Canadian Journal of Infectious Diseases and Medical Microbiology

Canadian Journal of Infectious Diseases and Medical Microbiology / 2020 / Article

Review Article | Open Access

Volume 2020 |Article ID 6934149 |

Igor Dumic, Cristian Madrid, Libardo Rueda Prada, Charles W. Nordstrom, Pahnwat Tonya Taweesedt, Poornima Ramanan, "Splenic Complications of Babesia microti Infection in Humans: A Systematic Review", Canadian Journal of Infectious Diseases and Medical Microbiology, vol. 2020, Article ID 6934149, 8 pages, 2020.

Splenic Complications of Babesia microti Infection in Humans: A Systematic Review

Academic Editor: Vidula Vachharajani
Received16 Jan 2020
Accepted25 Apr 2020
Published28 May 2020


Splenic complications of acute Babesia microti infection include splenomegaly, splenic infarct, and splenic rupture. These complications are relatively rarely reported, and the aim of this research was to synthetize data on this topic according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using the PubMed database. In this review, we find that unlike other severe complications of babesiosis, splenic infarct and rupture occur in younger and immunocompetent patients, and they do not correlate with parasitemia level. Furthermore, admission hemoglobin of 10 mg/dl or less, platelet count of 50 × 10⁹/L or less, presence of hemodynamic instability, and splenic rupture were associated independently with an increased risk of requiring splenectomy. As babesiosis is an emerging tick-borne zoonosis, we hope that this review will help to raise awareness among clinicians regarding this rare but potentially life-threatening complication.

1. Introduction

Babesiosis, also known as “Nantucket fever” or “malaria of the United States,” refers to an emerging vector-borne zoonosis caused by intraerythrocytic protozoans of the genus Babesia which infect and lyse red blood cells. In the US, babesiosis is endemic to the Pacific Northwest, Midwest, and the East Coast regions, particularly within the New England states [1, 2]. Its geographic distribution mimics that of Lyme disease, anaplasmosis, Powassan virus, and Borreliamiyamotoi infections, as all these pathogens are transmitted to humans through the same vector, Ixodes scapularis [1, 2]. The vast majority of cases in the US are caused by B. microti, with a smaller percentage of cases caused by B. duncani, found primarily in the NW US, and the recently reported B. divergens-like organisms [2, 3]. The first documented case in the US occurred in 1969, when an immunocompetent man from Massachusetts’ Nantucket Island was diagnosed with B. microti infection (hence the name, “Nantucket fever”) [1, 4].

Babesiosis is transmitted mainly through bites from infected I. scapularis ticks; however, in rare cases, transmission may occur via the transplacental route, blood transfusion, or by organ transplant [58]. The incidence of tick-borne diseases in the US is increasing due to multiple factors including enlarging deer and tick populations, increased proximity between humans and ticks due to rural development, expanded awareness of tick-borne infections, availability of better diagnostic methods, and the effects of climate change [8, 9]. Climate change is predicted to have a significant impact on the incidence of tick-borne infections in endemic regions, with one study estimating a greater than 20% increase in the incidence of Lyme disease assuming a 2°C increase in the annual average temperature in the coming decades [10]. Clinical manifestations of babesiosis range from mild flu-like symptoms to life-threatening multiorgan failure with a fatality rate of 6–21% [11]. Asplenic individuals, the elderly, and immunocompromised patients have higher mortality rates due to the development of severe complications [11, 12]. Severe complications of B. microti infection include acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), and liver or renal failure [1214]. Splenic rupture is a severe but rarely reported complication of B. microti infection.

There have been few published case reports on this topic with literature review of varying extent, and no systematic review has been performed thus far to the best of our knowledge. In this systematic review, we have described the clinical features, laboratory findings, and the management of patients with splenic complications during the acute infection with B. microti. We have also reviewed the risk factors associated with splenic lesions in patients suffering from the disease. Subsequently, the review will help in raising awareness, among clinicians, on the potentially life-threatening splenic complications resulting from human babesiosis.

2. Materials and Methods

2.1. Database and the Key Words (MeSH)

A systematic review of the literature following the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was performed using the PubMed database for case reports and case series of B. microti infection with splenic complication from the date of database inception to September 2019. The following key words alone and/or in combination were used: “babesiosis AND splenic rupture,” “Babesia microti AND splenic rupture,” “babesiosis AND splenic infarct,” “Babesia microti AND splenic infarct,” “babesiosis AND splenic laceration,” and “Babesia microti AND splenic laceration.”

2.2. Definitions

We defined splenic complication as splenomegaly, splenic rupture, or splenic infarct depending on the radiological findings described in case reports. The presence of hemoperitoneum was indicative of splenic rupture, whereas splenic infarct was associated with intact splenic capsule and absence of hemoperitoneum [15]. Splenomegaly was defined as the spleen weighing more than 400 g and/or measuring greater than 11 cm in craniocaudal length. Massive splenomegaly was defined as the spleen weighing above 1000 g and/or measuring greater than 20 cm in craniocaudal length [16, 17]. Parasitemia was classified as severe if more than 10% of erythrocytes were infected on blood smear examination [18]. Diagnosis of babesiosis was considered delayed (misdiagnosed) if disease was not suspected on admission, inappropriate antibiotics were administered for up to 48 hours after admission, or if diagnosis was obtained postmortem.

