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Quintans MDS, Vianna RADO, Velarde LGC, de Oliveira SA, Fernandes AR, Bueno AC, Cardoso CAA. Neurodevelopmental Outcomes in Children Vertically Exposed to Chikungunya Virus: A Two Years Follow-up Study. Pediatr Infect Dis J 2025; 44:154-160. [PMID: 39264193 DOI: 10.1097/inf.0000000000004534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/13/2024]
Abstract
OBJECTIVES To monitor by the first 24 months of life, children born to mothers with laboratory evidence of chikungunya virus (CHIKV) infection during pregnancy or up to 8 weeks before it, and to describe abnormalities in head circumference (HC), auditory and ophthalmological assessments and neuroimaging tests during the follow-up period. METHOD This is a observational, descriptive, longitudinal and prospective study of children born to mothers who had a rash and a positive test for CHIKV during pregnancy or up to 8 weeks before it. They were admitted between November 2015 and May 2019 in the outpatient multidisciplinary clinic to investigate acute exanthematous disease. The exposed children were followed up by a multidisciplinary team and underwent periodic measurements of the HC. The Denver II test was applied, in addition to transfontanellar ultrasound (TU) to evaluate neurodevelopmental outcomes during the study period. Ophthalmological and auditory examinations, echocardiography and laboratory tests were also included. RESULTS We included in the study 27 children vertically exposed to CHIKV. All children had a negative polymerase chain reaction test for the virus collected at the first outpatient visit (mean age of 16.8 days and standard deviation of 8 days). No clinical condition compatible with congenital infection at birth was reported. A change in HC characterized by macrocephaly and mild global delay development was observed in a 1-year-old child whose mother was infected in the peripartum, but with normal TU. Changes in the TU were observed in 2 other children with nonspecific subependymal cystic malformation that was not evident by the cranial computed tomography. The other children monitored showed normal results in the Denver II test, in the HC and TU. No changes were identified on ocular ophthalmoscopy or auditory brainstem response test. Two children had an increase in serum ferritin levels during the first year of life, with the others' inflammatory disease markers normal. CONCLUSIONS Our study added knowledge about the neurodevelopment of children exposed to CHIKV during pregnancy by a longitudinal and prospective follow-up, throughout their first 24 months of life. We did not observe a negative impact of exposure to the virus on the neurological examination, global developmental test or measurements of the HC of these children.
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Affiliation(s)
- Maria D S Quintans
- From the Maternal and Child Department, School of Medicine, Universidade Federal Fluminense
| | - Renata A de O Vianna
- From the Maternal and Child Department, School of Medicine, Universidade Federal Fluminense
| | - Luis G C Velarde
- Department of Statistics, Universidade Federal Fluminense
- Multi-User Laboratory for Support in Nephrology and Medical Sciences (LAMAP), School of Medicine, Universidade Federal Fluminense
| | - Solange A de Oliveira
- Multi-User Laboratory for Support in Nephrology and Medical Sciences (LAMAP), School of Medicine, Universidade Federal Fluminense
- Department of Clinical Medicine, School of Medicine, Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil
| | - Alexandre R Fernandes
- From the Maternal and Child Department, School of Medicine, Universidade Federal Fluminense
| | - Arnaldo C Bueno
- From the Maternal and Child Department, School of Medicine, Universidade Federal Fluminense
| | - Claudete A A Cardoso
- From the Maternal and Child Department, School of Medicine, Universidade Federal Fluminense
- Multi-User Laboratory for Support in Nephrology and Medical Sciences (LAMAP), School of Medicine, Universidade Federal Fluminense
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Martins MM, Medronho RDA, Raymundo CE, Prata-Barbosa A, da Cunha AJLA. Neonatal Microcephaly and Central Nervous System Abnormalities During the Zika Outbreak in Rio de Janeiro. Viruses 2025; 17:208. [PMID: 40006962 PMCID: PMC11860663 DOI: 10.3390/v17020208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 01/25/2025] [Accepted: 01/26/2025] [Indexed: 02/27/2025] Open
Abstract
This retrospective cohort study analyzed 7870 pregnant women, including 2269 with confirmed Zika virus (ZIKV) infection and 5601 without Zika infection, along with their fetuses and newborns. Data were sourced from multiple databases in the state of Rio de Janeiro, Brazil. A propensity score model was employed to control confounding factors and stratify outcomes by pregnancy trimester. Among ZIKV+ pregnant women, 49 cases of congenital microcephaly or congenital nervous system (CNS) abnormalities were identified (2.16%, or 193.9 cases in 10,000 live births), whereas 44 cases were identified among ZIKV- women (0.78%, or 71.4 cases in 10,000 live births). Multivariable analysis yielded an odds ratio of 2.46 (95% CI 1.30-4.64) overall, with 4.29 (95% CI 1.93-9.53) in the first trimester, 5.29 (95% CI 1.08-25.95) in the second trimester, and 0.68 (95% CI 0.21-2.14) in the third trimester. The most frequent findings among ZIKV+ cases included intracranial calcifications, ventriculomegaly, posterior fossa malformations, reduced brain volume, corpus callosum malformations, cortex dysplasia, lissencephaly, and pachygyria. Ophthalmologic abnormalities were detected in 55.5% of cases, and brainstem auditory evoked potential anomalies were reported in 33.3%. ZIKV infection can result in structural or functional anomalies. Given the absence of specific treatment for congenital Zika syndrome (CZS), clinical care should prioritize monitoring and managing neurological, motor, auditory, visual, and orthopedic disorders in all children with in utero ZIKV exposure, especially during the first and second trimesters of pregnancy.
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Affiliation(s)
- Marlos Melo Martins
- Division of Pediatric Neurology, Martagão Gesteira Institute of Childcare and Pediatrics, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-912, Brazil;
| | - Roberto de Andrade Medronho
- Department of Epidemiology and Public Health, School of Medicine, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-592, Brazil; (R.d.A.M.); (C.E.R.)
| | - Carlos Eduardo Raymundo
- Department of Epidemiology and Public Health, School of Medicine, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-592, Brazil; (R.d.A.M.); (C.E.R.)
| | - Arnaldo Prata-Barbosa
- Department of Pediatrics, D’Or Institute for Research and Education (IDOR), Rio de Janeiro 2281-100, Brazil
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Pieterse L, McDonald M, Abraham R, Griffin DE. Heterogeneous Ribonucleoprotein K Is a Host Regulatory Factor of Chikungunya Virus Replication in Astrocytes. Viruses 2024; 16:1918. [PMID: 39772225 PMCID: PMC11680317 DOI: 10.3390/v16121918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 12/05/2024] [Accepted: 12/10/2024] [Indexed: 01/11/2025] Open
Abstract
Chikungunya virus (CHIKV) is an emerging, mosquito-borne arthritic alphavirus increasingly associated with severe neurological sequelae and long-term morbidity. However, there is limited understanding of the crucial host components involved in CHIKV replicase assembly complex formation, and thus virus replication and virulence-determining factors, within the central nervous system (CNS). Furthermore, the majority of CHIKV CNS studies focus on neuronal infection, even though astrocytes represent the main cerebral target. Heterogeneous ribonucleoprotein K (hnRNP K), an RNA-binding protein involved in RNA splicing, trafficking, and translation, is a regulatory component of alphavirus replicase assembly complexes, but has yet to be thoroughly studied in the context of CHIKV infection. We identified the hnRNP K CHIKV viral RNA (vRNA) binding site via sequence alignment and performed site-directed mutagenesis to generate a mutant, ΔhnRNPK-BS1, with disrupted hnRNPK-vRNA binding, as verified through RNA coimmunoprecipitation and RT-qPCR. CHIKV ΔhnRNPK-BS1 demonstrated hampered replication in both NSC-34 neuronal and C8-D1A astrocytic cultures. In astrocytes, disruption of the hnRNPK-vRNA interaction curtailed viral RNA transcription and shut down subgenomic RNA translation. Our study demonstrates that hnRNP K serves as a crucial RNA-binding host factor that regulates CHIKV replication through the modulation of subgenomic RNA translation.
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Affiliation(s)
- Lisa Pieterse
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; (L.P.); (D.E.G.)
| | - Maranda McDonald
- Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA;
| | - Rachy Abraham
- Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA;
| | - Diane E. Griffin
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; (L.P.); (D.E.G.)
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Ferreira FCPADM, de Filippis AMB, Moreira MEL, de Campos SB, Fuller T, Lopes FCR, Brasil P. Perinatal and Neonatal Chikungunya Virus Transmission: A Case Series. J Pediatric Infect Dis Soc 2024; 13:576-584. [PMID: 39360854 PMCID: PMC11599154 DOI: 10.1093/jpids/piae102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 10/02/2024] [Indexed: 11/28/2024]
Abstract
BACKGROUND Large-scale epidemics in countries with high birth rates can create a concerning scenario where pregnant people are more likely to transmit the virus. In addition, increased international mobility has made arboviruses a growing problem for travelers. The increased risk of vertical transmission has been related to maternal viremia near delivery. Such transmission leads to severe infection of newborns and may be associated with subsequent neurological impairment including cerebral palsy. This case series provides an overview of clinical and laboratory findings in pregnant individuals with confirmed chikungunya virus (CHIKV) infection as well as the clinical effects on their newborn emphasizing the severity of neonatal chikungunya. METHODS An ambispective case series enrolled newborns with confirmed exposure to CHIKV in utero or in the neonatal period. RESULTS During the delivery period, the transmission rate among viremic individuals was approximately 62% (18/29). Fever, irritability, rash, and poor feeding in the first week of life were critical signs of neonatal chikungunya, highlighting its severity. CONCLUSION Close monitoring of healthy newborns during the first week of life is essential in areas affected by CHIKV epidemics, and in offspring of pregnant travelers who visited the outbreaks zones. This case series is intended to increase neonatologists' awareness of the possibility of mother-to-child transmission of CHIKV among newborns with a sepsis-like presentation. Prioritizing CHIKV vaccination for women of childbearing age should also be considered.
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Affiliation(s)
- Fátima C P A Di Maio Ferreira
- Follow-up Clinic, Neonatal Intensive Care Unit, Hospital Universtário Gaffrée e Guinle, Universidade Federal do Estado do Rio de Janeiro, Department of Pediatrics and Neonatology (UNIRIO), Rio de Janeiro, Brazil
| | - Ana M Bispo de Filippis
- Laboratório de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil
| | - Maria Elisabeth L Moreira
- Pesquisa Clínica Aplicada, Instituto Nacional da Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil
| | - Simone B de Campos
- Follow-up Clinic, Physiotherapy and Occupational Therapy Clinic, Hospital Universtário Gaffrée e Guinle, Universidade Federal do Estado do Rio de Janeiro (UNIRIO, Physiotherapy Departament), Rio de Janeiro, Brazil
| | - Trevon Fuller
- UCLA Institute for the Enviroment and Sustainability, Los Angeles, CA, USA
| | - Fernanda C R Lopes
- Departament of Radiology, Hospital Universitário Antônio Pedro, Universidade Federal Fluminense (UFF), Rio de Janeiro, Brazil
| | - Patrícia Brasil
- Laboratório de Doenças Febris Agudas, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil
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Silveira-Freitas JEP, Campagnolo ML, dos Santos Cortez M, de Melo FF, Zarpelon-Schutz AC, Teixeira KN. Long chikungunya? An overview to immunopathology of persistent arthralgia. World J Virol 2024; 13:89985. [PMID: 38984075 PMCID: PMC11229846 DOI: 10.5501/wjv.v13.i2.89985] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 02/09/2024] [Accepted: 04/12/2024] [Indexed: 06/24/2024] Open
Abstract
Chikungunya fever (CF) is caused by an arbovirus whose manifestations are extremely diverse, and it has evolved with significant severity in recent years. The clinical signs triggered by the Chikungunya virus are similar to those of other arboviruses. Generally, fever starts abruptly and reaches high levels, followed by severe polyarthralgia and myalgia, as well as an erythematous or petechial maculopapular rash, varying in severity and extent. Around 40% to 60% of affected individuals report persistent arthralgia, which can last from months to years. The symptoms of CF mainly represent the tissue tropism of the virus rather than the immunopathogenesis triggered by the host's immune system. The main mechanisms associated with arthralgia have been linked to an increase in T helper type 17 cells and a consequent increase in receptor activator of nuclear factor kappa-Β ligand and bone resorption. This review suggests that persistent arthralgia results from the presence of viral antigens post-infection and the constant activation of signaling lymphocytic activation molecule family member 7 in synovial macrophages, leading to local infiltration of CD4+ T cells, which sustains the inflammatory process in the joints through the secretion of pro-inflammatory cytokines. The term "long chikungunya" was used in this review to refer to persistent arthralgia since, due to its manifestation over long periods after the end of the viral infection, this clinical condition seems to be characterized more as a sequel than as a symptom, given that there is no active infection involved.
