Babesia Microti Infection Research Articles

Congenital Babesiosis After Maternal Infection With Borrelia burgdorferi and Babesia microti.

We describe the cases of 2 infants with congenital babesiosis born to mothers with prepartum Lyme disease and subclinical Babesia microti infection. The infants both developed anemia, neutropenia, and thrombocytopenia, and 1 infant required red blood cell transfusion. Both infants recovered with treatment. Additional studies are warranted to define the optimal management strategy for pregnant women with early Lyme disease in geographic areas in which B microti infection is endemic.

Risk Factors for Severe Infection, Hospitalization, and Prolonged Antimicrobial Therapy in Patients with Babesiosis.

Babesiosis is an emerging tick-borne disease transmitted by the hard tick Ixodes scapularis, which also transmits Lyme disease. Better gradation of prognostic indicators are needed to determine which patients may develop serious complications requiring hospitalization, and to provide early guidance on appropriate therapy. In this study, we evaluated 128 patients with smear or real time polymerase chain reaction-confirmed Babesia microti infections over a period of 16 years. Patients with asplenia or immunocompromising conditions were more likely to have severe infection (P < 0.01), require hospitalization (P < 0.01), or receive prolonged courses of antimicrobials (P < 0.01). Nausea or vomiting (P < 0.01) and diarrhea (P < 0.01) along with hyperbilirubinemia (P < 0.01) were predictive of severe infection, hospitalization, and prolonged antimicrobial therapy. Patients with concurrent Lyme disease were less likely to require hospitalization and had similar severity of disease and length of antibiotic treatment compared with those without Lyme disease.

Clinical and Molecular Evidence of Atovaquone Resistance in Babesia microti Infection Associated With Rituximab

Clinical and Molecular Evidence of Atovaquone Resistance in Babesia microti Infection Associated With Rituximab

A Case of Severe Babesiosis in a Patient with Crohnʼs Colitis on Adalimumab

A 56-year-old male with Crohn's ileocolitis complicated by fistula on maintenance treatment with adalimumab, presented to the emergency department with 10 days of spiking fevers, chills, fatigue, abdominal pain, and anorexia after a trip to Connecticut. Physical exam revealed fever, tachycardia, hypotension and hepatosplenomegaly. At presentation, he was mildly anemic and thrombocytopenic, with leukocytes at 5400/uL, alkaline phosphatase at 140 U/L, an elevated LDH and low haptoglobin. Thick peripheral blood smear suggested babesia microti infection, which was confirmed by DNA PCR. His parasitemia level was 5.7%. He was started on oral atovaquone 750mg every 12 hours and oral azithromycin 1g every 24 hours with improvement in his parasitemia level to 1.24% by day 6, 1% by day 10, and 0% by day 14. Babesiosis is a tick-borne illness caused by intraerythrocytic protozoa. While most cases are asymptomatic, a more severe clinical disease can be seen in patients with advanced age (greater than 40 years), asplenia and depressed cellular immunity. As seen in our patient, who was immunocompromised from treatment with a TNF-alpha inhibitor (adalimumab), impaired immunity resulted in a more severe infection and prolonged hospital course. His parasitemia level did not clear until after day 10 of treatment and he had to remain on the higher dose azithromycin/atovaquone combination therapy for 3 more weeks to avoid relapsing illness. In addition, among the inflammatory bowel disease (IBD) population, the often-vague presentation of severe babesiosis can mimic a Crohn's flare - potentially delaying initiation of antimicrobial therapy and increasing risk for morbidity and mortality in these already vulnerable patients. Given the dramatic rise in cases of babesiosis in the Northeast and upper Midwest over the last decade, early consideration of babesiosis among immunocompromised IBD patients presenting with fever and poorly localized symptoms is essential. Ultimately, this case report illustrates how the severity and clinical course of a babesiosis infection varies with the immune status of a patient and highlights the importance of early consideration of babesiosis in immunocompromised IBD patients presenting with fever and non-specific symptoms.Figure 1

Severe Babesia microti infection in an American immunocompetent patient diagnosed in Spain

We report a severe Babesia microti infection in an immunocompetent patient diagnosed in Spain. A 66-year-old woman coming from USA presented with fever, thrombocytopenia, and multiorgan failure. Intraerythrocytic parasites were observed in Giemsa-stained peripheral blood smears and B. microti was first suspected by optical microscopy and afterward confirmed by specific polymerase chain reaction (PCR). Patient received antibiotic therapy, vital support measures and one red blood cell (RBC) exchange procedure. After 15 days, patient recovered and she was transferred to her reference hospital. This case report highlights the importance of clinical suspicion by physicians in non-endemic areas to diagnose this entity, the differential diagnosis with malaria infection, and the indication of RBC exchange as a therapeutic apheresis modality in the management of severe forms.

