- Email: [email protected]
DO LEISHMANIA SEROTYPES MIMIC HUMAN BLOOD GROUP ANTIGENS?
505
antigens that react against blood group B and T antisera6,7 especially pertinent to our suggestion. The following points support the last two reports6,7 and are presented to advance the hypothesis that the distribution of the different types ofleishmania, and thus leishmaniasis as seen in man, may be influenced by the distribution of blood group antigens.
possess are
Leishmanial serotypes Leishmanial parsites synthesise glycoproteins that are released to the medium (termed EF for excreted factor) and are exploited for serotyping strains.8 Rabbit anti-leishmanial sera differentiate distinct serotypes, fortuitously and perhaps unfortunately, called A, B, and AB, that further resolve into a number of subserotypes. The EFs of the A and B leishmanial groups display specific reactivity with rabbit antisera in gel diffusion, but the parasites show
serological cross-reactivity. The recognition of EF by antibody depends on the carbohydrate segment of the molecule.9 Since EF and the parasite surface share antigenic determinants, immunodominant sugars would be expected to be similar. between ultrasonic and ruler dominal fat thickness.
Relationship
measurements
of ab-
Immunochemical similarity of leishmanial antigens
to
human ABO
blood group antigens
the professorial surgical unit, University College Hospital, London. The measurements were made when the patient was under anaesthesia, on the operating table in the same position for the operation to be undertaken. The incision line was marked and two to three ultrasonic measurements were made along it (P.J.B.). The subcutaneous fat was measured directly with a sterile steel ruler (M.W.M.W.), at exactly the same sites, after the initial incision had been made down to muscle or fascia. The edges of the incision were brought together to avoid the spread and flattening of subcutaneous fat. The ultrasonic and ruler measurements were, as mean ±SD, 25.6:t14.7 7 mm and ::t22.7 7 ± 15 · 4 mm, respectively. Paired values were plotted and the correlation was excellent (r = 0 99) (see figure). A difference of I .4 mm between the two means and of 0 .7 mm between the two standard deviations and the high correlation over a range of 8-65 mm of fat indicates close agreement. The body composition meter measures subcutaneous fat with an accuracy quite sufficient for clinical purposes, and for population surveys and in clinical practice a portable instrument has the advantages of speed and accuracy over a wide range of uncompressed fat thickness and applicability where in the field, in the clinic, in hospital, or at home. It would be especially useful inl obese subjects in whom callipers cannot be used. .
Besides sugars such as mannose and fucose, EF and the ABO antigens contain galactose, N-acetylglucosamine, and N-acetylgalactosamine. 10-12 EF does not contain sialic acid,lo and the sialic acid of BGA has little immunological significance". The lack aromatic peptide components of both EF and BGA totally amino acids and sulphur-containing residues.11,13 Such sugars and peptide constituents are also found in the immunologically active glycoproteins of Trichomonas foetus 1 and Trypanosoma cruzi 15 5 suggesting a widespread distribution of similar antigen molecules among the flagellates. Reaction of leishmanial parasites with anti-human blood group sera We and othershave shown that leishmanial serotype B strains (e.g., L. donovani, B2) are agglutinated by human blood typing antiB serum. Leishmanial serotype A strains (e.g., L. tropica, Ai) are agglutinated by human blood typing anti-A serum as well as by anti-M and anti-N sera. The B strain leishmanias were not agglutinated by anti-M or anti-N sera (C. L. Greenblatt, unpublished). Distribution of leishmanial serotypes and human blood groups We have studied the serotypes of over 330 leishmanial strains, covering most regions of the world where leishmaniasis is endemic. In the Middle East (Israel, Syria, Iraq, Iran, and Saudi Arabia), 98 of 109 isolates were either subserotype Al or A2. In East Africa
We thank Prof. C. G. Clark and Prof. J. C. Waterlow.
Department of
GL, Staveley JM. Blood group P substance in hydatid cyst fluids. Nature 1957; 179: 147-48.
2. Cameron
Human Nutrition,
London School of Hygiene and Tropical Medicine, and Department of Surgery, Faculty of Medical Sciences,
P. J. BALTA M. W. M. WARD A. M. TOMKINS
University College London, London WC1
DO LEISHMANIA SEROTYPES MIMIC HUMAN BLOOD GROUP ANTIGENS?
