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1.
J Med Entomol ; 2022 May 10.
Article in English | MEDLINE | ID: mdl-35535688

ABSTRACT

Aedes-borne viruses (ABVs) such as dengue (DENV), chikungunya (CHIKV), and Zika (ZIKV) contribute significantly to the global burden of infectious diseases, disproportionately affecting disadvantaged populations from tropical and subtropical urban areas. ABVs can be transmitted from female mosquitoes to their progeny by vertical transmission via transovarial and/or trans-egg vertical transmission and contribute to the maintenance of infected-mosquito populations year-round in endemic regions. This study describes the natural infection rate of DENV, CHIKV, and ZIKV in field-caught male Aedes (Sergentomyia) aegypti (Linnaeus) mosquitoes from Mérida, Yucatán, México, as a proxy for the occurrence of vertical virus transmission. We used indoor sequential sampling with Prokopack aspirators to collect all mosquitoes inside houses from ABV hotspots areas. Collections were performed in a DENV and CHIKV post-epidemic phase and during a period of active ZIKV transmission. We individually RT-qPCR tested all indoor collected Ae. aegypti males (1,278) followed by Sanger sequencing analysis for final confirmation. A total of 6.7% male mosquitoes were positive for ABV (CHIKV = 5.7%; DENV = 0.9%; ZIKV = 0.1%) and came from 21.0% (30/143) houses infested with males. Most ABV-positive male mosquitoes were positive for CHIKV (84.8%). The distribution of ABV-positive Ae. aegypti males was aggregated in a few households, with two houses having 11 ABV-positive males each. We found a positive association between ABV-positive males and females per house. These findings suggested the occurrence of vertical arbovirus transmission within the mosquito populations in an ABV-endemic area and, a mechanism contributing to viral maintenance and virus re-emergence among humans in post-epidemic periods.

2.
Virus Genes ; 2022 May 10.
Article in English | MEDLINE | ID: mdl-35536436

ABSTRACT

Dengue is a rapidly spreading arboviral disease that can be transmitted through any of the four types of dengue virus (DENV) serotypes. Previous studies have observed that individuals who have a pre-existing secondary infection due to a different dengue serotype, experience severe forms of this disease. During a DENV outbreak, a time-sensitive preliminary diagnosis of the origin of DENV might be useful in controlling the epidemic. Here, we developed a rapid and accurate one-step TB Green RT-PCR-based high-resolution melting (HRM) assay to identify and serotype DENV using serotyping primers based on the alignment with the E gene. This assay had a detection limit of 7.7 × 102 (DENV 1), 3.8 × 102 (DENV 2), 6.2 × 102 (DENV 3), and 1.2 × 103 (DENV 4) RNA copies/mL. No cross-reactivity with the Chikungunya, Zika, and Japanese encephalitis viruses was observed. The feasibility of using this assay for clinical diagnosis was evaluated in DENV-positive patient sera. The HRM assay and the RT-qPCR had complete matched results derived from DENV detection, including 51 serum positive and 20 serum negative. Additionally, eight DENV 2 strains in the same serotype were successfully differentiated by an HRM assay. Thus, this assay facilitated accurate detection and serotyping of DENV, along with the time-sensitive identification of the infectious focus of different DENVs.

3.
Cell Stem Cell ; 29(5): 810-825.e8, 2022 May 05.
Article in English | MEDLINE | ID: mdl-35523141

ABSTRACT

Trophoblast organoids derived from placental villi provide a 3D model system of human placental development, but access to first-trimester tissues is limited. Here, we report that trophoblast stem cells isolated from naive human pluripotent stem cells (hPSCs) can efficiently self-organize into 3D stem-cell-derived trophoblast organoids (SC-TOs) with a villous architecture similar to primary trophoblast organoids. Single-cell transcriptome analysis reveals the presence of distinct cytotrophoblast and syncytiotrophoblast clusters and a small cluster of extravillous trophoblasts, which closely correspond to trophoblast identities in the post-implantation embryo. These organoid cultures display clonal X chromosome inactivation patterns previously described in the human placenta. We further demonstrate that SC-TOs exhibit selective vulnerability to emerging pathogens (SARS-CoV-2 and Zika virus), which correlates with expression levels of their respective entry factors. The generation of trophoblast organoids from naive hPSCs provides an accessible 3D model system of the developing placenta and its susceptibility to emerging pathogens.


