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Effect of prior Zika and dengue virus exposure on the severity of a subsequent dengue infection in adults.

ABSTRACT: Given the structural similarity between Zika and dengue viruses, prior infection from one virus is hypothesized to modulate the severity of a subsequent infection from the other virus. A previous paediatric cohort study observed that a prior Zika infection may increase the risk of a subsequent symptomatic or severe dengue infection. The Colombo Dengue study is a prospective hospital-based cohort study in Sri Lanka that recruits symptomatic adult dengue patients within the first three days of fever. Anti-Dengue Envelope and anti-Zika NS1 IgG antibodies were tested by ELISA (Euroimmun, Lubeck, Germany) in all recruited patients. Associations between pre-morbid seroprevalence for either or both infections and adverse clinical outcomes of the current dengue infection were explored. A total of 507 dengue infected patients were assessed of whom 342 (68%) and 132 (26%) patients had anti-dengue IgG and anti-Zika IgG respectively. People with combined prior dengue and zika exposure as well as prior dengue exposure alone, were at increased risk of plasma leakage, compensated and uncompensated shock, and severe dengue (p < 0·05), compared to people without prior exposure to either infection. The effect of prior Zika exposure alone could not be established due to the small the number of primary dengue infections with prior Zika exposure.

SUBMITTER: Valencia BM

PROVIDER: S-EPMC9568574 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Effect of prior Zika and dengue virus exposure on the severity of a subsequent dengue infection in adults.

Valencia Braulio M BM Sigera Ponsuge C PC Weeratunga Praveen P Tedla Nicodemus N Fernando Deepika D Rajapakse Senaka S Lloyd Andrew R AR Rodrigo Chaturaka C

Scientific reports 20221014 1

Given the structural similarity between Zika and dengue viruses, prior infection from one virus is hypothesized to modulate the severity of a subsequent infection from the other virus. A previous paediatric cohort study observed that a prior Zika infection may increase the risk of a subsequent symptomatic or severe dengue infection. The Colombo Dengue study is a prospective hospital-based cohort study in Sri Lanka that recruits symptomatic adult dengue patients within the first three days of fev ...[more]

PMID: 36241869

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Project description:While progress has been made in characterizing humoral immunity to Zika virus (ZIKV) in humans, little is known regarding the corresponding T cell responses to ZIKV. Here, we investigate the kinetics and viral epitopes targeted by T cells responding to ZIKV and address the critical question of whether preexisting dengue virus (DENV) T cell immunity modulates these responses. We find that memory T cell responses elicited by prior infection with DENV or vaccination with tetravalent dengue attenuated vaccines (TDLAV) recognize ZIKV-derived peptides. This cross-reactivity is explained by the sequence similarity of the two viruses, as the ZIKV peptides recognized by DENV-elicited memory T cells are identical or highly conserved in DENV and ZIKV. DENV exposure prior to ZIKV infection also influences the timing and magnitude of the T cell response. ZIKV-reactive T cells in the acute phase of infection are detected earlier and in greater magnitude in DENV-immune patients. Conversely, the frequency of ZIKV-reactive T cells continues to rise in the convalescent phase in DENV-naive donors but declines in DENV-preexposed donors, compatible with more efficient control of ZIKV replication and/or clearance of ZIKV antigen. The quality of responses is also influenced by previous DENV exposure, and ZIKV-specific CD8 T cells from DENV-preexposed donors selectively upregulated granzyme B and PD1, unlike DENV-naive donors. Finally, we discovered that ZIKV structural proteins (E, prM, and C) are major targets of both the CD4 and CD8 T cell responses, whereas DENV T cell epitopes are found primarily in nonstructural proteins.IMPORTANCE The issue of potential ZIKV and DENV cross-reactivity and how preexisting DENV T cell immunity modulates Zika T cell responses is of great relevance, as the two viruses often cocirculate and Zika virus has been spreading in geographical regions where DENV is endemic or hyperendemic. Our data show that memory T cell responses elicited by prior infection with DENV recognize ZIKV-derived peptides and that DENV exposure prior to ZIKV infection influences the timing, magnitude, and quality of the T cell response. Additionally, we show that ZIKV-specific responses target different proteins than DENV-specific responses, pointing toward important implications for vaccine design against this global threat.

Project description:Zika virus (ZIKV) recently caused a pandemic complicated by Guillain-Barre syndrome (GBS) and birth defects. ZIKV is structurally similar to the dengue viruses (DENV) and in vitro studies suggest antibody dependent enhancement occurs in ZIKV infections preceded by DENV; however, the clinical significance of this remains unclear. We undertook a PRISMA-adherent systematic review of all current human and non-human primate (NHP) data to determine if prior infection with DENV, compared to DENV-naïve hosts, is associated with a greater risk of ZIKV clinical complications or greater ZIKV peak viremia in vivo. We identified 1146 studies in MEDLINE, EMBASE and the grey literature, of which five studies were eligible. One human study indicated no increase in the risk of GBS in ZIKV infections with prior DENV exposure. Two additional human studies showed a small increase in ZIKV viremia in those with prior DENV exposure; however, this was not statistically significant nor was it associated with an increase in clinical severity or adverse pregnancy outcomes. While no meta-analysis was possible using human data, a pooled analysis of the two NHP studies leveraging extended data provided only weak evidence of a 0.39 log10 GE/mL rise in ZIKV viremia in DENV experienced rhesus macaques compared to those with no DENV exposure (p = 0.22). Using a customized quality grading criteria, we further show that no existing published human studies have offered high quality measurement of both acute ZIKV and antecedent DENV infections. In conclusion, limited human and NHP studies indicate a small and non-statistically significant increase in ZIKV viremia in DENV-experienced versus DENV-naïve hosts; however, there is no evidence that even a possible small increase in ZIKV viremia would correlate with a change in ZIKV clinical phenotype. More data derived from larger sample sizes and improved sero-assays are needed to resolve this question, which has major relevance for clinical prognosis and vaccine design.

