- Email: [email protected]
SCREENING FOR TOXOPLASMOSIS IN PREGNANCY
1196 reflect both the
erythroid hypoplasia and the dyserythropoietic changes. Megaloblastic changes were infrequent, suprisingly in view of the fact that 69% of patients on zidovudine2 become markedly macrocytic. Only 4 of our patients had megaloblastic marrows; in 1 of these the changes were confined to the white cell series. 3 of the 4 patients with megaloblastic marrows were macrocytic; in none was the megaloblastic change severe. Dysplastic changes in the white cell series were noted in 3 patients and affected the megakaryocytic series in only 1. These bone marrow findings in patients receiving zidovudine differ from those in larger series of 75 HIV-positive bone marrows in which only 12 marrows were hypocellular and dysplastic change was noted in only 12. It is worrying that bone marrow changes in patients on zidovudine seem not to be readily reversed when the drug is withdrawn. In 2 patients in whom the drug had been discontinued 5 and 10 weeks before the bone marrow was examined hypocellularity was still present; similar findings have been described by Gill et al.4 Zidovudine has a short half life, so we conclude that long-term treatment may damage the bone marrow progenitor stem cell pool. The dysplastic changes seen in the erythroid and granulocytic cell lines are also disquieting. These findings have serious implications for the use of zidovudine in HIV positive but symptom-free individuals. Division of Pathology, St Stephen’s Hospital, London SW10 9TH
NAHEED MIR CHRISTINE COSTELLO
1. Dainiak N,
Worthington M, Riordan MA, Kreczko S, Goldman L 3 azido 3 deoxythymidine inhibits proliferation m vitro of human haemopoetic progenitor cells. Br J Haematol 1988; 69: 299-304. 2. Richman DD, et al. The toxicity of azidothymidine m the treatment of patients with AIDS and AIDS-related complex. N Engl Med 1987; 317: 192-97 J 3. Costello C. Haematological abnormalities in human immunodeficiency virus (HIV) disease. J Clin Pathol 1988; 41: 711-15 4. Gill PS, Ranck M, Bymes RK, Causey D Azidothymidine associated with bone marrow failure in the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1987; 107: 502-05.
DIABETES IN AIDS PATIENTS
with intense ketonuria was found at this time. Insulin treatment was prescribed with improvement of clinical and laboratory findings. He had no antibodies to CMV (IgM). Basal C-peptide was 0-9 ng/ml and insulin autoantibody was 1.% (normal 1—3%). Analysis of lymphocyte subsets showed: CD4 (T helper) 20% (normal 41-59%), CD8 (T suppressor) 41% (20-28%), and CD4/CD8 ratio 0 48 (11-2-9). At discharge the insulin dose required was 34 IU per day. We think that a decrease in the CD4 subset in AID S patients does not prevent the onset of clinical type I diabetes mellitus. Different forms of clinical onset of diabetes in these patients support an HIV involvement in its pathogensis.2 The occurrence of type I diabetes mellitus and its clinical and immunological features in this group of
patients requires study. VENDRELL I. CONGET A. MUÑOZ J. VIDAL A. NUBIOLA
J.
1 Brivet
F, Coffin B, Bedossa P,
et
al Pancreatic lesions in AIDS Lancet 1987;
n:
570-71 2 Vendrell
SIR,-Dr Joynson and Dr Payne (Oct 1, p 795) discuss screening
toxoplasmosis in pregnancy. Reporting long-term from et all have argued strongly for adequate treatment. Daffos France, In Austria, toxoplasmosis screening during pregnancy has been mandatory since 1974. From January, 1984, to December, 1987, 8289 deliveries took place in the obstetrics department at Innsbruck University. In 20 women (0-24%) a recent acute toxoplasma infection was diagnosed-on the basis of seroconversion, titres of specific IgG not below 1024, presence of IgM, and positive complement fixation test-between the 10th and 30th week of gestation (median 19 weeks). This frequency of recent toxoplasma infection in the Tyrol accords with the 0-30% found in Styria (another part of Austria)2 and with the results of Joynson and Payne. All women diagnosed were treated for 4 weeks with pyrimethamine and sulfadiazine, with the addition of folinic acid. In a few cases, spiramycin was used before the 20th gestation week. Treatment was tolerated well, and no significant changes in haemoglobin, haematocrit, leucocyte
for
acute
count, or platelet count were noted. 3 infants had specific IgG antibodies in blood
samples drawn from the umbilical cord artery immediately after delivery; specific IgM was detectable in none, however. In no case were clinical signs of cerebral calcification, chorioretinitis, myocarditis, or other typical sequelae of congenital toxoplasmosis seen. All infants were born between the 39th and 42nd gestational week. There were no significant alterations in umbilical artery pH (mean 7 27 [SD 008]), birthweight (3420 [447] g), or Apgar score. Thus, our data confirm those of Joynson and Payne on the prevalence of prenatal toxoplasmosis, and add weight to the importance of adequate treatment.
