Babesiosis in humans - a dangerous disease, but curable

Among the protozoal zoonotic diseases, babesiosis in humans is not as widely known as, for example, malaria or leishmaniasis.

Although parasitology collided with its causative agent in animals at the end of the XIX century. And in the possibility of infection of people, infectious disease doctors were convinced in the middle of the last century. And in the International Classification of Diseases (ICD-10) this acute vector-borne disease was given the code B60.0.

[1], [2], [3], [4]

Epidemiology

According to the International Society for Infectious Diseases statistics, in Europe the facts of the manifestation of babesiosis in humans are rarely recorded: from 1957, when the first case was accidentally detected (in the territory of the then Yugoslavia), no more than four dozen cases were officially recorded, mainly in Ireland, Great Britain and France. It is noteworthy that in the anamnesis all patients had splenectomy.

Also single cases with a pronounced clinical picture were recorded in Mexico, Colombia, South Africa, Egypt, Korea, China and Japan. Most of the patients were older than 45-50 years.

Almost 20-25% of patients have babesiosis combined with  Lyme disease.

The global incidence of human babesiosis has increased over time. For example, in China there is no endemic human babesiosis, but in the past three decades, patients with this disease appear more often.

According to official data for the Center for Global Health (CDC), in the United States from 2011 to 2014 inclusive, there were 5,542 cases of babesiosis in humans.

[5], [6], [7], [8], [9], [10], [11], [12]

Causes of the babesiosis

The only reason for babesiosis in humans is invasion, that is, the entry into the body of a variety of protozoa such as Babesia divergens and Babesia microti or Babesia belonging to the type Apicomplexa (or Sporozoea), the genus Plasmodium, the order Piroplasmidae.

The first subspecies is common in the European continent and in Asia, the second in the Western Hemisphere, and in both Eastern and Northern Australia, both subspecies are found. More about this microscopic parasite (its hosts, the biological cycle and reproduction) read in a separate publication -  Babesia.

The babesiosis pathogens infected with protists are bloodsucking arthropods, the parasites of vertebrates are ixodid mites: Ixodes ricinus (dog tick), Ixodes persulcatus (taiga mite), black mite (Ixode scapulari) and prefer the Pacific coast of Ixodes pacificus.

It is clear that the transmission pathways of babesiosis are transmissible - through  tick bites in humans, when, together with the salivary fluid secreted from the bite, the sporozoites of Babesia are ingested into the human blood.

Typically, the incubation period of parasitemia development after a tick bite is from one to four weeks, but sometimes it can be much longer.

In addition, other possible routes of infection include blood transfusions and donor organ transplants. Since 2003, the American Centers for Disease Control and Prevention documented more than 40 cases of babesiosis after transfusion of canned blood plasma and two cases of infection after allotransplantation.

[13], [14]

Risk factors

Among the main risk factors for babesiosis infectious diseases include living or visiting endemic regions and weakened human immunity. And this is not only HIV, but also the chronic diseases of any internal organs and oncology that suppress the immune system, as well as immunosuppressive therapy.

It is practically impossible to resist this transmissible disease, if a person underwent splenectomy, that is, his spleen was removed (the function of which is the destruction of dead cells and dead erythrocytes).

As in the case of other infections, children and the elderly are at increased risk of developing severe forms of babesiosis.

[15], [16], [17], [18], [19], [20], [21], [22]

Pathogenesis

Explaining the pathogenesis of this disease, experts note the ability of babesia to penetrate not simply into human blood, but into the cytoplasm of erythrocytes. The number of affected blood cells is usually 3-10% of the total mass of red blood cells, but it can range from less than 1% to 85%.

Further inside the red blood cells there is a transformation of the sporozoites of babesia into trophozoites, and then into the merozoites. The growth of their number simply breaks the red blood cells, and the reproductive cells of the parasite carry blood and attack new red blood cells.

Reproduction and pathological impact of babesies caught in the blood causes an inflammatory reaction (due to activation of pro-inflammatory cytokines) and hemolysis (massive death of red blood cells), which determines the Babesiosis clinic in humans.

Because of a sharp decrease in the level of red blood cells, hemolytic anemia (leading to oxygen starvation of all tissues) is observed; in the blood, the volume of the by-product of the lysis of erythrocytes of bilirubin increases (which is manifested by jaundice); toxic substances for the body, overloading the spleen and liver (with an increase in their size and a decrease in functions) enter the bloodstream. In addition, fragments of destroyed red blood cells can accumulate in the capillaries and cause microvascular stasis.

With increased hemolysis, the kidneys stop coping with blood filtration, in which hemoglobin is released from the damaged red blood cells. This iron-containing and oxygen-carrying protein "clogs up" the renal tubules, disrupting the production of urine and its excretion.

[23], [24], [25], [26]

Symptoms of the babesiosis

The severity of the disease and its manifestation depend on the state of the human immune system, and according to some data, half of the children and a quarter of previously healthy adults have no symptoms of babesiosis.

The first signs of this infection are nonspecific and most often manifest in the form of influenza-like symptoms: general weakness and malaise; fever (constant or periodic, with a temperature of up to + 40.5 ° C) - with chills and increased sweating; headaches, muscle aches and joint aches; loss of appetite. Such a clinical picture can be observed from several days to several months.

