Toxoplasmosis is a
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 parasitolog ...
caused by ''
Toxoplasma gondii
''Toxoplasma gondii'' () is an obligate intracellular parasitic protozoan (specifically an apicomplexan) that causes toxoplasmosis. Found worldwide, ''T. gondii'' is capable of infecting virtually all warm-blooded animals, but felids, such as d ...
'', an
apicomplexan.
Infections with toxoplasmosis are associated with a variety of neuropsychiatric and behavioral conditions.
Occasionally, people may have a few weeks or months of mild,
flu-like illness
Influenza-like illness (ILI), also known as flu-like syndrome or flu-like symptoms, is a medical diagnosis of possible influenza or other illness causing a set of common symptoms. These include fever, shivering, chills, malaise, dry cough, lo ...
such as muscle aches and tender
lymph nodes
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...
.
[ In a small number of people, eye problems may develop.][ In those with a weak immune system, severe symptoms such as ]seizure
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...
s and poor coordination may occur.[ If a person becomes infected during ]pregnancy
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but ca ...
, a condition known as congenital toxoplasmosis may affect the child.
Toxoplasmosis is usually spread by eating poorly cooked food that contains cysts
A cyst is a closed sac, having a distinct envelope and division compared with the nearby tissue. Hence, it is a cluster of cells that have grouped together to form a sac (like the manner in which water molecules group together to form a bubble) ...
, exposure to infected cat feces, and from an infected woman to their baby during pregnancy.[ Rarely, the disease may be spread by ]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 ...
.[ It is not otherwise spread between people.][ The parasite is known to reproduce sexually only in the ]cat family
Felidae () is the family of mammals in the order Carnivora colloquially referred to as cats, and constitutes a clade. A member of this family is also called a felid (). The term "cat" refers both to felids in general and specifically to the do ...
.[ However, it can infect most types of ]warm-blooded animals
Warm-blooded is an informal term referring to animal species which can maintain a body temperature higher than their environment. In particular, homeothermic species maintain a stable body temperature by regulating metabolic processes. The onl ...
, including humans. Diagnosis is typically by testing blood for antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
or by testing the amniotic fluid
The amniotic fluid is the protective liquid contained by the amniotic sac of a gravid amniote. This fluid serves as a cushion for the growing fetus, but also serves to facilitate the exchange of nutrients, water, and biochemical products betwee ...
in pregnant women for the parasite's DNA.
Prevention is by properly preparing and cooking food.[ Pregnant women are also recommended not to clean cat litter boxes or, if they must, to wear gloves and wash their hands afterwards.] Treatment of otherwise healthy people is usually not needed.[ During pregnancy, ]spiramycin
Spiramycin is a macrolide antibiotic and antiparasitic. It is used to treat toxoplasmosis and various other infections of soft tissues. Although used in Europe, Canada and Mexico, spiramycin is still considered an experimental drug in the United ...
or pyrimethamine
Pyrimethamine, sold under the brand name Daraprim among others, is a medication used with leucovorin (leucovorin is used to decrease side effects of pyrimethamine; it does not have intrinsic anti-parasitic activity) to treat the parasitic disea ...
/sulfadiazine
Sulfadiazine is an antibiotic. Used together with pyrimethamine, a dihydrofolate reductase inhibitor, it is the treatment of choice for toxoplasmosis, which is caused by a protozoan parasite. It is a second-line treatment for otitis media, p ...
and folinic acid
Folinic acid, also known as leucovorin, is a medication used to decrease the toxic effects of methotrexate and pyrimethamine. It is also used in combination with 5-fluorouracil to treat colorectal cancer and pancreatic cancer, may be used to tr ...
may be used for treatment.
Up to half of the world's population is infected by ''T. gondii'', but have no symptoms. In the United States, approximately 11% of people have been infected, while in some areas of the world this is more than 60%.[ Approximately 200,000 cases of congenital toxoplasmosis occur a year.] Charles Nicolle
Charles Jules Henri Nicolle (21 September 1866 – 28 February 1936) was a French bacteriologist who received the Nobel Prize in Medicine for his identification of lice as the transmitter of epidemic typhus.
Family
Nicolle was born to Aline L ...
and Louis Manceaux Louis Herbert Manceaux (1865–1934) was a French physician, parasitologist, and co-discover of ''Toxoplasma gondii'' with Charles Nicolle in 1908.
Biography
Manceaux's life is not well known, but he was physician-scientist recruited by Char ...
first described the organism in 1908.[ In 1941, transmission during pregnancy from a pregnant parent to their baby was confirmed.] There is tentative evidence that infection may affect people's behavior.
Signs and symptoms
Infection has three stages:
Acute
Acute toxoplasmosis is often asymptomatic in healthy adults.[ However, symptoms may manifest and are often ]influenza
Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms ...
-like: swollen lymph node
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
s, headaches, fever, and fatigue, or muscle aches and pains that last for a month or more. It is rare for a human with a fully functioning immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
to develop severe symptoms following infection. People with weakened immune systems are likely to experience headache, confusion, poor coordination, seizures, lung problems that may resemble tuberculosis or ''Pneumocystis jiroveci'' pneumonia (a common opportunistic infection that occurs in people with AIDS), or chorioretinitis caused by severe inflammation of the retina (ocular toxoplasmosis). Young children and immunocompromised
Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
people, such as those with HIV/AIDS, those taking certain types of chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
, or those who have recently received an organ transplant
Organ transplantation is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organs may be transpo ...
, may develop severe toxoplasmosis. This can cause damage to the brain (encephalitis
Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hallucinations, ...
) or the eyes ( necrotizing retinochoroiditis). Infants infected via placental transmission may be born with either of these problems, or with nasal malformations, although these complications are rare in newborns. The toxoplasmic 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 ...
s causing acute toxoplasmosis are referred to as tachyzoites
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 ...
, and are typically found in various tissues and body fluids, but rarely in blood or cerebrospinal fluid.
Swollen lymph node
Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cl ...
s are commonly found in the neck or under the chin, followed by the armpits and the groin. Swelling may occur at different times after the initial infection, persist, and recur for various times independently of antiparasitic treatment. It is usually found at single sites in adults, but in children, multiple sites may be more common. Enlarged lymph nodes will resolve within 1–2 months in 60% of cases. However, a quarter of those affected take 2–4 months to return to normal, and 8% take 4–6 months. A substantial number (6%) do not return to normal until much later.
Latent
Due to the absence of obvious symptoms, hosts easily become infected with ''T. gondii'' and develop toxoplasmosis without knowing it. Although mild, flu-like symptoms occasionally occur during the first few weeks following exposure, infection with ''T. gondii'' produces no readily observable symptoms in healthy human adults. In most immunocompetent
In immunology, immunocompetence is the ability of the body to produce a normal immune response following exposure to an antigen. Immunocompetence is the opposite of immunodeficiency (also known as ''immuno-incompetence'' or being ''immuno-comprom ...
people, the infection enters a latent phase, during which only bradyzoite
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 ...
s ( in tissue cysts) are present; these tissue cysts and even lesions can occur in the retina
The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...
s, alveolar Alveolus (; pl. alveoli, adj. alveolar) is a general anatomical term for a concave cavity or pit.
Uses in anatomy and zoology
* Pulmonary alveolus, an air sac in the lungs
** Alveolar cell or pneumocyte
** Alveolar duct
** Alveolar macrophage
* ...
lining of the lungs (where an acute infection may mimic a ''Pneumocystis jirovecii
''Pneumocystis jirovecii'' (previously ''P. carinii'') is a yeast-like fungus of the genus ''Pneumocystis''. The causative organism of ''Pneumocystis'' pneumonia, it is an important human pathogen, particularly among immunocompromised hosts. Pr ...
'' infection), heart, skeletal muscle, and the central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
(CNS), including the brain. Cysts form in the CNS (brain tissue
The human brain is the central organ of the human nervous system, and with the spinal cord makes up the central nervous system. The brain consists of the cerebrum, the brainstem and the cerebellum. It controls most of the activities of the ...
) upon infection with ''T. gondii'' and persist for the lifetime of the host. Most infants who are infected while in the womb have no symptoms at birth, but may develop symptoms later in life.[Randall Parker]
Humans Get Personality Altering Infections From Cats
. September 30, 2003
Reviews of serological
Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mi ...
studies have estimated that 30–50% of the global population has been exposed to and may be chronically infected with latent toxoplasmosis, although infection rates differ significantly from country to country. This latent state of infection has recently been associated with numerous disease burden
Disease burden is the impact of a health problem as measured by financial cost, mortality, morbidity, or other indicators. It is often quantified in terms of quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs). Both o ...
s, neural alterations, and subtle gender-dependent behavioral changes in immunocompetent humans, as well as an increased risk of motor vehicle collisions.
Skin
While rare, skin lesions may occur in the acquired form of the disease, including roseola
Roseola, also known as sixth disease, is an infectious disease caused by certain types of human herpes viruses. Most infections occur before the age of three. Symptoms vary from absent to the classic presentation of a fever of rapid onset follo ...
and erythema
Erythema (from the Greek , meaning red) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not assoc ...
multiforme-like eruptions, prurigo-like nodules, urticaria
Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasti ...
