Further evidence of spontaneous cure in human Chagas disease

Dias, João Carlos Pinto; Dias, Emmanuel; Filho, Olindo M.; Vitelli-Avelar, Danielle Marquete; Correia, Dalmo; Lages, Eliane; Prata, Áluízio

doi:10.1590/s0037-86822008000500014

Cited by 37 publications

(24 citation statements)

References 7 publications

(2 reference statements)

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“…Because the standard for determining a diagnosis of T. cruzi infection is based on at least 2 tests out of 3 conventional serological tests performed, we considered the conversion to negative serology on 2 or 3 tests as a possible indicator of cure. Although, spontaneous cure is a rare event documented in long-term untreated T. cruzi -infected subjects [20], [21], in this short-term study we have not recorded any case.…”

Section: Discussionmentioning

confidence: 54%

Impact of Aetiological Treatment on Conventional and Multiplex Serology in Chronic Chagas Disease

Viotti¹,

Vigliano²,

Alvarez³

et al. 2011

PLoS Negl Trop Dis

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BackgroundThe main criterion for treatment effectiveness in Chagas Disease has been the seronegative conversion, achieved many years post-treatment. One of the main limitations in evaluating treatment for chronic Chagas disease is the lack of reliable tests to ensure parasite clearance and to examine the effects of treatment. However, declines in conventional serological titers and a new multiplex assay can be useful tools to monitor early the treatment impact.Methodology/Principal FindingsChanges in antibody levels, including seronegative conversion as well as declines in titers, were serially measured in 53 benznidazole-treated and 89 untreated chronic patients in Buenos Aires, Argentina with a median follow-up of 36 months. Decrease of titers (34/53 [64%] treated vs. 19/89 [21%] untreated, p<0.001) and seronegative conversion (21/53, [40%] treated vs. 6/89, [7%] untreated, p<0.001) in at least one conventional serological test were significantly higher in the benznidazole-treated group compare with the untreated group. When not only complete seronegative conversion but also seronegative conversion on 2 tests and the decreases of titers on 2 or 3 tests were considered, the impact of treatment on conventional serology increased from 21% (11/53 subjects) to 45% (24/53 subjects). A strong concordance was found between the combination of conventional serologic tests and multiplex assay (kappa index 0.60) to detect a decrease in antibody levels pos-treatment.Conclusions/SignificanceTreatment with benznidazole in subjects with chronic Chagas disease has a major impact on the serology specific for T. cruzi infection in a shorter follow-up period than previously considered, reflected either by a complete or partial seronegative conversion or by a significant decrease in the levels of T. cruzi antibodies, consistent with a possible elimination or reduction of parasite load.

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Section: Discussionmentioning

confidence: 54%

Impact of Aetiological Treatment on Conventional and Multiplex Serology in Chronic Chagas Disease

Viotti¹,

Vigliano²,

Alvarez³

et al. 2011

PLoS Negl Trop Dis

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“…We hypothesize that these individuals have spontaneously cleared (or controlled) their T. cruzi infections and consequently are slowly seroreverting as antigenic stimulus to sustain high‐level seroreactivity is lost. Case reports of seroreversion in the absence of treatment were previously reported as well as seroreversion among untreated controls in benznidazole clinical trials …”

Section: Discussionmentioning

confidence: 97%

Bimodal distribution of Trypanosoma cruzi antibody levels in blood donors from a highly endemic area of Argentina: what is the significance of low‐reactive samples?

et al. 2015

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“…Although widely cited and the basis for recommending treatment of all seropositive subjects, 17,18 to our knowledge this concept has never been formally proven. Seroreversion in the absence of treatment has been previously described as a rare event 19‐21 and also documented among untreated controls in benznidazole clinical trials, 22,23 but the generally accepted explanation for these “rare cases” of possible seroreversion has been lack of reproducibility of the original serologic assays.…”

Section: Discussionmentioning

confidence: 99%

Antibody levels correlate with detection of Trypanosoma cruzi DNA by sensitive polymerase chain reaction assays in seropositive blood donors and possible resolution of infection over time

Sabino

Lee²,

Montalvo³

et al. 2012

Transfusion

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Background The clinical significance of anti-T. cruzi low-level reactive samples is incompletely understood. PCR-positive rates and antibody levels among seropositive blood donors in three countries are described. Methods Follow-up whole blood and plasma samples were collected from T. cruzi-seropositive donors from 2008-2010 in the US (n=195) and Honduras (n=58). Also 143 samples from Brazil in 1996-2002, originally positive by three serological assays, were available and paired with contemporary follow-up samples from these donors. All samples were retested with the FDA-approved Ortho ELISA. PCR assays were performed on coded sample panels by two laboratories (BSRI and ARC) that amplified kinetoplast minicircle DNA sequences of T. cruzi. Results PCR testing at BSRI yielded slightly higher overall sensitivity and specificity (33% and 98%) compared with the ARC lab (28% and 94%). Among seropositive donors, PCR-positive rates varied by country (p<0.0001) for the BSRI laboratory: Brazil (57%), Honduras (32%) and the US (14%). ELISA signal/cutoff (S/CO) ratios were significantly higher for PCR-positive compared to PCR-negative donors (p<0.05 for all comparisons). Additionally, PCR-negative Brazilian donors exhibited greater frequencies of antibody decline over time versus PCR-positive donors (p=0.003). Conclusion For all three countries, persistent DNA positivity correlated with higher ELISA S/CO values, suggesting that high-level seroreactivity reflects chronic parasitemia. The higher rate of PCR positivity for Brazilian donors was likely attributable to required reactivity on three assays available a decade ago. Significant S/CO declines in 10% of the PCR-negative Brazilian donors may indicate seroreversion following parasite clearance in the absence of treatment.

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Further evidence of spontaneous cure in human Chagas disease

Cited by 37 publications

References 7 publications

Impact of Aetiological Treatment on Conventional and Multiplex Serology in Chronic Chagas Disease

Impact of Aetiological Treatment on Conventional and Multiplex Serology in Chronic Chagas Disease

Bimodal distribution of Trypanosoma cruzi antibody levels in blood donors from a highly endemic area of Argentina: what is the significance of low‐reactive samples?

Antibody levels correlate with detection of Trypanosoma cruzi DNA by sensitive polymerase chain reaction assays in seropositive blood donors and possible resolution of infection over time

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