Babesiosis is a parasitic enzootic disease that is triggered by the infection of vertebrate erythrocytes with the protozoan Babesia species. Babesiosis is considered one of the most significant tick-borne infectious diseases in both domestic and wild mammals, and when it infects humans, it still poses substantial diagnostic and therapeutic challenges. This condition shares a plethora of clinical features with malaria (one of the most important parasitic diseases) and can be fatal – especially in the immunocompromised and the elderly.
The characteristic causative organism now identified as Babesia was discovered in 1888, by the researcher Babes, who was trying to find the pathogen that caused hemoglobinuria in cattle. Only five years after that, Kilbourne and Smith identified that ticks served as the arthropod vector for the species Babesia bigemina that was recognized to cause Texas cattle fever. This event is significant in that it established the first arthropod vector known to transmit an infectious microbe.
In humans, babesiosis was initially found in a splenectomized patient from Europe. However, most cases have been reported from the United States (especially in the northeastern states, as well as the upper midwestern parts). Most affected individuals have an intact spleen and are not known to have any immune deficiencies. Today sporadic cases are reported in Asia, Australia, South America and Europe.
Characteristics and Life Cycle of the Pathogen
Species of the genus Babesia are from the phylum Sporozoa that contains several important human pathogens, such as Plasmodium, Cryptosporidium and Toxoplasma. They also belong in the order Piroplasmida in the family Babesiidae (the other family is Theileriidae that lacks transovarial transmission which is a characteristic of Babesia).
The Babesia species infecting humans belong to four distinct clades: Babesia microti (a small Babesia) that itself exists as a species complex, other small Babesias (like Babesia duncani), small Babesia (including Babesia divergens) which are related to large Babesia, and finally, large Babesias infecting ungulates (including the KO1 strain). As phylogenetic analysis based on stringent molecular criteria develops further, new Babesia species will likely emerge with further revision of the taxonomy of this genus.
Apicomplexans (which includes the genus Babesia, as already mentioned) generally show at least three distinct stages of reproduction. These are gamogony (characterized by the formation and coalescence of gametes in the tick gut), sporogony (asexual reproduction that takes place in the salivary glands of the tick), and merogony (which is a term for asexual reproduction in the host).
A majority of human cases of babesiosis are the result of infection with Babesia microti species complex, but may also be caused by Babesia divergens (which infects cattle) or by Babesia odocoilei (which infect cervids). The primary tick vector of Babesia microti is Ixodes scapularis (commonly known as deer or blacklegged ticks), and its primary reservoir is the white-footed mouse (which may also harbor Borrela burgdorferi, a causative agent of Lyme disease).
During the life cycle of Ixodes scapularis, the three known active stages (i.e. larva, nymph and adult) require a meal of vertebrate blood to develop further to the next stage. The life cycle in the tick starts in the latter part of summer, with new larvae. These feed on blood from an infected mouse, which contains Babesia. The larvae then molt to become nymphs, while the parasites remain dormant.
Nymphs then transmit the parasite to the vertebrate hosts in the next season, which is usually in in late spring and early summer. Although all three developmental stages do feed on humans, the nymph is the most important vector, because of its minute size (akin to the size of a poppy seed) and summer activity. Therefore infected individuals may not recall a tick bite.
Once the parasite is in the human host, Babesias enter erythrocytes (red blood cells) where they undergo asexual replication (also known as budding). The multiplication of blood-stage parasites results in the clinical manifestations that arise after infections. It must be emphasized that humans are usually dead-end hosts.
Other potential ways of acquiring infection with Babesia parasites include receiving contaminated blood transfusion (as at the moment there are no tests licensed for donor screening), as well as transplacental/perinatal transmission from an infected mother to her baby. Babesia microti is responsible for most transfusion-mediated infections. About one in five of such cases end in fatality.
Reviewed by Liji Thomas, MD