, and maculopapular lesions. Newborns may have punctate macules, ecchymoses
A bruise, also known as a contusion, is a type of hematoma of tissue, the most common cause being capillaries damaged by trauma, causing localized bleeding that extravasates into the surrounding interstitial tissues. Most bruises occur close e ...
, or "blueberry muffin" lesions.
Diagnosis of cutaneous toxoplasmosis is based on the tachyzoite form of ''T. gondii'' being found in the epidermis
The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water rele ...
. It is found in all levels of the epidermis, is about 6 by 2 μm and bow-shaped, with the nucleus being one-third of its size. It can be identified by electron microscopy or by Giemsa stain
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 ...
ing tissue where the cytoplasm shows blue, the nucleus red.
Cause
Parasitology
In its lifecycle, ''T. gondii'' adopts several forms. Tachyzoites
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 ...
are responsible for acute infection; they divide rapidly and spread through the tissues of the body. Tachyzoites are also known as "tachyzoic merozoites", a descriptive term that conveys more precisely the parasitological nature of this stage. After proliferating, tachyzoites convert into bradyzoites
Apicomplexans, a group of intracellular parasites, have Biological life cycle, 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 a ...
, which are inside latent intracellular tissue cyst
A cyst is a closed sac, having a distinct envelope and cell division, division compared with the nearby Biological tissue, tissue. Hence, it is a cluster of Cell (biology), cells that have grouped together to form a sac (like the manner in which ...
s that form mainly in the muscles and brain. The formation of cysts is in part triggered by the pressure of the host immune system.[ The bradyzoites (also called "bradyzoic merozoites") are not responsive to antibiotics. Bradyzoites, once formed, can remain in the tissues for the lifespan of the host. In a healthy host, if some bradyzoites convert back into active tachyzoites, the immune system will quickly destroy them. However, in immunocompromised individuals, or in fetuses, which lack a developed immune system, the tachyzoites can run rampant and cause significant neurological damage.]
The parasite's survival is dependent on a balance between host survival and parasite proliferation. ''T. gondii'' achieves this balance by manipulating the host's immune response, reducing the host's immune response, and enhancing the parasite's reproductive advantage. Once it infects a normal host cell, it resists damage caused by the host's immune system, and changes the host's immune processes.
As it forces its way into the host cell, the parasite forms a parasitophorous vacuole
The parasitophorous vacuole (PV) is a structure produced by apicomplexan parasites in the cells of its host. The PV allows the parasite to develop while protected from the phagolysosomes of the host cell.
The PV is a bubble-like compartment mad ...
(PV) membrane from the membrane of the host cell. The PV encapsulates the parasite, and is both resistant to the activity of the endolysosomal system, and can take control of the host's mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
and endoplasmic reticulum
The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
.
When first invading the cell, the parasite releases ROP proteins from the bulb of the rhoptry
A rhoptry is a specialized secretory organelle. They are club-shaped organelles connected by thin necks to the extreme apical pole of the parasite. These organelles, like micronemes, are characteristic of the motile stages of Apicomplexa protozoa ...
organelle. These proteins translocate to the nucleus and the surface of the PV membrane where they can activate STAT
STAT, Stat. , or stat may refer to:
* Stat (system call), a Unix system call that returns file attributes of an inode
* ''Stat'' (TV series), an American sitcom that aired in 1991
* Stat (website), a health-oriented news website
* STAT protein, a ...
pathways to modulate the expression of cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
s at the transcriptional level, bind and inactivate PV membrane destroying IRG proteins, among other possible effects. Additionally, certain strains of T. ''gondii'' can secrete a protein known as GRA15, activating the NF-κB
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...
pathway, which upregulates the pro-inflammatory cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
IL-12 in the early immune response, possibly leading to the parasite's latent phase. The parasite's ability to secrete these proteins depends on its genotype and affects its virulence.
The parasite also influences an anti-apoptotic mechanism, allowing the infected host cells to persist and replicate. One method of apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
resistance is by disrupting pro-apoptosis effector proteins, such as BAX and BAK. To disrupt these proteins, ''T. gondii'' causes conformational changes to the proteins, which prevent the proteins from being transported to various cellular compartments where they initiate apoptosis events. ''T. gondii'' does not, however, cause downregulation of the pro-apoptosis effector proteins.
''T. gondii'' also has the ability to initiate autophagy
Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...
of the host's cells. This leads to a decrease in healthy, uninfected cells, and consequently fewer host cells to attack the infected cells. Research by Wang ''et al'' finds that infected cells lead to higher levels of autophagosomes in normal and infected cells. Their research reveals that ''T. gondii'' causes host cell autophagy using a calcium-dependent pathway. Another study suggests that the parasite can directly affect calcium being released from calcium stores, which are important for the signalling processes of cells.
The mechanisms above allow ''T. gondii'' to persist in a host. Some limiting factors for the toxoplasma is that its influence on the host cells is stronger in a weak immune system and is quantity-dependent, so a large number of ''T. gondii'' per host cell cause a more severe effect. The effect on the host also depends on the strength of the host immune system. Immunocompetent individuals do not normally show severe symptoms or any at all, while fatality or severe complications can result in immunocompromised individuals.
Since the parasite can change the host's immune response, it may also have an effect, positive or negative, on the immune response to other pathogenic threats. This includes, but is not limited to, the responses to infections by ''Helicobacter felis
''Helicobacter felis'' is a bacterial species in the Helicobacteraceae family, Campylobacterales order, Helicobacter genus. This bacterium is Gram-negative, microaerophilic, urease-positive, and spiral-shaped. Its type strain is CS1T (= ATCC 491 ...
'', ''Leishmania major
''Leishmania major'' is a species of parasite found in the genus '' Leishmania'', and is associated with the disease zoonotic cutaneous leishmaniasis (also known as Aleppo boil, Baghdad boil, Bay sore, Biskra button, Chiclero ulcer, Delhi boil, K ...
'', or other parasites, such as ''Nippostrongylus brasiliensis
''Nippostrongylus brasiliensis'' is a gastrointestinal roundworm that infects rodents, primarily rats. This worm is a widely studied parasite due to its simple lifecycle and its ability to be used in animal models. Its lifecycle similar to the hu ...
''.
Transmission
Toxoplasmosis is generally transmitted through the mouth when ''Toxoplasma gondii'' oocysts or tissue cysts are accidentally eaten.[ Congenital transmittance from mother to fetus can also occur. Transmission may also occur during the solid organ transplant process][ or hematogenous stem cell transplants.][
Oral transmission may occur through:
* Ingestion of raw or partly cooked meat, especially pork, lamb, or venison containing ''Toxoplasma'' cysts: Infection prevalence in countries where undercooked meat is traditionally eaten has been related to this transmission method. Tissue cysts may also be ingested during hand-to-mouth contact after handling undercooked meat, or from using knives, utensils, or cutting boards contaminated by raw meat.]
* Ingestion of unwashed fruit or vegetables that have been in contact with contaminated soil containing infected cat feces.[
* Ingestion of cat ]feces
Feces ( or faeces), known colloquially and in slang as poo and poop, are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the large intestine. Feces contain a relati ...
containing oocysts: This can occur through hand-to-mouth contact following gardening, cleaning a cat's litter box
A litter box, also known as a sandbox, cat box, litter tray, cat pan, potty, pot or litter pan, is an indoor feces and urine collection box for cats, as well as Domestic rabbit, rabbits, ferrets, miniature pigs, small dogs, and other pets that ...
, contact with children's sandpits; the parasite can survive in the environment for months.
* Ingestion of untreated, unfiltered water through direct consumption or utilization of water for food preparation.
* Ingestion of unpasteurized milk and milk products, particularly goat's milk.
* Ingestion of raw seafood.
Cats excrete the pathogen in their feces for a number of weeks after contracting the disease, generally by eating an infected intermediate host that could include mammals (like rodents) or birds. Oocyst shedding usually starts from the third day after ingestion of infected intermediate hosts, and may continue for weeks. The oocysts are not infective when excreted. After about a day, the oocyst undergoes a process called sporulation and becomes potentially pathogenic. In addition to cats, birds and mammals including human beings are also intermediate hosts of the parasite and are involved in the transmission process. However the pathogenicity varies with the age and species involved in infection and the mode of transmission of ''T. gondii''.
Toxoplasmosis may also be transmitted through solid organ transplants. Toxoplasma-seronegative recipients who receive organs from recently infected Toxoplasma-seropositive donors are at risk. Organ recipients who have latent toxoplasmosis are at risk of the disease reactivating in their system due to the immunosuppression occurring during solid organ transplant.[ Recipients of hematogenous stem cell transplants may experience higher risk of infection due to longer periods of immunosuppression.]
Heart and lung transplants provide the highest risk for toxoplasmosis infection due to the striated muscle making up the heart, which can contain cysts, and risks for other organs and tissues vary widely. Risk of transmission can be reduced by screening donors and recipients prior to the transplant procedure and providing treatment.[
]
Pregnancy precautions
Congenital
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...
toxoplasmosis is a specific form of toxoplasmosis in which an unborn fetus is infected via the placenta
The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mater ...
. Congenital toxoplasmosis is associated with fetal death and miscarriage, and in infants, it is associated with hydrocephalus, cerebral calcifications and chorioretinitis
Chorioretinitis is an inflammation of the choroid (thin pigmented vascular coat of the eye) and retina of the eye. It is a form of posterior uveitis. If only the choroid is inflamed, not the retina, the condition is termed choroiditis. The ophthalm ...
