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A case of miscarriage following blackwater fever
348 ~rRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE.
Vol. XXXIV. No. 4. January, 1941.
A CASE OF M I S C A R R I A G E F O L L O W I N G B L A C K W A T E R FEVER. BY
HENRY FOY AND
ATHENA KONDI Wellcome Trust Research Laboratories, Refugee Hospital, Thessaloniki.
During the course of our investigation on blackwater fever in Macedonia, we had admitted to our wards a 7-months pregnant woman suffering from blackwater fever. °* Previous cases of blackwater fever dhring pregnancy have been reported by STEPHENS (1937), THOMSON (1924) and THOMAS and MILLEN (1939), but in none of these cases were the babies available for necropsy nor was the placental blood examined for pigments or parasites. We are therefore reporting the following case as it throws some light on the non-passage of methaemalbumin through the placenta, and the complete absence of any sign of haemolysis in the baby. The patient, a woman of 31 years, 7 months pregnant, stated that she was "' feeling out of sorts " on the morning of 5th November and went to see her doctor who then, at 9 a.m., gave her a 1 gramme intramuscular injection of quinine bihydrochloride. At midday on 6th November--29 hours after the quinine injection--she first passed black urine and continued to do so throughout the day. On 7th November she entered the hospital and was then intensely icteric, nervous, vomiting, and obviously very ill. Her spleen was I I I (Hackett), liver palpable and tender, pulse rapid, and skin clammy. Her temperature was 37.8 ° C. She gave no previous history of blackwater fever either personal or in her family. A specimen of urine cathetered on her entrance to hospital contained 130 rag. per cent. haemoglobin, and 150 rag. per cent. methaemoglobin and had * We should like to tiaank the Director and Staff of The Refugee Hospital for all the assistance given us and, the Greek Ministry of Health for endless facilities granted to us in our work.
844
BLACKWATER FEVER.
a p H of 5.8 taken electrometrically. Numerous granular casts, kidney and pus cells were found in the urine. There were no R.B.C.s in the urine. Vein bloocL taken into heparin was as follows : - R.B.C., 2,450,000 Alkali reserve 51.6 c.c. CO~ Hb : (Dare) 7.8 grammes per cent. ; pH-(electrometric), 7.55 (Newcomer) 8.1 grammes per cent. OxyHb in Serum, 40 mg. per cent. Colour Index, 1.1 Methaemalbumin, 1 in 2 dilution Haematocrit, 24 per cent. Parasites, P. falciparum rings Mean Corp. Volume, 100/z 3 ..... /Direct. ++ Blhrubln~Indirect,/ 4.2 mg. per cent.. W.B:C., 3,960 During 7th and 8th November she continued to pass black or red urine containing haefiaoglobin and methaemoglobin, all specimens having an acid reaction. The last specimen passed at 9 p.m. on 8th November contained 104"mg. pe r cent. of haemoglobin and 94 mg. per cent. of methaemoglobin and had a p H of 5.9. At 1 a.m. midnight on 9th November (4 hours after the last urine examination) the woman gave birth to a 7-months' baby, which died about 3 hours. after birth. The dead child together with the placenta were examined in the laboratory at 9 a.m. on 9th November. The placenta was intact and appeared normal. Blood was drawn from it and centrifuged. The serum was reddish brown, and on spectroscopic examination was found to contain haemoglobin and methaemalbumin. It was loaded with falciparum schizonts. • The child had been dead for about 5 hours when it was examined, and it appeared to be a normal, well-formed 7-months' male child. There was no. icteric tinge to the skin or mucous membranes. With difficulty blood was drawn and centrifuged. The serum so obtained was clear to naked eye examination, but spectroscopically contained a faint band of haemoglobin in a cell 5 cm.. thick. This was, no doubt, traumatic. There was no trace whatever of a band in the red region of the spectrum in a cell 15 cm. thick, so that methaemalbumin could be definitely ruled out. There was no sign of either malaria parasites o r pigment in the infant's blood or spleen. At 11 a.m. on 9th November a sample of vein blood was taken from the mother. T h e red blood cell count had dropped to 2,010,000. There were 56 mg. per cent. of haemoglobin in the serufia and methaemalbumin in a concentration of 1 in 3. Indirect bilirubin, 3'8 mg, per cent. There were no. parasites, but traces of malaria pigment were found here and there in the thick film. Urine cathetered on the 9th contained traces of haemoglobin and methaemoglobin. Thereafter, the urine cleared and the woman made an uneventful recovery without any blood transfusion. She was, however, later removed to. the Psychiatrion.
HENRY FOYAND ATHENA KONDI.