Subject(s)
COVID-19 , Pluripotent Stem Cells , Zika Virus Infection , Zika Virus , Cell Differentiation , Female , Humans , Organoids , Placenta/metabolism , Placentation , Pluripotent Stem Cells/metabolism , Pregnancy , SARS-CoV-2 , Trophoblasts/metabolism , Zika Virus Infection/metabolism
4.
Sci Rep ; 12(1): 7810, 2022 May 12.
Article in English | MEDLINE | ID: mdl-35552469

ABSTRACT

Zika fever is an infectious disease caused by the Zika virus (ZIKV). The disease is claiming millions of lives worldwide, primarily in developing countries. In addition to vector control strategies, the most effective way to prevent the spread of ZIKV infection is vaccination. There is no clinically approved vaccine to combat ZIKV infection and curb its pandemic. An epitope-based peptide vaccine (EBPV) is seen as a powerful alternative to conventional vaccinations because of its low production cost and short production time. Nonetheless, EBPVs have gotten less attention, despite the fact that they have a significant untapped potential for enhancing vaccine safety, immunogenicity, and cross-reactivity. Such a vaccine technology is based on target pathogen's selected antigenic peptides called T-cell epitopes (TCE), which are synthesized chemically based on their amino acid sequences. The identification of TCEs using wet-lab experimental approach is challenging, expensive, and time-consuming. Therefore in this study, we present computational model for the prediction of ZIKV TCEs. The model proposed is an ensemble of decision trees that utilizes the physicochemical properties of amino acids. In this way a large amount of time and efforts would be saved for quick vaccine development. The peptide sequences dataset for model training was retrieved from Virus Pathogen Database and Analysis Resource (ViPR) database. The sequences dataset consist of experimentally verified T-cell epitopes (TCEs) and non-TCEs. The model demonstrated promising results when evaluated on test dataset. The evaluation metrics namely, accuracy, AUC, sensitivity, specificity, Gini and Mathew's correlation coefficient (MCC) recorded values of 0.9789, 0.984, 0.981, 0.987, 0.974 and 0.948 respectively. The consistency and reliability of the model was assessed by carrying out the five (05)-fold cross-validation technique, and the mean accuracy of 0.97864 was reported. Finally, model was compared with standard machine learning (ML) algorithms and the proposed model outperformed all of them. The proposed model will aid in predicting novel and immunodominant TCEs of ZIKV. The predicted TCEs may have a high possibility of acting as prospective vaccine targets subjected to in-vivo and in-vitro scientific assessments, thereby saving lives worldwide, preventing future epidemic-scale outbreaks, and lowering the possibility of mutation escape.

5.
FASEB J ; 36 Suppl 12022 May.
Article in English | MEDLINE | ID: mdl-35555790

ABSTRACT

Endothelial cells (ECs) are in the inner layer of blood vessels, and it controls the transportation of nutrition and essential molecules from the extracellular matrix to the intracellular space making a homeostasis environment. Vascular endothelium can be disrupted with viruses, which are among the main reasons for epidemic and pandemic outbreaks, and it leads to health issues such as cardiovascular-related diseases. Wide range of viruses can potentially target the endothelium including Dengue virus estimated to infect 390 million people per year. Zika virus leads to pregnancy complications such as preterm birth and miscarriage. Tick-borne encephalic damaged the central nervous system and, Hantavirus has a mortality rate of 38% through hantavirus pulmonary syndrome. Reviewing these several diseases, including SARS-CoV-2, has given an in-depth look at what the endothelial cells are going through when these viruses are infecting the host bodies. Following the virus infection, ECs are going through activation mode, which is accompanied with glycocalyx degradation, plasma leakage, phosphorylation of P120, and cadherin, increased proinflammatory responses and, disruption of barrier integrity. The SARS-CoV-2 pandemic has taken a global toll; With a total of 362 million cases, there are 5.63 million deaths occurring. With the usage of immunofluorescence and vascular permeability assay, we monitor how Human Umbilical Vascular Endothelial Cells (HUVEC) and Human Lung Microvascular Endothelial Cells (HLMVEC) are impacted when treated with UV-inactivated & heat-inactivated SARS-CoV-2, and tumor necrosis factor (TNF)-α. TNF-α is an inflammatory cytokine prominent during inflammation and its known to increase the permeability of endothelium. Like the TNF-α, both cells treated with UV-inactivated and heat-inactivated SARS-CoV2 demonstrated boosted permeability. With the considerable effect of SARS-CoV2 on the permeability of ECs, it is essential to understand the mechanisms and pathways behind the boosted leak, including the impact of the virus on the expression of adhesion molecules like platelet endothelial cell adhesion molecule (PECAM-1). One can see in the images of HUVEC and HLMVEC that SARS-CoV-2 diminish the localization of PECAM-1. On a non-treated negative control, cells are spaced evenly and are close to another since their junctions are not targeted. Once the cells are treated with either heat-inactivated or UV-inactivated SARS-CoV-2, PECAM-1 localization is disrupted, which can be seen from the space between cells since the PECAM-1 has been altered and is no longer holding the cells together. From those exact images, one can detect the enlarged and irregular shapes of nucleuses and change in morphology of these cells since the SARS-CoV-2 is not only altering the PECAM-1 complex but it can also modify various proteins and mRNAs. By combining information of various viruses and knowledge from our studies, we can understand the mechanisms of ECs and take measurements to protect ECs from viruses. In future experiments, we will detect if the PECAM-1 expression is lowered when treated with SARS-CoV-2 and TNF-α or if PECAM-1 is internalized in the cell. Moreover, we can do mRNA and immunoblotting analysis to elaborate the changes in protein pathways as a consequence of COVID-19.

