Co-infection Babesia – symptoms, diagnosis and treatment

babesia, a deadly tickborne parasite

Babesiosis is caused by a protozoa that infects red blood cells. They can be transmitted through a tick bite from blacklegged ticks. Babesia infections occur in specific regions in the northeast and upper Midwest United States. In addition Babesia can be transmitted via a contaminated blood transfusion. This appears to be an increasing problem because blood donors are rarely screened for parasites such as Babesia. Transmission from mother to unborn child is also documented.

The parasite is transmitted by ticks that can also transmit Lyme disease and therefor a patient could contract both diseases from the same tick bite. Healthy people recover without pharmaceutical intervention but the infection can be fatal in patients with a compromised immune system, individuals without a spleen, the elderly or people with concomitant Lyme disease.

Symptoms include fever, chills, sweats, muscle pain, joint pain, anorexia, nausea, vomiting and fatigue.

The Rise of babesiosis

More than 100 Babesia species have been reported but relatively few have been documented to cause human disease. These include, but are not limited to, B. microti, B. divergens, B. duncani and a currently unnamed agent designated MO1.

In 1888 the parasite was first discovered by Victor Babes when it caused severe disease in cattle and sheep. In 1893 it was identified as the cause of Texas cattle fever and they identified the tick as transmitting agent. It was long thought only affecting mammals but in 1957 the first case of babesiosis in a human was seen.

While research is increasing more species that can infect humans are being discovered. There are currently 12 species known to infect humans.

Babesia parasites have existed for hundreds of millions of years. Studies on their genetic composition have shown that the ancestors of these parasites already existed in the precursors of what we now know as ticks. They have co-evolved into the form by which we now know them. Long ago they even infected dinosaurs.

Nowadays Babesia is prevalent on the island off the coast of southern New England, from Cape Cod to Connecticut and from the Lower Hudson Valley to Maryland. Today the disease has spread to all of New England. Cases are also reported from the upper Midwest such as Wisconsin and Minnesota. Babesia was once a rare disease but has become a serious public health threat.

Coinfection with Lyme disease

Up to a fifth of the Lyme disease patients experience concurrent infection babesiosis. The prevalence of coinfections in ticks ranges from 2% to 13% and in rodents this ranges from 13% to 40% because rodents are exposed to multiple tick bites during their lifetime.

These are significant numbers because Babesia requires different treatment than given for Lyme disease. Coinfection with Lyme disease or anaplasmosis may predispose the patient to more severe disease. Imagine getting Malaria on top of Lyme disease. Coinfected patients are more likely to experience fatigue, headache, sweats, chills, anorexia, emotional liability and naussea than those with Lyme disease alone.

Patients with Babesia can remain symptomatic for years with constitutional, musculoskeletal and neurological problems. 50% patients coinfected with Babesia had symptoms for 3 months of longer compared to only 4% of the patients who only had Lyme disease.

Geographical distribution

geographical distrubition of babesia

According to the CDC Babesia infections occur in specific regions in the northeast (Rhode Island, Connecticut, Massachusets,Vemont, New Hampshire, Maine, New York, New Jersey, Delaware and Maryland) and the upper Midwest (Wisconsin and Minnesota) of the United States. Cases have also been reported in Texas, Alabama, South Carolina, Illinois, Ohio, Michigan and South Dakota.

B. duncani causes Babesia infections along the Pacific Coast of the United States and the presence of B. duncani is widespread across Canada with the highest occurrence in the Pacific coast region. Greater awareness of human babesiosis is needed in Canada and the threat to the security of the Canadian blood supply warrants further investigation. Cases are reported in Alberta, British Columbia, Manitoba, New Brunswick, Nova Scotia, Newfoundland, Labrador, Ontario, Prince Edward Island, Quebec and Saskatchewan.

In Europe B. divergens is the main cause of babesiosis in humans. Most cases are reported in France, the United Kingdom and Ireland but infections happen throughout Europe. B. microti and B. venatorum are the main cause of babesiosis in humans in China, Korea and Russia.

