Hepatitis E virus infection in Turkey

The real change in the American gun debate over the past decade has been the view of guns as a public health problem. The fact that over 30 000 Americans have died from gunshot wounds each year over the past three decades makes this an issue that any conscientious physician concerned with the public’s health cannot ignore.’ It is true that crime, including assault, in the UK is not less than that in the USA. Indeed, for certain types of crime, such as motor vehicle theft, the UK rates are higher than those of the USA.2 However, homicide rate is strikingly lower, and it takes a great deal of cognitive dissonance to believe that the differences in gun availability between the two countries do not play a part. Then there is the issue of suicide: it is an issue that the NRA and other gun advocates conveniently ignore, despite the fact that there are more firearm deaths from suicide than homicide.’ Undoubtedly, many of these deaths would occur irrespective of gun availability; however, the presence of a handgun in the home greatly increases the risk of suicide to members of the

household.3 The magnitude of this public health problem demands that it be discussed in the pages of medical journals, and not confined

sociological or criminology publications. Any other cause of death of this magnitude-whether it be AIDS, meningitis, or motor-vehicle crashes-would, and does, receive the attention of the medical community. The role of medical journals is to to

present the results of scientific research to the medical and public health community and provide a forum for discussion of its importance and public policy implications. Your editorial has served that end well.

Anti-HEV antibodies were detected in 4 cases, 1 of 25 anti-HAV IgM positive cases, 1 of 10 HCV positive patients, and 2 (11 %) of 18 non-A, non-B, non-C cases. In Turkey, less than 10% of acute hepatitis cases are classified as non-A, non-B, non-C hepatitis. Thus, it was estimated that HEV infections represented 4%, of all acute hepatitis cases. Moreover, serum samples from 24 other subjects who were previously anti-HEV positive by Genelabs test were reinvestigated for antibodies to HEV with the two tests. Only 7 (29%) of these subjects proved anti-HEV positive. These data confirm a higher rate of HEV infection in Turkey than that recorded in Europewhere anti-HEV antibodies are present in 0-4% of the general population and in 2.1 % of the hepatitis cases. However, as in Europe, the role of HEV is much less important than that of HAV, HBV, and HCV, and a prevalence of 6% in Turkey seems to be an overestimate. A more

probable figure is only 1-2 °/, .

P Coursaget, N

Depril

Institut de Virologie de Tours, Faculté de Pharmacie, 37042 Tours, France

O Sadi Yenen, S

Cavuslu, S Badur

Department of Infectious Diseases, Gulhane Military Medical Academy and Department of Microbiology, Istanbul Faculty of Medicine, Istanbul, Turkey

1

Coursaget P, Buisson Y, Depril N, et al. Mapping of linear B-cell epitopes on open reading frames 2 and 3 encoded proteins of hepatitis E virus using synthetic peptides. FEMS Microbiol Lett 1993; 109:

2

Zaaijer H, Mok M, Lelie PN, et al. Hepatitis E in the Netherlands: imported and endemic. Lancet 1993; 341: 826.

251-56.

Frederick P Rivara Harborview Injury Prevention and Research Center, University of Washington, Seattle, USA

Washington,

Jonathan P

Shepherd

Department of Oral Surgery, Medicine, and Pathology, University of Wales College of Medicine, UK

David P Farrington Institute of

1 2 3

Criminology, University of Cambridge, Cambridge CB3 9DT,

UK

Baker SP, O’Neill B, Ginsburg MJ, Li G. The injury fact book, 2nd ed. New York: Oxford University Press, 1992. Farrington DP, Langan PA. Changes in crime and punishment in England and America in the 1990’s. Justice Quart 1992; 9: 5-46. Kellermann AL, Rivara FP, Somes G, et al. Suicide in the home in relation to gun ownership. N Engl J Med 1992; 327: 467-72.

