1441
coagulation was noted in 8 patients.
16 had a
t( 15;17) translocation;
cytogenetic studies could not be done in 3 and a normal karyotype was noted in 1 early diagnosed relapse. ATRA was administered daily in two oral doses at 45 mg(m2 daily for 90 days as 10 mg capsules. ATRA was kindly provided by Prof Z. Y. Wang (Shanghai); since July, 1989, the drug has been produced by Roche France. To prevent side-effects, cold cream, lip salve, and eyedrops were given. Analgesics were prescribed when necessary for bone pain. Transfusions were given when the haemoglobin was under 8-0 g/dl or the platelet count was below 20 000/pl. Patients were generally followed up as outpatients. A complete remission (CR) was defmed as absence of blast cells in normal cellular bone marrow, and a normal peripheral blood count (haemoglobin over 12-0 g/dl, platelets over 100 000/pl, and polymorphonuclear cells over 1500/jil). CR was obtained in 19 patients within 1 (3 cases), 2 (11), or 3 (5) months. Cytopenia was corrected in 30 days for platelets, 50 days for neutrophils, and 60 days for anaemia; bone marrow became normal between day 30 and day 90. Transfusions were required in 6 patients, the last being on day 30. Heparin was prescribed for only 1 patient. Sterile conditions were not necessary and only 4 patients received antibiotics. 15 patients were in hospital for less than a week. WBC increased during the first 3 weeks, with characteristics of abnormal maturing cells. In 3 cases, hyperleucocytosis was associated with the persistent degradation of fibrinogen products,
leading fatal meningeal haemorrhage, retinal haemorrhage, and pericarditis and reversible renal failure. Hyperleucocytosis spontaneously decreased despite continued ATRA, and 3 of these patients went into CR. Morphologically three features characterised these cases: (1) bone to
cellularity remained the same; (2) changes in blast cells led maturing cells with near-normal morphology, and Auer rods in some mature cells confirmed differentiation; and (3) normal haematopoietic cells emerged. Adverse effects were dry skin and mucosae in all patients, and bone pain needing analgesics which spontaneously disappeared. Raised triglycerides (11patients) and transaminases (4) were marrow to
reversible once ATRA was discontinued. After 3 months of treatment with ATRA, 9 patients were treated with 6-mercaptopurine and methotrexate, and 6 of these relapsed; 2 received continuous ATRA therapy and both relapsed; and 1 patient was treated with methylglyoxal and cytarabine and relapsed. Since September, 1989,5 patients have been treated with monthly pulse chemotherapy and 2 patients have received allogeneic bone marrow transplantation; none have yet relapsed. In 5 cases of relapse after ATRA intensive chemotherapy (daunorubicin or mitoxantrone plus cytarabine) again achieved CR. Low dose cytarabine was tried in 2 cases without benefit, and in 2 other patients ATRA was prescribed again with no effect in 1 case. In 1 patient, low dose cytarabine followed by ATRA 60 mg/m2 resulted in a transient CR. In 1970 Sachs5 demonstrated in vitro that myeloid malignant cell lines revert to apparently normal cells, abolishing the dogma of the irreversibility of malignant cells. Differentiation in primary culture has proved more difficult. Low-dose cytarabine was the first approach to differentiation therapy, and this has been confirmed in acute non-lymphoblastic leukaemia.6 In vivo it is difficult to discriminate between cytotoxicity and differentiation via inhibition of proliferation. An efficient therapy would be one which induces leukaemic differentiation without inhibition of proliferation. Retinoic acids play an important part in normal differentiation and in the attenuation or complete reversal of malignant cell lines, including acute promyelocytic leukaemia.2,3In Huang and colleagues’4 study in the first attack of APL 23 CRs in 24 patients were achieved by ATRA at doses of 45-100 mg(sm2 daily. In our study with ATRA in first relapse 19 of 20 patients achieved CR within 3 months; such success is unusual in the treatment of relapses of acute promyelocytic leukaemia. This high rate of CR leads one to suggest bone marrow study not after the first remission obtained after chemotherapy, but at the second remission obtained with ATRA. Toxicity was negligible and the treatment was administered orally to outpatients, an equally unusual feature in acute leukaemia.
