NDLI: Assessing antibody decline after chemotherapy of early chronic Chagas disease patients

Content Provider	Springer Nature : BioMed Central
Author	Murphy, Niamh Cardinal, M. Victoria Bhattacharyya, Tapan Enriquez, Gustavo F. Macchiaverna, Natalia P. Alvedro, Alejandra Freilij, Héctor Martinez de Salazar, Pablo Molina, Israel Mertens, Pascal Gilleman, Quentin Gürtler, Ricardo E. Miles, Michael A.
Abstract	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.
Related Links	https://parasitesandvectors.biomedcentral.com/counter/pdf/10.1186/s13071-021-05040-6.pdf
Ending Page	12
Page Count	12
Starting Page	1
File Format	HTM / HTML
ISSN	17563305
DOI	10.1186/s13071-021-05040-6
Journal	Parasites & Vectors
Issue Number	1
Volume Number	14
Language	English
Publisher	BioMed Central
Publisher Date	2021-10-20
Access Restriction	Open
Subject Keyword	Parasitology Entomology Tropical Medicine Infectious Diseases Veterinary Medicine Veterinary Science Virology Trypanosoma cruzi Chagas disease Serology ELISA Rapid diagnostic test IgG IgG1 Pre-treatment Post-treatment Veterinary Medicine/Veterinary Science
Content Type	Text
Resource Type	Article
Subject	Veterinary Infectious Diseases Parasitology
Journal Impact Factor	3/2023
5-Year Journal Impact Factor	3.3/2023

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