, leading to encephalopathy and possibly blindness. A positive antibody titer
Titer (American English) or titre (British English) is a way of expressing concentration. Titer testing employs serial dilution to obtain approximate quantitative information from an analytical procedure that inherently only evaluates as positiv ...
indicates previous exposure and immunity, and largely ensures the unborn fetus' safety. A simple blood draw at the first prenatal doctor visit can determine whether or not a woman has had previous exposure and therefore whether or not she is at risk. If a woman receives her first exposure to ''T. gondii'' while pregnant, the fetus is at particular risk.
Not much evidence exists around the effect of education before pregnancy to prevent congenital toxoplasmosis. However educating parents before the baby is born has been suggested to be effective because it may improve food, personal and pet hygiene.[ More research is needed to find whether antenatal education can reduce congenital toxoplasmosis.][
For pregnant women with negative antibody titers, indicating no previous exposure to ''T. gondii'', serology testing as frequent as monthly is advisable as treatment during pregnancy for those women exposed to ''T. gondii'' for the first time dramatically decreases the risk of passing the parasite to the fetus. Since a baby's immune system does not develop fully for the first year of life, and the resilient cysts that form throughout the body are very difficult to eradicate with antiprotozoans, an infection can be very serious in the young.
Despite these risks, pregnant women are not routinely screened for toxoplasmosis in most countries, for reasons of cost-effectiveness and the high number of ]false positives
A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test result ...
generated; Portugal
Portugal, officially the Portuguese Republic ( pt, República Portuguesa, links=yes ), is a country whose mainland is located on the Iberian Peninsula of Southwestern Europe, and whose territory also includes the Atlantic archipelagos of ...
, France
France (), officially the French Republic ( ), is a country primarily located in Western Europe. It also comprises of Overseas France, overseas regions and territories in the Americas and the Atlantic Ocean, Atlantic, Pacific Ocean, Pac ...
, Austria
Austria, , bar, Östareich officially the Republic of Austria, is a country in the southern part of Central Europe, lying in the Eastern Alps. It is a federation of nine states, one of which is the capital, Vienna, the most populous ...
, Uruguay
Uruguay (; ), officially the Oriental Republic of Uruguay ( es, República Oriental del Uruguay), is a country in South America. It shares borders with Argentina to its west and southwest and Brazil to its north and northeast; while bordering ...
,
and Italy
Italy ( it, Italia ), officially the Italian Republic, ) or the Republic of Italy, is a country in Southern Europe. It is located in the middle of the Mediterranean Sea, and its territory largely coincides with the homonymous geographical re ...
are notable exceptions, and some regional screening programmes operate in Germany
Germany,, officially the Federal Republic of Germany, is a country in Central Europe. It is the second most populous country in Europe after Russia, and the most populous member state of the European Union. Germany is situated betwe ...
, Switzerland
). Swiss law does not designate a ''capital'' as such, but the federal parliament and government are installed in Bern, while other federal institutions, such as the federal courts, are in other cities (Bellinzona, Lausanne, Luzern, Neuchâtel ...
and Belgium
Belgium, ; french: Belgique ; german: Belgien officially the Kingdom of Belgium, is a country in Northwestern Europe. The country is bordered by the Netherlands to the north, Germany to the east, Luxembourg to the southeast, France to th ...
.[ As invasive ]prenatal
Prenatal development () includes the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal devel ...
testing incurs some risk to the fetus
A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal deve ...
(18.5 pregnancy losses per toxoplasmosis case prevented),[ ]postnatal
The postpartum (or postnatal) period begins after childbirth and is typically considered to end within 6 weeks as the mother's body, including hormone levels and uterus size, returns to a non-pregnant state. The terms puerperium, puerperal perio ...
or neonatal
An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...
screening is preferred. The exceptions are cases where fetal
A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal develo ...
abnormalities are noted, and thus screening can be targeted.[
Pregnant women should avoid handling ]raw meat
Raw meat generally refers to any type of uncooked muscle tissue of an animal used for food. In the meat production industry, the term ‘meat’ refers specifically to mammalian flesh, while the words ‘poultry’ and ‘seafood’ are used to ...
, drinking raw milk
Raw milk or unpasteurized milk is milk that has not been pasteurized, a process of heating liquid foods to kill pathogens for safe consumption and extending the shelf life.
Proponents of raw milk have asserted numerous supposed benefits to consu ...
(especially goat milk) and be advised to not eat raw or undercooked meat regardless of type. Because of the obvious relationship between ''Toxoplasma'' and cats it is also often advised to avoid exposure to cat feces, and refrain from gardening (cat feces are common in garden soil) or at least wear gloves when so engaged. Most cats are not actively shedding oocyst
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 ...
s, since they get infected in the first six months of their life, when they shed oocysts for a short period of time (1–2 weeks.) However, these oocysts get buried in the soil, sporulate and remain infectious for periods ranging from several months to more than a year. Numerous studies have shown living in a household with a cat is not a significant risk factor for ''T. gondii'' infection, though living with several kittens has some significance.
In 2006, a Czech research team discovered women with high levels of toxoplasmosis antibodies were significantly more likely to give birth to baby boys than baby girls. In most populations, the birth rate is around 51% boys, but people infected with ''T. gondii'' had up to a 72% chance of a boy.
Diagnosis
Diagnosis of toxoplasmosis in humans is made by biological, serological, histological, or molecular methods, or by some combination of the above. Toxoplasmosis can be difficult to distinguish from primary central nervous system lymphoma
Primary central nervous system lymphoma (PCNSL), also termed primary diffuse large B-cell lymphoma of the central nervous system (DLBCL-CNS), is a primary intracranial tumor appearing mostly in patients with severe immunodeficiency (typically pa ...
. It mimics several other infectious diseases so clinical signs are non-specific and are not sufficiently characteristic for a definite diagnosis. As a result, the possibility of an alternate diagnosis is supported by a failed trial of antimicrobial therapy (pyrimethamine
Pyrimethamine, sold under the brand name Daraprim among others, is a medication used with leucovorin (leucovorin is used to decrease side effects of pyrimethamine; it does not have intrinsic anti-parasitic activity) to treat the parasitic disea ...
, sulfadiazine
Sulfadiazine is an antibiotic. Used together with pyrimethamine, a dihydrofolate reductase inhibitor, it is the treatment of choice for toxoplasmosis, which is caused by a protozoan parasite. It is a second-line treatment for otitis media, p ...
, and folinic acid
Folinic acid, also known as leucovorin, is a medication used to decrease the toxic effects of methotrexate and pyrimethamine. It is also used in combination with 5-fluorouracil to treat colorectal cancer and pancreatic cancer, may be used to tr ...
(USAN
280px, "Samguk Sagi" Book 04. Silla's Records. In 512, Usan-guk(于山國)was Ulleungdo(鬱陵島)
Usan-guk, or the State of Usan, occupied Ulleung-do and the adjacent islands during the Korean Three Kingdoms period. According to th ...
: leucovorin)), i.e., if the drugs produce no effect clinically and no improvement on repeat imaging.
''T. gondii'' may also be detected in blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
, amniotic fluid
The amniotic fluid is the protective liquid contained by the amniotic sac of a gravid amniote. This fluid serves as a cushion for the growing fetus, but also serves to facilitate the exchange of nutrients, water, and biochemical products betwee ...
, or cerebrospinal fluid
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates.
CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
by using 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 ...
. ''T. gondii'' may exist in a host as an inactive cyst that would likely evade detection.
Serological
Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mi ...
testing can detect ''T. gondii'' antibodies in blood serum, using methods including the Sabin–Feldman dye test
A Sabin–Feldman dye test is a serologic test to diagnose for toxoplasmosis
Toxoplasmosis is a parasitic disease caused by '' Toxoplasma gondii'', an apicomplexan. Infections with toxoplasmosis are associated with a variety of neuropsychiatr ...
(DT), the indirect hemagglutination assay
The hemagglutination assay or haemagglutination assay (HA) and the hemagglutination inhibition assay (HI or HAI) were developed in 1941–42 by American virologist George Hirst as methods for quantifying the relative concentration of viruses, bact ...
, the indirect fluorescent antibody assay (IFA), the direct agglutination test, the latex agglutination test (LAT), the enzyme-linked immunosorbent assay (ELISA), and the immunosorbent agglutination assay test (IAAT).
The most commonly used tests to measure IgG
Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...
antibody are the DT, the ELISA, the IFA, and the modified direct agglutination test. IgG antibodies usually appear within a week or two of infection, peak within one to two months, then decline at various rates. ''Toxoplasma'' IgG antibodies generally persist for life, and therefore may be present in the bloodstream as a result of either current or previous infection.
To some extent, acute toxoplasmosis infections can be differentiated from chronic infections using an IgG avidity In biochemistry, avidity refers to the accumulated strength of ''multiple'' affinities of individual non-covalent binding interactions, such as between a protein receptor and its ligand, and is commonly referred to as functional affinity. Avidity di ...
test, which is a variation on the ELISA. In the first response to infection, toxoplasma-specific IgG has a low affinity for the toxoplasma antigen; in the following weeks and month, IgG affinity for the antigen increases. Based on the IgG avidity test, if the IgG in the infected individual has a high affinity, it means that the infection began three to five months before testing. This is particularly useful in congenital infection, where pregnancy status and gestational age at time of infection determines treatment.