2.3. Selection Criteria

We selected only definite cases of B. microti infection diagnosed by PCR, serology, and/or blood smear. We considered the blood smear alone diagnostic only in cases where the patient recovered following antibabesial therapy. Duplicate articles, articles in languages other than English, narrative review, and cases of babesiosis without splenic complication were excluded. The flowchart of selection of the final cases included in our analysis is illustrated in Figure 1.

2.4. Data Collection

Two researchers independently and blindly identified and selected the titles, abstracts, and full texts obtained in the database search. Discrepancies of the selected articles were resolved by consensus. After completing the PubMed PRISMA search, we completed a manual search by subsequently screening the reference lists of all selected articles. An Excel table was constructed, and for each case, we collected patient demographics, clinical presentation, medical comorbidities, vital signs on admission, time from presentation to diagnosis, type of splenic involvement, severity of parasitemia, patient’s immune status, presence of coinfection, treatment, and clinical outcome (Table 1) [13, 1941]. Of 34 cases reported, 19 cases were collected from single case reports; there were 4 case series, each including 2 cases [22, 23, 27, 37]. Finally, there was one case series including 7 patients from a single institution in Rhode Island, USA [39].

Case (ref)Year (author)AgeSexUS state, countryComorbid conditionsSymptoms duration PTP (days)Dx missed initiallyRemembers tick biteSIRS/HD unstable on admissionHgb (md/dl)Platelet (×109/L)CoinfectionParasitemia level (%)SplenomegalyType of splenic involvement PTA or AATransfusion (units)ICSAntibiotic treatmentSplenectomy

