 | This articlemay be too technical for most readers to understand. Pleasehelp improve it tomake it understandable to non-experts, without removing the technical details.(July 2020) (Learn how and when to remove this message) |
| Babesia | |
|---|---|
 | |
| Blood smear ofBabesia microti | |
Scientific classification | |
| Domain: | Eukaryota |
| Clade: | Diaphoretickes |
| Clade: | SAR |
| Clade: | Alveolata |
| Phylum: | Apicomplexa |
| Class: | Aconoidasida |
| Order: | Piroplasmida |
| Family: | Babesiidae |
| Genus: | Babesia Starcovici, 1893 |
| Species | |
B. microti ("Archaeopiroplasmida") group:[1][2] Western US ("Prototheilerids") group: | |
Babesia,[3][4] also calledNuttallia,[5] is anapicomplexan parasite that infects red blood cells and is transmitted byticks. Originally discovered by RomanianbacteriologistVictor Babeș in 1888; over 100 species ofBabesia have since been identified.[6][7]
Babesia comprises more than 100 species of tick-borne parasites that infect erythrocytes (red blood cells) in many vertebrate hosts.[8]
Babesia species infect livestock worldwide, wild and domestic vertebrate animals, and occasionally humans, where they cause the diseasebabesiosis.[9][7] In the United States,B. microti is the most common strain of the few that have been documented tocause disease in humans.
| Piroplasmida phylogeny (mtDNA)[2] |
Babesia is aprotozoan parasite found to infect vertebrate animals, mostly livestock mammals and birds, but also occasionally humans. Common names of the disease thatB. microti causes are Texas cattle fever, redwater fever, tick fever, and Nantucket fever.[7] The disease it causes in humans, babesiosis, is also called piroplasmosis.[9]
Babesia microti, however, is not part of the genusBabesia. Due to historical misclassifications, the protozoan has been labeled with many names, includingNuttallia,[5] and was renamed fromBabesia microti toTheileria microti based on evidence from 2006. Itsgenetic sequence, published in 2012, shows that the species belongs to neitherBabesia norTheileria, but instead to a separate genus.[10] Another "western" group is also separate from coreBabesia.[2]
The avianBabesia species are characterized as having ring andamoeboid forms, and fan-shaped or cruciform (cross-shaped) tetradschizonts. Developing parasites have only been reported in red blood cells.[11]
For centuries, the animal disease was known to be a serious illness for wild and domesticated animals, especially cattle. In 1888,Victor Babeș first identified the causative agent inRomania and believed it to be due to the bacterium he namedHaematococcus bovis. He documented the disease by describing signs of a severehemolytic illness seen uniquely in cattle and sheep.[7][12]
In 1893, AmericansTheobald Smith andFred Kilborne identified the parasite as the cause of Texas cattle fever, the same disease described by Babeș. They also identified thetick as the transmitting agent, a discovery which first introduced the concept ofarthropods functioning asdisease vectors.[13]
It was believed to be a disease that only affected nonhuman mammals, but in 1957, the first case ofbabesiosis was seen in a human.[9] The person had beensplenectomized, as were all people diagnosed with babesiosis until 1969, when the first case of babesiosis was diagnosed in a person who still had theirspleen. This proved the parasite was a potential pathogen in anyone.[14]
Babesia species showhost specificity, allowing many different subspecies ofBabesia to emerge, each infecting a different kind of vertebrate organism.[15] WhileB. bovis andBabesia bigemina prefer to infect cattle in tropical environments, they can infect other animals, such as thewhite-tailed deer.[15] Therefore, while the organism has the capacity to display host specificity, and thus increase transmission effectiveness, it can still infect a variety of hosts.[15] It achieves this through mutations and natural selection. In different environments, individual protozoa may develop mutations, which when they increase the protozoa'sfitness, allow the population to increase in number. This specificity explains whyBabesia species have such great genetic diversity.[15]
Babesia selfishly persists long-term in the host's system: The host gains no benefit from the parasite invasion and only suffers. This allows the parasite to exploit all resources offered by the host, to increase in number, and to increase the rate of transmission.[15] Too lethal an infection results in the host's death and the parasite is unable to spread, which is a loss from an evolutionary standpoint.[15] Different species ofBabesia are able to withstand the stress of the host's immune system. Infection typically stimulates theinnate immune system, and not thehumoral immune system.[15] This results in control of the infection, but also persistence and not clearance of the parasite.[15]
The genome ofB. microti has been sequenced and shows that the species does not belong to eitherBabesia orTheileria, but instead to a separate genus.[10] As of 2013[update], it is known that themitochondrial genome is linear like other sequencedApicomplexa mitochondrial genomes, although it was initially reported that it was circular.[16]
PartialRNA sequencing of caninepiroplasms has identified a number of additional species.[citation needed]
