Acta Tropica 184 (2018) 83–87

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Acta Tropica
journal homepage: www.elsevier.com/locate/actatropica

Polymerase chain reaction (PCR) in ocular and ganglionar toxoplasmosis T

and the effect of therapeutics for prevention of ocular involvement in South
American setting
Jorge Enrique Gómez Marína,b, Juan David Zuluagaa, Eunice Julied Pechené Campoa,
⁎
Jessica Triviñoa, Alejandra de-la-Torrea,c,
a
Grupo de Estudio en Parasitología Molecular (GEPAMOL), Centro de Investigaciones Biomédicas, Universidad del Quindío, Armenia, Colombia
b
Grupo de Investigación en Población Infantil (IPI), Hospital Universitario San Juan de Dios, Armenia, Colombia
c
Grupo de Investigación en Neurociencias (NeURos), Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia

A R T I C L E I N F O A B S T R A C T

Keywords: Introduction: Cases of toxoplasmosis present in South America tend to be more severe than that found in other
Ocular toxoplasmosis continents. Here, we present our clinical experience of ocular and ganglionar toxoplasmosis in the use of PCR,
Uveitis and of the treatment to prevent ocular involvement.
Toxoplasmic lymphadenitis Methodology: Retrospective analysis of clinical charts of patients with ocular and lymphadenitic toxoplasmosis at
Colombia
the parasitology and tropical medicine consultation in the “Universidad del Quindio” in Colombia. In total, 91
records of cases with ocular toxoplasmosis and 17 with lymphadenitis that underwent PCR analysis for B1
repeated sequence in blood, were compared to the results of 104 people with chronic asymptomatic tox-
oplasmosis. In addition, 41 clinical records were included from patients with confirmed toxoplasmic lympha-
denitis: 10 untreated, 6 that begun treatment after four months of symptoms, and 25 that were treated during the
first four months of symptoms and had a follow-up during at least one year.
Results: Patients with ocular toxoplasmosis or lymphadenitis had a higher probability of PCR positivity in
peripheral blood than chronic asymptomatic people. There were no cases of retinochoroiditis in 25 patients with
toxoplasmic lymphadenitis treated before 4 months of symptoms and followed during at least 12 months. In four
out of ten untreated cases, new lesions of retinochoroiditis presented after the symptoms of lymphadenitis.
Conclusions: Toxoplasmosisin South America exhibits different clinical behavior and this influences the la-
boratory results as well as the need for treatment in the case of lymphadenitis. Clinicians should be aware of the
geographical origin of the infection in order to adopt different therapeutic and diagnostic approaches.

1. Introduction Torre et al., 2014; Torres-Morales et al., 2014).

We accumulated clinical experience in the use of PCR for diagnosis
Toxoplasma gondii in South America can lead to more severe clinical in different clinical forms of toxoplasmosis (Cardona et al., 2011; Torres
forms than in other parts of the world, as has been demonstrated in et al., 2013a) as well about the efficacy of treatment of limphadenitic
clinical, parasitological and immunological studies (de-la-Torre et al., toxoplasmosis to prevent ocular involvement. Many reports over-
2013; Pfaff et al., 2014). This could be explained by the more virulent estimate the role of PCR performed in peripheral blood (Colombo et al.,
strains circulating in South America, compared with strains circulating 2005; Silveira et al., 2011) for the diagnosis of toxoplasmosis and very
in, for example, Europe (Alvarez et al., 2015; Morisset et al., 2008; Pfaff few have examined if there is a positivity in chronically infected
et al., 2014). South American strains of Toxoplasma possess a higher asymptomatic people. In addition, there is discussion about whether
frequency of virulent alleles including those that are analyzed in human treatment is necessary in patients with lymphadenitis, given the po-
clinical cases (Behnke et al., 2011; Niedelman et al., 2012; Sánchez tential serious side effects of antibiotics used for toxoplasmosis (Anton,
et al., 2014). The consequences for infected humans with this virulent 2009; Montoya and Remington, 1996). It is necessary to determine
strains is a dysregulation of the cytokines protective network (de-la- which prophylactic regime should be used after acute T. gondii infection

