Babesiosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Ilan Dock, B.S.

Babesiosis is caused by apicomplexan parasitic organism within the genus Babesia. B. Microti and B. divergens are the two species of Babesia that have been frequently reported as parasitic within human populations. Babesia parasites reproduce in red blood cells, where they can be seen as cross-shaped inclusions (4 merozoites asexually budding but attached together forming a structure looking like a “Maltese Cross”) and cause hemolytic anemia, quite similar to malaria.

Babesiosis is a vector-borne illness usually transmitted by ticks. Often referred to as “The Malaria of The North East,” babesiosis is a worldwide distributed disease, reported within tick endemic regions such as Asia, Europe, the United States. Key endemic areas within the United States include the northeastern coastal region including islands off the coast of New York, Massachusetts, and Rhode Island.

The most potent risk factors in the development of Babesiosis are a combined effort between environment and season. Babesia parasites are transmitted via tick bites in tick-populated areas.

Babesiosis was originally reported by the Romanian scientist, Victor Babes, in 1888. The disease was investigated for its renown infection in domesticated animals and cattle. In 1957, the first human babesiosis infection was documented in a splenectomized, Yugoslavian patient. All patients observed with babesiosis had also undergone a splenectomy, it wasn’t until 1969 that the infection was observed within a normal patient.

Babesia parasites reproduce in red blood cells, where they can be seen as cross-shaped inclusions (4 merozoites asexually budding but attached together forming a structure looking like a “Maltese Cross”) and cause hemolytic anemia, quite similar to malaria.

Note that unlike the Plasmodium parasites that cause malaria, Babesia species lack an exo-erythrotic phase, so the liver is usually not affected.

Babesiosis is caused by apicomplexan parasitic organism within the genus Babesia. B. Microti and B. divergens are the two species of Babesia that have been frequently reported as parasitic within human populations.

Babesiosis is a vector-borne illness usually transmitted by ticks. Often referred to as “The Malaria of The North East,” babesiosis is a worldwide distributed disease, reported within tick endemic regions such as Asia, Europe, the United States. Key endemic areas within the United States include the northeastern coastal region including islands off the coast of New York, Massachusetts, and Rhode Island. Cases have also been reported throughout the United States and Europe, though not as frequently as the United States, Northeastern coast. Reported cases have identified a median age of 62 years and a higher rate of infection amongst males. Other factors contributing the heightened infection rates are, tick activity by season, level of tick exposure, and an individual’s medical history.

The most potent risk factors in the development of Babesiosis are a combined effort between environment and season. Babesia parasites are transmitted via tick bites in tick-populated areas. Transmission occurs more frequently during the spring and summer in correlation with heightened periods of tick activity. Other risk factors include repeated exposure to the following potential I. scapularis and Ixodes rodent hosts; white-footed deer mice, rats, voles, chipmunks, and field mice; As well as blood transfusions from donors living within endemic areas.

Babesiosis causes a disease very similar to Malaria. In mild cases, people may experience mild fevers and anemia. In more severe cases, fevers go up to 105 degrees with shaking chills, and anemia (hemolytic anemia) can become severe. Organ failure may follow including adult respiratory distress syndrome.

History and Symptoms | Physical Examination | Laboratory Findings | Other Imaging Findings | Other Diagnostic Studies

A wide range of physical findings may be associated with patients suffering from babesiosis. Asymptomatic patients will generally appear healthy without any external signs of infection. However physical examination findings are variable depending on the severity of the infection as well as the patient’s medical history. For patients exhibiting symptoms apparent during physical examination, the most common physical findings may range from a moderate fever and minor display of flu-like symptoms to Hepatomegaly, Petechiae, Ecchymoses and Acute respiratory distress syndrome (ARDS).

Medical Therapy | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies

The mainstay of therapy for babesiosis is antimicrobial therapy. Patients with mild or moderate disease are treated with a combination of Atovaquone and Azithromycin. Patients with severe disease are treated with either Clindamycin or Clindamycin and Quinine. In life-threatening cases, exchange transfusion is performed.

