Survey on neutralizing antibodies against Zika virus eighteen months post-outbreak in two southern Thailand communities

Abstract Background: In 2016 and 2017, Zika virus (ZIKV) infection outbreaks occurred in two communities in southern Thailand. This re-immerging infection can widely spread by mosquito bites and cause serious complications in a central nervous system among children born to infected mothers. Thus, they should be protected. This study aims to (1) To determine the prevalence of neutralizing ZIKV antibodies in the post-outbreak areas among the general population and pregnancy women residing at various distances from the houses of the nearest index patients; (2) To examine the cross-neutralizing capacity of antibodies against ZIKV on other flaviviruses commonly found in the study areas; (3) To identify factors associated with the presence of neutralizing ZIKV antibodies.Methods: The two post-outbreak communities were visited at 18 months after the outbreaks. We enrolled (1) 18 confirmed ZIKV infected (index) cases, (2) sample of 554 neighbors in the outbreak areas who lived at various distances from the index patients’ houses, (3) 190 residents of non-outbreak areas, and (4) all pregnant women regardless of gestational age residing in the study areas (n = 805). All serum specimens underwent the plaque reduction neutralization test (PRNT). Ten randomly selected ZIKV seropositive and ten randomly selected seronegative specimens were tested for dengue virus serotypes 1-4 (DENV1-4) and Japanese encephalitis virus (JEV) antibodies using PRNT90. Serum titer above 1:10 was considered positive. Multiple logistic regression was used to assess factors associated with seropositivity.Results: Out of all 18 index cases, 9 remained seropositive. The seroprevalence (95% CI) in the two outbreak areas were 43.7% (35.9-51.6%) and 29.7% (23.3-36.0%) in general population, and 24.3% (20.1-28.8%) and 12.8% (9.7-16.5%) in pregnant women. Multivariate analysis showed that seropositivity was independent of the distance gradient from the index’s houses. However, being elderly was associated with seropositivity. DENV1-4 and JEV neutralizing antibodies were present in most ZIKV-positive and negative subsamples.Conclusion: Protective herd immunity for ZIKV infection is inadequate, especially among pregnant women in the two post-outbreak areas in southern Thailand.

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Survey on neutralizing antibodies against Zika virus eighteen months post-outbreak in two southern Thailand communities

10.21203/rs.3.rs-34709/v1 ◽

2020 ◽

Author(s):

Theerut Densathaporn ◽

Rassamee Sangthong ◽

Monvaris Sakolnapa ◽

Smonrapat Surasombatpattana ◽

Marisa Kemapunmanus ◽

...

Keyword(s):

General Population ◽

Pregnant Women ◽

Zika Virus ◽

Neutralizing Antibodies ◽

Zikv Infection ◽

Factors Associated ◽

Neutralizing Capacity ◽

Southern Thailand ◽

Outbreak Areas ◽

Index Cases

Abstract Background In 2016 and 2017, Zika virus (ZIKV) infection outbreaks occurred in two communities in southern Thailand. This re-immerging infection can widely spread by mosquito bites and cause serious complications in a central nervous system, especially in babies. Thus they should be protected. This study aims to (1) To determine the prevalence of neutralizing ZIKV antibodies in the post-outbreak areas among the general population and pregnancy women residing at various distances from the houses of the nearest index patients; (2) To examine the cross-neutralizing capacity of antibodies against ZIKV on other flaviviruses commonly found in the study areas; (3) To identify factors associated with the presence of neutralizing ZIKV antibodies. Methods The two post-outbreak communities were visited at 18 months after the outbreaks. We enrolled (1) 18 confirmed ZIKV infected (index) cases, (2) sample of 554 neighbors in the outbreak areas who lived at various distances from the index patients’ houses, (3) 190 residents of non-outbreak areas, and (4) all pregnant women regardless of gestational age residing in the study areas (n = 805). All serum specimens underwent the plaque reduction neutralization test (PRNT). Ten randomly selected ZIKV seropositive and ten randomly selected seronegative specimens were tested for dengue virus serotypes 1-4 (DENV1-4) and Japanese encephalitis virus (JEV) antibodies using PRNT. Serum titer above 1:10 was considered positive. Multiple logistic regression was used to assess factors associated with seropositivity. Results Out of all 18 index cases, 17 remained seropositive. The seroprevalence (95% CI) in the two outbreak areas were 66.5% (59.1-73.9%) and 45.6% (38.8-52.5%) in general population, and 41.0% (36.1-46.0%) and 23.5% (19.4-21.9%) in pregnant women. Multivariate analysis showed that seropositivity was independent of the distance gradient from the index’s houses. However, being elderly, poorly educated, and living far from a plantation was associated with seropositivity. DENV1-4 and JEV neutralizing antibodies were present in nearly all ZIKV-positive and negative subsamples. Conclusion Protective herd immunity for ZIKV infection is inadequate, especially among pregnant women in the two post-outbreak areas in southern Thailand.