⁎
Corresponding author at: Grupo de Investigación en Neurociencias (NeURos), Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Carrera 24 # 63 C 69, Bogotá,
Colombia.
E-mail address: [email protected] (A. de-la-Torre).

https://doi.org/10.1016/j.actatropica.2018.01.013
Received 2 November 2017; Accepted 22 January 2018
Available online 31 January 2018
0001-706X/ © 2018 Elsevier B.V. All rights reserved.
J.E. Gómez Marín et al. Acta Tropica 184 (2018) 83–87

in order to prevent ocular disease, as well as determine if all patients was made with indirect ophthalmoscopy. The patients were examined
with lymphadenitis should be treated to prevent an ulterior ocular in- using the Snellen visual acuity test at each control. Patients received
volvement(Jones et al., 2015). In this paper, we describe the behavior treatment orally with Pyrimethamine/Sulfadoxine (500 mg/25 mg),
of PCR assay in ocular and lymphadentic toxoplasmosis and how many three tablets once a week, during four weeks or Trimetrophrim-
patients seen at our consultation of tropical medicine developed re- Sulfametoxazol TMP (160 mg)/SMX (800 mg) every 12 h for 6 weeks
tinochoroiditis after the acute episode of toxoplasmic lymphadenitis, (Alavi and Alavi, 2010).
controlling for treatment.

2. Materials and methods 2.5. Serological tests

2.1. Design Serum samples were assayed by an indirect ELISA IgG commercial
assay (Human, Germany) at the “Centro de Investigaciones Biomedicas”
Retrospective analysis of clinical charts and laboratory results. at the “Universidad del Quindio”. Blood was centrifuged the same day
and serum stored at −20 °C until the test was performed one or two
2.2. Setting weeks later. ELISA assays for IgG and IgM anti-Toxoplasma were per-
formed with Human ELISA Kits (Germany), following the indications of
Consultation of parasitology and tropical medicine at the Health the manufacturers. IgG Toxoplasma avidity test was carried out as de-
center of the Quindio University (Colombia) during the period of June scribed previously (Torres et al., 2013a).
2009 to December 2015.

2.3. Study population and case definitions 2.6. Detection of T. gondii by PCR

Patients with lymphadenitic toxoplasmosis that visited the clinical A nested PCR amplification of the repetitive and conserved gene B1
consultation at the “Universidad del Quindio” were included. For each was performed as described previously (Torres et al., 2013b). Positive
patient the number of days with symptoms, the serological status, and control was DNA from RH strain and negative control was distilled
an eye fundoscopy examination were registered from clinical charts. We water in presence of primers. Control for contamination during DNA
included all the clinical records from patients that consulted for extraction was also included and consisted in a tube without template
mononucleosis-like syndrome (fever, pharyngitis, adenomegaly and but containing all reagents for DNA extraction and filled with the same
malaise) or with appearance of new enlarged lymph nodes as unique pipette after all clinical samples were served. An additional control was
manifestation and who were followed for a period of one year. We a blood sample from IgG negative patients for Toxoplasma. Sensitivity of
obtained primary data from medical records. The variables that were PCR was 1 fg of Toxoplasma DNA.
collected included gender, age, clinical manifestations, lymphadeno-
pathy location, complete ophthalmic examination, treatment received
and blood tests results (blood cell-count, IgM and IgG anti-Toxoplasma, 2.7. Ethical aspects
IgM test for anti-EBV, anti-HSV and anti-CMV). We defined a case as
toxoplasmic lymphadenitis by the presence of lymphadenophaties, with As a retrospective study, no informed consent was needed according
or without other symptoms, such as fever, gastrointestinal manifesta- to the Colombian legislation for research with humans (resolution
tions, myalgia, arthralgia, and/or asthenia, in addition to a positive IgG 008430 of 1993 by the Ministry of Health). The research group per-
and IgM anti-Toxoplasma tests. Exclusion criteria were IgG and IgM formed data analysis and the identity of patients is not revealed.
negatives for Toxoplasma and no possibility of follow-up. The clinical
diagnosis of ocular toxoplasmosis was based on the previously de-
scribed criteria (de-la-Torre et al., 2009). Active ocular toxoplasmosis 3. Results
was defined by the presence of an active creamy-white focal retinal
lesion eventually resulting in hyperpigmented retinochoroidal scars in 3.1. Frequency of PCR positive samples in peripheral blood sample
either eye. Central lesions were defined as lesions located within the
large vascular arcades. Size of lesions was recorded in disk diameters The positivity of PCR for B1 sequence was significantly greater in
and intensity of inflammation was measured by biomicroscopy by the peripheral blood of patients with ocular toxoplasmosis and lym-
counting the number of cells in the anterior chamber, when the lesions phadenitic toxoplasmosis than in chronic asymptomatic people
were inactive the results of the last inflammatory period were recorded (Table 1). However, within the group of patients with ocular tox-
from the clinical charts. Asymptomatic patients that had a serological oplasmosis, no differences were found between patients with the active
status of chronic infection (IgG anti-Toxoplasma positive and IgM anti- ocular form versus those with inactive scars or for the other clinical
Toxoplasma negative) and a fundoscopic eye examination negative for characteristics such as gender, number of lesions, number of in-
ocular lesions during a previous screening in a young adult population flammatory cells or levels of IgG anti-Toxoplasma (Table 2).
were requested to participate in the study as controls to determine the
prevalence of chorioretinal scars (de-la-Torre et al., 2007a). Table 1
Positivity of nested PCR for Toxoplasma B1 repeated sequence in ocular, ganglionar and
2.4. Ophthalmological follow up and treatment asymptomatic chronic infection.

