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Schistosomiasis and primary liver cell carcinoma
T~~~s~cmxis OFTWEROYALSOCIETYOFTROPICAL MEDICINEAND HYGIENE,V0~.73,N0.3,1979.
visceral leishmaniasis demonstrated by the detection of Leishmaniu amastigotes in smears prepared by spleen biopsy (slides examined by Charles Nicolle of the Pasteur Institute of Tunis). PATANE (1928) referred to a case from Tolmetta found during careful search in Cirenaica between 1912 and 1925: During his 20 Years of medical nractice in Trinoli. MA~Z~LANI (1933) diagnosed 11 cases, two of w-hi& were confirmed by bone marrow examination. From these historical data, we know that visceral leishmaniasis has been present for years in Libya, even if the number of cases reported is low. In this context, the observation of Dar merely confirms the previous reports and in doing so further emphasizes the need of careful search for the disease in this country. I am, etc., JEAN PIERRE DEDET Institut Pasteur, Unite’ de Parasitologic Experimentale, 25, rue du Docteur Roux, 75015-Paris References Dar, F. K. (1978). An autochthonous case of kalaazar in Libya. Transactions of the Royal Society of Tropical Medicine and Hygiene, 72, 555-556. Mazzolani, D. A. (1933). La leishmaniose viscerale infantile en Tripolitaine. Compte rendus du ler Congres international d’Hv&ne Mediterrane’enne. -1, 338-312. Patane, C. (1928). I1 posto attuale della Cirenaica nell’ enidemioloeia delle leishmaniasi nel Nord Africa.- Archivii Italian0 di Scienze Mediche Coloniale, 9, 69-83. (Quoted in Tropical Disease Bulletin (1929). 26. 315.) Tashim, 1.‘(1919). Sur l’existence en Tripolitaine de kala-azar et de la fievre mediterraneenne. Bulletin de la Societe de Pathologie exotique, 3, 511-512.
Accepted for publication
10th January,
1979.
and primary liver cell carcinoma SIR-I wonder if I may be allowed to comment on a statement made in your correspondence columns in “The possible relationship of Schistosoma infection and liver carcinoma” (MOTT. 1978) which has iust reached me. The writer states that the geographical prevalence of liver carcinoma corresponds to that of S. mansoni and S. japonicum. I cannot comment on S. .japonicum but I do not think this statement is true of mansoni infection. S. mansoni is uncommon in southern Nigeria (HINZ. 1968) where the incidence of liver-carcinoma -is hi& (EDINGTON & MACLEAN, 1965) whereas it is low in. Egypt where S. mansoni infection is nrevalent. In Bahia in Brazil. CHEEVER & ANDRADE (f967) in a large autopsy series found that hepatocellular carcinoma was more common in uninfected cases than in those suffering from mansoni infection. MARTINEZ-~L~LDONADO
CORRESPONDENCE
351
et al. (1965) considered that S. mansoni played no part in the aetiology of liver carcinoma in Puerto Rico. I do not think therefore that geographical studies would support the claim that there is a marked correlation between a high prevalence of S. munsoni and liver carcinoma. Nevertheless as the author points out HBs antigen has been associated with hepatosplenic schistosomiasis and experimentally it has been shown that schistosome infection renders the liver more sensitive to carcinogenic compounds and the growth of tumours is facilitated in some species of laboratory animals (DOMINGO et al., 1967; hu et al. 1969). It has also been considered that chronic mansoni infections promote disease caused by viral infections. The infection in mice decreased their resistance to S. typhimurium infection (ROCHA et al., 1971) and the sera of natients with heuatosplenic schistosomiasis were shown to have reduced anti-salmonella activity. Complement has also been shown to be reduced, as are the cellular defence mechanisms (FERNANDOS & ROCHA, 1967). It is of interest that ANDRADE & ABREU (1971) have noted an association of follicular lymphoma of the spleen in patients with hepatosplenic S. mansoni infections and EDINGTON et al. (1970) noted a significantly higher number of lymphomas in S. haematobium post-mortems when compared with controls. It is therefore possible that the effects of schistosomiasis on the reticula-endothelial system may have a cancer-promoting effect, especially in tumours of this system, which is similar to the suggestions put forward regarding the presence of holoendemic malaria and the Burkitt lymphoma. The writer has noted schistosomiasis associated with primary liver cell carcinoma in a boy aged 14 years and NKRUMAH (1964) recorded a similar finding in a boy aged eight years-ages at which liver cell carcinoma is uncommon in Nigeria and Ghana. The association may however be fortuitous and much further work requires to be done before an association between S. mansoni and liver cell cancer can be accepted. I am, etc., G. M. EDINGTON College of Medical Sciences, University of Maiduguri, Maiduguri, Nigeria
Schistosomiasis
References Andrade, Z. A. & Abreu, W. N. (1971). Follicular lymphoma of the spleen in patients with hepatosplenic schistosomiasis. American Journal of Tropical Medicine and Hygiene, 20, 237-242. Cheever, A. W. & Andrade, Z. A. (1967). Pathological lesions associated with Schistosoma mansoni infection in man. Transactions of the Royal Society of Tropical Medicine and Hygiene, 61, 626-639. Domingo, E. O., Warren, K. S. & Stenger, R. J. (1967). Increased incidence of hepatoma in mice with chronic schistosomiasis mansoni treated with a carcinogen. American Journal of Pathology, 51. 307-321. Edington, G. M. & Maclean, C. M. U. (1965). A cancer rate survey in Ibadan, Western Nigeria 1960-63. British Journal of Cancer, 19, 471-481.
