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1.
Nat Commun ; 12(1): 2530, 2021 05 05.
Article in English | MEDLINE | ID: mdl-33953197

ABSTRACT

Flaviviruses use a ~70 nucleotide stem-loop structure called stem-loop A (SLA) at the 5' end of the RNA genome as a promoter for RNA synthesis. Flaviviral polymerase NS5 specifically recognizes SLA to initiate RNA synthesis and methylate the 5' guanosine cap. We report the crystal structures of dengue (DENV) and Zika virus (ZIKV) SLAs. DENV and ZIKV SLAs differ in the relative orientations of their top stem-loop helices to bottom stems, but both form an intermolecular three-way junction with a neighboring SLA molecule. To understand how NS5 engages SLA, we determined the SLA-binding site on NS5 and modeled the NS5-SLA complex of DENV and ZIKV. Our results show that the gross conformational differences seen in DENV and ZIKV SLAs can be compensated by the differences in the domain arrangements in DENV and ZIKV NS5s. We describe two binding modes of SLA and NS5 and propose an SLA-mediated RNA synthesis mechanism.

2.
Rev Soc Bras Med Trop ; 54: e0891 2020, 2021.
Article in English | MEDLINE | ID: mdl-33950132

ABSTRACT

INTRODUCTION: Cerebrospinal fluid analysis contributes to the diagnosis and neuropathogenesis of neuroinvasive arboviruses. Neurological complications caused by dengue, Zika, and chikungunya infections have high clinical relevance because of their high potential to cause death or neurological deficits. We aimed to evaluate the use of cerebrospinal fluid assays for diagnostic support in neurological disorders associated with dengue, chikungunya, and Zika infections. METHODS: A systematic review was carried out by searching the electronic databases LILACS, PubMed, Scopus, and Embase for articles written in English, Portuguese, or Spanish in the last 19 years. Published studies were reviewed using the terms "dengue," "Zika", "chikungunya", alone or in combination with "cerebrospinal fluid" in the period from 2000 to 2019. RESULTS: A total of 98,060 studies were identified; of these, 1.1% (1,041 studies, 58,478 cases) used cerebrospinal fluid assays for neurological investigations. The most frequent neurological disorders included encephalitis (41.4%), congenital syndromes (17%), and microcephaly associated with Zika virus infections (8.9%). Neuroinvasive disorders were confirmed in 8.03% of 58,478 cases by specific cerebrospinal fluid analyses. The main methods used were IgM-specific antibodies (66%) and reverse transcription-polymerase chain reaction (10%). The largest number of scientific papers (29%) originated from Brazil, followed by India (18.4%) and the United States (14.4%). CONCLUSIONS: Although cerebrospinal fluid analysis is of great importance for increasing neurological diagnostic accuracy and contributes to the early diagnosis of neuroinvasive dengue, chikungunya, and Zika infections, it is underused in routine laboratory investigations worldwide.

3.
PLoS Negl Trop Dis ; 15(5): e0009397, 2021 May 05.
Article in English | MEDLINE | ID: mdl-33951038

ABSTRACT

The world's most important mosquito vector of viruses, Aedes aegypti, is found around the world in tropical, subtropical and even some temperate locations. While climate change may limit populations of Ae. aegypti in some regions, increasing temperatures will likely expand its territory thus increasing risk of human exposure to arboviruses in places like Europe, Northern Australia and North America, among many others. Most studies of Ae. aegypti biology and virus transmission focus on locations with high endemicity or severe outbreaks of human amplified urban arboviruses, such as dengue, Zika, and chikungunya viruses, but rarely on areas at the margins of endemicity. The objective in this study is to explore previously published global patterns in the environmental suitability for Ae. aegypti and dengue virus to reveal deviations in the probability of the vector and human disease occurring. We developed a map showing one end of the gradient being higher suitability of Ae. aegypti with low suitability of dengue and the other end of the spectrum being equal and higher environmental suitability for both Ae. aegypti and dengue. The regions of the world with Ae. aegypti environmental suitability and no endemic dengue transmission exhibits a phenomenon we term 'aegyptism without arbovirus'. We then tested what environmental and socioeconomic variables influence this deviation map revealing a significant association with human population density, suggesting that locations with lower human population density were more likely to have a higher probability of aegyptism without arbovirus. Characterizing regions of the world with established populations of Ae. aegypti but little to no autochthonous transmission of human-amplified arboviruses is an important step in understanding and achieving aegyptism without arbovirus.