Origin (clinical condition and origin of PCR positive/Total samples %*

According to our own protocol, at our consultation all patients with
samples) assayed
toxoplasmic lymphadenitis are recommended to be followed-up in four
different appointments at 1st, 3rd, 6th and 12th month after first con- Ocular toxoplasmosis – peripheral blood 60/91 65.9%
sultation. During each consultation, they were asked about new Ganglionar toxoplasmosis – peripheral 10/17 58.8%
blood
symptomatology with emphasis on ocular symptoms and we carried out
Asymptomatic chronic infection 33/104 31.0%
a physical examination including ophthalmoscopy and description of
the changes in lymphadenopathies. One drop of tropicamide 1% solu- * Statistical significant differences in positivity of ocular (p = .0000019) or ganglionar
tion was given to each eye for pupillary dilation. A retinal examination (p = .05) vs. chronic asymptomatic.

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Table 2
Clinical characteristics in patients with ocular toxoplasmosis and positivity of the nested PCR for B1 repeated sequence.

Clinical characteristic % positive (PCR positive/total assayed) or median value PCR positive (range) OR (IC 95%) p value
vs. median value (range) in PCR negative

Active ocular inflammation (exudative chorioretinal lesion) vs 65.9% (29/43) vs.64% (29/45) 1,14 (0.47–2.7) .82
inactive chorioretinal lesion
Bilateral lesions vs. unilateral lesions 72% (18/25) vs. 70.4% (31/44). 1.0 (0.3–4.1) 1.0
Macular vs. peripheral 60% (15/25) vs. 75.4% (40/53) 0.48 (0.17–1.34) .18
Gender (male vs. female) 74% (7/27) vs. 62.5% (40/64) 1.7 (0.6–4.6) .33
Median Age 27.7 (6–82) vs. 30.5 (2–77) – .46
Median number of cells in vitreous (range) 1.0 (0–4) vs 1.5 (0–3) – .68
Median number of chorioretinal scars (range) 3.2 (1–14) vs. 2 (1–7) – .21
Median size of the greater chorioretinal scar in disk diameters 2 (0–14) vs. 2 (0–4) – .67
(range)
Median levels of IgG anti-Toxoplasma -UI/ml- (range) 181 (19–501) vs. 207 (18–650) – .33