Case #1

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Ilan Dock, B.S.

Babesiosis was originally reported by the Romanian scientist, Victor Babes, in 1888.^[1] The disease was investigated for its renown infection in domesticated animals and cattle. In 1957, the first human babesiosis infection was documented in a splenectomized, Yugoslavian patient. All patients observed with babesiosis had also undergone a splenectomy, it wasn’t until 1969 that the infection was observed within a normal patient.^[1]

• Babesiosis was first discovered as a hemolytic infection in 1888 by the Romanian scientist, Victor Babes.^[1]
• Two Americans, Fred Kilborne and Theobald Smith discovered Babesia as the parasitic infection responsible for Texas Cattle Fever.^[1]

• In 1957, a splenectomized human patient is reported to suffer from a hemolytic illness likened to that of babesiosis. Babesia is identified as the parasite responsible for infection. All other reported patients suffering from the illness had also undergone a splenectomy until 1969.^[1]
• In 1969, the first babesiosis infection within a normal human patient, without a splenectomy, was documented.
• In 2011, the Center for Disease Control and Prevention, listed babesiosis as a nationally notifiable condition.^[2]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Tamar Sifri [2] Associate Editor(s)-in-Chief: Ilan Dock, B.S.

Babesia parasites reproduce in red blood cells, where they can be seen as cross-shaped inclusions (4 merozoites asexually budding but attached together forming a structure looking like a “Maltese Cross”) and cause hemolytic anemia, quite similar to malaria. Note that unlike the Plasmodium parasites that cause malaria, Babesia species lack an exo-erythrotic phase, so the liver is usually not affected. The cycle depends on two primary components, an infected vertebrate host and an infected tick. Transmission from a tick to a human occurs over the course of a complete blood meal. Inoculation rates will rapidly increase in direct correlation with the span of the tick’s blood meal.

• The Babesia microti life cycle involves two primary components, an infected vertebrate host (primarily the white-footed mouse “Peromyscus leucopus”), and a tick in the genus Ixodes. ^[1]

• Babesia organisms are detectable within 10 hours of tick ingestion.
• Parasitic organisms may still be detectable within erythrocytes until this point, however gametocytes begin to develop new organelles within 46 to 60 hours of ingestion.
• A notable physiological event occurs as gametocytes develop an arrowhead-shaped organelle.
• Research suggests that these arrowhead like structures are involved in gamete fusion.^[2]

• Zygotes maintain gamete’s arrowhead like structures.
• These structures are used by the Zygote to penetrate epithelial cells within the tick’s gut. Occurring within 80h of ingestion.
• Parasitic Organisms travel from epithelial cells in the tick gut to the salivary acini by means of the hemolymph.

• Three notable stages of sporozoite development occur within the tick’s salivary glands.

1. Formation of a multinucleate sporoblast within a hypertrophied host cell. (Results in three dimensional branching and an eventual foundation for sporozoite budding.)
2. Host begins feeding, resulting in the formation of sporozoite’s specialized organelles.
3. Budding of sporozoites. A single sporoblast may result in 5,000 to 10,000 sporozoites.^[2]

• During a blood meal, a Babesia-infected tick introduces sporozoites into the mouse host.
• Sporozoites enter erythrocytes and undergo asexual reproduction (budding).
• In the blood, some parasites differentiate into male and female gametes, although these cannot be distinguished by light microscopy.
• The definitive host is the tick. ^[2]

• Transmission occurs during a blood meal.
• Parasitic organism are transmitted through in the tick’s saliva.
• Tick transmission is an efficient transmission method since the tick’s saliva contains anti-inflammatory and immunosuppressive properties.
• Enabling transmission to occur largely undetected.

Transovarial transmission (also known as vertical, or hereditary, transmission) has been documented for “large” Babesia spp. but not for the “small” babesiae, such as B. microti (A).