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Survey on neutralizing antibodies against Zika virus eighteen months post-outbreak in two southern Thailand communities

10.21203/rs.3.rs-34709/v3 ◽

2020 ◽

Author(s):

Theerut Densathaporn ◽

Rassamee Sangthong ◽

Monvaris Sakolnapa ◽

Smonrapat Surasombatpattana ◽

Marisa Kemapunmanus ◽

...

Keyword(s):

General Population ◽

Pregnant Women ◽

Zika Virus ◽

Neutralizing Antibodies ◽

Zikv Infection ◽

Factors Associated ◽

Neutralizing Capacity ◽

Southern Thailand ◽

Outbreak Areas ◽

Index Cases

Abstract Background: In 2016 and 2017, Zika virus (ZIKV) infection outbreaks occurred in two communities in southern Thailand. This re-immerging infection can widely spread by mosquito bites and cause serious complications in a central nervous system among children born to infected mothers. Thus, they should be protected. This study aims to (1) To determine the prevalence of neutralizing ZIKV antibodies in the post-outbreak areas among the general population and pregnancy women residing at various distances from the houses of the nearest index patients; (2) To examine the cross-neutralizing capacity of antibodies against ZIKV on other flaviviruses commonly found in the study areas; (3) To identify factors associated with the presence of neutralizing ZIKV antibodies.Methods: The two post-outbreak communities were visited at 18 months after the outbreaks. We enrolled (1) 18 confirmed ZIKV infected (index) cases, (2) sample of 554 neighbors in the outbreak areas who lived at various distances from the index patients’ houses, (3) 190 residents of non-outbreak areas, and (4) all pregnant women regardless of gestational age residing in the study areas (n = 805). All serum specimens underwent the plaque reduction neutralization test (PRNT). Ten randomly selected ZIKV seropositive and ten randomly selected seronegative specimens were tested for dengue virus serotypes 1-4 (DENV1-4) and Japanese encephalitis virus (JEV) antibodies using PRNT90. Serum titer above 1:10 was considered positive. Multiple logistic regression was used to assess factors associated with seropositivity.Results: Out of all 18 index cases, 9 remained seropositive. The seroprevalence (95% CI) in the two outbreak areas were 43.7% (35.9-51.6%) and 29.7% (23.3-36.0%) in general population, and 24.3% (20.1-28.8%) and 12.8% (9.7-16.5%) in pregnant women. Multivariate analysis showed that seropositivity was independent of the distance gradient from the index’s houses. However, being elderly was associated with seropositivity. DENV1-4 and JEV neutralizing antibodies were present in most ZIKV-positive and negative subsamples.Conclusion: Protective herd immunity for ZIKV infection is inadequate, especially among pregnant women in the two post-outbreak areas in southern Thailand.

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Survey on neutralizing antibodies against Zika virus eighteen months post-outbreak in two southern Thailand communities

BMC Infectious Diseases ◽

10.1186/s12879-020-05654-8 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Theerut Densathaporn ◽

Rassamee Sangthong ◽

Monvaris Sakolnapa ◽

Smonrapat Surasombatpattana ◽

Marisa Kemapunmanus ◽

...

