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HANTAVIRUS DISEASE
158
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pregnancy termination could be considered at an early gestational age; and interpretation of clinical findings would be easier. We have shown that the rhesus antigens are expressed not on the trophoblast but on fetal erythrocytes only. Attempts to type for rhesus D in red cells isolated from minced biopsy material failed because too few fetal red cells were obtained. Studying material obtained by chorionic biopsy before pregnancy termination we found that many chorionic villi contained blood vessels from which fetal red blood cells could easily be obtained. It seemed reasonable to assume that these cells could be used for D-antigen determinations. An opportunity to test this arose when a gravida III, paran woman presented in the 8th week of pregnancy with a history of severe D and C isoimmunisation. Although having had an adequate dose of anti-D immunoglobulin after her first delivery, her second pregnancy resulted in the birth of a severely anaemic prehydropic, depressed child. Labour had been induced after 33 weeks of gestation. The child needed resuscitation, four exchange transfusions, and phototherapy but was discharged from the neonatal unit doing well. The husband was phenotype CcDee, which corresponds in 80% of cases with heterozygosity for the D antigen.’ The couple requested pregnancy termination unless the fetus could be proved to be Rh (D) negative. Chorionic biopsy was suggested and they agreed. At 9 weeks’ gestation biopsy was performed under real time ultrasound (sector scan). In the cell suspension obtained after chorionic biopsy, red cells were present, the vast majority of them of maternal origin. We were able to demonstrate the presence of rhesus D-positive cells among the red cells in this fluid by the mixed agglutination technique.2In this technique anti-D and bromelin are added to the washed packed cells from the fluid. After incubation at 37°C for 30 min and four washes the volume is readjusted to a 5% suspension and an equal volume of a 5% suspension of rhesus D positive cells is added. Rosette formation was seen after centrifugation in about 1% of the cells. 10 days later the pregnancy was terminated by suction curettage and we were able to isolate a sufficient number of red cells from the trophoblastic tissue to confirm the presence of rhesus D positive cells by standard and mixed agglutination technique. We believe that this is the first report of prenatal Rh(D) determination in the first trimester of pregnancy.
Hantaan virus, the agent of Korean haemorrhagic fever; its prototype strain is 76-118, the first well-studied isolate from the field mouse Apodemus agrarius corea.8The fact that hantaviruses, unlike other Bunyaviridae, do not seem to be arboviruses, is irrelevant to classification. Hantavirus can now replace such names as Hantaan-related virus or HFRS virus; Hantavirus infection can be used to describe infection in animals and man, regardless of clinical expression; Hantavirus disease would encompass all clinical manifestations allowing for absence of overt nephropathy, Hantavirus nephropathy being used when appropriate. "Muroid virus nephropathy" no longer seems adequate, now that the muroid virus has unveiled its identity and that insectivora have joined rodents as apparent virus reservoirs. "Haemorrhagic fever with renal syndrome" is awkward to trace in indexing systems and is misleading since it is rarely accompanied by symptomatic haemorrhage even in East Asia where hantaviruses that are more virulent for man are enzootic. HFRS is rather like calling viral meningitis "encephalitis with meningeal syndrome". Hantavirus should now be used in all proposed terminology: it will not be affected by language and will streamline communication. The resulting de-emphasis of "haemorrhagic fever" may even result in more diagnoses. Hantavirus is more than just a new addition to a list of names. There seems little to lose, and much to gain, if clinicians, scientists, and journals were to endorse this usage now. Rega Instituut, University of Leuven, B-3000 Leuven, Belgium Hôpital
Institute
Antwerp
Central Laboratory, Netherlands Red Cross Blood Transfusion Service, Amsterdam
M. B. VAN ’T VEER C. J. MAAS
6.
Department of Human Genetics, University Hospital, Leiden
G. C. BEVERSTOCK L. F. BERNINI
7. 8.