Hyperleucocytosis was a limiting side-effect in some cases. In our experience hyperleucocytosis is more frequent when the bone marrow is greatly infiltrated by malignant cells, when high disseminated intravascular coagulation is present before treatment, and when in vitro proliferation is observed. This situation is probably less frequent in first relapse but the risk of hyperleucocytosis must be emphasised if ATRA treatment is proposed at diagnosis. Unfortunately, both in patients treated at diagnosis’ and in those treated in first relapse, relapse occurred quite rapidly with maintenance ATRA. The alternate prescription of low-dose cytarabine and ATRA every month gave better results in the Chinese study. We suggest monthly pulse chemotherapy (or allogenic bone marrow transplantation) to maintain CR obtained with ATRA. Recent data suggest that an altered retinoic acid receptor alpha is generated by the t(15;17) specific translocation and that it may contribute to the leukaemogenesis and paradoxical effect of ATRA in these cells.8 We thank Dr P. Faure for help in drug handling, Professor Wang and Roche France for the drug, N. Balitrand for in vitro differentiation assays, and the haematologists in Paris, Orleans, Strasbourg, Clamart, Caen, and Bayonne who cared for the patients. Blood Disease Service,
Haematology Laboratory, Nuclear Medicine Service and INSERM Units 204 and 301, Hôpital Saint Louis, Paris 75010, France; and Haematology Service, Hôpital de Lille
LAURENT DEGOS CHRISTINE CHOMIENNE MARIE THÉRÈSE DANIEL ROLAND BERGER HERVÉ DOMBRET PIERRE FENAUX SYLVIE CASTAIGNE
in differentiation and carcinogenesis. Cancer Res 1983; 43: 3034-40. 2. Breitman TR, Keene BR, Hemmi H. Retinoic add induced differetiation of fresh human leukaemia cells and the human myelomonocytic leukaemia cell lines HL-60, U-937 and THP1. Cancer Surv 1983; 2: 265-91. 3. Chomienne C, Ballerini P, Balitrand N, et al. Differentiation of acute promyelocytic cells by all-trans retinoic acid II: in vitro studies: structure-function relationships. Blood (in press). 4. Huang ME, Ye HC, Chen SR, et al. Use of all-trans retinoic add in the treatment of acute promyleocytic leukaemia. Blood 1988; 72: 567-72. 1.
Sporn M, Roberts A. The role of retinoids
5. Sachs L. Control of normal cell differentiation and the
phenotypic reversion of malignancy in myeloid leukaemia. Nature 1978; 274: 535-39. 6. Tilly H, Castaigne S, Bordessoule D, et al. Low-dose cytarabine versus intensive chemotherapy in the treatment of acute nonlymphocytic leukaemia in the elderly. J Clin Oncol 1990; 8: 272-79.
Castaigne S, Chomienne C, Daniel MT, et al. All-trans retinoic add as a differentiation therapy for acute promyelocytic leukaemia I: clinical results. Blood (in press). 8. de The H, Chomienne C, Lanotte M, Degos L, Dejean A. The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus. Nature (in press).
7.
Hantavirus infection presenting renal failure
as
acute
SIR,-Hantavirus infection (epidemic nephropathy) is now recognised as quite a common cause of acute renal failure in western Europe. The infection is characterised by high fever, severe lumbar pain, conjunctival injection, inconstant thrombocytopenia, raised liver enzymes, and acute renal failure often requiring dialysis.l-4 The case reported here shows that Hantavirus infection may cause acute renal failure when none of the above clinical signs is present. A 29-year-old previously healthy man suddenly became ill with dizziness and vomiting. On the next day he had macroscopic haematuria and low-back pain which persisted for several days. He was admitted to hospital and oliguric acute renal failure was noted (serum creatinine 9-2 mg/dl, blood urea 183 mg/dl, diuresis below 400 ml daily). He was referred to our unit where one haemodialysis session was required. Urinary examination indicated massive haematuria, mild proteinuria, and no glycosuria. An ultrasound scan ruled out urinary obstruction and kidney stones. The kidneys were enlarged (length 11-5, parenchyma width 2-5 cm). Within 11 days renal function was normal (creatinine 1-3mg/dl, diuresis 2500 ml). On admission T-wave inversion had been found in chest leads V4-V6 but this disappeared 7 days later (virus myocarditis?).
