Human defenses to toxoplasmosis

Human defenses to toxoplasmosis

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Toxoplasmosis modifies the rat's brain to make them love (and be eaten by) cats. It also infects ~30% of humans, and modifies traits in several bad ways (i.e. schizophrenia and increased reaction time). However, humans are thought to be a "dead end" for the parasite. Thus, there is a significant selection pressure for humans to develop resistance but no (or almost no) pressure for toxoplasmosis to counter human resistance. If so, why are so many people infected?

Thus, there is a significant selection pressure for humans to develop resistance but no (or almost no) pressure for toxoplasmosis to counter human resistance.

Well, I think in this case "Significant" isn't qualified. Significant selective pressure can come in many forms, but as you mention about 30% of humans are infected with Toxopolasma, and the vast majority remain capable and functional. Remember that selective pressure applies to the ability to take advantage of resources and reproduce. People with toxoplasmosis are almost always capable of surviving and reproducing, so I doubt the pressure is all that much.

There is also significant incentive for Toxoplasma to develop the ability to adapt to humans, as it would open up a whole new resource for them to take advantage of. How fast the parasite is capable of adapting, or even if it's possible to eventually include humans in their life cycle, is something that would take some studying.

Our immune systems, in turn, try to kill the parasite regardless of whether we're being taken advantage of or not. You might be interested in reading up on the Red Queen Hypothesis - a theory that delineates how the immune system is at constant war with its environment and potential new threats.

As for your last question…

… why are so many people infected?

That's easy. :-)

Cats have become a popular pet, and most of the time the parasite doesn't significantly affect us. If either of those changes, you'll see a change in infection rates.

Human immunity to Toxoplasma gondii

Copyright: © 2019 Fisch et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001076), the UK Medical Research Council (FC001076), and the Wellcome Trust (FC001076). EMF was supported by a Wellcome Trust Career Development Fellowship (091664/B/10/Z). DF was supported by a Boehringer Ingelheim Fonds PhD fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Systems analysis points to links between Toxoplasma infection and common brain diseases

More than 2 billion people nearly one out of every three humans on earth, including about 60 million people in the United States have a lifelong infection with the brain-dwelling parasite Toxoplasma gondii. In the September 13, 2017, issue of Scientific Reports, 32 researchers from 16 institutions describe efforts to learn how infection with this parasite may alter, and in some cases amplify, several brain disorders, including epilepsy, Alzheimer's and Parkinson's diseases as well as some cancers.

When a woman gets infected with T. gondii during pregnancy and passes the parasite on to her unborn child, the consequences can be profound, including devastating damage to the brain, nervous system and eyes. There is growing evidence, however, that acquiring this infection later in life may be far from harmless. So the researchers began looking for connections between this chronic but seemingly dormant infection and its potential to alter the course of common neurologic disorders.

"We wanted to understand how this parasite, which lives in the brain, might contribute to and shed light on pathogenesis of other brain diseases," said Rima McLeod, MD, professor of ophthalmology & visual science and pediatrics and medical director of the Toxoplasmosis Center at the University of Chicago.

"We suspect it involves multiple factors," she said. "At the core is alignment of characteristics of the parasite itself, the genes it expresses in the infected brain, susceptibility genes that could limit the host's ability to prevent infection, and genes that control susceptibility to other diseases present in the human host. Other factors may include pregnancy, stress, additional infections, and a deficient microbiome. We hypothesized that when there is confluence of these factors, disease may occur."

For more than a decade, researchers have noted subtle behavior manipulations associated with a latent T. gondii infection. Rats and mice that harbor this parasite, for example, lose their aversion to the smell of cat urine. This is perilous for a rodent, making it easier for cats to catch and eat them. But it benefits cats, who gain a meal, as well as the parasites, who gain a new host, who will distribute them widely into the environment. An acutely infected cat can excrete up to 500 million oocysts in a few weeks' time. Even one oocyst, which can remain in soil or water for up to a year, is infectious.

A more recent study found a similar connection involving primates. Infected chimpanzees lose their aversion to the scent of urine of their natural predator, leopards.

The research team decided to search for similar effects in people. They focused on what they call the human "infectome" plausible links between the parasite's secreted proteins, expressed human microRNAs, the neural chemistry of the human host, and the multiple pathways that are perturbed by host-parasite interactions.

Using data collected from the National Collaborative Chicago-Based Congenital Toxoplasmosis Study, which has diagnosed, treated and followed 246 congenitally infected persons and their families since 1981, they performed a "comprehensive systems analysis," looking at a range of parasite-generated biomarkers and assessing their probable impact.

Working with the J Craig Venter Institute and the Institute of Systems Biology Scientists, they looked at the effect of infections of primary neuronal stem cells from the human brain in tissue culture, focusing on gene expression and proteins perturbed. Part of the team, including Huan Ngo from Northwestern University, Hernan Lorenzi at the J Craig Venter Institute, Kai Wang and Taek-Kyun Kim at the Institute for Systems Biology and McLeod, integrated host genetics, proteomics, transcriptomics and circulating microRNA datasets to build a model of these effects on the human brain.

Using what they called a "reconstruction and deconvolution," approach, the researchers identified perturbed pathways associated with neurodegenerative diseases as well as connections between toxoplasmosis, human brain disorders and some cancers.

T. gondii (I, II, III) infection of S-NSC alters localization of p50-NFkB(red) and Stat 3 (second panel, red): SAG1 (Green), Hoechst (blue) T. gondii, in NSC, expresses or alters host cells' neurotransmitters. Tyrosine Hydroxylase (red) in the infected NSCs that synthesizes dopamine is present in T. gondii (middle panels 40X, 60X). This is further exemplified in the furthest right panel by a dopamine-like immunostaining pattern in the parasite (green). The red arrow in the dopamine-like staining image points to a host cell dense perinuclear distribution of label. This suggests potential to influence neurotransmission in human NSC.

  • Small regulatory biomarkers bits of microRNA or proteins found in children with severe toxoplasmosis matched those found in patients with neurodegenerative diseases like Alzheimer's or Parkinson's disease.
  • The parasite was able to manipulate 12 human olfactory receptors in ways that mimicked the cat-mouse or the chimp-leopard exchange.
  • Evidence that gondii could increase the risk of epilepsy, "possibly by altering GABAergic signaling."
  • gondii infection was associated with a network of 1,178 human genes, many of which are modified in various cancers.

"Our results provide insights into mechanisms whereby this parasite could cause these associated diseases under some circumstances," the authors wrote. "This work provides a systems roadmap to design medicines and vaccines to repair and prevent neuropathological effects of T. gondii on the human brain."

"This study is a paradigm shifter," said co-author Dennis Steinler, PhD, director of the Neuroscience and Aging Lab at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University. "We now have to insert infectious disease into the equation of neurodegenerative diseases, epilepsy and neural cancers."

"At the same time," he added, "we have to translate aspects of this study into preventive treatments that include everything from drugs to diet to life style, in order to delay disease onset and progression."

This work was funded by the National Institutes of Health, the Mann Cornwell Family, the Engel family, the Rooney, Drago, and the Morel families, and "Taking out Toxo." The Institute for Systems Biology is partially supported by research contracts from the Defense Threat Reduction Agency and the Department of Defense. The J. Craig Venter Institute sequencing and analysis was funded by the National Institute of Allergy and Infectious diseases, as was parts of the work at the University of Chicago.

