Babesiosis
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Babesiosis or piroplasmosis is a
malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...
-like
parasitic disease A parasitic disease, also known as parasitosis, is an infectious disease caused by parasites. Parasites are organisms which derive sustenance from its host while causing it harm. The study of parasites and parasitic diseases is known as parasitolo ...
caused by infection with a
eukaryotic Eukaryotes () are organisms whose Cell (biology), cells have a cell nucleus, nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the ...
parasite in the order Piroplasmida, typically a ''
Babesia ''Babesia'', also called ''Nuttallia'', is an apicomplexan parasite that infects red blood cells and is transmitted by ticks. Originally discovered by the Romanian bacteriologist Victor BabeÈ™ in 1888, over 100 species of ''Babesia'' have since ...
'' or '' Theileria'', in the phylum
Apicomplexa The Apicomplexa (also called Apicomplexia) are a large phylum of parasitic alveolates. Most of them possess a unique form of organelle that comprises a type of non-photosynthetic plastid called an apicoplast, and an apical complex structure. Th ...
. Human babesiosis transmission via tick bite is most common in the Northeastern and Midwestern United States and parts of Europe, and sporadic throughout the rest of the world. It occurs in warm weather. People can get infected with ''Babesia'' parasites by the bite of an infected tick, by getting a blood transfusion from an infected donor of blood products, or by congenital transmission (an infected mother to her baby). Ticks transmit the human strain of babesiosis, so it often presents with other tick-borne illnesses such as
Lyme disease Lyme disease, also known as Lyme borreliosis, is a vector-borne disease caused by the ''Borrelia'' bacterium, which is spread by ticks in the genus ''Ixodes''. The most common sign of infection is an expanding red rash, known as erythema migran ...
. After trypanosomes, ''Babesia'' is thought to be the second-most common blood
parasite Parasitism is a close relationship between species, where one organism, the parasite, lives on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The entomologist E. O. Wilson has ...
of mammals. They can have major adverse effects on the health of domestic animals in areas without severe winters. In cattle the disease is known as Texas cattle fever or redwater.


Signs and symptoms

Half of all children and a quarter of previously healthy adults with ''Babesia'' infection are asymptomatic. When people do develop symptoms, the most common are fever and
hemolytic anemia Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonly ...
, symptoms that are similar to those of malaria. People with symptoms usually become ill 1 to 4 weeks after the bite, or 1 to 9 weeks after transfusion of contaminated blood products. A person infected with babesiosis gradually develops malaise and fatigue, followed by a fever. Hemolytic anemia, in which red blood cells are destroyed and removed from the blood, also develops. Chills, sweats, and
thrombocytopenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients a ...
are also common symptoms. Symptoms may last from several days to several months. Less common symptoms and physical exam findings of mild-to-moderate babesiosis: In more severe cases, symptoms similar to malaria occur, with fevers up to 40.5 Â°C (105 Â°F), shaking chills, and severe anemia (hemolytic anemia). Organ failure may follow, including adult respiratory distress syndrome. Sepsis in people who have had a
splenectomy A splenectomy is the surgical procedure that partially or completely removes the spleen. The spleen is an important organ in regard to immunological function due to its ability to efficiently destroy encapsulated bacteria. Therefore, removal of ...
can occur rapidly, consistent with overwhelming post-splenectomy infection. Severe cases are also more likely to occur in the very young, very old, and persons with immunodeficiency, such as
HIV/AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...
patients. A reported increase in human babesiosis diagnoses in the 2000s is thought to be caused by more widespread testing and higher numbers of people with immunodeficiencies coming in contact with ticks, the disease vector. Little is known about the occurrence of ''Babesia'' species in malaria-
endemic Endemism is the state of a species being found in a single defined geographic location, such as an island, state, nation, country or other defined zone; organisms that are indigenous to a place are not endemic to it if they are also found else ...
areas, where ''Babesia'' can easily be misdiagnosed as ''
Plasmodium ''Plasmodium'' is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of ''Plasmodium'' species involve development in a blood-feeding insect host which then injects parasites into a ver ...
''. Human patients with repeat babesiosis infection may exhibit premunity.