352
TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, VOL. 73, No. 3, 1979. CORRESPONDENCE
Edington, G. M., von Lichtenberg, F., Nwabuebo, I., Taylor, J. R. & Smith, J. N. (1970). Pathologic effects of schistosomiasis in Ibadan, Western State of Nigeria. American Journal of Tropical Research, 29, 837-847. Fernandos, D. J. & Rocha, H. (1967). Caracteristicas da reacao inflamatopio em pacientes corn forma hepatosplenica de esquistossome mansonica calazar. Revista do Instituto de Medicina Tropical de Sgo Pa&o, 9, 129-133. Hinz, E. (1966). Intestinal helminth infection in West Africa (Southern Nigeria). Zeitschrzft fiir Tropenmedizin und Parasitologic, 17, 427-442. Liu, L. B., Domingo, E. O., Stenger, R. J., Warren, K. S., Confer, D. B. & Johnson, E. A. (1969). An ultra structural study of the toxic and carcinogenic effects of 2-amino-5-azotoluene on the livers of schistosome-infected and uninfected mice. Cancer Medicine and Hygiene, 19, 982-995. Martinez-Maldonado, M., Girod, C. E., Ramirez De Arellano, G. & Ramirez, E. A. (1965). Liver cell carcinoma (hepatoma) in Puerto Rico. A survey of 26 cases. American Journal of Digestive Diseases, 10, 522-529. Mott, K. E. (1978). Possible relationship of Schistosoma infection and liver carcinoma. Transactions of the Royal Society of Tropical Medicine and Hygiene, 72, 552-553. Nkrumah, P. K. (1964). Primary carcinoma of the liver and post-necrotic cirrhosis in a Ghanian child with non-hepatic bilharziasis. Ghana Medical Journal, 3, 129-133. Rocha, H., Kirk, J. W. & Hearey! C. D. Jr. (1971). Prolonged Salmonella bacteremra in patients with Schistosoma mansoni infection. Archives of Internal Medicine, 128, 254-257.
Accepted for publication
Surface
26th January,
1979.