Toxoplasmosis is also a problem in transfusion medicine. In the Tyrol, since October, 1986, all voluntary blood donations have been routinely tested for neopterin, as a marker for the activation of cell-mediated immunity.3 Of 76 587 donors tested, 1242 (1’60%) had raised neopterin levels and 650 of these agreed to clinical and laboratory investigation. 6 donors had serological evidence of recent toxoplasmosis at the time of blood donation.4 Department of Obstetrics and Gynaecology,
SIR,-Dr Boudes (Sept 24, p 748) comments that the development of autoimmune type I diabetes may be prevented in AIDS patients by the progressive loss of helper (CD4+) T lymphocytes. A cytomegalovirus (CMV) tropism for pancreatic islet cells has been noted.’ We have seen an AIDS patients in whom a classical onset of type I diabetes with ketosis developed, despite a low helper T lymphocyte subset. A 29-year-old man had been diagnosed with AIDS six months before. He was admitted with progressive weight loss, polyuria, and polydipsia of one month’s duration. Hyperglycaemia (590 mg/dl)
Endocrinology and Diabetes Unit, and Microbiology Service, Hospital Clinic I Provincial, 08036 Barcelona, Spain
SCREENING FOR TOXOPLASMOSIS IN PREGNANCY
J, Nubiola A, Goday A, et al. HIV and the pancreas Lancet 1987, ii. 1212
Institute for Medical Chemistry and Biochemistry; and Central Institute for Blood Transfusion and Department of Immunology, University of Innsbruck, A-6020 Innsbruck, Austria
LOTHAR C. FUITH GILBERT REIBNEGGER MARTIN HONLINGER HELMUT WACHTER
F, Forestier F, Capella-Pavlovsky M, et al. Prenatal management of 746 pregnancies at risk for congenital toxoplasmosis N Engl J Med 1988, 318: 271-75 2. Mayer HO, Stunzner D, Rosanelli K Wertigkeit eines Toxoplasmose-Screenings Zentralbl Gynakol 1983; 105: 1097-100. 3. Fuchs D, Hausen A, Reibnegger G, Werner ER, Dierich MP, Wachter H. Neopterin as a marker for activated cell-mediated immunity application in HIV infection Immunol Today 1988; 9: 150-55 4 Honlinger M, Fuchs D, Hausen A, et al Serum-Neopterin-bestimmung zur zusatzlichen Sicherung der Bluttransfusion Dtsch Med Wochenschr (in press) 1 Daffos
PSITTACINE BIRDS AND CHLAMYDIA
SIR,-Dr Wreghitt and Dr Taylor (Sept 24, p 743), continuing the debate on imported psittacine birds and respiratory chlamydial infections, play down the significance of our material. We studied more than 160 000 sera referred to a central virus laboratory over a 17-year period, and found high titre antibody to chlamydia-specific antigen in less than 2%. However, in this extensive material, a serological diagnosis due to a single causative agent was obtained year by year in no more than 1-3% of cases, the highest rates being seen during influenza A epidemics.1 In Kleemola’s study up to one-third of pneumonias in Finnish recruits, who would not have been exposed to psittacine birds, were of chlamydial origin in some outbreaks.’ These chlamydia were shown by specific microimmunofluorescence serology to be TWAR strains, and this identification has been verified by isolation.’ A serological response in the complement-fixation test cannot be ascribed to C psrttaci, C trachorrtatis, or TWAR strains until isolation or specific
erythroid hypoplasia and the dyserythropoietic changes. Megaloblastic changes were infrequent, suprisingly in view of the fact that 69% of patients on zidovudine2 become markedly macrocytic. Only 4 of our patients had megaloblastic marrows; in 1 of these the changes were confined to the white cell series. 