scholarly journals Pregnant Women Infected with Zika Virus Show Higher Viral Load and Immunoregulatory Cytokines Profile with CXCL10 Increase

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 80
Author(s):  
Elizabeth Camacho-Zavala ◽  
Clara Santacruz-Tinoco ◽  
Esteban Muñoz ◽  
Rommel Chacón-Salinas ◽  
Ma Isabel Salazar-Sanchez ◽  
...  
Keyword(s):  
Viral Load ◽  
Inflammatory Response ◽  
Pregnant Women ◽  
Inflammatory Cytokines ◽  
Zika Virus ◽  
Epidemiological Surveillance ◽  
Congenital Defects ◽  
Serum Samples ◽  
Zikv Infection ◽  
Anti Inflammatory

Background: Zika virus (ZIKV) infection during pregnancy usually shows only mild symptoms and is frequently subclinical. However, it can be vertically transmitted to the fetus, causing microcephaly and other congenital defects. During pregnancy, the immune environment modifications can alter the response to viruses in general and ZIKV in particular. Objective: To describe the role of pregnancy in the systemic pro- and anti-inflammatory response during symptomatic ZIKV infection. Materials and Methods: A multiplex assay was used to measure 25 cytokines, chemokines, and receptors in 110 serum samples from pregnant and nonpregnant women with and without ZIKV infection with and without symptoms. Samples were collected through an epidemiological surveillance system. Results: Samples from pregnant women with ZIKV infection showed a higher viral load but had similar profiles of inflammatory markers as compared with nonpregnant infected women, except for CXCL10 that was higher in infected pregnant women. Notably, the presence of ZIKV in pregnancy favored a regulatory profile by significantly increasing anti-inflammatory cytokines such as interleukin (IL)-10, receptors IL-1RA, and IL-2R, but only those pro-inflammatory cytokines such as IL-6, interferon (IFN)-α, IFN-γ and IL-17 that are essential for the antiviral response. Interestingly, there were no differences between symptomatic and weakly symptomatic ZIKV-infected groups. Conclusion: Our results revealed a systemic anti-inflammatory cytokine and chemokine profile that could participate in the control of the virus. The anti-inflammatory response in pregnant women infected with ZIKA was characterized by high CXCL10, a cytokine that has been correlated with congenital malformations.

scholarly journals Microcephaly Outcomes among Zika Virus–Infected Pregnant Women in Honduras

2021 ◽  
Author(s):  
Jackeline Alger ◽  
Pierre Buekens ◽  
Maria Luisa Cafferata ◽  
Zulma Alvarez ◽  
Mabel Berrueta ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Head Circumference ◽  
Zika Virus ◽  
Regional Variation ◽  
Serum Samples ◽  
Zikv Infection ◽  
Prenatal Visit ◽  
The Mean ◽  
A Prospective Study ◽  
The Impact

The impact of Zika virus (ZIKV) infection on pregnancies shows regional variation emphasizing the importance of studies in different geographical areas. We conducted a prospective study in Tegucigalpa, Honduras, recruiting 668 pregnant women between July 20, 2016, and December 31, 2016. We performed Trioplex real-time reverse transcriptase–PCR (rRT-PCR) in 357 serum samples taken at the first prenatal visit. The presence of ZIKV was confirmed in seven pregnancies (7/357, 2.0%). Nine babies (1.6%) had microcephaly (head circumference more than two SDs below the mean), including two (0.3%) with severe microcephaly (head circumference [HC] more than three SDs below the mean). The mothers of both babies with severe microcephaly had evidence of ZIKV infection. A positive ZIKV Trioplex rRT-PCR was associated with a 33.3% (95% CI: 4.3–77.7%) risk of HC more than three SDs below the mean.

scholarly journals Zika Virus Infection in Pregnancy: Advanced Diagnostic Approaches in Dengue-Naive and Dengue-Experienced Pregnant Women and Possible Implication for Cross-Reactivity and Cross-Protection

2019 ◽  
Vol 8 (1) ◽  
pp. 56 ◽  
Author(s):  
Maurizio Zavattoni ◽  
Francesca Rovida ◽  
Elena Percivalle ◽  
Irene Cassaniti ◽  
Antonella Sarasini ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Zika Virus ◽  
Cross Reactivity ◽  
Cross Protection ◽  
Effector Memory ◽  
Congenital Defects ◽  
Zikv Infection ◽  
Effector Memory T Cells ◽  
Diagnostic Approaches

