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HEPATITIS B NOT TRANSMISSIBLE VIA FÆCAL-ORAL ROUTE
706
anti-HBs in order to explore the immune status of population relative to H.B.v. subtypes. This work
was
supported by Italian
Institute of Hygiene,
University of Genoa, Via Pastore 1, 16132 Genoa, Italy.
C.N.R.
FERNANDO L. PETRILLI PIETRO CROVARI SILVIO DE FLORA
HBs AND ANTI-HBs SURVEY IN MOTHER/INFANT PAIRS
SjR,—Having read the study described by Papaevangelou et al.’, we report our results from a similar survey. We tested at birth 311 mother/infant pairs for HBs and anti-HBs by R.I.A., and 53 of these pairs again 2-5 months after delivery (6 HBs-positive and 47 anti-HBs-positive pairs). At birth, 7 maternal and 4 cord-sera were HBs positive, and 75 maternal and 60 cord-sera were anti-HBs positive. After delivery, the 6 mothers were still antigenaemic, and, were judged to be symptom-free carriers. The children with cord-serum HBs positive were HBs negative, and 2 of them showed a slight positivity for anti-HBs when 3 months old. Of the 3 children with HBs-negative cord-sera, 1 showed a transient positivity for HBs at 11weeks and 2 were HBs/anti-HBs negative at 3 months. Of the 47 mother/infant pairs positive for anti-HBs, 41 mothers and 25 infants were still positive. Mothers and offspring are all healthy. Mothers HBs or anti-HBs positive very rarely had a past history of hepatitis; this supports the hypothesis that HB virus is a very common cause of infection. The presence of HBs in cord-serum was not related to its persistence, and it became transiently detectable in a baby whose cord-serum was negative. This finding indicates that HBs does not usually cross the placental barrier but is acquired at birth or afterwards. In a previous study2a baby, whose cord-serum was HBs positive, was HBs negative when 2 days old. The HBs carrier state in healthy mothers rarely seems to give rise to illness in their offspring; other studies have shown that children born of mothers affected by hepatitis during pregnancy have a high rate of HBs positivity or overt hepatitis 3-5. We tested 19 mothers who had had hepatitis during pregnancy, 2-6 years earlier, and their children. 8 mothers and 3 of their children were anti-HBs positive, and none was HBs positive; mothers and offspring were healthy and no child had
being healthy,
hepatitis. Anti-HBs found in cord-serum is maternal, and is present some months afterwards in nearly 50% of children. We are following its persistence and its effectiveness in preventing illness as described with specific globulins ;6 none of the mothers or of the HBs/ anti-HBs positive babies acquired hepatitis in the 5 months after delivery. One woman, HBs/anti-HBs negative at delivery, acquired B hepatitis 50 days after; her child was HBs negative. An important finding is that babies born of carrier mothers and with HBs-positive cord-serum may form anti-HBs, as de-
HEPATITIS B NOT TRANSMISSIBLE VIA FÆCAL-ORAL ROUTE SIR,-Until 1967 it was assumed that hepatitis B could be transmitted only by parenteral routes. In that year Krugman et al1 demonstrated that MS-2 serum, given orally, caused a subclinical form of the disease. Subsequently, many epidemiological studies demonstrated that hepatitis B developed in a large number of subjects who never received parenteral treatment. It was concluded that the fxcal-oral route musL be ih? maior means of transmission of the infection.2-4These conclusions du seem very convincing, for the following reasons: i. In Krugman’s experiments enormous amounts of virus (0-5 ml of serum) were administered. This rarely happens with naturally acquired infections. ii. The fasces of subjects with hepatitis B are not infectious. 45 subjects 5-7 who received orally relatively large amounts of faeces collected from 10 subjects with hepatitis B, did not show any symptoms of disease. Only a single individual,I of 5, given a fscal filtrate by injection,’ developed even doubtful hepatitis. iii. Hepatitis-B surface antigen (HBsAg) is not found in the fxces of infected subjects.8 iv. The intestinal mucosa and fsces of all subjects contain an inhibitor of HBsAg, which presumably also inhibits the infectivity of hepatitis-B virus.9-11 This inhibitor inactivates HBsAg reaching the intestines with the bile. In fact, HBsAg present in cholecystic bile is undetectable by the time it reaches the duo-
denum.12-14
For these reasons faecal-oral spread of hepatitis B seems unlikely. On the contrary, the major mechanism of transmission is the inapparent parenteral route. In fact, HBsAg can be present in various biological fluids. For example, saliva of subjects with acute hepatitis B is nearly always infectious because of the presence of traces of blood or occult blood. This saliva, if introduced by the oral route into normal subjects, can reach the bloodstream through the microlesions almost always present on the oral mucosa. The presence of the intestinal inhibitor would inactivate the hepatitis-B virus as it reaches the intestines.1o The sexual route must also be considered as an important inapparent parenteral route, because of the very common microlesions of the mucosa of sexual organs during intercourse. This is even more common in male homosexuals, many of whom have proctitic lesions. Conjunctival contagion must also be considered a further possible mode of
transmission. Department of Infectious Diseases, University of Naples, Nuovo Policlinico, Cappella dei Cangiani, Napoli, Italy.