Severe Babesia microti Infection in an Immunocompetent Host in Pennsylvania.

Babesiosis, due to infection by a tick-borne protozoan (predominantly Babesia microti in North America), is an emerging health risk that is expanding into new areas and may be unfamiliar to clinicians in locations not previously considered endemic. Manifestations of infection can range from asymptomatic to life threatening, with severe disease more likely in those who have had a splenectomy, are immunocompromised, have chronic medical conditions, or are over 50 years of age. In this article, we describe an elderly but otherwise healthy man from an area not generally considered endemic for babesiosis who presented with severe hemolysis, acute renal failure, and high-level Babesia microti parasitemia; serological results suggestive of possible coinfection by Borrelia burgdorferi (the agent of Lyme disease, which is carried by the same tick as is Babesia microti) also was found. This report highlights that severe babesiosis can occur in an apparently normal host and underscores the continued geographic expansion of this pathogen and the need for early recognition and therapy.

A prospective evaluation of chronic Babesia microti infection in seroreactive blood donors.

Babesia microti is the foremost infectious risk to the US blood supply for which a Food and Drug Administration (FDA)-licensed test is unavailable for donation screening. Characterization of the antibody response to B. microti and correlation with parasitemia is necessary to guide screening and donor management policies. During an FDA licensure trial, blood donors were prospectively screened (July-November 2013) using a B. microti-specific antibody enzyme immunoassay (EIA, Immunetics) in highly endemic (New York [NY]; n = 13,688), moderately endemic (Minnesota [MN]; n = 4583), and nonendemic (New Mexico [NM]; n = 8451) regions. Blood donors with repeat-reactive (RR) results participated in a 12-month prospective cohort study using B. microti EIA, immunofluorescent assay, polymerase chain reaction (PCR), blood smear, and clinical questionnaire. Thirty-seven (61.67%; 24 NY, seven MN, six NM) of 60 eligible RR donors enrolled in the study; 20 of 37 (54%) completed the 12-month follow-up visit of which 15 (75%) were still seroreactive. Nine PCR-positive donors were identified during index screening; five participated in the follow-up study, three were PCR positive at 6 months, and two remained positive at final follow-up (378 and 404 days). Most RR donors displayed low-level seroreactivity that was either stable or waning during follow-up. The level and pattern of reactivity correlated poorly with PCR positivity. The findings indicate prolonged seropositivity in blood donors. Although rare, asymptomatic, persistent PCR positivity supports the current policy of indefinite deferral for donors with a history of babesiosis or positive test results. Repeat testing by PCR and serology will be necessary if reinstatement is to be considered.

Persistence of babesiosis for >2 years in a patient on rituximab for rheumatoid arthritis

We report a patient who was being treated with rituximab for rheumatoid arthritis who developed Babesia microti infection that persisted for 26 months despite prolonged anti-babesia drug therapy. The explanation for the persistence was likely to have been the long-term immunocompromising effects of rituximab, as evidenced by seronegativity for B. microti antibodies that lasted for more than 1 year after onset of infection.

Babesia microti Infection in Pregnancy Mimicking HELLP Syndrome

Babesiosis during pregnancy is an uncommon cause of hemolysis during pregnancy and may have a similar presentation to hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. We report a case of a 34- year-old healthy gravida 3 para 1-0-1-1 at 38 weeks of gestation who was transferred to our tertiary care center for induction of labor for suspected HELLP syndrome. Peripheral blood smear from the referring hospital showed intraerythrocytic ring forms consistent with Babesia microti infection. She was treated with clindamycin and quinine and had a vaginal delivery of a healthy infant. This case demonstrates that although uncommon, babesiosis should be on the differential for imitators of HELLP syndrome to optimize treatment and outcomes.

Inhibitory effects of 19 antiprotozoal drugs and antibiotics on Babesia microti infection in BALB/c mice.