1 [19]2001 (Javed)85MNJ, USAHTNFever, chills, malaise (7–14)YesNoNo1223Yes (2)NoTCV + CLIN + QINo, expired
2 [20]2008 (Kuwaya ma)61MNJ, USANoneFever, chills, malaise, AP (180) intermittentYesNo (golfing)No1133No5YesR (AA)Yes (4)NoAZ + ATQ (7)Yes
3 [21]2008 (Froberg)56MMN, USAHTNNight sweats, malaise (NR)YesNRYes9.337Yes (LD)NRYesR (AA)NRNoNRYes
4 [22]2008 (Florescu)58MNJ, USANoneFever, AP, malaise, syncope (5)YesNoNo13.6209APG0.5YesINoAZ + ATQ (NR)No
5 [22]2008 (Florescu)75FNY, USAHTNNight sweats, malaise (NR)YesNoYes8.755NoNRYes (massive)INRNoAZ + ATQ QI + CLINNo, expired
6 [23]2008 (Sidertis)50MNJ, USANoneFever, AP, malaise, syncope (5)YesNo (golfing)Yes9.3458NR3YesR (PTA)Yes (2)NoAZ + ATQ (NR)Yes
7 [23]2008 (Sidertis)71MNJ, USANRSyncope (NR)NoNRYes9.272NRNRYesR (PTA)Yes (2)NoCLIN + QI (10)Yes
8 [24]2011 (Tobler)54MMA, USANoneNausea, chills, malaise, fever, AP (2)NoNoNo10.226No3YesR (PTA)Yes (platelet)NoAZ + ATQ (10)No
9 [25]2011 (Abbas)23MCT, USANoneFever, chills, weight loss, malaise LDN (0.5)YesYesNo6.878No30YesR (PTA)Yes (4)NoCLIN + QI (10)No
10 [26]2011 (Reis)70MNY, USANRFever, nausea, vomiting (3)NoNoNo8.590NoNRYesR (PTA)Yes (2)NoAZ + ATQ (14)No, SA embolization
11 [27]2011 (El Khouri)70MNY, USANoneFever, chills, malaise (4)NoNRNo10.177No8YesR (PTA)Yes (3)NoCLIN + QI AZ + ATQ (16)No, SA embolization
12 [27]2011 (El Khouri)36MNY, USANoneFever, headache, chills, cough (14)NoNRNo8.5133No3.5YesR (AA)NoNoAZ + ATQ (21)No
13 [28]2011 (Wormser)55MRI, USADiverticulosisFever, rash, AP (10)YesNRYes13.499NR0.1NRR (PTA)NRNoAZ + ATQ (42) relapse after 10-day courseYes
14 [29]2013 (Seible)83MMA, USANRFever, nausea, AP (2)NoNRNRNR66No14NRR (PTA)Yes exchangeNoCLIN + QI (30)No
15 [30]2013 (Leinwan d)48MCT, USANoneHeadache, AP, malaise (7)NoNo (camping)No10.5137No10YesR (PTA)NRNoAZ + ATQ (NS)No observation
16 [31]2014 (Usatti)54MCT, USANoneFever, headache, AP (2)YesNRYes10.6123NoNRYesR (PTA)Yes (2)NoAZ + ATQ (10)No
17 [32]2015 (Farber)59FCT, USAHLP depressionFever, chills, syncope, fatigue, AP (14)NoNo (gardening)Yes8.2127No1YesR (PTA)Yes (2)NoCLIN + AZ + ATQ (14)Yes
18 [33]2016 (Al Zoubi)72MEcuadorHTNFever, chills, weight loss, AP (NR)YesNRNo7.855No0.5YesINRNoATQ + PRG (NR)No
19 [34]2016 (Wong)56MNY, USADiabetesFever, malaise, night sweats (6)YesNo (landscaping)No10.7163Yes (LD)1.5NoINoNOAZ + ATQ (10)No SA embolization
20 [35]2017 (Permpalu ng)59MMA USAMVPHeadache, fever, AP (14)YesNRNR10.4156NoNRYesINoNoAZ + ATQ (10)No SA embolization
21 [36]2018 (Dumic)79FWI, USAHTN atrial fibrillation CADChest pain, dizziness (1)YesYesYes6.56.5Yes (LD)1.3NoR (PTA)Yes (4)NoAZ + ATQ (10) Doxy (21)Yes
22 [37]2018 (Blackwo od)51MRI, USAHTN atrial fibrillationFever, chills, malaise, AP (5)NoYesYes9.325NR0.25YesR (PTA)Yes (4)NoAZ + ATQ (14)Yes
23 [37]2018 (Blackwo od)61MRI, USAHTN, HLPFever, chills, malaise, AP (3)YesNo (gardening)Yes12.489NR0.44YesINoNoAZ + ATQ (NR)No
24 [38]2018 (Li)48MRI, USAAsthmaFever, chills, night sweats, AP (7)NRNRNo8.868NR0.22YESR (NR)NRNoNRNo SA embolization
25 [13]2018 (Patel)48MRI, USAAsthmaFever, chills, night sweats, AP (7)NRNRNo8.868NR0.22YesR (NR)NRNoNRNo SA embolization
26 [13]2018 (Patel)83MRI, USACKD COPDAP (1)NRNRYes11.394NR0.30NRR (NR)NRNoNRNo
27 [13]2018 (Patel)40MRI USADiabetesFever, malaise, night sweats (5)NRNRNo7.874NR0.07NRR (NR)NRNoNRNo
28 [13]2018 (Patel)51MRI, USAHTN atrial fibrillationNight sweats, headache, malaise, AP (3)NRNRYes8.725NR0.2518.2R (NR)NRNoNRYes
29 [13]2018 (Patel)48MRI, USANoneFatigue, AP (5)NRNRYes7.959NR0.2616R (NR)NRNoNRYes
30 [13]2018 (Patel)36MRI, USANoneFever, AP (4)NRNRNo10.680NR0.35NRR (NR)NRNoNRNo
31 [13]2018 (Patel)68MRI, USAHTNMalaise, AP (NR)NRNRNo6.6NRNR5NRR (NR)NRNoNRNo
32 [39]2018 (Kwon)50FSouth Korea (imported from NJ, USA)NoneHeadache, fever, AP, chills (NR)YesNR (gardening)No11.253NRNRNRINRNoATQ/+AZ (NR)No
33 [40]2019 (Alvi)60MCT, USAHTN, diabetes, HLPFever, chills, rigors, AP (7–10)YesNoYes10.236No11YesIYesNoNS AZ + ATQ (14)No observation
34 [41]2019 (Gupta)53MNY, USANoneFever, chills, weakness (7)NoNo (hiking)NR11.290NR1.5NRINoNoAZ + ATQ (NS)No observation

A: azithromycin; AA: after admission; AP: abdominal pain; APG: Anaplasma phagocytophilum; ATQ: atovaquone; CKD: chronic kidney disease; CLIN: clindamycin; CT: Connecticut; Dx: diagnosis; E. ch: Ehrlichia chaffeensis; F: female; HA: headache; HD: hemodynamic; Hgb: hemoglobin, HLP: hyperlipidemia; HTN: hypertension; I: infarction; ICS immunocompromised state; LD: Lyme disease; LDN: lymphadenopathy; M: male; MA: Massachusetts; MN: Minnesota; MVP mitral valve prolapse; NJ: New Jersey; NR: not reported; NS: not specified; NY: New York; PRG: proguanil; PTA: prior to admission; PTP: prior to presentation; QI: quinine; R: rupture; Ref: reference; SA: splenic artery; TCV: ticarcillin-clavulanic acid “SIRS: systemic inflammatory response syndrome”.
2.5. Statistical Analysis

The program Stata/MP 14.2 was used for statistical analysis. Patient characteristics are summarized using descriptive statistics; for example, medians and interquartile ranges (IQR) for continuous variables and counts and percentages for categorical variables. A multivariate regression model was used to assess the association of risk factors with splenectomy. Due to incomplete data in 4 cases, a total of 30 cases constituted the final sample. A value of <0.05 was defined as statistically significant.

