The Important Role of Laboratories in the Diagnosis and Prevention of Toxoplasma Infection

Abstract

Toxoplasma gondii is a high universal distribution intracellular parasite that causes toxoplasmosis, an infection of significant importance when pregnant women or immunosuppressed patients become infected. In immunocompetent humans, it is rarely a symptomatic disease. Diagnosis and prevention are essential to reduce severe health consequences in susceptible patients. Laboratories must play an important role in trying to avoid seroconversion, by helping in prevention and accurate diagnosis to facilitate patients\' access to treatment as early as possible. The main focus of this chapter is about the steps laboratories should take in diagnosing Toxoplasma gondii infection by using screening tests (ELISA, HAI, AD) or confirmatory tests (Sabin Feldman dye test, ISAGA, PCR, Isolation)—determining whether patients are toxoplasmosis positive or negative—and in being actively involved in the prevention of the infection. Failing to do this would make the future of these families a very difficult road to travel.

1. Introduction

Toxoplasma gondii infection affects a third of the world’s population. Although in people with a healthy immune system it does not cause disease and it is usually asymptomatic, in pregnancy and immunosuppressed patients it can cause serious side effects.

In pregnancy, congenital toxoplasmosis may cause severe consequences to the fetus, from death in uterus to late important clinical conditions such as cognitive impairment, blurry vision by inflammation of the retina, deafness, epilepsy, seizures, tuberculosis, Pneumocystis jiroveci pneumonia, or poor coordination.

In primary or secondary immunosuppressed patients who get Toxoplasma gondii infection, or a reactivation of the disease, unwanted sequelae can also occur [1, 2, 3, 4].

Laboratories should play an important role. “The important role of laboratories” should be getting involved and assuming the commitment not only in the diagnosis, but also in the prevention. They must bridge the gap between the attending physician and patients.

1.1 Pregnant women testing

If toxoplasmosis serology is unknown before women became pregnant, then start by finding it out as early as possible within the first trimester [1, 2, 3, 4].

An IgG test is the first thing to do to know the patient’s serology. Which test should be selected? Laboratories must maximize their available equipment, resources, and capabilities, to choose their tests. Do any test, it is better than doing nothing.

Once an IgG result is obtained, two paths will open:

1. If IgG serology result is negative, great care must be taken because even though these women are not infected, they are susceptible to become infected [3, 4, 5, 6]. This is why they must be followed. How? By warning about primary prevention measures (see Preventive Medicine) [1, 3, 4, 7, 8] and monitoring their IgG serology every month or at least once every three months to make sure not become infected during the rest of pregnancy (as shown in Figure 1a) [2, 9, 10].

2. If IgG serology result is positive, then the next step is to do a Toxo IgM test to be sure that it is not a potential seroconversion [1, 2, 3, 4].

Figure 1.

Pregnant women-testing. a. Negative. b. Past infection. c. Seroconversion. Note: Own elaboration.

1.2 Toxo IgM test result

After the IgM test result is ready, two new situations emerge the following:

1. If IgM result is negative means these women were toxoplasmosis positive before pregnancy. In this case, it is a past infection and they are immunized against the parasite infection. There is no risk of becoming infected during their pregnancy and their children are out of danger (displayed in Figure 1b)

2. If IgM result is positive, there is a high suspicion of a seroconversion (SC), in which case this must be confirmed (as illustrated in Figure 1c).

1.3 How to confirm a seroconversion

The way to confirm a SC will depend on capabilities and the laboratory scope. Now at this point there are two other new scenarios:

1. Routine Laboratories: could refer this sample to a reference laboratory to perform more specific tests such as Western blot, PCR, ISAGA M, ISAGA A, ISAGA E, and Avidity test [2]. If there is not a reference laboratory or a more complex one nearby, then deem the result equivocal with an observation suggesting to repeat the test in three weeks. When the new sample arrives and an increase in title is observed, seroconversion is confirmed [1, 2, 3, 4, 5, 7, 8, 11].

2. Reference Laboratories: must enlarge the sample with other specific tests such as those named above. At the time of delivery, isolation of Toxoplasma gondii parasite in placenta and umbilical blood cord can be done and, furthermore, studied the type of strain to which it belongs to know the degree of impact to the newborn [12, 13, 14, 15, 16, 17].