Zika virus (ZIKV) infection has been linked to congenital defects in fetuses and infants, as exemplified by the microcephaly epidemic in Brazil. Given the overlapping presence of Dengue virus (DENV) in the majority of ZIKV epidemic regions, advanced diagnostic approaches need to be evaluated to establish the role of pre-existing DENV immunity in ZIKV infection. From 2015 to 2017, five pregnant women with suspected ZIKV infection were investigated in Pavia, Italy. Among the five pregnant women, three were DENV–ZIKV immunologically cross-reactive, and two were DENV-naïve. Advanced diagnosis included the following: (i) NS1 blockade-of-binding (BOB) ELISA assay for ZIKV specific antibodies and (ii) ELISpot assay for the quantification of effector memory T cells for DENV and ZIKV. These novel assays allowed to distinguish between related flavivirus infections. The three DENV-experienced mothers did not transmit ZIKV to the fetus, while the two DENV-naive mothers transmitted ZIKV to the fetus. Pre-existing immunity in DENV experienced mothers might play a role in cross-protection.

scholarly journals Focal intra-colon cooling reduces organ injury and systemic inflammation after REBOA management of lethal hemorrhage in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Awadhesh K. Arya ◽  
Kurt Hu ◽  
Lalita Subedi ◽  
Tieluo Li ◽  
Bingren Hu
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Balloon Catheter ◽  
Organ Injury ◽  
Upper Body ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

AbstractResuscitative endovascular balloon occlusion of the aorta (REBOA) is a lifesaving maneuver for the management of lethal torso hemorrhage. However, its prolonged use leads to distal organ ischemia–reperfusion injury (IRI) and systemic inflammatory response syndrome (SIRS). The objective of this study is to investigate the blood-based biomarkers of IRI and SIRS and the efficacy of direct intestinal cooling in the prevention of IRI and SIRS. A rat lethal hemorrhage model was produced by bleeding 50% of the total blood volume. A balloon catheter was inserted into the aorta for the implementation of REBOA. A novel TransRectal Intra-Colon (TRIC) device was placed in the descending colon and activated from 10 min after the bleeding to maintain the intra-colon temperature at 37 °C (TRIC37°C group) or 12 °C (TRIC12°C group) for 270 min. The upper body temperature was maintained at as close to 37 °C as possible in both groups. Blood samples were collected before hemorrhage and after REBOA. The organ injury biomarkers and inflammatory cytokines were evaluated by ELISA method. Blood based organ injury biomarkers (endotoxin, creatinine, AST, FABP1/L-FABP, cardiac troponin I, and FABP2/I-FABP) were all drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated these increased organ injury biomarkers. Plasma levels of pro-inflammatory cytokines TNF-α, IL-1b, and IL-17F were also drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated the pro-inflammatory cytokines. In contrast, TRIC12°C significantly upregulated the levels of anti-inflammatory cytokines IL-4 and IL-10 after REBOA. Amazingly, the mortality rate was 100% in TRIC37°C group whereas 0% in TRIC12°C group after REBOA. Directly cooling the intestine offered exceptional protection of the abdominal organs from IRI and SIRS, switched from a harmful pro-inflammatory to a reparative anti-inflammatory response, and mitigated mortality in the rat model of REBOA management of lethal hemorrhage.

scholarly journals Plasma levels of melatonin, certain cytokines and placental growth factor at non-pharmacological correction of pineal function in pregnant women with intrauterine growth restriction

2020 ◽  
Vol 8 (2) ◽  
Author(s):  
A. Berbets ◽  
Keyword(s):  
Immune System ◽  
Growth Factor ◽  
Pineal Gland ◽  
Pregnant Women ◽  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Placental Growth Factor ◽  
Placental Insufficiency ◽  
Tnf Α ◽  
Anti Inflammatory