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Affiliation(s)
| | | | | | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Campus Anísio Teixeira, Vitória da Conquista, Bahia 45029-094, Brazil
| | - Ana Carla Zarpelon-Schutz
- Campus Toledo, Universidade Federal do Paraná, Toledo, Paraná 85919-899, Brazil
- Programa de Pós-graduação em Biotecnologia, Palotina, Universidade Federal do Paraná-Setor Palotina, Paraná 85950-000, Brazil
| | - Kádima Nayara Teixeira
- Campus Toledo, Universidade Federal do Paraná, Toledo, Paraná 85919-899, Brazil
- Programa Multicêntrico de Pós-graduação em Bioquímica e Biologia Molecular, Palotina, Universidade Federal do Paraná-Setor Palotina, Paraná 85950-000, Brazil
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Cruz-Holguín VJ, González-García LD, Velázquez-Cervantes MA, Arévalo-Romero H, De Jesús-González LA, Helguera-Repetto AC, León-Reyes G, Salazar MI, Cedillo-Barrón L, León-Juárez M. Collateral Damage in the Placenta during Viral Infection in Pregnancy: A Possible Mechanism for Vertical Transmission and an Adverse Pregnancy Outcome. Diseases 2024; 12:59. [PMID: 38534983 PMCID: PMC10969698 DOI: 10.3390/diseases12030059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 03/03/2024] [Accepted: 03/06/2024] [Indexed: 11/11/2024] Open
Abstract
In mammals, the placenta is a connection between a mother and a new developing organism. This tissue has a protective function against some microorganisms, transports nutrients, and exchanges gases and excretory substances between the mother and the fetus. Placental tissue is mainly composed of chorionic villi functional units called trophoblasts (cytotrophoblasts, the syncytiotrophoblast, and extravillous trophoblasts). However, some viruses have developed mechanisms that help them invade the placenta, causing various conditions such as necrosis, poor perfusion, and membrane rupture which, in turn, can impact the development of the fetus and put the mother's health at risk. In this study, we collected the most relevant information about viral infection during pregnancy which can affect both the mother and the fetus, leading to an increase in the probability of vertical transmission. Knowing these mechanisms could be relevant for new research in the maternal-fetal context and may provide options for new therapeutic targets and biomarkers in fetal prognosis.
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Affiliation(s)
- Victor Javier Cruz-Holguín
- Laboratorio de Virologia Perinatal y Diseño Molecular de Antigenos y Biomarcadores, Departamento de Inmunobioquimica, Instituto Nacional de Perinatología, Mexico City 11000, Mexico; (V.J.C.-H.); (L.D.G.-G.); (M.A.V.-C.)
- Departamento de Biomedicina Molecular, Centro de Investigación y Estudios Avanzados del IPN (CINVESTAV), Mexico City 07360, Mexico;
| | - Luis Didier González-García
- Laboratorio de Virologia Perinatal y Diseño Molecular de Antigenos y Biomarcadores, Departamento de Inmunobioquimica, Instituto Nacional de Perinatología, Mexico City 11000, Mexico; (V.J.C.-H.); (L.D.G.-G.); (M.A.V.-C.)
- Departamento de Biomedicina Molecular, Centro de Investigación y Estudios Avanzados del IPN (CINVESTAV), Mexico City 07360, Mexico;
- Posgrado de Inmunología, Escuela Nacional de Ciencias Biologócas (ENCB), Instituto Politecnico Naciona, Mexico City 11350, Mexico;
| | - Manuel Adrián Velázquez-Cervantes
- Laboratorio de Virologia Perinatal y Diseño Molecular de Antigenos y Biomarcadores, Departamento de Inmunobioquimica, Instituto Nacional de Perinatología, Mexico City 11000, Mexico; (V.J.C.-H.); (L.D.G.-G.); (M.A.V.-C.)
| | - Haruki Arévalo-Romero
- Laboratorio de Inmunologia y Microbiologia Molecular, Division Academica Multidisciplinaria de Jalpa de Méndez, Jalpa de Mendez 86205, Mexico;
| | | | | | - Guadalupe León-Reyes
- Laboratorio de Nutrigenética y Nutrigenómica, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico;
| | - Ma. Isabel Salazar
- Posgrado de Inmunología, Escuela Nacional de Ciencias Biologócas (ENCB), Instituto Politecnico Naciona, Mexico City 11350, Mexico;
- Laboratorio Nacional de Vacunología y Virus Tropicales (LNVyVT), Escuela Nacional de Ciencias Biologócas (ENCB), Instituto Politecnico Naciona, Mexico City 11350, Mexico
| | - Leticia Cedillo-Barrón
- Departamento de Biomedicina Molecular, Centro de Investigación y Estudios Avanzados del IPN (CINVESTAV), Mexico City 07360, Mexico;
| | - Moisés León-Juárez
- Laboratorio de Virologia Perinatal y Diseño Molecular de Antigenos y Biomarcadores, Departamento de Inmunobioquimica, Instituto Nacional de Perinatología, Mexico City 11000, Mexico; (V.J.C.-H.); (L.D.G.-G.); (M.A.V.-C.)
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de Lima RC, Valente LMM, Familiar Macedo D, de-Oliveira-Pinto LM, dos Santos FB, Mazzei JL, Siani AC, Nunes PCG, de Azeredo EL. Antiviral and Virucidal Activities of Uncaria tomentosa (Cat's Claw) against the Chikungunya Virus. Viruses 2024; 16:369. [PMID: 38543735 PMCID: PMC10974475 DOI: 10.3390/v16030369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 02/16/2024] [Accepted: 02/21/2024] [Indexed: 05/23/2024] Open
Abstract
Uncaria tomentosa (UT) is a medicinal plant popularly known as cat's claw belonging to the Rubiaceae family that has been reported to display antiviral and anti-inflammatory activities. The chikungunya virus (CHIKV) outbreaks constitute a Brazilian public health concern. CHIKV infection develops an abrupt onset of fever, usually accompanied by a skin rash, besides incapacitating polyarthralgia. There is no vaccine available or treatment for CHIKV infection. The present study evaluates the hydroalcoholic extract of UT bark as a potential antiviral against CHIKV. The in vitro antiviral activity of the UT extract against the Brazilian CHIKV strain was assessed using quantitative reverse transcription polymerase chain reaction, flow cytometry, and plaque assay. Results obtained demonstrated that UT inhibits CHIKV infection in a dose-dependent manner. At the non-cytotoxic concentration of 100 µg/mL, UT exhibited antiviral activity above 90% as determined by plaque reduction assay, and it reduced the viral cytopathic effect. Similarly, a significant virucidal effect of 100 µg/mL UT was observed after 24 and 48 h post-infection. This is the first report on the antiviral activity of UT against CHIKV infection, and the data presented here suggests UT as a potential antiviral to treat CHIKV infection.
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Affiliation(s)
- Raquel Curtinhas de Lima
- Laboratório das Interações Vírus Hospedeiros, Instituto Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil; (R.C.d.L.); (D.F.M.); (L.M.d.-O.-P.); (F.B.d.S.); (P.C.G.N.)
| | - Ligia Maria Marino Valente
- Instituto de Química, Universidade Federal do Rio de Janeiro, Av. Athos da Silveira Ramos, 149, Rio de Janeiro 21941-909, Brazil;
| | - Débora Familiar Macedo
- Laboratório das Interações Vírus Hospedeiros, Instituto Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil; (R.C.d.L.); (D.F.M.); (L.M.d.-O.-P.); (F.B.d.S.); (P.C.G.N.)
| | - Luzia Maria de-Oliveira-Pinto
- Laboratório das Interações Vírus Hospedeiros, Instituto Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil; (R.C.d.L.); (D.F.M.); (L.M.d.-O.-P.); (F.B.d.S.); (P.C.G.N.)
| | - Flavia Barreto dos Santos
- Laboratório das Interações Vírus Hospedeiros, Instituto Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil; (R.C.d.L.); (D.F.M.); (L.M.d.-O.-P.); (F.B.d.S.); (P.C.G.N.)
| | - José Luiz Mazzei
- Laboratório de Tecnologia para Biodiversidade em Saúde, Instituto de Tecnologia de Fármacos, Fundação Oswaldo Cruz, Rio de Janeiro 21041-250, Brazil; (J.L.M.); (A.C.S.)
| | - Antonio Carlos Siani
- Laboratório de Tecnologia para Biodiversidade em Saúde, Instituto de Tecnologia de Fármacos, Fundação Oswaldo Cruz, Rio de Janeiro 21041-250, Brazil; (J.L.M.); (A.C.S.)
| | - Priscila Conrado Guerra Nunes
- Laboratório das Interações Vírus Hospedeiros, Instituto Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil; (R.C.d.L.); (D.F.M.); (L.M.d.-O.-P.); (F.B.d.S.); (P.C.G.N.)
| | - Elzinandes Leal de Azeredo
- Laboratório das Interações Vírus Hospedeiros, Instituto Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil; (R.C.d.L.); (D.F.M.); (L.M.d.-O.-P.); (F.B.d.S.); (P.C.G.N.)
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Jacob-Nascimento LC, Portilho MM, Anjos RO, Moreira PSS, Stauber C, Weaver SC, Kitron U, Reis MG, Ribeiro GS. Detection of Chikungunya Virus RNA in Oral Fluid and Urine: An Alternative Approach to Diagnosis? Viruses 2024; 16:235. [PMID: 38400011 PMCID: PMC10891727 DOI: 10.3390/v16020235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 01/19/2024] [Accepted: 01/24/2024] [Indexed: 02/25/2024] Open
Abstract
To evaluate whether oral fluids (OF) and urine can serve as alternative, non-invasive samples to diagnose chikungunya virus (CHIKV) infection via RT-qPCR, we employed the same RNA extraction and RT-qPCR protocols on paired serum, OF and urine samples collected from 51 patients with chikungunya during the acute phase of the illness. Chikungunya patients were confirmed through RT-qPCR in acute-phase sera (N = 19), IgM seroconversion between acute- and convalescent-phase sera (N = 12), or IgM detection in acute-phase sera (N = 20). The controls included paired serum, OF and urine samples from patients with non-arbovirus acute febrile illness (N = 28) and RT-PCR-confirmed dengue (N = 16). Nine (47%) of the patients with positive RT-qPCR for CHIKV in sera and two (17%) of those with CHIKV infection confirmed solely via IgM seroconversion had OF positive for CHIKV in RT-qPCR. One (5%) patient with CHIKV infection confirmed via serum RT-qPCR was positive in the RT-qPCR performed on urine. None of the negative control group samples were positive. Although OF may serve as an alternative sample for diagnosing acute chikungunya in specific settings, a negative result cannot rule out an infection. Further research is needed to investigate whether OF and urine collected later in the disease course when serum becomes RT-qPCR-negative may be helpful in CHIKV diagnosis and surveillance, as well as to determine whether urine and OF pose any risk of CHIKV transmission.
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Affiliation(s)
- Leile Camila Jacob-Nascimento
- Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil; (L.C.J.-N.); (M.M.P.); (R.O.A.); (P.S.S.M.); (M.G.R.)
- Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador 40026-010, Brazil
| | - Moyra M. Portilho
- Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil; (L.C.J.-N.); (M.M.P.); (R.O.A.); (P.S.S.M.); (M.G.R.)
| | - Rosângela O. Anjos
- Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil; (L.C.J.-N.); (M.M.P.); (R.O.A.); (P.S.S.M.); (M.G.R.)
| | - Patrícia S. S. Moreira
- Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil; (L.C.J.-N.); (M.M.P.); (R.O.A.); (P.S.S.M.); (M.G.R.)
| | - Christine Stauber
- School of Public Health, Georgia State University, Atlanta, GA 30303, USA;
| | - Scott C. Weaver
- Department of Microbiology & Immunology and World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX 77555, USA;
| | - Uriel Kitron
- Department of Environmental Sciences, Emory University, Atlanta, GA 30322, USA;
| | - Mitermayer G. Reis
- Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil; (L.C.J.-N.); (M.M.P.); (R.O.A.); (P.S.S.M.); (M.G.R.)
- Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador 40026-010, Brazil
- Yale School of Public Health, Yale University, New Haven, CT 06520-8034, USA
| | - Guilherme S. Ribeiro
- Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil; (L.C.J.-N.); (M.M.P.); (R.O.A.); (P.S.S.M.); (M.G.R.)
- Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador 40026-010, Brazil
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Viral agents (2nd section). Transfusion 2024; 64 Suppl 1:S19-S207. [PMID: 38394038 DOI: 10.1111/trf.17630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Accepted: 12/02/2023] [Indexed: 02/25/2024]
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10
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Ahmed S, Sultana S, Kundu S, Alam SS, Hossan T, Islam MA. Global Prevalence of Zika and Chikungunya Coinfection: A Systematic Review and Meta-Analysis. Diseases 2024; 12:31. [PMID: 38391778 PMCID: PMC10888207 DOI: 10.3390/diseases12020031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 01/26/2024] [Accepted: 01/29/2024] [Indexed: 02/24/2024] Open
Abstract
Zika virus (ZIKV) and chikungunya virus (CHIKV) are arthropod-borne viruses with significant pathogenicity, posing a substantial health and economic burden on a global scale. Moreover, ZIKV-CHIKV coinfection imposes additional therapeutic challenges as there is no specific treatment for ZIKV or CHIKV infection. While a growing number of studies have documented the ZIKV-CHIKV coinfection, there is currently a lack of conclusive reports on this coinfection. Therefore, we performed a systematic review and meta-analysis to determine the true statistics of ZIKV-CHIKV coinfection in the global human population. Relevant studies were searched for in PubMed, Scopus, and Google Scholar without limitation in terms of language or publication date. A total of 33 studies containing 41,460 participants were included in this meta-analysis. The study protocol was registered with PROSPERO under the registration number CRD42020176409. The pooled prevalence and confidence intervals of ZIKV-CHIKV coinfection were computed using a random-effects model. The study estimated a combined global prevalence rate of 1.0% [95% CI: 0.7-1.2] for the occurrence of ZIKV-CHIKV coinfection. The region of North America (Mexico, Haiti, and Nicaragua) and the country of Haiti demonstrated maximum prevalence rates of 2.8% [95% CI: 1.5-4.1] and 3.5% [95% CI: 0.2-6.8], respectively. Moreover, the prevalence of coinfection was found to be higher in the paediatric group (2.1% [95% CI: 0.0-4.2]) in comparison with the adult group (0.7% [95% CI: 0.2-1.1]). These findings suggest that the occurrence of ZIKV-CHIKV coinfection varies geographically and by age group. The results of this meta-analysis will guide future investigations seeking to understand the underlying reasons for these variations and the causes of coinfection and to develop targeted prevention and control strategies.
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Affiliation(s)
- Saleh Ahmed
- Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
| | - Shabiha Sultana
- Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
| | - Shoumik Kundu
- Department of Chemistry and Biochemistry, Texas Tech University, 2500 Broadway St., Lubbock, TX 79409, USA
| | - Sayeda Sadia Alam
- Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh
| | - Tareq Hossan
- Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh
- Department of Internal Medicine, Division of Oncology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA
| | - Md Asiful Islam
- WHO Collaborating Centre for Global Women's Health, Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK
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11
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Chen H, Phuektes P, Yeo LS, Wong YH, Lee RCH, Yi B, Hou X, Liu S, Cai Y, Chu JJH. Attenuation of neurovirulence of chikungunya virus by a single amino acid mutation in viral E2 envelope protein. J Biomed Sci 2024; 31:8. [PMID: 38229040 DOI: 10.1186/s12929-024-00995-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 01/05/2024] [Indexed: 01/18/2024] Open
Abstract
BACKGROUND Chikungunya virus (CHIKV) has reemerged as a major public health concern, causing chikungunya fever with increasing cases and neurological complications. METHODS In the present study, we investigated a low-passage human isolate of the East/ Central/South African (ECSA) lineage of CHIKV strain LK(EH)CH6708, which exhibited a mix of small and large viral plaques. The small and large plaque variants were isolated and designated as CHIKV-SP and CHIKV-BP, respectively. CHIKV-SP and CHIKV-BP were characterized in vitro and in vivo to compare their virus production and virulence. Additionally, whole viral genome analysis and reverse genetics were employed to identify genomic virulence factors. RESULTS CHIKV-SP demonstrated lower virus production in mammalian cells and attenuated virulence in a murine model. On the other hand, CHIKV-BP induced higher pro-inflammatory cytokine levels, compromised the integrity of the blood-brain barrier, and led to astrocyte infection in mouse brains. Furthermore, the CHIKV-SP variant had limited transmission potential in Aedes albopictus mosquitoes, likely due to restricted dissemination. Whole viral genome analysis revealed multiple genetic mutations in the CHIKV-SP variant, including a Glycine (G) to Arginine (R) mutation at position 55 in the viral E2 glycoprotein. Reverse genetics experiments confirmed that the E2-G55R mutation alone was sufficient to reduce virus production in vitro and virulence in mice. CONCLUSIONS These findings highlight the attenuating effects of the E2-G55R mutation on CHIKV pathogenicity and neurovirulence and emphasize the importance of monitoring this mutation in natural infections.
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Affiliation(s)
- Huixin Chen
- Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Patchara Phuektes
- Division of Pathobiology, Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Li Sze Yeo
- School of Applied Science, Republic Polytechnic, Singapore, Singapore
| | - Yi Hao Wong
- Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Regina Ching Hua Lee
- Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Bowen Yi
- Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Xinjun Hou
- Temasek Life Sciences Laboratory, National University of Singapore, Singapore, Singapore
- Department of Biological Sciences, National University of Singapore, Singapore, Singapore
| | - Sen Liu
- Temasek Life Sciences Laboratory, National University of Singapore, Singapore, Singapore
| | - Yu Cai
- Temasek Life Sciences Laboratory, National University of Singapore, Singapore, Singapore
- Department of Biological Sciences, National University of Singapore, Singapore, Singapore
| | - Justin Jang Hann Chu
- Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- Collaborative and Translation Unit for HFMD, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
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12
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Mukhopadhyay K, Sengupta M, Misra SC, Majee K. Trends in emerging vector-borne viral infections and their outcome in children over two decades. Pediatr Res 2024; 95:464-479. [PMID: 37880334 DOI: 10.1038/s41390-023-02866-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 09/27/2023] [Accepted: 10/02/2023] [Indexed: 10/27/2023]
Abstract
This review utilizes quatitative methods and bibliometric data to analyse the trends of emerging and re-emerging vector-borne diseases, with a focus on their impact on pediatric population. To conduct this analysis, a systematic search of PubMed articles from the past two decades was performed, specifically looking at 26 different vector-borne viruses listed in WHO and CDC list of vector-borne viruses. The review found that diseases like Dengue, Zika, West Nile, and Chikungunya were frequently discussed in the literature. On the other hand, diseases such as Tick-borne encephalitis, Rift Valley fever, Venezuelan equine encephalitis, Sindbis fever, Venezuelan equine encephalitis, Ross River virus, and Eastern equine encephalitis showed an upward trend in publications, indicating potential resurgence. In addition to discussing trends and patterns, the review delves into the clinical manifestations and long-term effects of the top 10 viruses in children. It highlights various factors including deforestation, urbanization, global travel, and immunosuppression that contribute to disease emergence and resurgence. To effectively combat these vector-borne diseases, continuous surveillance is crucial. The review also emphasizes the importance of increased vaccination efforts and targeted research to address the health challenges they pose. IMPACT: This review employs quantitative analysis of publications to elucidate trends in emerging pediatric vector-borne viral diseases over two decades. Dengue, the most prevalent of these diseases, has spread to new regions. New strains of Japanese Encephalitis have caused outbreaks. Resurgence of Tick-borne Encephalitis, West Nile, and Yellow Fever due to vaccine hesitancy has also transpired. Continuous global surveillance, increased vaccination, and research into novel therapeutics are imperative to combat the substantial morbidity and mortality burden these diseases pose for children worldwide.
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Affiliation(s)
| | - Mallika Sengupta
- Microbiology, AIIMS Kalyani, Basantapur, Saguna, West Bengal, India
| | | | - Kiranmay Majee
- Student, AIIMS Kalyani, Basantapur, Saguna, West Bengal, India
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13
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Ogwuche J, Chang CA, Ige O, Sagay AS, Chaplin B, Kahansim ML, Paul M, Elujoba M, Imade G, Kweashi G, Dai YC, Hsieh SC, Wang WK, Hamel DJ, Kanki PJ. Arbovirus surveillance in pregnant women in north-central Nigeria, 2019-2022. J Clin Virol 2023; 169:105616. [PMID: 37944259 PMCID: PMC10841754 DOI: 10.1016/j.jcv.2023.105616] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 10/25/2023] [Accepted: 10/29/2023] [Indexed: 11/12/2023]
Abstract
BACKGROUND The adverse impact of Zika (ZIKV), dengue (DENV), and chikungunya (CHIKV) virus infection in pregnancy has been recognized in Latin America and Asia but is not well studied in Africa. Although originally discovered in sub-Saharan Africa the non-specific clinical presentation of arbovirus infection may have hampered our detection of adverse clinical outcomes and outbreak. OBJECTIVE This prospective study of arbovirus infection in pregnant women in north-central Nigeria sought to characterize the prevalence of acute arbovirus infection and determine the impact on pregnancy and infant outcomes. METHODS In Nigeria, we screened 1006 pregnant women for ZIKV, DENV and CHIKV IgM/IgG by rapid test (2019-2022). Women with acute infection were recruited for prospective study and infants were examined for any abnormalities from delivery through six months. A subset of rapid test-reactive samples were confirmed using virus-specific ELISAs and neutralization assays. RESULTS The prevalence of acute infection (IgM+) was 3.8 %, 9.9 % and 11.8 % for ZIKV, DENV and CHIKV, respectively; co-infections represented 24.5 % of all infections. The prevalence in asymptomatic women was twice the level of symptomatic infection. We found a significant association between acute maternal ZIKV/DENV/CHIKV infection and any gross abnormal birth outcome (p = 0.014). CONCLUSIONS Over three rainy seasons, regular acute infection with ZIKV, DENV, and CHIKV was observed with significantly higher rates in pregnant women without symptoms. The potential association arbovirus infection with abnormal birth outcome warrants further prospective study to ascertain the clinical significance of these endemic arboviruses in Africa.
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Affiliation(s)
| | - Charlotte Ajeong Chang
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Olukemi Ige
- Jos University Teaching Hospital, University of Jos, Jos, Nigeria
| | - Atiene S Sagay
- Jos University Teaching Hospital, University of Jos, Jos, Nigeria
| | - Beth Chaplin
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | | | - Michael Paul
- Jos University Teaching Hospital, University of Jos, Jos, Nigeria
| | | | - Godwin Imade
- Jos University Teaching Hospital, University of Jos, Jos, Nigeria
| | | | - Yu-Ching Dai
- Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA
| | - Szu-Chia Hsieh
- Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA
| | - Wei-Kung Wang
- Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA
| | - Donald J Hamel
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Phyllis J Kanki
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
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14
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de Andrade Vieira Alves F, Nunes PCG, Arruda LV, Salomão NG, Rabelo K. The Innate Immune Response in DENV- and CHIKV-Infected Placentas and the Consequences for the Fetuses: A Minireview. Viruses 2023; 15:1885. [PMID: 37766291 PMCID: PMC10535478 DOI: 10.3390/v15091885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 08/25/2023] [Accepted: 08/30/2023] [Indexed: 09/29/2023] Open
Abstract
Dengue virus (DENV) and chikungunya (CHIKV) are arthropod-borne viruses belonging to the Flaviviridae and Togaviridae families, respectively. Infection by both viruses can lead to a mild indistinct fever or even lead to more severe forms of the diseases, which are characterized by a generalized inflammatory state and multiorgan involvement. Infected mothers are considered a high-risk group due to their immunosuppressed state and the possibility of vertical transmission. Thereby, infection by arboviruses during pregnancy portrays a major public health concern, especially in countries where epidemics of both diseases are regular and public health policies are left aside. Placental involvement during both infections has been already described and the presence of either DENV or CHIKV has been observed in constituent cells of the placenta. In spite of that, there is little knowledge regarding the intrinsic earlier immunological mechanisms that are developed by placental cells in response to infection by both arboviruses. Here, we approach some of the current information available in the literature about the exacerbated presence of cells involved in the innate immune defense of the placenta during DENV and CHIKV infections.
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Affiliation(s)
- Felipe de Andrade Vieira Alves
- Laboratório de Ultraestrutura e Biologia Tecidual, Universidade do Estado do Rio de Janeiro/UERJ, Rio de Janeiro 20550170, RJ, Brazil; (F.d.A.V.A.); (L.V.A.)
- Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040900, RJ, Brazil
| | - Priscila Conrado Guerra Nunes
- Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040900, RJ, Brazil;
| | - Laíza Vianna Arruda
- Laboratório de Ultraestrutura e Biologia Tecidual, Universidade do Estado do Rio de Janeiro/UERJ, Rio de Janeiro 20550170, RJ, Brazil; (F.d.A.V.A.); (L.V.A.)
- Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040900, RJ, Brazil
| | - Natália Gedeão Salomão
- Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040900, RJ, Brazil
- Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040900, RJ, Brazil;
| | - Kíssila Rabelo
- Laboratório de Ultraestrutura e Biologia Tecidual, Universidade do Estado do Rio de Janeiro/UERJ, Rio de Janeiro 20550170, RJ, Brazil; (F.d.A.V.A.); (L.V.A.)
- Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040900, RJ, Brazil
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15
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Ogwuche J, Chang CA, Ige O, Sagay AS, Chaplin B, Kahansim ML, Paul M, Elujoba M, Imade G, Kweashi G, Dai YC, Hsieh SC, Wang WK, Hamel DJ, Kanki PJ. Arbovirus surveillance in pregnant women in north-central Nigeria, 2019-2022. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.08.04.23293671. [PMID: 37609234 PMCID: PMC10441490 DOI: 10.1101/2023.08.04.23293671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/24/2023]
Abstract
The adverse impact of Zika (ZIKV), dengue (DENV), and chikungunya (CHIKV) virus infection in pregnancy has been recognized in Latin America and Asia but is not well studied in Africa. In Nigeria, we screened 1006 pregnant women for ZIKV, DENV and CHIKV IgM/IgG by rapid test (2019-2022). Women with acute infection were recruited for prospective study and infants were examined for any abnormalities from delivery through six months. A subset of rapid test-reactive samples were confirmed using virus-specific ELISAs and neutralization assays. Prevalence of acute infection (IgM+) was 3.8%, 9.9% and 11.8% for ZIKV, DENV and CHIKV, respectively; co-infections represented 24.5% of all infections. Prevalence in asymptomatic women was twice the level of symptomatic infection. We found a significant association between acute maternal ZIKV/DENV/CHIKV infection and any gross abnormal birth outcome (p=0.014). Further prospective studies will contribute to our understanding of the clinical significance of these endemic arboviruses in Africa.
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16
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Bhattacharjee S, Ghosh D, Saha R, Sarkar R, Kumar S, Khokhar M, Pandey RK. Mechanism of Immune Evasion in Mosquito-Borne Diseases. Pathogens 2023; 12:635. [PMID: 37242305 PMCID: PMC10222277 DOI: 10.3390/pathogens12050635] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 04/20/2023] [Accepted: 04/21/2023] [Indexed: 05/28/2023] Open
Abstract
In recent decades, mosquito-borne illnesses have emerged as a major health burden in many tropical regions. These diseases, such as malaria, dengue fever, chikungunya, yellow fever, Zika virus infection, Rift Valley fever, Japanese encephalitis, and West Nile virus infection, are transmitted through the bite of infected mosquitoes. These pathogens have been shown to interfere with the host's immune system through adaptive and innate immune mechanisms, as well as the human circulatory system. Crucial immune checkpoints such as antigen presentation, T cell activation, differentiation, and proinflammatory response play a vital role in the host cell's response to pathogenic infection. Furthermore, these immune evasions have the potential to stimulate the human immune system, resulting in other associated non-communicable diseases. This review aims to advance our understanding of mosquito-borne diseases and the immune evasion mechanisms by associated pathogens. Moreover, it highlights the adverse outcomes of mosquito-borne disease.
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Affiliation(s)
| | - Debanjan Ghosh
- Department of Biotechnology, Pondicherry University, Puducherry 605014, India
| | - Rounak Saha
- Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry 605014, India
| | - Rima Sarkar
- DBT Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, India
| | - Saurav Kumar
- DBT Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, India
| | - Manoj Khokhar
- Department of Biochemistry, AIIMS, Jodhpur 342005, India
| | - Rajan Kumar Pandey
- Department of Medical Biochemistry and Biophysics, Karolinska Institute, 171 77 Solna, Sweden
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17
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Simon F, Caumes E, Jelinek T, Lopez-Velez R, Steffen R, Chen LH. Chikungunya: risks for travellers. J Travel Med 2023; 30:taad008. [PMID: 36648431 PMCID: PMC10075059 DOI: 10.1093/jtm/taad008] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 01/10/2023] [Accepted: 01/11/2023] [Indexed: 01/18/2023]
Abstract
RATIONALE FOR REVIEW Chikungunya outbreaks continue to occur, with changing epidemiology. Awareness about chikungunya is low both among the at-risk travellers and healthcare professionals, which can result in underdiagnosis and underreporting. This review aims to improve awareness among healthcare professionals regarding the risks of chikungunya for travellers. KEY FINDINGS Chikungunya virus transmission to humans occurs mainly via daytime-active mosquitoes, Aedes aegypti and Aedes albopictus. The areas where these mosquitoes live is continuously expanding, partly due to climate changes. Chikungunya is characterized by an acute onset of fever with joint pain. These symptoms generally resolve within 1-3 weeks, but at least one-third of the patients suffer from debilitating rheumatologic symptoms for months to years. Large outbreaks in changing regions of the world since the turn of the 21st century (e.g. Caribbean, La Réunion; currently Brazil, India) have resulted in growing numbers of travellers importing chikungunya, mainly to Europe and North America. Viremic travellers with chikungunya infection have seeded chikungunya clusters (France, United States of America) and outbreaks (Italy in 2007 and 2017) in non-endemic countries where Ae. albopictus mosquitoes are present. Community preventive measures are important to prevent disease transmission by mosquitoes. Individual preventive options are limited to personal protection measures against mosquito bites, particularly the daytime-active mosquitos that transmit the chikungunya virus. Candidate vaccines are on the horizon and regulatory authorities will need to assess environmental and host risk factors for persistent sequelae, such as obesity, age (over 40 years) and history of arthritis or inflammatory rheumatologic disease to determine which populations should be targeted for these chikungunya vaccines. CONCLUSIONS/RECOMMENDATIONS Travellers planning to visit destinations with active CHIKV circulation should be advised about the risk for chikungunya, prevention strategies, the disease manifestations, possible chronic rheumatologic sequelae and, if symptomatic, seek medical evaluation and report potential exposures.
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Affiliation(s)
- Fabrice Simon
- Service de Pathologie Infectieuse et Tropicale, Hôpital d’Instruction des Armées Laveran, Marseille, France
| | - Eric Caumes
- Centre de Diagnostic, Hôpital de l’Hôtel-Dieu, Paris, France
| | - Tomas Jelinek
- Berlin Centre for Travel and Tropical Medicine, Berlin, Germany
| | - Rogelio Lopez-Velez
- Ramón y Cajal Institute for Health Research (IRyCIS), Ramón y Cajal University Hospital, Madrid, Spain
| | - Robert Steffen
- Epidemiology, Biostatistics and Prevention Institute, WHO Collaborating Center on Travelers’ Health, University of Zurich, Zurich, Switzerland
- Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, TX, USA
| | - Lin H Chen
- Division of Infectious Diseases and Travel Medicine, Mount Auburn Hospital, Cambridge, MA, USA
- Faculty of Medicine, Harvard Medical School, Boston, MA, USA
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18
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Symptomatic Chikungunya Virus Infection and Pregnancy Outcomes: A Nested Case-Control Study in French Guiana. Viruses 2022; 14:v14122705. [PMID: 36560712 PMCID: PMC9787529 DOI: 10.3390/v14122705] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 11/26/2022] [Accepted: 11/28/2022] [Indexed: 12/07/2022] Open
Abstract
During the Chikungunya epidemic in the Caribbean and Latin America, pregnant women were affected by the virus in French Guiana. The question of the impact of the virus on pregnancy was raised because of the lack of scientific consensus and published data in the region. Thus, during the Chikungunya outbreak in French Guiana, a comparative study was set up using a cohort of pregnant women. The objective was to compare pregnancy and neonatal outcomes between pregnant women with Chikungunya virus (CHIKV) infection and pregnant women without CHIKV. Of 653 mothers included in the cohort, 246 mothers were included in the case-control study: 73 had CHIKV fever during pregnancy and 173 had neither fever nor CHIKV during pregnancy. The study did not observe any severe clinical presentation of CHIKV in the participating women. There were no intensive care unit admissions. In addition, the study showed no significant difference between the two groups with regard to pregnancy complications. However, the results showed a potential excess risk of neonatal ICU admission of the newborn when the maternal infection occurred within 7 days before delivery. These results suggest that special attention should be paid to neonates whose mothers were infected with CHIKV shortly before delivery.
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19
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Salomão N, Rabelo K, Avvad-Portari E, Basílio-de-Oliveira C, Basílio-de-Oliveira R, Ferreira F, Ferreira L, de Souza TM, Nunes P, Lima M, Sales AP, Fernandes R, de Souza LJ, Dias L, Brasil P, dos Santos F, Paes M. Histopathological and immunological characteristics of placentas infected with chikungunya virus. Front Microbiol 2022; 13:1055536. [PMID: 36466642 PMCID: PMC9714605 DOI: 10.3389/fmicb.2022.1055536] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 10/28/2022] [Indexed: 09/29/2023] Open
Abstract
Although vertical transmission of CHIKV has been reported, little is known about the role of placenta in the transmission of this virus and the effects of infection on the maternal-fetal interface. In this work we investigated five placentas from pregnant women who became infected during the gestational period. Four formalin-fixed paraffin-embedded samples of placenta (cases 1-4) were positive for CHIKV by RT-PCR. One (case 5) had no positive test of placenta, but had positive RT-PCR for CHIKV in the serum of the mother and the baby, confirming vertical transmission. The placentas were analyzed regarding histopathological and immunological aspects. The main histopathological changes were: deciduitis, villous edema, deposits, villous necrosis, dystrophic calcification, thrombosis and stem vessel obliteration. In infected placentas we noted increase of cells (CD8+ and CD163+) and pro- (IFN-γ and TNF-α) and anti-inflammatory (TGF-β and IL-10) cytokines compared to control placentas. Moreover, CHIKV antigen was detected in decidual cell, trophoblastic cells, stroma villi, Hofbauer cells, and endothelial cells. In conclusion, CHIKV infection seems to disrupt placental homeostasis leading to histopathological alterations in addition to increase in cellularity and cytokines overproduction, evidencing an altered and harmful environment to the pregnant woman and fetus.
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Affiliation(s)
- Natália Salomão
- Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
- Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Kíssila Rabelo
- Laboratório de Ultraestrutura e Biologia Tecidual, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Elyzabeth Avvad-Portari
- Departamento de Anatomia Patológica, Instituto da Mulher e da Criança Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Carlos Basílio-de-Oliveira
- Departamento de Anatomia Patológica, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Rodrigo Basílio-de-Oliveira
- Departamento de Anatomia Patológica, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Fátima Ferreira
- Departamento de Neonatologia, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Luiz Ferreira
- Departamento de Anatomia Patológica, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Thiara Manuele de Souza
- Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Priscila Nunes
- Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Monique Lima
- Laboratório Estratégico de Diagnóstico Molecular, Instituto Butantan, São Paulo, Brazil
| | - Anna Paula Sales
- Centro de Referência de Doenças Imuno-infecciosas (CRDI), Campos dos Goytacazes, Rio de Janeiro, Brazil
| | - Regina Fernandes
- Faculdade de Medicina de Campos, Campos dos Goytacazes, Rio de Janeiro, Brazil
- Laboratório de Biotecnologia, Universidade Estadual do Norte Fluminense, Campos dos Goytacazes, Rio de Janeiro, Brazil
| | - Luiz José de Souza
- Centro de Referência de Doenças Imuno-infecciosas (CRDI), Campos dos Goytacazes, Rio de Janeiro, Brazil
- Faculdade de Medicina de Campos, Campos dos Goytacazes, Rio de Janeiro, Brazil
| | - Laura Dias
- Hospital Geral Dr. Beda, CEPLIN – Uti Neonatal Nicola Albano, Campos dos Goytacazes, Rio de Janeiro, Brazil
| | - Patrícia Brasil
- Laboratório de Doenças Febris Agudas, Instituto Nacional de Infectologia Evandro Chagas, Fiocruz, Rio de Janeiro, Brazil
| | - Flavia dos Santos
- Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Marciano Paes
- Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
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20
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A Retrospective Study of the Seroprevalence of Dengue Virus and Chikungunya Virus Exposures in Nigeria, 2010–2018. Pathogens 2022; 11:pathogens11070762. [PMID: 35890007 PMCID: PMC9318586 DOI: 10.3390/pathogens11070762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 06/25/2022] [Accepted: 06/30/2022] [Indexed: 02/01/2023] Open
Abstract
Arboviruses are important public health threats in many regions of the world. Nigeria has experienced outbreaks of arboviruses over the past decades, leading to concerns of widespread endemicity, which are frequently misdiagnosed. This study aimed to determine the seroprevalence of dengue virus (DENV) (a flavivirus) and chikungunya virus (CHIKV) (an alphavirus) infections in three major population centers of Nigeria. A convenience sample of 701 sera was collected from both healthy and febrile participants between August 2010 and March 2018. Sera were tested for prior exposure to CHIKV virus and DENV using indirect IgG ELISA. Results showed that 54.1% (379/701) of participants were seropositive for anti-DENV antibodies, 41.3% (290/701) were seropositive for anti-CHIKV antibodies, and 20.1% (141/701) had previous exposure to both. The seropositivity for prior CHIKV exposure and prior exposure to DENV and CHIKV was significantly associated with age (CHIKV: OR = 2.7 (95% CI: 1.7–4.3); DENV and CHIKV: OR = 2.2 (95% CI: 1.2–4.0) for adults compared to participants under 18 years old). Overall, the high seropositivity across all age groups suggests that arboviral infections are prevalent in Nigeria and indicates that surveillance and further epidemiological studies are required to determine the true burden of these infections and the spectrum of diseases associated with these exposures.
