Differential Shedding and Antibody Kinetics of Zika and Chikungunya Viruses, Brazil

Abstract

In seroconversion panels obtained from patients from Brazil, diagnostic testing for Zika virus infection was improved by combining multiple antibody isotypes, techniques, and antigens, but sensitivity remained suboptimal. In contrast, chikungunya virus diagnostic testing was unambiguous. Recurrent recent arbovirus infections suggested by serologic data and unspecific symptoms highlight the need for exhaustive virologic testing.

Keywords: Brazil; Zika virus; arboviruses; chikungunya virus; diagnosis; flaviviruses; real time RT-PCR; serology; vector-borne infections; viruses.

Figure 1

Overview of diagnostic testing and shedding dynamics for Zika virus and CHIKV among patients in Brazil, 2016. A) Timeline of sampling and number of samples for each test. B, C) Zika virus (B) and CHIKV (C) loads in different body fluids at 1–5 and 5–9 dpo. Black dots indicate single samples. Red dots indicate samples taken 1–5 dpo that were negative 5–9 dpo. Dotted lines indicate paired samples that were positive at both time points. Bold line indicates the median. D, E) Viral loads of Zika virus (D) and CHIKV (E) in paired urine and serum samples from individual patients, 1–5 and 5–9 dpo. Data were analyzed using GraphPad Prism 5 (GraphPad Software, Inc., https://www.graphpad.com). CHIKV, chikungunya virus; dpo, days post–symptom onset; PRNT, plaque reduction neutralization test.

Figure 2

Zika virus and CHIKV antibody dynamics among samples from patients in Brazil, 2016. A) Percentage seroconversion for markers of acute infection with Zika virus and CHIKV (IgM NS1–based Zika virus ELISA, IgM envelope-based Zika virus ELISA, IgM μ-capture Zika virus ELISA, IgA NS1-based Zika virus ELISA, IgM CHIKV ELISA) at any time point. B) Median ELISA ratios for Zika virus and CHIKV IgM and IgA over time. C) Percentage seroconversion for markers of convalescence after Zika virus and CHIKV infection (IgG NS1-based Zika virus ELISA and IgG envelope-based Zika virus ELISA, Zika virus PRNT₅₀, IgG CHIKV ELISA) at any time point. D) Median ELISA ratios for Zika virus and CHIKV IgG over time. Numbers of specimens per time point are shown in Figure 1. Dashed lines indicate signal-to-cutoff ratios of >1.1 considered positive for all ELISAs except μ-capture ELISA, for which the dashed line indicates a signal-to-cutoff ratio of >10, considered positive by the manufacturer. See Appendix Figure 5 for the percentage de novo seroconversion of Zika virus and CHIKV in different assays per time point. CHIKV, chikungunya virus; dpo, days post–symptom onset; E, envelope; NS, nonstructural protein; PRNT, plaque reduction neutralization test.