Volume 24-12
June 15, 1998

[Table of Contents]

CONCURRENT BABESIOSIS AND LYME DISEASE DIAGNOSED IN ONTARIO

Introduction

Human babesiosis (caused by Babesia microti) and Lyme disease (caused by Borrelia burgdorferi) are among the most common tick-transmitted zoonoses. Recent evidence indicates that both diseases are emerging in the northeastern and Great Lakes regions of the United States as the deer tick (Ixodes scapularis), which transmits both infections, increases in geographic distribution^(1,2). Because B. microti and B. burgdorferi  reside in the same rodent reservoir (Peromyscus leucopus) and are transmitted by the same tick vector, human co-infection may be relatively common in endemic areas. In support of this contention, up to two-thirds of Long Island residents with Lyme disease have antibodies to Babesia species⁽³⁾. However, until recently, only three episodes of co-infection had been described and, in each case, a particularly severe illness was experienced and one individual died^(4-6). A recent report from New England found that the severity of symptoms and duration of illness in patients with concurrent babesiosis and Lyme disease was greater than for either infection alone⁽⁷⁾.

Ixodes scapularis ticks have been found in a number of provinces in Canada and 205 cases of Lyme disease were reported to public-health officials from 1984-1994 (105 locally acquired)⁽⁸⁾. However, there have been no previous reports of co-infections in Canada and, to our knowledge, no case of babesiosis has ever been reported in Canada. This report describes a co-infection of babesiosis and Lyme disease acquired by a Canadian traveler.

Case Report

A 59-year-old male from Toronto presented to The Toronto Hospital on 27 July 1997 because of persistent fever and night sweats.  The patient had recently returned from a 6-week trip to Nantucket, where he had vacationed in a summer home. There was no history of rural travel nor hiking or walking in the woods. Additional travel history included a trip to Hong Kong, Indonesia, and Singapore 7 months ealier.

The patient was well until 21 June 1997 when he noticed a small black "pinhead" lesion on his left biceps, which he removed. He subsequently developed a spreading erythema surrounding this lesion that spontaneously resolved after 2 to 3 days. On 26 June, he experienced a 2-day episode of fever, sweats, chills, myalgia, and fatigue, which was treated symptomatically with acetaminophen. He was then well until 21 July 1997 when the fever and chills returned.  In addition, he developed rigors, extreme fatigue, headache, myalgia, nausea, vomiting, and drenching night sweats. On 22 July, he saw his family physician who diagnosed a "viral infection". On presentation to The Toronto Hospital 5 days later, he was febrile (38.8^o C), pale, and appeared ill. He had a tachycardia of 130 beats/minute, mild splenomegaly, and occasional petechia on his extremities. The remainder of his examination was unremarkable.

Initial laboratory investigations revealed a normochromic, normocytic anemia of 106 g/L, leukopenia of 4.2 billion/L (normal 4.5 to 11.0), thrombocytopenia of 14 billion/L (normal 150 to 400), elevated lactate dehydrogenase at 799 U/L (normal 45 to 90), bilirubin 26 µmol/L (normal 2 to 17), aspartate aminotransferase 151 U/L (normal < 35), fibrinogen 4.22 g/L (normal 1.5 to 3.5), fibrin degradable products > 10 µg/mL (normal < 2.5), international normalized ratio 4.89 (normal 1.00), decreased haptoglobin < 0.12 g/L (normal 0.6 to 2.9), and D-dimers < 250 ng/mL (normal 500 to 1,000).  Urinalysis was positive for blood and hemoglobin.

His past medical history was significant for nephritis of unknown etiology at the age of 3 years, atrial fibrillation diagnosed in 1995, and a myocardial infarction in 1996 complicated by congestive heart failure. He had not previously undergone splenectomy nor had he ever received a blood transfusion. The patient's medications included coumadin 7.5 mg po od, cozaar 50 mg po od, lanoxin 0.125 mg po od, and acetylsalicylic acid 325 mg po od. He had no known allergies.

His travel history to southeast Asia, fever, and hemolytic picture suggested malaria; thick and thin films were ordered. Thick and thin films revealed many tiny ring forms, initially interpreted as Plasmodium falciparum malaria at 4% parasitemia. However, an astute senior technologist noted morphologic differences from P. falciparum malaria and correctly identified the protozoan organisms on the smears as trophozoites of B. microti.

