Babesiosis Differential Diagnoses
- Author: Burke A Cunha, MD; Chief Editor: Michael Stuart Bronze, MD more...
Babesiosis usually manifests as an undifferentiated acute febrile illness resembling malaria. Patients who present with a malarialike illness always should be questioned regarding the possibility of previous exposure to malaria.
Patients who previously had non– P falciparum malaria may be experiencing a relapse. Such a relapse may be diagnosed on the basis of prior exposure or infection up to 40 years previously with a non-falciparum malaria. Diagnosis requires demonstration of plasmodia in properly prepared and stained thick or thin blood smears. Patients with recrudescent malaria may have low levels of parasitemia and usually have increased malaria immunoglobulin G (IgG) titers.
Patients should also be questioned about a previous history of Lyme disease. Although the signs and symptoms of Lyme disease differ from those of babesiosis, the tick vector associated with Lyme disease (I scapularis) may also transmit Babesia organisms. Coinfections of babesiosis and Lyme disease are not common but can occur.
Ehrlichiosis is an acute febrile infection resembling Rocky Mountain spotted fever (RMSF). Although seropositivity to Lyme disease and ehrlichiosis is common in endemic areas, coinfections of babesiosis with RMSF or ehrlichiosis (ie, “spotless” RMSF) are rare because these zoonoses are transmitted by Dermacentor ticks rather than Ixodes ticks. Increased Ehrlichia titers with an IgG titer of 1:64 or greater or a 4-fold or greater change in antibody titers on immunofluorescent antibody (IFA) testing is diagnostic of ehrlichiosis.
Patients with ehrlichiosis often have leukopenia, anemia, and thrombocytopenia. The erythrocyte sedimentation rate (ESR) is minimally elevated. levels of serum transaminases may be mildly increased in ehrlichiosis, as in babesiosis, typhoid fever, and RMSF. Typhoid fever, RMSF, and Lyme disease may be differentiated from babesiosis, ehrlichiosis, and malaria on the basis of the presence or absence of hemolytic anemia, which is not a typical feature of the first 3 conditions.
Except for Lyme disease and typhoid fever, thrombocytopenia is a feature of all of these infectious diseases. Leukopenia is a common finding in typhoid fever, RMSF, babesiosis, and ehrlichiosis but is not a characteristic finding in Lyme disease.
Splenomegaly may be present in patients with typhoid fever, malaria, babesiosis, ehrlichiosis, and RMSF but is not a feature of Lyme disease.
Arthropod-borne viral infections may be confused with babesiosis. However, arboviral illnesses are characterized by their extreme rapidity of onset and their clinical severity, neither of which is typical of babesiosis unless the spleen is absent.
Relative bradycardia is a cardinal finding in many infectious diseases, including many arboviral infections (eg, yellow fever, dengue fever, and African hemorrhagic fever [Ebola]). Relative bradycardia is a common finding in patients with malaria, RMSF, and babesiosis but is not a feature of Lyme disease.
In rare cases, typhoidal Epstein-Barr virus (EBV) infection, mononucleosis, or typhoidal tularemia may be confused with babesiosis. EBV-specific antibody testing and tube agglutination testing for tularemia can help exclude these diagnostic possibilities if they are considered in the differential diagnosis.
Typhoid fever is suggested by a severe headache and an apathetic facies with few, if any, localizing signs. Splenomegaly may be present later in the course of the illness. A normal or slightly decreased peripheral white blood cell (WBC) count is the characteristic hematologic finding; the presence of eosinophilia or thrombocytopenia suggests an alternate diagnosis. Typhoid fever may be diagnosed by staining or culturing the organism in reticuloendothelial system (RES) tissues or body fluids (blood, urine, or feces).
Typhoid fever may resemble babesiosis in its clinical presentation. As with babesiosis, physical signs are usually absent in patients. Patients with typhoid fever often present with constipation rather than diarrhea, which may be helpful because neither constipation nor diarrhea is a feature of babesiosis.
Headache is a prominent feature of malaria and typhoid fever but is less prominent with babesiosis and ehrlichiosis and is mild if present in Lyme disease.
Human monocytic ehrlichiosis (HME), human granulocytic anaplasmosis (HGA), and human granulocytic ehrlichiosis (HGE) may be diagnosed serologically in patients with a nonspecific febrile illness in endemic areas. These may also be diagnosed through Wright stain of peripheral blood smears or buffy-coat preparations that demonstrate regularly stained cytoplasmic inclusions in monocytes or, less commonly, lymphocytes, which are mulberry-shaped and are called morulae. Morulae are seen more frequently in HME than in HGE.
Babesiosis rarely affects the lungs. However, patients with babesiosis may develop noncardiogenic pulmonary edema, which may resemble pneumonia on chest radiography.
Vannier E, Gewurz BE, Krause PJ. Human babesiosis. Infect Dis Clin North Am. 2008 Sep. 22(3):469-88, viii-ix. [Medline].
Joseph JT, Roy SS, Shams N, Visintainer P, Nadelman RB, Hosur S, et al. Babesiosis in Lower Hudson Valley, New York, USA. Emerg Infect Dis. 2011 May. 17(5):843-7. [Medline].
Dobroszycki J, Herwaldt BL, Boctor F, Miller JR, Linden J, Eberhard ML, et al. A cluster of transfusion-associated babesiosis cases traced to a single asymptomatic donor. JAMA. 1999 Mar 10. 281(10):927-30. [Medline].
