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Automated exchange transfusion for life-threatening plasmodium falciparum malaria—Lessons relating to prophylaxis and treatment
i
CASE REPORTS
Automated Exchange Transfusion for Life-threatening Plasmodium Falciparum Malaria-Lessons Relating to Prophylaxis ancl Treatment C. J. Mainwaring*‘,
Departmwt
of ‘Hmmtology
M. J. Leach’, N. Nayak2, S. T. Green*, D. A. Jones3 and D. A. Winfield’ trnd
Diseases, Ro;pl Hdlarnshil-e Hospital Service Twnt Centrei, Sheffield, UK.
‘bzfectious
NHS TrLlst
a~zd
National Blood
We report a case of traveller to Kenya who contracted severe plasmodium falciparum malaria complicated by disseminated intravascular coagulation and acute renal failure. She had taken no antimalarial prophylaxis in view of concerns in the media regarding the adverse effects of mefloquine. There was a protracted delay before the diagnosis ot malaria was made. Clinical recovery occurred following treatment with intravenous quinine, haemofiltration and manual/automated red-cell exchange transfusions. Automated red-cell exchange transfusion resulted in a marked decrease in the parasitaemia, before a response to quinine therapy would have been anticipated, leading to a successful outcome thereafter. In conjunction with other groups we therefore feel that exchange transfusions should be considered in seriously ill patients with falciparum malaria. multiorgan complications and parasitaemias greater than 10%. 0 1999 The British Infection Society
Introduction Malaria continues to be an increasing world health problem with the advent of increasing foreign travel. Plasmodium faalciparum is the most dangerous of the four types and responsible for the majority of deaths in people returning to the U.K. Wordwide an estimated three million people die per year following infection with malaria and in the U.K.. of 2363 reported cases. there were 10 deaths in 1997. Mortality rates have been reported to vary between 20-40(X, when parasitaemias are greater than 10% associated with secondary complications.’ Delay in diagnosis and institution of specific therapy also contribute to a decreased chance of survival.’ Conversely rapid reduction in parasitaemias and improved clinical outcome can be achieved by the use of exchange red-cell transfusions before antimalarial chemotherapy has had an opportunity to become effective.’ Exchange transfusions have been used in the management of falciparum malaria since 1974,j however, there have been very few randomized controlled trials to evaluate its efficacy. This particular case raised a number of important points regarding the management of falciparum malaria which are discussed in conjunction with the role of exchange transfusion in this potentially fatal infectious disease.
“Address correspondence to: C. J, Main\varing, Royal Hampshire County Hospital. Department of Haemalology, Romsey Road, Winchester. SO22 5DG Accepted for publication 10 August 1999. 0163.4453/99/060231
+ 13 9;12.00/0
Case Report A 30-year-old woman was admitted acutely for investigation of a febrile illness and jaundice by her own general practitioner. She had been unwell for 7 days with a flu-like illness having returned from a 2 week holiday in Kenya. She had decided to take no antimalarial prophylaxis after learning of gastrointestinal and neuropsychiatric side effects with mefloquine on a televised consumer affairs programme. Prior to admission she had been seer1 by two other general practitioners who felt the diagnosis was influenza despite the history of foreign travel to a malarial zone without prophylaxis. Clinically she was icteric, dehydrated and pyrexial. Isolated 4 cm hepatosplenomegaly was noted on abdominal examination. A full blood count confirmed an haemoglobin of Il.2 g/d]. total white-cell count 7.2 with a normal differential and a platelet count of only 2 x lO”/litre. Clotting screens were compatible with disseminated intravascular coagulation (DIC), with a raised prothrombin and kaolin cephalin clotting time, reduced fibrinogen and D-Dimers increased at 32 (normal range CO.25 yg/l). A blood film confirmed increased polychromasia with 26% of red cells containing multiple falciparum ring forms. Biochemical screens confirmed hepatorenal impairment with an unconjugated hyperbilirubinaemia ‘of 220 umolll, raised transaminases at 600 units/l. urea 11 mmol/l and creatinine of 150 ymol/l. Her random blood glucose was reduced at 1.5 mmol/l. Initial urine passed was dark brown in colour and positive for haemoglobin. The patient therefore had severe Plasmodium falciparum malaria complicated by acute renal failure and DIC. She was treated with intravenous 5% Dextrose infusions, intravenous quinine 20 mg/kg loading dose followed by 10 mgkg maintenance dose 8 hourly, catheterized and P 1999 The British Infection Societg