Keyword(s):

General Population ◽

Pregnant Women ◽

Zika Virus ◽

Neutralizing Antibodies ◽

Zikv Infection ◽

Factors Associated ◽

Neutralizing Capacity ◽

Southern Thailand ◽

Outbreak Areas ◽

Index Cases

Abstract Background In 2016 and 2017, Zika virus (ZIKV) infection outbreaks occurred in two communities in southern Thailand. This re-immerging infection can widely spread by mosquito bites and cause serious complications in a central nervous system among children born to infected mothers. Thus, they should be protected. This study aims to (1) To determine the prevalence of neutralizing ZIKV antibodies in the post-outbreak areas among the general population and pregnancy women residing at various distances from the houses of the nearest index patients; (2) To examine the cross-neutralizing capacity of antibodies against ZIKV on other flaviviruses commonly found in the study areas; (3) To identify factors associated with the presence of neutralizing ZIKV antibodies. Methods The two post-outbreak communities were visited at 18 months after the outbreaks. We enrolled (1) 18 confirmed ZIKV infected (index) cases, (2) sample of 554 neighbors in the outbreak areas who lived at various distances from the index patients’ houses, (3) 190 residents of non-outbreak areas, and (4) all pregnant women regardless of gestational age residing in the study areas (n = 805). All serum specimens underwent the plaque reduction neutralization test (PRNT). Ten randomly selected ZIKV seropositive and ten randomly selected seronegative specimens were tested for dengue virus serotypes 1–4 (DENV1–4) and Japanese encephalitis virus (JEV) antibodies using PRNT90. Serum titer above 1:10 was considered positive. Multiple logistic regression was used to assess factors associated with seropositivity. Results Out of all 18 index cases, 9 remained seropositive. The seroprevalence (95% CI) in the two outbreak areas were 43.7% (35.9–51.6%) and 29.7% (23.3–36.0%) in general population, and 24.3% (20.1–28.8%) and 12.8% (9.7–16.5%) in pregnant women. Multivariate analysis showed that seropositivity was independent of the distance gradient from the index’s houses. However, being elderly was associated with seropositivity. DENV1–4 and JEV neutralizing antibodies were present in most ZIKV-positive and negative subsamples. Conclusion Protective herd immunity for ZIKV infection is inadequate, especially among pregnant women in the two post-outbreak areas in southern Thailand.

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Risk Factors Associated with Persistence of Zika Virus Nucleic Acid in Serum and Semen

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx162.133 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S56-S57 ◽

Cited By ~ 1

Author(s):

Matthew Lozier ◽

Eli Rosenberg ◽

Katherine Doyle ◽

Laura Adams ◽

Liore Klein ◽

...

Keyword(s):

Pregnant Women ◽

Median Time ◽

Symptom Onset ◽

Zika Virus ◽

Diagnostic Testing ◽

Study Participation ◽

Rt Pcr ◽

Weibull Regression ◽

Factors Associated ◽

Index Cases

Abstract Background Identifying factors associated with time-to-loss of Zika virus (ZIKV) RNA in serum and semen is important to inform diagnostic testing and prevention recommendations. CDC currently recommends RT-PCR testing of serum up to two weeks after symptom onset. We evaluated such associations among participants of the Zika virus Persistence (ZiPer) study in Puerto Rico. Methods Patients presenting for care with Zika-like illness and ZIKV RNA detected by RT-PCR in serum or urine (index cases) were offered study participation. Index cases’ household members were offered study participation, and those with detectable ZIKV RNA were eligible for the prospective cohort. Serum and semen were collected weekly for the first month, and biweekly thereafter for participants with detectable ZIKV RNA in any fluid and at 2, 4, and 6 months post-enrollment for all others. We used chi-squared and Fischer’s exact tests to assess if detecting ZIKV RNA in specific specimens at any point was associated with sex, age, Zika-like symptoms (rash, fever, arthralgia, or conjunctivitis), or pregnancy. We performed Weibull regression models to estimate time-to-loss of ZIKV RNA in days post symptom onset (DPO) and evaluated associations between covariates and duration of detection. Results Among 295 participants, 260 (88.1%) had ZIKV RNA detected in serum at any point. Participants aged ≥18 years (n = 244) had a significantly longer median time-to-loss of ZIKV RNA in serum than participants aged < 18 years (n = 50) (13.1 vs. 7.8 DPO, respectively; P = 0.003) (Figure 1). Among women aged 18–39 years (n = 60), pregnant women (n = 9) had a significantly longer median time-to-loss of ZIKV RNA in serum than non-pregnant women (n = 51) (37.4 vs. 15.5 DPO, respectively; P = 0.0005) (Figure 2). The proportion of men who had detectable ZIKV RNA in semen at any point was significantly higher among men with conjunctivitis (47 of 82) than among men without conjunctivitis (3 of 14) (P = 0.01). No other associations were significant. Conclusion Time-to-loss of ZIKV RNA in serum was longer among adults than children, and conjunctivitis was associated with detecting ZIKV RNA in semen. This study provides evidence that time-to-loss of ZIKV RNA is longer among pregnant women than non-pregnant women. Findings may inform the recommended period to test pregnant women for ZIKV using RT-PCR. Disclosures All authors: No reported disclosures.

