Editing Toxoplasmosis (section)

==Diagnosis==

[[File:BrainToxoplasmosis MRI 2 09.png|thumb|MRI: Cerebral toxoplasmosis with primary involvement in the right occipital lobe (at left and below of the image). 48-year-old woman with [[AIDS]]]]
<!-- uncited, explain RhD Quite contrary to a low percentages of humans who manifest excesses in extracellular dopamine levels and are thus vulnerable to ''T. gondii'' that elevates dopamine levels in the brain, others, with some common genetic mutations can benefit from ''T. gondii''. This excludes RhD negative blood typed humans who do not have the genotypes that will be discussed in the following paragraphs.-->
Toxoplasmosis in humans is diagnosed through biological, serological, histological, or molecular methods, or by some combination of the above.<ref name="Hill_2002"/> Toxoplasmosis can be difficult to distinguish from [[primary central nervous system lymphoma]]. Its symptoms mimic several other infectious diseases, so clinical signs are non-specific and are not sufficiently characteristic for a definite diagnosis. A failed trial of antimicrobial therapy ([[pyrimethamine]], [[sulfadiazine]], and [[folinic acid]] ([[United States Adopted Name|USAN]]: leucovorin)), makes an alternative diagnosis more likely.{{cn|date=January 2023}}

''T. gondii'' may also be detected in [[blood]], [[amniotic fluid]], or [[cerebrospinal fluid]] by using [[polymerase chain reaction]].<ref name="SwitajEtc2005">{{cite journal |vauthors=Switaj K, Master A, Skrzypczak M, Zaborowski P |title=Recent trends in molecular diagnostics for ''Toxoplasma gondii'' infections |journal=Clinical Microbiology and Infection |volume=11 |issue=3 |pages=170–6 |year=2005 |pmid=15715713 |doi=10.1111/j.1469-0691.2004.01073.x |doi-access=free }}</ref> ''T.&nbsp;gondii'' may exist in a host as an inactive cyst that would likely evade detection.{{citation needed|date=January 2021}}

[[Serology|Serological]] testing can detect ''T.&nbsp;gondii'' antibodies in blood serum, using methods including the [[Sabin–Feldman dye test]] (DT), the indirect [[hemagglutination assay]], the [[Indirect fluorescent antibody|indirect fluorescent antibody assay (IFA)]], the [[direct agglutination test]], the [[latex agglutination test]] (LAT), the [[ELISA|enzyme-linked immunosorbent assay (ELISA)]], and the immunosorbent agglutination assay test (IAAT).<ref name="Hill_2002"/>

<!--sections of "IgG antibody" are taken directly from the 2002 Montoya paper-->
The most commonly used tests to measure [[IgG]] antibody are the DT, the ELISA, the IFA, and the modified direct agglutination test.<ref name="Montoya_2002">{{cite journal | author = Montoya JG | title = Laboratory diagnosis of ''Toxoplasma gondii'' infection and toxoplasmosis | journal = The Journal of Infectious Diseases | volume = 185 | issue = Suppl 1 | pages = S73–82 | year = 2002 | pmid = 11865443 | doi = 10.1086/338827 | doi-access = free }}</ref> IgG antibodies usually appear within a week or two of infection, peak within one to two months, then decline at various rates.<ref name="Montoya_2002"/> ''Toxoplasma'' IgG antibodies generally persist for life, and therefore may be present in the bloodstream as a result of either current or previous infection.<ref name="JonesPariseFiore2014">{{cite journal | vauthors = Jones JL, Parise ME, Fiore AE | title = Neglected parasitic infections in the United States: toxoplasmosis | journal = American Journal of Tropical Medicine and Hygiene | volume = 90 | issue = 5 | pages = 794–9 | year = 2014 | pmid = 24808246 | pmc = 4015566 | doi = 10.4269/ajtmh.13-0722 }}</ref>

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.<ref name="RemingtonThulliez2004">{{cite journal |last1=Remington |first1=Jack S. |last2=Thulliez |first2=Philippe |last3=Montoya |first3=Jose G. |title=Recent Developments for Diagnosis of Toxoplasmosis |journal=Journal of Clinical Microbiology |date=March 2004 |volume=42 |issue=3 |pages=941–945 |doi=10.1128/JCM.42.3.941-945.2004 |pmid=15004036 |pmc=356902 }}</ref>

<!--sections of "IgM antibody" are taken directly from the 2002 Montoya paper-->
In contrast to IgG, IgM antibodies can be used to detect acute infection but generally not chronic infection.<ref name="JonesPariseFiore2014"/> The IgM antibodies appear sooner after infection than the IgG antibodies and disappear faster than IgG antibodies after recovery.<ref name="Hill_2002"/> In most cases, ''T.&nbsp;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.&nbsp;gondii''-specific IgM within seven months.<ref name="JonesPariseFiore2014"/> However, IgM may be detectable months or years after infection, during the chronic phase, and false positives for acute infection are possible.<ref name="Montoya_2002"/>  The most commonly used tests for the measurement of IgM antibody are [[ELISA#Sandwich ELISA|double-sandwich IgM-ELISA]], the [[Indirect fluorescent antibody technique|IFA test]], and the immunosorbent agglutination assay (IgM-ISAGA). Commercial test kits often have low specificity, and the reported results are frequently misinterpreted.<ref name="Montoya_2002"/>