3 of the 4 patients with megaloblastic marrows were macrocytic; in none was the megaloblastic change severe. Dysplastic changes in the white cell series were noted in 3 patients and affected the megakaryocytic series in only 1. These bone marrow findings in patients receiving zidovudine differ from those in larger series of 75 HIV-positive bone marrows in which only 12 marrows were hypocellular and dysplastic change was noted in only 12. It is worrying that bone marrow changes in patients on zidovudine seem not to be readily reversed when the drug is withdrawn. In 2 patients in whom the drug had been discontinued 5 and 10 weeks before the bone marrow was examined hypocellularity was still present; similar findings have been described by Gill et al.4 Zidovudine has a short half life, so we conclude that long-term treatment may damage the bone marrow progenitor stem cell pool. The dysplastic changes seen in the erythroid and granulocytic cell lines are also disquieting. These findings have serious implications for the use of zidovudine in HIV positive but symptom-free individuals. Division of Pathology, St Stephen’s Hospital, London SW10 9TH
NAHEED MIR CHRISTINE COSTELLO
1. Dainiak N,
Worthington M, Riordan MA, Kreczko S, Goldman L 3 azido 3 deoxythymidine inhibits proliferation m vitro of human haemopoetic progenitor cells. Br J Haematol 1988; 69: 299-304. 2. Richman DD, et al. The toxicity of azidothymidine m the treatment of patients with AIDS and AIDS-related complex. N Engl Med 1987; 317: 192-97 J 3. Costello C. Haematological abnormalities in human immunodeficiency virus (HIV) disease. J Clin Pathol 1988; 41: 711-15 4. Gill PS, Ranck M, Bymes RK, Causey D Azidothymidine associated with bone marrow failure in the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1987; 107: 502-05.
DIABETES IN AIDS PATIENTS
with intense ketonuria was found at this time. Insulin treatment was prescribed with improvement of clinical and laboratory findings. He had no antibodies to CMV (IgM). Basal C-peptide was 0-9 ng/ml and insulin autoantibody was 1.% (normal 1—3%). Analysis of lymphocyte subsets showed: CD4 (T helper) 20% (normal 41-59%), CD8 (T suppressor) 41% (20-28%), and CD4/CD8 ratio 0 48 (11-2-9). At discharge the insulin dose required was 34 IU per day. We think that a decrease in the CD4 subset in AID S patients does not prevent the onset of clinical type I diabetes mellitus. Different forms of clinical onset of diabetes in these patients support an HIV involvement in its pathogensis.2 The occurrence of type I diabetes mellitus and its clinical and immunological features in this group of
patients requires study. VENDRELL I. CONGET A. MUÑOZ J. VIDAL A. NUBIOLA
J.
1 Brivet
F, Coffin B, Bedossa P,
et
al Pancreatic lesions in AIDS Lancet 1987;
n:
570-71 2 Vendrell
SIR,-Dr Joynson and Dr Payne (Oct 1, p 795) discuss screening
toxoplasmosis in pregnancy. Reporting long-term from et all have argued strongly for adequate treatment. Daffos France, In Austria, toxoplasmosis screening during pregnancy has been mandatory since 1974. From January, 1984, to December, 1987, 8289 deliveries took place in the obstetrics department at Innsbruck University. In 20 women (0-24%) a recent acute toxoplasma infection was diagnosed-on the basis of seroconversion, titres of specific IgG not below 1024, presence of IgM, and positive complement fixation test-between the 10th and 30th week of gestation (median 19 weeks). This frequency of recent toxoplasma infection in the Tyrol accords with the 0-30% found in Styria (another part of Austria)2 and with the results of Joynson and Payne. All women diagnosed were treated for 4 weeks with pyrimethamine and sulfadiazine, with the addition of folinic acid. In a few cases, spiramycin was used before the 20th gestation week. Treatment was tolerated well, and no significant changes in haemoglobin, haematocrit, leucocyte
for
acute
count, or platelet count were noted. 3 infants had specific IgG antibodies in blood
samples drawn from the umbilical cord artery immediately after delivery; specific IgM was detectable in none, however. In no case were clinical signs of cerebral calcification, chorioretinitis, myocarditis, or other typical sequelae of congenital toxoplasmosis seen. All infants were born between the 39th and 42nd gestational week. There were no significant alterations in umbilical artery pH (mean 7 27 [SD 008]), birthweight (3420 [447] g), or Apgar score. Thus, our data confirm those of Joynson and Payne on the prevalence of prenatal toxoplasmosis, and add weight to the importance of adequate treatment.
