Version July 2025
INTRODUCTION —
Babesiosis is an infectious disease caused by protozoa of the genus Babesia that infect and lyse red blood cells. Babesia spp are transmitted primarily by tick vectors after their acquisition from small mammal reservoir hosts. Transmission occasionally occurs through blood transfusion and rarely through organ transplantation or congenitally. Babesia protozoa infect mammals and cause lysis of host red blood cells [1-5].
Babesia microti is the primary agent of human babesiosis in the United States, particularly in the Northeast and upper Midwest where it is endemic. Most in Europe have been attributed to Babesia divergens, but the infection is sporadic. B. venatorum and Babesia crassa-like infections are endemic in northeastern China, and several cases of B. microti have been reported over a two-year period in southwestern China along the Myanmar border.
The clinical manifestations and diagnosis of babesiosis will be reviewed here. The microbiology, epidemiology, pathogenesis, treatment, and prevention of babesiosis are discussed separately. (See "Babesiosis: Microbiology, epidemiology, and pathogenesis" and "Babesiosis: Treatment and prevention".)
CLINICAL MANIFESTATIONS —
Babesia infections range from asymptomatic to severe and sometimes are fatal. The severity of infection depends on the Babesia species and the immune status of the host.
Infection due to B. microti — B. microti is the predominant species that infects humans in the United States. B. microti also causes disease in Asia, Australia, Central America, and Europe [1-6]. Clinical manifestations may be absent or range from mild to severe.
The incubation period of B. microti infection following a tick bite typically is one to four weeks; the incubation period after transfusion of contaminated blood products usually is three to seven weeks but has ranged from one week to six months [2,5,7].
Clinical manifestations of babesiosis may develop in individuals with subclinical infection who undergo splenectomy or initiate treatment with immunosuppressive drugs [8-10].
Asymptomatic infection — The discrepancy between seroprevalence and disease prevalence suggests that asymptomatic infection is common. One cohort study on Block Island, Rhode Island (a highly endemic area) identified asymptomatic B. microti infection in 40 percent of children and 20 percent of adults [11]. (See "Babesiosis: Microbiology, epidemiology, and pathogenesis", section on 'Incidence and prevalence'.)
Mild to moderate disease — Mild to moderate babesiosis typically occurs in immunocompetent patients and is associated with a parasitemia less than 4 percent.
Patients with mild to moderate disease usually experience gradual onset of fatigue and malaise accompanied by fever. Fever (>38°C) is intermittent or sustained and has been described as high as 40.9°C (105.6°F). Fever, fatigue, and malaise may be accompanied by one or more of the following [2,5,12-15]:
●Common: chills, sweats, and myalgia
●Less common: anorexia, headache, nausea, and dry cough
●Least common: arthralgia, shortness of breath, sore throat, neck stiffness, emotional lability, abdominal pain, vomiting, diarrhea, dark urine, conjunctival injection, photophobia, hyperesthesia, and weight loss
On physical examination, fever is the salient feature. Splenomegaly and/or hepatomegaly may be noted [12,15,16]. Uncommon physical findings include scleral icterus, jaundice, mild pharyngeal erythema, and retinopathy with splinter hemorrhages with or without retinal infarcts [5]. Lymphadenopathy is absent.
Rash is seldom associated with babesiosis; if an erythematous rash is observed, concurrent Lyme disease should be suspected. (See 'Coinfection with other tick-borne illnesses' below.)
Laboratory abnormalities associated with mild to moderate babesiosis include low hematocrit, low hemoglobin, elevated lactate dehydrogenase, low haptoglobin, and/or reticulocytosis [5]. Thrombocytopenia is common. The white blood cell count is normal, increased, or decreased; neutropenia may occur [17]. Liver enzymes are often elevated, including alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Total and indirect bilirubin, blood urea nitrogen, and/or serum creatinine levels may be elevated.
