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''Babesia'', also called ''Nuttallia'', is an
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. T ...
n parasite that infects red blood cells and is transmitted by
ticks 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 ...
. Originally discovered by the Romanian
bacteriologist A bacteriologist is a microbiologist, or similarly trained professional, in bacteriology -- a subdivision of microbiology that studies bacteria, typically Pathogenic bacteria, pathogenic ones. Bacteriologists are interested in studying and learnin ...
Victor Babeș Victor Babeș (; 28 July 1854 in Vienna – 19 October 1926 in Bucharest) was a Romanian physician, bacteriologist, academician and professor. One of the founders of modern microbiology, Victor Babeș is author of one of the first treatises of ba ...
in 1888, over 100 species of ''Babesia'' have since been identified. ''Babesia'' comprises more than 100 species of tick-borne parasites that infect erythrocytes (red blood cells) in many vertebrate hosts. ''Babesia'' species infect livestock worldwide, wild and domestic vertebrate animals, and occasionally humans, where they cause the disease
babesiosis Babesiosis or piroplasmosis is a malaria-like parasitic disease caused by infection with a eukaryotic parasite in the order Piroplasmida, typically a ''Babesia'' or ''Theileria'', in the phylum Apicomplexa. Human babesiosis transmission via ti ...
. In the United States, ''B. microti'' is the most common strain of the few which have been documented to cause disease in humans.


Classification

''Babesia'' is a
protozoan Protozoa (singular: protozoan or protozoon; alternative plural: protozoans) are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris. Histo ...
parasite found to infect vertebrate animals, mostly livestock mammals and birds, but also occasionally humans. Common names of the disease that ''Babesia microti'' causes are Texas cattle fever, redwater fever, tick fever, and Nantucket fever. The disease it causes in humans, babesiosis, is also called piroplasmosis. ''Babesia microti'', however, is not part of the genus ''Babesia''. Due to historical misclassifications, the protozoan has been labeled with many names, including ''Nuttallia,'' and was renamed from ''Babesia microti'' to ''Theileria microti'' based on evidence from 2006. Its
genetic sequence A nucleic acid sequence is a succession of bases signified by a series of a set of five different letters that indicate the order of nucleotides forming alleles within a DNA (using GACT) or RNA (GACU) molecule. By convention, sequences are usua ...
, published in 2012, shows that the species belongs to neither ''Babesia'' nor ''Theileria,'' but instead to a separate genus. Another "western" group is also separate from core ''Babesia''. The avian ''Babesia'' species are characterized as having ring and
amoeboid An amoeba (; less commonly spelled ameba or amœba; plural ''am(o)ebas'' or ''am(o)ebae'' ), often called an amoeboid, is a type of cell or unicellular organism with the ability to alter its shape, primarily by extending and retracting pseudopo ...
forms, and fan-shaped or cruciform (cross-shaped) tetrad
schizont Apicomplexans, a group of intracellular parasites, have life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an apicomplexan organism is ...
s. Developing parasites have only been reported in red blood cells.


History

For centuries, the animal disease was known to be a serious illness for wild and domesticated animals, especially cattle. In 1888,
Victor Babeș Victor Babeș (; 28 July 1854 in Vienna – 19 October 1926 in Bucharest) was a Romanian physician, bacteriologist, academician and professor. One of the founders of modern microbiology, Victor Babeș is author of one of the first treatises of ba ...
first identified the causative agent in
Romania Romania ( ; ro, România ) is a country located at the crossroads of Central Europe, Central, Eastern Europe, Eastern, and Southeast Europe, Southeastern Europe. It borders Bulgaria to the south, Ukraine to the north, Hungary to the west, S ...
and believed it to be due to the bacterium he named ''Haematococcus bovis''. He documented the disease by describing signs of a severe
hemolytic Hemolysis or haemolysis (), also known by several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may occur in vivo o ...
illness seen uniquely in cattle and sheep. In 1893, Americans
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
Fred Kilborne Fred may refer to: People * Fred (name), including a list of people and characters with the name Mononym * Fred (cartoonist) (1931–2013), pen name of Fred Othon Aristidès, French * Fred (footballer, born 1949) (1949–2022), Frederico Rodr ...
identified the parasite as the cause of Texas cattle fever, the same disease described by Babeș. They also identified the
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 ...
as the transmitting agent, a discovery which first introduced the concept of
arthropod Arthropods (, (gen. ποδός)) are invertebrate animals with an exoskeleton, a Segmentation (biology), segmented body, and paired jointed appendages. Arthropods form the phylum Arthropoda. They are distinguished by their jointed limbs and Arth ...
s functioning as
disease vector In epidemiology, a disease vector is any living agent that carries and transmits an infectious pathogen to another living organism; agents regarded as vectors are organisms, such as parasites or microbes. The first major discovery of a disease vec ...
s. It was believed to be a disease that only affected nonhuman mammals, but in 1957, the first case of
babesiosis Babesiosis or piroplasmosis is a malaria-like parasitic disease caused by infection with a eukaryotic parasite in the order Piroplasmida, typically a ''Babesia'' or ''Theileria'', in the phylum Apicomplexa. Human babesiosis transmission via ti ...
was seen in a human. The person had been splenectomized, as were all people diagnosed with babesiosis until 1969, when the first case of babesiosis was diagnosed in a person who still had their
spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .
. This proved the parasite was a potential pathogen in anyone.