1442
Laboratory investigation and blood cultures
ruled
By immunofluorescence antibodies were found for nephropathia epidemica (NE) at a titre of 512 (IgG); the titre for the Hanta type (Korean haemorrhagic fever) was 128 (IgG). By ELISA, with nucleocapsid antigen, the IgG titre for NE was 3212 units (normal below 100). IgM antibodies to NE and Hantaan were also detected. The IgG titre for Hanta type was only 88 units (normal below 100). of the virus.
Upon questioning the patient said that before
onset
he had
regularly walked his dog in forested areas. The acute renal failure in this case represents oligosymptomatic haemorrhagic fever with renal syndrome. We suggest that Hantavirus infection be excluded by serology in every case of acute renal failure of unknown origin. Departments of Medicine/Nephrology and Virology, University of Heidelberg, 6900 Heidelberg 1, Germany
MARTIN ZEIER KONRAD ANDRASSY LOTHAR ZÖLLER EBERHARD RITZ
1. Lähdevirta J.
Nephropathia epidemica in Finland: a clinical, histological epidemiological study. Ann Clin Res 1971; 3 (suppl 8): 1-154.
and
2. Editorial. Hantavirus disease. Lancet 1990; 336: 407. 3. van der Groen G. Haemorrhagic fever with renal syndrome: recent developments. Ann Soc Belge Med Trop 1985; 65: 121-35. 4. van Ypersele de Strihou CG, van der Groen G, Desmyter J. Nephropathie à Hantavirus en Europe occidentale: ubiquite des fièvres hèmorrhagiques avec syndrome renal. In: Crosnier J, Funck-Brentano J-L, Bach J-F, Grunfeld J-P, eds. Acutalités nephrologiques de l’Hôpital Necker. Paris: Flammarion, 1985.
Cryptococcus neoformans var gattii SIR,-Dr Ellis and Ms Pfeiffer (Oct 13, p 923) provide a fascinating of the ecology of Cryptococus neoformans var gattii. Cryptococcal meningitis is the commonest cause of chronic meningitis in adults admitted to Port Moresby General Hospital, Papua New Guinea, with 129 confirmed cases between 1978 and 1987.15of 6 isolates tested at this hospital proved to be C neoformans var gattii. There has been no evidence of immunosuppression (including HIV infection) in Papua New Guinea patients with cryptococcal meningitis, but the reported lower virulence of C neoformans var gattii has not been noted. All the patients with the 5 confirmed isolates had severe meningitis-3 had papillitis on fundoscopy, and 2 died during the first admission. The river red gum, Eucalyptus camaldulensis, is unlikely to be the host tree for C neoformans var gattii in Papua New Guinea since it is not indigenous to this country.2 An attempt to introduce the species in the Whagi Valley has been unsuccessful. Three indigenous eucalypts are common in the Papuan region where most cases of cryptococcus are seen: E papuana, E alba, and E confertiflora.2 These three species are also indigenous in Australia but are 3 restricted to the northern regions The possibility therefore arises that one or more of these eucalypts, besides E camaldulensis, is host to C neoformans var gattii in the Northern Territory where there is a high frequency of this infection in Australian aboriginals.4 account
Menzies School of Health Research, PO Box 41096, Casuarina, Northern Territory 0811, Australia
BART CURRIE
Conservation Commission, Northern Territory
TOM VIGUS GREG LEACH
Fairfield
Hospital for Infectious Diseases,
Fairfield, Victoria
Congenital hydrocephalus due to
out
septicaemia. Serological tests for systemic vasculitis were negative. Hantavirus serology proved recent infection with the Puumula type
BRIAN DWYER