SIR,-Lancet readers (April 14, p 847) are bewildered by the diversity of names for haemorrhagic fever with renal syndrome (HFRS) and its viruses. There are good historical reasons for this Babel of some sixty synonyms but it confuses physicians and 1 hampers literature searches (which makes Gajdusek’s bibliographyl all the more valuable). The confusion can now end. The HFRS agents
are
members of the
Bunyaviridae2
genically related to each other but not apparently Bunyaviridae. Those analysed share a unique nucleotide
antiother sequence to
the 3’ end of each of their three RNA segments, them from the other genera which also have distinctive 3’ ends. Dalrymple’s group has therefore proposed a new genus, Hantavirus, in the Bunyaviridae family,3,5,6 adding it to the recognised genera Bunyavirzis, Nairovirus, Phlebovirus, and Uukuvirus.There is little doubt that the International Committee on Taxonomy of Viruses, which has not yet pronounced on HFRS agents, will eventually accept this genus. The type species is at
3 distinguishin
VAN
YPERSELE
DE
STRIHOU
GUIDO
VAN DER
GROEN
Gajdusek DC, Goldgaber D, Millard E, Ono S. Bibliography of haemorrhagic fevers with renal syndrome (muroid virus nephropathies). National Institutes of Health, Bethesda, Maryland, 1982. 2. Schmaljohn CS, Hasty SE, Harrison SA, Dalrymple JM. Characterization of Hantaan virions, the prototype virus of hemorrhagic fever with renal syndrome. J Infect Dis 1983; 148: 1005-12. 3. Schmaljohn CS, Dalrymple JM. Analysis of Hantaan virus RNA: Evidence for a new genus of Bunyaviridae. Virology 1983; 131: 482-91. 4. Clerx-Van Haaster CM, Clerx JPM, Ushijima H, Akashi H, Fuller F, Bishop DHL
5.
HANTAVIRUS DISEASE
CHARLES of Tropical Medicine,
1.
J. BENNEBROEK
1. Mollison PL. Blood transfusion in clinical medicine, 6th ed. Oxford: Blackwell Scientific Publications. 1979: 297. 2. Jones AR, Silver S. The detection of minor erythrocyte populations by mixed agglutinates. Blood 1958; 13: 763-72.
JAN DESMYTER
Saint-Luc,
Brussels
Department of Obstetrics and Gynaecology, University Hospital, 2333AA Leiden, Netherlands
H. H. H. KANHAI GRAVENHORST
Universitaire
The 3’ terminal RNA sequences of Bunyaviruses and Nairoviruses (Bunyaviridae). evidence of end sequence generic differences within the virus family. J Gen Virol 1982; 61: 289-92. Schmaljohn CS, Hasty SE, Dalrymple JM. Antigenic and molecular properties of eight viruses in the newly proposed Hantavirus genus of Buynaviridae. Arthropod Borne Virus Information Exchange 1984 (March): 158-59. Schmaljohn CS, Dalrymple JM. Biochemical characterization of Hantaan virus In Bishop DHL, Compans R, eds. Segmented negative strand viruses. New York Academic Press, 1984: 117-24 Bishop DHL, Calisher CH, Casals J, et al. Bunyaviridae. Intervirology 1980, 14: 125-43. Lee HW, Lee PW, Johnson KM. Isolation ofthe etiologic agent of Korean hemorrhagic fever. J Infect Dis 1978, 137: 298-308.
HEPATIC ENCEPHALOPATHY: GABA OR AMMONIA?