Once SC is confirmed, the doctor in charge must be notified as soon as possible, so these women can be medicated to avoid parasites infect placenta and make sure the newborn does not have any immediate or late clinical consequences [1, 2, 3, 4, 5, 7, 8].

1.4 Newborns without her mother’s serology

Another different possible scenario could be to receive a child, without her mother’s serology. In this stage, follow them up, doing an IgG toxo test every three months until they are one-year-old [1, 2]. What information is obtained?:

1. At the beginning, during the first six months, the same mother’s serology is observed. The specific IgG crosses placenta so the results obtained will be a copy of their mother’s antibody titer. But when the baby’s immune system matures, mother's antibodies disappear. This is the moment to be more careful and make sure the parasite does not take advantage of it. This is the reason why the child’s IgG antibodies, until she/he is one year old, must be followed (as shown in Figure 2) [1, 2].

2. A congenital toxoplasmosis is suspected in the newborn when the IgG titer is significantly higher than the mother’s and the IgM is positive. The child is considered free of infection when the IgG is negative at age one (as illustrated in Figure 2). This might be the gold standard for laboratories, having peace of mind that a good work was done, and the mission was fulfilled [1, 2].

3. When a prenatal infection is suspected, an hemogram, hepatogram, and a urine analysis also should be applied as the initial control and value systemic compromise of the infection [1, 2].

Figure 2.

Newborns without her mother´s serology. Note: Own elaboration.

2. Kinetics of immunologic response

At the beginning of toxoplasmosis disease, during the first-week post-infection, IgM starts to appear. At this time, the role of Sabin Feldman test is fundamental because it detects IgG and IgM together. The next immunoglobulin (Ig) to appear is IgE, then IgA. IgG appears within the first month, stabilizes two or three months after infection has started, and persists throughout life (as shown in Figure 3) [1, 2, 3, 4, 5, 7, 8, 11].

2.1 IgG detects different Toxoplasma gondii antigens. First antigens to be detected by the IgG are membrane antigens and later intracytoplasmics ones [1].

2.2 To detect IgE, IgA and IgM ISAGA’s test is needed (see Diagnostics available tests).

2.3 IgM displays a special behavior in this disease. It can be found for more than two years [1, 3, 7, 8, 11, 18]. Hence, if it is found, be careful how its appearance is interpreted. Complement that finding using other tests like specific IgA and IgE must be done to confirm a SC.

2.4 IgA is found during about six months, if it is positive, it is a correct way to confirm a SC [1, 2, 3, 4, 5, 8, 11].

2.5 IgE falls fast. Only during the first three month of Toxoplasma gondii infection, it can be detected, but whenever is found, it also confirms the SC [1, 2, 3, 4, 5, 8, 11].

2.6 IgE and IgA together increase the chances of detecting seroconversion earlier [1, 2, 3, 4, 5, 8, 11]. Therefore, it is important not to waste time and confirm those questionable samples as soon as possible.

Figure 3.

Kinetics immunologic response. Note: Own elaboration.

3. Diagnostic available tests

There are direct and indirect methods to detect a Toxoplasmosis infection:

3.1 Direct methods

They are based on identifying the presence of Toxoplasma gondii parasite or their nucleic acid. The techniques within these methods are fresh observation, histological stains, histopathological analysis, PCR, PCR real time, parasite isolation.

The materials available to use are newborn blood, umbilical blood cord, placenta, amniotic fluid, LCR, vitreous humor, biopsies, and other fluids [1, 8].

3.1.1 PCR

It is based on detecting the parasite nucleic acid using the polymerase chain reaction.

3.1.2 Parasite isolation

It consists of detecting the parasite in biological samples (cell culture or mouse inoculation).

3.2 Indirect methods

All of these tests evidence specific antibodies. There are screening tests: indirect hemagglutination (HAI), direct agglutination (DA), immunoassays, and confirmatory tests: Sabin Feldman, ISAGA M, A and E, IFI IgG and IFI IgM, and avidity test.