3.2. Effect of treatment of lymphadenitic toxoplasmosis to prevent ocular diagnosis of “neuroretinitis and vitreitis” and requested Toxoplasma
involvement one year later antibodies. IgG anti-Toxoplasma antibodies were positive (73 UI/ml),
IgM anti-Toxoplasma assay positive and the IgG avidity index was 17%
We analyzed clinical records from 41 patients that assisted our (an index less than 30% indicates an infection acquired during less than
consultation with a mononucleosis-like syndrome or acute lymphade- four months). The first angiographic retinal study performed in January
nitis manifestations (appearance of new enlarged lymphadenopathies of 2013 reported in the right eye: loss of foveal brightness surrounded
as the only symptom), and confirmed as toxoplasmic lymphadenitis by by hemorrhagic lesions with enhanced hyperfluoresecence during ex-
the presence of positive IgG and IgM anti-Toxoplasma antibodies. In this amination time (Fig. 1a and b). He presented posterior vitreous de-
group of patients with confirmed toxoplasmic infection and follow-up tachment and thickening, cystoid macular edema and epiretinal mem-
during 12 months, 10 patients were untreated, 6 had begun treatment brane (Fig. 1c). He was treated with Pyrimethamine/Sulfadoxine 25/
after four months of symptoms and 25 consulted during the first four 500 mg three tablets once a week during four weeks plus oral Pre-
months of symptoms and were treated. In the group of patients treated dnisolone. A new retinal angiographic study taken 9 months later
during the first four months of symptoms, 22 patients received treat- (August 2013) reported the optic disk borders blurred, not excavation
ment with Pyrimethamine/Sulfadoxine and 3 were treated with and a star white lesion with some pigment within maculopapillary axis
Trimethoprim-Sulfamethoxazol, during at least four weeks. 1 additional and one additional hyperfluorescent lesion of one optic disk diameter,
patient received Clindamycin during two weeks because he had past affecting nasal fovea and optic disk. His best-corrected visual acuity
history of allergic reaction to Sulphonamids. All patients had enlarged (BCVA) was initially Hand-Movement (HM), and one year after first
cervical lymphadenopathies and some of them had multiple locations symptoms his final BCVA was 20/40. The second case was a 13-year-old
(occipital 20.6%; inguinal 8.8% and axillar 8.8%). At the first con- girl who presented in December 2013 cervical lymphadenopathies and
sultation, no visual impairment was referred and indirect ophthalmo- fever. She was treated symptomatically by a general practitioner. In
scopy examination was normal in all these cases. The median time for April of 2014 she manifested blurred vision, teichopsia and floaters,
consultation after onset of symptoms was 5 weeks (range 2–16 weeks). and consulted an ophthalmologist who referred to our consultation. We
The median period of follow-up was 25.5 months (range 12–416 performed ELISA assay IgG anti-Toxoplasma antibodies that reported
weeks). In the last consultation, all treated patients had normal fun- 138 UI/ml, IgM anti-Toxoplasma assay was positive and IgG avidity
doscopic examination without chorioretinal lesions. Two patients pre- index was 18%, indicating an infection acquired less than four months
sented symptoms of severe erythema multiforme (Stevens Johnson before. At the fundus examination she had an inflammatory perima-
Syndrome) during treatment with Pyrimethamine/Sulfadoxine. They cular lesion of 3 disk diameters (Fig. 2). BCVA was 20/200. A cervical
were treated with steroids and healed completely. The patients had right adenopathy, swallow, non-adherent was present at the examina-
completed the four doses of their toxoplasmosis treatment when tion of her neck. Trimetoprim (TMX)-Sulfametoxazol (SMZ) was in-
Stevens Johnson symptoms begun. itiated p.o: TMX (160 mg)/SMZ (800 mg) every 12 h p.o. during five
weeks plus oral Prednisolone (1 mg/kg daily) was given from the third
3.3. Description of chorioretinitis cases after lymphadenitic toxoplasmosis day of therapy and tapered over six weeks. Inflammation and BCVA
improved progressively: 20/70 on June 4th; 20/40 on July 16th, 20/40
Of 10 untreated patients examined after 12 months, six were not on August 6th and 20/25 on October 1st. The third case was a 10-year-
treated because they arrived at consultation after six months of the old boy who in December 2014 presented fever and cervical adeno-
onset of acute symptoms. The other four were not treated because they pathies. One month later (January 2015), he complained of blurred
initially consulted at another center and following presentation of the vision, finding in the physical examination a clouding of the lens of the
ocular manifestations, were then referred to our consultation. The left eye. On February 12th 2015 he underwent an iridotomy. Five days
median period between the first lymphadenitis manifestations and the later, an ocular ultrasound was performed, with findings of leucocoria
appearance of ocular lesions was 7.7 weeks (range 2.5–16 weeks). The and funnel-shaped total retinal detachment, and so he underwent a
first case was a 14-year-old boy, who went to a school trip at the retinopexia plus vitrectomy. In the same month, it was reported a po-
Caribbean region of Colombia in the month of November 2012. During sitive IgG and IgM anti-Toxoplasma, with an IgG avidity of 89%. He was
travel he drank unfiltered water in the mountains of Santa Marta (north treated by the service of pediatric infectious diseases, who prescribed
of Colombia). One week after the students returned to Bogotá many of him Trimetoprim/Sulfametoxazol (160 mg/800 mg) every 12 h for 6
them reported symptoms of fever, diarrhea and emesis. They were weeks. He finished the treatment with a visual acuity of 20/25 OD and
treated symptomatically and no additional studies were performed. The no light perception OS. The fourth case was a 54-year-old man who
aforementioned patient developed additionally lymphadenopathies and presented with cervical lymphadenopathies, fever, chills and diaphor-
he was studied for dengue and malaria, with negative results. Four esis. 20 days later, he complained of blurred vision, and so was tested
weeks later, the patient complained of blurred vision and floaters in his for IgG and IgM anti-Toxoplasma (9 October 2015), which were found
right eye. He consulted an ophthalmologist that made an initial to be positive. On the physical exam he showed a visual acuity 20/400

