Rafael Freitas de Oliveira França

Fundação Oswaldo Cruz

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Carlos Alexandre Antunes de Brito

Universidade Federal de Pernambuco

Celina Maria Turchi Martelli

Fundação Oswaldo Cruz

Lance Turtle

University of Liverpool

Cynthia Braga

Universidade Federal do Piauí

Benedito Antônio Lopes da Fonseca

Universidade de São Paulo

Ana da Silva Filipe

MRC University of Glasgow Centre for Virus Research

Jérôme Dimet

Centre Hospitalier Départemental Vendée

Nadia Ouamara

Centre Hospitalier Régional de Metz-Thionville

Massimo Gagliardi

University of Campania "Luigi Vanvitelli"

Stephanie T. Yerkovich

Menzies School of Health Research

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University of Oxford

966

Johns Hopkins Hospital

452

All India Institute of Medical Sciences Rishikesh

442

All India Institute of Medical Sciences Raipur

432

Inserm

332

Assistance Publique – Hôpitaux de Paris

201

Universidade de São Paulo

192

Fundação Oswaldo Cruz

186

Prince Charles Hospital

164

Université Paris Cité

152

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Cohort profile: Study on Zika virus infection in Brazil (ZIKABRA study)

PLoS ONE (2021)

Guilherme Amaral Calvet Edna Kara Sihem Landoulsi Ndema Habib Camila Bôtto-Menezes

Zika virus (ZIKV) has been detected in blood, urine, semen, cerebral spinal fluid, saliva, amniotic fluid, and breast milk. In most ZIKV infected individuals, the virus is detected in the blood to one week after the onset of symptoms and has been found to persist longer in urine and semen. To better understand virus dynamics, a prospective cohort study was conducted in Brazil to assess the presence and duration of ZIKV and related markers (viral RNA, antibodies, T cell response, and innate immunity) in blood, semen, saliva, urine, vaginal secretions/menstrual blood, rectal swab and sweat. The objective of the current manuscript is to describe the cohort, including an overview of the collected data and a description of the baseline characteristics of the participants. Men and women ≥ 18 years with acute illness and their symptomatic and asymptomatic household contacts with positive reverse transcriptase-polymerase chain reaction test for ZIKV in blood and/or urine were included. All participants were followed up for 12 months. From July 2017 to June 2019, a total of 786 participants (284 men, 502 women) were screened. Of these, 260 (33.1%) were enrolled in the study; index cases: 64 men (24.6%), 162 (62.3%) women; household contacts: 12 men (4.6%), 22 (8.5%) women. There was a statistically significant difference in age and sex between enrolled and not enrolled participants (p<0.005). Baseline sociodemographic and medical data were collected at enrollment from all participants. The median and interquartile range (IQR) age was 35 (IQR; 25.3, 43) for men and 36.5 years (IQR; 28, 47) for women. Following rash, which was one of the inclusion criteria for index cases, the most reported symptoms in the enrollment visit since the onset of the disease were fever, itching, arthralgia with or without edema, non-purulent conjunctivitis, headache, and myalgia. Ten hospitalizations were reported by eight patients (two patients were hospitalized twice) during follow up, after a median of 108 days following symptom onset (range 7 to 266 days) and with a median of 1.5 days (range 1 to 20 days) of hospital stay. A total of 4,137 visits were performed, 223 (85.8%) participants have attended all visits and 37 (14.2%) patients were discontinued.

Interquartile range

Zika Virus

10.1371/journal.pone.0244981

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Citations (9)

Functional Analysis of the FOXO3 Gene on the Induction of Fetal Hemoglobin in K562 Cells

Blood (2018)

Flávia Peixoto Albuquerque Pedro L. França-Neto Rafael Freitas de Oliveira França Aderson da Silva Araújo Fernando Ferreira Costa

FOXO3

FOXO1

10.1182/blood-2018-99-111994

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Citations (0)

Supplementary Material for: Tumor Growth Rate to Predict the Outcome of Patients with Neuroendocrine Tumors: Performance and Sources of Variability

Figshare (2020)

Clarisse Dromain Anders Sundin Pavan Najran Hector Vidal-Trueba Marco Dioguardi Burgio