All of them have their advantages and disadvantages (seeTables 1 and 2) [1, 3, 8, 11]. The choice depends on the kind of laboratory and resources available.

Test	Automatizable	Staff dependant	Need special equipment	Cost	Sensitivity for SC	Specificity
HAI	No	Yes	No	Low	Low*	Low
AD	No	Yes	No	Low	Low*	Low
ELISA	Var	Var	Var	Low	Var	Var
QML, CLIA, ELFA	Yes	No	Yes	Var	High	High
Avidity	Var	Var	Var	Var	High**	High

Table 1.

Screening tests. Routine Laboratories [1].

^*

Detects late infection.

^**

When the result is low and pregnancy is before the 16th week.

Var: Variable: Depends on the cost/benefit of the laboratory.

Note: Own elaboration.

Test	Automatizable	Staff dependant	Need special equipment	Cost	Sensitivity for SC	Specificity
Sabin Feldman*	No	Yes	No	Low	High	High
IFI IgG	No	Yes	Yes	Low	High	High
IFI IgM	No	Yes	Yes	Low	Low	High
ISAGA M	No	Yes	No	Low	Var	High
ISAGA A	No	Yes	No	Low	High	High
ISAGA E	No	Yes	No	Low	High	High
Western Blot	No	Yes	No	High	High^**	High
PCR in House, RT PCR	Var	Var	Yes	Var	Var	High
Isolation	No	Yes	No	Low	High	High

Table 2.

Confirmatory tests. Reference Laboratories [1].

^*

Reference reaction.

^**

For paired samples mother-child.

Var: Variable: Depends on the laboratories cost/benefits.

Note: Own elaboration.

3.2.1 Screening tests

This tests are used in Routine Laboratories (Table 1)

3.2.1.1 HAI

This technique is not recommendable. However, many laboratories still use it; therefore, it is necessary to warn that it detects late infection. It is useful only after three months of the onset of the infection.

3.2.1.2 AD

Direct agglutination consists of mixing a stabilized suspension of Toxoplasma gondii or latex particles sensitized with parasitic antigens, with the patient serum and observing agglutination reaction.

3.2.1.3 Immunoassays

The basis of these tests is to measure the specific union antigen-antibody IgG, by adding a detection complex. The antigen is attached to different supports. That is why there are a lot of available types and brands of immunoassays (ELISA, QML, CLIA, IFI), their variety depends on the following:

3.2.1.3.1 The kind of antigen that they use

There are membrane antigens that appear first (p30 (SAG-1), p22 (SAG-2)) and cytoplasmic antigens that can be detected later (p35 (GRA-8), ROP-1, GRA-6, GRA-7). According to the antigens that the immunoassay uses, the specific IgG can detect them within one or three weeks after infection has started [1]. Deciding which test to choose is one of the most important steps.

3.2.1.3.2 The support that is being used

Consist on the base where the antigens or antibodies are sustained. They can be microplates (ELISA), microparticles (QML, CLIA), slides (IFI), latex particles (AD), cells (HAI). The smaller they are, the more sensitive the test will be.

3.2.1.3.3 The detection complex is the other ítem to be considered

Conjugate-enzyme (ELISA), fluorescence (IFI), luminiscencia (CLIA), quimioluminiscencia (QML).

The sensitivity and specificity of different assays available depend on the combination of all of these variables; therefore, the choice made will depend on the cost/benefit of the laboratories available resources.

But the most important after selecting the tests is to follow the insert and do the test respecting it, doing exactly what it recommends and always use quality controls, internal and external ones, to compare the results and be sure that all samples have a certain result.

3.2.2 Confirmatory tests

These tests are used in Reference Laboratories (Table 2).

3.2.2.1 Sabin Feldman dye test (SF)

The test is based on complement-mediated cytolysis of antibody-coated live Toxoplasma gondii tachyzoites, which is indicated by their inability to take up methylene blue stain [19, 20, 21, 22].

This test deserves a special topic and is a reference method for serodiagnostic Toxoplasma gondii infection. Its importance is based on being the only one that detects IgG and IgM together. Therefore, it is the most specific and sensitive of all the indirect methods. There are cases that disagree between values comparing SF and other tests, because it is the first one to render a positive result. This test makes the difference to detect the seroconversion as soon as possible.