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Fig. 2. Funduscopy image of the left eye with choriorretinal scar after an episode of
toxoplasmic lymphadenitis, in 13 years-old girl.

OD and 20/40 OS, and a 3 cm left cervical lymphadenopathy. Fundo-

scopy showed OD with keratic precipitates and a macular exudative
lesion of 1.5 DD, OS with a macular fibrous scar, and vitreous white
condensations in both eyes. He was diagnosed with chorioretinitis and
he was treated with Pirimetamine/Sulfadoxine during 5 weeks plus oral
Prednisolone. After treatment, he attended a follow-up consultation
where we found an improvement in visual acuity, showing 20/100 OD
and 20/40 OS, and the fundoscopy with a considerable reduction in
inflammation, pigmentation of the lesion and without turbidity

4. Discussion

The experience reported here confirms previous reports which

showed that in ocular toxoplasmosis it is possible to detect Toxoplasma
DNA in peripheral blood samples without a direct relation of tox-
oplasma’s activity within the eye. It is therefore not useful to use PCR in
blood to determine the risk of reactivation or for diagnosis of ocular
toxoplasmosis (Bourdin et al., 2014). The same occurs in lymphadentic
toxoplasmosis where nearly half of patients are negative for PCR in
peripheral blood. The interest of detecting Toxoplasma DNA in per-
ipheral blood is for research purposes in order to analyze parasite
genotype (Sánchez et al., 2014).
There is a concern about B1 PCR specificity (Kompalic-Cristo et al.,
2004). However, this can be resolved by means of the nested PCR
methodology as we have used. For some reasons that could be linked to
strain differences (Wahab et al., 2010) it should be noted that our group
in Colombia and some from Brazil have reported more sensitivity for
diagnosis with B1 sequence as target for amplification than with RE
target (Kompalic-Cristo et al., 2007; Torres et al., 2013b). The presence
of Toxoplasma DNA in blood can be explained by incomplete control of
Fig. 1. Opthalmological studies in one case of retinochoroiditis after symptomatic ac- Toxoplasma proliferation in ocular toxoplasmosis. This is because not
quired toxoplasmosis. a. Retinal angiography study in January 2013 at the right eye of a
only has DNA been found but also alive Toxoplasma in chronic and in
16-year-old boy who presented with cervical, axillar and inguinal lymphadenopathies
active ocular forms (Silveira et al., 2011).
four weeks before visual symptoms. b. High definition Optical Coherence Tomography
(OCT) study in August of 2013 in the same boy, right eye (Spectral Domain Cirrus OCT, We also report an observational case series of treated and untreated
Zeiss). c. Retinal angiography study in August 2013, right eye. d. Visual field study in cases of toxoplasmic lymphadenitis. There were no cases of re-
June 2013, right eye. tinochoroiditis in treated patients, confirming the findings of the
Brazilian study where it was found that patients with systemic