Severe disease — Severe babesiosis often occurs in older and/or immunocompromised patients and is associated with parasitemia ≥4 percent (although severe disease can occur with parasitemia <4 percent). Severe babesiosis may lead to complications, including persistent or relapsing disease [12,15,16]. (See 'Complications' below and 'Relapse' below.)
Risk factors for severe babesiosis include age >50, neonatal prematurity, asplenia, malignancy, HIV infection, and immunosuppressive drugs. These are discussed further separately. (See "Babesiosis: Microbiology, epidemiology, and pathogenesis", section on 'Risk factors'.)
Clinical manifestations of severe disease are similar to those of mild to moderate disease but more intense. Nausea or vomiting and diarrhea are predictive of severe infection [16]. (See 'Mild to moderate disease' above.)
Laboratory test abnormalities associated with severe babesiosis are the same as those for mild to moderate babesiosis but more pronounced and of longer duration [5,18].
Radiographic findings associated with severe babesiosis may include pulmonary edema on chest radiograph and splenic infarct and/or splenic rupture on abdominal computed tomography scan [12,15].
Complications — Complications develop in nearly half of patients hospitalized with babesiosis [2]. The most common complications are renal insufficiency/failure, pulmonary failure, and congestive heart failure [12,19,20]. In one series including 22 patients requiring intensive care, the mortality rate was higher among those who developed acute respiratory distress syndrome (ARDS) than among those who did not (38 versus 14 percent); among those who developed ARDS, survivors were younger (mean age 55 versus 74 years) [21].
Other complications include severe anemia, atrial fibrillation, disseminated intravascular coagulation, liver impairment, shock, and confusion/delirium [21-23]. Complications are strongly associated with severe anemia (hemoglobin <10 g/dL) and, to a lesser degree, with high-grade parasitemia (≥10 percent) [12].
Splenic rupture is a rare complication. It typically occurs in otherwise healthy individuals who tend to be younger [4,24,25]. Splenic rupture is spontaneous (ie, nontraumatic) and is thought to result from excessive erythrophagocytosis in the red pulp. Intense abdominal pain is the chief complain. Most patients with splenic rupture present with mild splenomegaly (craniocaudal length <20 cm), have low parasitemia (median 1 percent), and do not present with other complications typically associated with severe babesiosis [9,24-27].
Warm autoimmune hemolytic anemia has been described as a late complication of babesiosis in asplenic individuals two to four weeks after symptoms and parasitemia have resolved [28]. (See "Warm autoimmune hemolytic anemia (AIHA) in adults".)
The babesiosis fatality rate has ranged from 1.5 to 3.3 percent in studies of hospitalized patients [19,20,29]. It is higher among patients with a splenic complication (splenomegaly, splenic infarct or splenic rupture; 6 percent) and among highly immunosuppressed patients with relapsing babesiosis (25 percent) [30-32].
Relapse — Relapsing babesiosis typically occurs in highly immunocompromised patients with probable impairment of Babesia antibody production, despite a standard course of antimicrobial therapy. These include patients with B cell lymphoma or other conditions treated with rituximab or other immunosuppressive agents, patients with malignancy who also are asplenic, patients with organ or stem cell transplantation, and patients with HIV/AIDS [30,31,33,34]. (See "Babesiosis: Microbiology, epidemiology, and pathogenesis", section on 'Risk factors'.)
Relapse usually occurs within a month or two after discontinuation of treatment, but the interval can be as short as a few days or as long as 3 months [30,31,35]. Confirmation that symptoms are due to relapse is best made by detection of the parasite on thin blood smear. (See 'Microscopy' below and "Babesiosis: Treatment and prevention", section on 'Immunocompromised patients'.)
Relapsing episodes of babesiosis tend to be less clinically severe than the initial episode of infection, however, failure to clear the infection requires long-term antimicrobial therapy. In such cases the mortality rate is approximately 20 percent [30].