In contrast to IgG, IgM antibodies can be used to detect acute infection but generally not chronic infection. The IgM antibodies appear sooner after infection than the IgG antibodies and disappear faster than IgG antibodies after recovery. In most cases, ''T. gondii''-specific IgM antibodies can first be detected approximately a week after acquiring primary infection and decrease within one to six months; 25% of those infected are negative for ''T. gondii''-specific IgM within seven months. However, IgM may be detectable months or years after infection, during the chronic phase, and false positives for acute infection are possible. The most commonly used tests for the measurement of IgM antibody are double-sandwich IgM-ELISA, the IFA test, and the immunosorbent agglutination assay (IgM-ISAGA). Commercial test kits often have low specificity, and the reported results are frequently misinterpreted.
In 2021, twenty commercial anti-''Toxoplasma'' IgG assays were evaluated in a systematic review
A systematic review is a Literature review, scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from publ ...
, in comparison with an accepted reference method. Most of them were enzyme-immunoassays, followed by agglutination tests, immunochromatographic tests, and a Western-Blot assay. The mean sensitivity of IgG assays ranged from 89.7% to 100% for standard titers and from 13.4% to 99.2% for low IgG titers. A few studies pointed out the ability of some methods, especially WB to detect IgG early after primary infection. The specificity of IgG assays was generally high, ranging from 91.3% to 100%; and higher than 99% for most EIA assays. The positive predictive value (PPV) was not a discriminant indicator among methods, whereas significant disparities (87.5%–100%) were reported among negative predictive values (NPV), a key-parameter assessing the ability to definitively rule out a ''Toxoplasma'' infection in patients at-risk for opportunistic infections.[ ]
Congenital
Recommendations for the diagnosis of congenital toxoplasmosis include: prenatal diagnosis based on testing
An examination (exam or evaluation) or test is an educational assessment intended to measure a test-taker's knowledge, skill, aptitude, physical fitness, or classification in many other topics (e.g., beliefs). A test may be administered verba ...
of amniotic fluid
The amniotic fluid is the protective liquid contained by the amniotic sac of a gravid amniote. This fluid serves as a cushion for the growing fetus, but also serves to facilitate the exchange of nutrients, water, and biochemical products betwee ...
and ultrasound
Ultrasound is sound waves with frequency, frequencies higher than the upper audible limit of human hearing range, hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hea ...
examinations; neonatal diagnosis based on molecular testing of placenta and cord blood
Cord blood (umbilical cord blood) is blood that remains in the placenta and in the attached umbilical cord after childbirth. Cord blood is collected because it contains stem cells, which can be used to treat hematopoietic and genetic disorders su ...
and comparative mother-child serologic tests and a clinical examination at birth; and early childhood diagnosis based on neurologic
Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal c ...
and ophthalmologic
Ophthalmology ( ) is a surgical subspecialty within medicine that deals with the diagnosis and treatment of eye disorders.
An ophthalmologist is a physician who undergoes subspecialty training in medical and surgical eye care. Following a medic ...
examinations and a serologic survey during the first year of life. During pregnancy, serological testing is recommended at three week intervals.
Even though diagnosis of toxoplasmosis heavily relies on serological detection of specific anti-''Toxoplasma'' immunoglobulin, serological testing has limitations. For example, it may fail to detect the active phase of ''T. gondii'' infection because the specific anti-''Toxoplasma'' IgG
Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...
or 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 ...
may not be produced until after several weeks of infection. As a result, a pregnant woman might test negative during the active phase of ''T. gondii'' infection leading to undetected and therefore untreated congenital toxoplasmosis. Also, the test may not detect ''T. gondii'' infections in immunocompromised patients because the titers of specific anti-''Toxoplasma'' IgG or IgM may not rise in this type of patient.
Many PCR-based techniques have been developed to diagnose toxoplasmosis using clinical specimens that include amniotic fluid, blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
, cerebrospinal fluid
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates.
CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
, and tissue biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
. The most sensitive PCR-based technique is nested PCR
Nested polymerase chain reaction (nested PCR) is a modification of polymerase chain reaction intended to reduce non-specific binding in products due to the amplification of unexpected primer binding sites.
Polymerase chain reaction
Polymerase chai ...
, followed by hybridization of PCR products. The major downside to these techniques is that they are time-consuming and do not provide quantitative data.
Real-time PCR is useful in pathogen detection, gene expression and regulation, and allelic discrimination. This PCR technique utilizes the 5' nuclease activity of ''Taq'' DNA polymerase to cleave a nonextendible, fluorescence-labeled hybridization probe during the extension phase of PCR. A second fluorescent dye, e.g., 6-carboxy-tetramethyl-rhodamine, quenches the fluorescence of the intact probe. The nuclease cleavage of the hybridization probe during the PCR releases the effect of quenching resulting in an increase of fluorescence proportional to the amount of PCR product, which can be monitored by a sequence detector.
Toxoplasmosis cannot be detected with immunostaining
In biochemistry, immunostaining is any use of an antibody-based method to detect a specific protein in a sample. The term "immunostaining" was originally used to refer to the immunohistochemical staining of tissue sections, as first described by A ...
. Lymph nodes affected by ''Toxoplasma'' have characteristic changes, including poorly demarcated reactive germinal centers
Germinal centers or germinal centres (GCs) are transiently formed structures within B cell zone (follicles) in secondary lymphoid organs – lymph nodes, ileal Peyer's patches, and the spleen – where mature B cells are activated, prolifer ...
, clusters of monocytoid B cells, and scattered epithelioid histiocyte
A histiocyte is a vertebrate cell that is part of the mononuclear phagocyte system (also known as the reticuloendothelial system or lymphoreticular system). The mononuclear phagocytic system is part of the organism's immune system. The histiocyt ...
s.
The classic triad of congenital toxoplasmosis includes: chorioretinitis
Chorioretinitis is an inflammation of the choroid (thin pigmented vascular coat of the eye) and retina of the eye. It is a form of posterior uveitis. If only the choroid is inflamed, not the retina, the condition is termed choroiditis. The ophthalm ...
, hydrocephalus
Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased intracranial pressure, pressure inside the skull. Older people may have headaches, double vision, poor ...
, and intracranial arteriosclerosis. Other consequences include sensorineural deafness, seizures, and intellectual disability.
Congenital toxoplasmosis may also impact a child's hearing. Up to 30% of newborns have some degree of sensorineural hearing loss. The child's communication skills may also be affected. A study published in 2010 looked at 106 patients, all of whom received toxoplasmosis treatment prior to 2.5 months. Of this group, 26.4% presented with language disorders.
Treatment
Treatment is recommended for people with serious health problems, such as people with HIV
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
whose CD4 counts are under 200 cells/mm3. Trimethoprim/sulfamethoxazole
Trimethoprim/sulfamethoxazole, sold under the brand name Bactrim among others, is a fixed-dose combination antibiotic medication used to treat a variety of bacterial infections. It consists of one part trimethoprim to five parts sulfamethoxazo ...
is the drug of choice to prevent toxoplasmosis, but not for treating active disease.
A 2012 study shows a promising new way to treat the active and latent form of this disease using two endochin-like quinolones.
Acute
The medications prescribed for acute toxoplasmosis are the following:
* Pyrimethamine
Pyrimethamine, sold under the brand name Daraprim among others, is a medication used with leucovorin (leucovorin is used to decrease side effects of pyrimethamine; it does not have intrinsic anti-parasitic activity) to treat the parasitic disea ...
– an antimalarial medication
Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young c ...
* Sulfadiazine
Sulfadiazine is an antibiotic. Used together with pyrimethamine, a dihydrofolate reductase inhibitor, it is the treatment of choice for toxoplasmosis, which is caused by a protozoan parasite. It is a second-line treatment for otitis media, p ...
– an antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
used in combination with pyrimethamine to treat toxoplasmosis
** Combination therapy is usually given with folic acid supplements to reduce incidence of thrombocytopaenia
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 and ...
.
** Combination therapy is most useful in the setting of HIV.
* 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 ...
* Spiramycin
Spiramycin is a macrolide antibiotic and antiparasitic. It is used to treat toxoplasmosis and various other infections of soft tissues. Although used in Europe, Canada and Mexico, spiramycin is still considered an experimental drug in the United ...
– an antibiotic used most often for pregnant women to prevent the infection of their children.
(other antibiotics, such as minocycline
Minocycline, sold under the brand name Minocin among others, is a tetracycline antibiotic medication used to treat a number of bacterial infections such as pneumonia. It is generally less preferred than the tetracycline doxycycline. It is also ...
, have seen some use as a salvage therapy
Salvage therapy, also known as rescue therapy, is a form of therapy given after an ailment does not respond to standard therapy. The most common diseases that require salvage therapy are HIV and various cancers. The term is not clearly defined; it ...
).
If infected during pregnancy, spiramycin is recommended in the first and early second trimesters while pyrimethamine/sulfadiazine and leucovorin
Folinic acid, also known as leucovorin, is a medication used to decrease the toxic effects of methotrexate and pyrimethamine. It is also used in combination with 5-fluorouracil to treat colorectal cancer and pancreatic cancer, may be used to tr ...
is recommended in the late second and third trimesters.