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symptomatic toxoplasmosis that received antiparasitic treatment had opportunistic infections by a real-time PCR assay [WWW document]. J.
less ocular involvement within three months of diagnosis (Arantes Neuroparasitol. 2, 1–6. http://dx.doi.org/10.4303/jnp/N110402.
Colombo, F.A., Vidal, J.E., Penalva De Oliveira, A.C., Hernandez, A.V., Bonasser-Filho, F.,
et al., 2015). Present results support these findings. In one large out- Nogueira, R.S., Focaccia, R., Pereira-Chioccola, V.L., 2005. Diagnosis of cerebral
break in British Columbia, Canada, the number of symptomatic patients toxoplasmosis in AIDS patients in Brazil: importance of molecular and immunological
with ocular toxoplasmosis was 19 of 100 acute outbreak-related cases methods using peripheral blood samples. J. Clin. Microbiol. 43, 5044–5047. http://
dx.doi.org/10.1128/JCM.43.10.5044-5047.2005.
(19%) and 8 of 20 patients with ocular involvement that had systemic de-la-Torre, A., González, G., Díaz-Ramirez, J., Gómez-Marín, J.E., 2007a. Screening by
symptoms, with a median time between systemic symptoms and ocular ophthalmoscopy for toxoplasma retinochoroiditis in Colombia. Am. J. Ophthalmol.
manifestations of 6 weeks (Bowie et al., 1997). This is very similar to http://dx.doi.org/10.1016/j.ajo.2006.09.048.
de-la-Torre, A., González, G., Díaz-Ramirez, J., Gómez-Marín, J.E., 2007b. Screening by
the median time for developing chorioretinitis symptoms in our cases (7 ophthalmoscopy for Toxoplasma retinochoroiditis in Colombia. Am. J. Ophthalmol.
weeks). In the most representative study performed in Brazil, the risk of 143, 354–356. http://dx.doi.org/10.1016/j.ajo.2006.09.048.
new chorioretinal lesions after diagnosis was of 10 per 100 persons/ de-la-Torre, A., López-Castillo, C.A., Gómez-Marín, J.E., 2009. Incidence and clinical
characteristics in a Colombian cohort of ocular toxoplasmosis. Eye (Lond) 23,
year (Arantes et al., 2015). One recent retrospective review of cases of
1090–1093. http://dx.doi.org/10.1038/eye.2008.219.
ocular toxoplasmosis seen in a referral center in the United States re- de-la- Torre, A., Sauer, A., Pfaff, A.W., Bourcier, T., Brunet, J., Speeg-Schatz, C.,
ported that 11.7% of patients with ocular disease had recently acquired Ballonzoli, L., Villard, O., Ajzenberg, D., Sundar, N., Grigg, M.E., Gomez-Marin, J.E.,
T. gondii infection (Jones et al., 2014). Present and previous results in Candolfi, E., 2013. Severe South American ocular toxoplasmosis is associated with
decreased ifn-γ/Il-17a and increased il-6/Il-13 intraocular levels. PLoS Negl. Trop.
Colombian patients indicates a similar risk and we have estimated that Dis. 7, e2541. http://dx.doi.org/10.1371/journal.pntd.0002541.
12% of Toxoplasma seropositive people in Colombia develop chorior- de-la-Torre, A., Pfaff, A.W., Grigg, M.E., Villard, O., Candolfi, E., Gomez-Marin, J.E.,
etinal scars (de-la-Torre et al., 2007b). We consider that specific anti- 2014. Ocular cytokinome is linked to clinical characteristics in ocular toxoplasmosis.
Cytokine 68, 23–31. http://dx.doi.org/10.1016/j.cyto.2014.03.005.
Toxoplasma treatment should be indicated in the context of toxoplasmic Jones, J.L., Bonetti, V., Holland, G.N., Press, C., Sanislo, S.R., Khurana, R.N., Montoya,