We are one of the laboratories that still use it as a routine method. A multicenter study of prevention of congenital toxoplasmosis, based on confirmed equivocal or indeterminate samples from other routine laboratories, gets as result that the 46% of the samples that were serodiagnostic as possible seroconversions in routine laboratories, were defined as cronics in our reference laboratory using SF and ISAGA M method. This means that all of those women would have been treated when not necessary [2].

The problems of most laboratories that stop using SF were maintained live tachyzoites of Toxoplasma gondii, each country's animal regulations, trained staff, dangerous to laboratory workers, costs, automation, interlaboratory standardization, accessibility of Western blot, better performance of new tests.

Because of them, probably the future of the SF dye test in reference laboratories could be changed for cellular culture, if possible, which is a valid alternative and could be the way to change the SF dye test without losing its advantages and quality.

3.2.2.2 ISAGA

It consists of capturing the specific antibody (IgM, IgA, or IgE) and then adding a stabilized suspension of Toxoplasma gondii to evidence specific Igs with direct agglutination.

3.2.2.3 Avidity Test

The avidity test measures the power of the union antigen-antibody. When it is recent, the union is weak, but when it is not recent, the union is strong. We could understand it like a traffic light (illustrated in Figure 3): When the result is low, the union is weak and it means high probability of seroconversion within the past three months (red light); if it is intermediate, then we must be alert and study the combination of the other different serologies we have (yellow light); and when the result is high, the union is strong and can be reassured that it is a more than four months old infection (green light).

It is important to consider that this test gives useful information only until the 16th week of pregnancy. Any time after the 16th week, the avidity test loses its importance [1, 3, 4, 8, 11]. Another consideration is that there are many brands of avidity tests available. They each have their own benchmarks and sometimes the results do not match up. Therefore, it is very important to consider the other confirmatory tests (see Available diagnostic tests) at the time of the final decision.

4. What should be done in Routine Laboratories for screening?

Here, the big question to answer what must be done in Routine Laboratories for screening, is: Only IgG? IgG and IgM?

Well, the answer is not an only one, the answer depends on the resources and the cost/benefit analysis.

Do only IgG tests should be done as frequently as possible, which means between every month and every three months, mínimum [1, 2, 3, 4, 5, 9, 10]. This is the only way to detect an early SC.

If IgM is added, chances of detecting seroconversion are much better [1, 2, 3, 4, 5] because those cases where the SC has just begun will be able to be detected.

This is certainly the best way to work. The decision will depend on the prevalence [2, 5, 6], the patient’s knowledge of this disease and their access to primary preventive measures (see Preventive Medicine) and laboratory resources.

5. What should be done in Reference Laboratories?

As a continuity on the previous topic, here is the great difference.

While Routine Laboratories can choose a lot of brands of kits, and do only IgG depending on their resources and cost/benefit analysis, Reference Laboratories cannot. That is what makes the difference.

Reference Laboratories must do, not only IgG and IgM, but also the most sensitive ones and have the best brands. Besides that, must do ISAGA´s Tests ISAGA M, ISAGA A, and ISAGA E, Western blot, PCR [8, 23], and if possible Sabin Feldman or Cellular Culture and sequence [12, 13, 14, 15, 16, 17, 19, 20, 21, 22, 23].

This difference is based on accurately diagnosing a seroconversion. Cannot report a doubt. If there is a doubt, the best they can do is to recommend retesting after two or three weeks, to allow the immunological system to mature. This is when a SC has just started and the titer of IgM is not enough to confirm it. Meanwhile, they should suggest doctors in charge start medicating them, as a preventive measure, until the result of the next sample is obtained.