Latent
In people with latent toxoplasmosis, the cysts are immune to these treatments, as the antibiotics do not reach the bradyzoite
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 ...
s in sufficient concentration.
The medications prescribed for latent toxoplasmosis are:
* Atovaquone – an antibiotic that has been used to kill ''Toxoplasma'' cysts inside 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 m ...
patients
* 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 ...
– an antibiotic that, in combination with atovaquone, seemed to optimally kill cysts in mice
Congenital
When a pregnant woman is diagnosed with acute toxoplasmosis, amniocentesis can be used to determine whether the fetus has been infected or not. When a pregnant woman develops acute toxoplasmosis, the tachyzoites
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 ...
have approximately a 30% chance of entering the placental tissue, and from there entering and infecting the fetus. As gestational age at the time of infection increases, the chance of fetal infection also increases.
If the parasite has not yet reached the fetus, spiramycin
Spiramycin is a macrolide antibiotic and antiparasitic. It is used to treat toxoplasmosis and various other infections of soft tissues. Although used in Europe, Canada and Mexico, spiramycin is still considered an experimental drug in the United ...
can help to prevent placental transmission. If the fetus has been infected, the pregnant woman can be treated with pyrimethamine
Pyrimethamine, sold under the brand name Daraprim among others, is a medication used with leucovorin (leucovorin is used to decrease side effects of pyrimethamine; it does not have intrinsic anti-parasitic activity) to treat the parasitic disea ...
and sulfadiazine
Sulfadiazine is an antibiotic. Used together with pyrimethamine, a dihydrofolate reductase inhibitor, it is the treatment of choice for toxoplasmosis, which is caused by a protozoan parasite. It is a second-line treatment for otitis media, p ...
, with folinic acid
Folinic acid, also known as leucovorin, is a medication used to decrease the toxic effects of methotrexate and pyrimethamine. It is also used in combination with 5-fluorouracil to treat colorectal cancer and pancreatic cancer, may be used to tr ...
, after the first trimester. They are treated after the first trimester because pyrimethamine has an antifolate effect, and lack of folic acid can interfere with fetal brain formation and cause thrombocytopaenia
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 and ...
. Infection in earlier gestational stages correlates with poorer fetal and neonatal outcomes, particularly when the infection is untreated.
Newborns who undergo 12 months of postnatal anti-toxoplasmosis treatment have a low chance of sensorineural hearing loss. Information regarding treatment milestones for children with congenital toxoplasmosis have been created for this group.
Epidemiology
''T. gondii'' infections occur throughout the world, although infection rates differ significantly by country. For women of childbearing age, a survey of 99 studies within 44 countries found the areas of highest prevalence are within Latin America
Latin America or
* french: Amérique Latine, link=no
* ht, Amerik Latin, link=no
* pt, América Latina, link=no, name=a, sometimes referred to as LatAm is a large cultural region in the Americas where Romance languages — languages derived f ...
(about 50–80%), parts of Eastern
Eastern may refer to:
Transportation
*China Eastern Airlines, a current Chinese airline based in Shanghai
*Eastern Air, former name of Zambia Skyways
*Eastern Air Lines, a defunct American airline that operated from 1926 to 1991
*Eastern Air Li ...
and Central Europe
Central Europe is an area of Europe between Western Europe and Eastern Europe, based on a common historical, social and cultural identity. The Thirty Years' War (1618–1648) between Catholicism and Protestantism significantly shaped the area' ...
(about 20–60%), the Middle East
The Middle East ( ar, الشرق الأوسط, ISO 233: ) is a geopolitical region commonly encompassing Arabian Peninsula, Arabia (including the Arabian Peninsula and Bahrain), Anatolia, Asia Minor (Asian part of Turkey except Hatay Pro ...
(about 30–50%), parts of Southeast Asia
Southeast Asia, also spelled South East Asia and South-East Asia, and also known as Southeastern Asia, South-eastern Asia or SEA, is the geographical United Nations geoscheme for Asia#South-eastern Asia, south-eastern region of Asia, consistin ...
(about 20–60%), and parts of Africa
Africa is the world's second-largest and second-most populous continent, after Asia in both cases. At about 30.3 million km2 (11.7 million square miles) including adjacent islands, it covers 6% of Earth's total surface area ...
(about 20–55%).
In the United States, data from the National Health and Nutrition Examination Survey
The National Health and Nutrition Examination Survey (NHANES) is a survey research program conducted by the National Center for Health Statistics (NCHS) to assess the health and nutritional status of adults and children in the United States, and to ...
(NHANES) from 1999 to 2004 found 9.0% of US-born persons 12–49 years of age were seropositive
Serostatus refers to the presence or absence of a serological marker in the blood. The presence of detectable levels of a specific marker within the serum is considered seropositivity, while the absence of such levels is considered seronegativity.
...
for IgG
Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...
antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
against ''T. gondii'', down from 14.1% as measured in the NHANES 1988–1994. In the 1999–2004 survey, 7.7% of US-born and 28.1% of foreign-born women 15–44 years of age were ''T. gondii'' seropositive. A trend of decreasing 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 ...
has been observed by numerous studies in the United States and many European countries. Toxoplasma gondii is considered the second leading cause of foodborne-related deaths and the fourth leading cause of foodborne-related hospitalizations in the United States.
The protist responsible for toxoplasmosis is ''T. gondii''. There are three major types of T. gondii responsible for the patterns of toxoplasmosis throughout the world. There are types I, II, and III. These three types of ''T. gondii'' have differing effects on certain hosts, mainly mice and humans due to their variation in genotypes.
* Type I: virulent in mice and humans, seen in people with AIDS
People With AIDS (PWA) means " person with HIV/AIDS", also sometimes phrased as, Person Living with AIDS. It is a term of self-empowerment, adopted by those with the virus in the early years of the pandemic (the 1980s), as an alternative to the p ...
.
* Type II: non-virulent in mice, virulent in humans (mostly Europe and North America), seen in people with AIDS.
* Type III: non-virulent in mice, virulent mainly in animals but seen to a lesser degree in humans as well.
Current serotyping
A serotype or serovar is a distinct variation within a species of bacteria or virus or among immune cells of different individuals. These microorganisms, viruses, or cells are classified together based on their surface antigens, allowing the epi ...
techniques can only separate type I or III from type II parasites.
Because the parasite poses a particular threat to fetuses when it is contracted during pregnancy, much of the global epidemiological
Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants of health and disease conditions in a defined population.
It is a cornerstone of public health, and shapes policy decisions and evidenc ...
data regarding ''T. gondii'' comes from seropositivity tests in women of childbearing age. Seropositivity tests look for the presence of antibodies against ''T. gondii'' in blood, so while seropositivity guarantees one has been exposed to the parasite, it does not necessarily guarantee one is chronically infected.
History
''Toxoplasma gondii
''Toxoplasma gondii'' () is an obligate intracellular parasitic protozoan (specifically an apicomplexan) that causes toxoplasmosis. Found worldwide, ''T. gondii'' is capable of infecting virtually all warm-blooded animals, but felids, such as d ...
'' was first described in 1908 by Nicolle and Manceaux in Tunisia, and independently by Splendore in Brazil.[ Splendore reported the ]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 ...
in a rabbit, while Nicolle and Manceaux identified it in a North African rodent, the gundi (Ctenodactylus gundi
The common gundi (''Ctenodactylus gundi'') is a species of rodent in the family Ctenodactylidae. It is found in Algeria, Libya, Morocco, and Tunisia. The parasitic organism '' Toxoplasma gondii'' was first described in 1908 in Tunis by Charles ...
). In 1909 Nicolle and Manceaux differentiated the protozoan from ''Leishmania
''Leishmania'' is a parasitic protozoan, a single-celled organism of the genus '' Leishmania'' that are responsible for the disease leishmaniasis. They are spread by sandflies of the genus ''Phlebotomus'' in the Old World, and of the genus '' ...
''. Nicolle and Manceaux then named it ''Toxoplasma gondii'' after the curved shape of its infectious stage (Greek root ''= bow).
The first recorded case of congenital toxoplasmosis was in 1923, but it was not identified as caused by ''T. gondii''. Janků (1923) described in detail the autopsy results of an 11-month-old boy who had presented to hospital with hydrocephalus
Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased intracranial pressure, pressure inside the skull. Older people may have headaches, double vision, poor ...
. The boy had classic marks of toxoplasmosis including chorioretinitis
Chorioretinitis is an inflammation of the choroid (thin pigmented vascular coat of the eye) and retina of the eye. It is a form of posterior uveitis. If only the choroid is inflamed, not the retina, the condition is termed choroiditis. The ophthalm ...
(inflammation of the choroid and retina of the eye). Histology revealed a number of "sporocytes", though Janků did not identify these as ''T. gondii''.
It was not until 1937 that the first detailed scientific analysis of ''T. gondii'' took place using techniques previously developed for analyzing viruses. In 1937 Sabin and Olitsky analyzed ''T. gondii'' in laboratory monkeys and mice. Sabin and Olitsky showed that ''T. gondii'' was an obligate intracellular parasite and that mice fed ''T. gondii''-contaminated tissue also contracted the infection. Thus Sabin and Olitsky demonstrated ''T. gondii'' as a pathogen
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 ...
transmissible between animals.