intrauterine HTLV-I infection SIR,-Human T-cell lymphotropic virus type I (HTLV-1) causes adult T-cell leukaemia/lymphoma (ATLL) and HTLV-Iassociated myelopathy (HAM). The major route of HTLV-I infection is generally thought to be postnatal transmission via breast milk.l.2 The detection of the HTLV-I antigen in cord blood lymphocytes has pointed to vertical transmission via germinal cells or transplacental or ascending infection We report a male infant with congenital hydrocephalus probably due to intrauterine HTLV-I infection. A 20-day-old infant (born at term, birthweight 3800 g) was admitted to our hospital because of macrocephalus, which had been diagnosed on ultrasonography at 36 weeks’ gestation; his head circumference at birth was 37 cm ( + 2.1SD). His family history was unremarkable. He was breastfed for only 1 week. Cranial computed tomography showed enlarged third and lateral ventricles. In addition, magnetic resonance imaging and ultasonongraphy revealed bilateral multiple cysts in the subependymal germinal matrix. Serum IgM was raised (47 mg/dl). TORCH screening of serum and cerebrospinal fluid was negative (toxoplasma, rubellaIgM, cytomegalovirus-IgM, and herpes simplex virus-IgM). Physical and neurological examinations were normal, apart from macrocephalus. Other laboratory tests were also normal. We diagnosed congenital hydrocephalus due to intrauterine infection. The baby showed slightly delayed motor development, but his head circumference increased in the normal range. His mother did not feel well enough to feed him and had lumbar pain soon after the delivery. About 6 weeks later her gait became slightly uncertain and she was incontinent. When the boy was 11 months old, she was diagnosed as having HTLV-I associated myelopathy. His serum anti-HTLV-1 titre 2560. Viral neurotropic infection in utero causing subependymal germinal matrix cysts has been well documented."We therefore conclude that our infant patient had congenital hydrocephalus due to intrauterine HTLV-I infection. We suggest that anti-HTLV should be looked for in patients with congenital neurotropic infection.
Division of Child Neurology, Tottori University Hospital, 86 Nishi-Machi, Yonago 683,
Japan
HITOSHI KAWAHARA JUN TOHYAMA MASUMI INGAKI KOUSAKU OHNO
1. Ando Y, Nakano S, Saito K, et al. Transmission of adult T-cell leukemia retrovirus (HTLV-I) from mother to child: comparison of bottle- with breast-fed babies Jpn J Cancer Res (Gann) 1987; 78: 322-24. 2. Tsuji Y, Doi H, Yamabe T, et al. Prevention of mother to child transmission of human T-lymphotropic virus-type I. Pediatrics 1990; 86: 11-17. 3. Komuro A, Hayami M, Fuju H, et al. Vertical transmission of adult T-cell leukemia virus. Lancet 1983;i: 240. 4. Shaw CM, Alvord EC Jr. Subependymal germinolysis. Arch Neurol 1974; 31: 374-81. 5. Shackelford GD, Fulling KH, Grasier CM. Cysts of the subependymal germinal matrix sonographic demonstration with pathologic correlation. Radiology 1983, 149: 117-21.
Anti-HCV false
positivity in malaria
SIR,-Dr Wong and colleagues report (Sept 22, p 750) a high rate of false-positive results for antibodies to hepatitis C virus (HCV) in serum samples from presumably healthy volunteers living in a malaria endemic area, with Chiron/Ortho ELISA. They also cast doubt on the test’s reliability in seroepidemiological analysis. We have investigated HCV infection in 65 male and 29 female patients (mean age 28 years; range 20-40) with Plasmodium falciparum malaria, admitted to Mbalmayo hospital, 40 km south of Yaounde, Cameroon. Samples were collected in 1987 and stored at 20°C until testing. Serum samples were screened for antibody to HCV with the Ortho-ELISA test and repeatedly reactive specimens were also tested with Abbott anti-HCV ELISA and Chiron’s recombinant immunoblot assay (RIBA). In addition, autoantibodies to extractable nuclear antigen (ENA) were measured -
P, John R, Naraqi S. Cryptococcal meningitis: a disease of the rural population Papua New Guinea. 23rd annual medical symposium of the Medical Society of Papua New Guinea (Madang, September, 1987; abstr). 2. Gressitt JL. Biogeography and ecology of New Guinea. The Hague Dr W Junk 1. Temu
in
Publishers, 1982: 437-56. 3. Boland DJ. Forest trees of Australia. Melbourne: Thomas Nelson, 1957: 208, 240,418. 4. Ellis DH. Cryptococcus neoformans var gatti in Australia. Clin Microbiol 1987; 24: J
430-31.
with an ELISA test.! 59 (63%) samples were positive with Ortho-ELISA in two repeated analyses; of these, 16 had an absorbance value over 24
coagulation was noted in 8 patients.