4.
Analyst ; 146(9): 2928-2935, 2021 May 04.
Article in English | MEDLINE | ID: mdl-33949387

ABSTRACT

Enhanced electrochemiluminescence (ECL) signals of CdS quantum dots capped with 3-mercaptopropionic acid (MPA@CdS QDs) have been observed after using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) to activate the carboxyl groups. The generated ECL signals are strong enough that their images can be captured using a Huawei mobile phone. A possible mechanism for the generation of enhanced ECL signals has been proposed. Then, a sandwich immunosensor platform for detecting Zika virus (ZIKV) was fabricated with silica microspheres as the carrier and MPA@CdS QDs as ECL signal labels. Due to the dual signal amplification of EDC activation and microsphere enrichment, good linearity from 1.0 fg mL-1 to 1.0 ng mL-1 was exhibited by the QD-based ECL immunosensor for ZIKV detection. The detection limit was 0.3 fg mL-1.

5.
Birth Defects Res ; 2021 May 05.
Article in English | MEDLINE | ID: mdl-33949803

ABSTRACT

BACKGROUND: Surveillance programs in low- and middle-income countries (LMICs) have difficulty in obtaining accurate information about congenital anomalies. METHODS: As part of the ZikaPLAN project, an International Committee developed an app for the description and coding of congenital anomalies that are externally visible at birth, for use in low resource settings. The "basic" version of the app was designed for a basic clinical setting and to overcome language and terminology barriers by providing diagrams and photos, sourced mainly from international Birth Defects Atlases. The "surveillance" version additionally allows recording of limited pseudonymized data relevant to diagnosis, which can be uploaded to a secure server, and downloaded by the surveillance program data center. RESULTS: The app contains 98 (88 major and 10 minor) externally visible anomalies and 12 syndromes (including congenital Zika syndrome), with definitions and International Classification of Disease v10 -based code. It also contains newborn examination videos and links to further resources. The user taps a region of the body, then selects among a range of images to choose the congenital anomaly that best resembles what they observe, with guidance regarding similar congenital anomalies. The "basic" version of the app has been reviewed by experts and made available on the Apple and Google Play stores. Since its launch in November 2019, it has been downloaded in 39 countries. The "surveillance" version is currently being field-tested. CONCLUSION: The global birth defects app is a mHealth tool that can help in developing congenital anomaly surveillance in low resource settings to support prevention and care.

6.
Am J Prev Med ; 2021 May 02.
Article in English | MEDLINE | ID: mdl-33952412

ABSTRACT

INTRODUCTION: Zika virus is primarily transmitted through mosquito bites. Because Zika virus infection during pregnancy can cause serious birth defects, reproductive-aged women need protection from Zika virus infection. This report describes Zika virus prevention behaviors among women aged 18-49 years and assesses whether pregnancy status and healthcare provider counseling increases Zika virus prevention behaviors. METHODS: A population-based cell phone survey of women aged 18-49 years living in Puerto Rico was conducted in July-November 2016. Data were analyzed in 2018-2019. Prevalence estimates and 95% CIs were calculated for Zika virus prevention behaviors. Adjusted prevalence ratios were estimated to examine the association of pregnancy status with healthcare provider counseling on Zika virus prevention behaviors, controlling for age, education, and health insurance status. RESULTS: Most women reported using screens on open doors/windows (87.7%) and eliminating standing water in/around their homes (92.3%). Other Zika virus prevention behaviors were less common (<33%). In adjusted analysis, pregnant women were more likely than women not at risk for unintended pregnancy to report using mosquito repellent every/most days (adjusted prevalence ratio=1.44, 95% CI=1.13, 1.85). Healthcare provider counseling was associated with receiving professional spraying/larvicide treatment (adjusted prevalence ratio=1.42, 95% CI=1.17, 1.74), sleeping under a bed net (adjusted prevalence ratio=2.37, 95% CI=1.33, 4.24), using mosquito repellent (adjusted prevalence ratio=1.57, 95% CI=1.40, 1.77), and wearing long sleeves/pants (adjusted prevalence ratio=1.32, 95% CI=1.12, 1.55). CONCLUSIONS: Receipt of healthcare provider counseling was more consistently associated with Zika virus prevention behaviors than pregnancy status. Healthcare provider counseling is an important strategy for increasing the uptake of Zika virus prevention behaviors among women aged 18-49 years.