6.
Cad Saude Publica ; 38(4): EN230621, 2022.
Article in English | MEDLINE | ID: mdl-35508025

ABSTRACT

This study aims to estimate fertility trends in Brazil in the 2010s and early 2020s during a period of back-to-back novel infectious disease outbreaks - Zika virus and COVID-19. We use Brazilian Ministry of Health and Association of Civil Registrar data from 2011-2021 to measure general fertility rates at the national and state levels. We also used seasonal ARIMA model to forecast fertility rates by month and state in 2021 and compared these forecasts with observed fertility rates. We find that fertility rates were steady over 2011-2015 with no statistically significant variation, followed by a sharp decline during the Zika outbreak in 2016 followed by a return to pre-Zika levels after the end of the epidemic. Furthermore, to evaluate the effect of the COVID-19 pandemic, we make comparisons with observed and forecast rates from 2020-2021, showing that declines were generally larger for observed than for forecast rates, yet statistically insignificant. We argue that the resurgence of the COVID-19 pandemic in 2021 might lead to further declines, as women might have not had enough time to adjust rebound from either the effects of the Zika epidemic. We also discuss the importance of timely availability of live births data during a public health crisis with immediate consequences for fertility rates.


Subject(s)
COVID-19 , Zika Virus Infection , Zika Virus , Brazil/epidemiology , COVID-19/epidemiology , Disease Outbreaks , Female , Fertility , Humans , Pandemics , Zika Virus Infection/epidemiology
7.
Cad Saude Publica ; 38(4): e00104221, 2022.
Article in English | MEDLINE | ID: mdl-35508028

ABSTRACT

This article uses a socio-anthropological framework to explore the stigmas around interactions with children born with congenital Zika syndrome caused by the Zika virus epidemic in two Brazilian municipalities. Semi-structured interviews were conducted with parents and other relatives. We reflected on the search for meaning when having a baby with unexpected body marks, the moral suffering, the societal ableism, the burden of care, and the need for support networks. We concluded that public policies, especially social policies (health, education, and social assistance), are essential for compensatory mechanisms, recognition, and social inclusion of these children and their families.


Subject(s)
Epidemics , Microcephaly , Zika Virus Infection , Zika Virus , Brazil/epidemiology , Child , Humans , Infant , Microcephaly/epidemiology , Microcephaly/etiology , Social Stigma , Zika Virus Infection/epidemiology
8.
Front Cell Infect Microbiol ; 12: 880860, 2022.
Article in English | MEDLINE | ID: mdl-35493734

ABSTRACT

Nonhuman primates (NHP) are particularly important for modeling infections with viruses that do not naturally replicate in rodent cells. Zika virus (ZIKV) has been responsible for sporadic epidemics, but in 2015 a disseminated outbreak of ZIKV resulted in the World Health Organization declaring it a global health emergency. Since the advent of this last epidemic, several NHP species, including the baboon, have been utilized for modeling and understanding the complications of ZIKV infection in humans; several health issues related to the outcome of infection have not been resolved yet and require further investigation. This study was designed to validate, in baboons, the molecular signatures that have previously been identified in ZIKV-infected humans and macaque models. We performed a comprehensive molecular analysis of baboons during acute ZIKV infection, including flow cytometry, cytokine, immunological, and transcriptomic analyses. We show here that, similar to most human cases, ZIKV infection of male baboons tends to be subclinical, but is associated with a rapid and transient antiviral interferon-based response signature that induces a detectable humoral and cell-mediated immune response. This immunity against the virus protects animals from challenge with a divergent ZIKV strain, as evidenced by undetectable viremia but clear anamnestic responses. These results provide additional support for the use of baboons as an alternative animal model to macaques and validate omic techniques that could help identify the molecular basis of complications associated with ZIKV infections in humans.