Coinfection with other tick-borne illnesses — Other pathogens transmitted by Ixodes scapularis ticks include Borrelia burgdorferi, Anaplasma phagocytophilum, Borrelia miyamotoi, Borrelia mayonii, Powassan virus, and Ehrlichia muris–like agent. One or more of these pathogens can cause coinfection along with B. microti or with other Babesia spp. (See "Diagnosis of Lyme disease" and "Human ehrlichiosis and anaplasmosis" and "Borrelia miyamotoi infection" and "Arthropod-borne encephalitides", section on 'Powassan virus'.)
Patients with Lyme disease and concurrent babesiosis may experience a greater number of acute symptoms for a longer duration than patients with Lyme disease alone [13,36,37]. In one study, concurrent Lyme disease had no effect on the severity of babesiosis [13]. In another study, the number and duration of symptoms in patients with babesiosis and Lyme disease were lower than in patients with babesiosis alone [37].
In a study including 128 patients diagnosed with babesiosis, coinfection with Lyme disease or anaplasmosis was found to lower the risk for hospitalization, although it did not lower the risk for babesiosis complications [16]. Diagnosis of Lyme disease may have alerted health care workers to the possibility of babesiosis and prompted laboratory testing for babesiosis, resulting in earlier detection and treatment, reducing likelihood of hospital admission.
In a subsequent study including 3521 patients with babesiosis, the rate of coinfection with B. burgdorferi was the highest, followed by ehrlichiosis and anaplasmosis (41, 3.7, and 0.3 percent, respectively) [38]. The risk for mortality at 90 days was lower among those with coinfection (0.43 versus 1.4 percent), suggesting that coinfection may be associated with earlier diagnosis and treatment and more rigorous follow-up.
Patients who have been diagnosed with Lyme disease should be evaluated for coinfection with pathogens that are endemic in the region if they have atypical symptoms or do not respond to standard antibiotic therapy for Lyme disease. Consideration should be given to testing for Lyme disease in patients with anaplasmosis, babesiosis, or other Ixodes infection because of the high rate of Lyme disease coinfection in these patients. (See "Diagnosis of Lyme disease" and "Human ehrlichiosis and anaplasmosis".)
Infection due to other species — The epidemiology of infection due to other Babesia species is discussed separately. (See "Babesiosis: Microbiology, epidemiology, and pathogenesis", section on 'Epidemiology'.)
B. divergens — B. divergens is the predominant Babesia species in Europe. Infection with B. divergens should be suspected when residents of areas where B. divergens has previously been reported or travelers from these areas present with symptoms consistent with babesiosis, particularly in the setting of asplenia. Nearly all symptomatic cases attributed to B. divergens have been reported in asplenic individuals, although asymptomatic and mild cases in immunocompetent people have been documented [39-42].
Symptoms of B. divergens infection in asplenic patients usually appear abruptly following an incubation period of one to three weeks. The presenting symptoms are persistent high fever (>41°C), shaking chills, intense sweats, headache, myalgia, and lumbar and abdominal pain. Dark urine and jaundice indicate severe intravascular hemolysis. On physical examination, mild hepatomegaly may be noted. Characteristic abnormal laboratory findings include low hemoglobin levels (4 to 8 g/dL) and high parasitemia, which can be as high as 80 percent [39]. B. divergens infection often was fatal despite antimicrobial therapy, but the fatality rate has decreased; this is thought to be due to immediate use of exchange transfusion and improvement in ICU supportive therapy [43,44].
B. divergens-like organisms — Cases of infection due to B. divergens–like organisms have been documented in the Midwest (Arkansas, Kentucky, Michigan, Missouri), the East Coast (Pennsylvania), and the West Coast (Washington state) [45-48]. All patients were >50 years and asplenic. Clinical manifestations and abnormal laboratory findings were similar to those reported for B. divergens and other Babesia spp. Peak parasitemia ranged from 15 to 41 percent.
In Europe, a case of B. divergens-like infection has been reported from France [49]. Another case was identified on the Canary Islands, off the coast of West Africa [50].