SlR,-In man, leishmanias are intracellular parasites causing longinfections that resist host defence. We suggest that the leishmanial parasite may utilise a system of camouflage or mimicry of host blood group antigens (BGA) to evade host defence mechanisms. The possible connection between BGAs and communicable disease in general has been considered in the review of term
Muschel.I
Parasite carbohydrate constituents are immunologically related to BGA (e.g., Echinococcus,2Trichinella, and other parasites3) or may be detected as raised titres of host isoagglutinin (e.g., hydatid disease,2 ascariasis, and malaria 3). With giardiasis4 and schistosomiasiss the prevalence of the disease or a specific syndrome differs within the ABO blood groups. Reports that leishmania 1 Muschel LH Blood groups,
disease, and selection. Bact Rev 1966; 30: 427-41.
3. Oliver-Gonzalez J. Immunological properties of polysaccharides from animal parasites. Ann Rev Microbiol 1954; 8: 353-61. 4. Barnes GL, Kay R. Blood groups in giardiasis. Lancet 1977; i: 808. 5. Pereira FEL, Bortolini EF, Carneiro JLA, et al. ABO blood groups and hepatosplenic form of schistosomiasis mansoni (Symmer’s fibrosis). Trans R Soc Trop Med Hyg 1979; 73: 238. 6. Decker-Jackson JE, Honigberg BM. Glycoproteins released by Leishmania donovani. Immunological relationships with host and bacterial antigens and preliminary biochemical analysis. J Protozool 1978; 25: 515-25. 7. Pardoe GI, Jaquet H, Hahn R, et al. The immunochemistry of surface antigens of Leishmania enrietti. Behring Inst Mitt 1975; 58: 30-39. 8. Schnur LF, Zuckerman A, Greenblatt CL. Leishmanial serotypes as distinguished by the gel diffusion of factors excreted in vitro and in vivo. Isr J Med Sci 1972; 8: 932-42. 9. Slutsky GM, El-On J, Greenblatt CL. Leishmanial excreted factor: protein-bound and free forms from promastigote cultures of Leishmania tropica and Leishmania donovani. Infect Immun 1979; 26: 916-24. 10. Slutzky GM, Greenblatt CL. Isolation of a carbohydrate-rich, imunologically active factor from cultures of Leishmania tropica FEBS Lett 1977; 80: 401-04. 11. Marcus DM. The ABO and Lewis blood-group system- immunochemistry, genetics and relation to human disease. N Engl J Med 1969; 280: 994-1006. 12. Jacobson RL, Slutzky GM, Greenblatt CL, Schnur LF. Surface rection of leishmania: Lectin mediated agglutination. Ann Trop Med Parasit (in press). 13. Slutzky GM, Schnur LF, Jacobson RL, Greenblatt CL. The lectin affinities of the leishmanial excreted factor. Isr J Med Sci 1980, 16: 559-60 14. Feinberg JG, Morgan WTJ The isolation of a specific substance and a glycogen-like polysaccharide from Tnchomonas foetus (var. Manley). Br J Exp Path 1953; 33: 104-18. 15. Alves MJM, Dolli W. Glycoproteins from Trypanosoma cruzi: partial purification by gel chromatography. FEBS Lett 1975; 52: 188-90
506 INTERFERON ASSAY AS A DIAGNOSTIC TEST
(Kenya, Ethiopia, and Sudan), 58 of 59 were subserotype B1 or B2.
