BRIEF CLINICAL OBSERVATIONS
PAROXYSMAL FLUCTUATIONS IN OBSERVEDPARASITEMIAIN PLASMODIUM FALCIPARUM MALARIA The last decade has seen a resurgence in malaria worldwide, and at the same time there is increasing resistance to standard prophylaxis against Plasmodium falciparum. With international travel increasing, cases of malaria are on the rise in the United States. The problem is further complicated by the high mortality from P. [alciparum malaria in returning travelers due to delay in recognition and treatment as well as a lack of acquired immunity [1]. It is, therefore, increasingly important for primary care physicians to be familiar with the presentation and management of malaria. Standard algorithms for the treatment of P. falciparum begin with an estimate of the extent of parasitemia based on examination of thin blood smears [2,3]. We report on a case of malaria in a returning traveler in
which the initial blood smear greatly underestimated the extent of infection and thus led to a delay in optimal therapy. We hope this case will serve to remind physicans of the potential seriousness of malaria and alert them to an infrequently reported presentation that may be more prevalent in travelers. A previously healthy 28-yearold woman presented with severe headache and fever 10 days after returning from a 5-week trip to Central and East Africa. She was compliant with chloroquine prop h y l a x i s and observed o t h e r standard precautions. During the trip, she noted only a few mosquito bites and no illnesses. On admission to the hospital, she underwent physical examination, the results of which were unremarkable except for an oral temperature of 39.5°C and mildly injected sclerae. Blood smears from an intravenous sample were examined by both the attending physicians and the hospital parasitology laboratory. These
showed P. [alciparum parasites in about one of every 10 oil immersion fields (approximately 0.05% parasitemia). She began to receive oral therapy with quinine sulfate 600 mg every 8 hours and tetracycline 500 mg every 6 hours and parenteral narcotics for severe headaches. Approximately 12 hours after admission, the patient reported feeling better and was able to eat breakfast. Her hematocrit was 38%; however, a blood smear showed a parasitemia of 22% (Figure 1). After a subsequent smear confirmed the severity of infection, the patient was transferred to the intensive care unit for intravenous quinidine and exchange transfusion. During the next 5 hours, her hematocrit fell to 25% despite a net transfusion of 2 units, and she became increasingly jaundiced. The exchange was discontinued, and transfusion to a hematocrit of 33% was performed. Twenty-four hours after the initiation of intravenous quinidine, her parasite-
Figure 1. Wright stain of thin blood smear 12 hours after admission showing a parasitemia of approximately 22°1o. The thin, delicate rings, and the high percentage of infected cells, multiply infected cells, and appliqu~ forms are characteristic of P. falciparum malaria (original magnification X1,250, reduced by 40%).
530
April 1991 The American Journal of Medicine Volume 90
BRIEF CLINICAL OBSERVATIONS
mia was less than 2%. The parasitemia continued to resolve after oral therapy was resumed. There were at no time signs of cerebral malaria, adult respiratory distress syndrome, disseminated intravascular coagulation, or transfusion reaction. The patient presented in this report had an alarming increase in malaria parasites as seen on peripheral smear over a period of 12 hours. A few authors have reported similar paroxysmal increases in the observed parasitemia in P. falciparum malaria [4,5], but most standard references on the subject do not emphasize this presentation. Such rapid and extreme fluctuations in the estimated parasitemia cannot be explained simply by parasite multiplication, since the in vitro potential rate of increase for P. falciparum is limited to 20-fold over 48 hours [6].Yet this patient was seen to have a startling 400fold increase in 12 hours. Paroxysmal parasitemia is more likely to result from features unique to the P. falciparum lifecycle. Red blood cellsthat contain the dividing schizonts of P. falciparum marginate and are not found in peripheral blood. A highly synchronous infection m a y at times show few ring forms followed suddenly by massive numbers of infected red blood cells as the majority of cycling parasites are s i m u l t a n e o u s l y released. The lack of acquired immunity in a t r a v e l e r from a n o n e n d e m i c country may also have allowed the parasitemia to increase more dramatically than in an immune individual. This case illustrates a presentation of P. falciparum malaria characterized by paroxysmal increases in parasite number in which the initial blood smear was unreliable in predicting the actual intensity of infection. Traditionally, once the diagnosis of P.