3. Results and Discussion

3.1. Demographic Data

The median patient age was 56 years (IQR 50–69.5). The youngest patient was 23, and the oldest was 85 years old. Of note, most other severe complications of babesiosis occurred primarily in the elderly [1, 2]. Curiously, while one recent study from a babesiosis-endemic area in the US reported a female predominance [14], we find that splenic complications occur almost exclusively in men. In our systematic review, 30 of 34 cases (88%) were males. Male predominance was also described in a recent case series (included in this systematic review) [13]; however, in that series, the median patient age was significantly lower (48 years). Furthermore, one recent retrospective study from Massachusetts showed that patients who developed splenic rupture were older than previously reported (median age 62) [42]. All reported cases in this review were from the US except for one patient who might have contracted the infection in Ecuador [33]. Another case was reported in South Korea; however, in that case, the disease had been acquired in New Jersey, USA [39]. In multivariate analysis, neither age nor sex was associated with splenectomy as an outcome (Table 2).

Dependent variable: splenectomyLPM

Age ≥55 years0.2717 (0.1539)
Male−0.0540 (0.1395)
Hypertension−0.1861 (0.1419)
Hemoglobin <10 mg/dl0.2795 (0.1178)
Platelets < 50 × 1090.3876 (0.1493)
Spleen rupture0.4359 (0.1579)
Hemodynamic instability0.4721 (0.1621)
Number of cases30

This table reports the estimates of a linear probability model (LMP) for the binary variable splenectomy. The R-squared value of 0.6752 indicates that 67.52% of the variance in the dependent variable (splenectomy) is explained by the regression model. It also has the simple interpretation that it equals the difference between the average predicted probability in the two groups. Because of the well-known heteroskedasticity in the LPM, heteroskedasticity-robust standard errors are reported in parentheses. value <0.01, value <0.05, and value <0.1.
3.2. Comorbidities and Immune Status

Unlike other severe complications of B. microti infection (such as ARDS, DIC, acute renal injury, acute liver failure, and severe hemolytic anemia), splenic rupture does not appear to correlate with host immune status. None of the reported cases were immunocompromised (Table 1). Additionally, among cases that reported comorbidities, 14 out of 32 patients (43.75%) had none. The most common comorbidity was hypertension occurring in 7 out of 32 patients (21.87%), but in multivariate analysis, the presence of hypertension was not associated with splenectomy.

3.3. Clinical Manifestation and Coinfection

The most common presenting symptoms in this cohort of patients who developed splenic complications were as follows: fever (26/34, 76%), abdominal pain (20/34, 58%), chills and malaise (16/34, 47% for both), headache (7/34, 20%), night sweats (5/34, 14%), and syncope (3/34, 8.8%). It is interesting to note that 42% of patients with splenic complications of babesiosis did not complain of abdominal pain. This finding may contribute to the delay in diagnosis or misdiagnosis that was observed in 60% of patients (17/27, in 7 cases [13] was not reported). Unfortunately, coinfection with other tick-borne illness was not documented in many cases. Hence, we were unable to statistically examine if coinfection contributed to the development of splenic infarct and/or rupture, or if it was associated with an increased frequency of splenectomy.

3.4. Laboratory Findings

In this systematic review, the majority of patients had evidence of various degree of anemia and thrombocytopenia. Overall anemia was present in 94% of patients (32/34), and thrombocytopenia was present in 87% of patients (29/33). The median hemoglobin concentration was 9.4 mg/dl (IQR 8.5–10.7), and the median platelet count was 77 × 10⁹/L (IQR 53–99). On multivariate analysis, hemoglobin concentration <10 mg/dl and thrombocytopenia of 50 × 10⁹/L or below were significantly associated with increased probability of requiring a splenectomy. Levels of parasitemia were documented in 26 of 34 cases (76%) and ranged from 0.1 to 30% (median 1%). Parasitemia levels generally correlate with severity of illness in both babesiosis and malaria [1, 2, 43], with parasitemia level above 10% considered to be severe infection. Among those cases with reported parasitemia levels, it is interesting to note that only 11.5% (3/26) of patients developed severe parasitemia. In fact, nearly half (46%) the patients who developed splenic complications from babesiosis had parasitemia level which was ≤1%. This observation that splenic complications of babesiosis do not correlate with the severity of parasitemia was consistent with findings from previous reports [13, 32, 36]. The persistence of parasitemia and rapidity of clearance following initiation of therapy were not described in the majority of cases, prohibiting our ability to evaluate these variables in relation to the outcome of interest (splenectomy).

3.5. Types of Splenic Complication

The spleen is an essential organ for the clearance of intraerythrocytic parasites such as Plasmodium spp. and Babesia spp [44, 45]. Due to the lack of experimental data on the pathophysiology of splenic rupture in human babesiosis, theories are drawn based on data from studies of pathophysiology of malaria-related splenic complications [4648].