''T. gondii'' was first described as a human pathogen in 1939 at Babies Hospital Morgan Stanley Children's Hospital of NewYork-Presbyterian (MSCH or CHONY) is a women's and children's hospital at 3959 Broadway, near West 165th Street, in the Washington Heights neighborhood of Manhattan, New York City. It is a part of NewYork-Pr ...
in New York City
New York, often called New York City or NYC, is the List of United States cities by population, most populous city in the United States. With a 2020 population of 8,804,190 distributed over , New York City is also the L ...
. Wolf, Cowen and Paige identified ''T. gondii'' infection in an infant girl delivered full-term by Caesarean
Caesarean section, also known as C-section or caesarean delivery, is the surgical procedure by which one or more babies are delivered through an incision in the mother's abdomen, often performed because vaginal delivery would put the baby or mo ...
section. The infant developed seizures and had chorioretinitis in both eyes at three days. The infant then developed encephalomyelitis and died at one month of age. Wolf, Cowen and Paige isolated ''T. gondii'' from brain tissue lesions. Intracranial injection of brain and spinal cord samples into mice, rabbits and rats produced encephalitis in the animals. Wolf, Cowen and Page reviewed additional cases and concluded that ''T. gondii'' produced recognizable symptoms and could be transmitted from mother to child.
The first adult case of toxoplasmosis was reported in 1940 with no neurological signs. Pinkerton and Weinman reported the presence of ''Toxoplasma'' in a 22-year-old man from Peru who died from a subsequent bacterial infection and fever.
In 1948, a serological dye test was created by Sabin and Feldman based on the ability of the patient's antibodies to alter staining of ''Toxoplasma''. The Sabin Feldman Dye Test is now the gold standard for identifying ''Toxoplasma'' infection.
Transmission of ''Toxoplasma'' by eating raw or undercooked meat was demonstrated by Desmonts et al. in 1965 Paris. Desmonts observed that the therapeutic consumption of raw beef or horse meat in a tuberculosis
Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...
hospital was associated with a 50% per year increase in ''Toxoplasma'' antibodies. This means that more ''T. gondii'' was being transmitted through the raw meat.
In 1974, Desmonts and Couvreur showed that infection during the first two trimesters produces most harm to the fetus, that transmission depended on when mothers were infected during pregnancy, that mothers with antibodies before pregnancy did not transmit the infection to the fetus, and that spiramycin
Spiramycin is a macrolide antibiotic and antiparasitic. It is used to treat toxoplasmosis and various other infections of soft tissues. Although used in Europe, Canada and Mexico, spiramycin is still considered an experimental drug in the United ...
lowered the transmission to the fetus.
''Toxoplasma'' gained more attention in the 1970s with the rise of immune-suppressant treatment given after organ or bone marrow transplants and the 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 m ...
epidemic of the 1980s. Patients with lowered immune system function are much more susceptible to disease.
Society and culture
"Crazy cat-lady"
"Crazy cat-lady syndrome" is a term coined by news organizations to describe scientific findings that link the parasite ''Toxoplasma gondii
''Toxoplasma gondii'' () is an obligate intracellular parasitic protozoan (specifically an apicomplexan) that causes toxoplasmosis. Found worldwide, ''T. gondii'' is capable of infecting virtually all warm-blooded animals, but felids, such as d ...
'' to several mental disorders
A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitti ...
and behavioral problems. The suspected correlation between cat ownership in childhood and later development of schizophrenia
Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...
suggested that further studies were needed to determine a risk factor for children; however, later studies showed that ''T. gondii'' was not a causative factor in later psychoses. Researchers also found that cat ownership does not strongly increase the risk of a ''T. gondii'' infection in pregnant women.
The term ''crazy cat-lady syndrome'' draws on both stereotype and popular cultural reference. It was originated as instances of the aforementioned afflictions were noted amongst the populace. A cat lady
A cat lady is a cultural archetype or stock character, most often depicted as a woman, a middle-aged or elderly spinster or widow, who has many cats. The term may be pejorative, or it may be affectionately embraced.
Usage and association
Women ...
is a cultural stereotype of a woman who compulsively hoards
A hoard or "wealth deposit" is an archaeological term for a collection of valuable objects or artifacts, sometimes purposely buried in the ground, in which case it is sometimes also known as a cache. This would usually be with the intention of ...
and dotes upon cats. The biologist Jaroslav Flegr
Jaroslav Flegr (born 12 March 1958) is a Czech parasitology, parasitologist, Evolution, evolutionary biologist, and author of the book Frozen Evolution (book), ''Frozen Evolution''. He is professor of biology at the Faculty of Science, Charles Un ...
is a proponent of the theory that toxoplasmosis affects human behaviour.
Notable cases
* Tennis player Arthur Ashe
Arthur Robert Ashe Jr. (July 10, 1943 – February 6, 1993) was an American professional tennis player who won three Grand Slam singles titles. He started to play tennis at six years old. He was the first black player selected to the Unite ...
developed neurological problems from toxoplasmosis (and was later found to be HIV
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
-positive).
* Actor Merritt Butrick
Merritt R. Butrick (September 3, 1959 – March 17, 1989) was an American actor, known for his roles on the teen sitcom ''Square Pegs'' (1982), in two '' Star Trek'' feature films, and a variety of other acting roles in the 1980s.
Early lif ...
was HIV-positive and died from toxoplasmosis as a result of his already-weakened immune system.
* Pedro Zamora
Pedro Pablo Zamora (born Pedro Pablo Zamora y Díaz, February 29, 1972 – November 11, 1994) was a Cuban-American AIDS educator and television personality.''Pedro Zamora'', WPBT Channel 2-New Florida, November 11–17, 2004, Oscar Lopez Produce ...
, reality television personality and HIV/AIDS activist, was diagnosed with toxoplasmosis as a result of his immune system being weakened by HIV.
* Prince François, Count of Clermont, pretender
A pretender is someone who claims to be the rightful ruler of a country although not recognized as such by the current government. The term is often used to suggest that a claim is not legitimate.Curley Jr., Walter J. P. ''Monarchs-in-Waiting'' ...
to the throne of France
France was ruled by Monarch, monarchs from the establishment of the West Francia, Kingdom of West Francia in 843 until the end of the Second French Empire in 1870, with several interruptions.
Classical French historiography usually regards Cl ...
had congenital toxoplasmosis; his disability caused him to be overlooked in the line of succession.
* Actress Leslie Ash
Leslie Ash (born 19 February 1960) is an English actress.
She is best known for her roles in ''C.A.T.S. Eyes'' (1985–1987), the BBC sitcom ''Men Behaving Badly'' (1992–1997), ITV drama '' Where the Heart Is'' (2000–2003), and BBC me ...
contracted toxoplasmosis in the second month of pregnancy.
* British middle-distance runner Sebastian Coe
Sebastian Newbold Coe, Baron Coe, (born 29 September 1956), often referred to as Seb Coe, is a British politician and former track and field athlete. As a middle-distance runner, Coe won four Olympic medals, including 1500 metres gold medal ...
contracted toxoplasmosis in 1983, which was probably transmitted by a cat while he trained in Italy.
* Tennis player Martina Navratilova
Martina Navratilova ( cs, Martina Navrátilová ; ; born October 18, 1956) is a Czech–American, former professional tennis player. Widely considered among the greatest tennis players of all time, Navratilova won 18 major singles titles, 31 maj ...
experienced toxoplasmosis during the 1982 US Open.
Other animals
Although ''T. gondii'' has the capability of infecting virtually all warm-blooded animals, susceptibility and rates of infection vary widely between different genera
Genus ( plural genera ) is a taxonomic rank used in the biological classification of living and fossil organisms as well as viruses. In the hierarchy of biological classification, genus comes above species and below family. In binomial nomenclat ...
and species
In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...
.[ ] Rates of infection in populations of the same species can also vary widely due to differences in location, diet, and other factors.
Although infection with ''T. gondii'' has been noted in several species of Asian primates, seroprevalence of ''T. gondii'' antibodies were found for the first time in toque macaques (''Macaca sinica
The toque macaque (; ''Macaca sinica'') is a reddish-brown-coloured Old World monkey endemic to Sri Lanka, where it is known as the ''rilewa'' or ''rilawa'' ( Sinhala: රිළවා), (hence "rillow" in the ''Oxford English Dictionary''). Its ...
'') that are endemic to the island of Sri Lanka.
Australian marsupials
Marsupials are any members of the mammalian infraclass Marsupialia. All extant marsupials are endemic to Australasia, Wallacea and the Americas. A distinctive characteristic common to most of these species is that the young are carried in a po ...
are particularly susceptible to toxoplasmosis. Wallabies
A wallaby () is a small or middle-sized macropod native to Australia and New Guinea, with introduced populations in New Zealand, Hawaii, the United Kingdom and other countries. They belong to the same taxonomic family as kangaroos and so ...
, koalas
The koala or, inaccurately, koala bear (''Phascolarctos cinereus''), is an arboreal herbivorous marsupial native to Australia. It is the only extant representative of the family Phascolarctidae and its closest living relatives are the womba ...
, wombats
Wombats are short-legged, muscular quadrupedal marsupials that are native to Australia. They are about in length with small, stubby tails and weigh between . All three of the extant species are members of the family Vombatidae. They are adap ...