Introduction: Tumor growth rate (TGR), percentage of change in tumor volume/month, has been previously identified as an early radiological biomarker for treatment monitoring in neuroendocrine tumor (NET) patients. We assessed the performance and reproducibility of TGR at 3 months (TGR_3m) as a predictor factor of progression-free survival (PFS), including the impact of imaging method and reader variability. Methods: Baseline and 3-month (±1 month) CT/MRI images from patients with advanced, grade 1–2 NETs were retrospectively reviewed by 2 readers. Influence of number of targets, tumor burden, and location of lesion on the performance of TGR_3m to predict PFS was assessed by uni/multivariable Cox regression analysis. Agreement between readers was assessed by Lin’s concordance coefficient (LCC) and kappa coefficient (KC). Results: A total of 790 lesions were measured in 222 patients. Median PFS was 22.9 months. On univariable analysis, number of lesions (≥4), tumor burden, and presence of liver metastases were significantly correlated with PFS. On multivariate analysis, ≥4 lesions (HR: 1.89 [95% CI: 1.01–3.57]), TGR_{3m ≥0.8%/month (HR: 4.01 [95% CI: 2.31–6.97]), and watch and wait correlated with shorter PFS. No correlation was found between TGR_3m and number of lesions (rho: −0.2; p value: 0.1930). No difference in mean TGR_3m across organs was shown (p value: 0.6). Concordance between readers was acceptable (LCC: 0.52 [95% CI: 0.38–0.65]; KC: 0.57, agreement: 81.55%). TGR_3m remained a significant prognostic factor when data from the second reader were employed (HR: 4.35 [95% CI: 2.44–7.79]; p value <0.001) regardless his expertise (HR: 1.21 [95% CI: 0.70–2.09]; p value: 0.493). Discussion/Conclusion: TGR_3m is a robust and early radiological biomarker able to predict PFS. It may be used to identify patients with advanced NETs who require closer radiological follow-up.}

10.6084/m9.figshare.13332716

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ZikaPLAN: addressing the knowledge gaps and working towards a research preparedness network in the Americas

Global Health Action (2019)

Annelies Wilder‐Smith Raman Preet Elizabeth B. Brickley Ricardo Arraes de Alencar Ximenes Demócrito de Barros Miranda-Filho

Zika Preparedness Latin American Network (ZikaPLAN) is a research consortium funded by the European Commission to address the research gaps in combating Zika and to establish a sustainable network with research capacity building in the Americas. Here we present a report on ZikaPLAN`s mid-term achievements since its initiation in October 2016 to June 2019, illustrating the research objectives of the 15 work packages ranging from virology, diagnostics, entomology and vector control, modelling to clinical cohort studies in pregnant women and neonates, as well as studies on the neurological complications of Zika infections in adolescents and adults. For example, the Neuroviruses Emerging in the Americas Study (NEAS) has set up more than 10 clinical sites in Colombia. Through the Butantan Phase 3 dengue vaccine trial, we have access to samples of 17,000 subjects in 14 different geographic locations in Brazil. To address the lack of access to clinical samples for diagnostic evaluation, ZikaPLAN set up a network of quality sites with access to well-characterized clinical specimens and capacity for independent evaluations. The International Committee for Congenital Anomaly Surveillance Tools was formed with global representation from regional networks conducting birth defects surveillance. We have collated a comprehensive inventory of resources and tools for birth defects surveillance, and developed an App for low resource regions facilitating the coding and description of all major externally visible congenital anomalies including congenital Zika syndrome. Research Capacity Network (REDe) is a shared and open resource centre where researchers and health workers can access tools, resources and support, enabling better and more research in the region. Addressing the gap in research capacity in LMICs is pivotal in ensuring broad-based systems to be prepared for the next outbreak. Our shared and open research space through REDe will be used to maximize the transfer of research into practice by summarizing the research output and by hosting the tools, resources, guidance and recommendations generated by these studies. Leveraging on the research from this consortium, we are working towards a research preparedness network.

Zika Virus

Preparedness

Capacity Building

Neglected Tropical Diseases

Global Health

10.1080/16549716.2019.1666566

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Citations (19)

Zika Virus Infection Alters the Circadian Clock Expression in Human Neuronal Monolayer and Neurosphere Cultures

Cellular and Molecular Neurobiology (2023)

Thaíse Yasmine Vasconcelos de Lima Cavalcanti Morganna Costa Lima Paula Bargi‐Souza Rafael Freitas de Oliveira França Rodrigo A. Peliciari‐Garcia

Neurosphere

10.1007/s10571-023-01445-2

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Citations (2)

The P-MAPA Immunomodulator Partially Prevents Apoptosis Induced by Zika Virus Infection in THP-1 Cells

Current Pharmaceutical Biotechnology (2020)

Morganna Costa Lima Elisa de Almeida Neves Azevedo Clarice Neuenschwander Lins de Morais Larissa Isabela Oliveira de Souza Bruno M. Carvalho

Background: Zika virus is an emerging arbovirus of global importance. ZIKV infection is associated with a range of neurological complications such as the Congenital Zika Syndrome and Guillain Barré Syndrome. Despite the magnitude of recent outbreaks, there is no specific therapy to prevent or to alleviate disease pathology. Objective: To investigate the role of P-MAPA immunomodulator in Zika-infected THP-1 cells. Methods: THP-1 cells were subjected to Zika virus infection (Multiplicity of Infection = 0.5) followed by treatment with P-MAPA for until 96 hours post-infection. After that, the cell death was analyzed by annexin + / PI + and caspase 3/ 7 + staining by flow cytometry. In addition, virus replication and cell proliferation were accessed by RT-qPCR and Ki67 staining, respectively. Results: We demonstrate that P-MAPA in vitro treatment significantly reduces Zika virus-induced cell death and caspase-3/7 activation on THP-1 infected cells, albeit it has no role in virus replication and cell proliferation. Conclusions: Our study reveals that P-MAPA seems to be a satisfactory alternative to inhibit the effects of Zika virus infection in mammalian cells.