In Latin America, there appears to be greater variation in all leishmanial serotypes, reflecting the greater complexity of New World leishmanial taxonomy. Could these geographical differences in the distribution of leishmanial serotypes be related to the distribution of human BGAs? Since both the ABO and MN(T) systems are expressed by the leishmanias, the relation between leishmanial and human blood group serotypes is probably complex. Ifwe consider, as a first approximation, only the ABO system, there appears to be a degree of correspondence with leishmanial serotypes. Thus, while a difference in frequency of leishmanial serotypes is evident in the Middle East when compared to East Africa, a concomitant reduction in the proportion of type A individuals resulting in a decrease in the ratio of A/B from approxin the Middle East to about 1.3:1 in East Africa is also seen.Other factors such as minor human blood groups, distribution of insect vectors and animal reservoirs and other considerations must be taken into account when trying to explain differences in distribution of leishmanial serotypes. Perhaps only in certain areas of Latin America can a direct association between leishmanial and blood group serotypes be considered. The indigenous population is more than 90% type 0, thus possessing both anti-A and anti-B antibodies. The leishmania isolated from this region show great variation in serotype and have been classified as Ai-A6, AIB2-A4B2, and indeterminant BX serotypes. Natives of the region are less severely affected by these leishmania than are an imported population (descendants of slaves brought from Africa), largely blood types A and B, who have destructive lesions. 17 Perhaps antibody pressure has been a factor in parsite variation and has forced each leishmania into its own ecological niche.
imatehy 2:1
Human immune responses to leishmania Marcus 11expressed the possible interaction of a parasite antigen and host BGA as follows: "Ifthe infectious agent possessed an A antigen, the anti-A antibody possessed by group 0 and B persons might contribute to host defence mechanisms; group A persons might be partially tolerant to the microorganisms and, consequently, exhibit an ineffective immune response". A similar phenomenon might aid in explaining a curious feature of antibody measurement in cutaneous leishmaniasis. L. donovani (type B?) or L. braziliensis (type A3B2) may be used as antigen to detect antibodies against L. tropica (type AI) by immunofluorescence, often with better results than with the homologous antigen. 18 These diagnostic studies did not take into account the ABO blood type of the patients. We would therefore expect that the serum of an infected person of B blood group would more easily detect by serology an A rather than a B leishmania, and vice versa.
Conclusion The arguments presented to support the interaction of leishmanial and human blood group serotypes are far from rigorous. However, considered together they are intriguing and seem to warrant a search of immunochemical, clinical, ecological, and epidemiological data to confirm or negate the suggestion. We thank Dr Cyril Levine of the reference laboratory for immunohaematology and blood groups, Central Laboratory, Israel Ministry of Health, Jerusalem, and Dr Theodore Dishon and Dr Uri Zehavi of the Hebrew University of Jerusalem for their assistance and advice. Our research is supported by grants from the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases.
Department of Protozoology and Kuvin Centre for the Study of Infectious and Tropical Diseases, Hebrew University-Hadassah Medical School, Jerusalem, Israel
CHARLES L. GREENBLATT
JEREMY D. KARK
SIR,-Interferon is found in the sera of certain patients with proved viral infections and may explain some of the general symptoms experienced. Its presence might also be exploited in diagnosis. Matthews and Lawrencel have shown that acute phase sera from confirmed cases of virus infection in hospital patients were often positive, whereas in bacterial infections they were negative. We have examined sera from 124 patients who had been thoroughly examined by virus isolation and serology: 69 children with febrile convulsions and a variety of associated symptoms such as pharyngitis;2 29 adults admitted to hospital during an influenza epidemic, tested for influenza virus and anti-influenza antibodies; and 26 adults with mild colds whose specimens were examined by inoculation of tissue cultures and organ cultures with electron
microscopy.3 RESULTS OF INTERFERON TESTS
* 17 patients from whom more than one excluded. Interferon was detected in 9.
Sera
isolated have been
diluted 1: 10 and added to cultures of V3 cells which challenged with vesicular stomatitis virus.The endpoint detected 1 reference unit 69/19 of human leucocyte interferon were
(IFNa). Interferon
was
detected in 45% of the children with febrile con-
vulsions, 34% of the adults with influenza, and 15% of the adults with colds. It was found in the sera of 19 of the 65 patients from whom one virus was isolated (table) and from 14 of the 38 in whom a staphylococcus was cultured from the throat or in whom no organisms were found. Interferon is not found in the sera ofhealthy persons by this technique. The number of positive results seems to be related to the severity of the virus infection and also, possibly, to the type of infecting organism. Thus it was positive in half of the influenza and parainfluenza cases, in less than half of the enterovirus and coronavirus infections, and in hardly any of the’ adenovirus and rhinovirus infections. The test is usually negative in infections with hepatitis and herpesviruses and always negative in uninfected subjects. The test was nevertheless positive in a substantial number of our patients whose illnesses resembled acute virus infections (such as febrile convulsions, acute gastroenteritis, and respiratory disease) but in whom tests for individual viruses were negative, so we believe the presence of interferon indicated that they had an otherwise unrecognised virus infection, although in some it may have been an infection with Haemophilus spp. The numbers are still small, but indicate to us that tests for serum interferon may be a useful adjunct in detecting infection with viruses, particularly those producing acute and severe disease, and that they may be positive in cases in which thorough diagnostic tests
LIONEL F. SCHNUR GERALD M. SLUTZKY 2.