Given the severity of his illness and the preceding rash consistent with erythema migrans, there were concerns of a co-infection with additional tick-borne agents. Lyme serology was ordered and reported as positive by enzyme-linked immunoabsorbent assay and IgM positive by specific Western blot test indicating a recent infection with B. burgdorferi. Serology for human monocytic ehrlichiosis (HME), caused by Ehrlichia chaffeensis, was reported as negative at 1:64 by immunofluorescence assay. Polymerase chain reaction assays for the agent associated with human granulocytic ehrlichiosis (HGE), caused by Ehrlichia equi-like organisms, were performed in our laboratory and were negative⁽⁹⁾.

The patient was treated with quinine 600 mg tid and clindamycin 600 mg tid for 7 days for the babesial infection and doxycycline 100 mg bid for 21 days for Lyme disease. He responded promptly to therapy and was smear negative by the fourth day. When seen in follow-up at 1 and 2 months, he was asymptomatic, all previous biochemical and hematologic abnormalities returned to normal, and smears for babesiosis were negative.

Discussion

This case represents the first description of human babesiosis and the first report of a co-infection with Lyme disease recognized in Canada. Human babesiosis in the northeast and Great Lakes regions of the United States is caused by B. microti, an intracellular parasite that may be confused with P. falciparum malaria both clinically and morphologically, as initially occurred in this case⁽¹⁰⁾. The morphologic features that permit discrimination from malaria include the presence of paired piriform stages and a tetrad configuration ("Maltese cross") formed by binary fission of the trophozoite to form four merozoites. These later forms are diagnostic for babesiosis but may be difficult to find. The absence of pigment and gametocytes in babesiosis may also be helpful distinguishing features. A new species of babesiosis (WA-1) which is morphologically identical to B. microti has been described on the west coast of the United States and in Missouri^(11,12). The nymph stages of I. scapularis are primarily responsible for transmission of both Lyme disease and babesiosis.

The nymph is < 3 mm long even when fully engorged, and most infected persons do not remember a tick bite⁽¹³⁾. It is probable that the small pinpoint lesion removed by the patient in this case was in fact an engorged nymphal-stage tick. Nymphs typically feed more actively in May and June resulting in a peak of clinical illness in July. As in this case, symptoms of babesiosis usually begin 1 to 4 weeks after a tick bite⁽¹³⁾.  The clinical spectrum ranges from a mild, self-limited illness to a serious life-threatening infection with severe hemolytic anemia, thrombocytopenia, renal failure and hypotension⁽¹³⁾. Mortality rates in the United States have been < 10%, and deaths more common in the elderly, those with splenectomy, and those with HIV infection^(13,14).

Co-infection with other tick-borne agents has recently been recognized as an important determinant of the outcome of infection with babesiosis. The disease caused by the co-infection with both Lyme disease and babesiosis was shown decades ago to be more severe in experimental animals⁽¹⁵⁾. This observation has now been extended to human co-infections. Krause and colleagues reported that 11% of patients with Lyme disease in southern New England are co-infected with babesiosis⁽⁷⁾. Co-infected patients had significantly more fatigue, headache, sweats, chills, anorexia, emotional lability, nausea, conjunctivitis, and splenomegaly than those with Lyme disease alone.  Furthermore, 50% of these patients were ill for >= 3 months compared to 7% with Lyme disease. This increase in the number and duration of symptoms may be attributed to immunosuppression associated with babesial infection^(7,15).

Recently, immunoserologic evidence of co-infection with a third tick-transmitted bacterial zoonosis, Ehrlichia species (HGE and HME), has been reported^(12,16,17).  In a sero-epidemiologic study of residents of Wisconsin and Minnesota, 9.4% of patients with Lyme disease had serologic evidence of co-infection: 5.2% with HGE, 2.1% with babesiosis, and 2.1% with both⁽¹⁶⁾. Similarly in Sonoma County, California, 23% of residents were seroreactive to antigens from one or more tick-borne agents: 1.4% to Lyme, 0.4% to HGE, 4.6% to HME, and 17.8% to babesia-like piroplasm WA-1⁽¹²⁾. These studies indicate that tick-borne diseases are widespread and prevalent in some regions of the United States. Travelers from Canada will be at risk when they visit these areas during tick season (generally from May to September in the northeast). Furthermore, I. scapularis ticks have been identified in approximately 250 locations in Canada⁽⁸⁾. Prolonged parasitemias that may accompany co-infection with babesiosis, or subclinical infection in Canadian travelers who acquire any of the tick-borne pathogens, may facilitate transmission of infection to I. scapularis  ticks in regions of Canada where they reside⁽⁷⁾. Finally, blood products are not routinely screened for B. microti or B. burgdorferi. Babesiosis may be transmitted by blood transfusion and is a cause of febrile transfusion reactions in endemic areas^(18,19).