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Prevalence of Zika virus neutralizing antibodies in healthy adults in Vietnam during and after the Zika virus epidemic season: a longitudinal population-based survey

10.21203/rs.2.23060/v1 ◽

2020 ◽

Author(s):

Co Thach Nguyen ◽

Meng Ling Moi ◽

Thi Quynh Mai Le ◽

Thi Thu Thuy Nguyen ◽

Thi Bich Hau Vu ◽

...

Keyword(s):

General Population ◽

Zika Virus ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Immunoglobulin M ◽

Control Measures ◽

Serum Samples ◽

Zikv Infection ◽

Epidemic Season ◽

Low Levels

Abstract Background: Between 2016 and 2019, 265 cases of Zika virus (ZIKV) infection were reported in Vietnam, predominantly in southern Vietnam. In 2016, a case of ZIKV-associated microcephaly was confirmed in the Central Highlands, and several members of the infant’s family were confirmed to be infected with ZIKV. However, data on the seroprevalence of ZIKV antibodies in the general population is limited. The purpose of this survey was to determine the level of immunity to ZIKV in the general population of the ZIKV epidemic region.Methods: A total of 879 serum samples were collected from 801 participants between January 2017 and July 2018, during and after the ZIKV epidemic in Vietnam. The samples were tested for anti-ZIKV immunoglobulin M (IgM) and immunoglobulin G (IgG), and anti-dengue virus (DENV) IgG antibodies using enzyme-linked immunosorbent assays (ELISA). Plaque-reduction neutralization test (PRNT) for ZIKV was performed on all samples, and for DENV on the samples that ZIKV neutralizing antibody positive.Results: A total of 83 (10.3%) participants had anti-ZIKV IgM. Of the 83, 6 were confirmed to be ZIKV positive using PRNT and anti-ZIKV IgG ELISA. Of the 718 participants who were anti-ZIKV IgM negative, a further 3 cases were confirmed to be ZIKV positive. Of the 9 participants with ZIKV infection, 5 lived in the same village as the infant with ZIKV-associated microcephaly and the other 4 lived in 2 neighboring communes. Repeat samples were collected from the 83 ZIKV IgM positive participants 1.5 years after the first collection. No new cases of ZIKV infection were detected. In addition, 2 of 3 participants with anti-ZIKV NS1 IgG demonstrated a 4- to 8-fold increase in ZIKV neutralizing antibody titer.Conclusion: ZIKV was present in the area around Krong Buk since at least 2016. While the low levels of circulation together with low seroprevalence suggests a limited outbreak in the region, the results also reflect on low levels of protective immunity to Zika within the population. These results provide a better understanding of the current ZIKV epidemic status in the region and demonstrate a need for implementation of more effective ZIKV infection control measures.

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Embryonic Stage of Congenital Zika Virus Infection Determines Fetal and Postnatal Outcomes in Mice

Viruses ◽

10.3390/v13091807 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1807

Author(s):

Eri Nakayama ◽

Yasuhiro Kawai ◽

Satoshi Taniguchi ◽

Jessamine E. Hazlewood ◽

Ken-ichi Shibasaki ◽

...