Additional authors include Ying Zhou, Kamal El Bissati, Ernest Mui, Laura Fraczek, Fiona L. Henriquez, Kelsey Wheeler, Ian Begeman, Carlos Naranjo-Galvis, Ney Alliey-Rodriguez and Shawn Withers from the University of Chicago Huan Ngo, Gwendolyn Noble and Charles N. Swisher from Northwestern University Hernan Lorenzi and Seesandra V. Rajagopala from the Craig Venter Institute Kai Wang, Taek-Kyun Kim, Yong Zhou and Leroy Hood from the Institute of Systems Biology, Seattle Craig W. Roberts from the 6University of Strathclyde, Glasgow Alexandre Montpetit from Genome Quebec, Montral, Canada Jenefer Blackwell from McGill University Sarra Jamieson from the University of Western Australia Roderick Davis from the University of Illinois-Chicago, Liliana Soroceanu from California Pacific Medical Center, Charles Cobbs from Tufts University, Kenneth Boyer and Peter Heydemann from Rush University Medical Center, Chicago Peter Rabiah from Northshore University Health System, Evanston, IL and Patricia Soteropoulos from Rutgers University.


Immunity is the ability to resist disease.

There are two types of immunity.

Active immunity.

This is the production of antibodies inside an organism when pathogens invade.

This is when pathogens enter the body in a normal way.

We develop a natural resistance in this way by the body producing antibodies against them.

Artificial active immunity.

This is when pathogens enter the body in an unnatural way e.g. vaccine.

A vaccine is a non-disease causing dose of a pathogen which triggers the production of antibodies.

Passive immunity.

This is when antibodies are passed from one organism to another.

This is when antibodies are passed from mother to child across the placenta or by breast milk.

Artificial passive immunity.

A person is given an injection containing antibodies made by another organism.

Example: anti tetanus injection. Antibodies are extracted from blood samples taken from horses which have been infected with tetanus bacteria.


Infection has three stages:

Acute Edit

Acute toxoplasmosis is often asymptomatic in healthy adults. [12] [13] However, symptoms may manifest and are often influenza-like: swollen lymph nodes, headaches, fever, and fatigue, [14] or muscle aches and pains that last for a month or more. It is rare for a human with a fully functioning immune system 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 blurred vision caused by severe inflammation of the retina (ocular toxoplasmosis). [14] Young children and immunocompromised people, such as those with HIV/AIDS, those taking certain types of chemotherapy, or those who have recently received an organ transplant, may develop severe toxoplasmosis. This can cause damage to the brain (encephalitis) or the eyes (necrotizing retinochoroiditis). [15] 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 trophozoites causing acute toxoplasmosis are referred to as tachyzoites, and are typically found in various tissues and body fluids, but rarely in blood or cerebrospinal fluid. [16]

Swollen lymph nodes 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. [17] 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. [18]

Latent Edit

Due to the absence of obvious symptoms, [12] [13] 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. [7] [19] In most immunocompetent people, the infection enters a latent phase, during which only bradyzoites (in tissue cysts) are present [20] these tissue cysts and even lesions can occur in the retinas, alveolar lining of the lungs (where an acute infection may mimic a Pneumocystis jirovecii infection), heart, skeletal muscle, and the central nervous system (CNS), including the brain. [21] Cysts form in the CNS (brain tissue) upon infection with T. gondii and persist for the lifetime of the host. [22] Most infants who are infected while in the womb have no symptoms at birth, but may develop symptoms later in life. [23]

Reviews of serological 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. [7] [24] [25] This latent state of infection has recently been associated with numerous disease burdens, [7] neural alterations, [22] [24] and subtle gender-dependent [ dubious – discuss ] behavioral changes in immunocompetent humans, [26] [27] as well as a increased risk of motor vehicle collisions. [28]

Skin Edit

While rare, skin lesions may occur in the acquired form of the disease, including roseola and erythema multiforme-like eruptions, prurigo-like nodules, urticaria, and maculopapular lesions. Newborns may have punctate macules, ecchymoses, or "blueberry muffin" lesions. Diagnosis of cutaneous toxoplasmosis is based on the tachyzoite form of T. gondii being found in the epidermis. [29] 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 staining tissue where the cytoplasm shows blue, the nucleus red. [30]

Parasitology Edit

In its lifecycle, T. gondii adopts several forms. [31] Tachyzoites 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. [32] After proliferating, tachyzoites convert into bradyzoites, which are inside latent intracellular tissue cysts that form mainly in the muscles and brain. The formation of cysts is in part triggered by the pressure of the host immune system. [33] 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. [31]

The parasite's survival is dependent on a balance between host survival and parasite proliferation. [33] 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. [33] Once it infects a normal host cell, it resists damage caused by the host's immune system, and changes the host's immune processes. [ citation needed ]

As it forces its way into the host cell, the parasite forms a parasitophorous vacuole (PV) membrane from the membrane of the host cell. [2] [34] 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 and endoplasmic reticulum. [2] [34]

When first invading the cell, the parasite releases ROP proteins from the bulb of the rhoptry organelle. [2] These proteins translocate to the nucleus and the surface of the PV membrane where they can activate STAT pathways to modulate the expression of cytokines at the transcriptional level, bind and inactivate PV membrane destroying IRG proteins, among other possible effects. [2] [34] [35] Additionally, certain strains of T. gondii can secrete a protein known as GRA15, activating the NF-κB pathway, which upregulates the pro-inflammatory cytokine IL-12 in the early immune response, possibly leading to the parasite's latent phase. [2] The parasite's ability to secrete these proteins depends on its genotype and affects its virulence. [2] [35]

The parasite also influences an anti-apoptotic mechanism, allowing the infected host cells to persist and replicate. One method of apoptosis resistance is by disrupting pro-apoptosis effector proteins, such as BAX and BAK. [36] 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. [36]

T. gondii also has the ability to initiate autophagy of the host's cells. [37] 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. [37] Their research reveals that T. gondii causes host cell autophagy using a calcium-dependent pathway. [37] Another study suggests that the parasite can directly affect calcium being released from calcium stores, which are important for the signalling processes of cells. [36]

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. [38] 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. [38]

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. [33] This includes, but is not limited to, the responses to infections by Helicobacter felis, Leishmania major, or other parasites, such as Nippostrongylus brasiliensis. [33]

Transmission Edit

Toxoplasmosis is generally transmitted through the mouth when Toxoplasma gondii oocysts or tissue cysts are accidentally eaten. [39] Congenital transmittance from mother to fetus can also occur. [40] Transmission may also occur during the solid organ transplant process [41] or hematogenous stem cell transplants. [42]

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. [43]
  • Ingestion of unwashed fruit or vegetables that have been in contact with contaminated soil containing infected cat feces. [44]
  • Ingestion of cat feces containing oocysts: This can occur through hand-to-mouth contact following gardening, cleaning a cat's litter box, contact with children's sandpits the parasite can survive in the environment for months. [45]
  • Ingestion of untreated, unfiltered water through direct consumption or utilization of water for food preparation. [46]
  • 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. [47] 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. [48]

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. [41] Recipients of hematogenous stem cell transplants may experience higher risk of infection due to longer periods of immunosuppression. [42]

Heart and lung transplants provide the highest risk for toxoplasmosis infection due to the striated muscle making up the heart, [41] which can contain cysts, and risks for other organs and tissues vary widely. [49] Risk of transmission can be reduced by screening donors and recipients prior to the transplant procedure and providing treatment. [49]

Pregnancy precautions Edit

Congenital toxoplasmosis is a specific form of toxoplasmosis in which an unborn fetus is infected via the placenta. [50] Congenital toxoplasmosis is associated with fetal death and miscarriage, and in infants, it is associated with neurologic deficits, neurocognitive deficits, and chorioretinitis. [6] A positive antibody titer 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. [6]