Different results have been achieved in the evaluation of antiparasitic drug activity in Mongolian jirds, hamsters, and BALB/c mice infected with Babesia microti. The aims of the present study were to find a preferable method for drug screening and to re-evaluate the activity of several drugs against B. microti. The activity of 19 drugs on B. microti-infected BALB/c mice was evaluated. The study was built on Peters' four-day suppressive test, and the pathogenicity of the blood from the treated mice was also used as indicator. The results showed that 15 of the 19 drugs had little or no in vivo effect against B. microti. The inhibitory rates of atovaquone and azithromycin were high at all doses, but the microscopy-negative blood of recovered mice was still infectious. Similar to robenidine hydrochloride at 25 and 50 mg/kg, primaquine at 100 mg/kg had a 100% inhibitory rate. Robenidine hydrochloride achieved a 100% inhibitory rate at 100 mg/kg, and the blood of recovered mice did not result in parasitemia in subpassage experiments. Parasite-negative blood from mice treated with antimalarial drugs (clinically used for babesiosis) still caused parasitemia in subpassage experiments. This suggests that these drugs cannot eradicate the parasites. Peters' four-day suppressive test and the pathogenicity of the blood from the treated mice are suitable methods for preliminary investigating possible drugs against B. microti. Considering that robenidine hydrochloride achieved the best activity against B. microti in BALB/c mice in our study, further studies are needed.

Utilization of a real-time PCR assay for diagnosis of Babesia microti infection in clinical practice

Babesiosis is an emerging tick-borne disease mainly caused Babesia microti, a protozoan that infects erythrocytes. Microscopic examination of blood smears is the current gold standard for detection of Babesia infection, but this diagnostic test has several limitations. We developed and assessed the clinical utilization of a multiplex real-time PCR assay targeting the 18S rRNA gene of B. microti and the human gapdh gene. The limit of detection of this PCR assay was approximately 1–3parasites/μl of blood. The assay showed a diagnostic sensitivity and probable specificity of 100% based on testing 145 retrospective and 185 prospective blood specimens from controls and patients with confirmed babesiosis. Notably, the PCR assay was more sensitive than blood smear examination in patients during and following anti-babesia drug therapy. Our study suggests that PCR testing is as good or better than a blood smear for detection of B. microti in routine clinical practice. PCR testing may confirm the presence of babesiosis in patients whose level of infection is too low for reliable microscopic detection.

Comparison of a quantitative PCR assay with peripheral blood smear examination for detection and quantitation of Babesia microti infection in humans

Using a real-time quantitative PCR (qPCR), we determined the number of DNA copies/mL of blood of a Babesia microti gene in infected patients. Thirty-six patients (whose median age was 62.5years and 75.0% were male) with at least 1 qPCR-positive blood sample were included in this analysis, including 16 with serial blood samples. Based on testing of serial blood samples, it could be demonstrated that the smear became negative while the qPCR remained positive. A moderate to strong correlation was found between the DNA copy number and the number of infected erythrocytes per milliliter of blood (Pearson's r=0.68, P<0.001). Based on limited data, the DNA copy number fell by a mean of 4.1–12.9% per day on active treatment and by 3.5–7.1% per day off therapy. qPCR methodology may permit systematic evaluations of the relative efficacy of various antiparasitic drug regimens and other therapeutic modalities, although a limitation of such testing is that DNA detection per se does not establish the presence of viable parasites.

Serological and Molecular Investigations of Babesia Microti in Dogs from Southern Italy

Piroplasmosis is now considered emerging tick-borne zoonosis worldwide and domestic animals have been proposed as potential reservoirs for some piroplasm infections. The aim of this research was to identify the frequency of Babesia microti infection in untravelled dogs from Southern Italy (Sicily). Blood samples from 89 dogs were examined for the presence of Babesia microti antibodies and DNA. The dogs were infested with ticks. Among the examined dogs only one (1.16%) had B. microti antibodies, associated to B. canis, A. phagocytophilum and R. conorii infections. In the PCR assay, the dog was also found positive for B. microti and R. conorii DNA, and negative for other microorganisms. The infected dog showed a non-specific flu-like syndrome, with depression, disorexia, hyperthermia (39.6°C), light dehydration, moderate lymphadenopathy and heavy tick infestation (>20). No significant changes were present in the cell blood count. To the best of our knowledge, this is the first report of serological and molecular identification of B. microti piroplasm in a dog from Southern Italy. Because specific antibodies and DNA were detected in an untraveled dog, babesiosis is probably due to an autochthonous tick infection. However, this study indicates that Babesia microti is not widely distributed in dog populations in Sicily, as demonstrated by low prevalence of infection. So, in Sicily the dog would not appear to represent a reservoir of infection, but rather an accidental host.

