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

Abstract

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.

Emerging and under-recognized Chagas cardiomyopathy in non-endemic countries

“…Our patient was not cured as antibody titres did not decrease significantly and did not become negative. However, this result is often not observed until 8 to 10 years post-treatment and then only in approximately 15% of treated adult subjects [27] . The main impact of the great latent time until the diagnosis of CCC is the lack of efficacy of the two approved drugs for antitrypanosomal therapy in chronically-infected patients.…”

“…PCR for T. cruzi was not performed initially because serology is the gold-standard for diagnosis of chronic CD [26,27] , despite being affected by cross-reactions with antibodies induced by other parasites, namely Leishmania and T. rangeli [28] . Due to this, two different serologic tests were performed to confirm the results.…”

Cost-effectiveness of Chagas disease screening in Latin American migrants at primary health-care centres in Europe: a Markov model analysis

“…8 However, we also contemplated a more optimistic rate of 50%, which substantially improved the ICER, based on new data for PCR follow-up testing suggesting that the efficacy of benznidazole (or at least the antiparasitic efficacy) in chronic Chagas disease could be higher than previously believed. 41 In the base case analysis, the model considered that 80% of the target population would be finally screened and treated.…”

“…25 Response to treatment was defined as conversion to negative of previously positive serology as described elsewhere. 8,26 Two scenarios were considered: a base-case 20% response to treatment, 5 years after receiving benznidazole, as reported by Viotti and colleagues; 8 and an assumption of a more optimistic 50% response to treatment, 5 years after receiving benznidazole. Spontaneous positive to negative conversion was not considered.…”

“…6 However, this practice is based on evidence from only one open-label, non-randomised, non-blinded trial and from other longitudinal studies that have shown decreased progression of cardiomyopathy and mortality. 7,8 In Europe, transmission from individuals infected with Tripanosoma cruzi (T cruzi), including from those who are asymptomatic, occurs either vertically or through transfusion of infected blood products or transplantation of infected organs. 9 Screening programmes are currently recommended in blood-banks and transplant settings and have already been implemented in some European countries, such as Spain, the UK, and Switzerland.…”