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IgG Subclasses and Congenital Transmission of Chagas Disease

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  • 1 Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina;
  • | 2 Laboratorio de Investigación de Enfermedades Infecciosas, Departamento de Ciencias Celulares y Moleculares, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru;
  • | 3 Miller School of Medicine, University of Miami, Miami, Florida;
  • | 4 Maternal Hospital Dr. Percy Boland, Santa Cruz, Bolivia;
  • | 5 Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;
  • | 6 Department of Medicine, Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina;
  • | 7 Asociación Benéfica PRISMA, Lima, Perú

ABSTRACT.

The mechanism of vertical transmission of Trypanosoma cruzi is poorly understood. In this study, we evaluated the role of IgG subclasses in the congenital transmission of Chagas disease. We conducted a case-control study in a public maternity hospital in Santa Cruz, Bolivia, enrolling women at delivery. Thirty women who transmitted T. cruzi to their newborns (cases), and 51 women who did not (controls) were randomly selected from 676 total seropositive women. Trypanosoma cruzi–specific IgG1, IgG2, and IgG3 levels were measured by in-house ELISA. The IgG4 levels were unmeasurable as a result of low levels in all participants. Quantitative polymerase chain reaction results and demographic factors were also analyzed. One-unit increases in normalized absorbance ratio of IgG1 or IgG2 levels increased the odds of congenital T. cruzi transmission in Chagas-seropositive women by 2.0 (95% CI: 1.1–3.6) and 2.27 (95% CI: 0.9–5.7), adjusted for age and previous blood transfusion. Odds of congenital transmission were 7.0 times higher in parasitemic mothers (95% CI: 2.3–21.3, P < 0.01) compared with nonparasitemic mothers. We observed that all mothers with IgG1 ≥ 4 were transmitters (sensitivity = 20%, specificity = 100%). Additionally, no mothers with IgG2 < 1.13 were transmitters (sensitivity = 100%, specificity = 21.6%). We demonstrated that IgG subclasses and parasite presence in blood are associated with vertical transmission of T. cruzi and could identify women at increased risk for congenital transmission by measuring IgG subclasses. These measures have potential as objective screening tests to predict the congenital transmission of Chagas.

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Author Notes

Address correspondence to Cristian Roca, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, E-mail: cristianroca@unc.edu or Natalie M. Bowman, Department of Medicine, Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, E-mail: nbowman@med.unc.edu.

Working group of Congenital Chagas in Bolivia and Peru: Federico Urquizu, Angela Giovana Vidal, Cynthia Paola Espinoza, Alejandra Pando, Celia Espinoza, Clariza Chavez, Jean Karla Velarde, Victoria Serrudo, Roberto Araya, Mirko Gorena, German Toledo.

Financial support: This work was supported by the Fogarty International Center at the National Institute of Health [5D43TW010074-04 to R.H.G]. This article will be published in PubMed Central for 12 months after publication in the Journal.

Authors’ addresses: Cristian Roca, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, and Laboratorio de Investigación de Enfermedades Infecciosas, Departamento de Ciencias Celulares y Moleculares, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru, E-mail: cristianroca@unc.edu. Edith S. Málaga-Machaca, Manuela R. Verastegui, and Edward Valencia-Ayala, Laboratorio de Investigación de Enfermedades Infecciosas, Departamento de Ciencias Celulares y Moleculares, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru, E-mails: edith.malaga@gmail.com, manuela.verastegui@upch.pe, and evalenciaa23@gmail.com. Billy Scola, Miller School of Medicine, University of Miami, Miami, FL, Email: scola.billy@gmail.com. Maria del Carmen Menduiña, Maternal Hospital Dr. Percy Boland, Santa Cruz, Bolivia, E-mail: carmi40@hotmail.com. Sassan Noazin, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, E-mail: snoazin1@jhu.edu. Natalie M. Bowman, Department of Medicine, Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, E-mail: nbowman@med.unc.edu. Freddy Tinajeros, Asociación Benéfica PRISMA, Lima, Perú, E-mail: ftinajeros@gmail.com. Robert H. Gilman, Laboratorio de Investigación de Enfermedades Infecciosas, Departamento de Ciencias Celulares y Moleculares, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, and Asociación Benéfica PRISMA, Lima, Perú, E-mail: gilmanbob@gmail.com.

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