Other viruses


May, 2019

Islands as Hotspots for Emerging Mosquito-Borne Viruses: A One-Health Perspective


Authors: Mavian C, Dulcey M, Munoz O, Salemi M, Vittor AY, Capua I.

Published in: Viruses. 2019; 11(1):11

Abstract During the past ten years, an increasing number of arbovirus outbreaks have affected tropical islands worldwide. We examined the available literature in peer-reviewed journals, from the second half of the 20th century until 2018, with the aim of gathering an overall picture of the emergence of arboviruses in these islands. In addition, we included information on environmental and social drivers specific to island setting that can facilitate the emergence of outbreaks. Within the context of the One Health approach, our review highlights how the emergence of arboviruses in tropical islands is linked to the complex interplay between their unique ecological settings and to the recent changes in local and global sociodemographic patterns. We also advocate for greater coordination between stakeholders in developing novel prevention and mitigation approaches for an intractable problem.




May, 2019

Lipidomic analysis reveals serum alteration of plasmalogens in patients infected with ZIKA virus


Authors: Queiroz A,Dantas Pinto IF, Lima M, et al.

Published in: Front Microbiol. 2019;10:753

Abstract Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the Flavivirus genus of the Flaviviridae family. Since the large outbreaks in French Polynesia in 2013-2014 and in Brazil in 2015, ZIKV has been considered a new public health threat. Similar to other related flavivirus, ZIKV is associated with mild and self-limiting symptoms such as rash, pruritus, prostration, headache, arthralgia, myalgia, conjunctivitis, lower back pain and, when present, a short-term low grade fever. In addition, ZIKV has been implicated in neurological complications such as neonatal microcephaly and Guillain-Barré syndrome in adults. Herein, serum lipidomic analysis was used to identify possible alterations in lipid metabolism triggered by ZIKV infection. Patients who presented virus-like symptoms such as fever, arthralgia, headache, exanthema, myalgia and pruritus were selected as the control group. Our study reveals increased levels of several phosphatidylethanolamine (PE) lipid species in the serum of ZIKV patients, the majority of them plasmenyl-phosphatidylethanolamine (pPE) (or plasmalogens) linked to polyunsaturated fatty acids. Constituting up to 20% of total phospholipids in humans, plasmalogens linked to polyunsaturated fatty acids are particularly enriched in neural membranes of the brain. The biosynthesis of plasmalogens requires functional peroxisomes, which are important sites for viral replication, including ZIKV. Thus, increased levels of plasmalogens in serum of ZIKV infected subjects suggest a link between ZIKV life cycle and peroxisomes. Our data provide important insights into specific host cellular lipids that are likely associated with ZIKV replication and may serve as platform for antiviral strategy against ZIKV.



Apr, 2019

Immunoglobulin-like Domain of HsFcμR as a Capture Molecule for Detection of Crimean-Congo Hemorrhagic Fever Virus- and Zika Virus-Specific IgM Antibodies


Authors: Rackow A, Ehmen C, von Possel R, et al.

Published in: Clin Chem. 2019;65(3):451-461.

Background The cellular surface molecule HsTOSO/FAIM3/HsFcμR has been identified as an IgM-specific Fc receptor expressed on lymphocytes. Here, we show that its extracellular immunoglobulin-like domain (HsFcμR-Igl) specifically binds to IgM/antigen immune complexes (ICs) and exploit this property for the development of novel detection systems for IgM antibodies directed against Crimean-Congo hemorrhagic fever virus (CCHFV) and Zika virus (ZIKV).

Methods His-tagged HsFcμR-Igl was expressed in Escherichia coli and purified by affinity chromatography, oxidative refolding, and size-exclusion chromatography. Specific binding of HsFcμR-Igl to IgM/antigen ICs was confirmed, and 2 prototypic ELISAs for the detection of anti-CCHFV and anti-ZIKV IgM antibodies were developed. Thereby, patient sera and virus-specific recombinant antigens directly labeled with horseradish peroxidase (HRP) were coincubated on HsFcμR-Igl-coated ELISA plates. Bound ICs were quantified by measuring turnover of a chromogenic HRP substrate.

Results Assay validation was performed using paired serum samples from 15 Kosovar patients with a PCR-confirmed CCHFV infection and 28 Brazilian patients with a PCR-confirmed ZIKV infection, along with a panel of a priori CCHFV/ZIKV-IgM-negative serum samples. Both ELISAs were highly reproducible. Sensitivity and specificity were comparable with or even exceeded in-house gold standard testing and commercial kits. Furthermore, latex beads coated with HsFcμR-Igl aggregated upon coincubation with an IgM-positive serum and HRP-labeled antigen but not with either component alone, revealing a potential for use of HsFcμR-Igl as a capture molecule in aggregation-based rapid tests.