SIR,—Your March 3 editorial is correct in stressing that hepatic encephalopathy is more likely to be related to the failure of the liver to remove toxic substances than to a failure of the liver to produce an essential substance. However, we were surprised at your dismissal of the role of ammonia and other toxins and at your statement that y-aminobutyric acid (GABA) "is the current front runner in the portal-systemic encephalopathy stakes", a conclusion based on the work of Schafer, Jones, and colleagues with their animal model (galactosamine-induced liver failure). The latest findings of Schafer and colleagues are that, in the absence of seizures, visual evoked potentials (VEP) associated with hyperammonaemic encephalopathy and toxin-induced coma (ie, combined ammonia, dimethyldisulphide, and octanoic acid) differ fundamentally from those associated with hepatic encephalopathy. 1,2 In contrast, VEP in early postictal coma induced by four different precipitating factors (including toxininduced seizures) resembled that- of late-stage hepatic encephalopathy. VEPs in this model were identical with those obtained in rabbits with coma induced by three drugs that "activate GABAergic neural mechanisms". Schafer et al concluded that
-
pregnancy termination could be considered at an early gestational age; and interpretation of clinical findings would be easier. We have shown that the rhesus antigens are expressed not on the trophoblast but on fetal erythrocytes only. Attempts to type for rhesus D in red cells isolated from minced biopsy material failed because too few fetal red cells were obtained. Studying material obtained by chorionic biopsy before pregnancy termination we found that many chorionic villi contained blood vessels from which fetal red blood cells could easily be obtained. It seemed reasonable to assume that these cells could be used for D-antigen determinations. An opportunity to test this arose when a gravida III, paran woman presented in the 8th week of pregnancy with a history of severe D and C isoimmunisation. Although having had an adequate dose of anti-D immunoglobulin after her first delivery, her second pregnancy resulted in the birth of a severely anaemic prehydropic, depressed child. Labour had been induced after 33 weeks of gestation. The child needed resuscitation, four exchange transfusions, and phototherapy but was discharged from the neonatal unit doing well. The husband was phenotype CcDee, which corresponds in 80% of cases with heterozygosity for the D antigen.’ The couple requested pregnancy termination unless the fetus could be proved to be Rh (D) negative. Chorionic biopsy was suggested and they agreed. At 9 weeks’ gestation biopsy was performed under real time ultrasound (sector scan). In the cell suspension obtained after chorionic biopsy, red cells were present, the vast majority of them of maternal origin. We were able to demonstrate the presence of rhesus D-positive cells among the red cells in this fluid by the mixed agglutination technique.2In this technique anti-D and bromelin are added to the washed packed cells from the fluid. After incubation at 37°C for 30 min and four washes the volume is readjusted to a 5% suspension and an equal volume of a 5% suspension of rhesus D positive cells is added. Rosette formation was seen after centrifugation in about 1% of the cells. 10 days later the pregnancy was terminated by suction curettage and we were able to isolate a sufficient number of red cells from the trophoblastic tissue to confirm the presence of rhesus D positive cells by standard and mixed agglutination technique. We believe that this is the first report of prenatal Rh(D) determination in the first trimester of pregnancy.
Hantaan virus, the agent of Korean haemorrhagic fever; its prototype strain is 76-118, the first well-studied isolate from the field mouse Apodemus agrarius corea.8The fact that hantaviruses, unlike other Bunyaviridae, do not seem to be arboviruses, is irrelevant to classification. Hantavirus can now replace such names as Hantaan-related virus or HFRS virus; Hantavirus infection can be used to describe infection in animals and man, regardless of clinical expression; Hantavirus disease would encompass all clinical manifestations allowing for absence of overt nephropathy, Hantavirus nephropathy being used when appropriate. "Muroid virus nephropathy" no longer seems adequate, now that the muroid virus has unveiled its identity and that insectivora have joined rodents as apparent virus reservoirs. "Haemorrhagic fever with renal syndrome" is awkward to trace in indexing systems and is misleading since it is rarely accompanied by symptomatic haemorrhage even in East Asia where hantaviruses that are more virulent for man are enzootic. HFRS is rather like calling viral meningitis "encephalitis with meningeal syndrome". Hantavirus should now be used in all proposed terminology: it will not be affected by language and will streamline communication. The resulting de-emphasis of "haemorrhagic fever" may even result in more diagnoses. Hantavirus is more than just a new addition to a list of names. There seems little to lose, and much to gain, if clinicians, scientists, and journals were to endorse this usage now. Rega Instituut, University of Leuven, B-3000 Leuven, Belgium Hôpital
Institute
Antwerp
Central Laboratory, Netherlands Red Cross Blood Transfusion Service, Amsterdam
M. B. VAN ’T VEER C. J. MAAS
6.
Department of Human Genetics, University Hospital, Leiden
G. C. BEVERSTOCK L. F. BERNINI
7. 8.