Genetics

''Babesia'' show
host specificity In biology and medicine, a host is a larger organism that harbours a smaller organism; whether a parasitic, a mutualistic, or a commensalist ''guest'' (symbiont). The guest is typically provided with nourishment and shelter. Examples include a ...
, allowing many different subspecies of ''Babesia'' to emerge, each infecting a different kind of vertebrate organism. While '' B. bovis'' and '' Babesia bigemina'' prefer to infect cattle in tropical environments, they can infect other animals, such as the
white-tailed deer The white-tailed deer (''Odocoileus virginianus''), also known as the whitetail or Virginia deer, is a medium-sized deer native to North America, Central America, and South America as far south as Peru and Bolivia. It has also been introduced t ...
. Therefore, while the organism has the capacity to display host specificity, and thus increase transmission effectiveness, it can still infect a variety of hosts. It achieves this through mutations and natural selection. In different environments, individual protozoa may develop mutations which, when they increase the protozoa's fitness, allow the population to increase their numbers. This specificity explains why ''Babesia'' have such great genetic diversity. ''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. 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. Different species of ''Babesia'' are able to withstand the stress of the host's immune system. Infection typically stimulates the
innate immune system The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...
, and not the humoral immune system. This results in control of the infection, but also persistence and not clearance of the parasite.


Genomics

The genome of ''B. microti'' has been sequenced and shows that the species does not belong to either ''Babesia'' or ''Theileria,'' but instead to a separate genus. , it is known that the
mitochondrial genome Mitochondrial DNA (mtDNA or mDNA) is the DNA located in mitochondria, cellular organelles within eukaryotic cells that convert chemical energy from food into a form that cells can use, such as adenosine triphosphate (ATP). Mitochondrial D ...
is linear like other sequenced
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. T ...
mitochondrial genomes, although it was initially reported that it was circular. Partial
RNA sequencing RNA-Seq (named as an abbreviation of RNA sequencing) is a sequencing technique which uses next-generation sequencing (NGS) to reveal the presence and quantity of RNA in a biological sample at a given moment, analyzing the continuously changing c ...
of canine
piroplasms Piroplasmida is an order of parasites in the phylum Apicomplexa. They divide by binary fission and as sporozoan parasites they possess sexual and asexual phases (sexual reproduction occurs in the tick gut). They include the tick parasites ''Bab ...
has identified a number of additional species.