1.
M. PIAZZA L. CACCIATORE V. MOLINARI L. PICCIOTTO
Krugman, S., Giles, J. P., Hammond, J. J. Am. med. Ass. 1967, 200, 365.
Szmuness, W., Prince, A. M. Am. J. Epidem. 1971, 94, 585. Hersh, T., Melnick, J. L., Goyal, R. K., Hollinger, F. B. N. Engl. J. Med. 1971, 285, 1363. 4. Bryan, J. A., Carr, H. E., Gregg, M. B. J. Am. med. Ass. 1973, 223,
2. 3.
279.
Institute of Infectious Diseases, Obstetric Department,
University of Rome, Rome, Italy.
L. V. CHIRCU M. MATTIACCI G. SCHIANO E. FRANCO A. PATELLA L. REVERBERI
1. Papaevangelou, G., Hoofnagle, J., Kremastinou, J. Lancet, 1974, ii, 746. 2. Chircu, L. V., Mattiacci, M. Aggiorn. Mal. Inf. Immun. 1974, 1, 35. 3. Merrill, D., Dubois, R., Kohler, P. New Engl. J. Med. 1972, 287, 1280. 4. Schweitzer, I., Wing, A., McPeack, C., Spears, R. J. Am. med. Ass. 1972,
220, 1092. 5. 6.
Wright, R., Perkins, J., Dower, B., Jerome, D. Br. med. J. 1970, iv, 719. Kohler, P., Dubois, R. Merrill, D., Bowes, W. New Engl. J. Med. 1974,
7
291, 1378. Hitchens, A., Gostling, J., O’Driscoll, W. Lancet, 1974, ii, 343.
5. Havens, W. P., Jr. J. exp. Med. 1946, 83, 441. 6. MacCallum, F. O., McFarlan, A. M., Miles, J. A. R. Med. Res. Coun. spec. Rep. Ser. 1951, N.273. 7. Neefe, J. R. Am. J. Med. 1946, 1, 3. 8. Wld Hlth Org. Tech. Rep. Ser. 1975, N.570. 9. 10.
Piazza, M., Di Stasio, G., De Marco, F. Br. med. J. 1971, iii, 772. Piazza, M., Di Stasio, G., Maio, G., Marzano, L. A. ibid. 1973, ii,
334. 11. Borchert, P., Ward, R. Communication to Hepatitis Scientific Memoranda, (H-567/1), October, 1973. 12. Serpeau, D., Mannoni, P., Dhumeaux, D., Berthelot, P. Lancet, 1971, ii, 1266. 13. Piazza, M., Cacciatore, L., Molinari, V., Gravina, E., Manzillo, G., Guadagnino, V., Tullio Cataldo, P., Maio, G. Rc. Atti. Accad. Sci. Med. Chir. 1974, 78, 166. 14. Piazza, M., Cacciatore, L., Molinari, V., Guadagnino, V., Tullio Cataldo, P., Borgia, G., Gravina, E., Manzillo, G., Maio, G. Pathologia Microbiol. (in the press).
anti-HBs in order to explore the immune status of population relative to H.B.v. subtypes. This work
was
supported by Italian
Institute of Hygiene,
University of Genoa, Via Pastore 1, 16132 Genoa, Italy.