Subject(s)
Zika Virus Infection , Zika Virus , Animals , Immunity, Cellular , Male , Papio , Viremia
9.
Article in English | MEDLINE | ID: mdl-35415761

ABSTRACT

BACKGROUND: In July 2021, an outbreak of chikungunya virus (CHIKV) was reported in a rural region of Maharashtra state, India. METHODS: Serum samples of symptomatic cases (n=33) were screened for dengue virus (DENV), CHIKV and Zika virus (ZIKV) by molecular and serological assays. RESULTS: The first case of ZIKV infection from Maharashtra was detected and confirmed by molecular and serological assays. Complete genome sequencing revealed that the ZIKV sequence belongs to the Asian genotype and had a closer homology with pre-epidemic strains present before 2007. CONCLUSIONS: ZIKV surveillance needs to be strengthened in the regions experiencing dengue and chikungunya outbreaks.

10.
PLoS One ; 17(4): e0265820, 2022.
Article in English | MEDLINE | ID: mdl-35395015

ABSTRACT

INTRODUCTION: The rapid expansion of the novel SARS-CoV-2 virus has raised serious public health concerns due to the possibility of misdiagnosis in regions where arboviral diseases are endemic. We performed the first study in northern Peru to describe the detection of SARS-CoV-2 IgM antibodies in febrile patients with a suspected diagnosis of dengue and chikungunya fever. MATERIALS AND METHODS: A consecutive cross-sectional study was performed in febrile patients attending primary healthcare centers from April 2020 through March 2021. Patients enrolled underwent serum sample collection for the molecular and serological detection of DENV and CHIKV. Also, serological detection of IgM antibodies against SARS-CoV-2 was performed. RESULTS: 464 patients were included during the study period, of which (40.51%) were positive for one pathogen, meanwhile (6.90%) presented co-infections between 2 or more pathogens. The majority of patients with monoinfections were positive for SARS-CoV-2 IgM with (73.40%), followed by DENV 18.09% and CHIKV (8.51%). The most frequent co-infection was DENV + SARS-CoV-2 with (65.63%), followed by DENV + CHIKV and DENV + CHIKV + SARS-CoV-2, both with (12.50%). The presence of polyarthralgias in hands (43.75%, p<0.01) and feet (31.25%, p = 0.05) were more frequently reported in patients with CHIKV monoinfection. Also, conjunctivitis was more common in patients positive for SARS-CoV-2 IgM (11.45%, p<0.01). The rest of the symptoms were similar among all the study groups. CONCLUSION: SARS-CoV-2 IgM antibodies were frequently detected in acute sera from febrile patients with a clinical suspicion of arboviral disease. The presence of polyarthralgias in hands and feet may be suggestive of CHIKV infection. These results reaffirm the need to consider SARS-CoV-2 infection as a main differential diagnosis of acute febrile illness in arboviruses endemic areas, as well as to consider co-infections between these pathogens.


Subject(s)
COVID-19 , Chikungunya Fever , Chikungunya virus , Coinfection , Dengue Virus , Dengue , Zika Virus Infection , Antibodies, Viral , Arthralgia , COVID-19/diagnosis , COVID-19/epidemiology , Chikungunya Fever/diagnosis , Chikungunya Fever/epidemiology , Coinfection/diagnosis , Coinfection/epidemiology , Cross-Sectional Studies , Dengue/diagnosis , Dengue/epidemiology , Fever/diagnosis , Humans , Immunoglobulin M , Peru/epidemiology , SARS-CoV-2 , Zika Virus Infection/epidemiology
11.
Am J Trop Med Hyg ; 2022 Apr 11.
Article in English | MEDLINE | ID: mdl-35405646

