Pathogenesis and Clinical Presentation of Babesiosis

Babesiosis is an illness similar to malaria, that is caused by the intraerythrocytic parasitic species from the genus Babesia, transmitted by ticks. In the last fifty years the epidemiology of babesiosis in humans has shifted from a handful of isolated cases to the established endemic disease in Europe and northeastern and midwestern United States.

The first human case of babesiosis was described in 1957 near Zagreb, a capital of Croatia. The affected individual was a young farmer without a spleen who had been taking care of cattle on tick-infested pastures. He subsequently presented with anemia, hemoglobinuria and fever, and succumbed to renal insufficiency in the second week of the illness. Although the causative agent was initially reported as Babesia bovis, it was most likely Babesia divergens (also a pathogen of cattle).

Pathogenesis of Babesiosis

As the parasite infects red blood cells in the human body, erythrocyte lysis occurs, which is associated with most of the clinical manifestations and complications of babesiosis – including hemolytic anemia, jaundice as a result of unconjugated hyperbilirubinemia, hemoglobinemia, hemoglobinuria, as well as renal failure due to acute tubular necrosis.

Proinflammatory cytokine release may be instigated when immune cells come into contact with the glycosylphosphatidylinositol anchors of babesial proteins, expressed either at the surface of the pathogen or the surface of infected erythrocytes. These cytokines thereupon prompt the production of downstream mediators (such as nitric oxide) which may destroy parasites, but can also be responsible for cellular damage when excessively produced.

The development of immunity to Babesia parasites in humans depends upon cellular and humoral factors, although the bulk of the evidence shows that the latter is of limited significance. The role of antibodies is restricted to a period when the parasites have found their way into the bloodstream, but not have yet become intracellular.

Therefore T cells are considered pivotal in the development of resistance to Babesia parasites, with CD4+ T helper cell subpopulation as the main player. Moreover, non-specific responses via macrophages and natural killer cells are also noteworthy in resistance to babesial infection.

Clinical Features of the Disease

In Europe, a majority of cases of human babesiosis are a result of infection by Babesia divergens, whereas in the US the main pathogenic species is Babesia microti. The severity of infection can be highly variable, and is primarily determined by the immune status of the infected host. Various clinical syndromes have been described – from completely asymptomatic infections, through mild or moderate viral-like illnesses, to severe presentations with a fulminant course that may result in death.

Most human infections with Babesia microti are subclinical. When clinical illness arises, the incubation period is between one and three weeks, although it can be up to six months (but typically one to nine weeks) when acquired through blood transfusions. The disease usually appears gradually, with fatigue and anorexia as dominant signs, as well as fever and generalized myalgia.

In cases of Babesia divergens infection the incubation period varies from one to four weeks. Initially the patient may feel slightly unwell, but at the time of the diagnosis the condition is more severe and characterized by fever, anemia, jaundice, prostration, nausea, vomiting and myalgia. Furthermore, hepatomegaly, pulmonary edema and oliguric renal failure may also occur.

Although animal studies suggest that Babeisa duncani, a rare species responsible for only several human infections recorded thus far, is more pathogenic than Babesia microti, its sparse occurrence does not allow any firm conclusions at this moment. Of the nine reported human cases there was one fatal account, one renal insufficiency and pulmonary edema, and the remainder had a somewhat mild clinical course or were without any symptoms.


  6. Chiodini PL. Babesiois. In: Farrar J, Hotez P, Junghanss T, Kang G, Lalloo D, White NJ, editors. Manson's Tropical Diseases, 23rd Edition. Elsevier Health Sciences, 2014; pp. 601-605.

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Last Updated: Feb 26, 2019

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university – University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.

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