Less common symptoms may be nausea, vomiting, abdominal pain; yellowing of the skin and darkening of the urine (if hemolytic anemia develops); the appearance of petechiae and ecchymoses; photophobia with reddening of the conjunctiva and hemorrhage into the retina; pain and redness in the throat or dry cough; stiff neck; hyperesthesia; shortness of breath; state of depression.

[27], [28], [29], [30]

Complications and consequences

Severe cases can have multiple consequences and complications:

• congestive heart and respiratory failure, pulmonary edema and acute respiratory distress syndrome;
• acute renal, renal-hepatic or multiple organ failure;
• severe hemolytic anemia;
• thrombocytopenia or coagulopathy.

Spontaneous rupture of the spleen, myocardial infarction may occur; develop a shock state with lethal consequences.

Patients with a distant spleen are in a worse state, since the blood is not cleared of infected red blood cells. This leads to a higher degree of parasitaemia, which ultimately causes hypoxemia and the subsequent threat of acute cardiopulmonary insufficiency.

In addition, in such patients, hemophagocytic syndrome, rejection of kidneys and other organs can occur, which leads to coma.

With long-term babesiosis with organic brain damage, the complications are neurological and mental.

[31], [32], [33], [34]

Diagnostics of the babesiosis

This infection is difficult to diagnose, and proper diagnosis of babesiosis requires high qualification in the field of medical parasitology. Complaints of the patient and physical (palpation) examination of the spleen and liver to identify the true cause is not enough

Blood tests are assigned in specialized laboratories that can adequately diagnose the infection of Babesia.

Blood tests are necessary, such as: a complete analysis with a differential (total leukocyte formula) and ESR; enzyme immunoassay (ELISA); PCR analysis; IgM ELISA, serological analysis for IgG and IgM; direct test of Coombs; analysis for LDH (lactate dehydrogenase); on common bilirubin and haptoglobin; on the level of serum creatinine and hepatic transaminases.

Urine is also used to detect hemoglobinuria and proteinuria.

Confirmation of the diagnosis by a parasitologist is the detection of Babesia under a microscope in a peripheral blood smear.

Instrumental diagnosis - chest X-ray - may be required for patients with respiratory complications.

[35], [36], [37]

Differential diagnosis

Differential diagnosis is designed to exclude malaria, acute anemia, granulocytic anaplasmosis (erlichiosis), tick-borne borreliosis (Lyme disease), fever ky, tularemia in the patient under examination.

Treatment of the babesiosis

Combined medicamentous treatment of babesiosis is carried out taking into account the severity of the disease.

For mild to moderate forms, Azithromycin (antibiotic-macrolide) and Atovacon (Atovokvon, Mepron, Malaron) are used as antiprotozoic hydroxynaphthoquinone agent for 7-12 days.

Azithromizine is administered intravenously: 500 mg once a day (the first three days) and until the end of the course of 250 mg per day; the infant dose is calculated by body weight. Atatovac is used for 750 mg every 12 hours.

For patients with severe babesiosis, parenteral administration of the antibiotic group of clindamycin clonamides (Cleocina) 0.5-0.6 g every 8-12 hours is necessary; Inside is taken Quinine, Hingamin, Chinocid or Chloroquine Phosphate (Chloroquine, Delagil) - 0.5-1 g at the same intervals.

Antibacterial drugs, as you know, can cause side effects: nausea, abdominal pain, intestinal disorders, etc. But their use as injections somewhat smoothes unwanted effects. They have side effects and antiprotozoals, but without them babesiosis treatment is impossible today. Although with a strong allergy to quinine, a combination of Clindamycin + Doxycycline + Azithromycin is used.

The result of treatment is assessed by the indications of blood smears on Babesia; if the smears are negative for at least two weeks, then the therapy was successful.

With a high level of parasitemia and hemolysis - to maintain the kidneys, liver and lungs in seriously ill patients - resort to exchange blood transfusion.

Prevention

Prevention reduces the risk of infection with babesia by using acaricidal repellents (with permethrin) to repel ticks - when people live, work or travel where these arthropods are found, and during walks in wooded areas with grassy cover (best to walk along the paths).

It is necessary to minimize the area of open areas of the skin: wear socks, closed shoes, long pants (filling them in socks) and a shirt with long sleeves. It is better to wear light clothing, on which it is easier to notice a crawling mite. The treatment of the dog's fur and a special collar should be protected from the pet's ticks.

After trips to the countryside and walks in the forest or park, you must shake out your clothes and carefully examine yourself and your pets.

Useful Information -  What to do after a tick bite

[38], [39], [40], [41], [42]

Forecast

Babesiosis has many serious consequences that affect the prognosis of the outcome of the disease.

Asymptomatic or subclinical infection in people with strong immunity can latently persist for a long time.

The mild form (without acute symptoms) can last for two or more months after treatment. Disease in severe form does not exclude persistent relapses and can lead to death (5% of cases). But in the presence of a healthy spleen, such an outcome is rare, but the attachment of nonspecific pneumonia worsens the prospects for rapid recovery.

But babesiosis in a person with a remote spleen and is more severe, and more often have co-infections: in such cases, the mortality rate can reach 50%.

Timely and correct diagnosis is extremely important. At the end of 2012 in Kiev - after a tick bite and as a result of an initially incorrectly diagnosed diagnosis - a six-year-old child died from babesiosis.

[43], [44]