ABSTRACT

Co-circulation of arthropod-borne viruses, particularly those with shared mosquito vectors like Zika (ZIKV) and Chikungunya (CHIKV), is increasingly reported. An accurate differential diagnosis between ZIKV and CHIKV is of high clinical importance, especially in the context of pregnancy, but remains challenging due to limitations in the availability of specialized laboratory testing facilities. Using data collected from the prospective pregnancy cohort study of the Microcephaly Epidemic Research Group, which followed up pregnant persons with rash during the peak and decline of the 2015-2017 ZIKV epidemic in Recife, Pernambuco, Brazil, this study aims to describe the geographic and temporal distribution of ZIKV and CHIKV infections and to investigate the extent to which ZIKV and CHIKV infections may be clinically differentiable. Between December 2015 and June 2017, we observed evidence of co-circulation with laboratory confirmation of 213 ZIKV mono-infections, 55 CHIKV mono-infections, and 58 sequential ZIKV/CHIKV infections (i.e., cases with evidence of acute ZIKV infection with concomitant serological evidence of recent CHIKV infection). In logistic regressions with adjustment for maternal age, ZIKV mono-infected cases had lower odds than CHIKV mono-infected cases of presenting with arthralgia (aOR, 99% CI: 0.33, 0.15-0.74), arthritis (0.35, 0.14-0.85), fatigue (0.40, 0.17-0.96), and headache (0.44, 0.19-1.90). However, sequential ZIKV/CHIKV infections complicated discrimination, as they did not significantly differ in clinical presentation from CHIKV mono-infections. These findings suggest clinical symptoms alone may be insufficient for differentiating between ZIKV and CHIKV infections during pregnancy and therefore laboratory diagnostics continue to be a valuable tool for tailoring care in the event of arboviral co-circulation.

12.
Front Immunol ; 13: 773191, 2022.
Article in English | MEDLINE | ID: mdl-35371036

ABSTRACT

Zika virus (ZIKV), despite being discovered six decades earlier, became a major health concern only after an epidemic in French Polynesia and an increase in the number of microcephaly cases in Brazil. Substantial evidence has been found to support the link between ZIKV and neurological complications in infants. The virus targets various cells in the brain, including radial glial cells, neural progenitor cells (NPCs), astrocytes, microglial and glioblastoma stem cells. It affects the brain cells by exploiting different mechanisms, mainly through apoptosis and cell cycle dysregulation. The modulation of host immune response and the inflammatory process has also been demonstrated to play a critical role in ZIKV induced neurological complications. In addition to that, different ZIKV strains have exhibited specific neurotropism and unique molecular mechanisms. This review provides a comprehensive and up-to-date overview of ZIKV-induced neuroimmunopathogenesis by dissecting its main target cells in the brain, and the underlying cellular and molecular mechanisms. We highlighted the roles of the different ZIKV host factors and how they exploit specific host factors through various mechanisms. Overall, it covers key components for understanding the crosstalk between ZIKV and the brain.


Subject(s)
Microcephaly , Nervous System Diseases , Neural Stem Cells , Zika Virus Infection , Zika Virus , Brain/pathology , Humans , Microcephaly/pathology , Nervous System Diseases/pathology , Neural Stem Cells/pathology , Zika Virus/physiology
13.
Rev Soc Bras Med Trop ; 55: e03062021, 2022.
Article in English | MEDLINE | ID: mdl-35416870

ABSTRACT

BACKGROUND: Guillian Barré syndrome (GBS) is an acute autoimmune polyradiculoneuropathy often associated with previous exposure to infectious agents. METHODS: A clinical cohort of 41 patients with GBS admitted to the Base Hospital Institute of the Federal District between May 2017 and April 2019 was followed up for 1 year. Serological tests for arbovirus detection and amplification of nucleic acids using polymerase chain reaction for zika virus (ZIKV), dengue virus (DENV), and chikungunya virus (CHIKV) were performed. RESULTS: The cohort consisted of 61% men with a median age of 40 years, and 83% had GBS-triggering events. A total of 54% had Grade 4 disability, 17% had Grade 3, 12% had Grade 2, 10% had Grade 5, and 7% had Grade 1. The classic form occurred in 83% of patients. Nerve conduction evaluations revealed acute demyelinating inflammatory polyneuropathy (51%), acute motor axonal neuropathy (17%), acute sensory-motor neuropathy (15%), and indeterminate forms (17%). Four patients were seropositive for DENV. There was no laboratory detection of ZIKV or CHIKV infection. Ninety percent of patients received human immunoglobulin. Intensive care unit admission occurred in 17.1% of the patients, and mechanical ventilation was used in 14.6%. One patient died of Bickerstaff's encephalitis. Most patients showed an improvement in disability at 10 weeks of follow-up. CONCLUSIONS: GBS in the Federal District showed a variable clinical spectrum, and it was possible to detect recent exposure to DENV.