Gerber MA, Shapiro ED, Krause PJ, Cable RG, Badon SJ, Ryan RW. The risk of acquiring Lyme disease or babesiosis from a blood transfusion. J Infect Dis. 1994 Jul. 170(1):231-4. [Medline].
Jacoby GA, Hunt JV, Kosinski KS, Demirjian ZN, Huggins C, Etkind P, et al. Treatment of transfusion-transmitted babesiosis by exchange transfusion. N Engl J Med. 1980 Nov 6. 303(19):1098-100. [Medline].
Leiby DA. Babesiosis and blood transfusion: flying under the radar. Vox Sang. 2006 Apr. 90(3):157-65. [Medline].
Mintz ED, Anderson JF, Cable RG, Hadler JL. Transfusion-transmitted babesiosis: a case report from a new endemic area. Transfusion. 1991 May. 31(4):365-8. [Medline].
Wittner M, Rowin KS, Tanowitz HB, Hobbs JF, Saltzman S, Wenz B, et al. Successful chemotherapy of transfusion babesiosis. Ann Intern Med. 1982 May. 96(5):601-4. [Medline].
Wormser GP, Lombardo G, Silverblatt F, El Khoury MY, Prasad A, Yelon JA, et al. Babesiosis as a cause of fever in patients undergoing a splenectomy. Am Surg. 2011 Mar. 77(3):345-7. [Medline].
White DJ, Talarico J, Chang HG, Birkhead GS, Heimberger T, Morse DL. Human babesiosis in New York State: Review of 139 hospitalized cases and analysis of prognostic factors. Arch Intern Med. 1998 Oct 26. 158(19):2149-54. [Medline].
Gubernot DM, Lucey CT, Lee KC, Conley GB, Holness LG, Wise RP. Babesia infection through blood transfusions: reports received by the US Food and Drug Administration, 1997-2007. Clin Infect Dis. 2009 Jan 1. 48(1):25-30. [Medline].
Kuwayama DP, Briones RJ. Spontaneous splenic rupture caused by Babesia microti infection. Clin Infect Dis. 2008 May 1. 46(9):e92-5. [Medline].
Froberg MK, Dannen D, Bernier N, Shieh WJ, Guarner J, Zaki S. Case report: spontaneous splenic rupture during acute parasitemia of Babesia microti. Ann Clin Lab Sci. 2008 Autumn. 38(4):390-2. [Medline].
Persing DH, Mathiesen D, Marshall WF, Telford SR, Spielman A, Thomford JW, et al. Detection of Babesia microti by polymerase chain reaction. J Clin Microbiol. 1992 Aug. 30(8):2097-103. [Medline]. [Full Text].
Krause PJ, Spielman A, Telford SR 3rd, et al. Persistent parasitemia after acute babesiosis. N Engl J Med. 1998 Jul 16. 339(3):160-5. [Medline].
Cunha BA, Cohen YZ, McDermott B. Fever of unknown origin (FUO) due to babesiosis in a immunocompetent host. Heart Lung. 2008 Nov-Dec. 37(6):481-4. [Medline].
Krause PJ, Lepore T, Sikand VK, Gadbaw J Jr, Burke G, Telford SR 3rd, et al. Atovaquone and azithromycin for the treatment of babesiosis. N Engl J Med. 2000 Nov 16. 343(20):1454-8. [Medline].
Vyas JM, Telford SR, Robbins GK. Treatment of refractory Babesia microti infection with atovaquone-proguanil in an HIV-infected patient: case report. Clin Infect Dis. 2007 Dec 15. 45(12):1588-90. [Medline].
Wormser GP, Prasad A, Neuhaus E, Joshi S, Nowakowski J, Nelson J, et al. Emergence of resistance to azithromycin-atovaquone in immunocompromised patients with Babesia microti infection. Clin Infect Dis. 2010 Feb 1. 50(3):381-6. [Medline].
Krause PJ, Gewurz BE, Hill D, et al. Persistent and relapsing babesiosis in immunocompromised patients. Clin Infect Dis. 2008 Feb 1. 46(3):370-6. [Medline].
Cushing M, Shaz B. Transfusion-transmitted babesiosis: achieving successful mitigation while balancing cost and donor loss. Transfusion. 2012 Jul. 52(7):1404-7. [Medline].
Herwaldt BL, Linden JV, Bosserman E, Young C, Olkowska D, Wilson M. Transfusion-associated babesiosis in the United States: a description of cases. Ann Intern Med. 2011 Oct 18. 155(8):509-19. [Medline].
Hildebrandt A, Gray JS, Hunfeld KP. Human babesiosis in Europe: what clinicians need to know. Infection. 2013 Dec. 41(6):1057-72. [Medline].
Kavanaugh MJ, Decker CF. Babesiosis. Dis Mon. 2012 Jun. 58(6):355-60. [Medline].
Vannier E, Krause PJ. Human babesiosis. N Engl J Med. 2012 Jun 21. 366(25):2397-407. [Medline].
Wroblewski HA, Kovacs RJ, Kingery JR, Overholser BR, Tisdale JE. High risk of QT interval prolongation and torsades de pointes associated with intravenous quinidine used for treatment of resistant malaria or babesiosis. Antimicrob Agents Chemother. 2012 Aug. 56(8):4495-9. [Medline]. [Full Text].