232
transfused 5 units of random donor platelet concentrates. In view of the critical nature of her illness with multiorgan failure a manual red-cell exchange transfusion was performed, 4 h after admission. owing to the unavailability of out of hours trained apheresis staff at this stage. Only 1000 ml (4 units packed redcells) were exchanged over a 4 h period because of haemodynamic instability with worsening hypotension. This reduced the parasitaemia to 23%. An abdominal ultrasound scan confirmed modest hepatosplenomegaly and normal sized kidneys. She remained hypotensive despite volume loading. requiring transfer to the intensive care unit and inotropic support. In view of the persisting marked parasitaemia a 2500 ml automated red cell exchange transfusion (IO units packed redcells) was performed using a Cobe Spectra cell separator some 1S h after admission reducin g the parasitaemia from 16% down to 0.5%. The procedure was completed within 2 h. Her renal function continued to deteriorate with the serum creatinine peaking at 490 umol/l and venous haemofiltration was necessary between days 4 and 14 after presentation. Following full supportive treatment the haemolysis, hepatitic abnormalities and IXC gradually resolved over a period of 2 weeks. Residual renal impairment persisted with a raised serum creatinine of 165 umol/l. She was eventually well enough for discharge home 2 7 days after admission. Currently. she remains well under the follow up of the infectious disease specialists.
iscussis There are several very important issues which arise from this case history. Firstly. the patient decided to take no antimalarial prophylaxis after the side effects of mefloquine (MQ). especially gastrointestinal and neuropsychiatric, were highlighted on a television programme for consumer affairs. Failure to take chemoprophglaxis followed by fat-al plasmodium falciparum malaria (PI%) is well described in travellers.’ In the IJ.K. mefloquine has been marketed for both prophylaxis and treatment of malaria since 1990, in association with increasing resistance to chloroquine and proguanil especially in Sub Saharan Africa. However, side effects are well described with nausea and diarrhoea reported in 47% of patients taking &IQ5 The main concern with MQ pertains to neuropsychiatric complications, the commonest being dose-dependant sleep disturbance. dizziness and mood changes. Seizures and psychoses have also been reported to occur in about I in 10600 taking MQ” and these side effects can persist for years. In view of these findings MQ should be avoided in those with a history of epilepsy or psychiatric disorders. Secondly. her condition was misdiagnosed as influenza by two different general practitioners despite the suggestive history, appropriate foreign travel and abstinence from prophylaxis. This delayed appropriate hospital admission and treatment by some 7 days. Regarding this question a retrospective study from 197991993 at a large Los Angeles medical centre: showed that of 20 patients subsequently found to have PFM, in only 12 was malaria considered. PFM was correctly specified in two and only four had antimalarial treatment in the emergency department. The commonest misdiagnoses were hepatitis and gastroenteritis. Better awareness is obviously required in both community and hospital based doctors in order to both diagnose malaria and effect prompt therapy. Thirdly the patient presented with life threatening falciparum malaria complicated by multiorgan failure but recovered following comprehensive supportive therapy on the intensive care unit.