The pineal gland produces the important hormone melatonin, the level of which in the blood of pregnant women decreases in case of placental insufficiency. The effect of dysfunction of the pineal gland on the immune system of pregnant women and on the angiogenic activity of the placenta during pregnancy remains insufficiently studied. Objective: to establish the effect of our method of non-drug correction of function of pineal gland on the state of the cytokine part of the immune system and on the synthesis of placental growth factor (PlGF) in pregnant women with placental insufficiency manifesting as fetal intrauterine growth restriction (IUGR). Material and methods. 46 pregnant women with IUGR at 30-36 weeks of gestation were examined. The group was divided into two subgroups: with non-drug correction of the pineal gland function (n = 25) and without correction (n = 21). The method of correction included a set of measures of following of lighting regimen, activity and sleep for 14 days. The control group consisted of 20 women with uncomplicated pregnancy. Levels of melatonin, PlGF, TNF-α, IL-1β, IL-6, IL-4, IL-10 were determined in the venous blood by enzyme-linked immunosorbent assay. Results. It was established that the concentration of melatonin in the blood of pregnant women with IUGR was significantly reduced, as well as the concentration of PlGF (p < 0.01). Significant changes were also found in pregnant women with placental insufficiency, namely, increased concentrations of proinflammatory cytokines, such as TNF-α (p < 0.05), IL-1-β (p < 0.001) and IL-6 (p < 0.05), comparing to healthy pregnant women. Also, in the group of pregnant women with IUGR the levels of anti-inflammatory cytokines IL-4 (p <0.001) and IL-10 (p < 0.001) were elevated in comparison to the control group. After application of the developed complex of non-drug correction of pineal gland function, the concentration of melatonin in the blood of pregnant women in the subgroup of correction increased significantly, comparing to the subgroup without correction (p < 0.001), as well as the level of PlGF (p < 0.05). Also, significantly lower levels of proinflammatory cytokines TNF-α, IL-1-β and IL-6 were observed in pregnant women in the subgroup of correction (p < 0.01). Regarding anti-inflammatory cytokines, under the influence of the developed complex of measures there was a decrease in the level of IL-4 and an increase in the level of IL-10 (p < 0.01). Conclusions. When the measures, aimed at non-drug correction of function of pineal gland, are applied in pregnant women with placental insufficiency, manifested as IUGR, the following changes are observed: increased of plasma levels of melatonin and placental growth factor, decreased of levels of proinflammatory cytokines. We suggest that the pineal gland exerts its effect on the immune system through melatonin, which moderates the activity of pro- and anti-inflammatory cytokines, thereby reducing the influence of inflammation on placental tissue, what results in increasing of concentrations of placental growth factor in the blood of pregnant women.

scholarly journals Zika Virus Serologic Diagnosis by NS1 ELISA in Curacao

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S302-S303 ◽  
Author(s):  
Samantha Manuel ◽  
Liane Virginia-Cova ◽  
Loubiela Joseph ◽  
Chris Roggeveen ◽  
Radjin Steingrover
Keyword(s):  
Zika Virus ◽  
Cross Reactivity ◽  
Pregnant Female ◽  
Serum Samples ◽  
Zikv Infection ◽  
Igm Elisa ◽  
Pcr Diagnosis ◽  
Two Samples ◽  
Negative Controls

Abstract Background Zika virus (ZIKV) was introduced in the Caribbean island of Curacao in January 2016. A commercially available ZIKV IgM and IgG ELISA was evaluated on patients that were PCR-positive for ZIKV. Methods ZIKV infection was established by PCR in urine samples. Samples from PCR-positive patients were selected for validation of a ZIKV NS1 IgG and IgM ELISA. Patients with a follow-up sample ≥ 2 weeks after initial presentation were used to assess the sensitivity of the assay. Samples of 15 historical controls with serological evidence of Dengue, Chikungunya or an unrelated viral infection were included to establish specificity and cross-reactivity. Results Fourteen patients with positive ZIKV PCR diagnosis had repeated serum samples drawn ≥ 2 weeks after the initial sample. The combined results of these repeated IgM and IgG tests resulted in a sensitivity of 92%. One pregnant female showed no presence of IgG or IgM in any of the two samples. Testing of the panel of historical ZIKV-negative controls resulted in a specificity of 100% in both the quantitative and semi-quantitative setting of the ELISA. One patient with known high-titers of antibodies against Chikungunya virus in the respective panel displayed borderline reactive results for ZIKV IgG in both quantitative and semi-quantitative setting of the assay. Conclusion In this PCR-positive ZIKV cohort of patients, the newly available ZIKV NS1 ELISA displayed excellent performance characteristics. Cross-reactivity was indicated for Chikungunya in one case. No cross-reactivity was found for Dengue virus infection. One pregnant female showed no signs of developing anti-ZIKV IgM or IgG in this study. In the light of intrauterine pathogenesis, the lack of development of maternal IgG during ZIKV infection is a concern. Disclosures All authors: No reported disclosures.

