Prediction of parasitological cure in children infected with Trypanosoma cruzi using a novel multiplex serological approach: an observational, retrospective cohort study

Medina, Laura Smeldy Jurado; Chassaing, Emeric; Ballering, Griselda; González, Nicolás; Marqué, Lola; Liehl, Peter; Pottel, Hans; Boer, Jasper de; Chatelain, Eric; Zrein, Maan; Altcheh, Jaime

doi:10.1016/s1473-3099(20)30729-5

Cited by 15 publications

(17 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Various T. cruzi antigens or antigenic fractions that elicit a serological response have been evaluated for post-treatment biomarkers [ 24 – 26 ], with relative success [ 24 ]. The MultiCruzi assay, a serological assay incorporating 15 T. cruzi -specific antigens, when used with an interpretation formula, has been proposed for use as a predictive tool to assess parasitological cure in infants and children [ 27 ]. In paediatric cases post-chemotherapy, antibody titres to the trypomastigote small surface antigen (TSSA) shared by TcII, TcV and TcVI (TSSA-II/V/VI) decreased significantly faster than those against crude parasite homogenates [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

Assessing antibody decline after chemotherapy of early chronic Chagas disease patients

et al. 2021

View full text Add to dashboard Cite

Background Chagas disease remains a significant public health problem in Latin America. There are only two chemotherapy drugs, nifurtimox and benznidazole, and both may have severe side effects. After complete chemotherapy of acute cases, seropositive diagnosis may revert to negative. However, there are no definitive parasitological or serological biomarkers of cure. Methods Following a pilot study with seven Bolivian migrants to Spain, we tested 71 serum samples from chronic patients (mean age 12.6 years) inhabiting the Argentine Chaco region. Benznidazole chemotherapy (5–8 mg/kg day, twice daily for 60 days) was administered during 2011–2016. Subsequently, pre-and post-chemotherapy serum samples were analysed in pairs by IgG1 and IgG ELISA using two different antigens and Chagas Sero K-SeT rapid diagnostic tests (RDT). Molecular diagnosis by kDNA-PCR was applied to post-treatment samples. Results Pilot data demonstrated IgG1 antibody decline in three of seven patients from Bolivia 1 year post-treatment. All Argentine patients in 2017 (averaging 5 years post-treatment), except one, were positive by conventional serology. All were kDNA-PCR-negative. Most (91.5%) pre-treatment samples were positive by the Chagas Sero K-SeT RDT, confirming the predominance of TcII/V/VI. IgG1 and IgG of Argentine patients showed significant decline in antibody titres post-chemotherapy, with either lysate (IgG, P = 0.0001, IgG1, P = 0.0001) or TcII/V/VI peptide antigen (IgG, P = 0.0001, IgG1, P = 0.0001). IgG1 decline was more discriminative than IgG. Antibody decline after treatment was also detected by the RDT. Incomplete treatment was associated with high IgG1 post-treatment titres against lysate (P = 0.013), as were IgG post-treatment titres to TcII/V/VI peptide (P = 0.0001). High pre-treatment IgG1 with lysate was associated with Qom ethnicity (P = 0.045). No associations were found between gender, age, body mass index and pre- or post-treatment antibody titres. Conclusions We show that following chemotherapy of early chronic Chagas disease, significant decline in IgG1 antibody suggests cure, whereas sustained or increased IgG1 is a potential indicator of treatment failure. Due to restricted sensitivity, IgG1 should not be used as a diagnostic marker but has promise, with further development, as a biomarker of cure. Graphical abstract We show that following chemotherapy of early chronic Chagas disease, a significant decline in IgG1 antibody suggests cure, whereas sustained or increased IgG1 is a potential indicator of treatment failure. Due to restricted sensitivity, IgG1 should not be used as a diagnostic marker but has promise, with further development, as a biomarker of cure.

show abstract

Section: Introductionmentioning

confidence: 99%

Assessing antibody decline after chemotherapy of early chronic Chagas disease patients

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Some of them have been proposed in recent years, such as the use of nonconventional serological techniques ( 18 , 19 ). In particular, the use of specific biomarkers, like anti-α-Gal lytic antibodies known as anti-F2/3 antibodies ( 8 , 20 – 22 ), has been evaluated. However, further studies are needed for their validation in adults as well as children.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of Nifurtimox in the Treatment of Chagas Disease: a Long-Term Retrospective Cohort Study in Children and Adults

Falk

Berenstein

Moscatelli

et al. 2022

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…The Multi-Cruzi immuno-assay used here is equivalent to the multiplex system described previously [ 29 – 31 ], adapted for mice serum samples. The technology allows multiple antigens to be combined in single wells of a 96-well microplate, using a printing process based on non-contact piezo electric impulsion of a defined volume of an antigenic solution.…”

Section: Methodsmentioning

confidence: 99%

“…This has become an important tool for drug testing and for studies on disease pathogenesis. Here, we have combined this pre-clinical model with an antibody multiplex assay system (Multi-Cruzi, InfYnity Biomarkers, Lyon, France) [ 29 – 31 ] as a means of developing improved serological procedures for diagnosis of Chagas disease and for confirming parasitological cure of chronic T . cruzi infections.…”

Section: Introductionmentioning

confidence: 99%

Comparing in vivo bioluminescence imaging and the Multi-Cruzi immunoassay platform to develop improved Chagas disease diagnostic procedures and biomarkers for monitoring parasitological cure

Francisco

Saade²,

Jayawardhana

et al. 2022

PLoS Negl Trop Dis

Self Cite

View full text Add to dashboard Cite

Background Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and is a serious public health problem throughout Latin America. With 6 million people infected, there is a major international effort to develop new drugs. In the chronic phase of the disease, the parasite burden is extremely low, infections are highly focal at a tissue/organ level, and bloodstream parasites are only intermittently detectable. As a result, clinical trials are constrained by difficulties associated with determining parasitological cure. Even highly sensitive PCR methodologies can be unreliable, with a tendency to produce “false-cure” readouts. Improved diagnostic techniques and biomarkers for cure are therefore an important medical need. Methodology/Principal findings Using an experimental mouse model, we have combined a multiplex assay system and highly sensitive bioluminescence imaging to evaluate serological procedures for diagnosis of T. cruzi infections and confirmation of parasitological cure. We identified a set of three antigens that in the context of the multiplex serology system, provide a rapid, reactive and highly accurate read-out of both acute and chronic T. cruzi infection. In addition, we describe specific antibody responses where down-regulation can be correlated with benznidazole-mediated parasite reduction and others where upregulation is associated with persistent infection. One specific antibody (IBAG39) highly correlated with the bioluminescence flux and represents a promising therapy monitoring biomarker in mice. Conclusions/Significance Robust, high-throughput methodologies for monitoring the efficacy of anti-T. cruzi drug treatment are urgently required. Using our experimental systems, we have identified markers of infection or parasite reduction that merit assessing in a clinical setting for the longitudinal monitoring of drug-treated patients.

show abstract

Prediction of parasitological cure in children infected with Trypanosoma cruzi using a novel multiplex serological approach: an observational, retrospective cohort study

Cited by 15 publications

References 22 publications

Assessing antibody decline after chemotherapy of early chronic Chagas disease patients

Assessing antibody decline after chemotherapy of early chronic Chagas disease patients

Effectiveness of Nifurtimox in the Treatment of Chagas Disease: a Long-Term Retrospective Cohort Study in Children and Adults

Comparing in vivo bioluminescence imaging and the Multi-Cruzi immunoassay platform to develop improved Chagas disease diagnostic procedures and biomarkers for monitoring parasitological cure

Contact Info

Product

Resources

About