6. Preventive medicine

Preventive medicine is another very important task to detect SC earlier than anything. There are three ways to do this:

6.1 Primary Preventive Medicine

There are many things to do to prevent Toxoplasma gondii infection. Precautionary measures consist of [1, 3, 4, 7, 8]:

1. Washing hands before handling foods.

2. After handling raw meat, wash hands with water and soap.

3. Not eating undercooked meat. It must be cooked at more than 66°C.

4. Not eating sausages.

5. When handling foods, a different cutting board for meat and raw vegetables must be used.

6. Cleaning the surface and utensils after using them with raw foods.

7. Cleaning fruits and vegetables very carefully. They must not be eaten if it is not known how they were washed.

8. Avoiding contact with unknown cats.

9. Wearing gloves for cleaning domestic cat excrement and washing hands carefully after.

10. Wearing gloves and washing hands carefully after practicing gardening.

There are a lot of things laboratories can do to make pregnant women aware of these precautionary measures and help them prevent Toxoplasma gondii infection. There are many ways to do this and it will depend on empathy, enthusiasm, and imagination. Some ideas are as follows:

• Add them in your report.

• Make brochures and give them to pregnant women at their gynecological consultation.

• Use all the social media networks (Internet, Twitter, Instagram, Web pages).

• Use your internal network at your job.

• Publish Posters, etc.

Congenital toxoplasmosis can cause miscarriage or stillbirth. In many cases, infants appear healthy at birth but they may develop adverse sequelae of the infection later in life, including decreased vision or blindness, decreased hearing or deafness, and mental and psychomotor retardation.

The idea is to focus on these measures and to make pregnant women aware of the Toxoplasma gondii infection and of the consequences they could face if this infection is not taken seriously.

As an example, we work in a Reference Laboratory Country and we receive samples from many cities in the country, to help them confirm those difficult results, with values near the cut off that routine laboratories cannot resolve because of their limited techniques. We are working on a prevention toxoplasmosis program named “CONTENER,” it means “Containing,” to expand our services to help more laboratories and concerned patients' get an accurate result. When this happens, our mission to help getting a final and accurate diagnosis to apply the right treatment as soon as possible is accomplished. “CONTENER” is also an Spanish acronym for “Contain against Toxoplasmosis in newborns and pregnant women”.

6.2 Secondary preventive medicine

If primary prevention did not work and a SC has happened, this preventive option appears. The secondary prevention is directed to protect the embryo or fetus when the mother has been infected during pregnancy. It is based on antiparasitic treatment until delivery. The most important thing in this situation is to start it as soon as possible. The sooner it starts, the more effective it will be [1, 3, 8].

The next step is to do serologic analysis on the paired mother-child. The ideal test to use is Western blot, but any IgG- and IgM-specific paired serology achieves. Some Reference centers suggest detection of DNA parasites using the blood cord of the newborn as an important complementary fact of great specificity and we also recommend isolation of the parasite in cord blood and placenta if it is possible [12, 13, 14, 15, 16, 17].

6.3 Third preventive medicine

This preventive measure is used when the other two fail. This next step is to make a referral to a specialist doctor who understands this disease and its importance to be medicated as soon as possible to prevent the immediate and late clinical consequences and perform all of the necessary studies and controls.

7. Laboratories role in pregnancy and newborn

After reviewing everything laboratories can do about these topics, it is necessary to highlight the following:

1. Study pregnant women serology before and during pregnancy with frequent controls [1, 2, 9, 10].

2. Use the best tests available with the resources at hand.

3. Do IgG and IgM if IgG is positive [1, 2, 3, 4, 7, 8, 11].

4. Send samples or refer them to specialized laboratories when cannot obtain an accurate result whenever a positive IgM result is obtain.

5. Have a fluid communication with the doctor in charge following pathologic serology results.

6. Be in contact with the pediatrician in charge of the newborn.

7. Do Preventive Medicine [1, 3, 4, 7, 8].

8. Spread as many precautionary measures as possible

9. Check periodic and paired serology evolution of those kids born from Toxoplasma gondii infected women, until they are one-year-old [1, 2, 4].

8. Laboratories role in other clinicals group.

8.1 Immunocompetent patients

Most toxoplasmosis infections are asymptomatic or have mild nonspecific symptoms, so these patients who have a healthy immune system, probably do not need to be diagnosed. This is the reason why occasional findings of circulating specific antibodies are common. Chronic infections are more frequent than acute ones [24] and patients should not require treatment because it is a self-limited disease.