Spleen size was documented in 26 patients. Of these, 23 had splenomegaly (88.5%) which is similar to findings from a recently published study that described it in 89% [42]. This is significantly higher than findings from a systematic review by Renzulli et al. [17] who found splenomegaly in 55% of patients with atraumatic splenic rupture. There was only one case of massive splenomegaly, and in 22 patients (95%), splenomegaly was mild. This is in contrast with malaria or viral infections such as EBV and CMV where splenic rupture is usually due to increased intracapsular pressure from massive splenomegaly. Splenic rupture (23 of 34 cases, 67.6%) was a more common complication of babesiosis than splenic infarct (11 of 34 cases, 32.4%). In multivariate analysis, development of splenic rupture was statistically significant with the increased probability of having a splenectomy.

3.6. Pathophysiology of Splenic Infarct and Rupture

Three main mechanisms by which B. microti might cause splenic complications have been proposed, and these draw parallels with studies on malaria-associated splenic rupture:(1)B. microti causes erythrocyte lysis by direct parasite invasion which leads to endothelial damage, formation of microthrombi, and release of vasoactive factors, resulting in localized necrosis of splenic tissue [34, 37].(2)Enhanced erythrocyte cytoadherence related to excessive proinflammatory cytokine production can cause mechanical obstruction of splenic microcirculation leading to infarction and rupture [47, 48]. Interestingly, this may occur even at low parasitemia levels, similar to infection with malaria [49].(3)The splenic macrophages are crucial in the clearance of infection, and in the process of “removal” of infected erythrocytes trapped in its venules, the spleen enlarges and subsequently may rupture. This final theory is supported by microscopic and macroscopic appearance of the ruptured spleens among patients infected with P. vivax. The spleen of these patients had significant red pulp hyperplasia with plasma cells, lymphocytes, immunoblasts, and large number of histiocytes exhibiting erythrophagocytic activity. On immunohistopathological analysis, these showed diffuse hypercellularity, massive proliferating plasma cells, and striking intrasinusoidal histiocytosis [5052].

3.7. Treatment and Outcome

In this systematic review, 2 patients died from babesiosis which corresponded to a mortality rate of 5.8%. This is lower than the previously reported mortality rates of patients who developed malaria-related splenic rupture [53]. Importantly, both patients who died were older (75 and 85 years old), and one was coinfected with Ehrlichia chaffeensis which might have contributed to his mortality. Additionally, in both cases, diagnosis was delayed, and this emphasizes the importance of timely diagnosis to decrease morbidity and mortality. All patients received antimicrobials although many cases did not document the duration of therapy. Most patients with documented antimicrobial therapy were treated with azithromycin and atovaquone (21/26, 81%). Of note, the emergence of resistance to azithromycin and atovaquone (as defined by microbiological relapse after completing initial antimicrobial course and while on therapy) has been described in 3 immunocompromised patients who required prolonged treatment for recurrent relapses [54].

Transfusion requirements were documented in 21 cases. Of these, 12 patients (57%) required transfusion of PRBC, 1 patient required transfusion of platelets, and 1 patient required an exchange transfusion. The average number of PRBC units transfused per patient was 2.8. Since January 2011, when babesiosis became a reportable disease, transfusion-transmitted babesiosis cases have sharply increased, and it is now the most common transfusion-transmitted pathogen [7, 55]. Since asplenic patients tend to have more severe disease, it is important to recognize the need to test patients for babesiosis if postsplenectomy fever develops. Furthermore, splenic rupture might be the first manifestation of babesiosis, and splenectomy can increase the severity of the disease [23, 36]. Of the 32 cases that survived which were described in this systematic review, 10 patients underwent splenectomy (31.2%) while 22 (68.8%) were managed conservatively with close observation, pain control, transfusion, hydration, and spleen preservation. In 12.5% of cases, splenic artery embolization was done to control the bleeding. Conservative management is preferable to avoid postoperative complications and complications from asplenia. Given the fact that all patients who develop splenic complications of babesiosis either live in or frequently visit Babesia endemic regions, splenic preservation is of utmost importance to decrease mortality in case of subsequent infections.

Our study has few limitations. We reviewed the cases that were only published in journals that are indexed in the PubMed database. Additionally, we have not reviewed cases published in languages other than English which contributes to publication bias.

4. Conclusion

This systematic review highlights the clinical presentation and outcomes of patients presenting with splenic complications of babesiosis. We note that splenic complications of babesiosis (unlike other severe complications of this infection) do not correlate with advanced patient age, host immunosuppression, or severity of parasitemia. Nearly half of the patients with splenic complications of babesiosis did not endorse abdominal pain which probably contributed to the delay in diagnosis or misdiagnosis that was observed in more than 60% of patients. In multivariate analysis, admission hemoglobin of 10 mg/dl or less, platelet count of 50 × 10⁹/L or less , presence of hemodynamic instability, and splenic rupture were associated with an increased risk of requiring splenectomy.

Conflicts of Interest

The authors declare that they have no conflicts of interest.