Toxoplasmosis is also a problem in transfusion medicine. In the Tyrol, since October, 1986, all voluntary blood donations have been routinely tested for neopterin, as a marker for the activation of cell-mediated immunity.3 Of 76 587 donors tested, 1242 (1’60%) had raised neopterin levels and 650 of these agreed to clinical and laboratory investigation. 6 donors had serological evidence of recent toxoplasmosis at the time of blood donation.4 Department of Obstetrics and Gynaecology,
SIR,-Dr Boudes (Sept 24, p 748) comments that the development of autoimmune type I diabetes may be prevented in AIDS patients by the progressive loss of helper (CD4+) T lymphocytes. A cytomegalovirus (CMV) tropism for pancreatic islet cells has been noted.’ We have seen an AIDS patients in whom a classical onset of type I diabetes with ketosis developed, despite a low helper T lymphocyte subset. A 29-year-old man had been diagnosed with AIDS six months before. He was admitted with progressive weight loss, polyuria, and polydipsia of one month’s duration. Hyperglycaemia (590 mg/dl)
Endocrinology and Diabetes Unit, and Microbiology Service, Hospital Clinic I Provincial, 08036 Barcelona, Spain
SCREENING FOR TOXOPLASMOSIS IN PREGNANCY
J, Nubiola A, Goday A, et al. HIV and the pancreas Lancet 1987, ii. 1212
Institute for Medical Chemistry and Biochemistry; and Central Institute for Blood Transfusion and Department of Immunology, University of Innsbruck, A-6020 Innsbruck, Austria
LOTHAR C. FUITH GILBERT REIBNEGGER MARTIN HONLINGER HELMUT WACHTER
F, Forestier F, Capella-Pavlovsky M, et al. Prenatal management of 746 pregnancies at risk for congenital toxoplasmosis N Engl J Med 1988, 318: 271-75 2. Mayer HO, Stunzner D, Rosanelli K Wertigkeit eines Toxoplasmose-Screenings Zentralbl Gynakol 1983; 105: 1097-100. 3. Fuchs D, Hausen A, Reibnegger G, Werner ER, Dierich MP, Wachter H. Neopterin as a marker for activated cell-mediated immunity application in HIV infection Immunol Today 1988; 9: 150-55 4 Honlinger M, Fuchs D, Hausen A, et al Serum-Neopterin-bestimmung zur zusatzlichen Sicherung der Bluttransfusion Dtsch Med Wochenschr (in press) 1 Daffos
PSITTACINE BIRDS AND CHLAMYDIA
SIR,-Dr Wreghitt and Dr Taylor (Sept 24, p 743), continuing the debate on imported psittacine birds and respiratory chlamydial infections, play down the significance of our material. We studied more than 160 000 sera referred to a central virus laboratory over a 17-year period, and found high titre antibody to chlamydia-specific antigen in less than 2%. However, in this extensive material, a serological diagnosis due to a single causative agent was obtained year by year in no more than 1-3% of cases, the highest rates being seen during influenza A epidemics.1 In Kleemola’s study up to one-third of pneumonias in Finnish recruits, who would not have been exposed to psittacine birds, were of chlamydial origin in some outbreaks.’ These chlamydia were shown by specific microimmunofluorescence serology to be TWAR strains, and this identification has been verified by isolation.’ A serological response in the complement-fixation test cannot be ascribed to C psrttaci, C trachorrtatis, or TWAR strains until isolation or specific