Not much evidence exists around the effect of education before pregnancy to prevent congenital toxoplasmosis. [51] However educating parents before the baby is born has been suggested to be effective because it may improve food, personal and pet hygiene. [51] More research is needed to find whether antenatal education can reduce congenital toxoplasmosis. [51]

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. [ citation needed ]

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 generated Portugal, [52] France, [53] Austria, [53] Uruguay, [54] and Italy [55] are notable exceptions, and some regional screening programmes operate in Germany, Switzerland and Belgium. [55] As invasive prenatal testing incurs some risk to the fetus (18.5 pregnancy losses per toxoplasmosis case prevented), [53] postnatal or neonatal screening is preferred. The exceptions are cases where fetal abnormalities are noted, and thus screening can be targeted. [53]

Pregnant women should avoid handling raw meat, drinking raw milk (especially goat milk) and be advised to not eat raw or undercooked meat regardless of type. [56] 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. [56] Most cats are not actively shedding oocysts, 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.) [57] However, these oocysts get buried in the soil, sporulate and remain infectious for periods ranging from several months to more than a year. [56] Numerous studies have shown living in a household with a cat is not a significant risk factor for T. gondii infection, [56] [58] [59] though living with several kittens has some significance. [60]

In 2006, a Czech research team [61] discovered women with high levels of toxoplasmosis antibodies were significantly more likely to have baby boys than baby girls. In most populations, the birth rate is around 51% boys, but women infected with T. gondii had up to a 72% chance of a boy. [62]

Diagnosis of toxoplasmosis in humans is made by biological, serological, histological, or molecular methods, or by some combination of the above. [57] Toxoplasmosis can be difficult to distinguish from primary central nervous system lymphoma. 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 diagnosis is made by a trial of therapy (pyrimethamine, sulfadiazine, and folinic acid (USAN: leucovorin)), if the drugs produce no effect clinically and no improvement on repeat imaging.

T. gondii may also be detected in blood, amniotic fluid, or cerebrospinal fluid by using polymerase chain reaction. [63] T. gondii may exist in a host as an inactive cyst that would likely evade detection. [ citation needed ]

Serological testing can detect T. gondii antibodies in blood serum, using methods including the Sabin–Feldman dye test (DT), the indirect hemagglutination assay, 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). [57]

The most commonly used tests to measure IgG antibody are the DT, the ELISA, the IFA, and the modified direct agglutination test. [64] IgG antibodies usually appear within a week or two of infection, peak within one to two months, then decline at various rates. [64] Toxoplasma IgG antibodies generally persist for life, and therefore may be present in the bloodstream as a result of either current or previous infection. [65]

To some extent, acute toxoplasmosis infections can be differentiated from chronic infections using an IgG avidity 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. [66]

In contrast to IgG, IgM antibodies can be used to detect acute infection but generally not chronic infection. [65] The IgM antibodies appear sooner after infection than the IgG antibodies and disappear faster than IgG antibodies after recovery. [57] 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. [65] However, IgM may be detectable months or years after infection, during the chronic phase, and false positives for acute infection are possible. [64] 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. [64]

In 2021, twenty commercial anti-Toxoplasma IgG assays were evaluated in a systematic review, in comparison with an accepted reference method. [67] 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. [67]

Congenital Edit

Recommendations for the diagnosis of congenital toxoplasmosis include: prenatal diagnosis based on testing of amniotic fluid and ultrasound examinations neonatal diagnosis based on molecular testing of placenta and cord blood and comparative mother-child serologic tests and a clinical examination at birth and early childhood diagnosis based on neurologic and ophthalmologic examinations and a serologic survey during the first year of life. [50] During pregnancy, serological testing is recommended at three week intervals. [68]

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 or IgM 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. [69] 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. [ citation needed ]

Many PCR-based techniques have been developed to diagnose toxoplasmosis using clinical specimens that include amniotic fluid, blood, cerebrospinal fluid, and tissue biopsy. The most sensitive PCR-based technique is nested PCR, followed by hybridization of PCR products. [69] The major downside to these techniques is that they are time-consuming and do not provide quantitative data. [69]

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. [69] A second fluorescent dye, e.g., 6-carboxy-tetramethyl-rhodamine, quenches the fluorescence of the intact probe. [69] 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. [69]

Toxoplasmosis cannot be detected with immunostaining. Lymph nodes affected by Toxoplasma have characteristic changes, including poorly demarcated reactive germinal centers, clusters of monocytoid B cells, and scattered epithelioid histiocytes.

The classic triad of congenital toxoplasmosis includes: chorioretinitis, hydrocephalus, and intracranial arteriosclerosis. [70] Other consequences include sensorineural deafness, seizures, and intellectual disability. [71]

Congenital toxoplasmosis may also impact a child's hearing. Up to 30% of newborns have some degree of sensorineural hearing loss. [72] 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. [73]

Treatment is recommended for people with serious health problems, such as people with HIV whose CD4 counts are under 200 cells/mm 3 . Trimethoprim/sulfamethoxazole 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. [74]

Acute Edit

The medications prescribed for acute toxoplasmosis are the following:

    — an antimalarial medication — an antibiotic used in combination with pyrimethamine to treat toxoplasmosis
    • Combination therapy is usually given with folic acid supplements to reduce incidence of thrombocytopaenia.
    • Combination therapy is most useful in the setting of HIV.

    (other antibiotics, such as minocycline, have seen some use as a salvage therapy).

    If infected during pregnancy, spiramycin is recommended in the first and early second trimesters while pyrimethamine/sulfadiazine and leucovorin is recommended in the late second and third trimesters. [76]

    Latent Edit

    In people with latent toxoplasmosis, the cysts are immune to these treatments, as the antibiotics do not reach the bradyzoites in sufficient concentration.

    The medications prescribed for latent toxoplasmosis are:

      — an antibiotic that has been used to kill Toxoplasma cysts inside AIDS patients [77] — an antibiotic that, in combination with atovaquone, seemed to optimally kill cysts in mice [78]

    Congenital Edit

    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 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. [31]

    If the parasite has not yet reached the fetus, spiramycin can help to prevent placental transmission. If the fetus has been infected, the pregnant woman can be treated with pyrimethamine and sulfadiazine, with folinic acid, 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. [79] Infection in earlier gestational stages correlates with poorer fetal and neonatal outcomes, particularly when the infection is untreated. [80]

    Newborns who undergo 12 months of postnatal anti-toxoplasmosis treatment have a low chance of sensorineural hearing loss. [81] Information regarding treatment milestones for children with congenital toxoplasmosis have been created for this group. [82]

    T. gondii infections occur throughout the world, although infection rates differ significantly by country. [25] For women of childbearing age, a survey of 99 studies within 44 countries found the areas of highest prevalence are within Latin America (about 50–80%), parts of Eastern and Central Europe (about 20–60%), the Middle East (about 30–50%), parts of Southeast Asia (about 20–60%), and parts of Africa (about 20–55%). [25]

    In the United States, data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004 found 9.0% of US-born persons 12–49 years of age were seropositive for IgG antibodies against T. gondii, down from 14.1% as measured in the NHANES 1988–1994. [83] 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. [83] A trend of decreasing seroprevalence has been observed by numerous studies in the United States and many European countries. [25] 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. [84]

    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. [85]

    • Type I: virulent in mice and humans, seen in people with AIDS.
    • 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 techniques can only separate type I or III from type II parasites. [86]

    Because the parasite poses a particular threat to fetuses when it is contracted during pregnancy, [87] much of the global epidemiological 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. [88]

    Toxoplasma gondii was first described in 1908 by Nicolle and Manceaux in Tunisia, and independently by Splendore in Brazil. [10] Splendore reported the protozoan in a rabbit, while Nicolle and Manceaux identified it in a North African rodent, the gundi (Ctenodactylus gundi). [39] In 1909 Nicolle and Manceaux differentiated the protozoan from Leishmania. [10] Nicolle and Manceaux then named it Toxoplasma gondii after the curved shape of its infectious stage (Greek root 'toxon'= bow). [10]

    The first recorded case of congenital toxoplasmosis was in 1923, but it was not identified as caused by T. gondii. [39] Janků (1923) described in detail the autopsy results of an 11-month-old boy who had presented to hospital with hydrocephalus. The boy had classic marks of toxoplasmosis including chorioretinitis (inflammation of the choroid and retina of the eye). [39] Histology revealed a number of "sporocytes", though Janků did not identify these as T. gondii. [39]

    It was not until 1937 that the first detailed scientific analysis of T. gondii took place using techniques previously developed for analyzing viruses. [10] 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. [10] Thus Sabin and Olitsky demonstrated T. gondii as a pathogen transmissible between animals.