  1. E. G. Vannier, M. A. Diuk-Wasser, C. Ben Mamoun, and P. J. Krause, “Babesiosis,” Infectious Disease Clinics of North America, vol. 29, no. 2, pp. 357–370, 2015. View at: Publisher Site | Google Scholar
  2. E. Vannier and P. J. Krause, “Human babesiosis,” New England Journal of Medicine, vol. 366, no. 25, pp. 2397–2407, 2012. View at: Publisher Site | Google Scholar
  3. M. J. Burgess, E. R. Rosenbaum, B. S. Pritt et al., “Possible transfusion-transmitted babesia divergens-like/mo-1 infection in an arkansas patient,” Clinical Infectious Diseases, vol. 64, no. 11, pp. 1622–1625, 2017. View at: Publisher Site | Google Scholar
  4. K. A. Western, G. D. Benson, N. N. Gleason, G. R. Healy, and M. G. Schultz, “Babesiosis in a massachusetts resident,” New England Journal of Medicine, vol. 283, no. 16, pp. 854–856, 1970. View at: Publisher Site | Google Scholar
  5. J. T. Joseph, K. Purtill, S. J. Wong et al., “Vertical transmission of Babesia microti, United States,” Emerging Infectious Diseases, vol. 18, no. 8, pp. 1318–1321, 2012. View at: Publisher Site | Google Scholar
  6. J. K. Cornett, A. Malhotra, and D. Hart, “Vertical transmission of babesiosis from a pregnant, splenectomized mother to her neonate,” Infectious Diseases in Clinical Practice, vol. 20, no. 6, pp. 408–410, 2012. View at: Publisher Site | Google Scholar
  7. D. A. Leiby, “Transfusion-transmitted babesia spp.: bull’s-eye on Babesia microti,” Clinical Microbiology Reviews, vol. 24, no. 1, pp. 14–28, 2011. View at: Publisher Site | Google Scholar
  8. M. B. Brennan, B. L. Herwaldt, J. J. Kazmierczak et al., “Transmission of Babesia microti parasites by solid organ transplantation,” Emerging Infectious Diseases, vol. 22, no. 11, 2016. View at: Publisher Site | Google Scholar
  9. K. L. Knapp and N. A. Rice, “Human coinfection with Borrelia burgdorferi ansd Babesia microti in the United States,” J Parasitol Res, vol. 2015, Article ID 587131, 11 pages, 2015. View at: Publisher Site | Google Scholar
  10. I. Dumic and E. Severnini, ““Ticking bomb”: the impact of climate change on the incidence of lyme disease,” Canadian Journal of Infectious Diseases and Medical Microbiology, vol. 2018, Article ID 5719081, 10 pages, 2018. View at: Publisher Site | Google Scholar
  11. J. C. Hatcher, P. D. Greenberg, J. Antique, and V. E. Jimenez-Lucho, “Severe babesiosis in long Island: review of 34 cases and their complications,” Clinical Infectious Diseases, vol. 32, no. 8, pp. 1117–1125, 2001. View at: Publisher Site | Google Scholar
  12. P. J. Krause, B. E. Gewurz, D. Hill et al., “Persistent and relapsing babesiosis in immunocompromised patients,” Clinical Infectious Diseases, vol. 46, no. 3, pp. 370–376, 2008. View at: Publisher Site | Google Scholar
  13. K. M. Patel, J. E. Johnson, R. Reece, and L. A. Mermel, “Babesiosis-associated splenic rupture: case series from a hyperendemic region,” Clinical Infectious Diseases, vol. 69, no. 7, pp. 1212–1217, 2019. View at: Publisher Site | Google Scholar
  14. M. Fida, C. Douglas, H. Ahmed, J. O’horo, and O. Abu Saleh, “Babesiosis: a retrospective review of 38 cases in the upper midwest,” Open Forum Infectious Diseases, vol. 6, no. 7, 2019. View at: Publisher Site | Google Scholar
  15. E. Unal, M. R. Onur, E. Akpinar et al., “Imaging findings of splenic emergencies: a pictorial review,” Insights into Imaging, vol. 7, no. 2, pp. 215–222, 2016. View at: Publisher Site | Google Scholar
  16. J. Chapman and A. M. Azevedo, Splenomegaly, StatPearls Publishing, Treasure Island, FL, USA, 2019,
  17. P. Renzulli, A. Hostettler, A. M. Schoepfer, B. Gloor, and D. Candinas, “Systematic review of atraumatic splenic rupture,” British Journal of Surgery, vol. 96, no. 10, pp. 1114–1121, 2009. View at: Publisher Site | Google Scholar
  18. M. J. Homer, I. Aguilar-Delfin, S. R. Telford, P. J. Krause, and D. H. Persing, “Babesiosis,” Clinical Microbiology Reviews, vol. 13, no. 3, pp. 451–469, 2000. View at: Publisher Site | Google Scholar
  19. M. Z. Javed, M. Srivastava, S. Zhang, and M. Kandathil, “Concurrent babesiosis and ehrlichiosis in an elderly host,” Mayo Clinic Proceedings, vol. 76, no. 5, pp. 563–565, 2001. View at: Publisher Site | Google Scholar
  20. D. P. Kuwayama and R. J. Briones, “Spontaneous splenic rupture caused by Babesia microti Infection,” Clinical Infectious Diseases, vol. 46, no. 9, pp. e92–e95, 2008. View at: Publisher Site | Google Scholar