7.
Jpn J Infect Dis ; 2021 Apr 30.
Article in English | MEDLINE | ID: mdl-33952765

ABSTRACT

Etiology of viral meningoencephalitis is frequently unidentified. Chikungunya virus (CHIKV) and Zika virus (ZIKV) have been known to affect the central nervous system, and should, therefore, be considered for diagnosis of meningoencephalitis since its outcome may be influenced by the etiologic agent, age and immunological condition of the patient. In this study we aimed to determine if CHIKV and ZIKV were the etiological agent of viral encephalitis in meningoencephalitis patients admitted to the main hospital of infectious disease in the city of Salvador, Brazil. From 1049 patients with neurological symptoms who were admitted to the hospital during the time of this study, 149 were enrolled and 20 (13.34%) tested positive for ZIKV (12%) or CHIKV (1.34%). No specific clinical manifestations were observed to be associated to the ZIKV or CHIKV infection. Determination of the etiology of meningitis' and encephalitis' causing agent is important for patient management and correct treatment.

8.
J R Soc Interface ; 18(178): 20210165, 2021 May.
Article in English | MEDLINE | ID: mdl-33947225

ABSTRACT

When a rare pathogen emerges to cause a pandemic, it is critical to understand its dynamics and the impact of mitigation measures. We use experimental data to parametrize a temperature-dependent model of Zika virus (ZIKV) transmission dynamics and analyse the effects of temperature variability and control-related parameters on the basic reproduction number (R0) and the final epidemic size of ZIKV. Sensitivity analyses show that these two metrics are largely driven by different parameters, with the exception of temperature, which is the dominant driver of epidemic dynamics in the models. Our R0 estimate has a single optimum temperature (≈30°C), comparable to other published results (≈29°C). However, the final epidemic size is maximized across a wider temperature range, from 24 to 36°C. The models indicate that ZIKV is highly sensitive to seasonal temperature variation. For example, although the model predicts that ZIKV transmission cannot occur at a constant temperature below 23°C (≈ average annual temperature of Rio de Janeiro, Brazil), the model predicts substantial epidemics for areas with a mean temperature of 20°C if there is seasonal variation of 10°C (≈ average annual temperature of Tampa, Florida). This suggests that the geographical range of ZIKV is wider than indicated from static R0 models, underscoring the importance of climate dynamics and variation in the context of broader climate change on emerging infectious diseases.