16 had a
t( 15;17) translocation;
cytogenetic studies could not be done in 3 and a normal karyotype was noted in 1 early diagnosed relapse. ATRA was administered daily in two oral doses at 45 mg(m2 daily for 90 days as 10 mg capsules. ATRA was kindly provided by Prof Z. Y. Wang (Shanghai); since July, 1989, the drug has been produced by Roche France. To prevent side-effects, cold cream, lip salve, and eyedrops were given. Analgesics were prescribed when necessary for bone pain. Transfusions were given when the haemoglobin was under 8-0 g/dl or the platelet count was below 20 000/pl. Patients were generally followed up as outpatients. A complete remission (CR) was defmed as absence of blast cells in normal cellular bone marrow, and a normal peripheral blood count (haemoglobin over 12-0 g/dl, platelets over 100 000/pl, and polymorphonuclear cells over 1500/jil). CR was obtained in 19 patients within 1 (3 cases), 2 (11), or 3 (5) months. Cytopenia was corrected in 30 days for platelets, 50 days for neutrophils, and 60 days for anaemia; bone marrow became normal between day 30 and day 90. Transfusions were required in 6 patients, the last being on day 30. Heparin was prescribed for only 1 patient. Sterile conditions were not necessary and only 4 patients received antibiotics. 15 patients were in hospital for less than a week. WBC increased during the first 3 weeks, with characteristics of abnormal maturing cells. In 3 cases, hyperleucocytosis was associated with the persistent degradation of fibrinogen products,
leading fatal meningeal haemorrhage, retinal haemorrhage, and pericarditis and reversible renal failure. Hyperleucocytosis spontaneously decreased despite continued ATRA, and 3 of these patients went into CR. Morphologically three features characterised these cases: (1) bone to
cellularity remained the same; (2) changes in blast cells led maturing cells with near-normal morphology, and Auer rods in some mature cells confirmed differentiation; and (3) normal haematopoietic cells emerged. Adverse effects were dry skin and mucosae in all patients, and bone pain needing analgesics which spontaneously disappeared. Raised triglycerides (11patients) and transaminases (4) were marrow to
reversible once ATRA was discontinued. After 3 months of treatment with ATRA, 9 patients were treated with 6-mercaptopurine and methotrexate, and 6 of these relapsed; 2 received continuous ATRA therapy and both relapsed; and 1 patient was treated with methylglyoxal and cytarabine and relapsed. Since September, 1989,5 patients have been treated with monthly pulse chemotherapy and 2 patients have received allogeneic bone marrow transplantation; none have yet relapsed. In 5 cases of relapse after ATRA intensive chemotherapy (daunorubicin or mitoxantrone plus cytarabine) again achieved CR. Low dose cytarabine was tried in 2 cases without benefit, and in 2 other patients ATRA was prescribed again with no effect in 1 case. In 1 patient, low dose cytarabine followed by ATRA 60 mg/m2 resulted in a transient CR. In 1970 Sachs5 demonstrated in vitro that myeloid malignant cell lines revert to apparently normal cells, abolishing the dogma of the irreversibility of malignant cells. Differentiation in primary culture has proved more difficult. Low-dose cytarabine was the first approach to differentiation therapy, and this has been confirmed in acute non-lymphoblastic leukaemia.6 In vivo it is difficult to discriminate between cytotoxicity and differentiation via inhibition of proliferation. An efficient therapy would be one which induces leukaemic differentiation without inhibition of proliferation. Retinoic acids play an important part in normal differentiation and in the attenuation or complete reversal of malignant cell lines, including acute promyelocytic leukaemia.2,3In Huang and colleagues’4 study in the first attack of APL 23 CRs in 24 patients were achieved by ATRA at doses of 45-100 mg(sm2 daily. In our study with ATRA in first relapse 19 of 20 patients achieved CR within 3 months; such success is unusual in the treatment of relapses of acute promyelocytic leukaemia. This high rate of CR leads one to suggest bone marrow study not after the first remission obtained after chemotherapy, but at the second remission obtained with ATRA. Toxicity was negligible and the treatment was administered orally to outpatients, an equally unusual feature in acute leukaemia.