3~
Comment.
The case is of interest in that the baby and the placenta were available for postmortem examination ; and also that a fairly complete laboratory examination of the woman was made both before and after the birth of the child. From an examination of the placental blood it Seems that methaemalbumin does not pass from the mother across the placenta to the chiid. It has aIready been shown that this pigment does not normaIly pass across the kidney to be excreted in the urine,* the only pigments present in the urine in blackwater fever being oxyhaemoglobin and methaemoglobin. Further, although the mother was undergoing haemolysis at the time the child was born (as shown by blood and urine examinations immediately before and after birth) there, was no trace of this haemolytic process in the serum of the child, which contained neither haemoglobin nor methaemalbumin ; nor was there any icteroid tinge of the skin or mucous membranes of the child. If the haemolysis of the mother was due to circulating haemolysins then these never penetrated the placenta to reach the offspring and produce haemolysis there. That the products of haemolysis were removed from the child is possible but not likely. It is not impossible that the red cells of the mother were more liable to haemolysis for some unknown reason, than those of the infant. Or, alternatively, the cells of the mother ,and child might have be~n equally liable to haemolysis when exposed to certain" unknown factors," but that t h e s e " unknown factors " did not pass the placenta and affect the red cells of the infant. It is also possible that all the haemolysin available was used up in producing the haemolysis in the mother, and that none was left over to bring about a haemolytic process in the child. This argument, that all the haemolysin is. used up, may explain why attempts to demonstrate the presence of haemolysins in cases of blackwater fever have, so far, failed. The lack Of parasites in the child may also be a factor in the absence of haemolysis in the child's blood. If the disintegration of malaria parasites can produce blackwater fever by the liberation of toxins, then the absence of parasites from the child might account for the absence of any sign of haemolysis, always supposing that the so-called toxins could not pass the placenta. Any, or all, of these explanations may fit the case, but until more evidence is available, no good purpose can be served by theorising. Cases of blackwater fever in pregnant women, where both the placenta and child are available for laboratory examination, are all too rare. Should they occur, we think that examinations on the lines we have indicated here may throw some light on the problem of blackwater fever. * I t has been recently shown (FAIRLEY, 1939) that methaemalbumin is dealt with by the liver, as is bilirubin, and never appears in the urine.
846
B L A C K W A T E R FEVER.
SUMMARY, 1. A case of blackwater fever in a pregnant woman who gave birth to a 7-months' child, which died shortly after birth and was available, together with the placenta, for postmortem examination. 2. The placenta was found to be loaded with P. falciparum parasites, and the serum contained both haemoglobin and methaemalbumin. 3. The baby had no parasites in the blood or spleen ; nor was methaemalbumin present in the serum. There were traces of traumatic haemoglobin in the serum. There was no icterus visible in the child's skin or mucous membranes. ' 4. The mother's blood, examined after the birth, contained both haemoglobin and methaemalbumin ; and the urine haemoglobin and methaemoglobin. 5. I t seems from this case that methaemalbumin does not pass over the placenta to the child. The absence of any sign of haemolysis in the child may be due to the fact : - (a) That any haemolysins circulating in the mother did not pass through the placenta to the child. (b) That any haemolysin present in the mother was only there in sufficient concentration to bring about haemolytic process in the mother, and none was available to produce a haemolytic process in the child. (c) Assuming that malaria parasites, or their metabolic products, are necessary for the production of blackwater fever, then the absence of all traces of parasites and malaria pigment from the baby may account for the absence of all signs of haemolysis in 'the child. Further, sensitization of the mother did not appear to affect the child. (d) That the cells of the mother weFe more liable to haemolysis than those of the child ; or had been sensitised by parasites or their metabolic products. Any or all of these possibilities may account for the absence of signs of haemolysis in the child; until m o r e evidence is available, speculation is not likely to be of much value. REFERENCES. FAIRLEY,N. HAMILTON. (1939). Proc. R. Soc. Med., 32 (10), 1278. THOMSON, J. G. (1924). Researches on blackwater fever in Southern Rhodesia. Mere. Lond. Sch. Hyg. trop. Med., 6.
STEPHENS,J. W.W. (1937). Blackwater Fever. Liverpool : University Press. THOMAS,RuFus C. & MILLEN~R. ~/~. (1939). Trans. R. Soc. trop. Med. Hyg., 82 (6), 743.
CORRIGENDUM.
or
Vol. 34, No. 2, August, 1940. FAIRLEY, •. HAMILTON. A peculiar haemolytic hypochromic anaemia. Page 179, line 8 : " sclerotic " r e a d " siderotic." PRINTED IN GREAT BRITAIN.