    T. gondii was first described as a human pathogen in 1939 at Babies Hospital in New York City. [10] [89] Wolf, Cowen and Paige identified T. gondii infection in an infant girl delivered full-term by Caesarean section. [39] 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. [10] Wolf, Cowen and Page reviewed additional cases and concluded that T. gondii produced recognizable symptoms and could be transmitted from mother to child. [39]

    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. [39]

    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. [10] [90] The Sabin Feldman Dye Test is now the gold standard for identifying Toxoplasma infection. [10]

    Transmission of Toxoplasma by eating raw or undercooked meat was demonstrated by Desmonts et al. in 1965 Paris. [10] Desmonts observed that the therapeutic consumption of raw beef or horse meat in a tuberculosis hospital was associated with a 50% per year increase in Toxoplasma antibodies. [10] 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 lowered the transmission to the fetus. [39]

    Toxoplasma gained more attention in the 1970s with the rise of immune-suppressant treatment given after organ or bone marrow transplants and the AIDS epidemic of the 1980s. [10] Patients with lowered immune system function are much more susceptible to disease.

    "Crazy cat-lady" Edit

    "Crazy cat-lady syndrome" is a term coined by news organizations to describe scientific findings that link the parasite Toxoplasma gondii to several mental disorders and behavioral problems. [91] [92] The suspected correlation between cat ownership in childhood and later development of schizophrenia suggested that further studies were needed to determine a risk factor for children [93] however, later studies showed that T. gondii was not a causative factor in later psychoses. [94] Researchers also found that cat ownership does not strongly increase the risk of a T. gondii infection in pregnant women. [56] [95]

    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 is a cultural stereotype of a woman who compulsively hoards and dotes upon cats. The biologist Jaroslav Flegr is a proponent of the theory that toxoplasmosis affects human behaviour. [96] [97]

    Notable cases Edit

    • Tennis player Arthur Ashe developed neurological problems from toxoplasmosis (and was later found to be HIV-positive). [98]
    • Actor Merritt Butrick was HIV-positive and died from toxoplasmosis as a result of his already-weakened immune system. [99] , reality television personality and HIV/AIDS activist, was diagnosed with toxoplasmosis as a result of his immune system being weakened by HIV. [100][101] , pretender to the throne of France had congenital toxoplasmosis his disability caused him to be overlooked in the line of succession.
    • Actress Leslie Ash contracted toxoplasmosis in the second month of pregnancy. [102]
    • British middle-distance runner Sebastian Coe contracted toxoplasmosis in 1983, which was probably transmitted by a cat while he trained in Italy. [103][104]
    • Tennis player Martina Navratilova suffered from toxoplasmosis during the 1982 US Open. [105]

    Although T. gondii has the capability of infecting virtually all warm-blooded animals, susceptibility and rates of infection vary widely between different genera and species. [108] [109] 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) that are endemic to the island of Sri Lanka. [110]

    Australian marsupials are particularly susceptible to toxoplasmosis. [111] Wallabies, koalas, wombats, pademelons and small dasyurids can be killed by it, with eastern barred bandicoots typically dying within about 3 weeks of infection. [112]

    It is estimated that 23% of wild swine worldwide are seropositive for T. gondii. [113] 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%). [113] Geographical regions located at higher latitudes and regions that experience warmer, humid climates are associated with increased seroprevalence of T. gondii among wild boar. [113] Wild boar infected with T. gondii pose a potential health risk for humans who consume their meat. [113]

    Livestock Edit

    Among livestock, pigs, sheep [114] and goats have the highest rates of chronic T. gondii infection. [115] The prevalence of T. gondii in meat-producing animals varies widely both within and among countries, [115] and rates of infection have been shown to be dramatically influenced by varying farming and management practices. [13] 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. [13] [44]

    In the United States, the percentage of pigs harboring viable parasites has been measured (via bioassay in mice or cats) to be as high as 92.7% and as low as 0%, depending on the farm or herd. [44] 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. [116] Along with pigs, sheep and goats are among the most commonly infected livestock of epidemiological significance for human infection. [115] Prevalence of viable T. gondii in sheep tissue has been measured (via bioassay) to be as high as 78% in the United States, [117] and a 2011 survey of goats intended for consumption in the United States found a seroprevalence of 53.4%. [118]

    Due to a lack of exposure to the outdoors, chickens raised in large-scale indoor confinement operations are not commonly infected with T. gondii. [13] Free-ranging or backyard-raised chickens are much more commonly infected. [13] A survey of free-ranging chickens in the United States found its prevalence to be 17–100%, depending on the farm. [119] 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. [120]

    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. [13] 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. [115] [44]

    Horses are considered resistant to chronic T. gondii infection. [13] 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. [44] [121]

    Domestic cats Edit

    In 1942, the first case of feline toxoplasmosis was diagnosed and reported in a domestic cat in Middletown, NY. [122] The investigators isolated oocysts from feline feces and found that the oocysts could be infectious for up to 12 months in the environment. [123]

    The seroprevalence of T. gondii in domestic cats, worldwide has been estimated to be around 30–40% [124] 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%. [124] A 2012 survey of 445 purebred pet cats and 45 shelter cats in Finland found an overall seroprevalence of 48.4%, [125] while a 2010 survey of feral cats from Giza, Egypt found a seroprevalence rate of 97.4%. [126] Another survey from Colombia recorded seroprevalence of 89.3%, whereas a Chinese study found just a 2.1% prevalence. [108]

    T. gondii infection rates in domestic cats vary widely depending on the cats' diets and lifestyles. [127] Feral cats 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. [128]

    Most infected cats will shed oocysts only once in their lifetimes, for a period of about one to two weeks. [124] This shedding can release millions of oocysts, each capable of spreading and surviving for months. [124] An estimated 1% of cats at any given time are actively shedding oocysts. [13]

    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. [129]

    Rodents Edit

    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. [130] [131] [132] 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 or with cat body odor, this avoidance is reduced or eliminated in infected animals. [130] [132] [133] Moreover, some evidence suggests this loss of aversion may be specific to feline odors: when given a choice between two predator odors (cat or mink), infected rodents show a significantly stronger preference to cat odors than do uninfected controls. [134] [135]

    In rodents, T. gondii–induced behavioral changes occur through epigenetic remodeling in neurons associated with observed behaviors [136] [137] for example, it modifies epigenetic methylation to induce hypomethylation of arginine vasopressin-related genes in the medial amygdala to greatly decrease predator aversion. [136] [137] 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 or enzyme inhibition in specific neurons produced alterations in drug-related behaviors. [138] [139] [140] Widespread histone–lysine acetylation in cortical astrocytes appears to be another epigenetic mechanism employed by T. gondii. [141] [142]