Hyperleucocytosis was a limiting side-effect in some cases. In our experience hyperleucocytosis is more frequent when the bone marrow is greatly infiltrated by malignant cells, when high disseminated intravascular coagulation is present before treatment, and when in vitro proliferation is observed. This situation is probably less frequent in first relapse but the risk of hyperleucocytosis must be emphasised if ATRA treatment is proposed at diagnosis. Unfortunately, both in patients treated at diagnosis’ and in those treated in first relapse, relapse occurred quite rapidly with maintenance ATRA. The alternate prescription of low-dose cytarabine and ATRA every month gave better results in the Chinese study. We suggest monthly pulse chemotherapy (or allogenic bone marrow transplantation) to maintain CR obtained with ATRA. Recent data suggest that an altered retinoic acid receptor alpha is generated by the t(15;17) specific translocation and that it may contribute to the leukaemogenesis and paradoxical effect of ATRA in these cells.8 We thank Dr P. Faure for help in drug handling, Professor Wang and Roche France for the drug, N. Balitrand for in vitro differentiation assays, and the haematologists in Paris, Orleans, Strasbourg, Clamart, Caen, and Bayonne who cared for the patients. Blood Disease Service,
Haematology Laboratory, Nuclear Medicine Service and INSERM Units 204 and 301, Hôpital Saint Louis, Paris 75010, France; and Haematology Service, Hôpital de Lille
LAURENT DEGOS CHRISTINE CHOMIENNE MARIE THÉRÈSE DANIEL ROLAND BERGER HERVÉ DOMBRET PIERRE FENAUX SYLVIE CASTAIGNE
in differentiation and carcinogenesis. Cancer Res 1983; 43: 3034-40. 2. Breitman TR, Keene BR, Hemmi H. Retinoic add induced differetiation of fresh human leukaemia cells and the human myelomonocytic leukaemia cell lines HL-60, U-937 and THP1. Cancer Surv 1983; 2: 265-91. 3. Chomienne C, Ballerini P, Balitrand N, et al. Differentiation of acute promyelocytic cells by all-trans retinoic acid II: in vitro studies: structure-function relationships. Blood (in press). 4. Huang ME, Ye HC, Chen SR, et al. Use of all-trans retinoic add in the treatment of acute promyleocytic leukaemia. Blood 1988; 72: 567-72. 1.
Sporn M, Roberts A. The role of retinoids
5. Sachs L. Control of normal cell differentiation and the
phenotypic reversion of malignancy in myeloid leukaemia. Nature 1978; 274: 535-39. 6. Tilly H, Castaigne S, Bordessoule D, et al. Low-dose cytarabine versus intensive chemotherapy in the treatment of acute nonlymphocytic leukaemia in the elderly. J Clin Oncol 1990; 8: 272-79.
Castaigne S, Chomienne C, Daniel MT, et al. All-trans retinoic add as a differentiation therapy for acute promyelocytic leukaemia I: clinical results. Blood (in press). 8. de The H, Chomienne C, Lanotte M, Degos L, Dejean A. The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus. Nature (in press).
7.
Hantavirus infection presenting renal failure
as
acute
SIR,-Hantavirus infection (epidemic nephropathy) is now recognised as quite a common cause of acute renal failure in western Europe. The infection is characterised by high fever, severe lumbar pain, conjunctival injection, inconstant thrombocytopenia, raised liver enzymes, and acute renal failure often requiring dialysis.l-4 The case reported here shows that Hantavirus infection may cause acute renal failure when none of the above clinical signs is present. A 29-year-old previously healthy man suddenly became ill with dizziness and vomiting. On the next day he had macroscopic haematuria and low-back pain which persisted for several days. He was admitted to hospital and oliguric acute renal failure was noted (serum creatinine 9-2 mg/dl, blood urea 183 mg/dl, diuresis below 400 ml daily). He was referred to our unit where one haemodialysis session was required. Urinary examination indicated massive haematuria, mild proteinuria, and no glycosuria. An ultrasound scan ruled out urinary obstruction and kidney stones. The kidneys were enlarged (length 11-5, parenchyma width 2-5 cm). Within 11 days renal function was normal (creatinine 1-3mg/dl, diuresis 2500 ml). On admission T-wave inversion had been found in chest leads V4-V6 but this disappeared 7 days later (virus myocarditis?).