scholarly journals 2801. Post-Natal Zika Virus Infection and Impact on Neurodevelopment Among a Cohort of Children in Rural Guatemala

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S990-S991
Author(s):  
Daniel Olson ◽  
Molly Lamb ◽  
Amy Connery ◽  
Kathryn Colborn ◽  
Muktha S Natrajan ◽  
...  
Keyword(s):  
Zika Virus ◽  
Receptive Language ◽  
Fine Motor ◽  
Serum Samples ◽  
Zikv Infection ◽  
Related Factors ◽  
Material Support ◽  
And Gender ◽  
The Impact ◽  
Research Grant

Abstract Background The impact of early post-natal Zika virus (ZIKV) infection on neurodevelopment (ND) is unknown. A prospective study of post-natal ZIKV infection in rural Guatemala (ZIKV study) enrolled a cohort of children ages 1–5 years, including children previously enrolled in a dengue virus (DENV) study during the 2015–2016 ZIKV epidemic. We evaluated ND outcomes by age and ZIKV infection status. Methods Subjects enrolled in the ZIKV study June 2017–April 2018 underwent ND testing using the Mullen Scales of Early Learning (MSEL) at baseline and 12 months later. ZIKV/DENV-1/2 FRNT50 was performed on enrollment and on banked serum samples from the 2015 to 2016 subset. ZIKV serostatus and MSEL scores were correlated using multiple linear mixed models, adjusted for age and gender when appropriate, to evaluate their association. Geolocation was used to explore clustering of ZIKV serostatus and MSEL score. Results We enrolled 183 children (43% female, mean age 3.2 years). Of these, 38 (21%) were classified as ZIKV-positive (+), 111 (61%) ZIKV-negative (-), 31 (17%) ZIKV-possible, and 3 (2%) ZIKV-indeterminate. ZIKV(+) cases and higher composite MSEL scores clustered in more densely populated areas (Figure 1). ZIKV(+) serostatus was associated with higher MSEL composite (increase in log score 0.09, P = 0.003) and subdomain scores: fine motor (0.13, P = 0.011), visual reception (0.15, P = 0.002), receptive language (0.09, P = 0.041), gross motor (0.14, P = 0.09), and expressive language (0.09, P = 0.058) (Figure 2). Of the 78 children (43%) with 2015–2016 samples, 46 (59%) remained ZIKV(−), 16 (21%) seroconverted from ZIKV(−) or possible/indeterminate to ZIKV(+), and 16 (21%) were indeterminate when enrolled in the ZIKV study. ZIKV seroconversion was associated with higher composite (0.13, P = 0.02) MSEL scores compared with ZIKV(−). Conclusion In this exploratory analysis, post-natal ZIKV infection was not associated with adverse ND outcomes in children age 1–5 years. Overall, ZIKV(+) status was associated with higher average ND scores than ZIKV(−), and scores decreased with age for most children, independent of ZIKV status. The correlation of ZIKV(+) status and higher MSEL scores may be confounded by geographic-related factors or other confounders. NIAID Contract HHSN272201300015I Task Order HHSN27200013 (Co-PIs: FMM & EJA). Disclosures Flor M. Munoz, M.D, Biocryst: Grant/Research Support; CDC: Research Grant; Moderna: Other Financial or Material Support, Safety Monitoring Board Member/Chair; NIH: Research Grant; Novavax: Research Grant; UP to Date: Author and Editor - Royalties, Other Financial or Material Support.

scholarly journals Atovaquone Inhibits Arbovirus Replication through the Depletion of Intracellular Nucleotides

2019 ◽  
Vol 93 (11) ◽  
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.

scholarly journals Low Aedes aegypti Vector Competence for Zika Virus from Viremic Rhesus Macaques