lymphadenitis in South America. A double-blind randomized trial is not J.G., 2014. Ocular toxoplasmosis in the United States: recent and remote infections.
indicated because it would expose patients to the possible development Clin. Infect. Dis. 60, 271–273. http://dx.doi.org/10.1093/cid/ciu793.
Jones, J.L., Bonetti, V., Holland, G.N., Press, C., Sanislo, S.R., Khurana, R.N., Montoya,
of irreversible retinochoroiditis. J.G., 2015. Ocular toxoplasmosis in the United States: recent and remote infections.
In conclusion, clinicians should be aware of the differences between Clin. Infect. Dis. 60, 271–273. http://dx.doi.org/10.1093/cid/ciu793.
toxoplasmosis in South American and clinical forms of the same disease Kompalic-Cristo, A., Nogueira, S.A., Guedes, A.L., Frota, C., González, L.F., Brandão, A.,
Amendoeira, M.R., Britto, C., Fernandes, O., 2004. Lack of technical specificity in the
in other parts of the world as, to the best of our current knowledge, the molecular diagnosis of toxoplasmosis. Trans. R. Soc. Trop. Med. Hyg. 98, 92–95.
consequences of diagnostic and therapeutic approaches can differ. http://dx.doi.org/10.1016/S0035-9203(03)00012-9.
Kompalic-Cristo, A., Frotta, C., Suárez-Mutis, M., Fernandes, O., Britto, C., 2007.
Evaluation of a real-time PCR assay based on the repetitive B1 gene for the detection
Competing interest
of Toxoplasma gondii in human peripheral blood. Parasitol. Res. 101, 619–625.
http://dx.doi.org/10.1007/s00436-007-0524-9.
None declared. Montoya, J.G., Remington, J.S., 1996. Toxoplasmic chorioretinitis in the setting of acute
acquired toxoplasmosis. Clin. Infect. Dis. 23, 277–282. http://dx.doi.org/10.1093/
clinids/23.2.277.
Funding source Morisset, S., Peyron, F., Lobry, J.R., Garweg, J., Ferrandiz, J., Musset, K., Gomez-Marin,
J.E., de la Torre, A., Demar, M., Carme, B., Mercier, C., Garin, J.F., Cesbron-Delauw,
Universidad del Quindio. M.-F., 2008. Serotyping of Toxoplasma gondii: striking homogeneous pattern be-
tween symptomatic and asymptomatic infections within Europe and South America.
Microbes Infect. 10, 742–747. http://dx.doi.org/10.1016/j.micinf.2008.04.001.
References Niedelman, W., Gold, D.A., Rosowski, E.E., Sprokholt, J.K., Lim, D., Farid Arenas, A.,
Melo, M.B., Spooner, E., Yaffe, M.B., Saeij, J.P.J., 2012. The rhoptry proteins ROP18
and ROP5 mediate Toxoplasma gondii evasion of the murine, but not the human,
Alavi, S.M., Alavi, L., 2010. Treatment of toxoplasmic lymphadenitis with co-trimoxazole:
interferon-gamma response. PLoS Pathog. 8, e1002784. http://dx.doi.org/10.1371/
double-blind, randomized clinical trial. Int. J. Infect. Dis. 14 (Suppl. 3), e67–9.
journal.ppat.1002784.
http://dx.doi.org/10.1016/j.ijid.2009.11.015.
Pfaff, A.W., de-la-Torre, A., Rochet, E., Brunet, J., Sabou, M., Sauer, A., Bourcier, T.,
Alvarez, C., de-la-Torre, A., Vargas, M., Herrera, C., Uribe-Huertas, L.D., Lora, F., Gomez-
Gomez-Marin, J.E., Candolfi, E., 2014. New clinical and experimental insights into
Marin, J.E., 2015. Striking divergence in toxoplasma ROP16 nucleotide sequences
Old World and neotropical ocular toxoplasmosis. Int. J. Parasitol. 44, 99–107. http://
from human and meat samples. J. Infect. Dis. 211, 2006–2013. http://dx.doi.org/10.
dx.doi.org/10.1016/j.ijpara.2013.09.007.
1093/infdis/jiu833.