AE, Kopéc AC, Domaniewska-Sobczak K. The distribution of the human blood groups and other polymorphisms. London: Oxford Univ Press; 1976. Walton BC, Valverde L. Racial differences in espundia. Ann Trop Med Parasit 1979;
16. Mourant
73: 23-29. 18. Wyler DJ, Weinbaum responses of human 215-21.
was
were
1. Matthews
17.
organism
3. 4.
FI, Herrod HR. Characterization of in vitro proliferative lymphocytes to leishmanial antigens. J Inf Dis 1979; 140:
5.
THJ, Lawrence MK. Serum interferon assay as a possible test for virus infections of man. Arch Virol 1979; 59: 35-38. Lewis HM, Parry JV, Parry RP, Davies HA, Sanderson PJ, Tyrrell DAJ, Valman HB. Role of viruses in febrile convulsions. Arch Dis Childh 1979; 54: 869-76 Larson HE, Reed SE, Tyrrell DAJ. Isolation of rhinoviruses and coronaviruses from 38 colds in adults. J Med Virol 1980; 5: 221-29. Atherton KT, Burke DC. Interferon induction by viruses and polynucleotides a differential effect of camptothecin. J Gen Virol 1975; 29: 297-304. Secher DE, Burke DC. A monoclonal antibody for large-scale purification of human leukocyte interferon. Nature 1980, 285: 446-50.
antigens that react against blood group B and T antisera6,7 especially pertinent to our suggestion. The following points support the last two reports6,7 and are presented to advance the hypothesis that the distribution of the different types ofleishmania, and thus leishmaniasis as seen in man, may be influenced by the distribution of blood group antigens.
possess are
Leishmanial serotypes Leishmanial parsites synthesise glycoproteins that are released to the medium (termed EF for excreted factor) and are exploited for serotyping strains.8 Rabbit anti-leishmanial sera differentiate distinct serotypes, fortuitously and perhaps unfortunately, called A, B, and AB, that further resolve into a number of subserotypes. The EFs of the A and B leishmanial groups display specific reactivity with rabbit antisera in gel diffusion, but the parasites show
serological cross-reactivity. The recognition of EF by antibody depends on the carbohydrate segment of the molecule.9 Since EF and the parasite surface share antigenic determinants, immunodominant sugars would be expected to be similar. between ultrasonic and ruler dominal fat thickness.
Relationship
measurements
of ab-
Immunochemical similarity of leishmanial antigens
to
human ABO
blood group antigens
the professorial surgical unit, University College Hospital, London. The measurements were made when the patient was under anaesthesia, on the operating table in the same position for the operation to be undertaken. The incision line was marked and two to three ultrasonic measurements were made along it (P.J.B.). The subcutaneous fat was measured directly with a sterile steel ruler (M.W.M.W.), at exactly the same sites, after the initial incision had been made down to muscle or fascia. The edges of the incision were brought together to avoid the spread and flattening of subcutaneous fat. The ultrasonic and ruler measurements were, as mean ±SD, 25.6:t14.7 7 mm and ::t22.7 7 ± 15 · 4 mm, respectively. Paired values were plotted and the correlation was excellent (r = 0 99) (see figure). A difference of I .4 mm between the two means and of 0 .7 mm between the two standard deviations and the high correlation over a range of 8-65 mm of fat indicates close agreement. The body composition meter measures subcutaneous fat with an accuracy quite sufficient for clinical purposes, and for population surveys and in clinical practice a portable instrument has the advantages of speed and accuracy over a wide range of uncompressed fat thickness and applicability where in the field, in the clinic, in hospital, or at home. It would be especially useful inl obese subjects in whom callipers cannot be used. .