B. duncani and related organisms — A small number of infections (<15) due to Babesia duncani and related organisms have been described on the West Coast of the United States. Cases range in severity from asymptomatic to fatal. Clinical manifestations are similar to those of B. microti infection, including fever, weakness, malaise, fatigue, chills, sweats, headache, myalgia, arthralgia, nausea, vomiting, anorexia, weight loss, and dark urine. Laboratory findings may include low hematocrit, thrombocytopenia, hyperbilirubinemia, and elevated liver enzymes.
Five symptomatic patients with tick-borne B. duncani infection have been documented. All were men, and four were asplenic [51,52]. Three asplenic men survived, but the fourth died. One of the surviving patients had severe disease including disseminated coagulation, pulmonary edema, and renal insufficiency but recovered with antibiotic therapy [51,52].
Three cases of transfusion-acquired B. duncani infections have been described [53-55]. The first case occurred in a 76-year-old normosplenic man. The second case was a premature male neonate who developed respiratory distress. The third case was a 59-year-old patient with sickle cell anemia and other comorbidities who required intensive care for severe anemia and acute renal failure. All three patients had severe illness but recovered with antibiotic therapy with or without exchange transfusion.
B. venatorum — Cases of B. venatorum initially were described in Europe. All five cases occurred in asplenic men aged >50 years. One patient experienced mild symptoms, including fatigue and dark urine. Another patient presented with weakness, shortness of breath, and lethargy. The other three patients experienced severe disease and were admitted to the hospital. Abnormal laboratory findings were similar to those reported for other Babesia spp. Parasitemia ranged from 1 to 30 percent. In one case, massive hemolysis required blood transfusion. In all five cases, symptoms resolved with antibiotic therapy, and parasitemia eventually cleared [56-58].
Cases of B. venatorum have been reported from mainland China [59,60]. The initial case report was an eight-year-old boy with an intact spleen who developed prolonged intermittent fever (38.6 to 41°C), shortness of breath, fatigue, malaise, and progressive weakness [59]. Laboratory tests demonstrated hemolytic anemia, thrombocytopenia, leukocytosis, and elevated bilirubin and lactate dehydrogenase. Symptoms abated within three days of therapy and parasitemia eventually cleared. Subsequently, a series of 48 cases with B. venatorum infection occurring over four years were reported from northeastern China [60]. Two-thirds of individuals were symptomatic and all had a spleen. Patients presented with fever (66 percent), fatigue (44 percent), headache (41 percent), and myalgia or arthralgia (38 percent), but chills were reported less often (9 percent) than among patients infected with B. microti in the United States (67 percent). No deaths were reported.
B. crassa-like organisms — A series of 58 cases of babesiosis caused by B. crassa was reported from northeastern China [61]. All subjects had an intact spleen and two-thirds were female. Among the 31 confirmed cases, age at infection ranged from 29 to 72 years. Mild to moderate fever was less frequent than among patients infected with B. microti (48 versus >80 percent) but headache was more frequent (74 versus 40 percent). Nausea and vomiting were noted among one-half of patients (52 percent). Laboratory findings included elevated total or indirect bilirubin (32 percent) and elevated liver enzymes (16 percent).
Two cases of B. crassa-like organisms have been reported from Europe; one from Slovenia and another from western France [62,63]. Both patients were asplenic and experienced severe illness requiring hospitalization [62,63].
DIAGNOSIS
Clinical approach
●Clinical suspicion – The diagnosis of babesiosis should be suspected in the following circumstances:
•Patients with typical clinical manifestations (fever, fatigue, chills, sweats, myalgia, anorexia, headache, nausea, and dry cough) and typical laboratory test abnormalities (hemolytic anemia, thrombocytopenia, and/or elevation of aminotransferases) in the setting of relevant epidemiologic exposure (eg, residents of endemic areas, travelers returning from endemic areas, or blood transfusion in the previous six months).