1442
Laboratory investigation and blood cultures
ruled
By immunofluorescence antibodies were found for nephropathia epidemica (NE) at a titre of 512 (IgG); the titre for the Hanta type (Korean haemorrhagic fever) was 128 (IgG). By ELISA, with nucleocapsid antigen, the IgG titre for NE was 3212 units (normal below 100). IgM antibodies to NE and Hantaan were also detected. The IgG titre for Hanta type was only 88 units (normal below 100). of the virus.
Upon questioning the patient said that before
onset
he had
regularly walked his dog in forested areas. The acute renal failure in this case represents oligosymptomatic haemorrhagic fever with renal syndrome. We suggest that Hantavirus infection be excluded by serology in every case of acute renal failure of unknown origin. Departments of Medicine/Nephrology and Virology, University of Heidelberg, 6900 Heidelberg 1, Germany
MARTIN ZEIER KONRAD ANDRASSY LOTHAR ZÖLLER EBERHARD RITZ
1. Lähdevirta J.
Nephropathia epidemica in Finland: a clinical, histological epidemiological study. Ann Clin Res 1971; 3 (suppl 8): 1-154.
and
2. Editorial. Hantavirus disease. Lancet 1990; 336: 407. 3. van der Groen G. Haemorrhagic fever with renal syndrome: recent developments. Ann Soc Belge Med Trop 1985; 65: 121-35. 4. van Ypersele de Strihou CG, van der Groen G, Desmyter J. Nephropathie à Hantavirus en Europe occidentale: ubiquite des fièvres hèmorrhagiques avec syndrome renal. In: Crosnier J, Funck-Brentano J-L, Bach J-F, Grunfeld J-P, eds. Acutalités nephrologiques de l’Hôpital Necker. Paris: Flammarion, 1985.
Cryptococcus neoformans var gattii SIR,-Dr Ellis and Ms Pfeiffer (Oct 13, p 923) provide a fascinating of the ecology of Cryptococus neoformans var gattii. Cryptococcal meningitis is the commonest cause of chronic meningitis in adults admitted to Port Moresby General Hospital, Papua New Guinea, with 129 confirmed cases between 1978 and 1987.15of 6 isolates tested at this hospital proved to be C neoformans var gattii. There has been no evidence of immunosuppression (including HIV infection) in Papua New Guinea patients with cryptococcal meningitis, but the reported lower virulence of C neoformans var gattii has not been noted. All the patients with the 5 confirmed isolates had severe meningitis-3 had papillitis on fundoscopy, and 2 died during the first admission. The river red gum, Eucalyptus camaldulensis, is unlikely to be the host tree for C neoformans var gattii in Papua New Guinea since it is not indigenous to this country.2 An attempt to introduce the species in the Whagi Valley has been unsuccessful. Three indigenous eucalypts are common in the Papuan region where most cases of cryptococcus are seen: E papuana, E alba, and E confertiflora.2 These three species are also indigenous in Australia but are 3 restricted to the northern regions The possibility therefore arises that one or more of these eucalypts, besides E camaldulensis, is host to C neoformans var gattii in the Northern Territory where there is a high frequency of this infection in Australian aboriginals.4 account
Menzies School of Health Research, PO Box 41096, Casuarina, Northern Territory 0811, Australia
BART CURRIE
Conservation Commission, Northern Territory
TOM VIGUS GREG LEACH
Fairfield
Hospital for Infectious Diseases,
Fairfield, Victoria
Congenital hydrocephalus due to
out
septicaemia. Serological tests for systemic vasculitis were negative. Hantavirus serology proved recent infection with the Puumula type
BRIAN DWYER