  21. M. K. Froberg, D. Dannen, N. Bernier, W. J. Shieh, J. Guarner, and S. Zaki, “Case report: spontaneous splenic rupture during acute parasitemia of Babesia microti,” Annals of Clinical & Laboratory Science, vol. 38, pp. 390–392, 2008. View at: Google Scholar
  22. D. Florescu, P. P. Sordillo, A. Glyptis et al., “Splenic infarction in human babesiosis: two cases and discussion,” Clinical Infectious Diseases, vol. 46, no. 1, pp. e8–e11, 2008. View at: Publisher Site | Google Scholar
  23. R. Siderits, N. Mikhail, C. Ricart, M. V. Abello-Poblete, C. Wilcox, and J. J. Godyn, “Babesiosis, significance of spleen function illustrated by postsplenectomy course in 3 cases,” Infectious Diseases in Clinical Practice, vol. 16, no. 3, pp. 182–186, 2008. View at: Publisher Site | Google Scholar
  24. W. D. Tobler, D. Cotton, T. Lepore et al., “Case report: successful non-operative management of spontaneous splenic rupture in a patient with babesiosis,” World Journal of Emergency Surgery, vol. 6, no. 1, 2011. View at: Publisher Site | Google Scholar
  25. H. M. Abbas, R. A. Brenes, M. S. Ajemian et al., “Successful conservative treatment of spontaneous splenic rupture secondary to babesiosis: a case report and literature review,” Connecticut Medicine, vol. 75, no. 3, pp. 143–146, 2011. View at: Google Scholar
  26. S. P. Reis, S. Maddineni, G. Rozenblit, and D. Allen, “Spontaneous splenic rupture secondary to Babesia microti infection: treatment with splenic artery embolization,” Journal of Vascular and Interventional Radiology, vol. 22, no. 5, pp. 732–734, 2011. View at: Publisher Site | Google Scholar
  27. M. Y. El Khoury, R. Gandhi, P. Dandache, G. Lombardo, and G. P. Wormser, “Non-surgical management of spontaneous splenic rupture due to Babesia microti infection,” Ticks and Tick-Borne Diseases, vol. 2, no. 4, pp. 235–238, 2011. View at: Publisher Site | Google Scholar
  28. G. P. Wormser, G. Lombardo, F. Silverblatt et al., “Babesiosis as a cause of fever in patients undergoing a splenectomy,” The American Surgeon, vol. 77, pp. 345–347, 2011. View at: Google Scholar
  29. D. M. Seible, S. A. M. Khatana, M. P. Solomon, and J. B. Parr, “Hoof beats may mean zebras: atraumatic splenic rupture,” The American Journal of Medicine, vol. 126, no. 9, pp. 778–780, 2013. View at: Publisher Site | Google Scholar
  30. J. C. Leinwand, J. P. Arroyo, D. Solomon, and L. J. Kaplan, “Babesia microti infection presenting as acute splenic laceration,” Surgical Infections, vol. 14, no. 4, pp. 412–414, 2013. View at: Publisher Site | Google Scholar
  31. N. Usatii, A. Khachatrian, and J. Stratidis, “Spontaneous splenic rupture due to Babesia microti infection: case report and review of the literature,” IDCases, vol. 1, no. 4, pp. 63–65, 2014. View at: Publisher Site | Google Scholar
  32. F. R. Farber, A. Muehlenbachs, and T. E. Robey, “Atraumatic splenic rupture from babesia: a disease of the otherwise healthy patient,” Ticks and Tick-Borne Diseases, vol. 6, no. 5, pp. 649–652, 2015. View at: Publisher Site | Google Scholar
  33. M. Al Zoubi, T. Kwak, J. Patel, M. Kulkarni, and C. A. Kallal, “Atypical challenging and first case report of babesiosis in Ecuador,” IDCases, vol. 4, pp. 15–17, 2016. View at: Publisher Site | Google Scholar
  34. D. Wong, “Babesia parasitemia causing splenic infarction: a review of the literature,” Case Reports in Internal Medicine, vol. 3, no. 3, p. 78, 2016. View at: Publisher Site | Google Scholar
  35. N. Permpalung, L. Valdivia, P. Seshadri, and C. F. Rowley, “Acute atraumatic splenic hemorrhage: babesiosis or acute infectious mononucleosis,” The American Journal of Medicine, vol. 130, no. 8, pp. e343–e344, 2017. View at: Publisher Site | Google Scholar
  36. I. Dumic, J. Patel, M. Hart, E. R. Niendorf, S. Martin, and P. Ramanan, “Splenic rupture as the first manifestation of Babesia microti infection: report of a case and review of literature,” American Journal of Case Reports, vol. 19, pp. 335–341, 2018. View at: Publisher Site | Google Scholar
  37. B. Blackwood and W. Binder, “Unusual complications from Babesia infection: splenic infarction and splenic rupture in two separate patients,” The Journal of Emergency Medicine, vol. 55, no. 5, pp. e113–e117, 2018. View at: Publisher Site | Google Scholar
