BRIEF CLINICAL OBSERVATIONS

PAROXYSMAL FLUCTUATIONS IN OBSERVED PARASITEMIA IN PLASMODIUM FALCIPARUM MALARIA

The last decade has seen a resur- gence in malaria worldwide, and at the same time there is increas- ing resistance to standard pro- phylaxis 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 mortali- ty from P. [alciparum malaria in returning travelers due to delay in recognition and treatment as well as a lack of acquired immu- nity [1]. It is, therefore, increas- ingly 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 ex- tent of parasitemia based on ex- amination of thin blood smears [2,3]. We report on a case of ma- laria in a returning traveler in

which the initial blood smear greatly underestimated the ex- tent of infection and thus led to a delay in optimal therapy. We hope this case will serve to re- mind 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-year- old 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 pro- phylaxis and observed other standard precautions. During the trip, she noted only a few mosqui- to bites and no illnesses. On ad- mission to the hospital, she un- derwent physical examination, the results of which were unre- markable except for an oral tem- perature of 39.5°C and mildly in- jected sclerae. Blood smears from an intravenous sample were ex- amined by both the attending physicians and the hospital para- s i t o logy l a b o r a t o r y . T h e s e

showed P. [alciparum parasites in about one of every 10 oil im- mersion 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 se- vere 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 parasi temia of 22% (Figure 1). After a subsequent smear confirmed the severity of infection, the patient was trans- ferred to the intensive care unit for intravenous quinidine and ex- change transfusion. During the next 5 hours, her hematocrit fell to 25% despite a net transfusion of 2 units, and she became in- creasingly jaundiced. The ex- change was discontinued, and transfusion to a hematocrit of 33% was performed. Twenty-four hours after the initiation of intra- venous quinidine, her parasite-

Figure 1. Wright stain of thin blood smear 12 hours after admission show- ing a parasitemia of approximately 22°1o. The thin, delicate rings, and the high percentage of infected cells, mul- tiply infected cells, and appliqu~ forms are characteristic of P. falciparum ma- laria (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 parasi- temia continued to resolve after oral therapy was resumed. There were at no time signs of cerebral malaria, adult respiratory dis- tress syndrome, disseminated in- travascular coagulation, or trans- fusion 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 re- ported similar paroxysmal in- creases in the observed parasite- mia in P. falciparum malaria [4,5], but most standard refer- ences on the subject do not em- phasize 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 400- fold increase in 12 hours. Parox- ysmal parasitemia is more likely to result from features unique to the P. falciparum life cycle. Red blood cells that contain the divid- ing schizonts of P. falciparum marginate and are not found in peripheral blood. A highly syn- chronous infection may at times show few ring forms followed suddenly by massive numbers of infected red blood cells as the majority of cycling parasites are s imul taneous ly released. The lack of acquired immunity in a t r ave le r f rom 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 presen- tation of P. falciparum malaria characterized by paroxysmal in- creases in parasite number in which the initial blood smear was unreliable in predicting the actu- al intensity of infection. Tradi- tionally, once the diagnosis of P.

falciparum malaria was made and definitive drug therapy initi- ated, frequent blood smears were not performed, as they were un- likely to alter therapy. Because exchange transfusion and intra- venous 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 lev- el of parasites (less than 5%). Ear- ly detection of those pat ients ~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 contin- uous 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 med- icine. New York: McGraw-Hill, 1990: 245-64. 3. Wyler DJ. Plasmodiumspecies (malaria). In: Man- del 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 M J, 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 Wel- fare, 1971: 267-8.

Submitted July'lO, 1990, and accepted in revised form October 1, 1990

(NOTE: Dr, Armitage is supported by National Insti- tutes of Health [NIH] Grant AG00144, and Dr. Blan- ton by NIH Grant AI27317.)

IRREVERSIBLE COMPLETE HEART BLOCK IN LYME DISEASE

Lyme disease is a multisystemic process with dermatologic, neu- rologic, and cardiac manifesta- tions caused by the spirochete Borrelia burgdorferi, transmit- ted to humans by the bite of a tick of the genus Ixodes. The most frequent cardiac manifestation is atrioventricular (AV) block char- acterized 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 re- ported, Steere [1] observed 20 pa- tients, 18 of whom showed differ- ent grades of AV block; complete heart block developed in eight patients. In all cases, these anom- alies were brief and returned to normal in I to 2 weeks. No bundle branch block was reported.

We report a case of a 20-year- old woman with Lyme disease and complete AV block that did not reverse after 6 weeks of treat- ment. On admission, results of clinical examination were nor- mal . 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 roent- genogram was normal. The Lyme disease was well documented by repeated serologic studies (indi- rect immunofluorescence) dem- onstrating high titers; the first sample showed a titer of 1:1,024 and a second sample 2 weeks af- ter initiation of treatment with penicillin showed a titer of 1:523. Blood cell counts, erythrocyte sedimentation rate, findings on biochemical studies, immuno- globulins, complement levels, an- tinuclear antibodies, anti-DNA, anti-smooth muscle antibodies, rheumatoid factor, and results of serologic tests for respiratory vi- ruses, Chlamydia, Mycoplasma, and syphilis were normal or nega-

April 1991 The American Journal of Medicine Volume 90 531