including exchange transfusions. Soni et ml.” showed in 1996 that haemolytic anaemia. high parasitaemia and renal failure are all independent, poor prognostic features at presentation. Most authorities agree exchange transfusions (ET) are indicated when greater than IO’% of red cells are parasitized with concurrent organ failure or with parasitaemias of greater than 30% in isolation’. The rationale for ET in such situations includes the rapid removal of malarial parasites and toxic by-products. decreased risk of intravascular haemolysis and endothelial damage which can lead to DIG and renal failure. plus improved oxgen carrying capacity. These properties are especially important when one cannot wait 12224 h for antimalarial drugs to work. These potential benefits need to be balanced against the risks of transfusion associated complications such as febrile/allergic reactions. red-cell alloantibody sensitisation and transmissable viral infections. There are numerous reported studies which have shown the benefit of ET in such circumstances.’ ‘(I but others have shown no benefit” or been managed successfully without ET.” One of the few randomized studies comparing antimalarial therapy with or without exchange transfusions was undertaken by Saddler et al. (1990) but only involved eight patients. All four patients who were exchanged survived but of the remainder three out of four died. There was however. no information to ascertain whether these two patient groups were comparably matched, the numbers of patients evaluated were very small and results did not achieve statistical significance. A review by Phillips et al. evaluated 40 patients with PFM who had been managed by ET over a 16-year period between 1974 and 1990. Five patients died despite ET and these shared certain adverse prognostic factors such as age greater than 50 years. mean pretreatment parasitaemias of 37% greater than four malaria related complications and mean duration of illness pre treatment of 8.6 days. The main advantage of ET was the rapid reduction in the level of parasitaemia. usually less than 6 h, when compared to standard antimalarial drug therapy. with the mean parasitaemia falling from a pretreatment level of 30% to 3%. Similar findings have been borne out by other investigators.‘4 As far as we are aware, however, there has been no comparative research performed to ascertain whether automated are more efficacious than manual exchange transfusions. The potential advantages of automated ET relate to greater volume of blood which can be exchanged over a shorter period of time. with more effective reduction in the parasitaemfa and less cardiovascular instability. Certainly automated ET has been shown to be more effective than manual procedures in the setting of sickle cell crises.’ 5 As a cautionary note there is a potential concern regarding positive reporting bias of cases successfully managed by BT and not reporting those with adverse outcomes. Additionally no consensus exists regarding the oplimal volume of blood required J’OJ successful ET. with case reports quoting between 1 and 10 litres and additionally whether one should be using whole blood or packed red cells. Ideally these questions and the whole role of ET in severe PFM need to be addressed in controlled randomized clinical trials. From our own experience, we feel that OUT patient’s condition was deteriorating rapidly until automated ET was commenced and the reduction in parasitaemia was too early to reflect a response to quinine therapy alone. Finally despite the aforementioned, following discharge from hospital she was left with residual renal impairment (creatinine 165 ymol/l) and subsequently developed a post-malaria retinopathy and peripheral neuropathy highlighting the considerable morbidity associated with this parasitic infection despite aggressive therapy.
233
Case Reports In summary, the lessons to be learned include, antimalarial prophylaxis is essential in all travellers to malaria zones and the importance of considering Ihe diagnosis of malaria in a patient presenting with a febrile illness following appropriate foreign travel and finally reinforces the value of automated ET in seriously ill patients with PIN high parasitaemias and multiorgan complications. in conjunction with specific antimalarial and full supportive therapy.
References 1 Stone WJ, Hanchett JE. Knepshield JH. Acute renal insufficiency due to falciparum malaria: review of 42 cases. Arch b?tei-11 Med 1972: 129: 620-628. 2 Kurathong S. Srichailtul T. Isarangkura l? Phanichphant S. Exchange transfusion in cerebral malaria complicated by dissemnated intravascular coagulation. Soutilensl Asin~? J Troy? Mrd PrUc Hmlth 1979: 10: 389~392. 3 Phillips P. Mantel S. Renny WB. Exchange transfusion as an adjunct to the treatment of severe falciparum malaria: case report and review. Rev 111Jccr Dis 1990: 12: 1100-I 108. 4 Espinosa G. Tortajada C. Gascon J. Miquel R, Nicolas JM. Nadal P. Corachan 31. Severe plasmodiurn falciparum malaria. Description of 5 casts. RclJisln Cfill Esptrnofn 1997: 197: 631-634. 5 Lobe1 HO. Bernard KW Williams SL. Hightower AW Patchen 1X. Campbell CC. Effectiveness and tolerance of long term malaria prophylaxis with mefloquine (need for a better dosing regimen). JAMA 1991: 265: 361-364.