Cause

''Babesia'' species are in the phylum
Apicomplexa The Apicomplexa (also called Apicomplexia) are a large phylum of parasitic alveolates. Most of them possess a unique form of organelle that comprises a type of non-photosynthetic plastid called an apicoplast, and an apical complex structure. Th ...
, which also has the protozoan parasites that cause
malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...
,
toxoplasmosis Toxoplasmosis is a parasitic disease caused by '' Toxoplasma gondii'', an apicomplexan. Infections with toxoplasmosis are associated with a variety of neuropsychiatric and behavioral conditions. Occasionally, people may have a few weeks or mont ...
, and
cryptosporidiosis Cryptosporidiosis, sometimes informally called crypto, is a parasitic disease caused by '' Cryptosporidium'', a genus of protozoan parasites in the phylum Apicomplexa. It affects the distal small intestine and can affect the respiratory tra ...
. Four clades of ''Babesia'' species infect humans. The main species in each clade are: # ''B. microti'' (<3 Âµm) # ''B. duncani'' # ''B. divergens'' (cattle parasite seen mostly in Europe) and ''B. venatorum'' (
roe deer The roe deer (''Capreolus capreolus''), also known as the roe, western roe deer, or European roe, is a species of deer. The male of the species is sometimes referred to as a roebuck. The roe is a small deer, reddish and grey-brown, and well-adapt ...
parasite, formerly called EU1), most closely related to the large ''Babesia'' clade # Large'' Babesia'' (>3 Âµm) mostly infects
ungulates Ungulates ( ) are members of the diverse clade Ungulata which primarily consists of large mammals with hooves. These include odd-toed ungulates such as horses, rhinoceroses, and tapirs; and even-toed ungulates such as cattle, pigs, giraffes, ca ...
, but also includes K01 strain (an isolated case observed in South Korea, see isolated cases)


Pathophysiology

''Babesia'' parasites reproduce in
red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
s, where they can be seen as cross-shaped inclusions (four merozoites asexually budding, but attached together forming a structure looking like a " Maltese cross") and cause hemolytic anemia, quite similar to malaria. Unlike the ''Plasmodium'' parasites that cause malaria, ''Babesia'' species lack an exoerythrocytic phase, so the liver is usually not affected. In nonhuman animals, '' Babesia canis rossi'', '' Babesia bigemina'', and ''
Babesia bovis ''Babesia bovis'' is an Apicomplexan single-celled parasite of cattle which occasionally infects humans. The disease it and other members of the genus ''Babesia'' cause is a hemolytic anemia known as babesiosis and colloquially called Texas catt ...
'' cause particularly severe forms of the disease, including a severe haemolytic anaemia, with positive erythrocyte-in-saline-agglutination test indicating an immune-mediated component to the haemolysis. Common sequelae include haemoglobinuria "red-water", disseminated intravascular coagulation, and "cerebral babesiosis" caused by sludging of erythrocytes in cerebral capillaries. In bovine species, the organism causes hemolytic anemia, so an infected animal shows pale mucous membranes initially. As the levels of bilirubin (a byproduct of red blood cell lysis) continue to increase, the visible mucous membranes become yellow in color (icterus) due to the failure of the liver to metabolize the excess bilirubin. Hemoglobinuria is seen due to excretion of red-blood-cell lysis byproducts via the kidneys. Fever of 40.5 Â°C (105 Â°F) develops due to release of inflammatory byproducts.


