BABESIOSIS

BABESIOSIS

Current diagnosis

• Suspect babesiosis in patients from Ixodes tick-endemic areas who present with a malaria-like illness (MLI) with fever, chills, headache, fatigue, and malaise.

• Clinically, babesiosis usually presents as an acute febrile illness with high fevers (>102 °F), relative bradycardia, and shaking chills accompanied by fatigue and myalgias.

•   Myalgias may suggest an influenza-like illness (ILI).

• Severe headaches may suggest an alternate diagnosis, e.g., meningitis.

• Some patients with babesiosis may be short of breath and may go on to develop acute respiratory distress syndrome (ARDS).

• Consider babesiosis for unexplained fevers following blood transfusion.

• In prolonged fevers that meet the definition of fever of unknown origin (FUO), consider babesiosis in patients from endemic areas.

• With babesiosis, there are usually no localizing signs except for splenomegaly. Importantly, no rash is present. If rash is present, consider an alternate diagnosis.

• In babesiosis, nonspecific laboratory test results, considered together, are helpful in excluding or narrowing diagnostic possibilities.

• Common nonspecific laboratory findings of babesiosis include a normal/slightly decreased white blood cell count, relative lymphopenia, atypical lymphocytes, thrombocytopenia, elevated total bilirubin, and high lactate dehydrogenase levels. Sera are mildly elevated.

•   The erythrocyte sedimentation rate is usually highly elevated (>90 mm/h) as are serum ferritinlevels.

• Definitive babesiosis diagnosis is by peripheral blood smears (thick and thin); thick smears are best for the detection of babesia and thin smears are best to assess the degree of parasitemia.

• In normal hosts, the degree of parasitemia is usually low (1%–5%), but high in compromised hosts (>10%). Severe babesiosis may occur in asplenic individuals (Howell-Jolly bodies reflect the degree of splenic dysfunction), the immunosuppressed, the elderly, and those with coinfections, e.g., ehrlichiosis, Lyme disease.

• If present, babesiosis is diagnosed by peripheral stained blood smears demonstrating the characteristic (but uncommon) “Maltese cross” in tetrads (four merozoites).

• In nonmalarious areas, babesiosis may be diagnosed by demonstrating intraerythrocytic ring forms on the peripheral smear.

• Babesiosis, like malaria, has intracellular ring forms, but babesiosis, unlike malaria, has no intracellular pigment (hemozoin).

• Alternatively, Babesia microti serology in the Northeastern United States is diagnostic if IgM titers are highly elevated (>1:64).

• Polymerase chain reaction to detect Babesia is more sensitive than blood smear review. It is particularly useful in patients with a low level of parasitemia.

Current therapy

• Preferred therapy is atovaquone (Mepron)1  plus azithromycin (Zithromax).1

•   Alternatively, clindamycin (Cleocin)1  plus quinine1  may be used.

• In addition to antibabesia therapy, exchange transfusion may be lifesaving in severe cases.

•   For severe cases, continue therapy until degree of parasitemia is <5%.

• Recurrent or persistent babesiosis should be treated for >2 weeks after resolution of parasitemia.

•   Doxycycline is not effective in babesiosis.

•   Coinfection with other tick-borne pathogens is rare, but possible.

1 Not FDA approved for this indication.

Epidemiology

Babesiosis is a tick-borne zoonosis that clinically presents as a malaria- like illness (MLI). There are many Babesia species, but only five are pathogenic in humans. The geographic distribution of babesiosis mimics that of hard-bodied Ixodes dammini (I. scapularis) ticks and their vertebrate hosts, e.g., dogs, cats, cattle, and rodents. The primary reservoir for babesiosis in the Northeastern United States is the white- footed mouse (I. dammini nymphs) and the white-tailed deer (I. dammini adults). Sporadic cases of babesiosis also occur in states with the tick vector/vertebrate hosts. Babesiosis may also be acquired by blood/blood product transfusions.