9.
Sci Rep ; 11(1): 9634, 2021 May 05.
Article in English | MEDLINE | ID: mdl-33953258

ABSTRACT

Zika virus (ZIKV) and dengue virus (DENV) are antigenically related mosquito-borne flaviviruses. ZIKV is becoming increasingly prevalent in DENV-endemic regions, raising the possibility that pre-existing immunity to one virus could modulate the response to a heterologous virus, although whether this would be beneficial or detrimental is unclear. Here, we analyzed sera from residents of a DENV-endemic region of Thailand to determine the prevalence of DENV-elicited antibodies capable of cross-neutralizing ZIKV. Sixty-one participants who were asymptomatic and unselected for viral serostatus were enrolled. Among them, 52 and 51 were seropositive for IgG antibody against DENV or ZIKV E proteins (ELISA assay), respectively. Notably, 44.23% (23/52) of DENV seropositive participants had serological evidence of multiple exposures to DENV, and these subjects had strikingly higher titers and broader reactivities of neutralizing antibodies (NAbs) against ZIKV and DENV heterotypes compared with participants with serological evidence of a single DENV infection (25/52, 48.1%). In total, 17 of the 61 participants (27.9%) had NAbs against ZIKV and all four DENV serotypes, and an additional 9 (14.8%) had NAbs against ZIKV and DENV1, 2, and 3. NAbs against DENV2 were the most prevalent (44/61, 72.1%) followed by DENV3 (38/61, 62.3%) and DENV1 (36/61, 59.0%). Of note, anti-ZIKV NAbs were more prevalent than anti-DENV4 NAbs (27/61, 44.3% and 21/61, 34.4%, respectively). Primary ZIKV infection was detected in two participants, confirming that ZIKV co-circulates in this region. Thus, residents of DENV-endemic regions with repeated exposure to DENV have higher titers of NAbs against ZIKV than individuals with only a single DENV exposure.

10.
Front Cell Infect Microbiol ; 11: 575346, 2021.
Article in English | MEDLINE | ID: mdl-33954117

ABSTRACT

Flaviviruses, as critically important pathogens, are still major public health problems all over the world. For instance, the evolution of ZIKV led to large-scale outbreaks in the Yap island in 2007. DENV was considered by the World Health Organization (WHO) as one of the 10 threats to global health in 2019. Enveloped viruses hijack a variety of host factors to complete its replication cycle. Phosphatidylserine (PS) receptor, AXL, is considered to be a candidate receptor for flavivirus invasion. In this review, we discuss the molecular structure of ZIKV and DENV, and how they interact with AXL to successfully invade host cells. A more comprehensive understanding of the molecular mechanisms of flavivirus-AXL interaction will provide crucial insights into the virus infection process and the development of anti-flavivirus therapeutics.

11.
J Neuroimmunol ; 356: 577590, 2021 Apr 28.
Article in English | MEDLINE | ID: mdl-33957540

ABSTRACT

A 50-years old male presented with quadriplegia and paresthesia and was diagnosed as Guillain-Barré syndrome (GBS). He was found positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) six weeks prior to the onset of weakness. GBS disability score was 4. Electrophysiology showed acute inflammatory demyelinating polyradiculopathy. Anti-SARS-CoV-2 IgG was found positive. Immunological tests for Campylobacter jejuni, Zika virus, Hepatitis E virus, Herpes Simplex virus, Haemophilus influanzae and Mycoplasma pneumoniae were negative. Patient received standard dose of intravenous immunoglobulin and after six months had almost complete recovery of muscle power. This case represents possible association of SARS-CoV-2 infection and GBS with good clinical outcome.

12.
Scientometrics ; : 1-16, 2021 Apr 26.
Article in English | MEDLINE | ID: mdl-33935332

ABSTRACT

During the previous Ebola and Zika outbreaks, researchers shared their data, allowing many published epidemiological studies to be produced only from open research data, to speed up investigations and control of these infections. This study aims to evaluate the dissemination of the COVID-19 research data underlying scientific publications. Analysis of COVID-19 publications from December 1, 2019, to April 30, 2020, was conducted through the PubMed Central repository to evaluate the research data available through its publication as supplementary material or deposited in repositories. The PubMed Central search generated 5,905 records, of which 804 papers included complementary research data, especially as supplementary material (77.4%). The most productive journals were The New England Journal of Medicine, The Lancet and The Lancet Infectious Diseases, the most frequent keyword was pneumonia, and the most used repositories were GitHub and GenBank. An expected growth in the number of published articles following the course of the pandemics is confirmed in this work, while the underlying research data are only 13.6%. It can be deduced that data sharing is not a common practice, even in health emergencies, such as the present one. High-impact generalist journals have accounted for a large share of global publishing. The topics most often covered are related to epidemiological and public health concepts, genetics, virology and respiratory diseases, such as pneumonia. However, it is essential to interpret these data with caution following the evolution of publications and their funding in the coming months.

