Trends in Parasitology
OpinionSerology for Toxoplasma in Immunocompromised Patients: Still Useful?
Section snippets
Toxoplasmosis, One of the Most Frequent Human Parasitic Infections
Toxoplasmosis is a widespread zoonosis caused by Toxoplasma gondii, an obligate intracellular protozoan parasite. Transmission in humans can result from the ingestion of oocysts (see Glossary) shed by infected felids and of cysts from undercooked meat of infected animals. After ingestion, both forms of the parasite transform into rapidly multiplying tachyzoites able to cause the death of all nucleated cells, leading to the dissemination of the parasite throughout the host’s tissues. Subsequent
Toxoplasmosis, a Severe Opportunistic Infection in Immunocompromised Patients
Immunocompromised patients are at risk for severe forms of toxoplasmosis as a consequence of several mechanisms (Figure 1). The first is the reactivation of tissue cysts containing parasites in seropositive individuals who suffer from a severe defect in cell-mediated immunity, in a variety of clinical contexts.
- (i)
Hematopoietic stem cell transplant (HSCT) recipients are specifically exposed to the risk of reactivation of pre-existing cysts and to their hematogenous dissemination, due to their
PCR Contributes to Asserting T. gondii Reactivation
The development of molecular tools for the detection of T. gondii DNA and their use in immunocompromised patients over the past decades have improved prevention and diagnosis in many aspects. Indeed, PCR-based diagnostic strategies have been validated in several major indications, the best performances being reported for quantitative RT-PCR targeting the 529 bp repeat region [35., 36., 37.].
To briefly review the literature, the main advantages of PCR are based on its high predictive positive
PCR-Based Diagnosis and Surveillance Strategies Have Intrinsic and Extrinsic Limitations
Recently, systematic monitoring allowing pre-emptive strategies was encouraged [7,43,48]. However, positive PCR in asymptomatic patients (e.g., Toxoplasma infection) is reported in up to 66% of positive PCRs in hematological patients [11,34,48,49]. There is a debate on their clinical predictive value and on how to manage them. Positive PCR at a distance of a proven clinical episode might also raise questions.
To date, in the absence of a syndrome-based approach, the molecular diagnosis of
Serology Has Several Unique Advantages
Antibody detection offers several clear advantages (Box 1) that allow compensating for the intrinsic limits of PCR and contributing to the management of immunocompromised patients in two ways.
In terms of prevention, serology brings several benefits when performed at the time of the diagnosis of immunosuppression, before and at the time of transplantation, and/or during the period of immunosuppression, according to clinical situations.
In the context of HSCT, serological tests among future
Serology Optimizes the Use of PCR for the Follow-up and Diagnosis of Patients at Risk
If toxoplasmosis follow-up of immunocompromised patients is mainly based on PCR, serology remains a complementary and interesting tool as well. In a European multicentric study on toxoplasmosis in recipients, PCR was found to be the most helpful diagnostic tool in 77 cases (89%), but serology allowed the diagnosis of toxoplasmosis in 28 cases out of 87 reported cases (32%) [44].
During the follow-up by PCR and serological tests of 70 allo-HSCT recipients at risk for toxoplasmosis, detection of
Serology Has Several Practical Advantages
Besides its technical performances, serology has the advantages of being cheap and not requiring sophisticated technical facilities, which is particularly relevant in settings where medical resources are scarcer (these are often located in areas of high T. gondii prevalence [5]) and of high frequency of HIV co-infections [66]. It can be automatized for large-scale testing or performed on filter paper.
Serological Diagnosis Has Limitations and Pitfalls That Should Not Be Overlooked
A large variety of assays are available on the market for the detection of specific anti-Toxoplasma IgG and IgM. They rely on different types of antigens and principles, including enzyme-linked immunosorbence, chemiluminescence, hemagglutination, indirect fluorescence, immunosorbent agglutination, and immunoblotting. Their performances are highly variable due to the absence of standardization that forbids comparing tests results across assays.