Clinical Features

In the Northeastern United States, babesiosis is usually B. microti and clinically manifests as an MLI. Babesiosis may be asymptomatic (IgG seropositive) or a mild, self-limited influenza-like illness (ILI). The incubation period for naturally acquired babesiosis is 1 to 6 weeks and 6 to 9 weeks for transfusion-acquired babesiosis. Clinical presentations in normal hosts are subacute with fever, fatigue, headache, malaise, and anorexia often mimicking Epstein-Barr virus infectious mononucleosis (with false-positive Monospot test results). Babesiosis presenting in patients with prolonged fevers of unknown origins (FUOs) and anorexia/weight loss may mimic a lymphoreticular malignancy. Presentation may be acute in those with impaired splenic function, those on immunosuppressives, or the elderly. Babesiosis may be viewed clinically as the “malaria of Long Island/Nantucket” as it presents with many malarial features, e.g., fever, chills, headache, sweats, myalgias. Excluding epidemiologic considerations, babesiosis differs in geographic distribution from malaria. Clinically, babesiosis differs from malaria in two important aspects. The clinical hallmarks of malaria are acute onset, intermittent fevers, and the classic “malaria paroxysm.” Babesia reproduce by asynchronous asexual budding, which is clinically manifest as constant/nonintermittent fever. With malaria, fevers are intermittent with fever periodicity related to the Plasmodium species. Only P. falciparum has no fever periodicity and like babesiosis has no hepatic phase. Malaria and babesiosis both have extraerythrocytic ring forms, but babesiosis has two distinct morphologic features: extracellular merozoites (tetrads), known as “Maltese crosses,” and no extraerythrocytic pigment, which malaria does have.

Unless the liver or spleen is enlarged, the physical features in babesiosis are limited to the fever. The fever curve of babesiosis is remittent without periodicity; fever is between 102 °F and 105 °F and accompanied by relative bradycardia. Rash is not a feature. When babesiosis is suspected, the presence of a rash is either indicative of coinfection, e.g., Lyme disease, or an alternative cause, e.g., viral or drug exanthem. Babesiosis should not be in the differential diagnosis of Rocky Mountain spotted fever with rash on the wrists/ankles.

Babesiosis may clinically resemble ehrlichiosis. Peripheral blood smears are the best way to differentiate babesiosis from ehrlichiosis. Nonspecific laboratory abnormalities in babesiosis include normal/decreased white blood cell (WBC) count (leukopenia). Relative lymphopenia is usually present. Atypical lymphocytes are frequently present in the peripheral smear. Thrombocytopenia is a constant finding. The erythrocyte sedimentation rate (ESR) is highly elevated (usually >90 mm/h and often >100 mm/h) as is C-reactive protein (CRP). Since the pathophysiology of babesiosis is that of an acute hemolytic anemia, like malaria, intravascular hemolysis in babesiosis is manifested by increased lactate dehydrogenase (LDH)/total bilirubin. Increased LDH and total bilirubin are the most sensitive indicators of the degree of intravascular hemolysis in babesiosis. The hemoglobin/hematocrit is decreased later in more severe cases.

Ferritin levels are highly elevated and prolonged (higher/longer) than would occur with acute-phase ferritin elevations. Since babesiosis impairs T cell function, as in malaria, serum protein electrophoresis often shows polyclonal gammopathy reflecting compensatory B cell hyperactivity. Serum transaminases are mildly elevated, but alkaline phosphatase is unelevated. Cold agglutinins are not a feature of babesiosis. In patients with decreased/absent splenic function, Howell-Jolly bodies are present in the peripheral smear. The number of Howell-Jolly bodies present is inversely proportional to the degree of splenic dysfunction.

Diagnosis of babesiosis is microscopic or serologic. Like malaria, babesiosis may be diagnosed on Giemsa stained blood smears. If malaria is not a diagnostic consideration (geographic distribution, blood transfusion), the presence of intraerythrocytic ring forms is diagnostic. Less common, but more specific, are pathognomonic tetrads (Maltese crosses) of babesiosis in peripheral smears. Also, unlike malaria, there is no extraerythrocytic pigment in babesiosis. Alternatively, elevated IgM Babesia species titers are diagnostic.

Therapy

The preferred therapy of babesiosis consists of 7 days combination therapy of azithromycin (Zithromax)1 plus atovaquone (Mepron).1 Alternatively, clindamycin (Cleocin)1 plus quinine1 for 7 days may be used (Table 1).