intrauterine HTLV-I infection SIR,-Human T-cell lymphotropic virus type I (HTLV-1) causes adult T-cell leukaemia/lymphoma (ATLL) and HTLV-Iassociated myelopathy (HAM). The major route of HTLV-I infection is generally thought to be postnatal transmission via breast milk.l.2 The detection of the HTLV-I antigen in cord blood lymphocytes has pointed to vertical transmission via germinal cells or transplacental or ascending infection We report a male infant with congenital hydrocephalus probably due to intrauterine HTLV-I infection. A 20-day-old infant (born at term, birthweight 3800 g) was admitted to our hospital because of macrocephalus, which had been diagnosed on ultrasonography at 36 weeks’ gestation; his head circumference at birth was 37 cm ( + 2.1SD). His family history was unremarkable. He was breastfed for only 1 week. Cranial computed tomography showed enlarged third and lateral ventricles. In addition, magnetic resonance imaging and ultasonongraphy revealed bilateral multiple cysts in the subependymal germinal matrix. Serum IgM was raised (47 mg/dl). TORCH screening of serum and cerebrospinal fluid was negative (toxoplasma, rubellaIgM, cytomegalovirus-IgM, and herpes simplex virus-IgM). Physical and neurological examinations were normal, apart from macrocephalus. Other laboratory tests were also normal. We diagnosed congenital hydrocephalus due to intrauterine infection. The baby showed slightly delayed motor development, but his head circumference increased in the normal range. His mother did not feel well enough to feed him and had lumbar pain soon after the delivery. About 6 weeks later her gait became slightly uncertain and she was incontinent. When the boy was 11 months old, she was diagnosed as having HTLV-I associated myelopathy. His serum anti-HTLV-1 titre 2560. Viral neurotropic infection in utero causing subependymal germinal matrix cysts has been well documented."We therefore conclude that our infant patient had congenital hydrocephalus due to intrauterine HTLV-I infection. We suggest that anti-HTLV should be looked for in patients with congenital neurotropic infection.
Division of Child Neurology, Tottori University Hospital, 86 Nishi-Machi, Yonago 683,
Japan
HITOSHI KAWAHARA JUN TOHYAMA MASUMI INGAKI KOUSAKU OHNO
1. Ando Y, Nakano S, Saito K, et al. Transmission of adult T-cell leukemia retrovirus (HTLV-I) from mother to child: comparison of bottle- with breast-fed babies Jpn J Cancer Res (Gann) 1987; 78: 322-24. 2. Tsuji Y, Doi H, Yamabe T, et al. Prevention of mother to child transmission of human T-lymphotropic virus-type I. Pediatrics 1990; 86: 11-17. 3. Komuro A, Hayami M, Fuju H, et al. Vertical transmission of adult T-cell leukemia virus. Lancet 1983;i: 240. 4. Shaw CM, Alvord EC Jr. Subependymal germinolysis. Arch Neurol 1974; 31: 374-81. 5. Shackelford GD, Fulling KH, Grasier CM. Cysts of the subependymal germinal matrix sonographic demonstration with pathologic correlation. Radiology 1983, 149: 117-21.
Anti-HCV false
positivity in malaria
SIR,-Dr Wong and colleagues report (Sept 22, p 750) a high rate of false-positive results for antibodies to hepatitis C virus (HCV) in serum samples from presumably healthy volunteers living in a malaria endemic area, with Chiron/Ortho ELISA. They also cast doubt on the test’s reliability in seroepidemiological analysis. We have investigated HCV infection in 65 male and 29 female patients (mean age 28 years; range 20-40) with Plasmodium falciparum malaria, admitted to Mbalmayo hospital, 40 km south of Yaounde, Cameroon. Samples were collected in 1987 and stored at 20°C until testing. Serum samples were screened for antibody to HCV with the Ortho-ELISA test and repeatedly reactive specimens were also tested with Abbott anti-HCV ELISA and Chiron’s recombinant immunoblot assay (RIBA). In addition, autoantibodies to extractable nuclear antigen (ENA) were measured -
P, John R, Naraqi S. Cryptococcal meningitis: a disease of the rural population Papua New Guinea. 23rd annual medical symposium of the Medical Society of Papua New Guinea (Madang, September, 1987; abstr). 2. Gressitt JL. Biogeography and ecology of New Guinea. The Hague Dr W Junk 1. Temu
in
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with an ELISA test.! 59 (63%) samples were positive with Ortho-ELISA in two repeated analyses; of these, 16 had an absorbance value over 24