Keyword(s):

Zika Virus ◽

Neutralizing Antibodies ◽

Neonatal Death ◽

Motor Behavior ◽

Wide Spectrum ◽

Fetal Loss ◽

Congenital Infection ◽

Sensory Function ◽

Zikv Infection ◽

Wide Range

Zika virus (ZIKV) infection during pregnancy causes a wide spectrum of congenital abnormalities and postnatal developmental sequelae such as fetal loss, intrauterine growth restriction (IUGR), microcephaly, or motor and neurodevelopmental disorders. Here, we investigated whether a mouse pregnancy model recapitulated a wide range of symptoms after congenital ZIKV infection, and whether the embryonic age of congenital infection changed the fetal or postnatal outcomes. Infection with ZIKV strain PRVABC59 from embryonic day 6.5 (E6.5) to E8.5, corresponding to the mid-first trimester in humans, caused fetal death, fetal resorption, or severe IUGR, whereas infection from E9.5 to E14.5, corresponding to the late-first to second trimester in humans, caused stillbirth, neonatal death, microcephaly, and postnatal growth deficiency. Furthermore, 4-week-old offspring born to dams infected at E12.5 showed abnormalities in neuropsychiatric state, motor behavior, autonomic function, or reflex and sensory function. Thus, our model recapitulated the multiple symptoms seen in human cases, and the embryonic age of congenital infection was one of the determinant factors of offspring outcomes in mice. Furthermore, maternal neutralizing antibodies protected the offspring from neonatal death after congenital infection at E9.5, suggesting that neonatal death in our model could serve as criteria for screening of vaccine candidates.

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Improved Immune Responses against Zika Virus after Sequential Dengue and Zika Virus Infection in Human

10.20944/preprints201808.0030.v1 ◽

2018 ◽

Cited By ~ 1

Author(s):

Felix G. Delgado ◽

Karina I. Torres ◽

Jaime E. Castellanos ◽

Consuelo Romero-Sánchez ◽

Etienne Simon-Lorière ◽

...

Keyword(s):

T Cell ◽

Immune Responses ◽

B Cell ◽

Zika Virus ◽

Neutralizing Antibodies ◽

Denv Infection ◽

T Cell Response ◽

Zikv Infection ◽

Cell Responses ◽

B Cell Responses

The high level of dengue virus (DENV) seroprevalence in areas where Zika virus (ZIKV) is circulating and the cross-reactivity between these two viruses have raised concerns on the risk of increased ZIKV disease severity for patients with a history of previous DENV infection. To determine the role of DENV pre-immunity in ZIKV infection, we analysed the T and B cell responses against ZIKV in donors with or without previous DENV infection. Using PBMCs from donors living in an endemic area in Colombia, we have identified, by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay, most of the immunodominant ZIKV T-cell epitopes in the non-structural proteins NS1, NS3 and NS5. Analyses of the T and B-cell responses in the same donors revealed a stronger T-cell response against peptides conserved between DENV and ZIKV, with a higher level of ZIKV-neutralizing antibodies in DENV-immune donors, in comparison with DENV-naïve donors. Strikingly, the potential for antibody mediated enhancement of ZIKV infection was reduced in donors with sequential DENV and ZIKV infection in comparison with donors with DENV infection only. Altogether, these data suggest that individuals with DENV immunity present improved immune responses against ZIKV.

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Distinct cellular immune signatures in acute Zika virus infection are associated with high or low persisting neutralizing antibody titers

10.1101/2021.05.27.446054 ◽

2021 ◽

Author(s):

Elizabeth E. McCarthy ◽

Pamela M. Odorizzi ◽

Emma Lutz ◽

Carolyn P. Smullin ◽

Iliana Tenvooren ◽

...