SIR,-Lancet readers (April 14, p 847) are bewildered by the diversity of names for haemorrhagic fever with renal syndrome (HFRS) and its viruses. There are good historical reasons for this Babel of some sixty synonyms but it confuses physicians and 1 hampers literature searches (which makes Gajdusek’s bibliographyl all the more valuable). The confusion can now end. The HFRS agents
are
members of the
Bunyaviridae2
genically related to each other but not apparently Bunyaviridae. Those analysed share a unique nucleotide
antiother sequence to
the 3’ end of each of their three RNA segments, them from the other genera which also have distinctive 3’ ends. Dalrymple’s group has therefore proposed a new genus, Hantavirus, in the Bunyaviridae family,3,5,6 adding it to the recognised genera Bunyavirzis, Nairovirus, Phlebovirus, and Uukuvirus.There is little doubt that the International Committee on Taxonomy of Viruses, which has not yet pronounced on HFRS agents, will eventually accept this genus. The type species is at
3 distinguishin
VAN
YPERSELE
DE
STRIHOU
GUIDO
VAN DER
GROEN
Gajdusek DC, Goldgaber D, Millard E, Ono S. Bibliography of haemorrhagic fevers with renal syndrome (muroid virus nephropathies). National Institutes of Health, Bethesda, Maryland, 1982. 2. Schmaljohn CS, Hasty SE, Harrison SA, Dalrymple JM. Characterization of Hantaan virions, the prototype virus of hemorrhagic fever with renal syndrome. J Infect Dis 1983; 148: 1005-12. 3. Schmaljohn CS, Dalrymple JM. Analysis of Hantaan virus RNA: Evidence for a new genus of Bunyaviridae. Virology 1983; 131: 482-91. 4. Clerx-Van Haaster CM, Clerx JPM, Ushijima H, Akashi H, Fuller F, Bishop DHL
5.
HANTAVIRUS DISEASE
CHARLES of Tropical Medicine,
1.
J. BENNEBROEK
1. Mollison PL. Blood transfusion in clinical medicine, 6th ed. Oxford: Blackwell Scientific Publications. 1979: 297. 2. Jones AR, Silver S. The detection of minor erythrocyte populations by mixed agglutinates. Blood 1958; 13: 763-72.
JAN DESMYTER
Saint-Luc,
Brussels
Department of Obstetrics and Gynaecology, University Hospital, 2333AA Leiden, Netherlands
H. H. H. KANHAI GRAVENHORST
Universitaire
The 3’ terminal RNA sequences of Bunyaviruses and Nairoviruses (Bunyaviridae). evidence of end sequence generic differences within the virus family. J Gen Virol 1982; 61: 289-92. Schmaljohn CS, Hasty SE, Dalrymple JM. Antigenic and molecular properties of eight viruses in the newly proposed Hantavirus genus of Buynaviridae. Arthropod Borne Virus Information Exchange 1984 (March): 158-59. Schmaljohn CS, Dalrymple JM. Biochemical characterization of Hantaan virus In Bishop DHL, Compans R, eds. Segmented negative strand viruses. New York Academic Press, 1984: 117-24 Bishop DHL, Calisher CH, Casals J, et al. Bunyaviridae. Intervirology 1980, 14: 125-43. Lee HW, Lee PW, Johnson KM. Isolation ofthe etiologic agent of Korean hemorrhagic fever. J Infect Dis 1978, 137: 298-308.
HEPATIC ENCEPHALOPATHY: GABA OR AMMONIA?
SIR,—Your March 3 editorial is correct in stressing that hepatic encephalopathy is more likely to be related to the failure of the liver to remove toxic substances than to a failure of the liver to produce an essential substance. However, we were surprised at your dismissal of the role of ammonia and other toxins and at your statement that y-aminobutyric acid (GABA) "is the current front runner in the portal-systemic encephalopathy stakes", a conclusion based on the work of Schafer, Jones, and colleagues with their animal model (galactosamine-induced liver failure). The latest findings of Schafer and colleagues are that, in the absence of seizures, visual evoked potentials (VEP) associated with hyperammonaemic encephalopathy and toxin-induced coma (ie, combined ammonia, dimethyldisulphide, and octanoic acid) differ fundamentally from those associated with hepatic encephalopathy. 1,2 In contrast, VEP in early postictal coma induced by four different precipitating factors (including toxininduced seizures) resembled that- of late-stage hepatic encephalopathy. VEPs in this model were identical with those obtained in rabbits with coma induced by three drugs that "activate GABAergic neural mechanisms". Schafer et al concluded that