Automated
Erythrocytapheresis Falciparum
Derek C. Macallan*l, Michaela John Parker-WiIliams2,
6 Steffen R. Fuchs E. Schildknccht J. Mcfloquine compared with other malaria chemoprophylactic regimens in tourists visiting East Africa. J.aizcet 1993: 341: 1299~1303. 7 Kyriacou DN. Spira AM, Talan IX. Mabey DC. Emergency department presentation and misdiagnosis of imported malaria. Am Emerg
in the Treatment Malaria
of Severe
Pocock2, Elizabeth Bishop2, David IH.Bevan2, Tom Harrison’ and Grant T. Robinson2
‘Departnxxt oj- InJxtious Diseasesand ‘Departmerzt
ofHaemntology,
St George’sHospital Medical Scl~ool,Londo~~,U.K.
Removal of parasitized erythrocytes is generally considered to be of value as adjunctive therapy in severe falciparum malaria with high parasitaemia. This is commonly achieved by exchange transfusion. We describe three cases of severe falciparum malaria treated by automated erythrocytapheresis (red cell exchange) in addition to quinine and conventional supportive therapy. Erythrocytapheresis consists of removal of the red-cell fraction by apheresis. Plasma, leukocyte and platelet fractions are returned to the patient. In all cases, dramatic reduction in parasitaemia was achieved within 2 h with subsequent complete clinical recovery. Erythrocytapheresis has significant advantages over exchange ’ transfusion in terms of speed, efficiency, haemodynamic stability and retention of plasma components such as clotting factors and may thus represent an improvement in adjunctive therapy for severe malaria. 0 1999 The British Infection Society
Introduction Palciparum significant
malaria mortality,
with parasitaemia particularly
if there
of more than 10% has a is evidence
of cerebral
involvemenl’,‘. The primary pathology is thought lo be related to sequestration of parasitized red cells in the microcirculation, particularly the cerebral vasculature. Although the mechanism of such oathogenesis is still unclear. manv authorities agree that. at high parasitaemia, removal of parasitized red-cells is an important adjunct to antimalarial chemlotherapy The use of exchange transfusion to achieve this was first described by Gyr et al. in 19743. The rationale behind such an approach is the rapid removal of parasitized cells preventing L
-Address Diseases. Accepted
correspondence to: Dr D. C. Macallan. Division of Infectious St George’s Hospital Medical School. London. SW1 7 ORE, U.K. for publication 10 August 1999.
-
CASE REPORTS
Automated Exchange Transfusion for Life-threatening Plasmodium Falciparum Malaria-Lessons Relating to Prophylaxis ancl Treatment C. J. Mainwaring*‘,
Departmwt
of ‘Hmmtology
M. J. Leach’, N. Nayak2, S. T. Green*, D. A. Jones3 and D. A. Winfield’ trnd
Diseases, Ro;pl Hdlarnshil-e Hospital Service Twnt Centrei, Sheffield, UK.
‘bzfectious
NHS TrLlst
a~zd
National Blood
We report a case of traveller to Kenya who contracted severe plasmodium falciparum malaria complicated by disseminated intravascular coagulation and acute renal failure. She had taken no antimalarial prophylaxis in view of concerns in the media regarding the adverse effects of mefloquine. There was a protracted delay before the diagnosis ot malaria was made. Clinical recovery occurred following treatment with intravenous quinine, haemofiltration and manual/automated red-cell exchange transfusions. Automated red-cell exchange transfusion resulted in a marked decrease in the parasitaemia, before a response to quinine therapy would have been anticipated, leading to a successful outcome thereafter. In conjunction with other groups we therefore feel that exchange transfusions should be considered in seriously ill patients with falciparum malaria. multiorgan complications and parasitaemias greater than 10%. 0 1999 The British Infection Society
Introduction Malaria continues to be an increasing world health problem with the advent of increasing foreign travel. Plasmodium faalciparum is the most dangerous of the four types and responsible for the majority of deaths in people returning to the U.K. Wordwide an estimated three million people die per year following infection with malaria and in the U.K.. of 2363 reported cases. there were 10 deaths in 1997. Mortality rates have been reported to vary between 20-40(X, when parasitaemias are greater than 10% associated with secondary complications.’ Delay in diagnosis and institution of specific therapy also contribute to a decreased chance of survival.’ Conversely rapid reduction in parasitaemias and improved clinical outcome can be achieved by the use of exchange red-cell transfusions before antimalarial chemotherapy has had an opportunity to become effective.’ Exchange transfusions have been used in the management of falciparum malaria since 1974,j however, there have been very few randomized controlled trials to evaluate its efficacy. This particular case raised a number of important points regarding the management of falciparum malaria which are discussed in conjunction with the role of exchange transfusion in this potentially fatal infectious disease.