Life cycle

The life cycle of ''B. microti'', which is typical of parasites in the genus, requires a biological stage in a rodent or deer
host A host is a person responsible for guests at an event or for providing hospitality during it. Host may also refer to: Places * Host, Pennsylvania, a village in Berks County People *Jim Host (born 1937), American businessman * Michel Host ...
. It is transmitted by
ticks 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 ...
of the family
Ixodidae The Ixodidae are the family of hard ticks or scale ticks, one of the three families of ticks, consisting of over 700 species. They are known as 'hard ticks' because they have a scutum or hard shield, which the other major family of ticks, the 'sof ...
between these hosts. To begin, the tick as the
definitive host In biology and medicine, a host is a larger organism that harbours a smaller organism; whether a parasitic, a mutualistic, or a commensalist ''guest'' (symbiont). The guest is typically provided with nourishment and shelter. Examples include a ...
becomes infected itself, as it takes up
gametocyte A gametocyte is a eukaryotic germ cell that divides by mitosis into other gametocytes or by meiosis into gametids during gametogenesis. Male gametocytes are called ''spermatocytes'', and female gametocytes are called ''oocytes''. Development ...
s when attached for a blood meal. It also introduces the Babesia into the intermediate host (e.g. cattle) when taking a blood meal. As ''Babesia'' enter the animal's
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 (erythrocytes), they are called
sporozoites Apicomplexans, a group of intracellular parasites, have life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an apicomplexan organism i ...
. Within the red blood cell, the protozoa become cyclical and develop into a
trophozoite A trophozoite (G. ''trope'', nourishment + ''zoon'', animal) is the activated, feeding stage in the life cycle of certain protozoa such as malaria-causing ''Plasmodium falciparum'' and those of the '' Giardia'' group. (The complement of the trophozo ...
ring. The trophozoites moult into
merozoites Apicomplexans, a group of intracellular parasites, have life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an apicomplexan organism is ...
, which have a tetrad structure coined a Maltese-cross form. 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. Rather than producing more and more trophozoites, some of the merozoites produce
gametocytes A gametocyte is a eukaryotic germ cell that divides by mitosis into other gametocytes or by meiosis into gametids during gametogenesis. Male gametocytes are called ''spermatocytes'', and female gametocytes are called ''oocytes''. Development ...
. The
gametes A gamete (; , ultimately ) is a haploid cell that fuses with another haploid cell during fertilization in organisms that reproduce sexually. Gametes are an organism's reproductive cells, also referred to as sex cells. In species that produce t ...
are
fertilized Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
in the tick gut and develop into
sporozoites Apicomplexans, a group of intracellular parasites, have life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an apicomplexan organism i ...
in the salivary glands. These are the sporozoites the infected tick introduces when it bites an intermediate host. Even as an incidental host, the phase changes which 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).


Seasonality


Temperature

Cold weather completely interrupts transmission. The emergence of tick-borne diseases has been found to coincide with climate change. 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.


Humidity

High humidity and rainfall accommodate ticks carrying ''Babesia''. This may explain why ''B. bigemina'' infection in cattle in the hilly region of
Meghalaya Meghalaya (, or , meaning "abode of clouds"; from Sanskrit , "cloud" + , "abode") is a states and union territories of India, state in northeastern India. Meghalaya was formed on 21 January 1972 by carving out two districts from the state of As ...
has increased. The life span and number of generations of ''Babesia microplus'' correlate with increasing the longevity of larvae and the number of annual generations. Warm, dry weather interferes with the Babesia life cycle within the tick. 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.


Transmission

''Babesia'' species are spread through the saliva of a tick when it bites. Already at its nymphal 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 of ''Babesia'' can be transmitted from a female tick to its offspring before migrating to salivary glands for feeding. ''B. microti'', the most common species in humans, has not been shown to transmit transovarially.
Ticks of domestic animals Ticks of domestic animals directly cause poor health and loss of production to their hosts. Ticks also transmit numerous kinds of viruses, bacteria, and protozoa between domestic animals. These microbes cause diseases which can be severely debilita ...
that transmit ''Babesia'' and cause much disease include the very widespread cattle ticks, ''Rhipicephalus (Boophilus) microplus'', and ''R.(B.) decoloratus''. These ticks have a strict one-host feeding cycle on cattle, so the ''Babesia'' can only be transmitted by the transovarial route. In the Americas, ''
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 wa ...
'' is the most common vector. This hard tick, commonly known as a deer tick, is also the vector for other tick-associated 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 ...
. Many species of ''Babesia'' only infect nonhuman mammalian hosts, most commonly cattle, horses, and sheep. ''B. microti'' and ''B. divergens'' are the two main pathogenic species in humans. Their reservoirs are theorized to be the
white-footed mouse The white-footed mouse (''Peromyscus leucopus'') is a rodent native to North America from Ontario, Quebec, Labrador, and the Maritime Provinces (excluding the island of Newfoundland) to the southwestern United States and Mexico. In the Maritimes, ...
(''Peromyscus leucopus''), voles from the Microtus genus, and the white-tailed deer (''Odocoileus virginianus''). These woodland species are hypothesized reservoirs because although they are known to harbor the disease, complete reservoir competence has not yet been shown. Most cases of transmission between humans are attributed to a tick vector. As of 2003, 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 ...
(CDC) acknowledged more than 40 cases of babesiosis contracted from transfusions of
packed red blood cells Packed red blood cells, also known as packed cells, are red blood cells that have been separated for blood transfusion. The packed cells are typically used in anemia that is either causing symptoms or when the hemoglobin is less than usually 70 ...
(PRBC), as well as two infections documented from organ transplantation. PRBC transfusions that cause infections were identified through testing the blood donor for ''B. microti'' antibodies. The occurrence of ''Babesia'' transmission through PRBC blood transfusions puts pressure on governmental organizations (such as the CDC) to heighten standard measures for screening blood donations. 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, and therefore a measurement of congenital transmission rate is not known at this time. Currently, no vectors for avian ''Babesia'' have been identified, but they are assumed to be ticks. ''Babesia'' species require competent vertebrate and invertebrate hosts to maintain transmission cycles.