  38. S. Li, B. Goyal, J. D. Cooper, A. Abdelbaki, N. Gupta, and Y. Kumar, “Splenic rupture from babesiosis, an emerging concern? a systematic review of current literature,” Ticks and Tick-Borne Diseases, vol. 9, no. 6, pp. 1377–1382, 2018. View at: Publisher Site | Google Scholar
  39. H. Y. Kwon, J. H. Im, Y.-K. Park, A. Durey, J.-S. Lee, and J. H. Baek, “Two imported cases of babesiosis with complication or co-infection with lyme disease in republic of Korea,” The Korean Journal of Parasitology, vol. 56, no. 6, pp. 609–613, 2018. View at: Publisher Site | Google Scholar
  40. A. Alvi, S. Gupta, P. Goyal, J. Pichardo, and J. Mattana, “Splenic infarction as a rare presentation of severe babesiosis,” IDCases, vol. 15, Article ID e00491, 2019. View at: Publisher Site | Google Scholar
  41. A. Gupta, P. Patel, K. Manvar, T. Kellner, and E. Guevara, “Splenic infarction in babesiosis: a rare presentation,” Clinical Case Reports, vol. 7, no. 8, pp. 1591–1595, 2019. View at: Publisher Site | Google Scholar
  42. A. Mojtahed, D. D. B. Bates, and P. F. Hahn, “Splenic findings in patients with acute babesiosis,” Abdominal Radiology, vol. 45, no. 3, 2020. View at: Publisher Site | Google Scholar
  43. A. Trampuz, M. Jereb, I. Muzlovic, and R. M. Prabhu, “Clinical review: severe malaria,” Critical Care, vol. 7, no. 4, pp. 315–323, 2003. View at: Publisher Site | Google Scholar
  44. V. Djokic, L. Akoolo, N. Parveen et al., “Babesia microti infection changes host spleen architecture and is cleared by a th1 immune response,” Frontiers in Microbiology, vol. 9, p. 85, 2018. View at: Publisher Site | Google Scholar
  45. V. Djokic, S. Primus, L. Akoolo, M. Chakraborti, and N. Parveen, “Age-related differential stimulation of immune response by Babesia microti and Borrelia burgdorferi during acute phase of infection affects disease severity,” Frontiers in Immunology, vol. 9, 2018. View at: Publisher Site | Google Scholar
  46. J.-H. Hwang and C.-S. Lee, “Malaria-induced splenic infarction,” The American Journal of Tropical Medicine and Hygiene, vol. 91, no. 6, pp. 1094–1100, 2014. View at: Publisher Site | Google Scholar
  47. R. M. Hemmer, D. A. Ferrick, and P. A. Conrad, “Role of t cells and cytokines in fatal and resolving experimental babesiosis: protection in TNFRp55 −/− mice infected with the human babesia wa1 parasite,” The Journal of Parasitology, vol. 86, no. 4, pp. 736–742, 2000. View at: Publisher Site | Google Scholar
  48. P. J. Krause, J. Daily, S. R. Telford, E. Vannier, P. Lantos, and A. Spielman, “Shared features in the pathobiology of babesiosis and malaria,” Trends in Parasitology, vol. 23, no. 12, pp. 605–610, 2007. View at: Publisher Site | Google Scholar
  49. P. Bonnard, J.-B. Guiard-Schmid, M. Develoux, W. Rozenbaum, and G. Pialoux, “Splenic infarction during acute malaria,” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 99, no. 1, pp. 82–86, 2005. View at: Publisher Site | Google Scholar
  50. A. Machado Siqueira, B. M. Lopes Magalhães, G. Cardoso Melo et al., “Spleen rupture in a case of untreated Plasmodium vivax infection,” PLoS Neglected Tropical Diseases, vol. 6, no. 12, Article ID e1934, 2012. View at: Publisher Site | Google Scholar
  51. K. M. Kim, B. K. Bae, and S. B. Lee, “Spontaneous splenic rupture in Plasmodium vivax malaria,” Annals of Surgical Treatment and Research, vol. 87, no. 1, pp. 44–46, 2014. View at: Publisher Site | Google Scholar
  52. P. A. Buffet, I. Safeukui, G. Deplaine et al., “The pathogenesis of Plasmodium falciparum malaria in humans: insights from splenic physiology,” Blood, vol. 117, no. 2, pp. 381–392, 2011. View at: Publisher Site | Google Scholar
  53. P. Imbert, C. Rapp, and P. A. Buffet, “Pathological rupture of the spleen in malaria: analysis of 55 cases (1958–2008),” Travel Medicine and Infectious Disease, vol. 7, no. 3, pp. 147–159, 2009. View at: Publisher Site | Google Scholar
  54. G. P. Wormser, A. Prasad, E. Neuhaus et al., “Emergence of resistance to azithromycin-atovaquone in immunocompromised patients with Babesia microti infection,” Clinical Infectious Diseases, vol. 50, no. 3, pp. 381–386, 2010. View at: Publisher Site | Google Scholar
  55. A. E. Levin and P. J. Krause, “Transfusion-transmitted babesiosis,” Current Opinion in Hematology, vol. 23, no. 6, pp. 573–580, 2016. View at: Publisher Site | Google Scholar

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