13.
Am J Trop Med Hyg ; 2021 May 03.
Article in English | MEDLINE | ID: mdl-33939632

ABSTRACT

The presence of Zika virus (ZIKV) in Indonesia has been recognized since the 1970s, but its transmission dynamics there have been poorly understood. To understand more fully the geographic distribution and burden of ZIKV disease, we performed retrospective serological tests on specimens collected from asymptomatic children age 5 to 9 years old living at 30 sites in 14 provinces. Of 870 serum samples tested, 9.2% were found to be positive for anti-ZIKV antibodies, as confirmed by plaque reduction neutralization assays. This was the same overall prevalence reported previously for 1- to 4-year-old children collected at the same sites at the same time. Together with geographic differences in seroprevalence between the age groups, these data suggest that, although ZIKV might be endemic in Indonesia, its occurrence has been focal and episodic.

14.
J Med Entomol ; 2021 May 03.
Article in English | MEDLINE | ID: mdl-33939805

ABSTRACT

Diseases caused by flaviviruses are a major public health burden across the world. In the past decades, South America has suffered dengue epidemics, the re-emergence of yellow fever and St. Louis encephalitis viruses, and the introduction of West Nile and Zika viruses. Many insect-specific flaviviruses (ISFs) that cannot replicate in vertebrate cells have recently been described. In this study, we analyzed field-collected mosquito samples from six different ecoregions of Argentina to detect flaviviruses. We did not find any RNA belonging to pathogenic flaviviruses or ISFs in adults or immature stages. However, flaviviral-like DNA similar to flavivirus NS5 region was detected in 83-100% of Aedes aegypti (L.). Despite being previously described as an ancient element in the Ae. aegypti genome, the flaviviral-like DNA sequence was not detected in all Ae. aegypti samples and sequences obtained did not form a monophyletic group, possibly reflecting the genetic diversity of mosquito populations in Argentina.

15.
Glia ; 2021 May 04.
Article in English | MEDLINE | ID: mdl-33942402

ABSTRACT

Some children with proven intrauterine Zika virus (ZIKV) infection who were born asymptomatic subsequently manifested neurodevelopmental delays, pointing to impairment of development perinatally and postnatally. To model this, we infected postnatal day (P) 5-6 (equivalent to the perinatal period in humans) susceptible mice with a mammalian cell-propagated ZIKV clinical isolate from the Brazilian outbreak in 2015. All infected mice appeared normal up to 4 days post-intraperitoneal inoculation (dpi), but rapidly developed severe clinical signs at 5-6 dpi. All nervous tissue examined at 5/6 dpi appeared grossly normal. However, anti-ZIKV positive cells were observed in the optic nerve, brain, and spinal cord; predominantly in white matter. Co-labeling with cell type specific markers demonstrated oligodendrocytes and astrocytes support productive infection. Rarely, ZIKV positive neurons were observed. In spinal cord white matter, which we examined in detail, apoptotic cells were evident; the density of oligodendrocytes was significantly reduced; and there was localized microglial reactivity including expression of the NLRP3 inflammasome. Together, our observations demonstrate that a clinically relevant ZIKV isolate can directly impact oligodendrocytes. As primary oligodendrocyte cell death can lead later to secondary autoimmune demyelination, our observations may help explain neurodevelopmental delays in infants appearing asymptomatic at birth and commend lifetime surveillance.

16.
Med Sci Monit ; 27: e932915, 2021 May 04.
Article in English | MEDLINE | ID: mdl-33942804

ABSTRACT

There have been rapid developments in safe and effective mRNA vaccines for zoonotic infections in the past year. Years of research have made these advances possible, leading to in vitro-transcribed (IVT) mRNA expressing therapeutic proteins. There are several advantages of mRNA vaccines that include their low-cost manufacturing process, large-scale and rapid production, and the ability to modify the vaccines in response to emerging infections and viral variants. The COVID-19 pandemic and successful vaccination programs for SARS-CoV-2 have highlighted the advantages of mRNA vaccines. Also, mRNA vaccines are in development for several other potential pandemic zoonotic infections, including Ebola virus, rabies virus, Zika virus, HIV-1, and influenza. There may also be hope for the control of pandemic avian influenza by the combination of improved and rapid viral genotyping and the rapid development and mass production of mRNA vaccines. This Editorial aims to present a brief overview of how mRNA vaccines may help control and future epidemic, pandemic, and endemic zoonotic virus infections.