Subject(s)
Arboviruses , Guillain-Barre Syndrome , Zika Virus Infection , Zika Virus , Adult , Female , Guillain-Barre Syndrome/complications , Guillain-Barre Syndrome/epidemiology , Guillain-Barre Syndrome/therapy , Humans , Male , Tertiary Care Centers , Zika Virus Infection/complications , Zika Virus Infection/diagnosis , Zika Virus Infection/epidemiology
14.
BMJ Glob Health ; 7(4)2022 Apr.
Article in English | MEDLINE | ID: mdl-35428678

ABSTRACT

INTRODUCTION: Arthropod-borne viruses (arboviruses) are of notable public health importance worldwide, owing to their potential to cause explosive outbreaks and induce debilitating and potentially life-threatening disease manifestations. This systematic review and meta-analysis aims to assess the relationship between markers of socioeconomic position (SEP) and infection due to arboviruses with mosquito vectors. METHODS: We conducted a systematic search on PubMed, Embase, and LILACS databases to identify studies published between 1980 and 2020 that measured the association of SEP markers with arbovirus infection. We included observational studies without geographic location or age restrictions. We excluded studies from grey literature, reviews and ecological studies. Study findings were extracted and summarised, and pooled estimates were obtained using random-effects meta-analyses. RESULTS: We identified 36 observational studies using data pertaining to 106 524 study participants in 23 geographic locations that empirically examined the relationship between socioeconomic factors and infections caused by seven arboviruses (dengue, chikungunya, Japanese encephalitis, Rift Valley fever, Sindbis, West Nile and Zika viruses). While results were varied, descriptive synthesis pointed to a higher risk of arbovirus infection associated with markers of lower SEP, including lower education, income poverty, low healthcare coverage, poor housing materials, interrupted water supply, marital status (married, divorced or widowed), non-white ethnicities and migration status. Pooled crude estimates indicated an increased risk of arboviral infection associated with lower education (risk ratio, RR 1.5 95% CI 1.3 to 1.9); I2=83.1%), interruption of water supply (RR 1.2; 95% CI 1.1 to 1.3; I2=0.0%) and having been married (RR 1.5 95% CI 1.1 to 2.1; I2=85.2%). CONCLUSION: Evidence from this systematic review suggests that lower SEP increases the risk of acquiring arboviral infection; however, there was large heterogeneity across studies. Further studies are required to delineate the relationship between specific individual, household and community-level SEP indicators and arbovirus infection risks to help inform targeted public health interventions. PROSPERO REGISTRATION NUMBER: CRD42019158572.


Subject(s)
Arbovirus Infections , Arboviruses , Zika Virus Infection , Zika Virus , Animals , Arbovirus Infections/epidemiology , Humans , Mosquito Vectors , Socioeconomic Factors
15.
Chaos ; 32(4): 041105, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35489839

ABSTRACT

Over the last decade, the release of Wolbachia-infected Aedes aegypti into the natural habitat of this mosquito species has become the most sustainable and long-lasting technique to prevent and control vector-borne diseases, such as dengue, zika, or chikungunya. However, the limited resources to generate such mosquitoes and their effective distribution in large areas dominated by the Aedes aegypti vector represent a challenge for policymakers. Here, we introduce a mathematical framework for the spread of dengue in which competition between wild and Wolbachia-infected mosquitoes, the cross-contagion patterns between humans and vectors, the heterogeneous distribution of the human population in different areas, and the mobility flows between them are combined. Our framework allows us to identify the most effective areas for the release of Wolbachia-infected mosquitoes to achieve a large decrease in the global dengue prevalence.


Subject(s)
Aedes/microbiology , Chikungunya Fever/prevention & control , Dengue/prevention & control , Mosquito Vectors/microbiology , Wolbachia/physiology , Zika Virus Infection/prevention & control , Animals , Chikungunya Fever/epidemiology , Chikungunya Fever/transmission , Dengue/epidemiology , Dengue/transmission , Humans , Mosquito Control/economics , Wolbachia/growth & development , Zika Virus Infection/epidemiology , Zika Virus Infection/transmission
16.
Int J Infect Dis ; 120: 201-204, 2022 Apr 22.
Article in English | MEDLINE | ID: mdl-35470025

ABSTRACT

OBJECTIVES: To describe the differences in clinical presentation and relative disease burden of congenital Zika syndrome (CZS)-associated microcephaly at 2 large hospitals in Salvador, Brazil that serve patients of different socioeconomic status (SES). METHODS: Clinical and serologic data were collected prospectively from pregnant women and their infants, who delivered at 2 study centers during the 2015-2016 Zika virus (ZIKV) epidemic in Salvador, Brazil. RESULTS: Pregnant women from Salvador, Brazil delivering in a low SES hospital had 3 times higher ZIKV exposure rate than women at a high SES hospital. However, different SES hospitals had similar prevalence of infants with CZS-associated microcephaly (10% vs 6%, p = 0.16) after controlling for ZIKV exposure in their mothers. CONCLUSIONS: Our study supports the positive association between low SES, high maternal ZIKV exposure, and high rates of CZS-associated microcephaly.