Conclusions Recombinant HsFcμR-Igl is a versatile capture molecule for IgM/antigen ICs of human and animal origin and can be applied for the development of both plate- and bead-based serological tests.



Dec, 2018

Late identification of Chikungunya virus in the central nervous system of a 2-month-old Infant: persistence of maternal-neonatal infection?


Authors: Di Maio Ferreira FCPA, da Silva ASV, Bispo de Filippis AM, Brasil P

Published in: J  Pediatric Infect Dis Soc. 2019 Jan 18

Abstract We report here a probable case of vertical transmission of chikungunya infection with confirmed maternal viremia close to labor that led to severe infection in the newborn. The newborn progressed with cutaneous lesions and irritability 2 months after vertical transmission, when chikungunya virus was detected in the infant’s CSF by a molecular diagnostic test (real-time polymerase chain reaction).



Dec, 2018

Zika virus infection and differential diagnosis in a cohort of HIV-infected patients


Authors: Calvet GA, Brasil P, Siqueira AM, et al.

Published in: J Acquir Immune Defic Syndr. 2018;79:237-243

Background Zika virus (ZIKV) emergence in South America revealed the lack of knowledge regarding clinical manifestations in HIV-infected individuals.Objectives:We described the clinical characteristics, laboratory manifestations, differential diagnosis, and outcome of ZIKV infection in a large, single-center cohort of HIV-infected patients.

Methods HIV-infected patients aged 18 years and older with clinical suspected arboviral disease from an ongoing cohort were followed from February 2015 through December 2015. Acute serum samples were tested for ZIKV, dengue virus (DENV), and chikungunya virus by real-time reverse transcriptase polymerase chain reaction, anti-DENV immunoglobulin (Ig)M/IgG, and syphilis assays; convalescent samples were tested for anti-DENV IgM/IgG; and urine samples were tested for ZIKV by real-time reverse transcriptase polymerase chain reaction. ZIKV disease was defined according to the Pan American Health Organization (PAHO) guidelines.

Results Of 101 patients, ZIKV was confirmed in 43 cases and suspected in 34, and another diagnosis was assumed for 24 patients (dengue, secondary/latent syphilis, respiratory infections, human parvovirus B19, adverse drug reaction, musculoskeletal disorders, and acute gastroenteritis). ZIKV-confirmed and ZIKV-suspected patients reported similar signs and symptoms. Pruritic rash was the most common symptom, followed by myalgia, nonpurulent conjunctivitis, arthralgia, prostration, and headache. In the short-term follow-up [median 67.5 days (interquartile range: 32–104.5)], CD4 cell count (Z = −0.831, P = 0.406) and HIV viral load (Z = −0.447, P = 0.655) did not change significantly after ZIKV infection. There were no hospitalizations, complications, or deaths.

Conclusions Among HIV-infected patients with suspected arboviral disease, 42.6% were ZIKV-infected. CD4 cell counts and HIV viral load were not different after ZIKV infection. Differential diagnosis with other diseases and adverse drug reaction should be evaluated.





Dec, 2018

Symptomatic Zika virus infection in infants, children, and adolescents living in Puerto Rico


Authors: Read JS, Torres-Velasquez B, Lorenzi O, et al.

Published in: JAMA Pediatr. 2018;172(7):686-693

Importance  Little information is available regarding Zika virus (ZIKV) infection in children.

Objective  To describe patients younger than 18 years who were infected with ZIKV and were enrolled in the Sentinel Enhanced Dengue and Acute Febrile Illness Surveillance System (SEDSS).

Design, Setting, and Participants  Children infected with ZIKV with 7 or fewer days of fever or emancipated minors aged 14 to 17 years with a generalized maculopapular rash, arthritis or arthralgia, or nonpurulent conjunctivitis were eligible for enrollment on or before December 31, 2016, in Puerto Rico. Patients were evaluated using ZIKV polymerase chain reaction testing at 7 or fewer days after the onset of symptoms. Available ZIKV polymerase chain reaction–positive specimens were evaluated to determine viral loads.

Exposures  Confirmed polymerase chain reaction–positive ZIKV infection.

Main Outcomes and Measures  Clinical characteristics and viral loads of symptomatic children with confirmed ZIKV infection.