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1345
Author(s):  
Rosilainy Surubi Fernandes ◽  
Mariana Rocha David ◽  
Filipe Vieira Santos De Abreu ◽  
Anielly Ferreira-de-Brito ◽  
Noemi R. Gardinali ◽  
...  
Keyword(s):  
Viral Load ◽  
Aedes Aegypti ◽  
Short Duration ◽  
Zika Virus ◽  
Rhesus Macaques ◽  
Vector Competence ◽  
Transmission Dynamics ◽  
Zikv Infection ◽  
Transmission Rates ◽  
Time Points

Despite worldwide efforts to understand the transmission dynamics of Zika virus (ZIKV), scanty evaluation has been made on the vector competence of Aedes aegypti fed directly on viremic human and non-human primates (NHPs). We blood-fed Ae. aegypti from two districts in Rio de Janeiro on six ZIKV infected pregnant rhesus macaques at several time points, half of which were treated with Sofosbuvir (SOF). Mosquitoes were analyzed for vector competence after 3, 7 and 14 days of incubation. Although viremia extended up to eight days post monkey inoculation, only mosquitoes fed on the day of the peak of viremia, recorded on day two, became infected. The influence of SOF treatment could not be assessed because the drug was administered just after mosquito feeding on day two. The global infection, dissemination and transmission rates were quite low (4.09%, 1.91% and 0.54%, respectively); no mosquito was infected when viremia was below 1.26 × 105 RNA copies/mL. In conclusion, Ae. aegypti vector competence for ZIKV from macaques is low, likely to be due to low viral load and the short duration of ZIKV viremia in primates suitable for infecting susceptible mosquitoes. If ZIKV infection in human and macaques behaves similarly, transmission of the Zika virus in nature is most strongly affected by vector density.

scholarly journals Zika Virus Infects Human Placental Mast Cells and the HMC-1 Cell Line, and Triggers Degranulation, Cytokine Release and Ultrastructural Changes

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 975 ◽  
Author(s):  
Kíssila Rabelo ◽  
Antônio José da Silva Gonçalves ◽  
Luiz José de Souza ◽  
Anna Paula Sales ◽  
Sheila Maria Barbosa de Lima ◽  
...  
Keyword(s):  
Mast Cells ◽  
Cell Line ◽  
Zika Virus ◽  
Post Infection ◽  
Immune Cell ◽  
Cell Types ◽  
Ultrastructural Changes ◽  
Congenital Defects ◽  
Zikv Infection ◽  
Intracellular Changes

Zika virus (ZIKV) is an emergent arthropod-borne virus whose outbreak in Brazil has brought major public health problems. Infected individuals have different symptoms, including rash and pruritus, which can be relieved by the administration of antiallergics. In the case of pregnant women, ZIKV can cross the placenta and infect the fetus leading to congenital defects. We have identified that mast cells in the placentae of patients who had Zika during pregnancy can be infected. This led to our investigation on the possible role of mast cells during a ZIKV infection, using the HMC-1 cell line. We analyzed their permissiveness to infection, release of mediators and ultrastructural changes. Flow cytometry detection of ZIKV-NS1 expression 24 h post infection in 45.3% of cells showed that HMC-1 cells are permissive to ZIKV infection. Following infection, β-hexosaminidase was measured in the supernatant of the cells with a notable release at 30 min. In addition, an increase in TNF-α, IL-6, IL-10 and VEGF levels were measured at 6 h and 24 h post infection. Lastly, different intracellular changes were observed in an ultrastructural analysis of infected cells. Our findings suggest that mast cells may represent an important source of mediators that can activate other immune cell types during a ZIKV infection, which has the potential to be a major contributor in the spread of the virus in cases of vertical transmission.

Levels of pro-inflammatory and anti-inflammatory cytokines and interferons in pregnant women with vaginal infections during vitamin D therapy

2019 ◽  
Vol 9_2019 ◽  
pp. 75-81
Author(s):  
Kostinov M.P. Kostinov ◽  
Ignat’eva M.A. Ignat’eva ◽  
Novikova S.V. Novikova ◽  
Shmit’ko A.D. Shmit’ko ◽  
Polishchuk V.B. Polishchuk ◽  
...  
Keyword(s):  
Vitamin D ◽  
Pregnant Women ◽  
Inflammatory Cytokines ◽  
Vaginal Infections ◽  
Anti Inflammatory
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