Hepatitis

E virus infection in

Turkey

SiR-Thomas and colleagues (June 19, p 1561) report a prevalence of anti-hepatitis E (HEV) of 6% in Turkey, suggesting a higher prevalence of this disease in that country than in European countries and the existence of a consequent number of HEV sporadic cases, since there is no evidence of non-A, non-B, non-C hepatitis outbreaks in this population. We have investigated anti-HEV antibodies in patients from the Istanbul area with non-A, non-B, non-C acute hepatitis (n = 18), and in patients with type A (25), type B (10), and type C (10) acute hepatitis. To detect anti-HEV antibodies, two enzyme-linked immunosorbent assays were used. The first’ was based on microtitre plates coated with synthetic peptides representing two epitopes from the open reading frame 3 of

HEV, and the second

beads coated with two recombinant antigens representing sequences from open reading frames 2 and 3 of HEV (Abbott Diagnostika, Wisbaden Delkeneim). Immunoglobulins bound to HEV antigens were detected with horseradish peroxidase labelled antibodies directed against human immunoglobulins in the second test, but against only human IgG in the first.

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on

Authors’reply SiR-We thank Coursaget and colleagues for their contribution to our understanding of the serological diagnosis of HEV infections. Currently, there is no serological gold standard for HEV diagnosis. Therefore, the sensitivity and specificity of an assay must be assessed either in experimentally-infected laboratory animals or in outbreak investigations. From such studies, it seems that multiple antigens from different HEV isolates must be incorporated into assays if they are to reliably detect IgM and IgG antibodies to HEV (anti-HEV).1 In addition, assays that detect only IgM anti-HEV will lose reactivity by 12 months, and will therefore give an underestimation of anti-HEV prevalence.2 In our investigation, we determined the rate of anti-HEV (5-9 [1’3%]) in the general population of Turkey by testing 1350 individuals, aged 15-88, from five regions of the country. Anti-HEV was associated with older age, residence in warmer climates, and lower socioeconomic indicators. The lower estimate of anti-HEV prevalence reported by Coursaget and colleagues may relate to both serological and epidemiological differences. The assay developed in Coursaget’s laboratory is apparently more reactive with IgM anti-HEV, since half those tested with his assay in an outbreak evaluation lost reactivity at 6-12 months.2 Therefore, the lower measurement of anti-HEV with this test is not unexpected. Unfortunately, the comparison of the assays used by Coursaget and that kindly provided to us by Genelabs was not based on serum samples from individuals evaluated in our study. Thus it is difficult to make any direct comparisons between our serological results. However, the selection of Coursaget’s patients from Istanbul, where we found the lowest prevalence of anti-HEV, and other possible differences in the ages or socioeconomic levels of his participants, may explain their lower estimate of anti-HEV. In addition, it is very difficult to estimate a population prevalence of HEV with a small sample size. The 11 % prevalence of anti-HEV that they report among 18 patients with acute non-A, non-B, non-C hepatitis carries a 95% CI of 17%.

In our investigation, anti-HEV was not detected in any of 105 persons under 26 years of age. This finding probably reflects recent improvements in sanitation resulting from the country’s economic development. Therefore, younger Turkish residents probably will, as Coursaget points out, have a prevalence of anti-HEV more similar to their European neighbours than to their parents’ generation. Future studies of the prevalence of anti-HEV in Turkey and other countries should account for the effects of age and socioeconomic factors. David L Thomas, Thomas C Quinn Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

1 Lok ASF, Yarbough PO, Kwan WK, Moeckli R. Comparison of reactivity to ORF2 and ORF3 HEV antigens in IgG and IgM anti-HEV assays. International symposium of viral hepatitis and liver

disease, Tokyo, Japan, 1993: abstract 694. 2 Coursaget P, Depril N, Buisson Y, et al. Peptide based ELISA for the detection of anti-HEV antibodies-application to the detection of HEV infections in France and Africa. International symposium of viral hepatitis and liver disease, Tokyo, Japan, 1993: abstract 684.

Screening for biliary atresia SIR-Referral, for investigation and assessment, of babies jaundiced beyond age 14 days has been advised.1,2 However, the UK Children’s Liver Disease Foundation (CLDF) has recommended that babies jaundiced at age 14 days have a urine and blood test (likely to mean venepuncture), although it is not clear how many will be jaundiced at that age. The commentary by Logan and Stanton (July 31, p 256) is both timely and helpful. They urge caution about the introduction of this new form of screening. They also refer to an unpublished study suggesting that 15% of babies are still jaundiced at age 2 weeks. They do not say

how these babies

were

fed.