The annual number of officially reported cases of Lyme disease has tripled to 30,000 but the actual number is 10 times higher than that. Routine surveillance only shows us part of the picture, and that the true number of illnesses is much greater. The same is probably true for the officially reported cases of babesiosis. From this we learn the absence of data is not a definite proof of absence. Which means it might be possible to contract Babesia in areas where it is not reported to be endemic.

Babesia symptoms

common babesia symptoms

The clinical symptoms of a Babesia infection are similar to malaria and range from asymptomatic to rapidly fatal. Most patients experience flu-like symptoms with fever, chills, sweats, muscle pain, joint pain, anorexia, naussea, vomiting or fatigue. In some the disease goes undetected when individuals remain asymptomatic. This can be problematic because the disease can be transmitted via blood transfusion.

Some patients need to be hospitalized due to a more serious course of the disease. Their fever is higher, their fatigue is worse and the chills are accompanied by sweating. Often the patients also suffer from overall malaise, abdominal pain and diarrhea. Complications of babesiosis include acute respiratory failure, dissimated intravascular coagulation, congestive heart failure, coma and renal failure.

Air hunger and fainting

Babesia lives in the red blood cells and steals oxygen. This results in low blood oxygen levels. Patients become fatigued, experience blood sugar crashes and lightheadedness after exertion. Enlarged blood cells filled with Babesia can impede passage trough capilaries. Babesia also increases clothing. In the worst case scenario this can mimic a mini-stroke but when the blood flow through capilaries is impeded and blood oxygen levels are low, patients can literally feel hungry for air. They can become light-headed or even faint.

Symptoms of severe infection

In those in whom the infection becomes severe, the fever may increase accompanied by severe chills and inflammation of the liver and spleen. Other symptoms include accumulation of fluid in the lungs, decreased blood pressure, rupturing of red blood cells, jaundice, dark urine, low numbers of neutrophils, low numbers of leukocytes, an increase in lymphocytes, abnormal platelet count, anemia and bruising.

The most serious problems happen when intravascular coagulation occurs. This causes excessive blood clotting in the blood vessels. In response, the body switches on the system to clear these clots causing bleeding everywhere. As a result, different organs can shut down and eventually death can follow. If this happens in the brain this can interfere with blood flow and cause seizures and stroke.

Function of the spleen

The spleen helps to clear the parasites from the blood. It produces antibodies that attack the parasites after which the parasites are killed by macrophages. In addition, it works as a sieve by filtering infected red blood cells from the blood. In patients severely affected, the spleen can rupture. In patients without a spleen a Babesia infection can be lethal.

Risk factors

No spleen high mortality rate
Weak immune system AIDS, corticosteroid therapy, concurrent Lyme disease
Elderly >50 years old

Diagnosing Babesia

Epidemiological data will inform your doctor whether Babesia is present in your region and whether your clinical symptoms can be caused by Babesia. Suspicion of Babesia will be confirmed with laboratory tests.

The clinical findings are often nonspecific and the diagnosis is made by microscopic identification of the Babesia parasite in your blood on Giemsa stain. Multiple blood smears must be examined because only a few red blood cells are infected in the early stage of the disease when most people seek medical attention.

According to doctor Richard Horowitz doctors should use a panel approach to diagnosing Babesia.

Blood smear

The main method of diagnosing Babesia infection is via microscopic analysis of the red blood cells to look at Babesia’s appearance and structure. The organisms have the appearance of a Maltese cross or ‘double pear’ sign inside infected red blood cells. Multiple blood smears must be examined because the organism is often only present in low numbers. In many cases only 1% of the red blood cells are infected. They are hard to see inside stained cells and lab technicians may have a hard time picking them up. This testing method is only useful during acute manifestations of the infection.

Polymerase Chain Reaction (PCR)

PCR detects the DNA of Babesia in a blood sample. It is able to pick up only a few copies of Babesia DNA. PCR has been shown to be slightly more sensitive than the detection of parasites on blood smear. There are some concerns with the accuracy of this test because it is species specific. When you have another species of Babesia infecting you than tested for your laboratory results come back negative.

Indirect Fluorescence Assay (IFA)

Both IgG and IgM antibodies to Babesia can be detected by indirect fluorescence assay. Almost all patients will have obtained a measurable antibody response 4-6 weeks after the onset of the infection. The main problem with this test is that it measures antibodies in the blood which are not always present in the early stage of the infection.

