2081. Building a Decision Tree with Serial Serology Measurements Improves Classification in a Flavivirus Co-circulation Region
Session: Poster Abstract Session: Diagnostics: Virology
Saturday, October 6, 2018
Room: S Poster Hall
Posters
  • 2081_IDWPOSTER.pdf (821.7 kB)
  • Background:

    RT-PCR (Reverse Transcriptase Polymerase Chain Reaction) is often considered the “gold standard” for diagnosis of Zika Virus (ZIKV) infection, however it has been shown to have low sensitivity. A possible remedy is to study ZIKV-specific IgG (ZsIgG) and IgM (ZsIgM) antibodies. However, the in-vitro cross-reactivities of Dengue Virus (DENV) and ZIKV-specific antibodies are well known, leading to diagnostic difficulties in an area with co-circulation of the two viruses. Our goal was to use Zika and Dengue serologic assays to build a classification model that improves upon the PPV of commercial kits while maintaining sensitivity.

    Methods:

    We conducted a prospective longitudinal study in Southern Mexico where DENV and ZIKV co-circulation occurs (NCT02831699). Patients were included in two cohorts: a cohort of subjects presenting with a febrile rash meeting WHO/PAHO Zika case definition and a household cohort. After signed consent, all subjects enrolled were evaluated on Study-visit Days 0, 3 and 7 (for fever rash cohort) and 28. We considered a subject “true positive” for ZIKV or DENV if RT-PCR positive at any time point. The healthy household cohort (with no positive RT-PCR) were considered “true negatives”.  We fit a statistical decision tree taking as inputs serial serology measurements and outputting a predicted disease category.  Funded in part by the NCI Contract No. HHSN261200800001E.  Funded in part by the Mexican Ministry of Health.

    Results:

    As of March 2018, we have 32 subjects in the Zika PCR+ group, 32 in the Dengue PCR+ group, and 68 in the household group. Our decision tree (Figure 1) achieved PPV of at least 90% on all three disease categories, while maintaining sensitivity above 50%. The highest PPV achieved by the kit manufacturer recommended cutoffs while maintaining a sensitivity of at least 10% on Zika PCR+ subjects is 30/114 (26%), and for Dengue PCR+ subjects is 21/30 (70%).

    Conclusion:

    Using serology data in a statistical decision tree improves the PPV exhibited by the kit manufacturer recommendations while still maintaining respectable sensitivity. Physicians in regions with co-circulating flaviviruses should be aware of the pitfalls of using only RT-PCR or using pre-established commercial cutoffs in the serology kits for diagnosis.


     

     

     

    Keith Lumbard, MS1, Fernando J. Arteaga Cabello, Bs, MSc.2, Aurelie Gouel-Cheron, MD, PhD3, Francisco Belaunzarán, MD, MSc2, Gabriel Nájera-Cancino, MD, MS4, Sandra Caballero-Sosa, MD, PhD5, Héctor Rincón-León, MD6, Emilia Del Carmen Ruis Hernandez, MD7, Pilar Ramos Cervantes, MSc8, M. Lourdes Guerrero, MD, MS2, John Beigel, MD1,9, Karina Trujillo-Murillo, PhD4, Gustavo Pedraza, CHEM2, Jesús Sepulveda, MD4, Kenia Melina Escobedo-Lopez, BS2, Nora K. Mora-Suarez, BS2, Monica Reyes-Romero, BS2, Violeta Ibarra-González, MS2, Julia Marínez-Lopez, BS2, Guillermo Ruiz-Palacios, MD, FIDSA10 and Sally Hunsberger, PhD3, (1)Clinical Research Directorate/Clinical Monitoring Research Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD, (2)Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico, (3)Biostatistics Research Branch, NIAID, Rockville, MD, (4)Hospital Regional de Alta Especialidad Ciudad Salud, Tapachula, Mexico, (5)Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Tapachula, Mexico, (6)Instituto Mexicano del Seguro Social, Tapachula, Mexico, (7)Hospital General Tapachula, Tapachula, Mexico, (8)Molecular Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico, Mexico, (9)NIAID, Bethesda, MD, (10)Comisión Coordinadora de los Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Mexico City, Mexico

    Disclosures:

    K. Lumbard, None

    F. J. Arteaga Cabello, None

    A. Gouel-Cheron, None

    F. Belaunzarán, None

    G. Nájera-Cancino, None

    S. Caballero-Sosa, None

    H. Rincón-León, None

    E. Del Carmen Ruis Hernandez, None

    P. Ramos Cervantes, None

    M. L. Guerrero, None

    J. Beigel, None

    K. Trujillo-Murillo, None

    G. Pedraza, None

    J. Sepulveda, None

    K. M. Escobedo-Lopez, None

    N. K. Mora-Suarez, None

    M. Reyes-Romero, None

    V. Ibarra-González, None

    J. Marínez-Lopez, None

    G. Ruiz-Palacios, None

    S. Hunsberger, None

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 3rd with the exception of research findings presented at the IDWeek press conferences.