    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. [143] Similarly, infected mice show alterations in patterns of locomotion 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. [144] Infected rodents have also been shown to have lower anxiety, using traditional models such as elevated plus mazes, open field arenas, and social interaction tests. [144] [145]

    Marine mammals Edit

    A University of California, Davis study of dead sea otters collected from 1998 to 2004 found toxoplasmosis was the cause of death for 13% of the animals. [146] Proximity to freshwater outflows into the ocean was a major risk factor. Ingestion of oocysts from cat feces is considered to be the most likely ultimate source. [147] Surface runoff containing wild cat feces and litter from domestic cats flushed down toilets are possible sources of oocysts. [148] [149] These same sources may have also introduced the toxoplasmosis infection to the endangered Hawaiian monk seal. [150] Infection with the parasite has contributed to the death of at least four Hawaiian monk seals. [150] A Hawaiian monk seal's infection with T. gondii was first noted in 2004. [151] The parasite's spread threatens the recovery of this highly endangered pinniped. The parasites have been found in dolphins and whales. [152] [153] Researchers Black and Massie believe anchovies, which travel from estuaries into the open ocean, may be helping to spread the disease. [154]

    Giant panda Edit

    Toxoplasma gondii has been reported as the cause of death of a giant panda kept in a zoo in China, who died in 2014 of acute gastroenteritis and respiratory disease. [107] 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.

    Chronic infection with T. gondii has traditionally been considered asymptomatic in people with normal immune function. [155] 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 or neurological disorders. [156] [155]

    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. [157] 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. [157]

    Mental health Edit

    Some evidence links T. gondii to schizophrenia. [155] Two 2012 meta-analyses found that the rates of antibodies to T. gondii in people with schizophrenia were 2.7 times higher than in controls. [158] [159] T. gondii antibody positivity was therefore considered an intermediate risk factor in relation to other known risk factors. [158] 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 might exist. [159] 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. [130] Sex differences in schizophrenia onset may be explained by a second peak of T. gondii infection incidence during ages 25–30 in females only. [160] Although a mechanism supporting the association between schizophrenia and T. gondii infection is unclear, studies have investigated a molecular basis of this correlation. [160] Antipsychotic drugs used in schizophrenia appear to inhibit the replication of T. gondii tachyzoites in cell culture. [130] 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. [161]

    Correlations have also been found between antibody titers to T. gondii and OCD, suicide in people with mood disorders including bipolar disorder. [156] [162] Positive antibody titers to T. gondii appear to be uncorrelated with major depression or dysthymia. [163] 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". [164]

    Neurological disorders Edit

    Individuals with multiple sclerosis show infection rates around 15% lower than the general public. [165]

    Traffic accidents Edit

    Latent T. gondii infection in humans has been associated with a higher risk of automobile accidents, potentially due to impaired psychomotor performance or enhanced risk-taking personality profiles. [156]

    Climate change Edit

    Climate change has been reported to affect the occurrence, survival, distribution and transmission of T. gondii. [166] T. gondii has been identified in the Canadian arctic, a location that was once too cold for its survival. [167] Higher temperatures increase the survival time of T. gondii. [166] More snowmelt and precipitation can increase the amount of T. gondii oocysts that are transported via river flow. [166] 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. [166] Urbanization and natural environmental degradation are also suggested to affect T. gondii transmission and increase risk of infection. [166]

    Influence of latent toxoplasmosis on human behaviour

    Toxoplasma-infected subjects have prolonged reaction times, as measured by a test of simple reaction times (Havlíček et al., 2001). The psychomotor performance gets worse with the level of development of the infection (estimated on the basis of a decrease in the concentration of specific anti-Toxoplasma antibodies). The performance of the subjects in the 3 min simple reaction time test suggests that toxoplasmosis impairs long-term concentration ability rather than maximum performance. The largest performance decrease in the test occurred in RhD negative subjects while the performance of RhD-positive heterozygotes was not influenced by the infection (Flegr et al., 2010 Novotná et al., 2008). The impaired psychomotor performance of infected subjects can explain the higher risk of traffic accidents and work accidents observed in four retrospective studies (Alvarado-Esquivel et al., 2012 Flegr et al., 2002 Kocazeybek et al., 2009 Yereli et al., 2006) and one prospective study (Flegr et al., 2009). The risk of traffic accident is again increased in RhD-negative drivers (Flegr et al., 2009). A double-blind observational study showed that Toxoplasma-infected men scored lower in clothes tidiness than uninfected men, whereas infected women scored higher (but not significantly so) than uninfected women (Lindová et al., 2006). Similarly, infected men scored lower and infected women scored higher in sociability. These outcomes match the results of the personality questionnaires. The infected rural male students scored higher in suspiciousness while infected rural female students scored lower in suspiciousness than their non-infected peers (Lindová et al., 2006), which again agrees with the results obtained with Cattell’s 16PF questionnaire. However, the very opposite was true for students of urban origin – infected male students showed lower and infected female students higher suspiciousness than their Toxoplasma-free peers. Using the method of experimental games, it was shown that both infected men and infected women were less altruistic than Toxoplasma-free subjects in the Dictator game while in the Trust game, the infected men were less altruistic and infected women were more altruistic than Toxoplasma-free men or women (Lindová et al., 2010).

    Concentration of steroid hormones in Toxoplasma-infected and Toxoplasma-free subjects

    Skin and immune cells coordinate defenses against assault

    As the human body's largest organ, the skin is responsible for protecting against a wide range of possible infections on all fleshy surfaces, from head to toe. So how exactly does the skin organize its defenses against such an array of threats?

    A new Yale study shows that the epidermis, the outermost layer of skin, is composed of an army of immune cells that station themselves at regular intervals across the skin's vast expanse to resist infection. When necessary, the researchers found, these immune system soldiers are able to reposition themselves to protect vulnerable areas.

    The study, published in the journal Nature Cell Biology, was conducted by the lab of Valentina Greco, the Carolyn Walch Slayman Professor of Genetics, at Yale School of Medicine.

    "It's a surveillance system with two separate roles," said Catherine Matte-Martone, manager of the Greco lab and co-first author of the study. "The skin controls the sentinels by mediating their numbers based on its own density, while they in turn provide dynamic coverage to prevent cracks in the skin's defenses."

    The epidermis contains two main types of immune system cells, Langerhans cells (LCs) and dendritic epidermal T cells (DETCs). In the study, the research team led by Matte-Martone and Sangbum Park, a researcher from Michigan State University (MSU), captured images of these immune system cells interacting with epithelial cells, the closely packed skin cells that comprise most of the epidermis.

    They found that the immune system cells are distributed in a distinct pattern, maintaining a minimum distance between the individual cells. According to the researchers, these immune cells seem to have the ability to avoid each other, preventing clusters in any locations and maintaining a consistent distribution.

    The phenomenon is similar to a property observed in neurons, in which scientists have observed a tendency of neurons from a single branch to avoid each other.

    "Our study suggests that LCs and DETCs appear to have a mechanism of 'self-avoidance,' similar to neuronal cells," said Park, an assistant professor at MSU and former postdoctoral fellow in the Greco lab at Yale.

    When the team removed some immune cells in one area, they observed that the remaining cells were able to reposition across the skin tissue to defend the gaps in coverage. They also found that they could disrupt the normal distribution of those cells by knocking out a gene known as Rac1 (Ras-related C3 botulinum toxin substrate 1), which regulates projections on immune cells called dendrites. This process, they hypothesize, helps maintain the distance between immune cells.