Most infections with B. microti are acquired by tick bite between May and September; three-fourths of cases are diagnosed from June through August. Transfusion-transmitted babesiosis may be acquired throughout the year. (See "Babesiosis: Microbiology, epidemiology, and pathogenesis", section on 'Transmission'.)
•Patients with Lyme disease, human granulocytic anaplasmosis, or other Ixodes-borne infections may be coinfected with Babesia spp because the causative agents of these infections are transmitted by the same Ixodes tick vector. (See 'Coinfection with other tick-borne illnesses' above.)
●Diagnostic tools
•Use of microscopy and PCR – Preferred tools for diagnosis of babesiosis include blood smear for identification of Babesia organisms and polymerase chain reaction (PCR) for detection of Babesia DNA [1]. (See 'Microscopy' below and 'Polymerase chain reaction' below.)
Confirmation of babesiosis should begin with evaluation of a thin blood smear, which has a rapid turn-around time and allows quantification of parasitemia, although it requires microscopy expertise (algorithm 1 and picture 1).
If microscopy expertise is not available, PCR testing should be performed. This test is more sensitive than microscopy and therefore is useful when parasitemia is low (<0.1 percent). In addition, PCR can identify Babesia species.
If symptoms persist but microscopy has been negative, repeat blood smear examination and/or PCR testing should be performed.
•Serology – Positive serology (a fourfold rise in Babesia immunoglobulin [Ig]G antibody titers between acute and convalescent sera) is of limited use for the diagnosis of acute disease but provides retrospective confirmation of Babesia infection [5]. (See 'Serology' below.)
Serology may be a useful adjunct to blood smear and PCR [4,5,64]. For patients with a positive Babesia antibody test, diagnostic confirmation with blood smear or PCR should be pursued. A single positive antibody test is not sufficient to establish a diagnosis because Babesia antibodies can persist in blood for a year or more following apparent clearance of infection, with or without treatment [1].
●Evaluation for other tick-borne illnesses – Patients diagnosed with babesiosis should be evaluated for coinfection with other Ixodes-borne pathogens endemic in the region, particularly Lyme disease. (See 'Coinfection with other tick-borne illnesses' above and "Diagnosis of Lyme disease" and "Human ehrlichiosis and anaplasmosis".)
Laboratory diagnostic tools — Tools for diagnosis of babesiosis include microscopy, PCR, and serology.
Microscopy — The diagnosis of babesiosis can be established by identification of Babesia organisms on thin blood smears (Wright or Giemsa staining under oil immersion). Thick blood smears can be difficult to interpret and only should be examined by an experienced microscopist [2,5,65]. The United States Centers for Disease Control and Prevention (CDC) can review blood smears that are difficult to interpret.
Microscopic diagnosis of babesiosis requires time and expertise. At least 300 microscopic fields should be reviewed before concluding that there is no infection. In the setting of very low parasitemia (particularly at the onset of symptoms), the diagnosis of babesiosis may require examination of multiple smears over several days. Automated cell readers should not be used to detect Babesia spp in red blood cells, as they do not reliably detect ring forms and merozoites.
B. microti trophozoites are round, oval, or pear-shaped and have a blue cytoplasm with red chromatin dots (picture 1). Multiple infections per cell may be observed. Ring forms are most common and may resemble those of Plasmodium falciparum. Babesiosis may be distinguished from malaria by the presence of merozoites arranged in tetrads (known as a "Maltese Cross"). This finding is uncommon but pathognomonic for babesiosis. Other features that distinguish Babesia from Plasmodium spp include presence of extracellular forms, absence of hemozoin deposit (appears as brownish pigment) in ring forms, and absence of gametocytes. Pictures of Babesia spp on blood smears are provided on the CDC website.
B. duncani trophozoites are indistinguishable from those of B. microti. Tetrads of B. duncani merozoites are observed more commonly than tetrads of B. microti [66]. B. divergens, B. divergens–like organisms, and B. venatorum are round or pear-shaped. They are typically arranged in pairs but can appear as tetrads in human erythrocytes [39,45-47,67].
