1038 of an effect due to standing waves. This precaution would likewise reduce the possibility of cavitation occurring in tissue. Department of Microbiology, University College, Cardiff, Glam. CF2 1TA.


Physics Department, Institute of Cancer Research, Belmont, Sutton, Surrey SM2 5PX. *Permanent address: Bioacoustics Research


Laboratory, University

scope to determine if all morphological forms of HBsAg cross the blood/brain barrier. In particular, if selective permeability for the smaller (22 nm) forms exists, the absence of Dane particles in this fluid would reduce the likelihood that HBsAg containing c.s.F. is infective. We are looking at this possibility, and until these studies are completed we agree with Dankert et al. and recommend that C.S.F. specimens of patients who are seropositive for HBsAg be labelled as such and be handled with caution.

of Illinois,

Urbana, Illimos 61801, U.S.A.


SiR,—There are two recent reports concerning hepatitis-B surface antigen (HBsAg) in cerebrospinal fluid (c.s.F.). Trepo et aLl detected HBsAg in the c.s.F. of only one of twenty patients who were seropositive for HBsAg. They concluded that HBsAg does not cross the blood/brain barrier and occasional weak positivity of c.s.F. signifies either increased permeability of the blood/brain barrier or contamination of the fluid by blood. However, Dankert et al.2 subsequently detected HBsAg in the c.s.F. of two of three HBsAg-seropositive leukaemic children in the absence of detectable haematorrhachis. These authors concluded that the c.s.F. of HBsAg positive leukaemic patients should be handled carefully. We have examined c.s.F. from two HBsAg-seropositive chimpanzees. The first animal was examined at time of death FINDINGS IN TWO



minute (c.p.m.) of test sample *Sample ratio units = Counts per of control c.p.m. sample with ratios above 2-6 recorded as HBsAg positive.

in the acute stage of experimental hepatitis-B infection. At necropsy the cervical dura was exposed and 5 ml of clear c.s.F. was aspirated. The procedure was done with direct visualisation of the dura and the fluid was not visibly contaminated by blood. The second chimpanzee has been a chronic HBsAg carrier for six years. Under phencyclidine anaesthesia 10 ml of C.S.F. was obtained from this animal by lumbar puncture. The fluid was clear, cell-count revealed 2 mononuclear cells/ml and no red blood-cells, and was negative for haematin by ’Hemastix’ test (Ames Laboratories). As shown in the table, both C.S.F. specimens were strongly positive for HBsAg by radioimmunoassay (Ausria 11),3 the HBsAg content of the c.s.F. samples (expressed as S.R. units) was equal to serum in animal no. 2 and two times that of corresponding serum in animal no. 1. The choroid plexus and C.S.F. physiology of the chimpanzee is similar to that of may/ Our findings suggest that HBsAg may be present in the c.s.F. of seropositive individuals. The high antigen content of our specimens further suggests that presence of HBsAg in C.S.F. is not due to minor or transient permeability of the blood/brain barrier or inadvertent contamination of c.s.F. with blood. It will be interesting to examine these specimens as well as specimens from seropositive patients with the electron microTrepo, C., Bolot, J. F., Robert, D., Serpetjian, M., Prince, A. M. Lancet, 1974, ii, 1514. 2. Dankert, J., Postma, A., De Vries, J. A., Zijlstra, J. B. ibid. 1975, i, 690. 3. Ling, C. M., Overby, L. R. J. Immun. 1972, 109, 834. 4. Iatropoulos, M. Personal communication. 1.

Phoenix Laboratories Division, Bureau of Epidemiology, Center for Disease Control, 4402 North 7th Street, Phoenix, Arizona 85014, U.S.A.




SIR,- The report by Dr Maupas and his co-workers (July 5,

9) of a higher prevalence of antibody to hepatitis-B core antigen in patients with primary hepatic carcinoma (P.H.C.) than in matched controls adds considerable weight to the hypothesis that hepatitis B and P.H.c. are causally related, which is already supported by the findings of other studies using different methods.I-3 However, Maupas and his coworkers admit that their study, as well as the previous ones, does not prove the causal nature of the relationship; indeed the association could be secondary, or the establishment of hepa5 toma could facilitate the persistent antigenaemia.4 An argument often quoted to support the aetiological significance of hepatitis-B viral infection in the development of r.tt.c. is the higher prevalence of hepatitis-B surface antigen (HBsAg) in the general population of areas, such as Africa, where P.H.C.


is very common.6 This concomitant variation cannot be explained in terms of a tumour effect on the establishment or persistence of hepatitis-B antigenxmia, since the incidence of P.H.C. is in general too low to affect the frequency and variation of HBsAg. On the other hand, the likelihood of the association being secondary cannot be excluded, since persistent antigenaemia may be related to defective cell-mediated immune response.7 8 Aflatoxin (one of the putative causes of P.H.C.9) and other toxins and several protozoal and other infections believed to affect the immunological prevailing in Africa, are 10 We to viruses. response thought that data from Greece informative. be might particularly HBsAg is very common in the general population of Greece, where apparently it has the highest prevalence in Europe (among Greek recruits, 6-3% were carriers; HBsAg was detected by counterimmunoelectrophoresis"). In other relevant aspects, however, the nosological situation in Greece is not very different from that in other European countries, and there is no indication of aflatoxin contamination of foodstuft’s, Therefore, if the incidence of P.H.C. in Greece were high, this could be taken as a very strong indication of the importance of hepatitis-B infection in the aetiology of P.H.C. Although there is circumstantial evidencel2 that this is indeed so, incidence or mortality-rates from P.H.C. in Greece have never been

reported. With the collaboration of the health-services branch of the Ministry of Social Services, we have examined death certificates for the years 1971, 1972, and 1973 to calculate annual 1. Sherlock, S., Fox, R. A., Niazi, S. P., Scheuer, P. J. Lancet, 1970, i, 1243 2. Hadziyannis, S. J., Merikas, G. E., Afroudakis, A. P. ibid. 1970, ii, 100. 3. Vogel, C. L., Anthony, P. P., Mody, N. J., Barker, L. F. ibid. p. 621 4. Kumar, S., Taylor, G. J. clin. Path. 1973, 26, 476. 5. Coady, A. Br. med. J. 1975, iii, 592. 6. British Medical Journal, 1975, ii, 647. 7. Dudley, F. J., Fox, R. A., Sherlock, S. Lancet, 1972, i, 723. 8. Kaklamanis, E., Trichopoulos, D., Papaevangelou, G., Drouga, M., Karalis, D. ibid 1975, i, 689. 9. Peers, F. G., Linsell, C. A. Br. J. Cancer, 1973, 27, 473. 10. Wedderburn, N. Lancet, 1970, ii, 1114. 11. Hadziyannis, S., Papaevangelou, G., Vissoulis, Ch. Vox Sang. 1973, 24, 89

Letter: Hepatitis-B surface antigen in cerebrospinal fluid.

1038 of an effect due to standing waves. This precaution would likewise reduce the possibility of cavitation occurring in tissue. Department of Microb...
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