17.
Antiviral Res ; 202: 105313, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35367280

ABSTRACT

After decades of being considered non-pathogenic, Zika virus (ZIKV) emerged as an important threat to human health during the epidemic of 2015-2016. ZIKV infections are usually asymptomatic, but can cause Guillain-Barré syndrome in adults and microcephaly in newborns. As there are currently no approved antiviral drugs against ZIKV, we tested anti-ZIKV activity of compounds from the NIH Clinical Collection for which we previously showed antiviral activity against the related dengue virus. One of the top hits from the screen was lacidipine, a 1,4-dihydropyridine calcium antagonist that is approved as an antihypertensive drug. Our data show that lacidipine is antiviral against ZIKV (strain H/PF/2013) in both Vero cells and induced pluripotent stem cell (iPSC)-derived human neural progenitor cells with IC50 values of 3.0 µM and <50 nM, respectively. The antiviral effect was also observed against four other ZIKV strains from the African and Asian lineages. Time-of-addition and replicon assays indicated that lacidipine acts at the post-entry stage of the viral replication cycle, inhibiting viral genome replication. Lacidipine altered the subcellular distribution of free cholesterol and neutral lipids, suggesting that the antiviral effect of lacidipine is mediated by altered trafficking of lipids. Together, these results identify lacidipine as a novel inhibitor of ZIKV replication that likely disturbs trafficking of lipids needed for replication organelle formation.

18.
J Virol ; 96(9): e0033322, 2022 May 11.
Article in English | MEDLINE | ID: mdl-35412344

ABSTRACT

Vertical transmission of Zika virus (ZIKV) leads with high frequency to congenital ZIKV syndrome (CZS), whose worst outcome is microcephaly. However, the mechanisms of congenital ZIKV neurodevelopmental pathologies, including direct cytotoxicity to neural progenitor cells (NPC), placental insufficiency, and immune responses, remain incompletely understood. At the cellular level, microcephaly typically results from death or insufficient proliferation of NPC or cortical neurons. NPC replicate fast, requiring efficient DNA damage responses to ensure genome stability. Like congenital ZIKV infection, mutations in the polynucleotide 5'-kinase 3'-phosphatase (PNKP) gene, which encodes a critical DNA damage repair enzyme, result in recessive syndromes often characterized by congenital microcephaly with seizures (MCSZ). We thus tested whether there were any links between ZIKV and PNKP. Here, we show that two PNKP phosphatase inhibitors or PNKP knockout inhibited ZIKV replication. PNKP relocalized from the nucleus to the cytoplasm in infected cells, colocalizing with the marker of ZIKV replication factories (RF) NS1 and resulting in functional nuclear PNKP depletion. Although infected NPC accumulated DNA damage, they failed to activate the DNA damage checkpoint kinases Chk1 and Chk2. ZIKV also induced activation of cytoplasmic CycA/CDK1 complexes, which trigger unscheduled mitotic entry. Inhibition of CDK1 activity inhibited ZIKV replication and the formation of RF, supporting a role of cytoplasmic CycA/CDK1 in RF morphogenesis. In brief, ZIKV infection induces mitotic catastrophe resulting from unscheduled mitotic entry in the presence of DNA damage. PNKP and CycA/CDK1 are thus host factors participating in ZIKV replication in NPC, and pathogenesis to neural progenitor cells. IMPORTANCE The 2015-2017 Zika virus (ZIKV) outbreak in Brazil and subsequent international epidemic revealed the strong association between ZIKV infection and congenital malformations, mostly neurodevelopmental defects up to microcephaly. The scale and global expansion of the epidemic, the new ZIKV outbreaks (Kerala state, India, 2021), and the potential burden of future ones pose a serious ongoing risk. However, the cellular and molecular mechanisms resulting in microcephaly remain incompletely understood. Here, we show that ZIKV infection of neuronal progenitor cells results in cytoplasmic sequestration of an essential DNA repair protein itself associated with microcephaly, with the consequent accumulation of DNA damage, together with an unscheduled activation of cytoplasmic CDK1/Cyclin A complexes in the presence of DNA damage. These alterations result in mitotic catastrophe of neuronal progenitors, which would lead to a depletion of cortical neurons during development.