Besides sugars such as mannose and fucose, EF and the ABO antigens contain galactose, N-acetylglucosamine, and N-acetylgalactosamine. 10-12 EF does not contain sialic acid,lo and the sialic acid of BGA has little immunological significance". The lack aromatic peptide components of both EF and BGA totally amino acids and sulphur-containing residues.11,13 Such sugars and peptide constituents are also found in the immunologically active glycoproteins of Trichomonas foetus 1 and Trypanosoma cruzi 15 5 suggesting a widespread distribution of similar antigen molecules among the flagellates. Reaction of leishmanial parasites with anti-human blood group sera We and othershave shown that leishmanial serotype B strains (e.g., L. donovani, B2) are agglutinated by human blood typing antiB serum. Leishmanial serotype A strains (e.g., L. tropica, Ai) are agglutinated by human blood typing anti-A serum as well as by anti-M and anti-N sera. The B strain leishmanias were not agglutinated by anti-M or anti-N sera (C. L. Greenblatt, unpublished). Distribution of leishmanial serotypes and human blood groups We have studied the serotypes of over 330 leishmanial strains, covering most regions of the world where leishmaniasis is endemic. In the Middle East (Israel, Syria, Iraq, Iran, and Saudi Arabia), 98 of 109 isolates were either subserotype Al or A2. In East Africa
We thank Prof. C. G. Clark and Prof. J. C. Waterlow.
Department of
GL, Staveley JM. Blood group P substance in hydatid cyst fluids. Nature 1957; 179: 147-48.
2. Cameron
Human Nutrition,
London School of Hygiene and Tropical Medicine, and Department of Surgery, Faculty of Medical Sciences,
P. J. BALTA M. W. M. WARD A. M. TOMKINS
University College London, London WC1
DO LEISHMANIA SEROTYPES MIMIC HUMAN BLOOD GROUP ANTIGENS?
SlR,-In man, leishmanias are intracellular parasites causing longinfections that resist host defence. We suggest that the leishmanial parasite may utilise a system of camouflage or mimicry of host blood group antigens (BGA) to evade host defence mechanisms. The possible connection between BGAs and communicable disease in general has been considered in the review of term
Muschel.I
Parasite carbohydrate constituents are immunologically related to BGA (e.g., Echinococcus,2Trichinella, and other parasites3) or may be detected as raised titres of host isoagglutinin (e.g., hydatid disease,2 ascariasis, and malaria 3). With giardiasis4 and schistosomiasiss the prevalence of the disease or a specific syndrome differs within the ABO blood groups. Reports that leishmania 1 Muschel LH Blood groups,
disease, and selection. Bact Rev 1966; 30: 427-41.