falciparum malaria was made and definitive drug therapy initiated, frequent blood smears were not performed, as they were unlikely to alter therapy. Because exchange transfusion and intravenous quinidine/quinine are now the indicated treatments for patients with severe infection (greater than 5% parasitemia) [1], there is new impetus to identify these patients early. Based on our experience with this patient and review of reports of similar cases, we would recommend that thin blood smears be obtained every 6 to 8 hours during the first 24 hours in patients whose initial thin blood smear shows a low level of parasites (less than 5%). Early detection of those patients ~hown to have high parasitemia will allow timely initiation of more aggressive therapy. KEITH S. ARMITAGE, M.D. RONALD E, BLANTON, M.D.
Case Western Reserve University and University Hospitals Cleveland, Ohio
1. Miller KO, Greenberg AE, Cambell CC. Treatment of severe malaria in the United States with a continuous infusion of quinidine gluconate and exchange transfusion. N Engl J Med 1989; 321: 65-70. 2. Miller LH, Warrell DA. Malaria. In: Warren KS, Mahmoud AAF, eds. Tropical and geographical medicine. New York: McGraw-Hill, 1990: 245-64. 3. Wyler DJ. Plasmodiumspecies(malaria). In: Mandel GL, Douglas RG, Bennett JE, eds. Principles and practice of infectious diseases. New York: Churchill Livingstone, 1990: 2056-66. 4. Coatney RG, Cooper WC, Young MD, McLendon SB. Studies in human malaria. Am J Hyg 1947; 46: 84-104. 5. Chiodini PL, Somerville M, Salam I, Tubbs HR, Wood MJ, Ellis CJ. Exchange transfusion in severe falciparum malaria. Trans R Soc Trop Med Hyg 1985; 79: 865-6. 6. Coatney RG, Collins WE, Warren M, Contacos PG. The primate malarias. Bethesda, Maryland: United States Department of Health, Education and Welfare, 1971: 267-8.
Submitted July'lO, 1990, and accepted in revised form October 1, 1990 (NOTE: Dr, Armitage is supported by National Institutes of Health [NIH] Grant AG00144, and Dr. Blanton by NIH Grant AI27317.)
April 1991
IRREVERSIBLE COMPLETE HEART BLOCK IN LYME DISEASE Lyme disease is a multisystemic process with dermatologic, neurologic, and cardiac manifestations caused by the spirochete Borrelia burgdorferi, transmitted to humans by the bite of a tick of the genus Ixodes. The most frequent cardiac manifestation is atrioventricular (AV) block characterized by rapid fluctuations in the grade [1-4]. This block is complete in up to 50% of cases [1,3,4]. In the largest series reported, Steere [1] observed 20 patients, 18 of whom showed different grades of AV block; complete heart block developed in eight patients. In all cases, these anomalies were brief and returned to normal in I to 2 weeks. No bundle branch block was reported. We report a case of a 20-yearold woman with Lyme disease and complete AV block that did not reverse after 6 weeks of treatment. On admission, results of clinical examination were normal. An e l e c t r o c a r d i o g r a m showed sinus rhythm with grade I AV block, intermittent grade II block, and left bundle branch block (Figure 1). A chest roentgenogram was normal. The Lyme disease was well documented by repeated serologic studies (indirect immunofluorescence) demonstrating high titers; the first sample showed a titer of 1:1,024 and a second sample 2 weeks after initiation of treatment with penicillin showed a titer of 1:523. Blood cell counts, erythrocyte sedimentation rate, findings on biochemical studies, immunoglobulins, complement levels, antinuclear antibodies, anti-DNA, anti-smooth muscle antibodies, rheumatoid factor, and results of serologic tests for respiratory viruses, Chlamydia, Mycoplasma, and syphilis were normal or nega-
The American Journal of Medicine
Volume 90
531
PAROXYSMAL FLUCTUATIONS IN OBSERVEDPARASITEMIAIN PLASMODIUM FALCIPARUM MALARIA The last decade has seen a resurgence in malaria worldwide, and at the same time there is increasing resistance to standard prophylaxis against Plasmodium falciparum. With international travel increasing, cases of malaria are on the rise in the United States. The problem is further complicated by the high mortality from P. [alciparum malaria in returning travelers due to delay in recognition and treatment as well as a lack of acquired immunity [1]. It is, therefore, increasingly important for primary care physicians to be familiar with the presentation and management of malaria. Standard algorithms for the treatment of P. falciparum begin with an estimate of the extent of parasitemia based on examination of thin blood smears [2,3]. We report on a case of malaria in a returning traveler in