Epidemiology

Of the species to infect humans, ''B. microti'' is most common in the Americas, whereas ''B. divergens'' is the predominant strain found in Europe.
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 elsew ...
areas are regions of tick habitat, including the forest regions of the northeastern United States and temperate regions of Europe. Ixodidae, the tick vectors of ''B. microti'', also transmit the better-known ''
Borrelia burgdorferi ''Borrelia burgdorferi'' is a bacterial species of the spirochete class in the genus ''Borrelia'', and is one of the causative agents of Lyme disease in humans. Along with a few similar genospecies, some of which also cause Lyme disease, it make ...
'', 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. Prevalence of babesiosis in malaria-endemic regions remains unknown due to the likelihood of misdiagnosis as malaria. As the disease results in a high number of asymptomatic individuals, many populations can possess high
seroprevalence Seroprevalence is the number of persons in a population who test positive for a specific disease based on serology (blood serum) specimens; often presented as a percent of the total specimens tested or as a proportion per 100,000 persons tested. As ...
without much documentation of illness. For example, in Rhode Island and Nantucket, seroprevalence has been measured to be 20–25%. Prevalence of babesiosis is mostly documented during the months of May to September, when tick activity in endemic regions is high. There are 15 avian species of Babesia, and four Babesia have been reported from sea hosts. Babesia poelea was described from
brown boobies The brown booby (''Sula leucogaster'') is a large seabird of the booby family Sulidae, of which it is perhaps the most common and widespread species. It has a pantropical range, which overlaps with that of other booby species. The gregarious brow ...
(''Sula leucogaster'') on Sand Island, Johnston Atoll, Central Pacific. ''B. poelea'' was reported from a
masked booby The masked booby (''Sula dactylatra''), also called the masked gannet or the blue-faced booby, is a large seabird of the booby and gannet family, Sulidae. First described by the French naturalist René-Primevère Lesson in 1831, the masked bo ...
(''Sula dactylatra melanops'') from
Desnoeufs Island Desnœufs Island is an island in Seychelles, lying at the southern edge of the Amirantes group, in the Outer Islands, with a distance of 321 km south of Victoria, Seychelles. History The origin of the name seems to be its French meaning, ...
, Amirantes,
Seychelles Seychelles (, ; ), officially the Republic of Seychelles (french: link=no, République des Seychelles; Creole: ''La Repiblik Sesel''), is an archipelagic state consisting of 115 islands in the Indian Ocean. Its capital and largest city, V ...
. ''Babesia peircei'' has been observed in 2 species of penguins, the
jackass penguin The African penguin (''Spheniscus demersus''), also known as Cape penguin or South African penguin, is a species of penguin confined to southern African waters. Like all extant penguins, it is flightless, with a streamlined body and wings stiff ...
(''Sphenicus demersus'') from South Africa and the
little penguin The little penguin (''Eudyptula minor'') is a species of penguin from New Zealand. They are commonly known as little blue penguins or blue penguins owing to their slate-blue plumage and are also known by their Māori name . The Australian lit ...
(''Eduyptula minor'') from southern Australia. ''Babesia bennetti'' was associated from the
yellow-legged gull The yellow-legged gull (''Larus michahellis'') is a large gull found in Europe, the Middle East and North Africa, which has only recently achieved wide recognition as a distinct species. It was formerly treated as a subspecies of either the Casp ...
(''Larus cachinnans'') from Benidorm Island off the coast of Spain. ''Babesia uriae'' was found in
common murre The common murre or common guillemot (''Uria aalge'') is a large auk. It has a circumpolar distribution, occurring in low-Arctic and boreal waters in the North Atlantic and North Pacific. It spends most of its time at sea, only coming to land to ...
s in California. About 40 cases of human babesiosis, caused by intraerythrocytic
protozoans Protozoa (singular: protozoan or protozoon; alternative plural: protozoans) are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris. Histor ...
(protozoa inside red blood cells) of the genus ''Babesia'', were reported in Europe.