Project description:BackgroundZika virus (ZIKV) emerged in northeast Brazil in 2015 and spread rapidly across the Americas, in populations that have been largely exposed to dengue virus (DENV). The impact of prior DENV infection on ZIKV infection outcome remains unclear. To study this potential impact, we analyzed the large 2016 Zika epidemic in Managua, Nicaragua, in a pediatric cohort with well-characterized DENV infection histories.Methods and findingsSymptomatic ZIKV infections (Zika cases) were identified by real-time reverse transcription PCR and serology in a community-based cohort study that follows approximately 3,700 children aged 2-14 years old. Annual blood samples were used to identify clinically inapparent ZIKV infections using a novel, well-characterized serological assay. Multivariable Poisson regression was used to examine the relation between prior DENV infection and incidence of symptomatic and inapparent ZIKV infection. The generalized-growth method was used to estimate the effective reproduction number. From January 1, 2016, to February 28, 2017, 560 symptomatic ZIKV infections and 1,356 total ZIKV infections (symptomatic and inapparent) were identified, for an overall incidence of 14.0 symptomatic infections (95% CI: 12.9, 15.2) and 36.5 total infections (95% CI: 34.7, 38.6) per 100 person-years. Effective reproduction number estimates ranged from 3.3 to 3.4, depending on the ascending wave period. Incidence of symptomatic and total ZIKV infections was higher in females and older children. Analysis of the effect of prior DENV infection was performed on 3,027 participants with documented DENV infection histories, of which 743 (24.5%) had experienced at least 1 prior DENV infection during cohort follow-up. Prior DENV infection was inversely associated with risk of symptomatic ZIKV infection in the total cohort population (incidence rate ratio [IRR]: 0.63; 95% CI: 0.48, 0.81; p < 0.005) and with risk of symptomatic presentation given ZIKV infection (IRR: 0.62; 95% CI: 0.44, 0.86) when adjusted for age, sex, and recent DENV infection (1-2 years before ZIKV infection). Recent DENV infection was significantly associated with decreased risk of symptomatic ZIKV infection when adjusted for age and sex, but not when adjusted for prior DENV infection. Prior or recent DENV infection did not affect the rate of total ZIKV infections. Our findings are limited to a pediatric population and constrained by the epidemiology of the site.ConclusionsThese findings support that prior DENV infection may protect individuals from symptomatic Zika. More research is needed to address the possible immunological mechanism(s) of cross-protection between ZIKV and DENV and whether DENV immunity also modulates other ZIKV infection outcomes such as neurological or congenital syndromes.

Project description:Background and aimsElucidating whether prior dengue potentially confers cross-protection against COVID-19 is of public health importance in tropical countries at risk of overlapping dengue and COVID-19 epidemics. However, studies to date have yielded conflicting results. We aimed to assess effects of recent prior dengue infection on risk and severity of subsequent SARS-CoV-2 infection among adult Singaporeans.MethodsA retrospective cohort study including all adult Singaporeans aged ≥18 years was conducted from 1 July 2021 through 31 October 2022, when a dengue outbreak driven by the DENV3 serotype preceded subsequent waves of SARS-CoV-2 Delta/Omicron transmission in Singapore. SARS-CoV-2 and dengue infection status were classified using national registries. Cox regression models adjusted for demographics, COVID-19 vaccination status, comorbidity, and socioeconomic-status were used to assess risks and severity (hospitalization, severe illness) of SARS-CoV-2 infection occurring after previous recorded dengue infection.ResultsA total of 3 366 399 individuals were included, contributing 1 399 696 530 person-days of observation. A total of 13 434 dengue infections and 1 253 520 subsequent SARS-CoV-2 infections were recorded; with an average of 94.7 days (standard deviation = 83.8) between dengue infection and SARS-CoV-2 infection. Preceding dengue infection was associated with a modest increase in risk of subsequent SARS-CoV-2 infection (adjusted hazards ratio [aHR] = 1.13; 95% confidence interval [CI], 1.08-1.17), and significantly elevated risk of subsequent COVID-19 hospitalization (aHR = 3.25; 95% CI, 2.78-3.82) and severe COVID-19 (aHR = 3.39; 95% CI, 2.29-5.03).ConclusionsIncreased risk of SARS-CoV-2 infection and adverse COVID-19 outcomes were observed following preceding dengue infection in a national population-based cohort of adult Singaporeans. This observation is of significance in tropical countries with overlapping dengue and COVID-19 outbreaks.

Dataset Information

Effect of prior Zika and dengue virus exposure on the severity of a subsequent dengue infection in adults.

Publications

Effect of prior Zika and dengue virus exposure on the severity of a subsequent dengue infection in adults.

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