which the initial blood smear greatly underestimated the extent of infection and thus led to a delay in optimal therapy. We hope this case will serve to remind physicans of the potential seriousness of malaria and alert them to an infrequently reported presentation that may be more prevalent in travelers. A previously healthy 28-yearold woman presented with severe headache and fever 10 days after returning from a 5-week trip to Central and East Africa. She was compliant with chloroquine prop h y l a x i s and observed o t h e r standard precautions. During the trip, she noted only a few mosquito bites and no illnesses. On admission to the hospital, she underwent physical examination, the results of which were unremarkable except for an oral temperature of 39.5°C and mildly injected sclerae. Blood smears from an intravenous sample were examined by both the attending physicians and the hospital parasitology laboratory. These
showed P. [alciparum parasites in about one of every 10 oil immersion fields (approximately 0.05% parasitemia). She began to receive oral therapy with quinine sulfate 600 mg every 8 hours and tetracycline 500 mg every 6 hours and parenteral narcotics for severe headaches. Approximately 12 hours after admission, the patient reported feeling better and was able to eat breakfast. Her hematocrit was 38%; however, a blood smear showed a parasitemia of 22% (Figure 1). After a subsequent smear confirmed the severity of infection, the patient was transferred to the intensive care unit for intravenous quinidine and exchange transfusion. During the next 5 hours, her hematocrit fell to 25% despite a net transfusion of 2 units, and she became increasingly jaundiced. The exchange was discontinued, and transfusion to a hematocrit of 33% was performed. Twenty-four hours after the initiation of intravenous quinidine, her parasite-
Figure 1. Wright stain of thin blood smear 12 hours after admission showing a parasitemia of approximately 22°1o. The thin, delicate rings, and the high percentage of infected cells, multiply infected cells, and appliqu~ forms are characteristic of P. falciparum malaria (original magnification X1,250, reduced by 40%).
530
April 1991 The American Journal of Medicine Volume 90
BRIEF CLINICAL OBSERVATIONS
mia was less than 2%. The parasitemia continued to resolve after oral therapy was resumed. There were at no time signs of cerebral malaria, adult respiratory distress syndrome, disseminated intravascular coagulation, or transfusion reaction. The patient presented in this report had an alarming increase in malaria parasites as seen on peripheral smear over a period of 12 hours. A few authors have reported similar paroxysmal increases in the observed parasitemia in P. falciparum malaria [4,5], but most standard references on the subject do not emphasize this presentation. Such rapid and extreme fluctuations in the estimated parasitemia cannot be explained simply by parasite multiplication, since the in vitro potential rate of increase for P. falciparum is limited to 20-fold over 48 hours [6].Yet this patient was seen to have a startling 400fold increase in 12 hours. Paroxysmal parasitemia is more likely to result from features unique to the P. falciparum lifecycle. Red blood cellsthat contain the dividing schizonts of P. falciparum marginate and are not found in peripheral blood. A highly synchronous infection m a y at times show few ring forms followed suddenly by massive numbers of infected red blood cells as the majority of cycling parasites are s i m u l t a n e o u s l y released. The lack of acquired immunity in a t r a v e l e r from a n o n e n d e m i c country may also have allowed the parasitemia to increase more dramatically than in an immune individual. This case illustrates a presentation of P. falciparum malaria characterized by paroxysmal increases in parasite number in which the initial blood smear was unreliable in predicting the actual intensity of infection. Traditionally, once the diagnosis of P.