“Address correspondence to: C. J, Main\varing, Royal Hampshire County Hospital. Department of Haemalology, Romsey Road, Winchester. SO22 5DG Accepted for publication 10 August 1999. 0163.4453/99/060231
+ 13 9;12.00/0
Case Report A 30-year-old woman was admitted acutely for investigation of a febrile illness and jaundice by her own general practitioner. She had been unwell for 7 days with a flu-like illness having returned from a 2 week holiday in Kenya. She had decided to take no antimalarial prophylaxis after learning of gastrointestinal and neuropsychiatric side effects with mefloquine on a televised consumer affairs programme. Prior to admission she had been seer1 by two other general practitioners who felt the diagnosis was influenza despite the history of foreign travel to a malarial zone without prophylaxis. Clinically she was icteric, dehydrated and pyrexial. Isolated 4 cm hepatosplenomegaly was noted on abdominal examination. A full blood count confirmed an haemoglobin of Il.2 g/d]. total white-cell count 7.2 with a normal differential and a platelet count of only 2 x lO”/litre. Clotting screens were compatible with disseminated intravascular coagulation (DIC), with a raised prothrombin and kaolin cephalin clotting time, reduced fibrinogen and D-Dimers increased at 32 (normal range CO.25 yg/l). A blood film confirmed increased polychromasia with 26% of red cells containing multiple falciparum ring forms. Biochemical screens confirmed hepatorenal impairment with an unconjugated hyperbilirubinaemia ‘of 220 umolll, raised transaminases at 600 units/l. urea 11 mmol/l and creatinine of 150 ymol/l. Her random blood glucose was reduced at 1.5 mmol/l. Initial urine passed was dark brown in colour and positive for haemoglobin. The patient therefore had severe Plasmodium falciparum malaria complicated by acute renal failure and DIC. She was treated with intravenous 5% Dextrose infusions, intravenous quinine 20 mg/kg loading dose followed by 10 mgkg maintenance dose 8 hourly, catheterized and P 1999 The British Infection Societg
232
transfused 5 units of random donor platelet concentrates. In view of the critical nature of her illness with multiorgan failure a manual red-cell exchange transfusion was performed, 4 h after admission. owing to the unavailability of out of hours trained apheresis staff at this stage. Only 1000 ml (4 units packed redcells) were exchanged over a 4 h period because of haemodynamic instability with worsening hypotension. This reduced the parasitaemia to 23%. An abdominal ultrasound scan confirmed modest hepatosplenomegaly and normal sized kidneys. She remained hypotensive despite volume loading. requiring transfer to the intensive care unit and inotropic support. In view of the persisting marked parasitaemia a 2500 ml automated red cell exchange transfusion (IO units packed redcells) was performed using a Cobe Spectra cell separator some 1S h after admission reducin g the parasitaemia from 16% down to 0.5%. The procedure was completed within 2 h. Her renal function continued to deteriorate with the serum creatinine peaking at 490 umol/l and venous haemofiltration was necessary between days 4 and 14 after presentation. Following full supportive treatment the haemolysis, hepatitic abnormalities and IXC gradually resolved over a period of 2 weeks. Residual renal impairment persisted with a raised serum creatinine of 165 umol/l. She was eventually well enough for discharge home 2 7 days after admission. Currently. she remains well under the follow up of the infectious disease specialists.