Mild symptoms could be: high fever, astenia, headache, muscle pain, anorexia, cough, throat pain, lymphadenopathies, and splenomegaly (when there is involvement of the mesenteric nodes) and they must be differentiated with other diseases.

The most characteristic symptom that needs to be differentiated is lymphadenitis: In this case, the role of laboratories gains importance in giving an accurate diagnosis to specialist doctors, not to start treatment, but to rule out other pathologies that do need it.

8.2 Immunosuppressed patients

These patients are susceptible to develop diseases that may cause severe sequelae depending on the type of infection. Referring to toxoplasmosis, two types of illness can be developed: severe primary infection and reactivation of a latent infection.

For example, immune deficiency conditions such as AIDS and organ transplantation can cause fatal toxoplasmic encephalitis [24, 25, 26, 27]. Hence, the role of laboratories in these cases is fundamental to accompany other diagnostics methods such as RMN and TC.

To diagnose, direct methods in samples, such as LCR, lymph nodes, vitreous humor, bone marrow (see Diagnostic available tests), should be used. Even though these tests do not have high sensitivity, they have a high-positive predictive value (VPP) when the result is positive, and when it is negative (negative predictive value (VPN)) it will alert doctors to a risk of a primary infection. Hence, periodic serological controls and preventive measures should be carried out.

8.2.1 VIH patients

Encephalitis with brain injuries is the most common sequelae when patients are HIV positive and have the disease [24, 25, 26, 27]. The role of laboratories is to complement results obtained, with others such as TC and RMN and biopsy.

Direct methods like PCR or isolation can be useful in fluids such as LCR, BAL, biopsies.

Serology results are important to predict risk of infection or reactivation: SF test has a VPN del 99,7% and a VPP of 88% and other serologies, IgG above 1/256 with CD4 lymphocytes less than 150 cel/mm3, ISAGA M 12%, ISAGA A 38% e ISAGA E 25%.

8.2.2 Transplanted patients

Myocarditis, neumonitis, and SNC compromised could happen in transplanted patients with reactivation of toxoplasmosis. Laboratories importance is based on knowing serologies, donor, and recipient, so that doctors in charge can be alert to any risk of infection or reactivation [24].

8.2.3 Ocular toxoplasma infection

Toxoplasmosis is a major cause of retinochoroiditis, especially in individuals with an impaired immune system. It is so important to diagnose a toxoplasma infection when ocular infection occurs, because this acute infection must be treated. The consequences of not doing so, could bring serious complications: When a cyst ruptures, retinochoroiditis presents an intense inflammatory reaction that tends to scarring. In immunodeficiency conditions, necrosis occurs and a retinal detachment, uveitis, and then secondary glaucoma could be presented [24, 26].

The laboratories roles are based on direct detection of the parasite in vitreous humor and confirmatory serology (see Diagnostic available tests). The high VPP of these results with ocular lesions helps treatment as soon as possible to avoid the worse lesions.

8.2.3.1 Hodgkin disease and other lymphomas

Must be also differentiated from toxoplasmosis. Laboratories direct methods in any material like biopsia of nodes is as important as indirect methods, both to rule out or to confirm toxoplasma infection.

9. Conclusions

In conclusion, the laboratories mission should be:

9.1 In pregnancy and newborns

1. Prevent parasite Toxoplasma gondii from infecting pregnant women. If a parasite passes the placenta without treatment, the risk of infection is 40-50% [2].

2. Do the best as possible with the resources at hand, to monitor seronegative pregnant women to make sure they do not become infected. Keep in mind that the most common maternal infections are asymptomatic.

3. Have a fluid communication with the attending physician to alert them once a pathological result is found.

4. If a pregnant woman gets Toxoplasma gondii infection, prevent the parasite from passing the placenta and infecting the future newborn by diagnosing accurately, in order to administer the appropriate medicine. Pregnant women and fetuses must receive treatment to minimize clinical consequences [1, 2, 3, 4, 7, 8].

5. Take care of newborns until they are one-year-old and their immune system matures. The majority of these babies are born without symptoms [1, 2, 3, 4].