The lifecycle ofB. microti, which is typical of parasites in the genus, requires a biological stage in a rodent or deerhost. It is transmitted byticks of the familyIxodidae between these hosts. To begin, the tick as thedefinitive host becomes infected itself, as it takes upgametocytes when attached for a blood meal. It also introduces theBabesia into the intermediate host (e.g. cattle) when taking a blood meal. AsBabesia enter the animal'sred blood cells (erythrocytes), they are calledsporozoites. Within the red blood cell, the protozoa become cyclical and develop into atrophozoite ring. The trophozoites moult intomerozoites, which have a tetrad structure coined aMaltese-cross form.[17] Trophozoite and merozoite growth ruptures the host erythrocyte, leading to the release of vermicules, the infectious parasitic bodies, which rapidly spread the protozoa throughout the blood.[9] Rather than producing more and more trophozoites, some of the merozoites producegametocytes. Thegametes arefertilized in the tick gut and develop intosporozoites in the salivary glands. These are the sporozoites the infected tick introduces when it bites an intermediate host. Even as anincidental host, the phase changes that occur in the parasite are the same within humans as in the biological hosts.Babesia can be diagnosed at the trophozoite stage, and can also be transmitted from human to human through the tick vector, through blood transfusions, or through congenital transmission (an infected mother to her baby).[18][6]
Cold weather completely interrupts transmission.[19] The emergence of tick-borne diseases has been found to coincide with climate change.[20] The correlation between climate change and the incidence of tick-borne diseases is not known to be strong enough to count as a major factor.[20]
High humidity and rainfall accommodate ticks carryingBabesia.[21] This may explain whyB. bigemina infection in cattle in the hilly region ofMeghalaya has increased.[21] The lifespan and number of generations ofB. microplus correlate with increasing the longevity of larvae and the number of annual generations.[21] Warm, dry weather interferes with theBabesia lifecycle within the tick.[19] Warm, wet weather increases the intensity of infestation—the population is able to thrive due to the relatively fluid environment, making water and nutrients more accessible.[19]
Babesia species are spread through the saliva of a tick when it bites. Already at itsnymphal stage, a tick bites into the skin for a blood meal. The tick, if not removed, stays attached for three to four days, with longer periods of feeding associated with a higher probability of acquiring the parasite. The parasite can survive in the tick as it molts through its various developmental stages, resulting in all tick stages being potentially infectious. Some species ofBabesia can be transmitted from a female tick to its offspring before migrating to salivary glands for feeding.[9]B. microti, the most common species in humans, has not been shown totransmit transovarially.[6]
Ticks of domestic animals that transmitBabesia and cause much disease include the very widespread cattle ticks,Rhipicephalus (Boophilus)microplus, andR.(B.) decoloratus. These ticks have a strict one-host feeding cycle on cattle, so theBabesia can only be transmitted by the transovarial route.
In the Americas,Ixodes scapularis is the most common vector. This hard tick, commonly known as a deer tick, is also the vector for other tick-associated illnesses, such asLyme disease. Many species ofBabesia only infect nonhuman mammalian hosts, most commonly cattle, horses, and sheep.B. microti andB. divergens are the two main pathogenic species in humans. Their reservoirs are theorized to be thewhite-footed mouse (Peromyscus leucopus),voles from theMicrotus genus, and the white-tailed deer (Odocoileus virginianus).[22] These woodland species are hypothesized reservoirs because although they are known to harbor the disease, complete reservoir competence has not yet been shown.[23]
Most cases of transmission between humans are attributed to a tick vector. As of 2003, theCenters for Disease Control and Prevention (CDC) acknowledged more than 40 cases of babesiosis contracted from transfusions ofpacked red blood cells (PRBC), as well as two infections documented from organ transplantation. PRBC transfusions that cause infections were identified through testing the blood donor forB. microti antibodies.[24] The occurrence ofBabesia transmission through PRBC blood transfusions puts pressure on governmental organizations (such as the CDC) to heighten standard measures forscreening blood donations.[citation needed]
Transmission is also possible through congenital transmission (from an infected mother to her baby). As symptoms may not appear, many women may not be aware they are infected during pregnancy, so a measurement of congenital transmission rate is not known at this time.[18]
Currently, no vectors for avianBabesia have been identified, but they are assumed to be ticks.[11]Babesia species require competent vertebrate and invertebrate hosts to maintain transmission cycles.[25]