C.N.R.
FERNANDO L. PETRILLI PIETRO CROVARI SILVIO DE FLORA
HBs AND ANTI-HBs SURVEY IN MOTHER/INFANT PAIRS
SjR,—Having read the study described by Papaevangelou et al.’, we report our results from a similar survey. We tested at birth 311 mother/infant pairs for HBs and anti-HBs by R.I.A., and 53 of these pairs again 2-5 months after delivery (6 HBs-positive and 47 anti-HBs-positive pairs). At birth, 7 maternal and 4 cord-sera were HBs positive, and 75 maternal and 60 cord-sera were anti-HBs positive. After delivery, the 6 mothers were still antigenaemic, and, were judged to be symptom-free carriers. The children with cord-serum HBs positive were HBs negative, and 2 of them showed a slight positivity for anti-HBs when 3 months old. Of the 3 children with HBs-negative cord-sera, 1 showed a transient positivity for HBs at 11weeks and 2 were HBs/anti-HBs negative at 3 months. Of the 47 mother/infant pairs positive for anti-HBs, 41 mothers and 25 infants were still positive. Mothers and offspring are all healthy. Mothers HBs or anti-HBs positive very rarely had a past history of hepatitis; this supports the hypothesis that HB virus is a very common cause of infection. The presence of HBs in cord-serum was not related to its persistence, and it became transiently detectable in a baby whose cord-serum was negative. This finding indicates that HBs does not usually cross the placental barrier but is acquired at birth or afterwards. In a previous study2a baby, whose cord-serum was HBs positive, was HBs negative when 2 days old. The HBs carrier state in healthy mothers rarely seems to give rise to illness in their offspring; other studies have shown that children born of mothers affected by hepatitis during pregnancy have a high rate of HBs positivity or overt hepatitis 3-5. We tested 19 mothers who had had hepatitis during pregnancy, 2-6 years earlier, and their children. 8 mothers and 3 of their children were anti-HBs positive, and none was HBs positive; mothers and offspring were healthy and no child had
being healthy,
hepatitis. Anti-HBs found in cord-serum is maternal, and is present some months afterwards in nearly 50% of children. We are following its persistence and its effectiveness in preventing illness as described with specific globulins ;6 none of the mothers or of the HBs/ anti-HBs positive babies acquired hepatitis in the 5 months after delivery. One woman, HBs/anti-HBs negative at delivery, acquired B hepatitis 50 days after; her child was HBs negative. An important finding is that babies born of carrier mothers and with HBs-positive cord-serum may form anti-HBs, as de-
HEPATITIS B NOT TRANSMISSIBLE VIA FÆCAL-ORAL ROUTE SIR,-Until 1967 it was assumed that hepatitis B could be transmitted only by parenteral routes. In that year Krugman et al1 demonstrated that MS-2 serum, given orally, caused a subclinical form of the disease. Subsequently, many epidemiological studies demonstrated that hepatitis B developed in a large number of subjects who never received parenteral treatment. It was concluded that the fxcal-oral route musL be ih? maior means of transmission of the infection.2-4These conclusions du seem very convincing, for the following reasons: i. In Krugman’s experiments enormous amounts of virus (0-5 ml of serum) were administered. This rarely happens with naturally acquired infections. ii. The fasces of subjects with hepatitis B are not infectious. 45 subjects 5-7 who received orally relatively large amounts of faeces collected from 10 subjects with hepatitis B, did not show any symptoms of disease. Only a single individual,I of 5, given a fscal filtrate by injection,’ developed even doubtful hepatitis. iii. Hepatitis-B surface antigen (HBsAg) is not found in the fxces of infected subjects.8 iv. The intestinal mucosa and fsces of all subjects contain an inhibitor of HBsAg, which presumably also inhibits the infectivity of hepatitis-B virus.9-11 This inhibitor inactivates HBsAg reaching the intestines with the bile. In fact, HBsAg present in cholecystic bile is undetectable by the time it reaches the duo-
denum.12-14
For these reasons faecal-oral spread of hepatitis B seems unlikely. On the contrary, the major mechanism of transmission is the inapparent parenteral route. In fact, HBsAg can be present in various biological fluids. For example, saliva of subjects with acute hepatitis B is nearly always infectious because of the presence of traces of blood or occult blood. This saliva, if introduced by the oral route into normal subjects, can reach the bloodstream through the microlesions almost always present on the oral mucosa. The presence of the intestinal inhibitor would inactivate the hepatitis-B virus as it reaches the intestines.1o The sexual route must also be considered as an important inapparent parenteral route, because of the very common microlesions of the mucosa of sexual organs during intercourse. This is even more common in male homosexuals, many of whom have proctitic lesions. Conjunctival contagion must also be considered a further possible mode of
transmission. Department of Infectious Diseases, University of Naples, Nuovo Policlinico, Cappella dei Cangiani, Napoli, Italy.