Breastfeeding is associated with higher prevalence of neonatal jaundice and higher peak bilirubin levels.1,3 At age 2 weeks some babies will still have physiological jaundice, being at the "tail end" of a declining curve of bilirubin concentrations. Transcutaneous bilirubin measurement at age 3 weeks4 revealed that 5 out of 16 breast-fed babies had raised bilirubin, defined as above 3 mg/dL (51-3 µmol/L), and many will not have been clinically jaundiced. In 893 babies we founds clinically persistent jaundice, confirmed by blood sampling, in 2-4% of breast-fed and in no formula-fed babies at 3 weeks of age. Since 45% of babies were formula fed, persistent jaundice was present only in 1.3%, of all babies. Gartner6 commented that this was higher than other estimates of prolonged jaundice in the newborn (0.5%)) but that our figure may have been an underestimate because we only included babies who were still jaundiced on discharge from hospital. No babies with abnormal conjugated bilirubin levels were found in our small

sample. It seems inevitable therefore that more breast than formulafed infants would be subject to investigation at age 14 days in the proposed screening programme. It is not yet clear what

if 3 weeks, as proposed by Logan and Stanton, had been chosen as the age for investigation of otherwise well babies, without the

potential of a high false-positive rate. Roderick MacFaul Paediatric Department, Pinderfields Hospital, Wakefield WF1 4DG, UK

Newman TB, Maisels MJ. Evaluation and treatment of jaundice in the term newborn: a kinder, gentler approach. Pediatrics 1992; 89: 809-18. 2 Mackinlay GA. Jaundice persisting beyond 14 days after birth. BMJ 1993; 306: 1426-27 3 Kivihan C, James EJP. The natural history of neonatal jaundice. Pediatrics 1984; 74: 364-70. 4 Maisels MJ, D’Arcangelo MR. Breast feeding and jaundice in the first six weeks of life, abstracted. Pediatr Res 1983; 17: 324A. 5 Winfield CR, MacFaul R. Clinical study of prolonged jaundice in breast and bottle fed babies. Arch Dis Child 1978; 53: 506-07. 6 Gartner L. Year book of pediatrics. Chicago: Year Book, 1980: 39-40. 1

Gallbladder dysfunction induced by botulinum A toxin SIR-A 43-year-old woman with blepharospasm since 1984 received three series of injections of botulinum A toxin into the orbicularis oculi muscles between 1986 and 1992 with good therapeutic effect. About 3 weeks after each session (3 ng toxin-haemagglutinin-complex, equivalent to 120 mU; Dysport), she developed single episodes of biliary colics without having had any history of gallbladder disease. All investigations were normal except for biliary sludge on ultrasound in the last episode in 1992. In December, 1992, cholecystectomy was done. No further biliary colic occurred after the next two botulinum-A-toxin injections. To examine the relation between locally administered botulinum toxin1 and a distant effect on gallbladder function, fasting gallbladder volume by planimetry (represented by the largest possible area); and gallbladder emptying 45 min after a standard fatty meal were measured by ultrasound in six patients before and after injections of botulinum A toxin on days 0, 8,15,22, and 29.2,3 In all four patients who received 12-5 ng botulinum A toxin, gallbladder emptying, measured by an insufficient reduction in size, was abnormal on day 8 or 15 compared with day 0 (table). No sonographic abnormalities could be found in the two patients who received lower doses. None of the patients recorded any gastrointestinal symptoms on a daily written questionnaire during the observation period. Botulinum toxin blocks acetylcholine release, predominantly at the skeletal neuromuscular junction but also at cholinergic terminals in the autonomic nervous system.4 Therapeutically, botulinum toxin acts on cardiovascular autonomic pathways.s Our observations provide evidence for dose-dependent impaired gastrointestinal autonomic

pathways. Recurring biliary colics, as we saw, might have been induced by a systemic effect of botulinum A toxin, producing

impact the CLDF campaign has had on parents and on primary care, laboratory, and paediatric services. Newman and Maisels’ advising caution in the use of phototherapy earlier in the neonatal period,! states: "at a time when paediatricians are trying to promote breast feeding in the face of considerable odds (early discharge from hospital, the rapid return of mothers to the work force, commercial marketing of formula etc) we should pay attention to an intervention which has a negative impact on the nursing mother". This comment is apposite to the screening now under discussion since mothers may see this screening as just another medical intervention being applied to a significant proportion of healthy babies. Earlier identification of biliary atresia can probably be achieved

*Toxin-haemagglutinin-complex. Table: Gallbladder volume (%) after treatment with botulinum A toxin in patients with torticollis or blepharospasm

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