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21
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Nyamwaya DK, Otiende M, Mwango L, Kariuki SM, Otieno B, Omuoyo DO, Githinji G, Kitsao BS, Karanja HK, Gitonga JN, de Laurent ZR, Davies A, Mwarumba S, Agoti CN, Thumbi SM, Hamaluba MM, Newton CR, Bejon P, Warimwe GM. Incidence of chikungunya virus infections among Kenyan children with neurological disease, 2014-2018: A cohort study. PLoS Med 2022; 19:e1003994. [PMID: 35550620 PMCID: PMC9135332 DOI: 10.1371/journal.pmed.1003994] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/26/2022] [Accepted: 04/19/2022] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND Neurological complications due to chikungunya virus (CHIKV) infection have been described in different parts of the world, with children being disproportionately affected. However, the burden of CHIKV-associated neurological disease in Africa is currently unknown and given the lack of diagnostic facilities in routine care it is possible that CHIKV is an unrecognized etiology among children with encephalitis or other neurological illness. METHODS AND FINDINGS We estimated the incidence of CHIKV infection among children hospitalized with neurological disease in Kilifi County, coastal Kenya. We used reverse transcriptase polymerase chain reaction (RT-PCR) to systematically test for CHIKV in cerebrospinal fluid (CSF) samples from children aged <16 years hospitalized with symptoms of neurological disease at Kilifi County Hospital between January 2014 and December 2018. Clinical records were linked to the Kilifi Health and Demographic Surveillance System and population incidence rates of CHIKV infection estimated. There were 18,341 pediatric admissions for any reason during the 5-year study period, of which 4,332 (24%) had CSF collected. The most common clinical reasons for CSF collection were impaired consciousness, seizures, and coma (47%, 22%, and 21% of all collections, respectively). After acute investigations done for immediate clinical care, CSF samples were available for 3,980 admissions, of which 367 (9.2%) were CHIKV RT-PCR positive. Case fatality among CHIKV-positive children was 1.4% (95% CI 0.4, 3.2). The annual incidence of CHIKV-associated neurological disease varied between 13 to 58 episodes per 100,000 person-years among all children <16 years old. Among children aged <5 years, the incidence of CHIKV-associated neurological disease was 77 per 100,000 person-years, compared with 20 per 100,000 for cerebral malaria and 7 per 100,000 for bacterial meningitis during the study period. Because of incomplete case ascertainment due to children not presenting to hospital, or not having CSF collected, these are likely minimum estimates. Study limitations include reliance on hospital-based surveillance and limited CSF sampling in children in coma or other contraindications to lumbar puncture, both of which lead to under-ascertainment of incidence and of case fatality. CONCLUSIONS In this study, we observed that CHIKV infections are relatively more common than cerebral malaria and bacterial meningitis among children hospitalized with neurological disease in coastal Kenya. Given the wide distribution of CHIKV mosquito vectors, studies to determine the geographic extent of CHIKV-associated neurological disease in Africa are essential.
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Affiliation(s)
| | - Mark Otiende
- KEMRI-Wellcome Trust Research Programme, Nairobi, Kenya
| | - Lilian Mwango
- KEMRI-Wellcome Trust Research Programme, Nairobi, Kenya
| | | | | | | | | | | | | | | | | | - Alun Davies
- KEMRI-Wellcome Trust Research Programme, Nairobi, Kenya
| | | | | | - Samuel M. Thumbi
- Paul G Allen School for Global Animal Health, Washington State University, Washington, United States of America
- Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom
- Center for Epidemiological Modelling and Analysis, Institute of Tropical and Infectious Diseases, University of Nairobi, Nairobi, Kenya
| | | | | | - Philip Bejon
- KEMRI-Wellcome Trust Research Programme, Nairobi, Kenya
- Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom
| | - George M. Warimwe
- KEMRI-Wellcome Trust Research Programme, Nairobi, Kenya
- Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom
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22
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Placental Alterations in a Chikungunya-Virus-Infected Pregnant Woman: A Case Report. Microorganisms 2022; 10:microorganisms10050872. [PMID: 35630317 PMCID: PMC9144120 DOI: 10.3390/microorganisms10050872] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Revised: 03/16/2022] [Accepted: 03/17/2022] [Indexed: 02/04/2023] Open
Abstract
Chikungunya virus (CHIKV) is an arthropod-borne virus first isolated in Tanzania, Africa. The virus has spread to Asia as well as South and Central America through infected Aedes mosquitoes. Vertical transmission may also occur, and was first documented during a chikungunya outbreak in La Réunion Island in 2005. Since then, some authors have been discussing the role of the placenta in maternal–fetal CHIKV transmission. CHIKV infection is characterized by fever, headache, rash, and arthralgia. However, atypical manifestations and clinical complications, including neurological, cardiac, renal, ocular, and dermal, may occur in some cases. In this report, we describe the case of a pregnant woman infected by CHIKV during the third trimester of gestation, who presented with severe dermatological manifestations during the epidemic in Rio de Janeiro, Brazil in 2019. CHIKV RNA and antigens were detected in the placental tissue, which presented with histopathological (deciduitis, fibrin deposition, edema, fetal vessel thickening, and chorioamnionitis) and ultrastructural alterations (cytotrophoblast with mitochondrial swelling and dilated cisterns in endoplasmic reticulum, vesicles in syncytiotrophoblasts, and thickening of the basement membrane of the endothelium).
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23
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Nyamwaya DK, Thumbi SM, Bejon P, Warimwe GM, Mokaya J. The global burden of Chikungunya fever among children: A systematic literature review and meta-analysis. PLOS GLOBAL PUBLIC HEALTH 2022; 2:e0000914. [PMID: 36962807 PMCID: PMC10022366 DOI: 10.1371/journal.pgph.0000914] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 11/17/2022] [Indexed: 12/24/2022]
Abstract
Chikungunya fever (CHIKF) is an arboviral illness that was first described in Tanzania (1952). In adults, the disease is characterised by debilitating arthralgia and arthritis that can persist for months, with severe illness including neurological complications observed in the elderly. However, the burden, distribution and clinical features of CHIKF in children are poorly described. We conducted a systematic literature review and meta-analysis to determine the epidemiology of CHIKF in children globally by describing its prevalence, geographical distribution, and clinical manifestations. We searched electronic databases for studies describing the epidemiology of CHIKF in children. We included peer-reviewed primary studies that reported laboratory confirmed CHIKF. We extracted information on study details, sampling approach, study participants, CHIKF positivity, clinical presentation and outcomes of CHIKF in children. The quality of included studies was assessed using Joanna Briggs Institute Critical Appraisal tool for case reports and National Institute of Health quality assessment tool for quantitative studies and case series. Random-effects meta-analysis was used to estimate the pooled prevalence of CHIKF among children by geographical location. We summarised clinical manifestations, laboratory findings, administered treatment and disease outcomes associated with CHIKF in children. We identified 2104 studies, of which 142 and 53 articles that met the inclusion criteria were included in the systematic literature review and meta-analysis, respectively. Most of the selected studies were from Asia (54/142 studies) and the fewest from Europe (5/142 studies). Included studies were commonly conducted during an epidemic season (41.5%) than non-epidemic season (5.1%). Thrombocytopenia was common among infected children and CHIKF severity was more prevalent in children <1 year. Children with undifferentiated fever before CHIKF was diagnosed were treated with antibiotics and/or drugs that managed specific symptoms or provided supportive care. CHIKF is a significant under-recognised and underreported health problem among children globally and development of drugs/vaccines should target young children.
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Affiliation(s)
- Doris K Nyamwaya
- KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
- Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom
| | - Samuel M Thumbi
- Paul G Allen School for Global Health, Washington State University, Pullman, Washington, United States of America
- Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom
- Center for Epidemiological Modelling and Analysis, Institute of Tropical and Infectious Diseases, University of Nairobi, Nairobi, Kenya
| | - Philip Bejon
- KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
- Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom
| | - George M Warimwe
- KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
- Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom
| | - Jolynne Mokaya
- KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
- Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom
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24
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Constant LEC, Rajsfus BF, Carneiro PH, Sisnande T, Mohana-Borges R, Allonso D. Overview on Chikungunya Virus Infection: From Epidemiology to State-of-the-Art Experimental Models. Front Microbiol 2021; 12:744164. [PMID: 34675908 PMCID: PMC8524093 DOI: 10.3389/fmicb.2021.744164] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 09/07/2021] [Indexed: 12/27/2022] Open
Abstract
Chikungunya virus (CHIKV) is currently one of the most relevant arboviruses to public health. It is a member of the Togaviridae family and alphavirus genus and causes an arthritogenic disease known as chikungunya fever (CHIKF). It is characterized by a multifaceted disease, which is distinguished from other arbovirus infections by the intense and debilitating arthralgia that can last for months or years in some individuals. Despite the great social and economic burden caused by CHIKV infection, there is no vaccine or specific antiviral drugs currently available. Recent outbreaks have shown a change in the severity profile of the disease in which atypical and severe manifestation lead to hundreds of deaths, reinforcing the necessity to understand the replication and pathogenesis processes. CHIKF is a complex disease resultant from the infection of a plethora of cell types. Although there are several in vivo models for studying CHIKV infection, none of them reproduces integrally the disease signature observed in humans, which is a challenge for vaccine and drug development. Therefore, understanding the potentials and limitations of the state-of-the-art experimental models is imperative to advance in the field. In this context, the present review outlines the present knowledge on CHIKV epidemiology, replication, pathogenesis, and immunity and also brings a critical perspective on the current in vitro and in vivo state-of-the-art experimental models of CHIKF.
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Affiliation(s)
- Larissa E. C. Constant
- Departamento de Biotecnologia Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
- Laboratório de Biotecnologia e Bioengenharia Estrutural, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Bia F. Rajsfus
- Departamento de Biotecnologia Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
- Laboratório de Biotecnologia e Bioengenharia Estrutural, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Pedro H. Carneiro
- Laboratório de Biotecnologia e Bioengenharia Estrutural, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Tháyna Sisnande
- Laboratório de Biotecnologia e Bioengenharia Estrutural, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Ronaldo Mohana-Borges
- Laboratório de Biotecnologia e Bioengenharia Estrutural, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Diego Allonso
- Departamento de Biotecnologia Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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25
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Chikungunya and arthritis: An overview. Travel Med Infect Dis 2021; 44:102168. [PMID: 34563686 DOI: 10.1016/j.tmaid.2021.102168] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 09/08/2021] [Accepted: 09/15/2021] [Indexed: 12/22/2022]
Abstract
Chikungunya is caused by CHIKV (chikungunya virus), an emerging and re-emerging arthropod-vectored viral infection that causes a febrile disease with primarily long term sequelae of arthralgia and myalgia and is fatal in a small fraction of infected patients. Sporadic outbreaks have been reported from different parts of the world chiefly Africa, Asia, the Indian and Pacific ocean regions, Europe and lately even in the Americas. Currently, treatment is primarily symptomatic as no vaccine, antibody-mediated immunotherapy or antivirals are available. Chikungunya belongs to a family of arthritogenic alphaviruses which have many pathophysiological similarities. Chikungunya arthritis has similarities and differences with rheumatoid arthritis. Although research into arthritis caused by these alphaviruses have been ongoing for decades and significant progress has been made, the mechanisms underlying viral infection and arthritis are not well understood. In this review, we give a background to chikungunya and the causative virus, outline the history of alphavirus arthritis research and then give an overview of findings on arthritis caused by CHIKV. We also discuss treatment options and the research done so far on various therapeutic intervention strategies.
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26
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Gupta S, Mishra KP, Gupta R, Singh SB. Andrographolide - A prospective remedy for chikungunya fever and viral arthritis. Int Immunopharmacol 2021; 99:108045. [PMID: 34435582 DOI: 10.1016/j.intimp.2021.108045] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 08/01/2021] [Accepted: 08/01/2021] [Indexed: 12/14/2022]
Abstract
AIM Andrographolide, the major bioactive compound of the plant Andrographis paniculata, exerts anti-inflammatory, cyto-, neuro- and hepato-protective effects. Traditional remedies for infectious diseases include A. paniculata for maladies like fever, pain, rashes which are associated with chikungunya and other arboviral diseases. Since andrographolide and A. paniculata have potent antiviral properties, the present review aims to provide a comprehensive report of symptoms and immunological molecules involved in chikungunya virus (CHIKV) infection and the therapeutic role of andrographolide in the mitigation of chikungunya and associated symptoms. MATERIALS AND METHODS Studies on the therapeutic role of A. paniculata and andrographolide in chikungunya and other viral infections published between 1991 and 2021 were searched on various databases. RESULTS AND DISCUSSION The havoc created by chikungunya is due to the associated debilitating symptoms including arthralgia and myalgia which sometimes remains for years. The authors reviewed and summarized the various symptoms and immunological molecules related to CHIKV replication and associated inflammation, oxidative and unfolded protein stress, apoptosis and arthritis. Additionally, the authors suggested andrographolide as a remedy for chikungunya and other arboviral infections by highlighting its role in the regulation of molecules involved in unfolded protein response pathway, immunomodulation, inflammation, virus multiplication, oxidative stress, apoptosis and arthritis. CONCLUSION The present review demonstrated the major complications associated with chikungunya and the role of andrographolide in alleviating the chikungunya associated symptoms to encourage further investigations using this promising compound towards early development of an anti-CHIKV drug. Chemical Compound studied: andrographolide (PubChem CID: 5318517).