Keyword(s):

Zika Virus ◽

Neutralizing Antibodies ◽

Viral Infections ◽

Immune Cell ◽

Acute Infection ◽

Neutralizing Antibody ◽

Natural Immunity ◽

Zikv Infection ◽

Antibody Titers ◽

Cellular Immune

Although the formation of a durable neutralizing antibody response after an acute viral infection is a key component of protective immunity, little is known about why some individuals generate high versus low neutralizing antibody titers to infection or vaccination. Infection with Zika virus (ZIKV) during pregnancy can cause devastating fetal outcomes, and efforts to understand natural immunity to this infection are essential for optimizing vaccine design. In this study, we leveraged the high-dimensional single-cell profiling capacity of mass cytometry (CyTOF) to deeply characterize the cellular immune response to acute and convalescent ZIKV infection in a cohort of blood donors in Puerto Rico incidentally found to be viremic during the 2015-2016 epidemic in the Americas. During acute ZIKV infection, we identified widely coordinated responses across innate and adaptive immune cell lineages. High frequencies of multiple activated innate immune subsets, as well as activated follicular helper CD4+ T cells and proliferating CD27-IgD- B cells, during acute infection were associated with high titers of ZIKV neutralizing antibodies at 6 months post-infection. On the other hand, low titers of ZIKV neutralizing antibodies were associated with immune features that suggested a cytotoxic-skewed immune "set-point." Our study offers insight into the cellular coordination of immune responses and identifies candidate cellular biomarkers that may offer predictive value in vaccine efficacy trials for ZIKV and other acute viral infections aimed at inducing high titers of neutralizing antibodies.

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Atovaquone Inhibits Arbovirus Replication through the Depletion of Intracellular Nucleotides

Journal of Virology ◽

10.1128/jvi.00389-19 ◽

2019 ◽

Vol 93 (11) ◽

Cited By ~ 12

Author(s):

Angelica Cifuentes Kottkamp ◽

Elfie De Jesus ◽

Rebecca Grande ◽

Julia A. Brown ◽

Adam R. Jacobs ◽

...

Keyword(s):

Viral Replication ◽

Pregnant Women ◽

Vulnerable Populations ◽

Zika Virus ◽

Ex Vivo ◽

Pyrimidine Biosynthesis ◽

Zikv Infection ◽

Antiviral Therapies ◽

Virion Production ◽

Women And Children

ABSTRACT Arthropod-borne viruses represent a significant public health threat worldwide, yet there are few antiviral therapies or prophylaxes targeting these pathogens. In particular, the development of novel antivirals for high-risk populations such as pregnant women is essential to prevent devastating disease such as that which was experienced with the recent outbreak of Zika virus (ZIKV) in the Americas. One potential avenue to identify new and pregnancy-acceptable antiviral compounds is to repurpose well-known and widely used FDA-approved drugs. In this study, we addressed the antiviral role of atovaquone, an FDA Pregnancy Category C drug and pyrimidine biosynthesis inhibitor used for the prevention and treatment of parasitic infections. We found that atovaquone was able to inhibit ZIKV and chikungunya virus virion production in human cells and that this antiviral effect occurred early during infection at the initial steps of viral RNA replication. Moreover, we were able to complement viral replication and virion production with the addition of exogenous pyrimidine nucleosides, indicating that atovaquone functions through the inhibition of the pyrimidine biosynthesis pathway to inhibit viral replication. Finally, using an ex vivo human placental tissue model, we found that atovaquone could limit ZIKV infection in a dose-dependent manner, providing evidence that atovaquone may function as an antiviral in humans. Taken together, these studies suggest that atovaquone could be a broad-spectrum antiviral drug and a potential attractive candidate for the prophylaxis or treatment of arbovirus infection in vulnerable populations, such as pregnant women and children. IMPORTANCE The ability to protect vulnerable populations such as pregnant women and children from Zika virus and other arbovirus infections is essential to preventing the devastating complications induced by these viruses. One class of antiviral therapies may lie in known pregnancy-acceptable drugs that have the potential to mitigate arbovirus infections and disease, yet this has not been explored in detail. In this study, we show that the common antiparasitic drug atovaquone inhibits arbovirus replication through intracellular nucleotide depletion and can impair ZIKV infection in an ex vivo human placental explant model. Our study provides a novel function for atovaquone and highlights that the rediscovery of pregnancy-acceptable drugs with potential antiviral effects can be the key to better addressing the immediate need for treating viral infections and preventing potential birth complications and future disease.

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