Diagnosis

Only specialized laboratories can adequately diagnose ''Babesia'' infection in humans, so ''Babesia'' infections are considered highly under-reported. It develops in patients who live in or travel to an endemic area or receive a contaminated
blood transfusion Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...
within the preceding 9 weeks, so this aspect of the medical history is vital. Babesiosis may be suspected when a person with such an exposure history develops persistent fevers and hemolytic anemia. The definitive diagnostic test is the identification of parasites on a Giemsa-stained thin-film blood smear. So-called "Maltese cross formations" on the blood film are diagnostic (
pathognomonic Pathognomonic (rare synonym ''pathognomic'') is a term, often used in medicine, that means "characteristic for a particular disease". A pathognomonic sign is a particular sign whose presence means that a particular disease is present beyond any doub ...
) of babesiosis, since they are not seen in malaria, the primary differential diagnosis. Careful examination of multiple smears may be necessary, since ''Babesia'' may infect less than 1% of circulating red blood cells, thus be easily overlooked. Serologic testing for antibodies against ''Babesia'' (both IgG and
IgM Immunoglobulin M (IgM) is one of several isotypes of antibody (also known as immunoglobulin) that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antig ...
) can detect low-level infection in cases with a high clinical suspicion, but negative blood film examinations. Serology is also useful for differentiating babesiosis from malaria in cases where people are at risk for both infections. Since detectable antibody responses require about a week after infection to develop, serologic testing may be falsely negative early in the disease course. A
polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) ...
(PCR) test has been developed for the detection of ''Babesia'' from the peripheral blood. PCR may be at least as sensitive and specific as blood-film examination in diagnosing babesiosis, though it is also significantly more expensive. Most often, PCR testing is used in conjunction with blood film examination and possibly serologic testing. Other laboratory findings include decreased numbers of red blood cells and platelets on
complete blood count A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cells and pl ...
. In animals, babesiosis is suspected by observation of clinical signs (hemoglobinuria and anemia) in animals in endemic areas. Diagnosis is confirmed by observation of merozoites on thin film blood smear examined at maximum magnification under oil using Romonovski stains (methylene blue and eosin). This is a routine part of the veterinary examination of dogs and ruminants in regions where babesiosis is endemic. ''Babesia canis'' and ''B. bigemina'' are "large ''Babesia'' species" that form paired merozoites in the erythrocytes, commonly described as resembling "two pears hanging together", rather than the "Maltese cross" of the "small ''Babesia'' species". Their merozoites are around twice the size of small ones. Cerebral babesiosis is suspected ''in vivo'' when neurological signs (often severe) are seen in cattle that are positive for ''B. bovis'' on blood smear, but this has yet to be proven scientifically. Outspoken red discoloration of the grey matter ''post mortem'' further strengthens suspicion of cerebral babesiosis. Diagnosis is confirmed ''post mortem'' by observation of ''Babesia''-infected erythrocytes sludged in the cerebral cortical capillaries in a brain smear.