falciparum malaria was made and definitive drug therapy initiated, frequent blood smears were not performed, as they were unlikely to alter therapy. Because exchange transfusion and intravenous quinidine/quinine are now the indicated treatments for patients with severe infection (greater than 5% parasitemia) [1], there is new impetus to identify these patients early. Based on our experience with this patient and review of reports of similar cases, we would recommend that thin blood smears be obtained every 6 to 8 hours during the first 24 hours in patients whose initial thin blood smear shows a low level of parasites (less than 5%). Early detection of those patients ~hown to have high parasitemia will allow timely initiation of more aggressive therapy. KEITH S. ARMITAGE, M.D. RONALD E, BLANTON, M.D.
Case Western Reserve University and University Hospitals Cleveland, Ohio
1. Miller KO, Greenberg AE, Cambell CC. Treatment of severe malaria in the United States with a continuous infusion of quinidine gluconate and exchange transfusion. N Engl J Med 1989; 321: 65-70. 2. Miller LH, Warrell DA. Malaria. In: Warren KS, Mahmoud AAF, eds. Tropical and geographical medicine. New York: McGraw-Hill, 1990: 245-64. 3. Wyler DJ. Plasmodiumspecies(malaria). In: Mandel GL, Douglas RG, Bennett JE, eds. Principles and practice of infectious diseases. New York: Churchill Livingstone, 1990: 2056-66. 4. Coatney RG, Cooper WC, Young MD, McLendon SB. Studies in human malaria. Am J Hyg 1947; 46: 84-104. 5. Chiodini PL, Somerville M, Salam I, Tubbs HR, Wood MJ, Ellis CJ. Exchange transfusion in severe falciparum malaria. Trans R Soc Trop Med Hyg 1985; 79: 865-6. 6. Coatney RG, Collins WE, Warren M, Contacos PG. The primate malarias. Bethesda, Maryland: United States Department of Health, Education and Welfare, 1971: 267-8.
Submitted July'lO, 1990, and accepted in revised form October 1, 1990 (NOTE: Dr, Armitage is supported by National Institutes of Health [NIH] Grant AG00144, and Dr. Blanton by NIH Grant AI27317.)
April 1991
IRREVERSIBLE COMPLETE HEART BLOCK IN LYME DISEASE Lyme disease is a multisystemic process with dermatologic, neurologic, and cardiac manifestations caused by the spirochete Borrelia burgdorferi, transmitted to humans by the bite of a tick of the genus Ixodes. The most frequent cardiac manifestation is atrioventricular (AV) block characterized by rapid fluctuations in the grade [1-4]. This block is complete in up to 50% of cases [1,3,4]. In the largest series reported, Steere [1] observed 20 patients, 18 of whom showed different grades of AV block; complete heart block developed in eight patients. In all cases, these anomalies were brief and returned to normal in I to 2 weeks. No bundle branch block was reported. We report a case of a 20-yearold woman with Lyme disease and complete AV block that did not reverse after 6 weeks of treatment. On admission, results of clinical examination were normal. An e l e c t r o c a r d i o g r a m showed sinus rhythm with grade I AV block, intermittent grade II block, and left bundle branch block (Figure 1). A chest roentgenogram was normal. The Lyme disease was well documented by repeated serologic studies (indirect immunofluorescence) demonstrating high titers; the first sample showed a titer of 1:1,024 and a second sample 2 weeks after initiation of treatment with penicillin showed a titer of 1:523. Blood cell counts, erythrocyte sedimentation rate, findings on biochemical studies, immunoglobulins, complement levels, antinuclear antibodies, anti-DNA, anti-smooth muscle antibodies, rheumatoid factor, and results of serologic tests for respiratory viruses, Chlamydia, Mycoplasma, and syphilis were normal or nega-
The American Journal of Medicine
Volume 90
531