• Several thousand sporozoites are transmitted in the dermis surrounding the tick’s mouth.
• A successful inoculation requires 10,000-25,000 sporozoites. Therefore there is a direct correlation between the duration of tick feeding and probability of contracting the disease.
• Infection rates reach nearly 100% when an infected tick feed to repletion.^[2]
• Sporozoites primarily infect erythrocytes.
• Certain species of Babesia will infect lymphocytes.
• Infection results in multinucleate schizont which bud into merozoites and cause cell lysing.
• Merozoites infect further erythrocytes through the formation of a parsitophorous vacuole, a process called invagination.
• Post-invasion the vacuole membrane disintegrates revealing a remaining single membrane, unlike plasmodium infection which retains both the host and parasitic membrane.^[2]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Ilan Dock, B.S.

Babesiosis is caused by apicomplexan parasitic organism within the genus Babesia. B. Microti and B. divergens are the two species of Babesia that have been frequently reported as parasitic within human populations. Babesia parasites reproduce in red blood cells, where they can be seen as cross-shaped inclusions (4 merozoites asexually budding but attached together forming a structure looking like a “Maltese Cross”) and cause hemolytic anemia, quite similar to malaria.

• The genus babesiidae hosts over 100 species of Babesia. However, Babesia Microti (B.Microti) and Babesia Divergens (B. Divergens) are most frequently reported as the apicomplexan parasitic organisms responsible for causing human infections (Babesiosis.)

• Babesia are transmitted through a Tick vector, most notably the Ixodidae tick family.

• Babesia was named after Victor Babes, the physician and scientist who originally discovered the parasite as the primary culprit in the hemolytic illness, Babesiosis. ^[1]

• Human pathogenic species are most frequently reported as B. Microti and B. Divergens. ^[3]
• Babesia parasites reproduce in red blood cells, where they can be seen as cross-shaped inclusions (4 merozoites asexually budding but attached together forming a structure looking like a “Maltese Cross”) and cause hemolytic anemia, quite similar to malaria.

• Infection as a result of B. Microti can result in either an asymptomatic infection or a number of malaria-like symptoms. Infection may be fatal and those who are immunocompromised or have undergone a splenectomy are at an increased risk of death. The incubation of B. Microti is between 1-8 weeks, after which malaria-like symptoms will appear. Parasitemia levels may rise percentages in the high 80’s, yielding fatal results. However high level of parasitemia are most often correlated to immunocompromised or splenectomized patients. ^[4]
• Infection as a result of B. Divergens is often associated with a higher rate of fatality. Incubation periods for B. Divergens are less than those of B. Microti at an average of 1-4 weeks. Symptoms also differ with severe complications such as shock-like symptoms. ^[4]
• Babesiosis, the disease attributed to Babesia infection is a tick-borne illness. Thus transmission occurs as a result of a tick bite and a higher rate of transmission is associated with longer blood meal periods.

• Transmission may also occur in as a result of blood transfusion from blood collected in an endemic area. ^[5]

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Babesiosis must be differentiated from other tick-borne diseases that cause fever, soreness, and rash, such as Lyme disease, Rocky Mountain Spotted fever, and Colorado tick fever.

Babesiosis may commonly be misdiagnosed as the following diseases:

• Lyme disease
• Malaria
• Colorado tick fever
• Ehrlichiosis & Anaplasmosis
• Bartonellosis
• Rickettsiosis
• Taluremia
• Q fever
• Leptospirosis

The following is a list of common tick-borne diseases and their associated symptoms:

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ilan Dock, B.S.

Babesiosis is a vector-borne illness usually transmitted by ticks. Often referred to as “The Malaria of The North East,” babesiosis is a worldwide distributed disease, reported within tick endemic regions such as Asia, Europe, the United States. Key endemic areas within the United States include the northeastern coastal region including islands off the coast of New York, Massachusetts, and Rhode Island. Cases have also been reported throughout the United States and Europe, though not as frequently as the United States, Northeastern coast. Reported cases have identified a median age of 62 years and a higher rate of infection amongst males. Other factors contributing the heightened infection rates are, tick activity by season, level of tick exposure, and an individual’s medical history.