Treatment

Treatment of asymptomatic carriers should be considered if parasites are still detected after 3 months. In mild-to-moderate babesiosis, the treatment of choice is a combination of atovaquone and azithromycin. This regimen is preferred to clindamycin and
quinine Quinine is a medication used to treat malaria and babesiosis. This includes the treatment of malaria due to '' Plasmodium falciparum'' that is resistant to chloroquine when artesunate is not available. While sometimes used for nocturnal le ...
because it has fewer side effects. The standard course is 7 to 10 days, but this is extended to at least 6 weeks in people with
relapsing In internal medicine, relapse or recidivism is a recurrence of a past (typically medical) condition. For example, multiple sclerosis and malaria often exhibit peaks of activity and sometimes very long periods of dormancy, followed by relapse or ...
disease. Even mild cases are recommended to be treated to decrease the chance of inadvertently transmitting the infection by donating blood. In severe babesiosis, the combination of clindamycin and quinine is preferred. In life-threatening cases, exchange transfusion is performed. In this procedure, the infected red blood cells are removed and replaced with uninfected ones. Imizol is a drug used for treatment of babesiosis in dogs. Extracts of the poisonous,
bulbous In botany, a bulb is structurally a short stem with fleshy leaves or leaf basesBell, A.D. 1997. ''Plant form: an illustrated guide to flowering plant morphology''. Oxford University Press, Oxford, U.K. that function as food storage organs durin ...
plant ''
Boophone disticha ''Boophone'' is a small genus of herbaceous, perennial and bulbous plants in the Amaryllis family (Amaryllidaceae, subfamily Amaryllidoideae.) It consists of two confirmed species distributed across South Africa to Kenya and Uganda. It is closel ...
'' are used in the
folk medicine Traditional medicine (also known as indigenous medicine or folk medicine) comprises medical aspects of traditional knowledge that developed over generations within the folk beliefs of various societies, including indigenous peoples, before the ...
of
South Africa South Africa, officially the Republic of South Africa (RSA), is the Southern Africa, southernmost country in Africa. It is bounded to the south by of coastline that stretch along the Atlantic Ocean, South Atlantic and Indian Oceans; to the ...
to treat
equine Equinae is a subfamily of the family Equidae, which have lived worldwide (except Indonesia and Australia) from the Hemingfordian stage of the Early Miocene (16 million years ago) onwards. They are thought to be a monophyletic grouping.B. J. Ma ...
babesiosis. ''B. disticha'' is a member of the daffodil family Amaryllidaceae and has also been used in preparations employed as
arrow poisons Arrow poisons are used to poison arrow heads or darts for the purposes of hunting and warfare. They have been used by indigenous peoples worldwide and are still in use in areas of South America, Africa and Asia. Notable examples are the poisons se ...
, hallucinogens, and in
embalming Embalming is the art and science of preserving human remains by treating them (in its modern form with chemicals) to forestall decomposition. This is usually done to make the deceased suitable for public or private viewing as part of the funeral ...
. The plant is rich in alkaloids, some of which display an action similar to that of scopolamine.


Epidemiology

Babesiosis is a vector-borne illness usually transmitted by ''
Ixodes scapularis ''Ixodes scapularis'' is commonly known as the deer tick or black-legged tick (although some people reserve the latter term for '' Ixodes pacificus'', which is found on the west coast of the US), and in some parts of the US as the bear tick. It w ...
''
tick Ticks (order Ixodida) are parasitic arachnids that are part of the mite superorder Parasitiformes. Adult ticks are approximately 3 to 5 mm in length depending on age, sex, species, and "fullness". Ticks are external parasites, living by ...
s. ''B. microti'' uses the same tick vector as Lyme disease, and may occur in conjunction with Lyme. The organism can also be transmitted by blood transfusion. Ticks of domestic animals, especially ''Rhipicephalus (Boophilus) microplus'' and ''R. (B.) decoloratus'' transmit several species of ''Babesia'' to livestock, causing considerable economic losses to farmers in tropical and subtropical regions. In the United States, the majority of babesiosis cases are caused by ''B. microti'', and occur in the Northeast and northern Midwest from May through October. Areas with especially high rates include eastern Long Island, Fire Island,
Nantucket Island Nantucket () is an island about south from Cape Cod. Together with the small islands of Tuckernuck and Muskeget, it constitutes the Town and County of Nantucket, a combined county/town government that is part of the U.S. state of Massachuse ...
, and Martha's Vineyard. The
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
now requires state health departments to report infections usin
Form OMB No. 0920-0728
In 2014, Rhode Island had an incidence of 16.3 reported infections per 100,000 people. In Europe, ''B. divergens'' is the primary cause of infectious babesiosis and is transmitted by ''I. ricinus''. Babesiosis has emerged in Lower Hudson Valley, New York, since 2001. In Australia, one locally-acquired case of B. microti has been reported, which was fatal. A subsequent investigation found no additional evidence of human Babesiosis in over 7000 patient samples, leading the authors to conclude that Babesiosis was rare in Australia. A similar disease in cattle, commonly known as tick fever, is spread by ''
Babesia bovis ''Babesia bovis'' is an Apicomplexan single-celled parasite of cattle which occasionally infects humans. The disease it and other members of the genus ''Babesia'' cause is a hemolytic anemia known as babesiosis and colloquially called Texas catt ...
'' and ''B. bigemina'' in the introduced cattle tick '' Rhipicephalus microplus''. This disease is found in eastern and northern Australia.