The diagnosis of babesiosis with microscopy should include quantification of parasitemia, ie, the percentage of Babesia-infected red blood cells (RBCs). This can be done by examining a monolayer of RBCs using the oil immersion objective at 100x. (See "Laboratory tools for diagnosis of malaria".)
The level of parasitemia is generally between 0.1 and 10 percent but has been as high as 80 percent [2]. Mild to moderate babesiosis is associated with parasitemia <4 percent, whereas severe babesiosis is associated with parasitemia ≥4 percent [5].
Polymerase chain reaction
●Clinical diagnosis – Diagnosis of babesiosis can be established using PCR-based amplification of Babesia DNA. PCR is especially useful in the setting of low-level parasitemia (eg, in asymptomatic carriers, at the onset of symptoms, or during convalescence). It also enables species identification and parasite quantification [2,10,68].
Real-time PCR assays target the Babesia 18S rRNA gene and have 100 percent specificity [68-72]. The limit of detection has ranged from 0.07 to 10 parasites/microliter of blood [68-71,73].
Parasite DNA may be detectable by PCR for several months following completion of antibiotic therapy and resolution of symptoms [10]. In untreated asymptomatic individuals, Babesia DNA has been detected as long as 404 days [74]. Babesia DNA has persisted for as long as 26 months in the setting of immunosuppression [10,75].
●Blood donation screening – Two nucleic acid test (NAT) assays that detect 18S rRNA gene copies and transcripts have been developed for the purpose of blood donation screening. These assays detect four Babesia species (B. microti, B. divergens, B. duncani, and B. venatorum). Their performance is similar for the detection of B. microti (95 percent detection probability: 3.0 versus 2.8 infected RBCs) but differ for other species (B. divergens: 1.8 versus 16.3; B. duncani: 3.1 versus 52.0) [76,77].
In 2022, the American Red Cross reported the results of blood donation screening for the first 13 months of NAT implementation. Among 1.8 million units screened in 13 endemic states and Washington, DC, 365 units were NAT-reactive. During that time, no cases of transfusion-transmitted babesiosis was reported. In contrast, between 2010 and 2020 when donor blood was not screened, 183 cases were investigated for suspected transfusion-transmitted babesiosis. A positive donor was identified in 102 of these cases, confirming transfusion transmission [78,79].
Serology — Serology may be used for diagnostic confirmation of babesiosis and species identification [80]. Serology should be interpreted with caution because onset of symptoms sometimes precedes the rise in antibody titer and because antibody may persist for more than a year, making it difficult to distinguish current from recent or past infection [2,39,64].
The antigen used for serologic testing should be that of the suspected Babesia species. Indirect fluorescent antibody testing (IFAT) is the most common serologic test. A standardized IFAT to detect B. microti–specific IgG is available through the CDC [81-83]. The IFAT also is offered by commercial diagnostic laboratories. The IFAT that uses whole B. microti antigen has a sensitivity of 88 to 96 percent and a specificity of 90 to 100 percent [82]. Enzyme-linked immunosorbent assay (ELISA) and Western blot assays have been developed but are not routinely used for the diagnosis of acute babesiosis [81,83].
A fourfold rise in Babesia IgG titer between acute and convalescent sera confirms recent infection; a single positive antibody titer seldom can distinguish current from past infection. The antibody titer that defines the threshold for a positive serologic test for a particular species can differ between laboratories. During the acute phase of illness, B. microti IgG titers usually exceed 1:1024 but typically decline to ≤1:64 within 6 to 12 months [10]. IgM antibody is usually detected two weeks after onset of illness. A positive IgM titer is suggestive of recent infection but must be accompanied by a positive IgG titer to establish a diagnosis [2,81]. The correlation between antibody titers and symptoms is poor [84].