iscussis There are several very important issues which arise from this case history. Firstly. the patient decided to take no antimalarial prophylaxis after the side effects of mefloquine (MQ). especially gastrointestinal and neuropsychiatric, were highlighted on a television programme for consumer affairs. Failure to take chemoprophglaxis followed by fat-al plasmodium falciparum malaria (PI%) is well described in travellers.’ In the IJ.K. mefloquine has been marketed for both prophylaxis and treatment of malaria since 1990, in association with increasing resistance to chloroquine and proguanil especially in Sub Saharan Africa. However, side effects are well described with nausea and diarrhoea reported in 47% of patients taking &IQ5 The main concern with MQ pertains to neuropsychiatric complications, the commonest being dose-dependant sleep disturbance. dizziness and mood changes. Seizures and psychoses have also been reported to occur in about I in 10600 taking MQ” and these side effects can persist for years. In view of these findings MQ should be avoided in those with a history of epilepsy or psychiatric disorders. Secondly. her condition was misdiagnosed as influenza by two different general practitioners despite the suggestive history, appropriate foreign travel and abstinence from prophylaxis. This delayed appropriate hospital admission and treatment by some 7 days. Regarding this question a retrospective study from 197991993 at a large Los Angeles medical centre: showed that of 20 patients subsequently found to have PFM, in only 12 was malaria considered. PFM was correctly specified in two and only four had antimalarial treatment in the emergency department. The commonest misdiagnoses were hepatitis and gastroenteritis. Better awareness is obviously required in both community and hospital based doctors in order to both diagnose malaria and effect prompt therapy. Thirdly the patient presented with life threatening falciparum malaria complicated by multiorgan failure but recovered following comprehensive supportive therapy on the intensive care unit.
including exchange transfusions. Soni et ml.” showed in 1996 that haemolytic anaemia. high parasitaemia and renal failure are all independent, poor prognostic features at presentation. Most authorities agree exchange transfusions (ET) are indicated when greater than IO’% of red cells are parasitized with concurrent organ failure or with parasitaemias of greater than 30% in isolation’. The rationale for ET in such situations includes the rapid removal of malarial parasites and toxic by-products. decreased risk of intravascular haemolysis and endothelial damage which can lead to DIG and renal failure. plus improved oxgen carrying capacity. These properties are especially important when one cannot wait 12224 h for antimalarial drugs to work. These potential benefits need to be balanced against the risks of transfusion associated complications such as febrile/allergic reactions. red-cell alloantibody sensitisation and transmissable viral infections. There are numerous reported studies which have shown the benefit of ET in such circumstances.’ ‘(I but others have shown no benefit” or been managed successfully without ET.” One of the few randomized studies comparing antimalarial therapy with or without exchange transfusions was undertaken by Saddler et al. (1990) but only involved eight patients. All four patients who were exchanged survived but of the remainder three out of four died. There was however. no information to ascertain whether these two patient groups were comparably matched, the numbers of patients evaluated were very small and results did not achieve statistical significance. A review by Phillips et al. evaluated 40 patients with PFM who had been managed by ET over a 16-year period between 1974 and 1990. Five patients died despite ET and these shared certain adverse prognostic factors such as age greater than 50 years. mean pretreatment parasitaemias of 37% greater than four malaria related complications and mean duration of illness pre treatment of 8.6 days. The main advantage of ET was the rapid reduction in the level of parasitaemia. usually less than 6 h, when compared to standard antimalarial drug therapy. with the mean parasitaemia falling from a pretreatment level of 30% to 3%. Similar findings have been borne out by other investigators.‘4 As far as we are aware, however, there has been no comparative research performed to ascertain whether automated are more efficacious than manual exchange transfusions. The potential advantages of automated ET relate to greater volume of blood which can be exchanged over a shorter period of time. with more effective reduction in the parasitaemfa and less cardiovascular instability. Certainly automated ET has been shown to be more effective than manual procedures in the setting of sickle cell crises.’ 5 As a cautionary note there is a potential concern regarding positive reporting bias of cases successfully managed by BT and not reporting those with adverse outcomes. Additionally no consensus exists regarding the oplimal volume of blood required J’OJ successful ET. with case reports quoting between 1 and 10 litres and additionally whether one should be using whole blood or packed red cells. Ideally these questions and the whole role of ET in severe PFM need to be addressed in controlled randomized clinical trials. From our own experience, we feel that OUT patient’s condition was deteriorating rapidly until automated ET was commenced and the reduction in parasitaemia was too early to reflect a response to quinine therapy alone. Finally despite the aforementioned, following discharge from hospital she was left with residual renal impairment (creatinine 165 ymol/l) and subsequently developed a post-malaria retinopathy and peripheral neuropathy highlighting the considerable morbidity associated with this parasitic infection despite aggressive therapy.