In summary, malaria should always be considered in febrile travelers and in cases of fever of unknown origin, even in those without a travel history⁽²⁰⁾. But clinicians should also consider babesiosis in the differential diagnosis of febrile travelers returning from enzootic areas of the United States where, during the tick season (May to September), infection with B. microti and B. burgdorferi is not uncommon. Furthermore, we suggest that all patients with a documented tick-transmitted infection be evaluated for co-infection with other known tick-borne agents, particularly if symptoms are severe or persist after therapy. Given the current levels of travel between Canada and the United States, and the emergence of Lyme disease, babesiosis, and ehrlichiosis, we must anticipate an increase in the number of imported cases of these tick-borne pathogens in Canadians. Prompt recognition of cases, accurate identification, and appropriate initial management is crucial in reducing morbidity and mortality associated with these infections.

References

1. White DJ, Chang HG, Benach JL et al. The geographic spread and temporal increase of the Lyme disease epidemic. JAMA 1991;266:1230-36.

2. Daniels TJ, Falco RC, Schwartz I et al. Deer ticks (Ixodes scapularis) and the agents of Lyme disease and human granulocytic ehrlichiosis in a New York City park. Emerging Infect Dis 1997;3:353-55.

3. Benach JL, Coleman JL, Habicht GS et al. Serologic evidence for simultaneous occurrences of Lyme disease and babesiosis. J Infect Dis 1985;152:473-78.

4. Grunwaldt E, Barbour AG, Benach JL. Simultaneous occurrence of babesiosis and Lyme disease. N Engl J Med 1983;308:1166.

5. Marcus LC, Steere AC, Duray PH et al. Fatal pericarditis in a patient with coexistent Lyme disease and babesiosis: demonstration of spirochetes in the myocardium. Ann Intern Med 1985:103:374-76.

6. Golightly LM, Hirschorn LR, Weller PF. Fever and headache in a splenectomized woman. Rev Infect Dis 1989;11:629-37.

7. Krause PJ, Telford III SR, Spielman A et al. Concurrent Lyme disease and babesiosis: evidence for increased severity and duration of illness. JAMA 1996;275:1657-60.

8. ProMED. Lyme Disease - Canada. URL: <http://www.promed.org>. Date of access: 23 Aug. 1997.

9. Sumner JW, Nicholson WL, Massung RF.  PCR amplification and comparison of nucleotide sequences from the groESL heat shock operon of Ehrlichia species. J Clin Microbiol 1997;35:2087-92.

10. Loutan L, Rossier J, Zufferey G et al. Imported babesiosis diagnosed as malaria. Lancet 1993;342:749.

11. Quick RE, Herwaldt BL, Thomford JW et al. Babesiosis in Washington state: a new species of Babesia? Ann Intern Med 1993:119:284-90.

12. Fritz CL, Kjemtrup AM, Conrad PA et al. Seroepidemiology of emerging tickborne infectious diseases in a northern California community. J Infect Dis 1997;175:1432-39.

13. Spach DH, Liles WC, Campbell GL et al. Tick-borne diseases in the United States. N Engl J Med 1993;329:936-47.

14. Benezra D, Brown AE, Polsky B et al. Babesiosis and infection with human immunodeficiency virus. Ann Intern Med 1987;107:944.

15. Purvis AC. Immunodepression in Babesia microti infections. Parasitology 1977;75:197-205.

16. Mitchell PD, Reed KD, Hofkes JM. Immunoserologic evidence of co-infection with Borrelia burgdorferi, Babesia microti, and human granulocytic Ehrlichia species in residents of Wisconsin and Minnesota. J Clin Microbiol 1996;34:724-27.

17. Magnarelli LA, Dumler S, Anderson JF et al. Coexistence of antibodies to tick-borne pathogens of babesiosis, ehrlichiosis, and Lyme borreliosis in human sera. J Clin Microbiol 1995;33:3054-57.

18. Mintz ED, Anderson JF, Cable RG et al. Transfusion-transmitted babesiosis: a case from an endemic area. Transfusion 1991;31:365-68.

19. Herwaldt BL, Kjemtrup AM, Conrad PA et al. Transfusion-transmitted babesiosis in Washington State: first reported case caused by a WA-1 type parasite. J Infect Dis 1997;175:1259-62.

20. Baqi M, Gamble K, Keystone JS et al. Malaria: probably locally acquired in Toronto, Ontario. Can J Infect Dis. In press.

Source: C dos Santos, MD, K Kain, MD, Tropical Disease Unit, The Toronto Hospital and University of Toronto, Toronto, ON.

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