Assays for B. microti antibody do not detect B. divergens, B. duncani, or B. venatorum antibody. Cross-reactivity has been observed between B. divergens and B. divergens–like organisms and between B. divergens and B. venatorum [46,47,85]. There have been too few cases of B. duncani infection to validate an indirect fluorescent antibody test for this organism. Sera from individuals exposed to Babesia spp can weakly cross-react with Plasmodium antigen when tested at lower dilutions [43,65].
Radiographic studies — Patients with respiratory symptoms should undergo chest radiography to evaluate for pulmonary edema and/or other findings consistent with ARDS. In the rare event that a patient with babesiosis and left upper quadrant tenderness is suspected of having splenic infarction and/or splenic rupture, an abdominal computed tomography should be considered. (See 'Complications' above.)
DIFFERENTIAL DIAGNOSIS —
The differential diagnosis of babesiosis includes:
●Malaria – Malaria is characterized by fever and anemia. Other clinical manifestations also mirror those of babesiosis, including fatigue, headache, arthralgia, myalgia, and nausea. The diagnosis of malaria should be suspected in the setting of relevant epidemiologic exposure and is established by visualization of parasites on peripheral smear or use of a rapid diagnostic test. Babesiosis may be distinguished from malaria on thin blood smear by the presence of merozoites arranged in tetrads (known as a "Maltese Cross"; this finding is uncommon but pathognomonic for babesiosis), absence of hemozoin deposit (appears as brownish pigment) in ring forms, and absence of gametocytes. (See 'Microscopy' above and "Malaria: Clinical manifestations and diagnosis in nonpregnant adults and children" and "Laboratory tools for diagnosis of malaria".)
●Other infections transmitted by Ixodes ticks – Etiologic agents include Anaplasma phagocytophilum, Borrelia burgdorferi, Borrelia mayonii, Borrelia miyamotoi, Ehrlichia muris–like infection, and Powassan virus. The clinical manifestations of these diseases are often similar to those of babesiosis and include fever, malaise, headache, myalgia, and arthralgia. Distinguishing features that are not found with babesiosis include erythema migrans rash (B. burgdorferi) and meningoencephalitis (Powassan virus). Laboratory features shared by several of these infections include thrombocytopenia and elevated transaminases. The diagnosis of these diseases is established by microscopy, polymerase chain reaction, and/or serology. (See 'Coinfection with other tick-borne illnesses' above and "Human ehrlichiosis and anaplasmosis" and "Borrelia miyamotoi infection".)
●Rickettsioses – Patient with rickettsial infection typically present with fever, headache, thrombocytopenia, leukopenia, and transaminase elevation. Petechial rash and/or eschar may develop after several days of illness. (See "Epidemiology, clinical manifestations, and diagnosis of Rocky Mountain spotted fever" and "Other spotted fever group rickettsial infections".)
●Leptospirosis – Leptospirosis is a bacterial infection characterized by fever, myalgia, headache, and conjunctival suffusion. Modest elevation of hepatic transaminases may be observed. The diagnosis is established by serology. (See "Leptospirosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)
●Viral hepatitis (hepatitis A, B, C, D, and E) – These entities are characterized by elevated transaminases. Hepatitis A and E are acute infections transmitted by the fecal-oral route whereas hepatitis B, C, and D can present acutely or chronically and are transmitted by body fluids. (See related topics.)
●Bacteremia – Meningococcal, pneumococcal, and staphylococcal bacteremia may be associated with fulminant anemia, thrombocytopenia, hepatic abnormalities, disseminated intravascular coagulation, and acute respiratory distress syndrome. The diagnosis is established by identification of the pathogen on culture. (See related topics.)
●Noninfectious causes of hemolytic anemia – Noninfectious causes of hemolytic anemia are summarized in the table (table 1). Clinical manifestations include pallor, jaundice, and splenomegaly. (See "Diagnosis of hemolytic anemia in adults".)
●HELLP (hemolysis, elevated liver enzymes, and low platelet count) – In pregnant women, babesiosis may be confused with the HELLP syndrome [86]. The diagnosis of HELLP is established by laboratory criteria. (See "HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)".)