3. Oliver-Gonzalez J. Immunological properties of polysaccharides from animal parasites. Ann Rev Microbiol 1954; 8: 353-61. 4. Barnes GL, Kay R. Blood groups in giardiasis. Lancet 1977; i: 808. 5. Pereira FEL, Bortolini EF, Carneiro JLA, et al. ABO blood groups and hepatosplenic form of schistosomiasis mansoni (Symmer’s fibrosis). Trans R Soc Trop Med Hyg 1979; 73: 238. 6. Decker-Jackson JE, Honigberg BM. Glycoproteins released by Leishmania donovani. Immunological relationships with host and bacterial antigens and preliminary biochemical analysis. J Protozool 1978; 25: 515-25. 7. Pardoe GI, Jaquet H, Hahn R, et al. The immunochemistry of surface antigens of Leishmania enrietti. Behring Inst Mitt 1975; 58: 30-39. 8. Schnur LF, Zuckerman A, Greenblatt CL. Leishmanial serotypes as distinguished by the gel diffusion of factors excreted in vitro and in vivo. Isr J Med Sci 1972; 8: 932-42. 9. Slutsky GM, El-On J, Greenblatt CL. Leishmanial excreted factor: protein-bound and free forms from promastigote cultures of Leishmania tropica and Leishmania donovani. Infect Immun 1979; 26: 916-24. 10. Slutzky GM, Greenblatt CL. Isolation of a carbohydrate-rich, imunologically active factor from cultures of Leishmania tropica FEBS Lett 1977; 80: 401-04. 11. Marcus DM. The ABO and Lewis blood-group system- immunochemistry, genetics and relation to human disease. N Engl J Med 1969; 280: 994-1006. 12. Jacobson RL, Slutzky GM, Greenblatt CL, Schnur LF. Surface rection of leishmania: Lectin mediated agglutination. Ann Trop Med Parasit (in press). 13. Slutzky GM, Schnur LF, Jacobson RL, Greenblatt CL. The lectin affinities of the leishmanial excreted factor. Isr J Med Sci 1980, 16: 559-60 14. Feinberg JG, Morgan WTJ The isolation of a specific substance and a glycogen-like polysaccharide from Tnchomonas foetus (var. Manley). Br J Exp Path 1953; 33: 104-18. 15. Alves MJM, Dolli W. Glycoproteins from Trypanosoma cruzi: partial purification by gel chromatography. FEBS Lett 1975; 52: 188-90
506 INTERFERON ASSAY AS A DIAGNOSTIC TEST
(Kenya, Ethiopia, and Sudan), 58 of 59 were subserotype B1 or B2.
In Latin America, there appears to be greater variation in all leishmanial serotypes, reflecting the greater complexity of New World leishmanial taxonomy. Could these geographical differences in the distribution of leishmanial serotypes be related to the distribution of human BGAs? Since both the ABO and MN(T) systems are expressed by the leishmanias, the relation between leishmanial and human blood group serotypes is probably complex. Ifwe consider, as a first approximation, only the ABO system, there appears to be a degree of correspondence with leishmanial serotypes. Thus, while a difference in frequency of leishmanial serotypes is evident in the Middle East when compared to East Africa, a concomitant reduction in the proportion of type A individuals resulting in a decrease in the ratio of A/B from approxin the Middle East to about 1.3:1 in East Africa is also seen.Other factors such as minor human blood groups, distribution of insect vectors and animal reservoirs and other considerations must be taken into account when trying to explain differences in distribution of leishmanial serotypes. Perhaps only in certain areas of Latin America can a direct association between leishmanial and blood group serotypes be considered. The indigenous population is more than 90% type 0, thus possessing both anti-A and anti-B antibodies. The leishmania isolated from this region show great variation in serotype and have been classified as Ai-A6, AIB2-A4B2, and indeterminant BX serotypes. Natives of the region are less severely affected by these leishmania than are an imported population (descendants of slaves brought from Africa), largely blood types A and B, who have destructive lesions. 17 Perhaps antibody pressure has been a factor in parsite variation and has forced each leishmania into its own ecological niche.
imatehy 2:1
Human immune responses to leishmania Marcus 11expressed the possible interaction of a parasite antigen and host BGA as follows: "Ifthe infectious agent possessed an A antigen, the anti-A antibody possessed by group 0 and B persons might contribute to host defence mechanisms; group A persons might be partially tolerant to the microorganisms and, consequently, exhibit an ineffective immune response". A similar phenomenon might aid in explaining a curious feature of antibody measurement in cutaneous leishmaniasis. L. donovani (type B?) or L. braziliensis (type A3B2) may be used as antigen to detect antibodies against L. tropica (type AI) by immunofluorescence, often with better results than with the homologous antigen. 18 These diagnostic studies did not take into account the ABO blood type of the patients. We would therefore expect that the serum of an infected person of B blood group would more easily detect by serology an A rather than a B leishmania, and vice versa.
Conclusion The arguments presented to support the interaction of leishmanial and human blood group serotypes are far from rigorous. However, considered together they are intriguing and seem to warrant a search of immunochemical, clinical, ecological, and epidemiological data to confirm or negate the suggestion. We thank Dr Cyril Levine of the reference laboratory for immunohaematology and blood groups, Central Laboratory, Israel Ministry of Health, Jerusalem, and Dr Theodore Dishon and Dr Uri Zehavi of the Hebrew University of Jerusalem for their assistance and advice. Our research is supported by grants from the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases.