, pademelon
Pademelons are small, furry, hopping mammals in the genus ''Thylogale'', found in Australia and New Guinea. They are some of the smallest members of the macropod family (Macropodidae), which includes the similar-looking but larger kangaroos an ...
s and small dasyurids can be killed by it, with eastern barred bandicoot
The eastern barred bandicoot (''Perameles gunnii'') is a nocturnal, rabbit-sized marsupial endemic to southeastern Australia, being native to the island of Tasmania and mainland Victoria. It is one of three surviving bandicoot species in the ge ...
s typically dying within about 3 weeks of infection.
It is estimated that 23% of wild swine worldwide are seropositive for ''T. gondii''. Seroprevalence varies across the globe with the highest seroprevalence in North America (32%) and Europe (26%) and the lowest in Asia (13%) and South America (5%). Geographical regions located at higher latitudes and regions that experience warmer, humid climates are associated with increased seroprevalence of ''T. gondii'' among wild boar. Wild boar infected with ''T. gondii'' pose a potential health risk for humans who consume their meat.
Livestock
Among livestock
Livestock are the domesticated animals raised in an agricultural setting to provide labor and produce diversified products for consumption such as meat, eggs, milk, fur, leather, and wool. The term is sometimes used to refer solely to animals ...
, pigs, sheep[ ] and goats have the highest rates of chronic ''T. gondii'' infection. The prevalence of ''T. gondii'' in meat-producing animals varies widely both within and among countries, and rates of infection have been shown to be dramatically influenced by varying farming and management practices. For instance, animals kept outdoors or in free-ranging environments are more at risk of infection than animals raised indoors or in commercial confinement operations.
Pigs
Worldwide, the percentage of pigs harboring viable parasites has been measured to be 3–71.43% and in the United States (via bioassay
A bioassay is an analytical method to determine the concentration or potency of a substance by its effect on living animals or plants (''in vivo''), or on living cells or tissues(''in vitro''). A bioassay can be either quantal or quantitative, dir ...
in mice or cats) to be as high as 92.7% and as low as 0%, depending on the farm or herd. Surveys of seroprevalence (''T. gondii'' antibodies in blood) are more common, and such measurements are indicative of the high relative seroprevalence in pigs across the world. Neonatal piglets have been found to experience the entire range of severity, including progression to stillbirth
Stillbirth is typically defined as fetal death at or after 20 or 28 weeks of pregnancy, depending on the source. It results in a baby born without signs of life. A stillbirth can result in the feeling of guilt or grief in the mother. The term ...
. This was especially demonstrated in the foundational Thiptara et al. 2006, reporting a litter birth of three stillborns and six live in Thailand. This observation has been relevant not only to that country but to toxoplasmosis control in porciculture
Pig farming or pork farming or hog farming is the raising and breeding of domestic pigs as livestock, and is a branch of animal husbandry. Pigs are farmed principally for food (e.g. pork: bacon, ham, gammon) and skins.
Pigs are amenable to ...
around the world.
Sheep
Along with pigs, sheep and goats are among the most commonly infected livestock of epidemiological significance for human infection. Prevalence of viable ''T. gondii'' in sheep tissue has been measured (via bioassay) to be as high as 78% in the United States, and a 2011 survey of goats intended for consumption in the United States found a seroprevalence of 53.4%.
Chickens
Due to a lack of exposure to the outdoors, chickens raised in large-scale indoor confinement operations are not commonly infected with ''T. gondii''. Free-ranging or backyard-raised chickens are much more commonly infected. A survey of free-ranging chickens in the United States found its prevalence to be 17–100%, depending on the farm. Because chicken meat is generally cooked thoroughly before consumption, poultry is not generally considered to be a significant risk factor for human ''T. gondii'' infection.
Cattle
Although cattle and buffalo can be infected with ''T. gondii'', the parasite is generally eliminated or reduced to undetectable levels within a few weeks following exposure. Tissue cysts are rarely present in buffalo meat or beef, and meat from these animals is considered to be low-risk for harboring viable parasites.[ ]
Horses
Horses are considered resistant to chronic ''T. gondii'' infection. However, viable cells have been isolated from US horses slaughtered for export, and severe human toxoplasmosis in France has been epidemiologically linked to the consumption of horse meat
Horse meat forms a significant part of the culinary traditions of many countries, particularly in Eurasia. The eight countries that consume the most horse meat consume about 4.3 million horses a year. For the majority of humanity's early existe ...
.
Domestic cats
In 1942, the first case of feline toxoplasmosis was diagnosed and reported in a domestic cat in Middletown, New York. The investigators isolated oocysts from feline feces and found that the oocysts could be infectious for up to 12 months in the environment.
The seroprevalence of ''T. gondii'' in domestic cat
The cat (''Felis catus'') is a domestic species of small carnivorous mammal. It is the only domesticated species in the family Felidae and is commonly referred to as the domestic cat or house cat to distinguish it from the wild members o ...
s, worldwide has been estimated to be around 30–40% and exhibits significant geographical variation. In the United States, no official national estimate has been made, but local surveys have shown levels varying between 16% and 80%. A 2012 survey of 445 purebred
Purebreds are "cultivated varieties" of an animal species achieved through the process of selective breeding. When the lineage of a purebred animal is recorded, that animal is said to be "pedigreed". Purebreds breed true-to-type which means the p ...
pet cats and 45 shelter cats in Finland
Finland ( fi, Suomi ; sv, Finland ), officially the Republic of Finland (; ), is a Nordic country in Northern Europe. It shares land borders with Sweden to the northwest, Norway to the north, and Russia to the east, with the Gulf of B ...
found an overall seroprevalence of 48.4%, while a 2010 survey of feral cats from Giza, Egypt
Giza (; sometimes spelled ''Gizah'' arz, الجيزة ' ) is the second-largest city in Egypt after Cairo and fourth-largest city in Africa after Kinshasa, Lagos and Cairo. It is the capital of Giza Governorate with a total population of 9.2 ...
found a seroprevalence rate of 97.4%. Another survey from Colombia recorded seroprevalence of 89.3%, whereas a Chinese (Guangdong
Guangdong (, ), alternatively romanized as Canton or Kwangtung, is a coastal province in South China on the north shore of the South China Sea. The capital of the province is Guangzhou. With a population of 126.01 million (as of 2020) ...
) study found just a 2.1% prevalence.
''T. gondii'' infection rates in domestic cats vary widely depending on the cats' diets and lifestyles. Feral cat
A feral cat or a stray cat is an unowned domestic cat (''Felis catus'') that lives outdoors and avoids human contact: it does not allow itself to be handled or touched, and usually remains hidden from humans. Feral cats may breed over dozens ...
s that hunt for their food are more likely to be infected than domestic cats, and naturally also depends on the prevalence of ''T. gondii''-infected prey such as birds and small mammals
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
.
Most infected cats will shed oocysts only once in their lifetimes, for a period of about one to two weeks. This shedding can release millions of oocysts, each capable of spreading and surviving for months. An estimated 1% of cats at any given time are actively shedding oocysts.
It is difficult to control the cat population with the infected oocysts due to lack of an effective vaccine. This remains a challenge in most cases and the programs that are readily available are questionable in efficacy.
Rodents
Infection with ''T. gondii'' has been shown to alter the behavior of mice and rats in ways thought to increase the rodents' chances of being preyed upon by cats. Infected rodents show a reduction in their innate aversion to cat odors; while uninfected mice and rats will generally avoid areas marked with cat urine
Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra.
Cel ...
or with cat body odor, this avoidance is reduced or eliminated in infected animals. Moreover, some evidence suggests this loss of aversion may be specific to feline odors: when given a choice between two predator
Predation is a biological interaction where one organism, the predator, kills and eats another organism, its prey. It is one of a family of common feeding behaviours that includes parasitism and micropredation (which usually do not kill th ...
odors (cat or mink
Mink are dark-colored, semiaquatic, carnivorous mammals of the genera ''Neogale'' and '' Mustela'' and part of the family Mustelidae, which also includes weasels, otters, and ferrets. There are two extant species referred to as "mink": the A ...
), infected rodents show a significantly stronger preference to cat odors than do uninfected controls.
In rodents, ''T. gondii''–induced behavioral changes occur through epigenetic remodeling in neurons associated with observed behaviors; for example, it modifies epigenetic methylation to induce hypomethylation of arginine vasopressin
Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then trave ...
-related genes in the medial amygdala to greatly decrease predator aversion. Similar epigenetically induced behavioral changes have also been observed in mouse models of addiction, where changes in the expression of histone-modifying enzymes via gene knockout
A gene knockout (abbreviation: KO) is a genetic technique in which one of an organism's genes is made inoperative ("knocked out" of the organism). However, KO can also refer to the gene that is knocked out or the organism that carries the gene kno ...
or enzyme inhibition
An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a sp ...
in specific neurons produced alterations in drug-related behaviors. Widespread histone–lysine acetylation in cortical astrocytes
Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endo ...
appears to be another epigenetic mechanism employed by ''T. gondii''.
''T. gondii''-infected rodents show a number of behavioral changes beyond altered responses to cat odors. Rats infected with the parasite show increased levels of activity and decreased neophobic behavior. Similarly, infected mice show alterations in patterns of locomotion
Locomotion means the act or ability of something to transport or move itself from place to place.
