Alric L, et al. Hepatitis E is an autochthonous disease in industrialized countries. Analysis of 23 patients in South-West France over a 13-month period and comparison with hepatitis A. Gastroenterol Clin Biol. 2006;30:757-62.
(3.) Ijaz S, Arnold E, Banks M, Bendall RP, Cramp ME, Cunningham R, et al. Non-travel-associated hepatitis E in England and Wales England and Wales are both constituent countries of the United Kingdom, that together share a single legal system: English law. Legislatively, England and Wales are treated as a single unit (see State (law)) for the conflict of laws. : demographic, clinical, and molecular epidemiological characteristics. J Infect Dis. 2005; 192:1166-72.
(4.) Li TC, Chijiwa K, Sera N, Ishibashi T, Etoh Y, Shinohara Y, et al. Hepatitis E virus transmission from wild boar meat. Emerg Infect Dis. 2005;11:1958-60.
(5.) Arankalle VA, Chobe LP. Hepatitis E virus: can it be transmitted parenterally? J Viral Hepat. 1999;6:161-4.
(6.) Psichogiou MA, Tassopoulos NC, Papatheodoridis GV, Tzala E, Klarmann R, Witteler H, et al. Hepatitis E virus infection in a cohort of patients with acute non-A, non-B hepatitis non-A, non-B hepatitis
n. Abbr. NANB hepatitis
Hepatitis that is caused by a virus that is antigenically different from hepatitis viruses A and B. . J Hepatol. 1995;23: 668-73.
(7.) Boxall E, Herborn A, Kochethu G, Pratt G, Adams D, Ijaz S, et al. Transfusion-transmitted hepatitis E in a 'nonhyperendemic' country. Transfus Med. 2006; 16:79-83.
(8.) Lu L, Li C, Hagedorn CH. Phylogenetic analysis of global hepatitis E virus sequences: genetic diversity, subtypes and zoonosis Zoonosis Definition
Zoonosis, also called zoonotic disease refers to diseases that can be passed from animals, whether wild or domesticated, to humans. . Rev Med Virol. 2006;16:5-36.
(9.) Arora NK, Nanda SK, Gulati S, Ansari IH, Chawla MK, Gupta SD, et al. Acute viral hepatitis types E, A, and B singly and in combination in acute liver failure Acute liver failure is the appearance of severe complications rapidly after the first signs of liver disease (such as jaundice), and indicates that the liver has sustained severe damage (loss of function of 80-90% of liver cells). in children in north India. J Med Virol. 1996;48:215-21.
Address for correspondence: Philippe Colson, Laboratoire de Virologic, Federation Hospitaliere de Bacteriologie-Virologie Clinique et d'Hygiene, CHRU CHRU Centre Hospitalier Régional Universitaire (French: Regional University Hospital) Timone, 264 rue Saint-Pierre 13385, Marseille CEDEX 05, France; email address: philippe.colson@ ap-hm.fr