• Key endemic areas within the United States include the northeastern coastal region, in the specific states and regions as listed: ^[1]

• New York – Eastern Long-Island and its barrier island, Fire Island. As well as Shelter Island.

• Massachusetts- Cape Cod, as well as Islands off the Massachusetts coast such as Nantucket Island and Martha’s Vineyard.

• Rhode Island- Block Island.

• Other United States regions to have reported at least a single instance of infection include the Western states of California and Washington; Central states of Wisconsin, Minnesota, Nebraska, North Dakota, South Dakota , Indiana, Michigan, and Missouri; Northeastern states of Connecticut , New Jersey, New Hampshire, Delaware, Maine, Vermont and Maryland; and in the Southern states of Virginia, South Carolina, Louisiana, Texas, and Georgia. However reported cases of Babesiosis are less prevalent in these aforementioned states than those referred to previously on the Northeastern coast.^[1]

• Geographically, increased populations of deer, either by means of restocking or states environmental and hunting sanctions, has seemingly contributed to the heightened prevalence of Babesiosis in the United States.
• Analysis of patient blood smears for an antibody specific to B microti on the United State’s Northeastern coast suggests that rates of infection fluctuate seasonally and geographically.^[1]
• Other contributing factors to the heightened infection rate within these areas may be attributed to an increasing trend in outdoor recreational activity within the aforementioned endemic areas.

• In 2013, 27 states (all of which are previously listed excluding: Alabama, Oregon, Tennessee, West Virginia, and Wyoming where screening results reported zero occurrences of the disease) conducted a patient population survey for reported Babesiosis.
• The findings resulted in a total 1,762 reported cases.
• Comparison of Babesiosis infection rates over the years presents difficulty as it was only declared a nationally notifiable condition by the CDC in January 2011.
• Yet an analysis of the data collected by the CDC between the years of 2011 and 2013 reveals a heightened increase of nearly 500 more reported cases in 2013. *Furthermore the total prevalence of the disease is practically unattainable as many of the North American cases are non-reported and asymptomatic. ^[1]

• In Europe, babesia transmission is primarily the fault of Ixodes ricinus (a European species of ticks). Due to the wide distribution of the species through the European continent, reported cases are not isolated to specific regions.
• Unlike more common cases of the disease in the United States, babesiosis is a rather rare occurrence in Europe.
• The disease has also proven a higher morbidity rate.
• Of the 39 European cases published, all were reported as clinically severe and required immediate action.
• However, of the reported babesiosis cases reported thus far, the majority have been identified as previously immunocompromised or had undergone a splenectomy. ^{[1] [2]}

• Infected populations have also been recorded in regards to sex and age. Of the total, 1,762 cases reported to the CDC in 2013, findings indicate a median age of 62 years, as well as a distribution of infection between males and females at 65% and 32% respectively. ^[1]

• Severity of Babesiosis varies as infection with Babesia parasites can be asymptomatic or cause a mild non-specific illness, although it may also result in severe disease. However most severe cases occur in the very young, very old, or persons with underlying medical conditions (such as immunodeficiency) and those without a spleen, they can occur in normal individuals. ^[2]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Ilan Dock, B.S.

The most potent risk factors in the development of Babesiosis are a combined effort between environment and season. Babesia parasites are transmitted via tick bites in tick-populated areas. Transmission occurs more frequently during the spring and summer in correlation with heightened periods of tick activity. Other risk factors include repeated exposure to the following potential I. scapularis and Ixodes rodent hosts; white-footed deer mice, rats, voles, chipmunks, and field mice.^[1][2]

Further examples of Babesia mammalian hosts also include deer populations. Although unlike the rodent transmission, transmission of Babesia from deer to human populations is likely a result of an infected nymph bite. Reduction tactics therefore include reduced contact and increased proximity from rodent, deer, and tick populations in endemic areas.