Isolated cases

A table of isolated cases of babesiosis, which may be underestimated given how widely distributed the tick vectors are in temperate latitudes.


History

The disease is named for the genus of the causative organism, which was named after the Romanian
bacteriologist A bacteriologist is a microbiologist, or similarly trained professional, in bacteriology -- a subdivision of microbiology that studies bacteria, typically pathogenic ones. Bacteriologists are interested in studying and learning about bacteria, ...
Victor BabeÈ™. In 1888, Victor BabeÈ™ identified the microorganisms in red blood cells as the cause of febrile
hemoglobinuria Hemoglobinuria is a condition in which the oxygen transport protein hemoglobin is found in abnormally high concentrations in the urine. The condition is caused by excessive intravascular hemolysis, in which large numbers of red blood cells (RBCs) ...
in cattle. In 1893,
Theobald Smith Theobald Smith FRS(For) HFRSE (July 31, 1859 – December 10, 1934) was a pioneering epidemiologist, bacteriologist, pathologist and professor. Smith is widely considered to be America's first internationally-significant medical research scienti ...
and Frederick Kilborne discovered that a tick was the vector for transmission in Texas cattle. The agent was ''B. bigemina''. This was the first demonstration that an
arthropod Arthropods (, (gen. ποδός)) are invertebrate animals with an exoskeleton, a segmented body, and paired jointed appendages. Arthropods form the phylum Arthropoda. They are distinguished by their jointed limbs and cuticle made of chiti ...
could act as a disease vector to transmit an infectious agent to a vertebrate host. In 1957, the first human case was documented in a splenectomized Croatian herdsman. The agent was ''B. divergens''. In 1969, the first case was reported in an immunocompetent individual on Nantucket Island. The agent was ''B. microti'', and the vector was the tick '' I. scapularis''.
Equine Equinae is a subfamily of the family Equidae, which have lived worldwide (except Indonesia and Australia) from the Hemingfordian stage of the Early Miocene (16 million years ago) onwards. They are thought to be a monophyletic grouping.B. J. Ma ...
babesiosis (caused by the protozoan '' Theileria equi'') is also known as piroplasmosis (from the
Latin Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through the power of the ...
''piro'', meaning
pear Pears are fruits produced and consumed around the world, growing on a tree and harvested in the Northern Hemisphere in late summer into October. The pear tree and shrub are a species of genus ''Pyrus'' , in the family Rosaceae, bearing the po ...
+
Greek Greek may refer to: Greece Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group. *Greek language, a branch of the Indo-European language family. **Proto-Greek language, the assumed last common ancestor ...
''plasma'', a thing formed).


Other animals

Veterinary treatment of babesiosis does not normally use antibiotics. In livestock and animals, diminazen (Berenil), imidocarb, or trypan blue would be the drugs of choice for treatment of ''B. canis rossi'' (dogs in Africa), ''B. bovis'', and ''B. bigemina'' (cattle in Southern Africa). In acute cases in cattle, blood transfusion may be carried out. A vaccine is effective against ''B. canis canis'' (dogs in the Mediterranean region), but is ineffective against ''B. c. rossi''. ''B. imitans'' causes a mild form of the disease that frequently resolves without treatment (dogs in Southeast Asia).


References


External links

*
Public domain The public domain (PD) consists of all the creative work to which no exclusive intellectual property rights apply. Those rights may have expired, been forfeited, expressly waived, or may be inapplicable. Because those rights have expired, ...
source from which the first version of this article was derived. * *
"Babesiosis: Overview"
€”''The Merck Veterinary Manual''
Current status of Equine piroplasmosis worldwide
at OIE. WAHID Interface—OIE World Animal Health Information Database
Disease card
€”OIE {{Flea-borne diseases Babesia Protozoal diseases Tick-borne diseases Zoonoses