A retrospective serological survey on human babesiosis in Belgium

In Europe, most clinical babesiosis cases in humans have been attributed to Babesia divergens and Babesia sp. EU1. Babesia microti infection of humans occurs mainly in the United States; although a case of autochthonous B. microti infection and serological evidence of infection have been reported in Europe. The Indirect Fluorescent Antibody Test was used to screen sera from 199 anonymous Belgian patients with history of tick bite and clinical symptoms compatible with a tick-borne disease. The serological screen detected positive reactivity in 9% (n = 18), 33.2% (n = 66), and 39.7% (n = 79) of the samples against B. microti, B. divergens, and Babesia sp. EU1, respectively. Thus, evidence of contact among three potentially zoonotic species of Babesia and humans has been confirmed in Belgium. Preventive action and development of better diagnostic tools should help in prevention of clinical cases and to clarify the true burden of such infection for individuals and public health.

Macrophages are the determinant of resistance to and outcome of nonlethal Babesia microti infection in mice.

In the present study, we examined the contributions of macrophages to the outcome of infection with Babesia microti, the etiological agent of human and rodent babesiosis, in BALB/c mice. Mice were treated with clodronate liposome at different times during the course of B. microti infection in order to deplete the macrophages. Notably, a depletion of host macrophages at the early and acute phases of infection caused a significant elevation of parasitemia associated with remarkable mortality in the mice. The depletion of macrophages at the resolving and latent phases of infection resulted in an immediate and temporal exacerbation of parasitemia coupled with mortality in mice. Reconstituting clodronate liposome-treated mice at the acute phase of infection with macrophages from naive mice resulted in a slight reduction in parasitemia with improved survival compared to that of mice that received the drug alone. These results indicate that macrophages play a crucial role in the control of and resistance to B. microti infection in mice. Moreover, analyses of host immune responses revealed that macrophage-depleted mice diminished their production of Th1 cell cytokines, including gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). Furthermore, depletion of macrophages at different times exaggerated the pathogenesis of the infection in deficient IFN-γ(-/-) and severe combined immunodeficiency (SCID) mice. Collectively, our data provide important clues about the role of macrophages in the resistance and control of B. microti and imply that the severity of the infection in immunocompromised patients might be due to impairment of macrophage function.

Prevalence and molecular characterizations of Toxoplasma gondii and Babesia microti from small mammals captured in Gyeonggi and Gangwon Provinces, Republic of Korea

A survey was conducted to determine the distribution and prevalence of Toxoplasma gondii and Babesia microti infections in small mammals captured in Gyeonggi and Gangwon Provinces, Republic of Korea (ROK). The serological prevalence of T. gondii (ELISA) and B. microti (IFAT) was 2.3% (15/667) and 2.1% (14/667), respectively. DNA extracts from small mammal heart tissues were screened by PCR for T. gondii and B. microti targeting regions of the GRA5 gene and the 18S rRNA and β-tubulin genes, respectively. Only 0.17% (1/578) of Apodemus agrarius was positive of T. gondii by PCR, while 0.52% (3/578) was positive of B. microti. All other small mammal species [Micromys minutus (16), Mus musculus (3), Myodes regulus (22), Microtus fortis (6), and Crocidura lasiura (42)] were negative for both T. gondii and B. microti. Based on sequence polymorphism and phylogenetic analysis, T. gondii closely aligned with Type I, a highly virulent strain, while B. microti positive samples closely aligned with US-type B. microti and others observed in the ROK, Russia, and Japan. These results indicate that A. agrarius is a reservoir for both T. gondii and B. microti in the ROK.