17.
Article in English | MEDLINE | ID: mdl-33944623

ABSTRACT

A clinical and entomological investigation was performed to identify flavivirus infections in humans and mosquitoes in impoverished areas of Guerrero, a coastal state in southwestern Mexico. A total of 639 patients with acute febrile illness and 830 resting female mosquitoes in low-income communities of Guerrero in 2019 were tested for evidence of flavivirus infection. Sera were collected from all patients and screened at a dilution of 1:20 by plaque reduction neutralization test (PRNT) using dengue virus (DENV)2. A total of 431 (67.4%) patients were seropositive. Sera from a subset of seropositive patients (n = 263) were tested for flavivirus NS1 by enzyme-linked immunosorbent assay. Forty-eight (18.3%) sera contained viral antigen. All NS1-positive sera were titrated and further tested by PRNT using DENV-1 to -4, St. Louis encephalitis virus, West Nile virus, and Zika virus (ZIKV). Seven patients were seropositive for DENV-1, five patients were seropositive for DENV-2, one patient was seropositive for DENV-3, and two patients each were seropositive for DENV-4 and ZIKV. The remainder had secondary flavivirus infections or antibodies to an undetermined flavivirus. Comparative PRNTs were also performed on 60 randomly selected NS1-negative sera, identifying patients seropositive for DENV-2, DENV-3, and ZIKV. The entomological investigation yielded 736 Aedes aegypti and 94 Culex quinquefasciatus that were sorted into 183 pools and 20 pools, respectively. Mosquitoes were assayed for flavivirus RNA by RT-PCR and Sanger sequencing. DENV-2 RNA was detected in three pools of A. aegypti. In summary, we provide evidence for the concurrent circulation of all four DENVs and ZIKV in Guerrero, Mexico. The public health authorities reported no cases of DENV-3, DENV-4, and ZIKV in Guerrero in 2019 and thus, we provide evidence of under-reporting in the region.

18.
San Salvador; MINSAL; may. 03, 2021. 11 p. ilus, graf, tab, mapas.
Non-conventional in Spanish | LILACS, BISSAL | ID: biblio-1222335

ABSTRACT

Resumen de eventos de notificación hasta SE 16/2021. Alertas internacionales. Situación epidemiológica de dengue. Situación epidemiológica de zika y chikungunya. Infección respiratoria aguda. Neumonías. Situación mundial del 2019-nCov (OMS. Vigilancia centinela de influenza y otros virus respiratorios. Vigilancia centinela de rotavirus. Enfermedad diarreica aguda. Fiebre tifoidea


Summary of notification events up to SE 16/2021. International alerts. Epidemiological situation of dengue. Epidemiological situation of Zika and Chikungunya. Acute respiratory infection. Pneumonia Global situation 2019-nCov (WHO. Sentinel surveillance of influenza and other respiratory viruses. Sentinel surveillance for rotavirus. Acute diarrheal disease. Typhoid fever


Subject(s)
Epidemiology , Surveillance , Electronic Publications , Notification
19.
J Pediatr Urol ; 2021 Apr 18.
Article in English | MEDLINE | ID: mdl-33934997