Disease

Bovine babesiosis caused by '' B. bovis'' is an important constraint for cattle industries worldwide.


In humans

Signs of infection with ''B. microti'' usually arise one to eight weeks after a bite from an infectious tick. Infections from ''B. divergens'' have a shorter latent period, usually ranging from one to three weeks. The severity of ''B. 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, and
malaise As a medical term, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. The word has existed in French since at least the 12th century. The term is often used ...
. In severe cases effects of parasitic multiplication, symptoms like
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 ...
,
jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...
, shortness of breath, and
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) ...
have been documented. Individuals with normal immune function and healthy spleens often recover without treatment. Splenectomized patients are more susceptible to contracting the disease and can die within five to eight days of symptom onset. They have severe hemolytic anemia, and occasional
hepatomegaly Hepatomegaly is the condition of having an enlarged liver. It is a non-specific medical sign having many causes, which can broadly be broken down into infection, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdomi ...
has been documented.
Parasitemia Parasitemia is the quantitative content of parasites in the blood. It is used as a measurement of parasite load in the organism and an indication of the degree of an active parasitic infection. Systematic measurement of parasitemia is important in ...
levels can reach up to 85% in patients without spleens, compared to 1–10% in individuals with spleens and effective immune systems. Complications include
acute respiratory failure Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as hypoxemia; a rise ...
,
congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
, and
kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
. Infections can be fatal in 5–10% of hospitalized patients, with increased risk of death in the
immunosuppressed Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reacti ...
, the elderly, and those also infected with
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 ...
. ''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 into
shock Shock may refer to: Common uses Collective noun *Shock, a historic commercial term for a group of 60, see English numerals#Special names * Stook, or shock of grain, stacked sheaves Healthcare * Shock (circulatory), circulatory medical emergen ...
-like symptoms with
pulmonary edema Pulmonary edema, also known as pulmonary congestion, is excessive edema, liquid accumulation in the parenchyma, tissue and pulmonary alveolus, air spaces (usually alveoli) of the lungs. It leads to impaired gas exchange and may cause hypoxemia an ...
and kidney failure. In birds The
pathogenicity In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
of ''B. uriae'' for
murres ''Uria'' is a genus of seabirds in the auk family known in Britain as guillemots, in most of North America as murres, and in Newfoundland and Labrador as turr. These are medium-sized birds with mainly brown or black plumage in the breeding sea ...
is currently unknown. Birds were found with
lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classifi ...
s, anemia and respiratory difficulty, and tissues of avian hosts were affected. ''Babesia peircei'' infections can cause mild anemia,
leukocytosis Leukocytosis is a condition in which the white cell (leukocyte count) is above the normal range in the blood. It is frequently a sign of an inflammatory response, most commonly the result of infection, but may also occur following certain parasit ...
, and impairment of hepatic function in
African penguin The African penguin (''Spheniscus demersus''), also known as Cape penguin or South African penguin, is a species of penguin confined to southern African waters. Like all extant penguins, it is flightless, with a streamlined body and wings stiff ...
s.


Diagnostic tests

As a protozoan parasite, the most effective way to identify ''Babesia'' infection is through blood sample testing.