Molecular Detection and Seroprevalence ofBabesia microti among Stock Farmers in Khutul City, Selenge Province, Mongolia

Babesiosis is an emerging tick-borne disease in humans worldwide; however, little is known about the frequency of infection or prevalence of this disease in other parts of the world, excluding North America. In this study, we aimed to investigate Babesia microti infection frequency in a human population in Mongolia. One hundred blood samples were collected from stock farmers living in Khutul city of Selenge province, Mongolia. The sera and DNA from blood samples were evaluated for the presence of B. microti infection by using indirect fluorescent antibody (IFA) tests and PCR. The positive detection rates obtained using the IFA tests and PCR assays were 7% and 3%, respectively. This study is the first to detect of B. microti infections based on antibody seroprevalence or PCR assays for the presence of B. microti DNA in a Mongolian population.

Hepatosplenic alpha/beta T-cell lymphoma masquerading as cirrhosis.

A 59-year-old man with diabetes mellitus, prior hepatitis B infection and recently diagnosed cirrhosis with prior Babesiosis presented to our institution from an outside hospital with six months of worsening abdominal pain, myalgias and fevers. On admission, physical examination revealed jaundice, hepatosplenomegaly and diffuse lymphadenopathy. Laboratory investigations demonstrated mild anemia, thrombocytopenia, hyperbilirubinemia and elevated lactate dehydrogenase. Tests for human immunodeficiency virus, and active Babesia microti infection were negative, however Epstein-Barr virus DNA by quantitative PCR was markedly elevated. CT scan revealed features suggestive of a cirrhotic liver without focal mass lesions as well as massive splenomegaly with axillary, retroperitoneal and inguinal lymphadenopathy. Bone marrow and lymph node biopsies were obtained which ultimately revealed hepatosplenic T-cell lymphoma. The patient's initial liver biopsy from five months prior to presentation was re-evaluated by our institution's pathologists. Histologic analysis showed hepatic sinusoidal and portal infiltration of atypical lymphocytes morphologically identical to those present on the more recently excised lymph node tissue. The hepatic sinusoidal lymphoid cells were strongly positive for CD2, CD3 and CD5 whereas CD4, CD8 stained only minor subsets of the T cells. Subsequent flow cytometric immunophenotypying of peripheral blood identified T-cell receptor alpha/beta positive cells that lacked CD4 and CD8 (double negative alpha/beta T cells). Given the established bone marrow involvement, he was diagnosed with stage IV disease and treated with chemotherapy. His clinical course involved multiple hospitalizations complicated by hyponatremia, neutropenic fevers and pulmonary emboli. Following his fourth cycle of chemotherapy, he developed worsening liver failure and expired approximately three months after initial diagnosis of lymphoma. Hepatosplenic lymphoma of alpha/beta T cells is a rare malignancy with largely unclear risk factors and varied clinical presentations. Notably, diffuse infiltration of liver parenchyma is a prominent feature and the disease can mimic cirrhosis clinically as well as radiographically. Early recognition of this aggressive lymphoma is important and should be considered in the evaluation of patients in whom the etiology of cirrhosis remains in question.

Babesia microti:an unusual travel-related disease

BackgroundHuman babesiosis is a rare tick-borne infectious disease. The clinical presentation ranges from an asymptomatic form to a life threatening infection with severe hemolysis. Human babesiosis due to Babesia microti is the most common and is endemic in North America.Case presentationWe report a European patient with severe pancytopenia and reactive hemophagocytosis related to a Babesia microti infection. Babesia infection was acquired during a travel in the USA.ConclusionBabesiosis should be considered in patients who traveled in endemic areas, especially North America for the most common agent Babesia microti.

Effect of Sex Steroids on Babesia microti Infection in Mice

Sex-based-differences are known to affect susceptibility to protozoan infections, but their effects on parasitemia and clinical symptoms in Babesia infections remain unclear. We examined the sex-based susceptibility of various mouse strains to Babesia microti Munich strain infection. In all strains, male mice exhibited significantly higher peak parasitemia and more severe anemia than female mice. Testosterone and estradiol-17β treatment caused an increase in parasitemia and aggravation of anemia. Orchidectomized male mice receiving testosterone exhibited smaller splenic macrophage populations three days after infection, smaller B cell populations 10 days after infection, and reduced splenic tumor necrosis factor-α and interferon-γ mRNA expression than mice that did not receive testosterone. Mice receiving estradiol-17β did not exhibit immunosuppressive effects. Thus, a weakened and delayed innate immunity response may lead to acquired immunity failure. The results suggested that testosterone directly affects T or B cells, leading to delayed acquired immunity, dramatically increased parasitemia, and severe anemia.