Locomotion may refer to:
Motion
* Motion (physics)
* Robot locomotion, of man-made devices
By environment
* Aquatic locomotion
* Flight
* Locomo ...
and exploratory behavior during experimental tests. These patterns include traveling greater distances, moving at higher speeds, accelerating for longer periods of time, and showing a decreased pause-time when placed in new arenas. Infected rodents have also been shown to have lower anxiety
Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
, using traditional models such as elevated plus maze
The elevated plus maze (EPM) is a test measuring anxiety in laboratory animals that usually uses rodents as a screening test for putative anxiolytic or anxiogenic compounds and as a general research tool in neurobiological anxiety research su ...
s, open field arenas, and social interaction tests.
Marine mammals
A University of California, Davis
The University of California, Davis (UC Davis, UCD, or Davis) is a public land-grant research university near Davis, California. Named a Public Ivy, it is the northernmost of the ten campuses of the University of California system. The institut ...
study of dead sea otter
The sea otter (''Enhydra lutris'') is a marine mammal native to the coasts of the northern and eastern North Pacific Ocean. Adult sea otters typically weigh between , making them the heaviest members of the weasel family, but among the small ...
s collected from 1998 to 2004 found toxoplasmosis was the cause of death for 13% of the animals. Proximity to freshwater outflows into the ocean was a major risk factor. Ingestion of oocysts
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 ...
from cat feces is considered to be the most likely ultimate source. Surface runoff
Surface runoff (also known as overland flow) is the flow of water occurring on the ground surface when excess rainwater, stormwater, meltwater, or other sources, can no longer sufficiently rapidly infiltrate in the soil. This can occur when th ...
containing wild cat feces and litter from domestic cats flushed down toilets are possible sources of oocysts. These same sources may have also introduced the toxoplasmosis infection to the endangered Hawaiian monk seal
The Hawaiian monk seal (''Neomonachus schauinslandi'') is an endangered species of earless seal in the family Phocidae that is endemic to the Hawaiian Islands.
The Hawaiian monk seal is one of two extant monk seal species; the other is the Med ...
. Infection with the parasite has contributed to the death of at least four Hawaiian monk seals. A Hawaiian monk seal's infection with ''T. gondii'' was first noted in 2004. The parasite's spread threatens the recovery of this highly endangered pinniped. The parasites have been found in dolphins and whales. Researchers Black and Massie believe anchovies, which travel from estuaries into the open ocean, may be helping to spread the disease.
Giant panda
''Toxoplasma gondii'' has been reported as the cause of death of a giant panda
The giant panda (''Ailuropoda melanoleuca''), also known as the panda bear (or simply the panda), is a bear species endemic to China. It is characterised by its bold black-and-white coat and rotund body. The name "giant panda" is sometimes us ...
kept in a zoo in China, who died in 2014 of acute gastroenteritis
Gastroenteritis, also known as infectious diarrhea and gastro, is an inflammation of the gastrointestinal tract including the stomach and intestine. Symptoms may include diarrhea, vomiting, and abdominal pain. Fever, lack of energy, and dehydra ...
and respiratory disease
Respiratory diseases, or lung diseases, are pathology, pathological conditions affecting the organs and tissues that make gas exchange difficult in Breathing, air-breathing animals. They include conditions of the respiratory tract including the t ...
. Although seemingly anecdotal, this report emphasizes that all warm-blooded species are likely to be infected by ''T. gondii'', including endangered species such as the giant panda.
Research
Chronic infection with ''T. gondii'' has traditionally been considered asymptomatic
In medicine, any disease is classified asymptomatic if a patient tests as carrier for a disease or infection but experiences no symptoms. Whenever a medical condition fails to show noticeable symptoms after a diagnosis it might be considered asy ...
in people with normal immune function. Some evidence suggests latent infection may subtly influence a range of human behaviors and tendencies, and infection may alter the susceptibility to or intensity of a number of psychiatric
Psychiatry is the medical specialty devoted to the diagnosis, prevention, and treatment of mental disorders. These include various maladaptations related to mood, behaviour, cognition, and perceptions. See glossary of psychiatry.
Initial psychi ...
or neurological disorders.[
In most of the current studies where positive correlations have been found between ''T. gondii'' antibody titers and certain behavioral traits or neurological disorders, ''T. gondii'' seropositivity tests are conducted after the onset of the examined disease or behavioral trait; that is, it is often unclear whether infection with the parasite increases the chances of having a certain trait or disorder, or if having a certain trait or disorder increases the chances of becoming infected with the parasite.] Groups of individuals with certain behavioral traits or neurological disorders may share certain behavioral tendencies that increase the likelihood of exposure to and infection with ''T. gondii''; as a result, it is difficult to confirm causal relationships between ''T. gondii'' infections and associated neurological disorders or behavioral traits.
Mental health
Some evidence links ''T. gondii'' to schizophrenia
Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...
.[ Two 2012 meta-analyses found that the rates of ]antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
to ''T. gondii'' in people with schizophrenia were 2.7 times higher than in controls. ''T. gondii'' antibody positivity was therefore considered an intermediate risk factor in relation to other known risk factors. Cautions noted include that the antibody tests do not detect toxoplasmosis directly, most people with schizophrenia do not have antibodies for toxoplasmosis, and publication bias
In published academic research, publication bias occurs when the outcome of an experiment or research study biases the decision to publish or otherwise distribute it. Publishing only results that show a significant finding disturbs the balance o ...
might exist.[ While the majority of these studies tested people already diagnosed with schizophrenia for ''T. gondii'' antibodies, associations between ''T. gondii'' and schizophrenia have been found prior to the onset of schizophrenia symptoms.] Sex differences in the age of schizophrenia onset may be explained in part by a second peak of ''T. gondii'' infection incidence during ages 25–30 in females only. Although a mechanism supporting the association between schizophrenia and ''T. gondii'' infection is unclear, studies have investigated a molecular basis of this correlation. Antipsychotic drugs
Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of oth ...
used in schizophrenia appear to inhibit the replication of ''T. gondii'' tachyzoites in cell culture. Supposing a causal link exists between ''T. gondii'' and schizophrenia, studies have yet to determine why only some individuals with latent toxoplasmosis develop schizophrenia; some plausible explanations include differing genetic susceptibility, parasite strain differences, and differences in the route of the acquired ''T. gondii'' infection.
Correlations have also been found between antibody titer
Titer (American English) or titre (British English) is a way of expressing concentration. Titer testing employs serial dilution to obtain approximate quantitative information from an analytical procedure that inherently only evaluates as positiv ...
s to ''T. gondii'' and OCD, as well as suicide
Suicide is the act of intentionally causing one's own death. Mental disorders (including depression, bipolar disorder, schizophrenia, personality disorders, anxiety disorders), physical disorders (such as chronic fatigue syndrome), and s ...
among people with mood disorders including bipolar disorder
Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...
. Positive antibody titers to ''T. gondii'' appear to be uncorrelated with major depression
Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introdu ...
or dysthymia. Although there is a correlation between ''T. gondii'' and many psychological disorders, the underlying mechanism is unclear. A 2016 study of 236 persons with high levels of toxoplasmosis antibodies found that "there was little evidence that T. gondii was related to increased risk of psychiatric disorder, poor impulse control, personality aberrations or neurocognitive impairment".
Neurological disorders
Latent infection has been linked to Parkinson's disease and Alzheimer's disease.
Individuals with multiple sclerosis show infection rates around 15% lower than the general public.
Traffic accidents
Latent ''T. gondii'' infection in humans has been associated with a higher risk of automobile accidents, potentially due to impaired psychomotor learning, psychomotor performance or enhanced risk-taking personality profiles.
Climate change
Climate change has been reported to affect the occurrence, survival, distribution and transmission of ''T. gondii''. ''T. gondii'' has been identified in the Canadian arctic, a location that was once too cold for its survival. Higher temperatures increase the survival time of ''T. gondii''. More snowmelt and precipitation can increase the amount of ''T. gondii'' oocysts that are transported via river flow. Shifts in bird, rodent, and insect populations and migration patterns can impact the distribution of ''T. gondii'' due to their role as reservoir and vector. Urbanization and natural environmental degradation are also suggested to affect ''T. gondii'' transmission and increase risk of infection.
See also
* Toxoplasmic chorioretinitis
* TORCH complex, TORCH infection
* Pyrimethamine
Pyrimethamine, sold under the brand name Daraprim among others, is a medication used with leucovorin (leucovorin is used to decrease side effects of pyrimethamine; it does not have intrinsic anti-parasitic activity) to treat the parasitic disea ...
References
:* Parts of this article are taken from the public domai
CDC factsheet: Toxoplasmosis
Bibliography
*
*
*
*
External links
How a cat-borne parasite infects humans
(National Geographic)
*
Toxoplasmosis
at Health Protection Agency (HPA), United Kingdom
Medical Image Database
Video-Interview
with Professor Robert Sapolsky on Toxoplasmosis and its effect on human behavior (24:27 min)
*
{{Authority control
Conoidasida
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Health issues in pregnancy
Mind-altering parasites
Parasitic infestations, stings, and bites of the skin
Poultry diseases
Protozoal diseases
Zoonoses
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Biology of bipolar disorder
Biology of obsessive–compulsive disorder
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