hepatitis B antigen and urinary schistosomiasis SIR-A recent letter in the Transactions (MOTT, 1978) emphasizes the problem of the relationship between surface B antigen and schistosomiasis. This hypothesis, first suggested by some authors in West Africa (BARBOTIN & OUDART, 1972) has been supported by other workers (SAI~~OT et.al., 1973; COLETTE et al.. 1976). Thev suggest that the schistosome itself could play- a &ict role as a carrier of the virus, as do parasite larvae with virus and bacteria. Another way of transmission of hepatitis B virus could be through the excoriation which follows the active cutaneous penetration of the larvae. In the tropics, hepatitis B virus is so widespread that this probably facilitates such a transmission route. However, there is no general agreement that there is an increased prevalence of HBsAg in subjects with schistosomiasis or other parasitic infections which are transmitted through the skin (LEWIS et al., 1972; DIEBOLT & LINHARD, 1974). It is suggested that the higher frequency of the surface
antigen found in patients with hepatosplenic schistosomiasis is due more to the related liver damage than to parasitic disease (LYRA et al., 1976). In a preliminary investigation carried out in Somalia we initially confirmed a high HBs antigenaemia in patients infected with Schistosoma haematobium (DELIA et al., 1977). The prevalence (25.9 y!) was higher than that found in controls (11%) or in subjects with leprosy; furthermore, there was a significant difference in the prevalence of HBsAg between patients with leprosy who carried concomitant parasitic infections (40%) and leprosy patients without helminthiasis (9 %). Again in Somalia, contrasting results were obtained in a subsequent survey aimed at determining the prevalence of ‘e’ antigen in these patients (no e-antigen was found with-a low rate of anti-e antibodies). The prevalence of HBsAg among the patients with urinary schistosomiasis was 14.8 % but the frequency of the antigen among controls reached the value of 34% (NUTI et al., 1978). The most recent study carried out in Somalia for the detection of HBsAg by ELISA in 67 patients infected with S. haematobium gave the following results: a frequency of 19’4% in the patients and 10 y0 among controls, with no statistically significant difference (l? < 0.5) between the two groups. A comparative analysis of the frequency of surface B antigen in three surveys carried out in Somalia in the last few years based on different methods has shown a prevalence of 25 -9 % by direct haemagglutination, 14 *8 % by radio-immunoassay and 19.4% using ELISA (unfortunately it has not been possible for us to use at the same time the three different methods on the same serum samples). Clearly, more work is needed. We are, etc., M. NUTI S. ~DULLAHI ELMI c. ALAR10 P. PALERMO
Department of Tropical and Infectious Diseases, Rome University and Department of Pharmacology, Mogadishu University References Barbotin, M. & Oudart, J. L. (1972). Intestinal parasites and epidemiology of Australian antigen in Africa. British Medical Journal, ii, 653. Colette, J., Garrigue, G. & Sellin, B. (1976). Rapport entre la presence de l’antigene HBs et les helminthiases. Nouvelle Presse Medicale, 24, 1540. Delia, S., Nuti, M. & Soro, S. (1977). Rapporti tra HBsAg e parassitosi : osservazioni in pazienti e con schistosomiasi. con anchilostomiasi Quaderni Sclavo di Diagnostica, 13, 238-243. Diebolt, G. & Linhard, J. (1974). Variation de la frequence de l’antigene et de l’anticorps HB en Afrique Noire. Me’decine Tropicale, 34, 529-544. Lewis, E. A., Montefiore, D., Smith, J. A. & Sogbetun, A. 0. (1972). Intestinal parasites and Au antigen transmission in Africa. British Medical Journal, iv, 549.
visceral leishmaniasis demonstrated by the detection of Leishmaniu amastigotes in smears prepared by spleen biopsy (slides examined by Charles Nicolle of the Pasteur Institute of Tunis). PATANE (1928) referred to a case from Tolmetta found during careful search in Cirenaica between 1912 and 1925: During his 20 Years of medical nractice in Trinoli. MA~Z~LANI (1933) diagnosed 11 cases, two of w-hi& were confirmed by bone marrow examination. From these historical data, we know that visceral leishmaniasis has been present for years in Libya, even if the number of cases reported is low. In this context, the observation of Dar merely confirms the previous reports and in doing so further emphasizes the need of careful search for the disease in this country. I am, etc., JEAN PIERRE DEDET Institut Pasteur, Unite’ de Parasitologic Experimentale, 25, rue du Docteur Roux, 75015-Paris References Dar, F. K. (1978). An autochthonous case of kalaazar in Libya. Transactions of the Royal Society of Tropical Medicine and Hygiene, 72, 555-556. Mazzolani, D. A. (1933). La leishmaniose viscerale infantile en Tripolitaine. Compte rendus du ler Congres international d’Hv&ne Mediterrane’enne. -1, 338-312. Patane, C. (1928). I1 posto attuale della Cirenaica nell’ enidemioloeia delle leishmaniasi nel Nord Africa.- Archivii Italian0 di Scienze Mediche Coloniale, 9, 69-83. (Quoted in Tropical Disease Bulletin (1929). 26. 315.) Tashim, 1.‘(1919). Sur l’existence en Tripolitaine de kala-azar et de la fievre mediterraneenne. Bulletin de la Societe de Pathologie exotique, 3, 511-512.