Results  Of 7191 children enrolled in SEDSS on or before December 31, 2016, only those with confirmed ZIKV infection (351 participants) were included in this study. Participants who had confirmed ZIKV infection included 25 infants (7.1%), 69 children (19.7%) aged 1 to 4 years, 95 (27.1%) aged 5 to 9 years, and 162 (46.1%) aged 10 to 17 years. Among these, 260 patients (74.1%) presented for evaluation of ZIKV infection at fewer than 3 days after the onset of symptoms, 340 (96.9%) were discharged to home after evaluation, and 349 (99.4%) had fever, 280 (79.8%) had a rash, 243 (69.2%) had facial or neck erythema, 234 (66.7%) had fatigue, 223 (63.5%) had headache, 212 (60.4%) had chills, 206 (58.7%) had pruritus, and 204 (58.1%) had conjunctival hyperemia. Of 480 specimens collected (317 serum and 163 urine specimens) from 349 children, the median number of days after the onset of symptoms was lower for children who had serum specimens (1 day [interquartile range (IQR), 1-2 days]) than for children who had urine specimens (2 [1-3] days) (P < .001). Of 131 children who had both serum and urine specimens collected on the same day, the median viral load was higher in serum than in urine (median [IQR], 23 098 [8784-88 242] copies/mL for serum vs 9966 [2815-52 774] copies/mL for urine; P = .02). When a single serum sample from each of 317 patients was analyzed, there were no statistically significant differences in median viral loads according to age, sex, or disposition. However, the median serum viral load varied significantly according to the number of days after the onset of symptoms (0 days, 106 778 [IQR, 9772-1 571 718] copies/mL; 1 day, 46 299 [10 663-255 030] copies/mL; 2 days, 20 678 [8763-42 458] copies/mL; and ≥3 days, 15 901 [5135-49 248] copies/mL; P = .001).

Conclusions and Relevance  This study represents the largest study to date of ZIKV infection in the pediatric population. Most children infected with ZIKV had fever, rash, and conjunctival hyperemia. The children usually presented for evaluation at fewer than 3 days after the onset of symptoms. Viral loads for ZIKV were higher in serum vs urine specimens. Median viral loads in serum specimens differed significantly according to the number of days after the onset of symptoms.


Dec, 2018

Genetic evidence of Zika virus in mother’s breast milk and body fluids of a newborn with severe congenital defects


Authors: Giovanetti M, Goes de Jesus J, Lima de Maia M, Junior JX, et al.

Published in: Clin Microbiol Infect.2018;24(10):1111-1112

Abstract On the basis of the upsurge in the number of newborns with neurologic disorders in the northeast, in November 2015 the Brazilian Ministry of Health declared a public health emergency of national concern [1]. On the basis of evidence for a potential association between microcephaly and other neurologic disorders and Zika virus (ZIKV) infection, the World Health Organization declared a public health emergency of international concern on 1 February 2016. Here we report genetic evidence of ZIKV RNA in the mother’s breast milk and in the serum and urine of a newborn with severe congenital defects.



Dec, 2018

Clinical and laboratory profile of Zika and dengue infected patients: lessons learned from the co-circulation of dengue, Zika and chikungunya in Brazil


Authors: Azeredo EL, dos Santos FB, Barbosa LS, et al.

Published in: PLoS Curr. 2018 Feb 15;10

Background The current triple epidemic caused by dengue, zika and chikungunya constitutes a serious health problem in Brazil. The aim of this study was to investigate acute samples (up to the 7 days of symptoms) from patients presenting acute fever syndrome suspected as arboviral infection and characterize the clinical and laboratorial profile during the co-circulation of dengue, zika and chikungunya in Campo Grande, Mato Grosso do Sul (MS), midwest region of Brazil.

Methods All suspected cases (n=134) were tested by using serological and molecular diagnostic tests including DENV, ZIKV and CHIKV RT-PCR, Dengue nonstructural protein 1 (NS1) antigen capture ELISA, anti- DENV IgM ELISA and anti-CHIKV IgM ELISA. In addition, clinical, hematological and biochemical parameters of infected patients were analyzed.

Results It was observed that 79.1% of the blood samples were confirmed for ZIKV and/or DENV infection Of those, 38.0% patients were DENV monoinfected, 26.8% were ZIKV monoinfected and 13.4% were DENV/ZIKV co-infected. Seven patients presented Chikungunya IgM antibodies indicating a previous CHIKV infection. Common symptoms included fever, rash, arthralgia, myalgia, prostration, headache and conjunctivitis. Statistical analysis showed that pruritus and edema were associated with ZIKV infection while prostration and vomiting were more associated with dengue. Additionally, total protein and ALT levels were significantly different in DENV patients compared to ZIKV ones. Some DENV infected patients as well as co-infected needed hospitalization and venous hydration. Otherwise, most ZIKV infected patients presented mild clinical course. Among the pregnant women studied (n=11), three were ZIKV monoinfected while four were DENV monoinfected and two were DENV-1/ZIKV coinfected. In general, normal birth outcomes were observed except for the death due to respiratory insufficiency of one baby born to a mother coinfected with DENV-1/ZIKV.