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Affiliation(s)
- Swati Gupta
- Division of Epidemiology and Communicable Diseases, Indian Council of Medical Research (ICMR), Ansari Nagar, New Delhi 110029, India.
| | - K P Mishra
- Defence Research and Development Organization (DRDO)-HQ, Rajaji Marg, New Delhi 110011, India
| | - Rupali Gupta
- Department of Neurology, Duke University Medical Center, Durham, NC, United States
| | - S B Singh
- National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
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27
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Manzoor KN, Javed F, Ejaz M, Ali M, Mujaddadi N, Khan AA, Khattak AA, Zaib A, Ahmad I, Saeed WK, Manzoor S. The global emergence of Chikungunya infection: An integrated view. Rev Med Virol 2021; 32:e2287. [PMID: 34428335 DOI: 10.1002/rmv.2287] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 08/08/2021] [Accepted: 08/09/2021] [Indexed: 11/08/2022]
Abstract
Chikungunya virus (CHIKV) is one of the emerging viruses around the globe. It belongs to the family Togaviridae and genus Alphavirus and is an arthropod borne virus that transmits by the bite of an infected mosquito, mainly through Aedes aegypti and Aedes albopcitus. It is a spherical, enveloped virus with positive single stranded RNA genome. It was first discovered during 1952-53 in Tanganyika, after which outbreaks were documented in many regions of the world. CHIKV has two transmission cycles; an enzootic sylvatic cycle and an urban cycle. CHIKV genome contains 11,900 nucleotides and two open reading frames and shows great sequence variability. Molecular mechanisms of virus host-cell interactions and the pathogenesis of disease are not fully understood. The disease involves three phases; acute, post-acute and chronic with symptoms including high-grade fever, arthralgia, macupapular rashes and headache. There is no licensed vaccine or specific treatment for CHIKV infection. This lack of specific interventions combined with difficulties in making a precise diagnosis together make the disease difficult to manage. In this review we aim to present the current knowledge of global epidemiology, transmission, structure, various aspects of diagnosis as well as highlight potential antiviral drugs and vaccines against CHIKV.
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Affiliation(s)
| | - Farakh Javed
- Department of Biomedical Sciences, Pak-Autria Fachhochschule: Institute of Applied Sciences & Technology, Haripur, Pakistan
| | - Muhammad Ejaz
- Department of Microbiology, The University of Haripur, Haripur, Pakistan
| | - Mubashar Ali
- Department of Microbiology, The University of Haripur, Haripur, Pakistan
| | - Neelam Mujaddadi
- Department of Microbiology, The University of Haripur, Haripur, Pakistan
| | - Abid Ali Khan
- Institute of Precision Medicine, Hochschule Furtwangen University, Furtwangen im Schwarzwald, Germany
| | - Aamer Ali Khattak
- Department of Medical Lab Technology, The University of Haripur, Haripur, Pakistan
| | - Assad Zaib
- Department of Medical Lab Technology, The University of Haripur, Haripur, Pakistan
| | - Ibrar Ahmad
- Center for Human Genetics, Hazara University, Mansehra, Pakistan
| | - Waqar Khalid Saeed
- Department of Biomedical Sciences, Pak-Autria Fachhochschule: Institute of Applied Sciences & Technology, Haripur, Pakistan
| | - Sobia Manzoor
- Atta-ur-Rehman school of applied biosciences, National University of science and Technology, Islamabad, Pakistan
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28
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Traverse EM, Hopkins HK, Vaidhyanathan V, Barr KL. Cardiomyopathy and Death Following Chikungunya Infection: An Increasingly Common Outcome. Trop Med Infect Dis 2021; 6:108. [PMID: 34206332 PMCID: PMC8293388 DOI: 10.3390/tropicalmed6030108] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 06/14/2021] [Accepted: 06/18/2021] [Indexed: 12/13/2022] Open
Abstract
Chikungunya virus (CHIKV) is vectored by Aedes aegypti and Aedes albopictus mosquitoes and is found throughout tropical and sub-tropical regions. While most infections cause mild symptoms such as fever and arthralgia, there have been cases in which cardiac involvement has been reported. In adults, case reports include symptoms ranging from tachycardia and arrythmia, to myocarditis and cardiac arrest. In children, case reports describe symptoms such as arrythmia, myocarditis, and heart failure. Case reports of perinatal and neonatal CHIKV infections have also described cardiovascular compromise, including myocardial hypertrophy, ventricular dysfunction, myocarditis, and death. Myocarditis refers to inflammation of the heart tissue, which can be caused by viral infection, thus becoming viral myocarditis. Since viral myocarditis is linked as a causative factor of other cardiomyopathies, including dilated cardiomyopathy, in which the heart muscle weakens and fails to pump blood properly, the connection between CHIKV and the heart is concerning. We searched Pubmed, Embase, LILACS, and Google Scholar to identify case reports of CHIKV infections where cardiac symptoms were reported. We utilized NCBI Virus and NCBI Nucleotide to explore the lineage/evolution of strains associated with these outbreaks. Statistical analysis was performed to identify which clinical features were associated with death. Phylogenetic analysis determined that CHIKV infections with cardiac symptoms are associated with the Asian, the East Central South African, and the Indian Ocean lineages. Of patients admitted to hospital, death rates ranged from 26-48%. Myocarditis, hypertension, pre-existing conditions, and the development of heart failure were significantly correlated with death. As such, clinicians should be aware in their treatment and follow-up of patients.
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Affiliation(s)
- Elizabeth M. Traverse
- Center for Global Health and Infectious Disease Research, University of South Florida, Tampa, FL 33612, USA; (E.M.T.); (H.K.H.)
| | - Hannah K. Hopkins
- Center for Global Health and Infectious Disease Research, University of South Florida, Tampa, FL 33612, USA; (E.M.T.); (H.K.H.)
| | | | - Kelli L. Barr
- Center for Global Health and Infectious Disease Research, University of South Florida, Tampa, FL 33612, USA; (E.M.T.); (H.K.H.)
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29
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Hibl BM, Dailey Garnes NJM, Kneubehl AR, Vogt MB, Spencer Clinton JL, Rico-Hesse RR. Mosquito-bite infection of humanized mice with chikungunya virus produces systemic disease with long-term effects. PLoS Negl Trop Dis 2021; 15:e0009427. [PMID: 34106915 PMCID: PMC8189471 DOI: 10.1371/journal.pntd.0009427] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Accepted: 05/02/2021] [Indexed: 12/13/2022] Open
Abstract
Chikungunya virus (CHIKV) is an emerging, mosquito-borne alphavirus responsible for acute to chronic arthralgias and neuropathies. Although it originated in central Africa, recent reports of disease have come from many parts of the world, including the Americas. While limiting human CHIKV cases through mosquito control has been used, it has not been entirely successful. There are currently no licensed vaccines or treatments specific for CHIKV disease, thus more work is needed to develop effective countermeasures. Current animal research on CHIKV is often not representative of human disease. Most models use CHIKV needle inoculation via unnatural routes to create immediate viremia and localized clinical signs; these methods neglect the natural route of transmission (the mosquito vector bite) and the associated human immune response. Since mosquito saliva has been shown to have a profound effect on viral pathogenesis, we evaluated a novel model of infection that included the natural vector, Aedes species mosquitoes, transmitting CHIKV to mice containing components of the human immune system. Humanized mice infected by 3-6 mosquito bites showed signs of systemic infection, with demonstrable viremia (by qRT-PCR and immunofluorescent antibody assay), mild to moderate clinical signs (by observation, histology, and immunohistochemistry), and immune responses consistent with human infection (by flow cytometry and IgM ELISA). This model should give a better understanding of human CHIKV disease and allow for more realistic evaluations of mechanisms of pathogenesis, prophylaxis, and treatments.
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Affiliation(s)
- Brianne M. Hibl
- Center for Comparative Medicine, Baylor College of Medicine, Houston, Texas, United States of America
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America
| | - Natalie J. M. Dailey Garnes
- Section of Infectious Disease, Department of Internal Medicine, Baylor College of Medicine, Houston, Texas, United States of America
- Section of Pediatric Infectious Diseases, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America
| | - Alexander R. Kneubehl
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America
| | - Megan B. Vogt
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America
- Integrative Molecular and Biomedical Sciences Graduate Program, Baylor College of Medicine, Houston, Texas, United States of America
| | - Jennifer L. Spencer Clinton
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America
| | - Rebecca R. Rico-Hesse
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America
- * E-mail:
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de St Maurice A, Ervin E, Chu A. Ebola, Dengue, Chikungunya, and Zika Infections in Neonates and Infants. Clin Perinatol 2021; 48:311-329. [PMID: 34030816 DOI: 10.1016/j.clp.2021.03.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Emerging infectious diseases, including Ebola, chikungunya, Zika, and dengue, may have significant impacts on maternal-fetal dyads and neonatal outcomes. Pregnant women infected with Ebola demonstrate high mortality and very low evidence of neonatal survival. Maternal chikungunya infection can result in high rates of perinatal transmission, and infected neonates demonstrate variable disease severity. Dengue can be transmitted to neonates via vertical transmission or perinatal transmission. Zika is characterized by mild disease in pregnant women, but congenital infection can be severe. Treatment largely is supportive for these diseases, and vaccine development remains under way, with promising recent advances, notably for Ebola.
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Affiliation(s)
- Annabelle de St Maurice
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Los Angeles, 924 Westwood Boulevard, Suite 900, CA 90095, USA.
| | - Elizabeth Ervin
- Post-baccalaureate Premedical Program, University of Michigan, Office of Graduate and Postdoctoral Studies, 2960 Taubman Health Science Library, 1135 Catherine Street, Ann Arbor, MI 48109, USA
| | - Alison Chu
- Division of Neonatology and Developmental Biology, Department of Pediatrics, 10833 Le Conte Avenue, MDCC B2-411, Los Angeles, CA 90095, USA
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31
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Gupta V, Gupta N, Pandita A. Neonate with chikungunya. Clin Case Rep 2021; 9:e04351. [PMID: 34136251 PMCID: PMC8190531 DOI: 10.1002/ccr3.4351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Revised: 03/31/2021] [Accepted: 05/03/2021] [Indexed: 11/27/2022] Open
Abstract
Chikungunya although rare should be considered in any neonate presenting with fever and facial hyperpigmentation or encephalopathy especially in endemic areas.
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Vertical transmission of chikungunya virus: A systematic review. PLoS One 2021; 16:e0249166. [PMID: 33891622 PMCID: PMC8064608 DOI: 10.1371/journal.pone.0249166] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 03/13/2021] [Indexed: 01/23/2023] Open
Abstract
Objectives To describe and estimate the frequency of pregnancy outcomes, clinical and laboratory characteristics of vertical transmission of CHIKV in the neonate. Study design We performed a systematic review evaluating the clinical presentation of perinatally-acquired CHIKV infection in neonates. The search was performed using Medline (via PubMed), LILACS, Web of Science, Scielo, Google Scholar and Open grey to identify studies assessing vertical transmission of CHIKV up to November 3, 2020. There were no search restrictions regarding the study type, the publication date or language. Studies with no documented evidence of CHIKV infection in neonates (negative RT-PCR or absence of IgM) were excluded. Results From the 227 studies initially identified, 42 were selected as follows: 28 case reports, 7 case series, 2 cross-sectional studies and 5 cohort studies, for a total of 266 CHIKV infected neonates confirmed by serological and/or molecular tests. The vertical transmission rate was 50% in the Reunion Island outbreak, which was the subject of the majority of the studies; the premature delivery were reported in 19 (45.2%) studies; the rate of fetal distress was 19.6% of infected babies and fetal loss occurred in 2% of the cases. Approximately 68.7% of newborns were diagnosed with encephalopathy or encephalitis after perinatally acquired CHIKV. Most of the infected neonates were born healthy, developing CHIKV sepsis clinical syndrome within the first week of life. Conclusions We alert neonatologists to the late manifestations of neonatal CHIKV infection, relevant to the management and reduction of morbidity. A limitation of our review was that it was not possible to carry out meta-analysis due to differences in study design and the small number of participants.