Vol. XXXIV. No. 4. January, 1941.
A CASE OF M I S C A R R I A G E F O L L O W I N G B L A C K W A T E R FEVER. BY
HENRY FOY AND
ATHENA KONDI Wellcome Trust Research Laboratories, Refugee Hospital, Thessaloniki.
During the course of our investigation on blackwater fever in Macedonia, we had admitted to our wards a 7-months pregnant woman suffering from blackwater fever. °* Previous cases of blackwater fever dhring pregnancy have been reported by STEPHENS (1937), THOMSON (1924) and THOMAS and MILLEN (1939), but in none of these cases were the babies available for necropsy nor was the placental blood examined for pigments or parasites. We are therefore reporting the following case as it throws some light on the non-passage of methaemalbumin through the placenta, and the complete absence of any sign of haemolysis in the baby. The patient, a woman of 31 years, 7 months pregnant, stated that she was "' feeling out of sorts " on the morning of 5th November and went to see her doctor who then, at 9 a.m., gave her a 1 gramme intramuscular injection of quinine bihydrochloride. At midday on 6th November--29 hours after the quinine injection--she first passed black urine and continued to do so throughout the day. On 7th November she entered the hospital and was then intensely icteric, nervous, vomiting, and obviously very ill. Her spleen was I I I (Hackett), liver palpable and tender, pulse rapid, and skin clammy. Her temperature was 37.8 ° C. She gave no previous history of blackwater fever either personal or in her family. A specimen of urine cathetered on her entrance to hospital contained 130 rag. per cent. haemoglobin, and 150 rag. per cent. methaemoglobin and had * We should like to tiaank the Director and Staff of The Refugee Hospital for all the assistance given us and, the Greek Ministry of Health for endless facilities granted to us in our work.
844
BLACKWATER FEVER.
a p H of 5.8 taken electrometrically. Numerous granular casts, kidney and pus cells were found in the urine. There were no R.B.C.s in the urine. Vein bloocL taken into heparin was as follows : - R.B.C., 2,450,000 Alkali reserve 51.6 c.c. CO~ Hb : (Dare) 7.8 grammes per cent. ; pH-(electrometric), 7.55 (Newcomer) 8.1 grammes per cent. OxyHb in Serum, 40 mg. per cent. Colour Index, 1.1 Methaemalbumin, 1 in 2 dilution Haematocrit, 24 per cent. Parasites, P. falciparum rings Mean Corp. Volume, 100/z 3 ..... /Direct. ++ Blhrubln~Indirect,/ 4.2 mg. per cent.. W.B:C., 3,960 During 7th and 8th November she continued to pass black or red urine containing haefiaoglobin and methaemoglobin, all specimens having an acid reaction. The last specimen passed at 9 p.m. on 8th November contained 104"mg. pe r cent. of haemoglobin and 94 mg. per cent. of methaemoglobin and had a p H of 5.9. At 1 a.m. midnight on 9th November (4 hours after the last urine examination) the woman gave birth to a 7-months' baby, which died about 3 hours. after birth. The dead child together with the placenta were examined in the laboratory at 9 a.m. on 9th November. The placenta was intact and appeared normal. Blood was drawn from it and centrifuged. The serum was reddish brown, and on spectroscopic examination was found to contain haemoglobin and methaemalbumin. It was loaded with falciparum schizonts. • The child had been dead for about 5 hours when it was examined, and it appeared to be a normal, well-formed 7-months' male child. There was no. icteric tinge to the skin or mucous membranes. With difficulty blood was drawn and centrifuged. The serum so obtained was clear to naked eye examination, but spectroscopically contained a faint band of haemoglobin in a cell 5 cm.. thick. This was, no doubt, traumatic. There was no trace whatever of a band in the red region of the spectrum in a cell 15 cm. thick, so that methaemalbumin could be definitely ruled out. There was no sign of either malaria parasites o r pigment in the infant's blood or spleen. At 11 a.m. on 9th November a sample of vein blood was taken from the mother. T h e red blood cell count had dropped to 2,010,000. There were 56 mg. per cent. of haemoglobin in the serufia and methaemalbumin in a concentration of 1 in 3. Indirect bilirubin, 3'8 mg, per cent. There were no. parasites, but traces of malaria pigment were found here and there in the thick film. Urine cathetered on the 9th contained traces of haemoglobin and methaemoglobin. Thereafter, the urine cleared and the woman made an uneventful recovery without any blood transfusion. She was, however, later removed to. the Psychiatrion.
HENRY FOYAND ATHENA KONDI.
3~
Comment.