Accepted for publication
10th January,
1979.
and primary liver cell carcinoma SIR-I wonder if I may be allowed to comment on a statement made in your correspondence columns in “The possible relationship of Schistosoma infection and liver carcinoma” (MOTT. 1978) which has iust reached me. The writer states that the geographical prevalence of liver carcinoma corresponds to that of S. mansoni and S. japonicum. I cannot comment on S. .japonicum but I do not think this statement is true of mansoni infection. S. mansoni is uncommon in southern Nigeria (HINZ. 1968) where the incidence of liver-carcinoma -is hi& (EDINGTON & MACLEAN, 1965) whereas it is low in. Egypt where S. mansoni infection is nrevalent. In Bahia in Brazil. CHEEVER & ANDRADE (f967) in a large autopsy series found that hepatocellular carcinoma was more common in uninfected cases than in those suffering from mansoni infection. MARTINEZ-~L~LDONADO
CORRESPONDENCE
351
et al. (1965) considered that S. mansoni played no part in the aetiology of liver carcinoma in Puerto Rico. I do not think therefore that geographical studies would support the claim that there is a marked correlation between a high prevalence of S. munsoni and liver carcinoma. Nevertheless as the author points out HBs antigen has been associated with hepatosplenic schistosomiasis and experimentally it has been shown that schistosome infection renders the liver more sensitive to carcinogenic compounds and the growth of tumours is facilitated in some species of laboratory animals (DOMINGO et al., 1967; hu et al. 1969). It has also been considered that chronic mansoni infections promote disease caused by viral infections. The infection in mice decreased their resistance to S. typhimurium infection (ROCHA et al., 1971) and the sera of natients with heuatosplenic schistosomiasis were shown to have reduced anti-salmonella activity. Complement has also been shown to be reduced, as are the cellular defence mechanisms (FERNANDOS & ROCHA, 1967). It is of interest that ANDRADE & ABREU (1971) have noted an association of follicular lymphoma of the spleen in patients with hepatosplenic S. mansoni infections and EDINGTON et al. (1970) noted a significantly higher number of lymphomas in S. haematobium post-mortems when compared with controls. It is therefore possible that the effects of schistosomiasis on the reticula-endothelial system may have a cancer-promoting effect, especially in tumours of this system, which is similar to the suggestions put forward regarding the presence of holoendemic malaria and the Burkitt lymphoma. The writer has noted schistosomiasis associated with primary liver cell carcinoma in a boy aged 14 years and NKRUMAH (1964) recorded a similar finding in a boy aged eight years-ages at which liver cell carcinoma is uncommon in Nigeria and Ghana. The association may however be fortuitous and much further work requires to be done before an association between S. mansoni and liver cell cancer can be accepted. I am, etc., G. M. EDINGTON College of Medical Sciences, University of Maiduguri, Maiduguri, Nigeria
Schistosomiasis
References Andrade, Z. A. & Abreu, W. N. (1971). Follicular lymphoma of the spleen in patients with hepatosplenic schistosomiasis. American Journal of Tropical Medicine and Hygiene, 20, 237-242. Cheever, A. W. & Andrade, Z. A. (1967). Pathological lesions associated with Schistosoma mansoni infection in man. Transactions of the Royal Society of Tropical Medicine and Hygiene, 61, 626-639. Domingo, E. O., Warren, K. S. & Stenger, R. J. (1967). Increased incidence of hepatoma in mice with chronic schistosomiasis mansoni treated with a carcinogen. American Journal of Pathology, 51. 307-321. Edington, G. M. & Maclean, C. M. U. (1965). A cancer rate survey in Ibadan, Western Nigeria 1960-63. British Journal of Cancer, 19, 471-481.
352
TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, VOL. 73, No. 3, 1979. CORRESPONDENCE
Edington, G. M., von Lichtenberg, F., Nwabuebo, I., Taylor, J. R. & Smith, J. N. (1970). Pathologic effects of schistosomiasis in Ibadan, Western State of Nigeria. American Journal of Tropical Research, 29, 837-847. Fernandos, D. J. & Rocha, H. (1967). Caracteristicas da reacao inflamatopio em pacientes corn forma hepatosplenica de esquistossome mansonica calazar. Revista do Instituto de Medicina Tropical de Sgo Pa&o, 9, 129-133. Hinz, E. (1966). Intestinal helminth infection in West Africa (Southern Nigeria). Zeitschrzft fiir Tropenmedizin und Parasitologic, 17, 427-442. Liu, L. B., Domingo, E. O., Stenger, R. J., Warren, K. S., Confer, D. B. & Johnson, E. A. (1969). An ultra structural study of the toxic and carcinogenic effects of 2-amino-5-azotoluene on the livers of schistosome-infected and uninfected mice. Cancer Medicine and Hygiene, 19, 982-995. Martinez-Maldonado, M., Girod, C. E., Ramirez De Arellano, G. & Ramirez, E. A. (1965). Liver cell carcinoma (hepatoma) in Puerto Rico. A survey of 26 cases. American Journal of Digestive Diseases, 10, 522-529. Mott, K. E. (1978). Possible relationship of Schistosoma infection and liver carcinoma. Transactions of the Royal Society of Tropical Medicine and Hygiene, 72, 552-553. Nkrumah, P. K. (1964). Primary carcinoma of the liver and post-necrotic cirrhosis in a Ghanian child with non-hepatic bilharziasis. Ghana Medical Journal, 3, 129-133. Rocha, H., Kirk, J. W. & Hearey! C. D. Jr. (1971). Prolonged Salmonella bacteremra in patients with Schistosoma mansoni infection. Archives of Internal Medicine, 128, 254-257.