Table 1

Babesiosis

 

Preferred Therapy                                                                                                   Alternate Therapy
Azithromycin (Zithromax)1 500 mg PO × 1, then 250 mg PO q24h × 7 days

plus

Atovaquone suspension (Mepron)1 750 mg PO q12h × 7 days

Clindamycin (Cleocin)1 600 mg PO q8h × 7 days

plus

Quinine1 650 mg PO q8h × 7 days

From Cunha BA, editor. Antibiotic Essentials. 12th ed. Sudbury, MA: Jones & Bartlett; 2013, p. 253–268.

1  Not FDA approved for this indication.

Treatment failure may occur in those with impaired T cell function, e.g., patients with HIV or with decreased splenic function. In such cases, exchange transfusion may be lifesaving.

References

1.     Bonoan J.T., Johnson D.H., Cunha B.A. Life-threatening babesiosis in an asplenic patient treated with exchange transfusion, azithromycin and atovaquone. Heart Lung. 1998;27:424–428.

2.    Cunha B.A., Raza M., Schmidt A. Highly elevated serum ferritin levels are a diagnostic marker in babesiosis. Clin Infect Dis. 2015;60:827–829.

3.     Cunha B.A., Mickail N., Laguerre M. Babesiosis mimicking Epstein Barr Virus (EBV) infectious mononucleosis: another cause of false positive Monospot test. J Infect. 2012;62:531–532.

4.    Cunha B.A., Cohen Y.Z., McDermott B. Fever of unknown origin (FUO) due to babesiosis in an immunocompetent host. Heart Lung. 2008;37:481–484.

5.     Cunha B.A., Nausheen S., Szalsa D. Pulmonary complications of Babesiosis: case report and literature review. Eur J Clin Microbiol Infect Dis. 2007;26:505–508.

6.      Cunha B.A., Crean J., Rosenbaum G. Lipid abnormalities in babesiosis. Am J Med. 2000;15:758–759.

7.      Cunha C.B. Infectious diseases differential diagnosis. In: Cunha B.A., ed. Antibiotic Essentials. ed 12th Sudbury, MA: Jones & Bartlett; 2013:474–506.

8.      Hildebrandt A., Gray J.S., Hunfeld K.P. Human babesiosis in Europe: what clinicians need to know. Infection. 2013;41:1057– 1072.

9.       Kim N., Rosenbaum G.S., Cunha B.A. Relative bradycardia and lymphopenia in patients with babesiosis. Clin Infect Dis. 1998;26:1218–1219.

10.      Krause P.J., Daily J., Telford S.R., et al. Shared features in the pathology of babesiosis and malaria. Trends Parasitol. 2007;23:605–610.

11.      Larkin J.M. Ticks and tick-related illness. Med Health RI. 2008;91:209–211.

12.     Leiby D.A. Transfusion-transmitted Babesia spp: bull’s-eye on Babesia microti. Clin Microbiol Rev. 2011;24:14–28.

13.    Merch K., Holmaas G., Frolander P.S., et al. Severe human Babesia divergens infection in Norway. Int J Infect Dis. 2014;23:37–38.

14.     Nathavitharana R.R., Mitty J.A. Diseases from North America: focus on tick-borne infections. Clin Med. 2015;15:74–77.

15.    Panduranga V., Kumar A. Severe babesiosis presenting as acute respiratory distress syndrome in an immunocompetent patient. Conn Med. 2014;78:289–291.

16.     Rosenbaum G.S., Johnson D.H., Cunha B.A. Atypical lymphocytosis in babesiosis. Clin Infect Dis. 1995;20:203–204.

17.    Sharon K.P., Krause P.J. Babesiosis. In: Cunha B.A., ed. Tickborne infectious diseases diagnosis and management. New York: Information Healthcare; 2007:111–120.

18.     Usmani-Brown S., Halperin J.J., Krause P.J. Neurological manifestations of human babesiosis. Handb Clin Neurol. 2013;114:199–203.

19.      Wudhikarn K., Perry E.H., Kemperman M., et al. Transfusion- transmitted babesiosis in an immunocompromised patient: a case report and review. Am J Med. 2011;124:800–805.

1  Not FDA approved for this  indication.

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