Attention should also be paid to the possibility for
Good Practice Rules Are Required to Maximize the Yield of Serology
Good practice rules need to be strictly followed, regardless of the techniques used. First, subsequent tests for a given patient need to be performed at the same laboratory, using the same test, in order to be able to compare test results and identify any significant increase in IgG titers. Second, all tests should be performed by biologists trained to recognize nonspecific or persistent IgM [69] or passive transfer of IgG [68] and knowledgeable of additional tests to be performed in case of
Promising New Serological Tests Are to Be Expected
Following the current trend for modernization of tools for the molecular diagnosis of infections, new tests and approaches have recently been developed in order to increase the robustness, performances, and friendliness of antibody detection [71]. They include rapid individual finger prick tests [72] and tests to be performed on oral fluid in order to reduce blood spoliation [73,74]. Plasmonic gold chip tests have also been developed on blood and saliva, which yield almost perfect performances
Serology Is Also a Valuable Tool for Epidemiological Surveillance and Research
These new tests will be useful for the routine management of patients at risk, but also help in performing seroprevalence surveys to document the fast changing epidemiology of T. gondii infection worldwide [5], which results from the industrialization of food production chains and increasing urbanization. Such changes are likely to impact the management of patients, if fewer are at risk of reactivation and a large number exposed to a risk of primary infection. New strategies will have to be
Concluding Remarks
Toxoplasma reactivation or primary infection in the immunocompromised affects a wide variety of patients and, without treatment, may have extremely serious consequences. New indications for transplantation, and the use of biotherapies, further increase the number of patients requiring specific monitoring to diagnose toxoplasmosis. Reactivation of Toxoplasma cysts present in the seropositive patient or in the transplanted organ is more frequent than primary infections. These situations represent
Acknowledgments
Hervé Pelloux is member of the European Study Group for Clinical Parasitology of the European Society for Clinical Microbiology and Infectious Diseases.
Glossary
- Avidity
- avidity reflects the strength of binding of IgG antibodies to a Toxoplasma antigen. It increases with time, due to the maturation of the hypervariable regions of the antibodies. IgG avidity testing is an interesting tool to distinguish between a recent and a past infection when both Toxoplasma gondii-specific IgG and IgM are detected in a serum sample. Indeed, a high avidity result indicates a past infection, dating from more than 3 to 5 months according to the assay.
- Bradyzoite
- the latent
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Risk of reactivated toxoplasmosis in haematopoietic stem cell transplant recipients: a prospective cohort study in a setting withholding prophylaxis
2022, Clinical Microbiology and InfectionCitation Excerpt :Our diagnostic strategy was based on qPCR targeting the 529 bp repeat element, validated in numerous studies [12,24,25] to provide the best performance for the diagnosis of toxoplasmosis in immunosuppressed patients. We have also performed simultaneous serological testing because it was reported useful even after HSCT [5,26,27], while being feasible and inexpensive. However, our results do not favour this practice since we did not detect specific IgM in any patient.
Frequency and parasite load of Toxoplasma gondii in hemodialysis patients based on RE gene by real-time PCR
2021, Gene ReportsCitation Excerpt :Pregnant mothers' abortions, respiratory complications, heart complications, and encephalitis in people with AIDS), ocular complications in infants, and so on are all risky AIDS complications (Ali and Başak, 2019; Binquet et al., 2019; Peyron et al., 2019). To complete the introduction, although today serological methods are the most common diagnostic methods for Toxoplasmosis, but due to false positives and negatives in the diagnosis, molecular methods are gradually used (Dupont et al., 2021; Khan and Noordin, 2020). T. gondii have a high genetic diversity and RE gene is one of the commonly genomic repeats of it (Fallahi et al., 2014; Schares et al., 2018).
Detection of the B1 gene of Toxoplasma gondii by PCR in the feces of domestic cats
2024, Semina:Ciencias AgrariasSeroprevalence of Anti-Toxoplasma gondii Antibodies among Patients with Cancer at Hiwa Cancer Hospital in Sulaimani City, Kurdistan Region, Iraq
2023, Iranian Journal of Parasitology
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These authors contributed equally to this work