OUTBREAK OF ENTERICALLY TRANSMITTED NON-A, NON-B HEPATITIS AMONG SCHOOLCHILDREN

1199 Ten children with constipation (seven male, three female aged 1-10 years) and ten children without constipation (six male, four female, aged 1-12 years) were studied. Effective (EASP) and maximum (MASP) anal sphincter pressures were 34 (SD 0-2) cm water and 60-3 (3-3) cm, respectively, in constipated children and 27 (0’3)cm and 593 (33) cm in the controls. EASP was greater in the constipated children than in the controls (p <0 001) but there was no significant difference in MASP. Department of Paediatrics, Turkish Health and Therapy Foundation, Memorial Ahmet Örs Hospital, 06510 Emek, Ankara, Turkey

I. SAFA KAYA UGUR DILMEN MEHMET CEYHAN

Department of Urology, Gulhane Military Medical Academy

REMZI SAGLAM

Bright TC. Urethral pressure profile: current concepts. J Urol 1977; 118: 418-22. 2. McGuire EJ Combined radiographic and manometric assessment of urethral sphincter function. J Urol 1977; 118: 632-35. 1.

CREUTZFELDT-JAKOB DISEASE, SPIROPLASMAS, AND CRYSTALLINE ARTIFACTS

SIR,-Creutzfeldt-Jakob disease (CJD) is caused by an unidentified infectious agent. One school of thought implicates subviral prions.1 Another indicts spiroplasma: spiroplasma-like inclusions have been observed in patients with CJD,z,3 Spiroplasma mirum provokes spongiform encephalopathy in the rat,’ and scrapie-associated fibril protein seems to be serologically similar to the fibril protein purified from S mirum.1 In 1980 Gray et al6 reported spiral membranous inclusions in the axoplasm of a 51-year-old woman who had symptoms suggestive of CJD, but we believe that they erroneously interpreted crystalline artifacts as spiroplasma fragments. The structure reported by Gray et al and the crystalline artifacts we observe when searching for spiroplasmas

formvar films stained in 2% phosphotungstic acid at pH 6-3 are (figure, a and b). As an example, S sabaudiense and the clearly distinguishable outline of its plasma membrane (figure, c) resemble neither of the above structures. This specimen (c) was prepared in a similar manner to that illustrated in (b) and shows the helical morphology of the exponential growth phase. The branching shown in (a) is typical of crystals we observe. Not all spiroplasmas seem to share the pathogenic capacity of S mirum. The mosquito isolate, S sabaudiense, did not produce death or significant weight loss on intracerebral inoculation into day-old suckling mice, nor did it survive for more than 48 h at 37°C in spiroplasma growth medium SP4. However, antibody to this organism has been reported in a 35-year-old patient with amyotrophic lateral sclerosis and a 70-year-old male "control" during a serological study of five spiroplasmas and central-nervoussystem disorders.7 on

very similar

Department of Bacteriology, Virology, and Parasitology, Faculty of Medicine, 29285 Brest, France

I. HUMPHERY-SMITH C. CHASTEL

1. Prusiner SB. Prions and neurodegenerative diseases. N Engl J Med 1987; 317: 1571-81. 2. Bastian FO. SpirOplasma-like inclusions in Creutzfeldt-Jakob disease. Arch Pathol Lab Med 1979; 103: 665-69. 3 Bastian FO, Hart MN, Cancilla PA. Additional evidence of spiroplasma in Creutzfeldt-Jakob disease. Lancet 1981; i: 660. 4. Bastian FO, Pumell DM, Tully JG. Neuropathology of spiroplasma infection in rat brain Am J Pathol 1984; 114: 496-514. 5 Bastian FO, Jennings RA, Gardner WA. Antiserum to scrapie-associated fibril protein cross-reacts with Spiroplasma mirum fibril proteins. J Clin Microbiol 1987; 25: 2430-31 6. Gray A, Francis RJ, Scholtz CL Spiroplasma and Creutzfeldt-Jakob disease Lancet 1980, ii 152 7 Chastel C, Le Goff F, Goas JY, Goaguen J, Kerdraon G, Simitzis-Le Flohic AM. Serosurvey on the possible role of mosquito spiroplasma in central nervous system disorders in man. Zbl Bacteriol Hyg (in press).