1.
M. PIAZZA L. CACCIATORE V. MOLINARI L. PICCIOTTO
Krugman, S., Giles, J. P., Hammond, J. J. Am. med. Ass. 1967, 200, 365.
Szmuness, W., Prince, A. M. Am. J. Epidem. 1971, 94, 585. Hersh, T., Melnick, J. L., Goyal, R. K., Hollinger, F. B. N. Engl. J. Med. 1971, 285, 1363. 4. Bryan, J. A., Carr, H. E., Gregg, M. B. J. Am. med. Ass. 1973, 223,
2. 3.
279.
Institute of Infectious Diseases, Obstetric Department,
University of Rome, Rome, Italy.
L. V. CHIRCU M. MATTIACCI G. SCHIANO E. FRANCO A. PATELLA L. REVERBERI
1. Papaevangelou, G., Hoofnagle, J., Kremastinou, J. Lancet, 1974, ii, 746. 2. Chircu, L. V., Mattiacci, M. Aggiorn. Mal. Inf. Immun. 1974, 1, 35. 3. Merrill, D., Dubois, R., Kohler, P. New Engl. J. Med. 1972, 287, 1280. 4. Schweitzer, I., Wing, A., McPeack, C., Spears, R. J. Am. med. Ass. 1972,
220, 1092. 5. 6.
Wright, R., Perkins, J., Dower, B., Jerome, D. Br. med. J. 1970, iv, 719. Kohler, P., Dubois, R. Merrill, D., Bowes, W. New Engl. J. Med. 1974,
7
291, 1378. Hitchens, A., Gostling, J., O’Driscoll, W. Lancet, 1974, ii, 343.
5. Havens, W. P., Jr. J. exp. Med. 1946, 83, 441. 6. MacCallum, F. O., McFarlan, A. M., Miles, J. A. R. Med. Res. Coun. spec. Rep. Ser. 1951, N.273. 7. Neefe, J. R. Am. J. Med. 1946, 1, 3. 8. Wld Hlth Org. Tech. Rep. Ser. 1975, N.570. 9. 10.
Piazza, M., Di Stasio, G., De Marco, F. Br. med. J. 1971, iii, 772. Piazza, M., Di Stasio, G., Maio, G., Marzano, L. A. ibid. 1973, ii,
334. 11. Borchert, P., Ward, R. Communication to Hepatitis Scientific Memoranda, (H-567/1), October, 1973. 12. Serpeau, D., Mannoni, P., Dhumeaux, D., Berthelot, P. Lancet, 1971, ii, 1266. 13. Piazza, M., Cacciatore, L., Molinari, V., Gravina, E., Manzillo, G., Guadagnino, V., Tullio Cataldo, P., Maio, G. Rc. Atti. Accad. Sci. Med. Chir. 1974, 78, 166. 14. Piazza, M., Cacciatore, L., Molinari, V., Guadagnino, V., Tullio Cataldo, P., Borgia, G., Gravina, E., Manzillo, G., Maio, G. Pathologia Microbiol. (in the press).