Of the species to infect humans,B. microti is most common in the Americas, whereasB. divergens is the predominant strain found in Europe.Endemic areas are regions of tick habitat, including the forest regions of the Northeastern United States and temperate regions of Europe.[26] Ixodidae, the tick vectors ofB. microti, also transmit the better-knownBorrelia burgdorferi, the causative agent of Lyme disease. For reasons that remain unclear, in areas endemic to both Lyme disease and babesiosis, Lyme disease transmission prevails and is more predominant in the region.[9] Prevalence of babesiosis in malaria-endemic regions remains unknown due to the likelihood of misdiagnosis as malaria.[27] As the disease results in a high number of asymptomatic individuals, many populations can possess highseroprevalence without much documentation of illness. For example, in Rhode Island and Nantucket, seroprevalence has been measured to be 20–25%.[9] Prevalence of babesiosis is mostly documented from May to September, when tick activity in endemic regions is high.[26]
The avianBabesia include 15 species, and fourBabesia species have been reported from sea hosts.B. poelea was described frombrown boobies (Sula leucogaster) on Sand Island, Johnston Atoll, Central Pacific.[28]B. poelea was reported from amasked booby (Sula dactylatra melanops) fromDesnoeufs Island,Amirantes,Seychelles.[29]B. peircei has been observed in two species of penguins, thejackass penguin (Sphenicus demersus) from South Africa and thelittle penguin (Eduyptula minor) from southern Australia.[30][31]B. bennetti was associated from theyellow-legged gull (Larus cachinnans) fromBenidorm Island off the coast of Spain.[31]B. uriae was found incommon murres in California.
About 40 cases of human babesiosis, caused by intraerythrocyticprotozoans (protozoa inside red blood cells) of the genusBabesia, were reported in Europe.[32]
Bovine babesiosis caused byB. bovis is an important constraint for cattle industries worldwide.[citation needed]
Signs of infection withB. microti usually arise one to eight weeks after a bite from an infectious tick.[26] Infections fromB. divergens have a shorter latent period, usually ranging from one to three weeks.[27] The severity ofB. microti infections varies. For 25% of cases in adults and 50% of cases in children, the disease is asymptomatic or mild with flu-like symptoms. In other cases, symptoms are characterized by irregular fevers, chills, headaches, general lethargy, pain, andmalaise.[9] In severe cases, effects of parasitic multiplication, symptoms such ashemolytic anemia,jaundice, shortness of breath, andhemoglobinuria have been documented.[7][27] Individuals with normal immune function and healthy spleens often recover without treatment.[9]
Splenectomized patients are more susceptible to contracting the disease and can die within five to eight days of symptom onset.[26] They have severe hemolytic anemia, and occasionalhepatomegaly has been documented.Parasitemia levels can reach up to 85% in patients without spleens, compared to 1–10% in individuals with spleens and effective immune systems.[27]
Complications includeacute respiratory failure,congestive heart failure, andkidney failure. Infections can be fatal in 5–10% of hospitalized patients, with increased risk of death in theimmunosuppressed, the elderly, and those also infected with Lyme disease.[27]B. divergens infections have a much higher fatality rate (42%) and present with more severe symptoms. Infected individuals experience hemoglobinuria followed by jaundice, a persistently high fever, chills, and sweats. If left untreated,B. divergens infections can develop intoshock-like symptoms withpulmonary edema and kidney failure.[27]
In birds
Thepathogenicity ofB. uriae for murres is currently unknown. Birds were found withlesions, anemia and respiratory difficulty, and tissues of avian hosts were affected.[11]B. peircei infections can cause mild anemia,leukocytosis, and impairment ofhepatic function inAfrican penguins.[33]
As a protozoan parasite, the most effective way to identifyBabesia infection is throughblood sample testing.
Babesia species enterred blood cells (erythrocytes) at the sporozoite stage. Within the red blood cell, the protozoa become cyclical and develop into a trophozoite ring. The trophozoites moult into merozoites, which have a tetrad structure coined aMaltese-cross form.[17] This tetrad morphology seen withGiemsa staining of a thinblood smear is unique toBabesia, and distinguishes it fromPlasmodium falciparum, a protozoan of similar morphology that causes malaria. Trophozoite and merozoite growth ruptures the host erythrocyte, leading to the release of vermicules, the infectious parasitic bodies, which rapidly spread the protozoa throughout the blood.[9]It is important to pay attention to particular morphologies ofBabesia in blood smears, because of its great similarity to the malarial parasitePlasmodium falciparum. This has resulted in many patients with babesiosis being misdiagnosed. The few distinguishing factors forBabesia include protozoa with varying shapes and sizes, the potential to containvacuoles, and the lack of pigment production. Trophozoites appearing in a tetrad formation within an erythrocyte are also indicative ofBabesia.[citation needed]
Despite much study of babesiosis and malaria, misdiagnosis with blood smear can be frequent and problematic. To supplement a blood smear, diagnoses should be made with anindirect fluorescent antibody (IFA) test, which has a much higherspecificity than stained blood smears, with antibody detection in 88-96% of infected patients.[6] Diagnostic measures through antibody testing are also particularly useful for identifyingserum prevalence in asymptomatic individuals. Due to the transmissibility ofBabesia through blood transfusions, IFA testing would be an effective means of screening for the disease in blood donations.