233
Case Reports In summary, the lessons to be learned include, antimalarial prophylaxis is essential in all travellers to malaria zones and the importance of considering Ihe diagnosis of malaria in a patient presenting with a febrile illness following appropriate foreign travel and finally reinforces the value of automated ET in seriously ill patients with PIN high parasitaemias and multiorgan complications. in conjunction with specific antimalarial and full supportive therapy.
References 1 Stone WJ, Hanchett JE. Knepshield JH. Acute renal insufficiency due to falciparum malaria: review of 42 cases. Arch b?tei-11 Med 1972: 129: 620-628. 2 Kurathong S. Srichailtul T. Isarangkura l? Phanichphant S. Exchange transfusion in cerebral malaria complicated by dissemnated intravascular coagulation. Soutilensl Asin~? J Troy? Mrd PrUc Hmlth 1979: 10: 389~392. 3 Phillips P. Mantel S. Renny WB. Exchange transfusion as an adjunct to the treatment of severe falciparum malaria: case report and review. Rev 111Jccr Dis 1990: 12: 1100-I 108. 4 Espinosa G. Tortajada C. Gascon J. Miquel R, Nicolas JM. Nadal P. Corachan 31. Severe plasmodiurn falciparum malaria. Description of 5 casts. RclJisln Cfill Esptrnofn 1997: 197: 631-634. 5 Lobe1 HO. Bernard KW Williams SL. Hightower AW Patchen 1X. Campbell CC. Effectiveness and tolerance of long term malaria prophylaxis with mefloquine (need for a better dosing regimen). JAMA 1991: 265: 361-364.
Automated
Erythrocytapheresis Falciparum
Derek C. Macallan*l, Michaela John Parker-WiIliams2,
6 Steffen R. Fuchs E. Schildknccht J. Mcfloquine compared with other malaria chemoprophylactic regimens in tourists visiting East Africa. J.aizcet 1993: 341: 1299~1303. 7 Kyriacou DN. Spira AM, Talan IX. Mabey DC. Emergency department presentation and misdiagnosis of imported malaria. Am Emerg
in the Treatment Malaria
of Severe
Pocock2, Elizabeth Bishop2, David IH.Bevan2, Tom Harrison’ and Grant T. Robinson2
‘Departnxxt oj- InJxtious Diseasesand ‘Departmerzt
ofHaemntology,
St George’sHospital Medical Scl~ool,Londo~~,U.K.
Removal of parasitized erythrocytes is generally considered to be of value as adjunctive therapy in severe falciparum malaria with high parasitaemia. This is commonly achieved by exchange transfusion. We describe three cases of severe falciparum malaria treated by automated erythrocytapheresis (red cell exchange) in addition to quinine and conventional supportive therapy. Erythrocytapheresis consists of removal of the red-cell fraction by apheresis. Plasma, leukocyte and platelet fractions are returned to the patient. In all cases, dramatic reduction in parasitaemia was achieved within 2 h with subsequent complete clinical recovery. Erythrocytapheresis has significant advantages over exchange ’ transfusion in terms of speed, efficiency, haemodynamic stability and retention of plasma components such as clotting factors and may thus represent an improvement in adjunctive therapy for severe malaria. 0 1999 The British Infection Society
Introduction Palciparum significant
malaria mortality,
with parasitaemia particularly
if there
of more than 10% has a is evidence
of cerebral
involvemenl’,‘. The primary pathology is thought lo be related to sequestration of parasitized red cells in the microcirculation, particularly the cerebral vasculature. Although the mechanism of such oathogenesis is still unclear. manv authorities agree that. at high parasitaemia, removal of parasitized red-cells is an important adjunct to antimalarial chemlotherapy The use of exchange transfusion to achieve this was first described by Gyr et al. in 19743. The rationale behind such an approach is the rapid removal of parasitized cells preventing L
-Address Diseases. Accepted
correspondence to: Dr D. C. Macallan. Division of Infectious St George’s Hospital Medical School. London. SW1 7 ORE, U.K. for publication 10 August 1999.
-