    The findings illustrate how specialized cell types can cooperate to carry out a larger role within the body.

    "It is fascinating to observe how these different cell types co-exist and interact together in a developmental context rather than an immunological one," Martone said.

    Other Yale authors include Ann Haberman, director of the In Vivo Imaging Facility at Yale, and David Gonzalez, manager of both the Imaging Facility and the Greco Lab.

    How is toxoplasmosis transmitted?

    Toxoplasmosis (in humans) occurs from eating improperly cooked meat, especially lamb (mutton), pork, and deer (venison), or from drinking unpasteurized milk contaminated with Toxoplasma gondii. Cooking meat (inner temperature about 70°C or 160°F) or freezing it (about -18°C or 0°F) should destroy the parasite.

    Toxoplasma gondii can also be transmitted by handling contaminated animals, raw meat or having contact with food (e.g. raw or under cooked pork or beef), water, dirt (soil), or dust contaminated with cat feces. Direct contamination is possible through open wounds. If people do not wash their hands after contact with contaminated material or before eating or drinking, the organism is transferred from the hands to the mouth and is then swallowed. Infection from blood transfusions and organ transplants from infected donors is rare, but it has been reported.

    Toxoplasma gondii has been found in the kidneys, bladder and intestine of infected humans. There have been rare cases of organ transplant recipients acquiring toxoplasmosis infection.

    Contaminated human urine and feces could possibly be a source of infection but transmission from this source has not been proved.

    Person to person transmission occurs only from mother to child. A pregnant woman who acquires toxoplasmosis infection can pass the organism to the developing fetus through the placenta. The risk of the fetus being affected and the severity of the disease depends on what stage during pregnancy the mother acquires the infection. The baby is most at risk if the mother becomes infected in the third trimester, but the earlier in the pregnancy the infection occurs, the more serious the outcome for the baby. Many early infections end in stillbirth or miscarriage. Infants who survive may have issues such as seizures, enlarged liver and spleen, yellowing of skin and eyes (jaundice) or severe eye infections. Some effects are not seen at birth, and may occur in their teen years or later.

    Human defenses to toxoplasmosis - Biology

    To update clinical information about ocular toxoplasmosis. Part II reviews the spectrum of disease manifestations and factors that influence severity of disease. Implications for disease management are discussed.



    Selected articles from the medical literature, information from several recent scientific meetings, and the author's personal experiences were reviewed critically in preparation for the LX Edward Jackson Memorial Lecture.


    The appearance of toxoplasmic retinochoroiditis lesions varies with duration of active retinal infection and intensity of inflammation. Severe ocular disease occurs in immunocompromised hosts. Older patients who are recently infected with Toxoplasma gondii may have a higher prevalence of ocular involvement and more severe ocular disease because of altered host defenses. Most disease-producing isolates of T. gondii belong to one of three clonal lineages (types I, II, III) type I has been associated with severe disease in both animals and human beings. Many observational studies suggest a benefit of short-term antimicrobial therapy for toxoplasmic retinochoroiditis in immunocompetent patients, although the efficacy of these treatments has not been proven in randomized clinical trials. Intermittent trimethoprim/sulfamethoxazole treatment was associated with fewer recurrences than placebo during a 20-month randomized clinical trial.


    Variations in disease characteristics may be related to host, parasite, or environmental factors. The genotype of the infecting parasite appears to be an important determinant of disease severity in immunocompetent patients. Secondary prophylaxis may reduce the rate of recurrences in high-risk patients. A better clinical understanding of ocular toxoplasmosis can lead to more effective prevention and treatment strategies.

    Supported, in part, by Research to Prevent Blindness, Inc., New York, NY, the Skirball Foundation, Los Angeles, CA, and the David May II Endowed Professorship. Additional support was provided by the Emily Plumb Estate and Trust Gift for resources utilized in the Jules Stein Eye Institute Clinical Research Center. Dr. Holland is a recipient of a Research to Prevent Blindness Physician-Scientist Award.


    Immunocompetent patients have an excellent prognosis, and lymphadenopathy and other symptoms generally resolve within weeks of infection.

    Toxoplasmosis in immunodeficient patients often relapses if treatment is stopped. Suppressive therapy and immune reconstitution significantly reduce the risk of recurrent infection.

    Multiple complications may occur in persons with congenital toxoplasmosis, including mental retardation, seizures, deafness, and blindness. Treatment may prevent the development of untoward sequelae in symptomatic and asymptomatic infants with congenital toxoplasmosis. Infants with congenitally acquired toxoplasmosis generally have a good prognosis and are on average developmentally identical to noninfected infants by the fourth year of life.

    Toxoplasmic encephalitis and brain abscess can result in permanent neurologic sequelae, depending on the location of the lesion and the extent of local damage and inflammation. Basal ganglia seem to be preferentially involved. Seizure disorder or focal neurologic deficits may occur in persons with CNS toxoplasmosis.

    Ophthalmic complications

    Toxoplasmosis is the most common cause of intraocular inflammation and posterior uveitis in immunocompetent patients throughout the world. Toxoplasmosis is responsible for approximately 30-50% of all posterior uveitis cases in the United States.

    Retinochoroiditis is a relatively common manifestation of T gondii infection. Ocular toxoplasmosis occurs when cysts deposited in or near the retina become active, producing tachyzoites. Focal necrotizing retinitis is the characteristic lesion, but retinal scars from prior reactivation are typically present. Presentation usually involves eye pain and decreased visual acuity. Adults who acquired disease in infancy usually present with bilateral eye involvement. Adults with acute infection generally present with unilateral ocular involvement. [37, 38, 36, 39]

    Depending on the location and severity of toxoplasmic retinochoroiditis, infection can result in permanent retinal scarring and loss of visual acuity. Recurrent episodes are common, resulting in multiple areas of retinal scarring and functional loss. (See the images below.)

    --> Ophthalmic toxoplasmosis. Used with permission of Anton Drew, ophthalmic photographer, Adelaide, South Australia. --> Acute macular retinitis associated with primary acquired toxoplasmosis, requiring immediate systemic therapy.

    Vascular endothelial growth factor (VEGF) has been shown to be a key molecular player in the pathogenesis of choroidal neovascular membrane (CNV). In the current era of anti-VEGF therapy, the extraordinary results obtained in CNV secondary to age-related macular degeneration have been extrapolated to other causes of CNV with apparent good results. [40, 41] Currently available anti-VEGF agents include bevacizumab, ranibizumab, and pegaptanib sodium.

    Secondary glaucoma may occur with anterior uveitis that is secondary to the obstruction of the outflow channels by the inflammatory cells. This condition may or may not be reversible.

    Destruction of the trabecula by chronic inflammation and anterior synechiae may also create a chronic pharmacologically nonresponsive glaucoma.

    Other ocular complications include:

    Persistent vitreous opacities

    Morbidity and mortality

    Acute toxoplasmosis is asymptomatic in 80-90% of healthy hosts. In some apparently immunologically healthy patients, however, the acute infection progresses and may have lethal consequences.

    Although a relatively small percentage of toxoplasmosis cases are congenital, they tend to account for most acute and fatal infections.

    In immunosuppressed patients, T gondii infection, like other opportunistic infections, can lead to rapidly progressive, fatal disease. Indeed, toxoplasmosis is recognized as a major cause of neurologic morbidity and mortality among patients with advanced HIV disease.