Morphology

''Babesia'' species enter
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 (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 a Maltese-cross form. This tetrad morphology seen with
Giemsa staining Giemsa stain (), named after German chemist and bacteriologist Gustav Giemsa, is a nucleic acid stain used in cytogenetics and for the histopathological diagnosis of malaria and other parasites. Uses It is specific for the phosphate groups of ...
of a thin
blood smear A blood smear, peripheral blood smear or blood film is a thin layer of blood smeared on a glass microscope slide and then stained in such a way as to allow the various blood cells to be examined microscopically. Blood smears are examined in the ...
is unique to ''Babesia'', and distinguishes it from ''
Plasmodium falciparum ''Plasmodium falciparum'' is a Unicellular organism, unicellular protozoan parasite of humans, and the deadliest species of ''Plasmodium'' that causes malaria in humans. The parasite is transmitted through the bite of a female ''Anopheles'' mosqu ...
'', 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. It is important to pay attention to particular morphologies of ''Babesia'' in blood smears, because of its great similarity to the malarial parasite ''Plasmodium falciparum''. This has resulted in many patients with babesiosis being misdiagnosed. The few distinguishing factors for ''Babesia'' include protozoa with varying shapes and sizes, the potential to contain
vacuole A vacuole () is a membrane-bound organelle which is present in plant and fungal cells and some protist, animal, and bacterial cells. Vacuoles are essentially enclosed compartments which are filled with water containing inorganic and organic mo ...
s, and the lack of pigment production. Trophozoites appearing in a tetrad formation within an erythrocyte are also indicative of ''Babesia''. 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 an indirect fluorescent antibody (IFA) test. IFA testing has a much higher specificity than stained blood smears, with antibody detection in 88-96% of infected patients. Diagnostic measures through antibody testing are also particularly useful for identifying serum prevalence in asymptomatic individuals. Due to the transmissibility of ''Babesia'' through blood transfusions, IFA testing would be an effective means of screening for the disease in blood donations. Historically, babesiosis diagnosis was carried out with
xenodiagnosis Xenodiagnosis is a diagnostic method used to document the presence of infectious disease microorganisms or pathogens by exposing possibly infected tissue to a vector and then examining the vector for the presence of the microorganisms or pathogen ...
in
hamster Hamsters are rodents (order Rodentia) belonging to the subfamily Cricetinae, which contains 19 species classified in seven genera.Fox, Sue. 2006. ''Hamsters''. T.F.H. Publications Inc. They have become established as popular small pets. The b ...
s for ''B. microti'' and in
gerbil The Mongolian gerbil or Mongolian jird (''Meriones unguiculatus'') is a small rodent belonging to the subfamily Gerbillinae. Their body size is typically , with a tail, and body weight , with adult males larger than females. The animal is use ...
s for ''B. divergens''. This diagnostic technique has been abandoned in favor of faster diagnostic measures.