OUTBREAK OF ENTERICALLY TRANSMITTED NON-A, NON-B HEPATITIS AMONG SCHOOLCHILDREN

SIR,-Outbreaks of enterically transmitted non-A, non-B hepatitis (NANBH) usually affect young adults." Children seem to be spared from both epidemic and sporadic5 enterically transmitted

(a) Structure artifact (

x

observed by Gray et al 36 000); (c) S sabaudiense (

( x

000); (b) crystalline 14 000).

x 72

NANBH. We report an outbreak among children aged 9-15 years, at a school in Talegaon, 25 km from Pune, India. On Sept 4, 1988, information was received from the school authorities that a few cases of hepatitis had occurred among the residents during the previous week. The school authorities checked the water supply for the hostel, which came from a well, and found it contaminated. Blood samples were collected from all those at the hostel (188) and from the 18 adult staff members. Symptoms were noted. Sera were screened for alanine aminotransferase (ALT). 67 (35-5%) children and 4 (22%) staff, including the cook, had raised ALT levels (44-200 IU/I; mean 120[SD 52 1] IU/1). Only 9 icteric cases were noted among 67 students with raised ALT levels. Among the adults 2 were icteric. No symptoms were reported by 39 children; 6 complained of nausea or abdominal pain. Influenza-like symptoms were present in 13 children. All sera were tested for HBsAg by ELISA. 3 of the children’s sera were positive for HBsAg and negative for anti-HBc-IgM (’Corzyme-M’, Abbott) while none of the adults were positive. Only 95 sera (alternately selected) were tested for antibodies to hepatitis A virus (anti-HAV; ’HAVAB’, Abbott); of these 92 were positive, implying that most of them had previous exposure to HAV. Blood samples were collected a week later from 60 children who had had high ALT levels. During this period 2 children who had had normal ALT levels earlier became icteric, and blood was collected from them too. (6 more children with high ALT levels earlier also became icteric, giving a total of 17 icteric cases among the children.) For these 62 children investigations revealed 17 icteric

1200

(27%),1 HBsAg positive, no anti-HAV-IgM positives, 2 with IgM cytomegalovirus antibody (neither icteric), and 26 with hepatomegaly (42%). The 4 adults with raised ALT levels were HBsAg, anti-HBcIgM, and anti-HAV-IgM negative. Thus, it appears that most of

(cytomegalovirus, Coxsackie B, rubella) antigens. Such an approach has been used in studies of viral hepatitis B (with hepatocytederived and viral antigens)?.8

the

Italy

cases

due to NANBH. All those affected recovered uneventfully. This is the first report of an outbreak of enterically transmitted NANBH among children. From January to September, 1988, 43 hepatitis cases among children were investigated by us in Pune, and 39 were due to HAV, which is a typical frequency for hepatitis among children in India. In earlier epidemics of NANBH few children were affected.l-4 Whether this was due to less exposure, dose dependence, or previously acquired, short-lived immunity is not clear. The Talegaon epidemic suggests that children are susceptible to the disease and that the ratio between icteric and non-icteric episodes in children is about 1:4. cases were

We thank the school authorities and also Mr C. L. Ramamoorthy, Mrs L. P. Chobe, and Miss M. R. Pote for technical assistance.

Hepatitis Unit, National Institute of Virology, Pune 411 001, India

VIDYA A. ARANKALLE MANDEEP S. CHADHA SANJAY M. MEHENDALE KALYAN BANERJEE

1. Viswanathan R. Infectious hepatitis in Delhi

(1955-56): a critical study; epidemiology. Res 1957; 45 (suppl): 1-30. Indian Med J 2. Khuroo MS Study of an epidemic non-A, non-B hepatitis. Possibility of another human hepatitis virus distinct from post-transfusion non-A, non-B type Am J Med 1980; 80: 818-24. 3. Kane MA, Bradley DW, Shrestha SM, et al. Epidemic non-A, non-B hepatitis in Nepal. Recovery of possible etiologic agent and transmission studies in marmosets. JAMA 1984; 252: 3140-45. 5. Myint HLT, Myint MS, Klin T, et al A clinical and epidemiologic study of an epidemic of non-A, non-B hepatitis in Rangoon. Am J Trop Med Hyg 1985; 34: 1183-89. 5. Ramalingaswami V, Purcell RH. Water-bornenon-A, non-B hepatitis. Lancet 1988; ii: 571-73

PATHOGENESIS OF TYPE I DIABETES

SIR,-Dr de Berardinis and colleagues (Oct 8, p 823) show that a CD4-positive T cell clone from a diabetic patient can lyse HLA class II matched islet cells, and they state that this process may be important in the pathogenesis of type I diabetes. However, it is hazardous to speculate about pathogenesis on the basis of a single experiment. A CD4-positive T cell clone, grown in vitro after activating the T cell receptor via an anti-Vp8 antibody and derived from one cell circulating in the peripheral blood of a newly diagnosed diabetic patient, lysed HLA class II matched islet cells in vitro (and not just beta cells) from a normal individual. These islet cells had been induced in vitro