Another risk factor, though rare, may be attributed to the transmission of Babesiosis via blood transfusion. In certain cases, Babesiosis is asymptomatic and contaminated blood may inadvertently be drawn from donors within endemic areas. Furthermore case reports also indicate rare occurrences of transmission via transplacental and perinatal pathways. ^[3]

Age may be an associated risk factor as well. A recent study performed by the Central for Disease Control and Prevention (CDC), identifies 62 years as the median age of reported babesiosis cases in the United States.^[1]

Furthermore the study incorporated patients with ages ranging from infantry (less than a year) to individuals of over 100 years. Of the observed cases, 65% were documented as males and 32% as female. However no further determinations were provided about the correlations between age, sex and a heightened risk of contracting the disease.^[1]

• Being bitten by an infected tick

• Residing in an endemic area, primarily the Northeastern, United States coast

• Repeated exposure to common I. scapularis and Ixodes hosts; white-footed deer mice, rats, voles, chipmunks, and field mice

• Outdoor recreational activity during seasons of high tick activity

• Patients with a medical history including a splenectomy or any immunocompromising diseases

• Receiving a blood transfusion from a donor residing in an endemic area
• Elderly individuals are more susceptible to infection (Most cases occur within patients of 50 to 60 years)

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ilan Dock, B.S.

The prognosis is usually good for individuals will regularly functioning immune systems and proper treatment. Severe illness is commonly associated with individuals with weaker immune systems including young children, the elderly, and immunocompromised populations. The reason for this heightened level of illness severity is, most likely, directly correlated with heightened levels of parasitemia in blood. Thus it is important for individuals within these populations to receive swift and proper treatment. Babesiosis may remain asymptomatic or manifest into a sever illness. Asymptomatic populations will not recognize any obvious signs or symptoms commonly associated with a babesiosis infection. Symptomatic populations will undergo an incubation period between 1-6 weeks prior to experiencing non-specific flu-like symptoms, or in severe cases, malaria-like symptoms. Further complications may include heart problems, low blood pressure,kidney failure, severe breathing problems, and severe hemolytic anemia (hemolysis).

Progression of a babesiosis infection may present itself in a variety of clinical manifestations. The severity of these clinical manifestations are potentially a direct reflection of blood parasitemia levels in the blood.

• Chronic infection within asymptomatic populations remain within the incubation stage.

• There are no further clinical manifestations

• Clinical manifestations may occur as an asymptomatic patient becomes immuno-compromised or naturally ages.

• Incubation period of 1-6 weeks, however may incubate as long as 3 months.
• Clinical manifestations will present themselves as non-specific flu like symptoms.
• Common symptoms will include fever, headache, muscle aches, and pain.
• Severe illness may occur in older and immuno compromised populations. Severe illness will present itself as malaria-like.
• Symptoms associated with a severe infection include nausea, emesis, night sweats, and anorexia.

• Severe hemolysis may lead to jaundice.
• Other complications include a Shock-like state, renal failure, and pulmonary edema.

• Heightened levels of parasitemia in blood.
• Severe anemia, hemolysis, thrombocytopenia, leukopenia, and eventually death.

Babesiosis can be a very severe illness with complications including:^[1]

• Acute respiratory distress syndrome
• Heart problems
• Low blood pressure
• Kidney failure
• Severe breathing problems
• Severe hemolytic anemia (hemolysis)
• A very low platelet count (thrombocytopenia)
• Disseminated intravascular condition (DIC)
• Jaundice
• Hemoglobinuria

• The prognosis is usually good for individuals with normally functioning immune systems and proper treatment.
• Clinical manifestations with occur and become more severe as parasitemia levels heighten in blood.
• Severe illness (heightened levels of parasitemia) may be fatal and must therefore be closely monitored in young children, the elderly, and individuals with compromised immune systems.