    However, the incidence of toxoplasmosis (including CNS disease) in patients with AIDS has declined dramatically, likely due to the evolution of highly active antiretroviral therapy (HAART) and the routine use of prophylaxis against P (carinii) jiroveci and T gondii. The incidence of CNS toxoplasmosis decreased from 5.4 cases per 1000 person-years between 1990 and 1992 to 2.2 cases per 1000 persons-years between 1996 and 1998. [42] The routine use of cotrimoxazole prophylaxis in the United States and internationally has also likely significantly decreased the incidence of CNS toxoplasmosis.


    Lindsay DS, Dubey JP. Toxoplasma gondii: the changing paradigm of congenital toxoplasmosis. Parasitology. 2011 Sep 9. 1-3. [Medline].

    Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet. 2004 Jun 12. 363(9425):1965-76. [Medline].

    Di Mario S, Basevi V, Gagliotti C, Spettoli D, Gori G, D'Amico R, et al. Prenatal education for congenital toxoplasmosis. Cochrane Database Syst Rev. 2013 Feb 28. 2:CD006171. [Medline].

    [Guideline] Kaplan JE, Benson C, Holmes KH, Brooks JT, Pau A, Masur H. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009 Apr 10. 58:1-207 quiz CE1-4. [Medline].

    Jones JL, Kruszon-Moran D, Sanders-Lewis K, Wilson M. Toxoplasma gondii infection in the United States, 1999 2004, decline from the prior decade. Am J Trop Med Hyg. 2007 Sep. 77(3):405-10. [Medline].

    Martin AM, Liu T, Lynn BC, Sinai AP. The Toxoplasma gondii parasitophorous vacuole membrane: transactions across the border. J Eukaryot Microbiol. 2007 Jan-Feb. 54(1):25-8. [Medline].

    Phan L, Kasza K, Jalbrzikowski J, Noble AG, Latkany P, Kuo A, et al. Longitudinal study of new eye lesions in children with toxoplasmosis who were not treated during the first year of life. Am J Ophthalmol. 2008 Sep. 146(3):375-384. [Medline]. [Full Text].

    Freeman K, Tan HK, Prusa A, Petersen E, Buffolano W, Malm G, et al. Predictors of retinochoroiditis in children with congenital toxoplasmosis: European, prospective cohort study. Pediatrics. 2008 May. 121(5):e1215-22. [Medline].

    Latkany P. Ocular Disease Due to Toxoplasma gondii. Weiss LM, Kim K, eds. Toxoplasma gondii the Model Apicomplexan: Perspectives and Methods. London, United Kingdom: Academic Press 2007. 101-31.

    Villard O, Filisetti D, Roch-Deries F, Garweg J, Flament J, Candolfi E. Comparison of enzyme-linked immunosorbent assay, immunoblotting, and PCR for diagnosis of toxoplasmic chorioretinitis. J Clin Microbiol. 2003 Aug. 41(8):3537-41. [Medline]. [Full Text].

    Nagineni CN, Detrick B, Hooks JJ. Toxoplasma gondii infection induces gene expression and secretion of interleukin 1 (IL-1), IL-6, granulocyte-macrophage colony-stimulating factor, and intercellular adhesion molecule 1 by human retinal pigment epithelial cells. Infect Immun. 2000 Jan. 68(1):407-10. [Medline]. [Full Text].

    Yamamoto JH, Vallochi AL, Silveira C, Filho JK, Nussenblatt RB, Cunha-Neto E, et al. Discrimination between patients with acquired toxoplasmosis and congenital toxoplasmosis on the basis of the immune response to parasite antigens. J Infect Dis. 2000 Jun. 181(6):2018-22. [Medline].

    Cordeiro CA, Moreira PR, Costa GC, Dutra WO, Campos WR, Oréfice F, et al. Interleukin-1 gene polymorphisms and toxoplasmic retinochoroiditis. Mol Vis. 2008. 14:1845-9. [Medline]. [Full Text].

    Cordeiro CA, Moreira PR, Andrade MS, Dutra WO, Campos WR, Oréfice F, et al. Interleukin-10 gene polymorphism (-1082G/A) is associated with toxoplasmic retinochoroiditis. Invest Ophthalmol Vis Sci. 2008 May. 49(5):1979-82. [Medline].

    Cordeiro CA, Moreira PR, Costa GC, Dutra WO, Campos WR, Oréfice F, et al. TNF-alpha gene polymorphism (-308G/A) and toxoplasmic retinochoroiditis. Br J Ophthalmol. 2008 Jul. 92(7):986-8. [Medline].

    Montoya JG, Remington JS. Toxoplasmic chorioretinitis in the setting of acute acquired toxoplasmosis. Clin Infect Dis. 1996 Aug. 23(2):277-82. [Medline].

    Gras L, Wallon M, Pollak A, Cortina-Borja M, Evengard B, Hayde M, et al. Association between prenatal treatment and clinical manifestations of congenital toxoplasmosis in infancy: a cohort study in 13 European centres. Acta Paediatr. 2005 Dec. 94(12):1721-31. [Medline].

    Thiébaut R, Leproust S, Chêne G, Gilbert R. Effectiveness of prenatal treatment for congenital toxoplasmosis: a meta-analysis of individual patients' data. Lancet. 2007 Jan 13. 369(9556):115-22. [Medline].

    Luft BJ, Remington JS. Toxoplasmic encephalitis in AIDS. Clin Infect Dis. 1992 Aug. 15(2):211-22. [Medline].

    Porter SB, Sande MA. Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome. N Engl J Med. 1992 Dec 3. 327(23):1643-8. [Medline].

    Torok E, Moran E, Cooke F. Toxoplasmosis. Oxford Handbook of Infectious Diseases and Microbiology. New York: Oxford University Press 2009:567 Vol 1:

    Hofman P, Bernard E, Michiels JF, Thyss A, Le Fichoux Y, Loubière R. Extracerebral toxoplasmosis in the acquired immunodeficiency syndrome (AIDS). Pathol Res Pract. 1993 Sep. 189(8):894-901. [Medline].

    Flegr J. Influence of latent Toxoplasma infection on human personality, physiology and morphology: pros and cons of the Toxoplasma-human model in studying the manipulation hypothesis. J Exp Biol. 2013 Jan 1. 216:127-33. [Medline].

    Henriquez SA, Brett R, Alexander J, Pratt J, Roberts CW. Neuropsychiatric disease and Toxoplasma gondii infection. Neuroimmunomodulation. 2009. 16(2):122-33. [Medline].

    Yolken RH, Dickerson FB, Fuller Torrey E. Toxoplasma and schizophrenia. Parasite Immunol. 2009 Nov. 31(11):706-15. [Medline].

    Miman O, Kusbeci OY, Aktepe OC, Cetinkaya Z. The probable relation between Toxoplasma gondii and Parkinson's disease. Neurosci Lett. 2010 May 21. 475(3):129-31. [Medline].

    Kusbeci OY, Miman O, Yaman M, Aktepe OC, Yazar S. Could Toxoplasma gondii have any role in Alzheimer disease?. Alzheimer Dis Assoc Disord. 2011 Jan-Mar. 25(1):1-3. [Medline].

    Barry MA, Weatherhead JE, Hotez PJ, Woc-Colburn L. Childhood parasitic infections endemic to the United States. Pediatr Clin North Am. 2013 Apr. 60(2):471-85. [Medline].

    Smith RE, Ganley JP. Ophthalmic survey of a community. 1. Abnormalities of the ocular fundus. Am J Ophthalmol. 1972 Dec. 74(6):1126-30. [Medline].