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Ginige S, Flower R, Viennet E. Neonatal Outcomes From Arboviruses in the Perinatal Period: A State-of-the-Art Review. Pediatrics 2021; 147:peds.2020-009720. [PMID: 33737375 DOI: 10.1542/peds.2020-009720] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/04/2020] [Indexed: 11/24/2022] Open
Abstract
Since the 2016 Zika outbreak and the understanding of the teratogenic effect of this infection, there has been a newfound interest in arbovirus infections and their effects on pregnancy, resulting in numerous publications in the last 5 years. However, limited literature focuses on arbovirus infection in different stages of pregnancy and their effect on the neonate. There is currently no consensus management of perinatal acquisition of arboviruses, and current evidence is largely anecdotal observational reports. Teratogens can have different effects on the developing fetus depending on the time of infection, so infections during pregnancy should be analyzed by trimester. A better understanding of arbovirus infection in the perinatal period is required to assist obstetric, neonatal, and pediatric clinicians in making decisions about the management of mother and neonate. Our objective was to assess the evidence of adverse neonatal outcomes for several arboviral infections when contracted during the perinatal period to guide clinicians in managing these patients. There are 8 arboviruses for which neonatal outcomes from maternal acquisition in the perinatal period have been reported, with the most data for dengue and Chikungunya virus infections. The evidence reviewed in this article supports the adoption of preventive strategies to avoid ticks and mosquitoes close to the date of delivery. For the other arbovirus infections, further community-based cohort studies during outbreaks are required to evaluate whether these infections have a similar teratogenic impact.
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Salomão N, Brendolin M, Rabelo K, Wakimoto M, de Filippis AM, dos Santos F, Moreira ME, Basílio-de-Oliveira CA, Avvad-Portari E, Paes M, Brasil P. Spontaneous Abortion and Chikungunya Infection: Pathological Findings. Viruses 2021; 13:v13040554. [PMID: 33806252 PMCID: PMC8067258 DOI: 10.3390/v13040554] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Revised: 01/15/2021] [Accepted: 01/21/2021] [Indexed: 01/18/2023] Open
Abstract
Intrauterine transmission of the Chikungunya virus (CHIKV) during early pregnancy has rarely been reported, although vertical transmission has been observed in newborns. Here, we report four cases of spontaneous abortion in women who became infected with CHIKV between the 11th and 17th weeks of pregnancy. Laboratorial confirmation of the infection was conducted by RT-PCR on a urine sample for one case, and the other three were by detection of IgM anti-CHIKV antibodies. Hematoxylin and eosin (H&E) staining and an electron microscopy assay allowed us to find histopathological, such as inflammatory infiltrate in the decidua and chorionic villi, as well as areas of calcification, edema and the deposition of fibrinoid material, and ultrastructural changes, such as mitochondria with fewer cristae and ruptured membranes, endoplasmic reticulum with dilated cisterns, dispersed chromatin in the nuclei and the presence of an apoptotic body in case 1. In addition, by immunohistochemistry (IHC), we found a positivity for the anti-CHIKV antibody in cells of the endometrial glands, decidual cells, syncytiotrophoblasts, cytotrophoblasts, Hofbauer cells and decidual macrophages. Electron microscopy also helped in identifying virus-like particles in the aborted material with a diameter of 40–50 nm, which was consistent with the size of CHIKV particles in the literature. Our findings in this study suggest early maternal fetal transmission, adding more evidence on the role of CHIKV in fetal death.
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Affiliation(s)
- Natália Salomão
- Interdisciplinary Medical Research Laboratory Rio de Janeiro, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil;
| | - Michelle Brendolin
- Acute Febrile Diseases Laboratory, Evandro Chagas National Infectiology Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, Brazil; (M.B.); (M.W.)
| | - Kíssila Rabelo
- Ultrastructure and Tissue Biology Laboratory Rio de Janeiro, Rio de Janeiro State University, Rio de Janeiro 20551-030, Brazil;
| | - Mayumi Wakimoto
- Acute Febrile Diseases Laboratory, Evandro Chagas National Infectiology Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, Brazil; (M.B.); (M.W.)
| | - Ana Maria de Filippis
- Flaviviruses Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil;
| | - Flavia dos Santos
- Viral Immunology Laboratory, Oswaldo Cruz Institute Rio de Janeiro, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil;
| | - Maria Elizabeth Moreira
- National Institute of Women, Children and Adolescents Health Fernandes Figueira, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil; (M.E.M.); (E.A.-P.)
| | - Carlos Alberto Basílio-de-Oliveira
- Pathological Anatomy, Gaffrée Guinle University Hospital Rio de Janeiro, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-004, Brazil;
| | - Elyzabeth Avvad-Portari
- National Institute of Women, Children and Adolescents Health Fernandes Figueira, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil; (M.E.M.); (E.A.-P.)
| | - Marciano Paes
- Interdisciplinary Medical Research Laboratory Rio de Janeiro, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil;
- Correspondence: (M.P.); (P.B.)
| | - Patrícia Brasil
- Acute Febrile Diseases Laboratory, Evandro Chagas National Infectiology Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, Brazil; (M.B.); (M.W.)
- Correspondence: (M.P.); (P.B.)
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Khongwichit S, Chansaenroj J, Thongmee T, Benjamanukul S, Wanlapakorn N, Chirathaworn C, Poovorawan Y. Large-scale outbreak of Chikungunya virus infection in Thailand, 2018-2019. PLoS One 2021; 16:e0247314. [PMID: 33690657 PMCID: PMC7946318 DOI: 10.1371/journal.pone.0247314] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Accepted: 02/04/2021] [Indexed: 01/12/2023] Open
Abstract
Between 2018 and 2019, the incidence of chikungunya was approximately 15,000 cases across 60 provinces in Thailand. Here, the clinical presentations in chikungunya, emergent pattern, and genomic diversity of the chikungunya virus (CHIKV) causing this massive outbreak were demonstrated. A total of 1,806 sera samples from suspected cases of chikungunya were collected from 13 provinces in Thailand, and samples were tested for the presence of CHIKV RNA, IgG, and IgM using real-time PCR, enzyme-linked immunoassay (ELISA), commercial immunoassay (rapid test). The phylogenetic tree of CHIKV whole-genome and CHIKV E1 were constructed using the maximum-likelihood method. CHIKV infection was confirmed in 547 (42.2%) male and 748 (57.8%) female patients by positive real-time PCR results and/or CHIKV IgM antibody titers. Unsurprisingly, CHIKV RNA was detected in >80% of confirmed cases between 1 and 5 days after symptom onset, whereas anti-CHIKV IgM was detectable in >90% of cases after day 6. Older age was clearly one of the risk factors for the development of arthralgia in infected patients. Although phylogenetic analysis revealed that the present CHIKV Thailand strain of 2018–2020 belongs to the East, Central, and Southern African (ECSA) genotype similar to the CHIKV strains that caused outbreaks during 2008–2009 and 2013, all present CHIKV Thailand strains were clustered within the recent CHIKV strain that caused an outbreak in South Asia. Interestingly, all present CHIKV Thailand strains possess two mutations, E1-K211E, and E2-V264A, in the background of E1-226A. These mutations are reported to be associated with virus-adapted Aedes aegypti. Taken together, it was likely that the present CHIKV outbreak in Thailand occurred as a result of the importation of the CHIKV strain from South Asia. Understanding with viral genetic diversity is essential for epidemiological study and may contribute to better disease management and preventive measures.
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Affiliation(s)
- Sarawut Khongwichit
- Department of Pediatrics, Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Jira Chansaenroj
- Department of Pediatrics, Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Thanunrat Thongmee
- Department of Pediatrics, Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | | | - Nasamon Wanlapakorn
- Department of Pediatrics, Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Division of Academic Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Chintana Chirathaworn
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Tropical Medicine Cluster, Chulalongkorn University, Bangkok, Thailand
- * E-mail: (YP); (CC)
| | - Yong Poovorawan
- Department of Pediatrics, Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- * E-mail: (YP); (CC)
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Ribeiro IM, Souto PCS, Borbely AU, Tanabe ELL, Cadavid A, Alvarez AM, Bueno J, Agudelo O, Robles RG, Ayala-Ramírez P, Sacerdoti F, Szasz T, Damiano AE, Ibarra C, Escudero C, Lima VV, Giachini FR. The limited knowledge of placental damage due to neglected infections: ongoing problems in Latin America. Syst Biol Reprod Med 2021; 66:151-169. [PMID: 32482148 DOI: 10.1080/19396368.2020.1753850] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
The placenta works as a selective barrier, protecting the fetus from potential infections that may affect the maternal organism during pregnancy. In this review, we will discuss several challenging infections that are common within Latin American countries and that may affect the maternal-fetal interface and pose risks to fetal development. Specifically, we will focus on emerging infectious diseases including the arboviruses, malaria, leishmaniasis, and the bacterial foodborne disease caused by Shiga toxin-producing Escherichia coli. We will also highlight some topics of interest currently being studied by research groups that comprise an international effort aimed at filling the knowledge gaps in this field. These topics address the relationship between exposure to microorganisms and placental abnormalities, congenital anomalies, and complications of pregnancy. ABBREVIATIONS ADE: antibody-dependent enhancement; CCL2: monocyte chemoattractant protein-1; CCL3: macrophage inflammatory protein-1 α; CCL5: chemokine (C-C motif) ligand 5; CHIKV: chikungunya virus; DCL: diffuse cutaneous leishmaniasis; DENV: dengue virus; Gb3: glycolipid globotriaosylceramyde; HIF: hypoxia-inducible factor; HUS: hemolytic uremic syndrome; IFN: interferon; Ig: immunoglobulins; IL: interleukin; IUGR: intrauterine growth restriction; LCL: localized cutaneous leishmaniasis; LPS: lipopolysaccharid; MCL: mucocutaneous leishmaniasis; NO: nitric oxide; PCR: polymerase chain reaction; PGF: placental growth factor; PM: placental malaria; RIVATREM: Red Iberoamericana de Alteraciones Vasculares em transtornos del Embarazo; sVEGFR: soluble vascular endothelial growth factor receptor; STEC: shiga toxin-producing Escherichia coli; stx: shiga toxin protein; TNF: tumor necrosis factor; TOAS: T cell original antigenic sin; Var2CSA: variant surface antigen 2-CSA; VEGF: vascular endothelial growth factor; VL: visceral leishmaniasis; WHO: world health organization; YFV: yellow fever virus; ZIKV: Zika virus.
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Affiliation(s)
- Isabela Moreti Ribeiro
- Laboratory of Vascular Biology and Histopathology, Institute of Health Sciences and Health, Federal University of Mato Grosso , Barra Do Garcas, Brazil
| | - Paula Cristina Souza Souto
- Laboratory of Vascular Biology and Histopathology, Institute of Health Sciences and Health, Federal University of Mato Grosso , Barra Do Garcas, Brazil
| | - Alexandre U Borbely
- Cell Biology Laboratory, Institute of Health and Biological Sciences, Federal University of Alagoas , Alagoas, Brazil
| | - Eloiza Lopes Lira Tanabe
- Cell Biology Laboratory, Institute of Health and Biological Sciences, Federal University of Alagoas , Alagoas, Brazil
| | - Angela Cadavid
- Grupo Reproducción, Facultad De Medicina Universidad De Antioquia , Medellin, Colombia
| | - Angela M Alvarez
- Grupo Reproducción, Facultad De Medicina Universidad De Antioquia , Medellin, Colombia
| | - Julio Bueno
- Grupo Reproducción, Facultad De Medicina Universidad De Antioquia , Medellin, Colombia
| | - Olga Agudelo
- Grupo Salud Y Comunidad, Facultad De Medicina Universidad De Antioquia , Medellin, Colombia
| | - Reggie García Robles
- Physiological Sciences Department, Faculty of Medicine, Pontificia Universidad Javeriana , Bogotá, Colombia
| | - Paola Ayala-Ramírez
- Human Genetics Institute, Facultad De Medicina, Pontificia Universidad Javeriana , Bogotá, Colombia
| | - Flavia Sacerdoti
- Laboratorio De Fisiopatogenia, Instituto De Fisiología Y Biofísica Bernardo Houssay (IFIBIO)- CONICET- Departamento De Fisiología, Facultad De Medicina, Universidad De Buenos Aires . Buenos Aires, Argentina
| | - Theodora Szasz
- Departamento of Physiology, Augusta University , Augusta, USA
| | - Alicia E Damiano
- Cátedra De Biología Celular Y Molecular, Departamento De Ciencias Biológicas, Facultad De Farmacia Y Bioquímica, Universidad De Buenos Aires . Buenos Aires, Argentina.,Laboratorio De Biología De La Reproducción, Instituto De Fisiología Y Biofísica Bernardo Houssay (IFIBIO)- CONICET- Facultad De Medicina, Universidad De Buenos Aires . Buenos Aires, Argentina
| | - Cristina Ibarra
- Cátedra De Biología Celular Y Molecular, Departamento De Ciencias Biológicas, Facultad De Farmacia Y Bioquímica, Universidad De Buenos Aires . Buenos Aires, Argentina
| | - Carlos Escudero
- Vascular Physiology Laboratory, Group of Research and Innovation in Vascular Health (GRIVAS Health), Basic Sciences Department Faculty of Sciences, Universidad Del Bio-Bio , Chillan, Chile
| | - Victor V Lima
- Laboratory of Vascular Biology and Histopathology, Institute of Health Sciences and Health, Federal University of Mato Grosso , Barra Do Garcas, Brazil
| | - Fernanda R Giachini
- Laboratory of Vascular Biology and Histopathology, Institute of Health Sciences and Health, Federal University of Mato Grosso , Barra Do Garcas, Brazil
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Waechter R, Ingraham E, Evans R, Cudjoe N, Krystosik A, Isaac R, Watts A, Noël T, Landon B, Fernandes M, Mapp-Alexander V, Suresh P, Mitchell G, Macpherson C, Gérardin P, LaBeaud AD. Pre and postnatal exposure to Chikungunya virus does not affect child neurodevelopmental outcomes at two years of age. PLoS Negl Trop Dis 2020; 14:e0008546. [PMID: 33017393 PMCID: PMC7535067 DOI: 10.1371/journal.pntd.0008546] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 06/30/2020] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND The 2005-06 chikungunya virus (CHIKV) outbreak in La Réunion suggested that mothers could transmit CHIKV to their neonates while viremic during the intrapartum period, and more than half of the infected neonates showed impaired neurodevelopment at two years of age. However, data sparsity precluded an overview of the developmental impact of vertical infection within the whole prenatal period. OBJECTIVE & METHODS The current study assessed two-year old children born to mothers who were infected during the 2014 CHIKV outbreak in Grenada to determine the neurodevelopmental impact of perinatal CHIKV infection throughout gestation. Mother and child infection status were confirmed by serologic testing (IgG and IgM) for CHIKV. Cognitive, fine motor, gross motor, language and behavioral outcomes were assessed at two years of age on the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA). RESULTS No differences in neurodevelopmental outcomes were observed between two-year-old children born to mothers infected with CHIKV during gestation (n = 149) and those born to mothers not infected with CHIKV (n = 161). No differences were found in INTER-NDA scores between children infected with CHIKV (n = 47) and children not infected with CHIKV (n = 592). Likewise, there were no differences between children infected with CHIKV post-partum (n = 19) versus children not infected with CHIKV (n = 592). CONCLUSION Our findings suggest that children exposed and/or infected with CHIKV outside of the intrapartum period experience no significant neurodevelopmental delay at two years of age, as measured by the INTER-NDA, compared to their unexposed and/or uninfected peers. These results complement those of previous studies which showed a neurodevelopmental risk only for children infected during the intrapartum period, while the mother was highly viremic. These results might be reassuring for women of childbearing age and public health officials in CHIKV-endemic regions.