Zika Virus

Multiplicity of infection

Vero cell

Microcephaly

10.2174/1389201021666200602140005

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Citations (1)

Guillain-Barré syndrome during the Zika virus outbreak in Northeast Brazil: An observational cohort study

Journal of the Neurological Sciences (2020)

Sonja E. Leonhard Susan K. Halstead Suzannah Lant Maria de Fátima Pessoa Militão de Albuquerque Carlos Alexandre Antunes de Brito

ObjectiveTo determine the clinical phenotype of Guillain-Barré syndrome (GBS) after Zika virus (ZIKV) infection, the anti-glycolipid antibody signature, and the role of other circulating arthropod-borne viruses, we describe a cohort of GBS patients identified during ZIKV and chikungunya virus (CHIKV) outbreaks in Northeast Brazil.MethodsWe prospectively recruited GBS patients from a regional neurology center in Northeast Brazil between December 2014 and February 2017. Serum and CSF were tested for ZIKV, CHIKV, and dengue virus (DENV), by RT-PCR and antibodies, and serum was tested for GBS-associated antibodies to glycolipids.ResultsSeventy-one patients were identified. Forty-eight (68%) had laboratory evidence of a recent arbovirus infection; 25 (52%) ZIKV, 8 (17%) CHIKV, 1 (2%) DENV, and 14 (29%) ZIKV and CHIKV. Most patients with a recent arbovirus infection had motor and sensory symptoms (72%), a demyelinating electrophysiological subtype (67%) and a facial palsy (58%). Patients with a recent infection with ZIKV and CHIKV had a longer hospital admission and more frequent mechanical ventilation compared to the other patients. No specific anti-glycolipid antibody signature was identified in association with arbovirus infection, although significant antibody titres to GM1, GalC, LM1, and GalNAc-GD1a were found infrequently.ConclusionA large proportion of cases had laboratory evidence of a recent infection with ZIKV or CHIKV, and recent infection with both viruses was found in almost one third of patients. Most patients with a recent arbovirus infection had a sensorimotor, demyelinating GBS. We did not find a specific anti-glycolipid antibody signature in association with arbovirus-related GBS.

Zika Virus

10.1016/j.jns.2020.117272

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Citations (30)

Evidence of Zika Virus Reinfection by Genome Diversity and Antibody Response Analysis, Brazil

Emerging infectious diseases (2024)

Márcia da Costa Castilho Ana María Bispo de Filippis Laís Ceschini Machado Thaise Yasmine Vasconcelos de Lima Calvanti Morganna Costa Lima

Abstract We generated 238 Zika virus (ZIKV) genomes from 135 persons in Brazil who had samples collected over 1 year to evaluate virus persistence. Phylogenetic inference clustered the genomes together with previously reported ZIKV strains from northern Brazil, showing that ZIKV has been remained relatively stable over time. Temporal phylogenetic analysis revealed limited within-host diversity among most ZIKV-persistent infected associated samples. However, we detected unusual virus temporal diversity from >5 persons, uncovering the existence of divergent genomes within the same patient. All those patients showed an increase in neutralizing antibody levels, followed by a decline at the convalescent phase of ZIKV infection. Of interest, in 3 of those patients, titers of neutralizing antibodies increased again after 6 months of ZIKV infection, concomitantly with real-time reverse transcription PCR re-positivity, supporting ZIKV reinfection events. Altogether, our findings provide evidence for the existence of ZIKV reinfection events.

Zika Virus

10.3201/eid3002.230122

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Citations (3)

Neurological manifestations of COVID-19 in adults and children

Brain (2022)

Sung‐Min Cho Nicole White Lavienraj Premraj Denise Battaglini Jonathon P. Fanning

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age.

Anosmia

Dysgeusia

myalgia

Stroke

10.1093/brain/awac332

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Citations (68)

Can urbanisation influence alcohol consumption by Indigenous groups? A brief analysis of Brazilian data

Drug and Alcohol Review (2021)

Thiago R. do Carmo Lucas Gomes Santos Alécio Vinícius Sá Gomes e Farias Mariana Peixoto de Lima Cavalcanti Gabriel dos Santos Dias

10.1111/dar.13420

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