6. If they do not receive treatment, the possibilities of having immediate or late clinical consequences could be up to 80%, which would make those families’ future very difficult [1, 2, 8].

9.2 In other clinical groups

The role of laboratory diagnosis through direct methods on any material received and indirect methods (screening or confirmatory serologic assays) plays a main role in the differential diagnosis from other diseases. This is where the major effort must be made:

9.2.1 Immunocompetent patients

Laboratories become important to rule out Toxoplasma gondii infection so doctors can be able to focus on other pathologies.

9.2.2 HIV

Laboratories must follow HIV patients for the risk of infection or reactivation, when the count of linfocitos CD4 is less than 150/mm3. Therefore, the serology results are a complement when an increase of the titer of IgG and IgM appears. If treatment responds favorably in seroreactive patients, it also reinforces diagnosis [24, 25, 26, 27].

9.2.3 Transplant

Bone Marrow or solid organ transplantation must be periodically monitored by laboratories; in order to be alert for reactivation and when donor and/or receptor are serology positive previous to the transplant.

9.2.4 Chorioretinitis

Laboratories should play an important role in doing PCR and/or isolation in vitreous humor, besides confirmatory serology such as IgG, ISAGA M, ISAGA A, and ISAGA E. It is very important to notify doctors to start treatment as soon as possible and thus avoid complications [24].

9.2.5 Hodking disease and other lymphoma

Confirming Toxoplasma gondii infection or ruling it out should be the purpose of laboratories. Doctors must be aware of the diagnosis to know what steps to follow.

9.3 Choice of tests

1. No matter what combination of tests is used, the best must be done with the resources at hand.

2. Not every laboratory has the same budget to afford the best brand. It is of utmost importance to responsibly follow the test’s insert instructions, and to use internal and external quality controls.

3. Refer to reference laboratories; those samples with gray area or unclear results for obtaining an accurate and final result.

If laboratories do this, they can be rest assured that they did their best in making sure future children are born free of clinical consequences or ruling out the disease or confirming toxoplasmosis from any other pathology.

9.4 Result information

1. If there are any doubts about the result and there is no reference laboratory within reach, the report should include information such as: “gray zone” and under observations, suggesting repeating the test in two or three weeks . When the new sample arrives, comparing both sample titles.

2. Use observations to communicate to doctors any advice: for example, “Retesting recommended”, “Expand with more specific tests,” or “The result corresponds to the cut-off value.”

To conclude: All of these objectives are equally important: From getting involved in primary prevention to doing the best job possible.

In other words, working together as a team with the attending doctors, focusing on responsibility, efficiency, quality, and commitment in order to provide the best service to patients; are certainly key to “The important role of laboratories” “Towards new perspectives on Toxoplasma gondii.”

Acknowledgments

I would like to thank:

My dear childhood friend Patricia Negritto, her dedication and commitment just for empathy, helping and accompanying, motivated, and moved me.

D. Sc Liliana Carral and D. Sc. Federico Kaufer for opening the doors to the world of toxoplasmosis for me and for their support, trust, and teaching.

Dr. Cristina Freuler for her support and confidence.

D.Sc. Jorgelina Blejer: for her empathy, motivation, teaching, and professionalism.

Cecilia Miñones for her help, friendship, and professionalism.

Silvia Sabo for her predisposition, commitment, help, and understanding.

My coworkers Matías Messina and Ricardo Medina for making me enjoy every day of my work. It is very easy and pleasant to work with them.

Guillermo Omar Di Stasio for inspiring me with his book “Tu ventaja diferencial” and helping me in a special moment.

Tomy: for being the best son, so empathetic, kind, funny, charming, and companion.

My father, Jorge Schneider, for teaching me above all, that there is no obstacle that cannot be overcome.

My mom who accompanies me from wherever she is.

And to all my friends who support me, motivate me, and teach me every day how important it is to have people in life with whom to share moments, good, and not so good ones (Zule, Vero, Lily, Gaby, Faby, Mary, Marce, Tere, Nancy, Lore, Normi, Bea).

Thank God for always be by my side and showing me the signs where I should go.

Conflict of interest

The author declares no conflict of interest