Accepted for publication
Surface
26th January,
1979.
hepatitis B antigen and urinary schistosomiasis SIR-A recent letter in the Transactions (MOTT, 1978) emphasizes the problem of the relationship between surface B antigen and schistosomiasis. This hypothesis, first suggested by some authors in West Africa (BARBOTIN & OUDART, 1972) has been supported by other workers (SAI~~OT et.al., 1973; COLETTE et al.. 1976). Thev suggest that the schistosome itself could play- a &ict role as a carrier of the virus, as do parasite larvae with virus and bacteria. Another way of transmission of hepatitis B virus could be through the excoriation which follows the active cutaneous penetration of the larvae. In the tropics, hepatitis B virus is so widespread that this probably facilitates such a transmission route. However, there is no general agreement that there is an increased prevalence of HBsAg in subjects with schistosomiasis or other parasitic infections which are transmitted through the skin (LEWIS et al., 1972; DIEBOLT & LINHARD, 1974). It is suggested that the higher frequency of the surface
antigen found in patients with hepatosplenic schistosomiasis is due more to the related liver damage than to parasitic disease (LYRA et al., 1976). In a preliminary investigation carried out in Somalia we initially confirmed a high HBs antigenaemia in patients infected with Schistosoma haematobium (DELIA et al., 1977). The prevalence (25.9 y!) was higher than that found in controls (11%) or in subjects with leprosy; furthermore, there was a significant difference in the prevalence of HBsAg between patients with leprosy who carried concomitant parasitic infections (40%) and leprosy patients without helminthiasis (9 %). Again in Somalia, contrasting results were obtained in a subsequent survey aimed at determining the prevalence of ‘e’ antigen in these patients (no e-antigen was found with-a low rate of anti-e antibodies). The prevalence of HBsAg among the patients with urinary schistosomiasis was 14.8 % but the frequency of the antigen among controls reached the value of 34% (NUTI et al., 1978). The most recent study carried out in Somalia for the detection of HBsAg by ELISA in 67 patients infected with S. haematobium gave the following results: a frequency of 19’4% in the patients and 10 y0 among controls, with no statistically significant difference (l? < 0.5) between the two groups. A comparative analysis of the frequency of surface B antigen in three surveys carried out in Somalia in the last few years based on different methods has shown a prevalence of 25 -9 % by direct haemagglutination, 14 *8 % by radio-immunoassay and 19.4% using ELISA (unfortunately it has not been possible for us to use at the same time the three different methods on the same serum samples). Clearly, more work is needed. We are, etc., M. NUTI S. ~DULLAHI ELMI c. ALAR10 P. PALERMO
Department of Tropical and Infectious Diseases, Rome University and Department of Pharmacology, Mogadishu University References Barbotin, M. & Oudart, J. L. (1972). Intestinal parasites and epidemiology of Australian antigen in Africa. British Medical Journal, ii, 653. Colette, J., Garrigue, G. & Sellin, B. (1976). Rapport entre la presence de l’antigene HBs et les helminthiases. Nouvelle Presse Medicale, 24, 1540. Delia, S., Nuti, M. & Soro, S. (1977). Rapporti tra HBsAg e parassitosi : osservazioni in pazienti e con schistosomiasi. con anchilostomiasi Quaderni Sclavo di Diagnostica, 13, 238-243. Diebolt, G. & Linhard, J. (1974). Variation de la frequence de l’antigene et de l’anticorps HB en Afrique Noire. Me’decine Tropicale, 34, 529-544. Lewis, E. A., Montefiore, D., Smith, J. A. & Sogbetun, A. 0. (1972). Intestinal parasites and Au antigen transmission in Africa. British Medical Journal, iv, 549.