Conclusions Herein, we provide evidence of the co-circulation of DENV, ZIKV and CHIKV infections in the Campo Grande, MS, Brazil, with a high frequency of DENV-1/ZIKV coinfection. Laboratorial diagnosis poses a challenge where those arboviruses are endemic and differential diagnosis proved to imperative for cases characterization. The knowledge about disease severity during arbovirus coinfections is still scarce and there are several issues emphasizing the importance of adequate management of patients at risk areas.



Dec, 2018

Human T cell responses to Dengue and Zika virus infection compared to Dengue/Zika coinfection


Authors: Badolato-Corrêa J, Sánchez-Arcila JC, et al.

Published in: Immun Inflamm Dis.2018; 6(2):194–206

Introduction Zika virus (ZIKV) and dengue virus (DENV) co‐circulated during latest outbreaks in Brazil, hence, it is important to evaluate the host cross‐reactive immune responses to these viruses. So far, little is known about human T cell responses to ZIKV and no reports detail adaptive immune responses during DENV/ZIKV coinfection.

Methods Here, we studied T cells responses in well‐characterized groups of DENV, ZIKV, or DENV/ZIKV infected patients and DENV‐exposed healthy donors. We evaluated chemokine receptors expression and single/multifunctional frequencies of IFNγ, TNF, and IL2‐producing T cells during these infections. Even without antigenic stimulation, it was possible to detect chemokine receptors and IFNγ, TNF, and IL2‐producing T cells from all individuals by flow cytometry. Additionally, PBMCs’ IFNγ response to DENV NS1 protein and to polyclonal stimuli was evaluated by ELISPOT.

Results DENV and ZIKV infections and DENV/ZIKV coinfections similarly induced expression of CCR5, CX3CR1, and CXCR3 on CD4 and CD8 T cells. DENV/ZIKV coinfection decreased the ability of CD4+ T cells to produce IFNγ+, TNF+, TNF + IFNγ+, and TNF + IL2+, compared to DENV and ZIKV infections. A higher magnitude of IFNγ response to DENV NS1 was found in donors with a history of dengue infection, however, a hyporesponsiveness was found in acute DENV, ZIKV, or DENV/ZIKV infected patients, even previously infected with DENV.

Conclusion Therefore, we emphasize the potential impact of coinfection on the immune response from human hosts, mainly in areas where DENV and ZIKV cocirculate.



Oct, 2018

Evidence for multiple sylvatic transmission cycles during the 2016-2017 yellow fever virus outbreak, Brazil


Authors: Moreira-Soto A, Torres MC, Lima de Mendonça MC, et al.

Published in: Clin Microbiol Infect. 2018;24(9):1019.e1-1019.e4

Objectives Since December 2016, Brazil has experienced an unusually large outbreak of yellow fever (YF). Whether urban transmission may contribute to the extent of the outbreak is unclear. The objective of this study was to characterize YF virus (YFV) genomes and to identify spatial patterns to determine the distribution and origin of YF cases in Minas Gerais, Espírito Santo and Rio de Janeiro, the most affected Brazilian states during the current YFV outbreak.

Methods We characterized near-complete YFV genomes from 14 human cases and two nonhuman primates (NHP), sampled from February to April 2017, retrieved epidemiologic data of cases and used a geographic information system to investigate the geospatial spread of YFV.

Results All YFV strains were closely related. On the basis of signature mutations, we identified two cocirculating YFV clusters. One was restricted to the hinterland of Espírito Santo state, and another formed a coastal cluster encompassing several hundred kilometers. Both clusters comprised strains from humans living in rural areas and NHP. Another NHP lineage clustered in a basal relationship. No signs of adaptation of YFV strains to human hosts were detected.

Conclusions Our data suggest sylvatic transmission during the current outbreak. Additionally, cocirculation of two distinct YFV clades occurring in humans and NHP suggests the existence of multiple sylvatic transmission cycles. Increased detection of YFV might be facilitated by raised awareness for arbovirus-mediated disease after Zika and chikungunya virus outbreaks. Further surveillance is required, as reemergence of YFV from NHPs might continue and facilitate the appearance of urban transmission cycles.