19.
Sex Reprod Healthc ; 32: 100722, 2022 Mar 31.
Article in English | MEDLINE | ID: mdl-35381437

ABSTRACT

BACKGROUND: In 2016, a Public Health Emergency of International Concern (PHEIC) was declared in response to the rise of microcephaly cases among newborns in Northeastern Brazil. A common reactionary measure by public health authorities was to recommend women postpone pregnancy to avoid the possible perinatal transmission of Zika virus (ZIKV). METHODS: The purpose of this study was to assess how women in Fortaleza, Brazil conceptualize pregnancy; experience facilitators and barriers to pregnancy avoidance; perceive the authorities' recommendation to postpone pregnancy due to the ZIKV outbreak; and recall their experiences during the ZIKV epidemic. Qualitative methods, specifically a Rapid Anthropological Assessment (RAA), were utilized in this study. Data collection included semi-structured interviews, triangulated with observations and informal interviews with community members. RESULTS: The sample included 35 women (18-39 years old) who exclusively utilized the national public health care system. Findings indicated that all participants perceived the ZIKV pregnancy-postponement recommendation to be counter-cultural to Brazilian social norms. Overall women's self-perceived agency to prevent pregnancy was low due to social expectations and lack of trust for contraceptives. ZIKV prevention was not seen as a reason to utilize contraceptives. Interestingly, only women who self-perceived as more affluent were willing to attempt pregnancy prevention for educational, occupational, or financial opportunity. CONCLUSION: Pregnancy postponement as a response to a ZIKV epidemic ignores gaps in reproductive agency and defies social norms, making it unrealistic and counter-cultural. Future ZIKV health recommendations must be culturally aligned with the population, and address barriers and motivators for family planning.

20.
Vector Borne Zoonotic Dis ; 22(4): 252-262, 2022 04.
Article in English | MEDLINE | ID: mdl-35404115

ABSTRACT

Background: Emergence of mosquito-borne arboviruses has caused significant public health burden. The life cycle of arboviruses comprises sylvatic and urban cycles, including a wildlife reservoir, a human host, and an arthropod vector. However, many questions remain on the sylvatic cycles of arboviruses. In this study, we investigate the prevalence of IgG antibodies to arboviruses of public health importance in African bats. Material and Methods: We collected dried blood spots from bats in Cameroon, Guinea, and the Democratic Republic of the Congo (DRC). To detect IgG antibodies to 10 antigens of 6 arboviruses (Dengue, Zika, West Nile, Usutu, Chikungunya, and O'nyong nyong viruses), we adapted a previously validated multiplex detection assay based on the Luminex technology. Results: We tested samples from 2579 bats, representing 1917 frugivorous and 641 insectivorous bats distributed in 7 families and 21 species. Overall, 218/2579 (8.45%) bat samples reacted with at least 1 of the 10 antigens tested. The highest prevalence was observed against Usutu virus with 2.3% (59/2579), followed by 1.9% (49/2579) and 1.35% (35/2579) for the Dengue virus serotypes 4 and 3, respectively. The global seroprevalence varied by country and collection site: 11% (151/1376) in Cameroon, 3.5% (20/565) in DRC, and 7.3% (47/638) in Guinea. The highest rates were observed in Hypsignathus monstrosus (17.9%), Rousettus aegyptiacus (16.4%), and Eidolon helvum (10.7%), and in species from the insectivorous Molossidae family (7.8-8.9%). Finally, we observed changes in seroprevalence over the year in E. helvum and H. monstrosus colonies, which could be related to population structure. Conclusion: On more than 2500 bat samples tested, we showed variable IgG seroprevalences against multiple arboviruses. Overall, the prevalence of IgG antibodies of 8.45% against arboviruses found in bats suggest that they could play a role in arboviruses cycles in the wild, in addition to other animal species.


Subject(s)
Arboviruses , Chiroptera , Zika Virus Infection , Zika Virus , Animals , Antibodies, Viral , Cameroon/epidemiology , Democratic Republic of the Congo/epidemiology , Guinea , Humans , Immunoglobulin G , Mosquito Vectors , Seroepidemiologic Studies , Zika Virus Infection/veterinary
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