Department of Protozoology and Kuvin Centre for the Study of Infectious and Tropical Diseases, Hebrew University-Hadassah Medical School, Jerusalem, Israel
CHARLES L. GREENBLATT
JEREMY D. KARK
SIR,-Interferon is found in the sera of certain patients with proved viral infections and may explain some of the general symptoms experienced. Its presence might also be exploited in diagnosis. Matthews and Lawrencel have shown that acute phase sera from confirmed cases of virus infection in hospital patients were often positive, whereas in bacterial infections they were negative. We have examined sera from 124 patients who had been thoroughly examined by virus isolation and serology: 69 children with febrile convulsions and a variety of associated symptoms such as pharyngitis;2 29 adults admitted to hospital during an influenza epidemic, tested for influenza virus and anti-influenza antibodies; and 26 adults with mild colds whose specimens were examined by inoculation of tissue cultures and organ cultures with electron
microscopy.3 RESULTS OF INTERFERON TESTS
* 17 patients from whom more than one excluded. Interferon was detected in 9.
Sera
isolated have been
diluted 1: 10 and added to cultures of V3 cells which challenged with vesicular stomatitis virus.The endpoint detected 1 reference unit 69/19 of human leucocyte interferon were
(IFNa). Interferon
was
detected in 45% of the children with febrile con-
vulsions, 34% of the adults with influenza, and 15% of the adults with colds. It was found in the sera of 19 of the 65 patients from whom one virus was isolated (table) and from 14 of the 38 in whom a staphylococcus was cultured from the throat or in whom no organisms were found. Interferon is not found in the sera ofhealthy persons by this technique. The number of positive results seems to be related to the severity of the virus infection and also, possibly, to the type of infecting organism. Thus it was positive in half of the influenza and parainfluenza cases, in less than half of the enterovirus and coronavirus infections, and in hardly any of the’ adenovirus and rhinovirus infections. The test is usually negative in infections with hepatitis and herpesviruses and always negative in uninfected subjects. The test was nevertheless positive in a substantial number of our patients whose illnesses resembled acute virus infections (such as febrile convulsions, acute gastroenteritis, and respiratory disease) but in whom tests for individual viruses were negative, so we believe the presence of interferon indicated that they had an otherwise unrecognised virus infection, although in some it may have been an infection with Haemophilus spp. The numbers are still small, but indicate to us that tests for serum interferon may be a useful adjunct in detecting infection with viruses, particularly those producing acute and severe disease, and that they may be positive in cases in which thorough diagnostic tests
LIONEL F. SCHNUR GERALD M. SLUTZKY 2.
AE, Kopéc AC, Domaniewska-Sobczak K. The distribution of the human blood groups and other polymorphisms. London: Oxford Univ Press; 1976. Walton BC, Valverde L. Racial differences in espundia. Ann Trop Med Parasit 1979;
16. Mourant
73: 23-29. 18. Wyler DJ, Weinbaum responses of human 215-21.
was
were
1. Matthews
17.
organism
3. 4.
FI, Herrod HR. Characterization of in vitro proliferative lymphocytes to leishmanial antigens. J Inf Dis 1979; 140:
5.
THJ, Lawrence MK. Serum interferon assay as a possible test for virus infections of man. Arch Virol 1979; 59: 35-38. Lewis HM, Parry JV, Parry RP, Davies HA, Sanderson PJ, Tyrrell DAJ, Valman HB. Role of viruses in febrile convulsions. Arch Dis Childh 1979; 54: 869-76 Larson HE, Reed SE, Tyrrell DAJ. Isolation of rhinoviruses and coronaviruses from 38 colds in adults. J Med Virol 1980; 5: 221-29. Atherton KT, Burke DC. Interferon induction by viruses and polynucleotides a differential effect of camptothecin. J Gen Virol 1975; 29: 297-304. Secher DE, Burke DC. A monoclonal antibody for large-scale purification of human leukocyte interferon. Nature 1980, 285: 446-50.