Sánchez, V., De-la-Torre, A., Gómez-Marín, J.E., 2014. Characterization of ROP18 alleles
Anton, E., 2009. Current therapy for isolated toxoplasmic lymphadenopathy. Oral Surg.
in human toxoplasmosis. Parasitol. Int. 63, 463–469. http://dx.doi.org/10.1016/j.
Oral Med. Oral Pathol. Oral Radiol. Endodontol. 107, 450. http://dx.doi.org/10.
parint.2013.10.012.
1016/j.tripleo.2008.11.026.
Silveira, C., Vallochi, a.L., Rodrigues da Silva, U., Muccioli, C., Holland, G.N.,
Arantes, T.E.F., Silveira, C., Holland, G.N., Muccioli, C., Yu, F., Jones, J.L., Goldhardt, R.,
Nussenblatt, R.B., Belfort, R., Rizzo, L.V., 2011. Toxoplasma gondii in the peripheral
Lewis, K.G., Belfort, R., 2015. Ocular involvement following postnatally acquired
blood of patients with acute and chronic toxoplasmosis. Br. J. Ophthalmol. 95,
Toxoplasma gondii infection in Southern Brazil: a 28-year experience. Am. J.
396–400. http://dx.doi.org/10.1136/bjo.2008.148205.
Ophthalmol. 159, 1002–1012. http://dx.doi.org/10.1016/j.ajo.2015.02.015. e2.
Torres, E., Rivera, R., Cardona, N., Sanchez, V., Lora, F., Gómez-Marín, J.E., 2013a.
Behnke, M.S., Khan, A., Wootton, J.C., Dubey, J.P., Tang, K., Sibley, L.D., 2011. Virulence
Evaluation of IgG anti-toxoplasma avidity and polymerase chain reaction in the
differences in Toxoplasma mediated by amplification of a family of polymorphic
postnatal diagnosis of congenital toxoplasmosis. Pediatr. Infect. Dis. J. 32, 693–695.
pseudokinases. Proc. Natl. Acad. Sci. U. S. A. 108, 9631–9636. http://dx.doi.org/10.
http://dx.doi.org/10.1097/INF.0b013e31828807a4.
1073/pnas.1015338108.
Torres, E., Rivera, R., Cardona, N., Sanchez, V., Lora, F., Gómez-Marín, J.E., 2013b.
Bourdin, C., Busse, A., Kouamou, E., Touafek, F., Bodaghi, B., Le Hoang, P., Mazier, D.,
Evaluation of IgG anti-toxoplasma avidity and polymerase chain reaction in the
Paris, L., Fekkar, A., 2014. PCR-based detection of Toxoplasma gondii DNA in blood
postnatal diagnosis of congenital toxoplasmosis. Pediatr. Infect. Dis. J. 32, 693–695.
and ocular samples for diagnosis of ocular toxoplasmosis. J. Clin. Microbiol. 52,
http://dx.doi.org/10.1097/INF.0b013e31828807a4.
3987–3991. http://dx.doi.org/10.1128/JCM.01793-14.
Torres-Morales, E., Taborda, L., Cardona, N., De-la-Torre, A., Sepulveda-Arias, J.C.,
Bowie, W.R., King, A.S., Werker, D.H., Isaac-Renton, J.L., Bell, A., Eng, S.B., Marion, S.A.,
Patarroyo, M.A., Gomez-Marin, J.E., 2014. Th1 and Th2 immune response to P30 and
1997. Outbreak of toxoplasmosis associated with municipal drinking water: the BC
ROP18 peptides in human toxoplasmosis. Med. Microbiol. Immunol. 203, 315–322.
Toxoplasma Investigation Team. Lancet 350, 173–177.
http://dx.doi.org/10.1007/s00430-014-0339-0.
Cardona, N., Basto, N., Parra, B., Zea, A.F., Pardo, C.A., Bonelo, A., Gomez-Marin, Jorge
Wahab, T., Edvinsson, B., Palm, D., Lindh, J., 2010. Comparison of the AF146527 and B1
Enrique, 2011. Detection of toxoplasma DNA in the peripheral blood of HIV-positive
repeated elements, two real-time PCR targets used for detection of Toxoplasma
patients with neuro-opportunistic infections by a real-time PCR assay [WWW
gondii. J. Clin. Microbiol. 48, 591–592. http://dx.doi.org/10.1128/JCM.01113-09.
Dtoxoplasma DNA in the peripheral blood of HIV-positive patients with neuro-

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