<!--This section is adapted from the 2021 systematic review paper-->
In 2021, twenty commercial anti-''Toxoplasma'' IgG assays were evaluated in a [[systematic review]], in comparison with an accepted reference method.<ref name="Robert-GangneuxGuegan2021"/> 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 and negative predictive values|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.<ref name="Robert-GangneuxGuegan2021">{{cite journal|last1=Robert-Gangneux|first1=Florence|last2=Guegan|first2=Hélène|title=Anti-''Toxoplasma'' IgG assays: What performances for what purpose? A systematic review|journal=Parasite|volume=28|year=2021|pages=39|doi=10.1051/parasite/2021035|pmid=33904818|pmc=8078101|doi-access=free}} {{openaccess}}</ref>

===Congenital===
[[File:Toxoplasmosis, Congenital.jpg|thumb|Child with congenital toxoplasmosis]]
Recommendations for the diagnosis of congenital toxoplasmosis include: prenatal diagnosis based on [[Amniocentesis|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.<ref name="Sterkers_2011"/> During pregnancy, serological testing is recommended at three week intervals.<ref name="Sensini2006">{{cite journal |last1=Sensini |first1=A. |title=Toxoplasma gondii infection in pregnancy: opportunities and pitfalls of serological diagnosis |journal=Clinical Microbiology and Infection |date=June 2006 |volume=12 |issue=6 |pages=504–512 |doi=10.1111/j.1469-0691.2006.01444.x |pmid=16700697 |doi-access=free }}</ref>

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.&nbsp;gondii'' infection because the specific anti-''Toxoplasma'' [[Immunoglobulin G|IgG]] or [[Immunoglobulin M|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.&nbsp;gondii'' infection leading to undetected and therefore untreated congenital toxoplasmosis.<ref name="Lin_2000">{{cite journal |vauthors=Lin MH, Chen TC, Kuo TT, Tseng CC, Tseng CP | title = Real-time PCR for quantitative detection of ''Toxoplasma gondii'' | journal = Journal of Clinical Microbiology | volume = 38 | issue = 11 | pages = 4121–5 | year = 2000 | pmid = 11060078 | pmc = 87551 | doi = 10.1128/JCM.38.11.4121-4125.2000}}</ref> Also, the test may not detect ''T.&nbsp;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|date=January 2021}}

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.<ref name="Lin_2000"/> The major downside to these techniques is that they are time-consuming and do not provide quantitative data.<ref name="Lin_2000"/>

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.<ref name="Lin_2000"/> A second fluorescent dye, e.g., 6-carboxy-tetramethyl-rhodamine, quenches the fluorescence of the intact probe.<ref name="Lin_2000"/> 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.<ref name="Lin_2000"/>

Lymph nodes affected by ''Toxoplasma'' have characteristic changes, including poorly demarcated reactive [[germinal centers]], clusters of monocytoid B cells, and scattered epithelioid [[histiocyte]]s.{{cn|date=January 2023}}

The classic triad of congenital toxoplasmosis includes: [[chorioretinitis]], [[hydrocephalus]], and [[intracranial arteriosclerosis]].<ref>{{cite journal|last1=Jones|first1=J|last2=Lopez|first2=A|last3=Wilson|first3=M|title=Congenital toxoplasmosis|journal=American Family Physician|date=15 May 2003|volume=67|issue=10|pages=2131–8|pmid=12776962}}</ref> Other consequences include sensorineural deafness, seizures, and intellectual disability.<ref>{{MedlinePlusEncyclopedia|001360|Congenital toxoplasmosis}}</ref>

Congenital toxoplasmosis may also impact a child's hearing. Up to 30% of newborns have some degree of sensorineural hearing loss.<ref>{{cite journal |last1=Corrêa |first1=Camila |last2=Maximino |first2=Luciana |last3=Weber |first3=Silke |title=Hearing Disorders in Congenital Toxoplasmosis: A Literature Review |journal=International Archives of Otorhinolaryngology |date=7 August 2017 |volume=22 |issue=3 |pages=330–333 |doi=10.1055/s-0037-1605377 |pmc=6033603 |pmid=29983776 }}</ref> 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.<ref>{{cite journal |last1=De Resende |first1=Luciana Macedo |last2=Andrade |first2=Gláucia Queiroz Manzan de |last3=Azevedo |first3=Marisa Frasson de |last4=Perissinoto |first4=Jacy |last5=Vieira |first5=Andrêza Batista Cheloni |title=Congenital toxoplasmosis: Auditory and language outcomes in early diagnosed and treated children |journal=Scientia Medica |date=16 April 2010 |volume=20 |issue=1 |pages=13 |doi=10.15448/1980-6108.2010.1.5927 |doi-broken-date=1 November 2024 |url=https://revistaseletronicas.pucrs.br/scientiamedica/article/view/5927 }}</ref>