Historically, babesiosis diagnosis was carried out withxenodiagnosis inhamsters forB. microti and ingerbils forB. divergens.[9] This diagnostic technique has been abandoned in favor of faster diagnostic measures.
Several methods are available to manage and treat babesiosis in animals.[citation needed]
In humans, many spontaneously recover, having only experienced mild symptoms not diagnosed as the disease. This is almost always seen inB. microti infections, which are generally more common in the United States. ForB. divergens and more severeB. microti infections, the standard treatment historically for symptomatic individuals was oral or intravenousclindamycin with oralquinine.[6] With the results of research completed in 2000, however, treatment regimens have been increasingly leaning towards oralatovaquone with oralazithromycin. The latter are preferred, as they are equally effective in all but the most severe cases and exhibit fewer associatedadverse reactions.[34] In severe cases,blood exchange transfusions have been performed to lower the parasitic load in an individual.[9] Other measures include addressing and correcting abnormal clinical signs.[7]
In seabirds,primaquine has been used in a study to show effective treatment on infected hosts.[35] Treatment for babesiosis consisted of primaquine (1 mg/kg PO q24h for 10 days; primaquinephosphate 1.76%m/v in stabilized solution, Primaquin Solution, MedPet Ltd,Benrose, South Africa). After, treatment was followed by a phospholipid supplement (1 capsule/bird PO q24h for 12 days; deoiled, enrichedphospholipids from soybeans, 300 mg/capsule, Essentiale Extreme,Sanofi Aventis Ltd,Midrand, South Africa); as an attempt to mitigate potentialhepatotoxic effects of primaquine. To prevent transmission ofBabesia and other tickborne pathogens, all birds with visibleectoparasites are treated with pesticide powder (carbaryl 50 g/kg) upon admission, and the facilities are thoroughly cleaned on a daily basis.[35]
In 1906, efforts were made toeradicate the tick vector of bovine babesiosis in the United States. This eradication was recorded as being successfully completed.[7] The disease was eradicated from the United States by 1943, except for a permanent quarantine area along the Texas/Mexico border, where cattle fever ticks are still found.[36]
Effective control can be achieved byvaccination with liveattenuatedphenotypes of the parasite. The vaccines have a number of drawbacks, so better, safer vaccines are still being researched.[citation needed] In recent[when?] years, a number of parasite proteins withimmunogenic potential have been discovered. Throughpolymerase chain reaction,genetic sequencing, and bioinformatics analysis of the genes, a high degree of conservation (98–100%) was found among Brazilian isolates ofB. bovis and theT2Bo isolate. Thus, these genes are considered for inclusion in arecombinant cocktail vaccine for cattle babesiosis caused byB. bovis.[citation needed]
The most effective public health measure forBabesia is to avoid tick exposure. This can be through personal prevention such as avoiding tick-infested areas (especially during high tick season between May and September), remaining covered with light clothing, searching for ticks after being outdoors, and removing discovered ticks from the skin.[27] Other measures include applyingDEET, a common repellent that is effective against ticks and insects. (For people who react adversely to DEET, alternative insect repellents should be used.) On a state level, if health departments are particularly motivated, tick elimination is a possibility. In 1906, efforts were made to eradicate the tick vector of the bovine disease form of babesiosis in the United States. This eradication was recorded as being successfully completed four decades later.[7]
Complete eradication through vector control would be a long-term project, which would significantly reduce the prevalence of both babesiosis and Lyme disease, but as public health departments are often short on funding, preventive measures are more recommended.[citation needed]
Due to the relatively low prevalence of the human disease and the presence of several reservoirs, babesiosis has not been a candidate for vaccines. In regions whereticks of domestic animals are routinely controlled with chemicalacaricides to reduce incidence of infection withB. bovis andB. bigemina, the risk to humans from these parasites is reduced.
Figure 2. Panel of computer-generated electronic images of photomicrographs ofBabesia-infected erythrocytes on a Giemsa-stained smear of peripheral blood...
Authority control databases: National |
|---|