ABSTRACT

INTRODUCTION: We have previously reported on neurogenic bladder dysfunction among Congenital Zika Vírus Syndrome (CZS) patients, but it is unknown how they will respond to treatment. OBJECTIVE: To assess whether children with neurological lower urinary tract dysfunction and CZS will respond to Standard therapies. METHODOLOGY: A prospective observational cohort study of children with CZS referred for urological assessment between 2016 and 2020 to our quaternary center in Brazil. Urological protocol included clinical history, urinalysis and culture, renal and bladder ultrasonography and urodynamic study. Patients were treated based on findings from the first evaluation, with oxybutynin chloride for overactive bladder and low bladder compliance, clean intermittent catheterization for ineffective bladder emptying, or dual therapy when both were observed. Urological outcomes were evaluated between the first and second visits considering patient's adherence. Outcomes measured included clinical, imaging, and urodynamic variables. Data was analyzed using the IBM SPSS 22 software. RESULTS: From the cohort of 90 patients, 56 completed the second urodynamic assessment and were included. One presented underactive bladder and 55 overactive bladder. Among these 55, 39 were adherent and 16 non-adherents to the prescribed treatment. Among the 39 adherents, 8 adhered regularly to oxybutynin and clean intermittent catheterization (CIC), 29 to oxybutynin alone, and two to catheterization alone. During follow-up, the number of patients with urinary tract infection and postvoid residual increased, but all other parameters had improved. Renal and bladder ultrasonography improved in 10, maximum bladder pressure decreased in 22 and maximum cystometric capacity and compliance increased in 14 patients. Sixteen patients did not adhere regularly to the prescribed treatment and although the number of patients with urinary tract infection reduced with antibiotic therapy, their bladder capacity and compliance did not improve during follow-up. DISCUSSION: Ultrasonographic and urodynamic improvements were observed after 10.8 ± 7.5 months of treatment, including one patient with ureterohydronephrosis that resolved. Adherence to CIC remains a challenge and reflected in the number of patients presenting urinary tract infection and postvoid residual. The immediate clinical relevance is the major study strength, given the previously uncharacterized therapy options for this patient population. The number of patients remains one of the study limitations, reducing our ability to perform more advanced statistical analyses. CONCLUSION: Patients with Zika-related neurological lower urinary tract dysfunction may benefit from conventional therapies. Results confirmed ultrasonographic and urodynamic improvements after treatment, although not statically significant. Adherence to treatment, specifically to CIC, remains a challenge.

20.
J Virol ; 2021 Mar 31.
Article in English | MEDLINE | ID: mdl-33789994

ABSTRACT

The mosquito-borne Zika virus (ZIKV) spread rapidly into regions where dengue virus (DENV) is endemic, and flavivirus cross-reactive T cell responses have been observed repeatedly in animal models and in humans. Pre-existing cellular immunity to DENV is thought to contribute to protection in subsequent ZIKV infection, but the epitope targets of cross-reactive T cell responses have not been comprehensively identified. Using human blood samples from the DENV-endemic regions of Nicaragua and Sri Lanka that were collected before the global spread of ZIKV in 2016, we employed an in vitro expansion strategy to map ZIKV T cell epitopes in ZIKV-unexposed, DENV-seropositive donors. We identified 93 epitopes across the ZIKV proteome, and we observed patterns of immunodominance that were dependent on antigen size and sequence identity to DENV. We confirmed the immunogenicity of these epitopes through a computational HLA binding analysis, and we showed that cross-reactive T cells specifically recognize ZIKV peptides homologous to DENV sequences. We also found that these CD4 responses were derived from the memory T cell compartment. These data have implications for understanding the dynamics of flavivirus-specific T cell immunity in endemic areas.ImportanceMultiple flaviviruses, including Zika (ZIKV) and the four serotypes of dengue (DENV) viruses, are prevalent in the same large tropical and equatorial areas inhabited by hundreds of millions of people. The interplay of DENV and ZIKV infection is especially relevant, as these two viruses are endemic in largely overlapping regions, have significant sequence similarity, and share the same arthropod vector. Here, we define the targets of pre-existing immunity to ZIKV in unexposed subjects collected in dengue-endemic areas. We demonstrate that pre-existing immunity to DENV could shape ZIKV-specific responses, and DENV-ZIKV cross-reactive T cells can be expanded by stimulation with ZIKV peptides. The issue of potential ZIKV and DENV cross-reactivity is of relevance for understanding patterns of natural immunity, as well as for the development of diagnostic tests and vaccines.

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