The case is of interest in that the baby and the placenta were available for postmortem examination ; and also that a fairly complete laboratory examination of the woman was made both before and after the birth of the child. From an examination of the placental blood it Seems that methaemalbumin does not pass from the mother across the placenta to the chiid. It has aIready been shown that this pigment does not normaIly pass across the kidney to be excreted in the urine,* the only pigments present in the urine in blackwater fever being oxyhaemoglobin and methaemoglobin. Further, although the mother was undergoing haemolysis at the time the child was born (as shown by blood and urine examinations immediately before and after birth) there, was no trace of this haemolytic process in the serum of the child, which contained neither haemoglobin nor methaemalbumin ; nor was there any icteroid tinge of the skin or mucous membranes of the child. If the haemolysis of the mother was due to circulating haemolysins then these never penetrated the placenta to reach the offspring and produce haemolysis there. That the products of haemolysis were removed from the child is possible but not likely. It is not impossible that the red cells of the mother were more liable to haemolysis for some unknown reason, than those of the infant. Or, alternatively, the cells of the mother ,and child might have be~n equally liable to haemolysis when exposed to certain" unknown factors," but that t h e s e " unknown factors " did not pass the placenta and affect the red cells of the infant. It is also possible that all the haemolysin available was used up in producing the haemolysis in the mother, and that none was left over to bring about a haemolytic process in the child. This argument, that all the haemolysin is. used up, may explain why attempts to demonstrate the presence of haemolysins in cases of blackwater fever have, so far, failed. The lack Of parasites in the child may also be a factor in the absence of haemolysis in the child's blood. If the disintegration of malaria parasites can produce blackwater fever by the liberation of toxins, then the absence of parasites from the child might account for the absence of any sign of haemolysis, always supposing that the so-called toxins could not pass the placenta. Any, or all, of these explanations may fit the case, but until more evidence is available, no good purpose can be served by theorising. Cases of blackwater fever in pregnant women, where both the placenta and child are available for laboratory examination, are all too rare. Should they occur, we think that examinations on the lines we have indicated here may throw some light on the problem of blackwater fever. * I t has been recently shown (FAIRLEY, 1939) that methaemalbumin is dealt with by the liver, as is bilirubin, and never appears in the urine.
846
B L A C K W A T E R FEVER.
SUMMARY, 1. A case of blackwater fever in a pregnant woman who gave birth to a 7-months' child, which died shortly after birth and was available, together with the placenta, for postmortem examination. 2. The placenta was found to be loaded with P. falciparum parasites, and the serum contained both haemoglobin and methaemalbumin. 3. The baby had no parasites in the blood or spleen ; nor was methaemalbumin present in the serum. There were traces of traumatic haemoglobin in the serum. There was no icterus visible in the child's skin or mucous membranes. ' 4. The mother's blood, examined after the birth, contained both haemoglobin and methaemalbumin ; and the urine haemoglobin and methaemoglobin. 5. I t seems from this case that methaemalbumin does not pass over the placenta to the child. The absence of any sign of haemolysis in the child may be due to the fact : - (a) That any haemolysins circulating in the mother did not pass through the placenta to the child. (b) That any haemolysin present in the mother was only there in sufficient concentration to bring about haemolytic process in the mother, and none was available to produce a haemolytic process in the child. (c) Assuming that malaria parasites, or their metabolic products, are necessary for the production of blackwater fever, then the absence of all traces of parasites and malaria pigment from the baby may account for the absence of all signs of haemolysis in 'the child. Further, sensitization of the mother did not appear to affect the child. (d) That the cells of the mother weFe more liable to haemolysis than those of the child ; or had been sensitised by parasites or their metabolic products. Any or all of these possibilities may account for the absence of signs of haemolysis in the child; until m o r e evidence is available, speculation is not likely to be of much value. REFERENCES. FAIRLEY,N. HAMILTON. (1939). Proc. R. Soc. Med., 32 (10), 1278. THOMSON, J. G. (1924). Researches on blackwater fever in Southern Rhodesia. Mere. Lond. Sch. Hyg. trop. Med., 6.
STEPHENS,J. W.W. (1937). Blackwater Fever. Liverpool : University Press. THOMAS,RuFus C. & MILLEN~R. ~/~. (1939). Trans. R. Soc. trop. Med. Hyg., 82 (6), 743.
CORRIGENDUM.
or
Vol. 34, No. 2, August, 1940. FAIRLEY, •. HAMILTON. A peculiar haemolytic hypochromic anaemia. Page 179, line 8 : " sclerotic " r e a d " siderotic." PRINTED IN GREAT BRITAIN.