Babesia Life cycle

The Babesia life cycle involves two hosts, which include a rodent, primarily the white-footed mouse and a blacklegged tick.

An infected tick introduces Babesia into the mouse. These enter the red blood cells and reproduce. Eventually they rupture the red blood cell which leads to the release of the parasite into the blood stream. A clean tick then becomes infected by taking up Babesia parasites during a blood meal from the infected mouse.

Humans enter the cycle when bitten by infected ticks. During the blood meal the  infected tick introduces the sporozoites in the human host. These enter the red blood cells and undergo asexual replication. These then differentiale into gametes. The multiplication of the blood-stage parasites are responsible for the clinical symptoms. Humans can then pass on the infection via blood transfusion and the Babesia can be transmitted from an infected mother to her baby during pregnancy or delivery.

In these different stages the Babesia develop in different morphological forms called sporozoites, gametes, ookinetes and merozonites. All four stages can be present in the body at the same time. This increases their survivability. (See the Babesia life cycle infographic below).

This cycle repeats itself every several months and parasites flood the blood stream which causes a relapse of symptoms.

babesia life cycle

Babesia Treatment

CDC guidelines for Babesia

Atovaquone + Azithromycin

Atovaquone 750 twice a day

Azithromycin on the first day, give a total dose in the range of 500–1000 mg orally; on subsequent days, give a total daily dose in the range of 250–1000 mg

Duration of treatment is 7-10 days. Resistance is reported in the literature.

Clindamycin + Quinine

Clindamycin 600mg orally 3 times a  day, or 300–600 mg intravenously 4 times a day

650 mg orally 3 times a day.

This treatment combination is mainly used in patients with serious infection. Clindamycin 600mg orally 3x daily (or intravenously) plus quinine 650mg orally 3x daily.

Duration of treatment is also 7-10 days.

Clindamycine + Quinine treatment is often associated with side effects such as tinnitus, vertigo and intestinal problems. Resistance is also reported for this combination.

A red blood cell exchange transfusion is potentially life-saving in adjunct to antimicrobial therapy and is indicated in patients with high parasitemia (more than 10%).

Treatment failure

Due to extensive use of anti-Babesia medication in livestock resistance is becoming common. Treatment of 7-10 days is associated with a high relapse rate. In patients with a compromised immune system it is recommended to treat for at least 6 weeks. There are many case reports of patients who relapse after completion of a 7-10 day treatment.

Other drugs

Other drugs have been used to treat babesiosis. The combination of pentamidine and cotrimoxazol was found to be moderately effective in clearing Babesia divergens but potential adverse reactions of pentamidine, however, limit the use of this combination.

Doxycycline has antimalarial effects

Artemether/Lumefantrine this is a semisynthetic derivative of artemisia annua.

Atovaquone/Proguanil produces naussea and other unpleasant side-effects but can be used when Atovaquone + Azithromycine therapy has failed.

Mefloquine this drug is associated with severe side-effect. It causes insomnia, changes in mood, irritability, restlessness and poor concentration.

Blood transfusion transmitted Babesia

There is a concern that transfusion transmitted cases of babesiosis are underestimated because there is no licensed blood donation screening test. In a study from 2016 scientists performed IFA’s and PCR’s to screen for B. microti antibodies and dna. Donations that tested positive by at least one method were removed from the blood supply. Infected donors provided follow up blood samples to study clearance rates of B. microti dna and antibodies.

Of the 89,153 blood donations from 60,512 blood donors 335 donations were confirmed positive for B. microti. 13% of the pcr positive donations were antibody negative. Hamster were infected with pcr positive material to measure rates of infectivity. 54% of these positive donations infected the hamsters.

After a one year follow up dna clearance was seen in 86%. In Connecticut and Masachusets where 93% of the positive samples had been found investigators noted that there were no transfusion transmitted cases of babesiosis from screened donations during the study period as compared with 14 cases from unscreened donations.

The authors conclude that screening for B. microti can identify infected blood donations and reduce the risk of transfusion transmitted babesiosis.

In March 2018, FDA approved the first B. microti screening tests for U.S. blood donors, who can feel fine despite being infected.