    Rico-Torres CP, Figueroa-Damián R, López-Candiani C, Macías-Avilés HA, Cedillo-Peláez C, Cañedo-Solares I, et al. Molecular Diagnosis and Genotyping of Cases of Perinatal Toxoplasmosis in Mexico. Pediatr Infect Dis J. 2011 Dec 14. [Medline].

    Desmonts G, Couvreur J. Congenital toxoplasmosis. A prospective study of 378 pregnancies. N Engl J Med. 1974 May 16. 290(20):1110-6. [Medline].

    McCannel CA, Holland GN, Helm CJ, Cornell PJ, Winston JV, Rimmer TG. Causes of uveitis in the general practice of ophthalmology. UCLA Community-Based Uveitis Study Group. Am J Ophthalmol. 1996 Jan. 121(1):35-46. [Medline].

    Glasner PD, Silveira C, Kruszon-Moran D, Martins MC, Burnier Júnior M, Silveira S, et al. An unusually high prevalence of ocular toxoplasmosis in southern Brazil. Am J Ophthalmol. 1992 Aug 15. 114(2):136-44. [Medline].

    de-la-Torre A, López-Castillo CA, Gómez-Marín JE. Incidence and clinical characteristics in a Colombian cohort of ocular toxoplasmosis. Eye (Lond). 2009 May. 23(5):1090-3. [Medline].

    Gómez-Marín JE, de-la-Torre A, Barrios P, Cardona N, Alvarez C, Herrera C. Toxoplasmosis in military personnel involved in jungle operations. Acta Trop. 2011 Dec 9. [Medline].

    Holland GN, Crespi CM, ten Dam-van Loon N, Charonis AC, Yu F, Bosch-Driessen LH, et al. Analysis of recurrence patterns associated with toxoplasmic retinochoroiditis. Am J Ophthalmol. 2008 Jun. 145(6):1007-1013. [Medline].

    Remington JS. Toxoplasmosis in the adult. Bull N Y Acad Med. 1974 Feb. 50(2):211-27. [Medline]. [Full Text].

    McCabe RE, Brooks RG, Dorfman RF, Remington JS. Clinical spectrum in 107 cases of toxoplasmic lymphadenopathy. Rev Infect Dis. 1987 Jul-Aug. 9(4):754-74. [Medline].

    Monnet D, Averous K, Delair E, Brézin AP. Optical coherence tomography in ocular toxoplasmosis. Int J Med Sci. 2009. 6(3):137-8. [Medline]. [Full Text].

    Benevento JD, Jager RD, Noble AG, Latkany P, Mieler WF, Sautter M, et al. Toxoplasmosis-associated neovascular lesions treated successfully with ranibizumab and antiparasitic therapy. Arch Ophthalmol. 2008 Aug. 126(8):1152-6. [Medline]. [Full Text].

    Ben Yahia S, Herbort CP, Jenzeri S, Hmidi K, Attia S, Messaoud R, et al. Intravitreal bevacizumab (Avastin) as primary and rescue treatment for choroidal neovascularization secondary to ocular toxoplasmosis. Int Ophthalmol. 2008 Aug. 28(4):311-6. [Medline].

    Sacktor N, Lyles RH, Skolasky R, Kleeberger C, Selnes OA, Miller EN, et al. HIV-associated neurologic disease incidence changes:: Multicenter AIDS Cohort Study, 1990-1998. Neurology. 2001 Jan 23. 56(2):257-60. [Medline].

    Salviz M, Montoya JG, Nadol JB, Santos F. Otopathology in Congenital Toxoplasmosis. Otol Neurotol. 2013 Apr 17. [Medline].

    Frenkel JK. Toxoplasmosis. Pediatr Clin North Am. 1985 Aug. 32(4):917-32. [Medline].

    Dodds EM, Holland GN, Stanford MR, Yu F, Siu WO, Shah KH, et al. Intraocular inflammation associated with ocular toxoplasmosis: relationships at initial examination. Am J Ophthalmol. 2008 Dec. 146(6):856-65.e2. [Medline].

    Abdul-Ghani R. Polymerase chain reaction in the diagnosis of congenital toxoplasmosis: more than two decades of development and evaluation. Parasitol Res. 2011 Mar. 108(3):505-12. [Medline]. [Full Text].

    Tlamcani Z, Lemkhenete Z, Lmimouni BE. Toxoplasmosis: The value of molecular methods in diagnosis compared to conventional methods. J Microbiol Infect Dis. 2013. 3(2):93-99. [Full Text].

    Paquet C, Yudin MH. Toxoplasmosis in pregnancy: prevention, screening, and treatment. J Obstet Gynaecol Can. 2013 Jan. 35(1):78-9. [Medline].

    Ashburn D, Chatterton JM, Evans R, Joss AW, Ho-Yen DO. Success in the toxoplasma dye test. J Infect. 2001 Jan. 42(1):16-9. [Medline].

    Pinon JM, Chemla C, Villena I, et al. Early neonatal diagnosis of congenital toxoplasmosis: value of comparative enzyme-linked immunofiltration assay immunological profiles and anti-Toxoplasma gondii immunoglobulin M (IgM) or IgA immunocapture and implications for postnatal therapeutic strategies. J Clin Microbiol. 1996 Mar. 34(3):579-83. [Medline]. [Full Text].

    Lappalainen M, Hedman K. Serodiagnosis of toxoplasmosis. The impact of measurement of IgG avidity. Ann Ist Super Sanita. 2004. 40(1):81-8. [Medline].

    Levy RM, Mills CM, Posin JP, Moore SG, Rosenblum ML, Bredesen DE. The efficacy and clinical impact of brain imaging in neurologically symptomatic AIDS patients: a prospective CT/MRI study. J Acquir Immune Defic Syndr. 1990. 3(5):461-71. [Medline].

    Peyron F, L'ollivier C, Mandelbrot L, Wallon M, Piarroux R, Kieffer F, et al. Maternal and Congenital Toxoplasmosis: Diagnosis and Treatment Recommendations of a French Multidisciplinary Working Group. Pathogens. 2019 Feb 18. 8 (1):pii: E24. [Medline]. [Full Text].

    Dunay IR, Gajurel K, Dhakal R, Liesenfeld O, Montoya JG. Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current Clinical Practice. Clin Microbiol Rev. 2018 Oct. 31 (4):e00057-17. [Medline]. [Full Text].

    Rezaei F, Sarvi S, Sharif M, Hejazi SH, Pagheh AS, Aghayan SA, et al. A systematic review of Toxoplasma gondii antigens to find the best vaccine candidates for immunization. Microb Pathog. 2019 Jan. 126:172-184. [Medline]. [Full Text].

    Sobrin L, Kump LI, Foster CS. Intravitreal clindamycin for toxoplasmic retinochoroiditis. Retina. 2007 Sep. 27(7):952-7. [Medline].

    Soheilian M, Ramezani A, Azimzadeh A, Sadoughi MM, Dehghan MH, Shahghadami R, et al. Randomized trial of intravitreal clindamycin and dexamethasone versus pyrimethamine, sulfadiazine, and prednisolone in treatment of ocular toxoplasmosis. Ophthalmology. 2011 Jan. 118(1):134-41. [Medline].

    Soheilian M, Sadoughi MM, Ghajarnia M, Dehghan MH, Yazdani S, Behboudi H, et al. Prospective randomized trial of trimethoprim/sulfamethoxazole versus pyrimethamine and sulfadiazine in the treatment of ocular toxoplasmosis. Ophthalmology. 2005 Nov. 112(11):1876-82. [Medline].

    Reich M, Mackensen F. Ocular toxoplasmosis: background and evidence for an antibiotic prophylaxis. Curr Opin Ophthalmol. 2015 Nov. 26 (6):498-505. [Medline].


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