to

express HLA class II

antigens. Even though most activated T cells circulating in the peripheral blood of patients with insulin-dependent diabetes mellitus (IDDM) appear to be CD4-positive,’ the majority of T cells surrounding affected islets in the pancreas of these patients are CD8-positive.2-4 CD8-positive cytotoxic T cells are likely to mediate rapid destruction of normal pancreatic islets engrafted into diabetic identical twinssince normal islet cells express HLA class I and not class II antigens. The inductive role for T cell cytotoxicity of HLA class IIantigen expression on the surface of beta cells in vivo in IDDM is still unproven and alternative explanations need to be considered. Thus, CD8-positive suppressor cells recognise antigens in association with HLA class II molecules (F. Melchers, International Symposium on AIDS, S. Marino, Oct 12, 1988) and expression of class II antigens by islet beta cells may partly represent a "protective" mechanism of antigen-specific suppressor cell recruitment. The complex interactions of genetic factors, autoimmune reactions, and viral infections leading to type I diabetes have not yet been elucidated. The sudden, acute, and sometimes fatal mode of presentation is preceded in most cases by a lengthy pathological process.’ Future studies should concentrate on this crucial, pre-symptomatic period and evaluate prospectively humoral and cellular immune reactions to both islet-cell-derived and viral

USL Corvo, 88060 S. Maria de Catanzaro,

SANDRO VENTO TIZIANA GAROFANO

1. de Berardinis P, Londei M, Kahan M, et al. The majority of the activated T cells m the blood of insulin dependent diabetes mellitus (IDDM) patients are CD4-positive. Clin Exp Immunol 1988, 73: 255-59 2. Gepts W, Le Compte PM. The pathology of type I (juvenile) diabetes. 2nd ed In Volk BW, Arquilla CR, eds. The diabetic pancreas. New York Plenum, 1985: 337-65 3. Bottazzo GF, Dean BM, McNally JM, Mackay EH, Swift PGF, Gamble DR. In situ characterization of autoimmune phenomena and expression of HLA molecules in pancreas in diabetic insulitis. N Engl J Med 1985; 313: 353-60. 4. Foulis AK, Farquharsaon MA. Aberrant expression of HLA-DR antigens by insulin containing beta cells in recent onset type I diabetes mellitus. Diabetes 1986, 35: 1215-24. 5 Sutherland DWR, Chin PL, Goetz FC, Elick BA, Najarian JS Minnesota experience with 81 pancreatic transplants since 1978 Transplant Proc 1984, 16: 129-37 6. Eisenbarth GS. Type I diabetes mellitus: a chronic autoimmune disease. N Engl J Med 1986, 314: 1360-68. 7 Vento S, Rondanelli EG, Ranieri S, O’Brien CJ, Williams R, Eddleston ALWF. Prospective study of cellular immunity to hepatitis-B-virus antigens from the early incubation phase of acute hepatitis B. Lancet 1987; ii: 119-22 8. Vento S, McFarlane BM, Garofano-Vento T, et al. Senal study of liver-directed autoantibodies and autoreactive T-lymphocytes in acute viral hepatitis B

J Antoimmunity (in press).

BLOOD TESTING BEFORE PRESCRIBING ORAL CONTRACEPTION IN AFRICA

SIR,-We have taken part in family planning programmes in Africa. The implementation of oral contraception has often been difficult because expensive blood tests had to be done first. We asked the 139 African family planning professionals who attended six United Nations Fund for Population Activities courses in Mauritius and Belgium in 1987 and 1988 to complete a questionnaire. They were generally well informed about the practices in their 32 countries (18 French, 9 English, 5 Portuguese speaking). Participants were told that confidentiality was guaranteed and that country-specific results would not be published. 12 participants did not know the practice in their countries. 46 (from 19 countries) stated that blood testing was recommended or required but for 10 of those 19 countries a mixture of positive and negative answers was registered. 13 of the 19 countries were French speaking, 3 were English speaking, and 3 others were Portuguese speaking. When blood testing was recommended the following analyses were done: blood sugar (94%), glucose tolerance (22%), cholesterol (65%), and triglycerides (54%). Other analyses were recommended in 44% of cases. 35% of participants thought that the analyses recommended were indeed done. 78% believed that analyses were necessary, but 76% conceded that such analyses restrict access to family planning. It seems that blood testing before pill prescription is used in more than one half of the African countries investigated. The usefulness of such analyses is controversial in industrialised countries, and several textbooks’do not mention it. In Africa, blood tests are even more questionable, because heart attacks, venous thromboembolic disease, and hypertension seem to be less common in developing countries than in industrialised ones,3and smoking among women and hypercholesterolaemia are also relatively rare in developing countries. Annual mortality related to pill use has been estimated to be 1 in 100 000 women in Africa.’ This figure is much lower than the maternal mortality rate, which is over 1000 per 100 000 live births in some parts of that continent. Since family planning can reduce maternal mortality,s access to contraceptive methods should be as wide as possible. Expensive and often unfeasible blood testing before pill prescription could limit this accessibility and should be avoided. At least one African country has lately abandoned this practice. We hope that the usefulness of blood testing will be debated in other countries as well. We thank R. Johnson and all the staff members of the regional training in family health, Mauritius, for their help; and P. Delvoye and S. Wesel

centre