Treatment

Several methods are available to manage and treat babesiosis in animals. In humans, many spontaneously recover, having only experienced mild symptoms not diagnosed as the disease. This is almost always seen in ''B. microti'' infections, which are generally more common in the United States. For ''B. divergens'' and more severe ''B. microti'' infections, the standard treatment historically for symptomatic individuals was oral or intravenous
clindamycin Clindamycin is an antibiotic medication used for the treatment of a number of bacterial infections, including osteomyelitis (bone) or joint infections, pelvic inflammatory disease, strep throat, pneumonia, acute otitis media (middle ear infec ...
with oral
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 leg cr ...
. With the results of research completed in 2000, however, treatment regimens have been increasingly leaning towards oral
atovaquone Atovaquone, sold under the brand name Mepron, is an antimicrobial medication for the prevention and treatment of ''Pneumocystis jirovecii'' pneumonia (PCP). Atovaquone is a chemical compound that belongs to the class of naphthoquinones. Atovaq ...
with oral
azithromycin Azithromycin, sold under the brand names Zithromax (in oral form) and Azasite (as an eye drop), is an antibiotic medication used for the treatment of a number of bacterial infections. This includes middle ear infections, strep throat, pneumon ...
. The latter are preferred, as they are equally effective in all but the most severe cases and exhibit fewer associated
adverse reaction An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term complica ...
s. In severe cases, blood exchange transfusions have been performed to lower the
parasitic load Parasitic load is a term used with regard to electrical appliances, railway locomotives and internal combustion engines. With regard to electrical appliances, it represents the power consumed even when the appliance is shut off, that is standby p ...
in an individual. Other measures include addressing and correcting abnormal clinical signs. In seabirds,
primaquine Primaquine is a medication used to treat and prevent malaria and to treat ''Pneumocystis'' pneumonia. Specifically it is used for malaria due to ''Plasmodium vivax'' and ''Plasmodium ovale'' along with other medications and for prevention if othe ...
has been used in a study to show effective treatment on infected hosts. Treatment for babesiosis consisted of primaquine (1 mg/kg PO q24h for 10 days; primaquine
phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phospho ...
1.76%m/v in stabilized solution, Primaquin Solution, MedPet Ltd,
Benrose Benrose is a suburb of Johannesburg, South Africa. Slightly south of the Johannesburg CBD, it is next door to Jeppestown and Belgravia. It is light industry and commercial suburb. It is located in Region F of the City of Johannesburg Metropolitan ...
, South Africa). After, treatment was followed by a phospholipid supplement (1 capsule/bird PO q24h for 12 days; deoiled, enriched
phospholipid Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
s from soybeans, 300 mg/capsule, Essentiale Extreme,
Sanofi Aventis Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Syn ...
Ltd,
Midrand Midrand is a former municipality in central Gauteng, South Africa. It is situated in-between Centurion and Sandton and now forms part of the City of Johannesburg Metropolitan Municipality. History Midrand was established as a municipality in 198 ...
, South Africa); as an attempt to mitigate potential
hepatotoxic Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn fro ...
effects of primaquine. To prevent transmission of Babesia and other tickborne pathogens, all birds with visible
ectoparasites 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 ...
are treated with pesticide powder (
carbaryl Carbaryl (1-naphthyl methylcarbamate) is a chemical in the carbamate family used chiefly as an insecticide. It is a white crystalline solid previously sold under the brand name Sevin, which was a trademark of the Bayer Company. The Sevin tradem ...
50 g/kg) upon admission, and the facilities are thoroughly cleaned on a daily basis.


Prevention in animals

In 1906, efforts were made to
eradicate The word "Eradication" is derived from Latin word "radix" which means "root". It may refer to: *Eradication of infectious diseases (human), the reduction of the global incidence of an infectious disease in humans to zero *Eradication of infectiou ...
the tick vector of bovine babesiosis in the United States. This eradication was recorded as being successfully completed four decades later. Effective control can be achieved by
vaccination Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...
with live attenuated
phenotypes In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
of the parasite. The vaccines have a number of drawbacks, so better, safer vaccines are still being researched. In recent years, a number of parasite proteins with
immunogenic Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted: * Wanted immunogenicity typically relates to vaccines, where the injectio ...
potential have been discovered. Through
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) t ...
, genetic sequencing, and bioinformatics analysis of the genes, a high degree of conservation (98–100%) was found among Brazilian isolates of ''B. bovis'' and the
T2Bo T, or t, is the twentieth Letter (alphabet), letter in the Latin alphabet, used in the English alphabet, modern English alphabet, the alphabets of other western European languages and others worldwide. Its name in English is English alphabe ...
isolate. Thus, these genes are considered for inclusion in a recombinant cocktail vaccine for cattle babesiosis caused by ''B. bovis''.


Prevention in humans

The most effective public health measure for ''Babesia'' 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. Other measures include applying
DEET ''N'',''N''-Diethyl-''meta''-toluamide, also called DEET () or diethyltoluamide, is the most common active ingredient in insect repellents. It is a slightly yellow oil intended to be applied to the skin or to clothing and provides protection ag ...
, 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. 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. 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 where
ticks of domestic animals Ticks of domestic animals directly cause poor health and loss of production to their hosts. Ticks also transmit numerous kinds of viruses, bacteria, and protozoa between domestic animals. These microbes cause diseases which can be severely debilita ...
are routinely controlled with chemical
acaricide Acaricides are pesticides that kill members of the arachnid subclass ''Acari'', which includes ticks and mites. Acaricides are used both in medicine and agriculture, although the desired selective toxicity differs between the two fields. Termino ...
s to reduce incidence of infection with ''B. bovis'' and ''B. bigemina'', the risk to humans from these parasites will be reduced.


References


External links

*
Fact Sheet from the New York State Department of Health



CDC Laboratory Identification of Parasites of Public Health Concern: Babesiosis
{{Taxonbar, from=Q797656 Apicomplexa genera Parasites of humans Tick-borne diseases