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Tick-borne infections (including Lyme disease, ehrlichiosis, babesiosis, rickettsial infections, and others)".)
SUMMARY AND RECOMMENDATIONS
●Clinical manifestations – Clinical manifestations of Babesia infection range from asymptomatic to severe; the disease is sometimes fatal. The severity of illness depends on the species and the immune status of the host.
•Babesia microti – B. microti is the predominant species in the United States. The incubation period of B. microti infection following a tick bite typically is one to four weeks; the incubation period after transfusion of contaminated blood products typically is three to seven weeks but can be up to six months. (See 'Clinical manifestations' above and 'Infection due to B. microti' above.)
-Mild to moderate disease – Mild to moderate B. microti infection typically occurs in immunocompetent patients and is associated with parasitemia <4 percent. Patients usually experience gradual onset of fatigue and malaise accompanied by fever. Other common symptoms include chills, sweats, myalgia, anorexia, headache, nausea, and dry cough. Laboratory abnormalities include low hematocrit, low hemoglobin, elevated lactate dehydrogenase, low haptoglobin, reticulocytosis, thrombocytopenia, elevated liver enzymes, and elevated creatinine. (See 'Mild to moderate disease' above.)
-Severe disease – Severe B. microti infection often occurs in immunocompromised patients and is associated with parasitemia ≥4 percent (although it can occur with parasitemia <4 percent). Symptoms and laboratory abnormalities are similar to those seen with mild to moderate babesiosis but more pronounced. Complications include renal insufficiency or renal failure, acute respiratory distress syndrome, congestive heart failure, disseminated intravascular coagulation, shock, splenic rupture, confusion/delirium, and persistent relapsing disease. (See 'Severe disease' above and 'Complications' above.)
-Risk factors for severe disease – Risk factors for severe B. microti infection include age >50, neonatal prematurity, asplenia, malignancy, HIV infection, and immunosuppressive drugs. Relapsing babesiosis (despite a standard course of antimicrobial therapy) typically occurs in highly immunocompromised patients. These include patients with malignancy (especially B cell lymphoma) or other conditions treated with rituximab or other immunosuppressive agents, patients with malignancy who also are asplenic, patients with organ or stem cell transplantation, and patients with HIV/AIDS. (See 'Severe disease' above and 'Relapse' above.)
•Other Babesia spp – B. divergens is the predominant species in Europe. Nearly all symptomatic cases attributed to B. divergens occur in asplenic individuals and are severe. Disease caused by Babesia venatorum has ranged from mild in immunocompetent individuals (mainland China) to severe in immunocompromised patients (Europe). (See 'Infection due to other species' above.)
●Diagnosis
•Clinical suspicion – The diagnosis of babesiosis should be suspected in patients with typical clinical manifestations and laboratory features in the setting of relevant epidemiologic exposure (eg, residents of endemic areas, travelers returning from endemic areas, or blood transfusion in the previous six months). (See 'Clinical approach' above.)
•Clinical approach – Diagnostic evaluation for babesiosis should begin with evaluation of thin blood smear(s), which has a rapid turn-around time but requires microscopy expertise (algorithm 1 and picture 1). PCR is particularly useful when parasitemia is low and can distinguish among Babesia species. If symptoms persist but microscopy has been negative, repeat blood smear examination should be performed in conjunction with PCR testing. In the absence of microscopy expertise, PCR testing should be performed. Both smear and PCR allow quantification of parasitemia.
•Coinfection – Patients with babesiosis, an Ixodes-borne infection, should be evaluated for coinfection with other locally endemic Ixodes-borne pathogens. (See 'Clinical approach' above and 'Coinfection with other tick-borne illnesses' above.)
ACKNOWLEDGMENT —
The UpToDate editorial staff acknowledges Jeffrey A Gelfand, MD, FACP, who contributed to earlier versions of this topic review.