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Affiliation(s)
- Randall Waechter
- Department of Neuroscience and Physiology and Behavioral Sciences, School of Medicine, St. George’s University, St. George’s, Grenada, West Indies
- Windward Islands Research and Education Foundation, St. George’s, Grenada, West Indies
| | - Erinique Ingraham
- Windward Islands Research and Education Foundation, St. George’s, Grenada, West Indies
| | - Roberta Evans
- Windward Islands Research and Education Foundation, St. George’s, Grenada, West Indies
| | - Nikita Cudjoe
- Windward Islands Research and Education Foundation, St. George’s, Grenada, West Indies
| | - Amy Krystosik
- Stanford University, School of Medicine, Department of Pediatrics, Division of Infectious Disease, California, United States of America
| | - Rashida Isaac
- Windward Islands Research and Education Foundation, St. George’s, Grenada, West Indies
| | - Ashlee Watts
- Windward Islands Research and Education Foundation, St. George’s, Grenada, West Indies
| | - Trevor Noël
- Windward Islands Research and Education Foundation, St. George’s, Grenada, West Indies
- Office of Research, St. George’s University, St. George’s, Grenada, West Indies
| | - Barbara Landon
- Windward Islands Research and Education Foundation, St. George’s, Grenada, West Indies
- Psychological Services Center, St. George’s University, St. George’s, Grenada, West Indies
| | - Michelle Fernandes
- Faculty of Medicine, Department of Paediatrics, University Hospitals Southampton, University of Southampton, Southampton, United Kingdom
- Nuffield Department of Women’s & Reproductive Health, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
| | - Veronica Mapp-Alexander
- Windward Islands Research and Education Foundation, St. George’s, Grenada, West Indies
- School of Veterinary Medicine, St. George’s University, St. George’s, Grenada, West Indies
| | - Priyanka Suresh
- Stanford University, School of Medicine, Department of Pediatrics, Division of Infectious Disease, California, United States of America
| | - George Mitchell
- Office of Chief Medical Officer, Ministry of Health, St, George’s, Grenada, West Indies
| | - Calum Macpherson
- Windward Islands Research and Education Foundation, St. George’s, Grenada, West Indies
- Office of Research, St. George’s University, St. George’s, Grenada, West Indies
| | - Patrick Gérardin
- INSERM CIC1410, Centre Hospitalier Universitaire de la Réunion, Saint Pierre, Réunion / Unité Mixte 134 PIMIT (Université de La Réunion, CNRS 9192, INSERM U1187, IRD 249), Sainte Clotilde, Réunion
| | - A. Desiree LaBeaud
- Stanford University, School of Medicine, Department of Pediatrics, Division of Infectious Disease, California, United States of America
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38
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Perinatal chikungunya induced scalded skin syndrome. IDCases 2020; 22:e00969. [PMID: 33088712 PMCID: PMC7558828 DOI: 10.1016/j.idcr.2020.e00969] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 09/22/2020] [Accepted: 09/22/2020] [Indexed: 11/21/2022] Open
Abstract
Chikungunya is a rapidly emerging infectious disease worldwide caused by a virus that belongs to the Togaviridae family. It can have varied presentations, but vesiculobullous lesions are commonly described. A widespread dissemination of such lesions, however, is extremely rare. Person-to-person transmission has not been documented, but rare reports have described maternal-fetal vertical transmission. We herein describe a unique case of congenital chikungunya resulting in a staphylococcal scalded skin syndrome-like presentation and discuss the clinical presentation, underlying pathophysiology, and how to differentiate this condition from true Stevens Johnson Syndrome-Toxic epidermal Necrolysis (SJS-TEN).
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39
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Corrêa DG, Di Maio Ferreira FCPDA, Hygino da Cruz LC, Brasil P, Rueda Lopes FC. Longitudinal brain magnetic resonance imaging of children with perinatal Chikungunya encephalitis. Neuroradiol J 2020; 33:532-537. [PMID: 32955404 DOI: 10.1177/1971400920959070] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Chikungunya virus can be transmitted perinatally leading to serious neurological sequelae. We report the longitudinal evolution of the brain magnetic resonance imaging aspects of three cases of mother-to-child Chikungunya virus transmission. The first magnetic resonance imaging scan presented brain cavitations, with or without corpus callosum diffusion restriction. Follow-up scans showed reduction in the volume of cavitations, with resolution of the restricted diffusion. However, one patient presented with a normal brain magnetic resonance image, despite the delay in neurocognitive development.
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Affiliation(s)
- Diogo Goulart Corrêa
- Department of Radiology, Clínica de Diagnóstico por Imagem (CDPI)/DASA, Brazil.,Department of Radiology, Hospital Universitário Antônio Pedro, Brazil
| | | | | | - Patrícia Brasil
- Department of Infectious Diseases, Fundação Oswaldo Cruz, Brazil
| | - Fernanda Cristina Rueda Lopes
- Department of Radiology, Clínica de Diagnóstico por Imagem (CDPI)/DASA, Brazil.,Department of Radiology, Hospital Universitário Antônio Pedro, Brazil
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40
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Oschwald A, Petry P, Kierdorf K, Erny D. CNS Macrophages and Infant Infections. Front Immunol 2020; 11:2123. [PMID: 33072074 PMCID: PMC7531029 DOI: 10.3389/fimmu.2020.02123] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 08/05/2020] [Indexed: 12/11/2022] Open
Abstract
The central nervous system (CNS) harbors its own immune system composed of microglia in the parenchyma and CNS-associated macrophages (CAMs) in the perivascular space, leptomeninges, dura mater, and choroid plexus. Recent advances in understanding the CNS resident immune cells gave new insights into development, maturation and function of its immune guard. Microglia and CAMs undergo essential steps of differentiation and maturation triggered by environmental factors as well as intrinsic transcriptional programs throughout embryonic and postnatal development. These shaping steps allow the macrophages to adapt to their specific physiological function as first line of defense of the CNS and its interfaces. During infancy, the CNS might be targeted by a plethora of different pathogens which can cause severe tissue damage with potentially long reaching defects. Therefore, an efficient immune response of infant CNS macrophages is required even at these early stages to clear the infections but may also lead to detrimental consequences for the developing CNS. Here, we highlight the recent knowledge of the infant CNS immune system during embryonic and postnatal infections and the consequences for the developing CNS.
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Affiliation(s)
- Alexander Oschwald
- Faculty of Medicine, Institute of Neuropathology, University of Freiburg, Freiburg, Germany.,Faculty of Biology, University of Freiburg, Freiburg, Germany
| | - Philippe Petry
- Faculty of Medicine, Institute of Neuropathology, University of Freiburg, Freiburg, Germany.,Faculty of Biology, University of Freiburg, Freiburg, Germany
| | - Katrin Kierdorf
- Faculty of Medicine, Institute of Neuropathology, University of Freiburg, Freiburg, Germany.,CIBBS Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany.,Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Daniel Erny
- Faculty of Medicine, Institute of Neuropathology, University of Freiburg, Freiburg, Germany
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41
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Yockey LJ, Lucas C, Iwasaki A. Contributions of maternal and fetal antiviral immunity in congenital disease. Science 2020; 368:608-612. [PMID: 32381717 DOI: 10.1126/science.aaz1960] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Accepted: 04/03/2020] [Indexed: 12/19/2022]
Abstract
Viral infections during pregnancy can have devastating consequences on pregnancy outcomes, fetal development, and maternal health. In this review, we examine fetal and maternal immune defense mechanisms that mediate resistance against viral infections and discuss the range of syndromes that ensue when such mechanisms fail, from fetal developmental defects to establishment of chronic infection. Further, we highlight the role of maternal immune activation, or uncontrolled inflammation triggered by viral infections during pregnancy, and its potential downstream pathological effects, including tissue damage and fetal demise. Insights into the respective contributions of direct viral toxicity versus fetal and maternal immune responses that underlie the pathogenesis of congenital disease will guide future treatment strategies.
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Affiliation(s)
- Laura J Yockey
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.,Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Carolina Lucas
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Akiko Iwasaki
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA. .,Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06512, USA.,Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA
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42
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Cerbino-Neto J, Mesquita EC, Amancio RT, Brasil PEAAD. Events preceding death among chikungunya virus infected patients: a systematic review. Rev Soc Bras Med Trop 2020; 53:e04312019. [PMID: 32401863 PMCID: PMC7269536 DOI: 10.1590/0037-8682-0431-2019] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 03/24/2020] [Indexed: 12/20/2022] Open
Abstract
Since its re-emergence in the late 1990s, there have been reports of Chikungunya fever (CHIK-F) presenting with severe or atypical findings. There is little knowledge regarding the clinical events leading to the death of patients with CHIK-F. This study aimed to systematically review the literature regarding CHIK-F and identify clinical features preceding death. We searched PubMed, Scopus, Embase, Lilacs, and IsiWeb for case-reports, case-series, or cohorts of CHIK-F reporting at least one death, up to December 2019. Fifty-seven reports were analyzed, including 2140 deaths. Data about specific clinical events that precede death are scarce. The central tendency of time between disease onset and death ranged from 2 days to 150 days. The most common clinical findings among decedents were fever (22.0%), arthralgia (15.7%), myalgia (10.7%), and headache (8.2%). Excluding pediatric populations, the reported central tendency of age among the decedents was 53 or older, with a non-weighted median of 67, ranging up to 80 years old. Authors mentioned organic dysfunction in 91.2% reports. Among all the 2140 decedents, the most common dysfunctions were cardiovascular (7.2%), respiratory (6.4%), neurological (5.4%), renal (4.2%), liver (3.0%), and hematological (1.3%) dysfunction. Exacerbation of previous diabetes (5.6%) or hypertension (6.9%) was mentioned as conditions preceding death. Currently, older age, primary neurological, cardiovascular, or respiratory dysfunction and a previous diagnosis of diabetes or hypertension are the main clinical events preceding death.
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Affiliation(s)
- José Cerbino-Neto
- Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil
| | | | - Rodrigo Teixeira Amancio
- Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil
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43
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Srivastava P, Kumar A, Hasan A, Mehta D, Kumar R, Sharma C, Sunil S. Disease Resolution in Chikungunya-What Decides the Outcome? Front Immunol 2020; 11:695. [PMID: 32411133 PMCID: PMC7198842 DOI: 10.3389/fimmu.2020.00695] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Accepted: 03/27/2020] [Indexed: 12/14/2022] Open
Abstract
Chikungunya disease (CHIKD) is a viral infection caused by an alphavirus, chikungunya virus (CHIKV), and triggers large outbreaks leading to epidemics. Despite the low mortality rate, it is a major public health concern owing to high morbidity in affected individuals. The complete spectrum of this disease can be divided into four phases based on its clinical presentation and immunopathology. When a susceptible individual is bitten by an infected mosquito, the bite triggers inflammatory responses attracting neutrophils and initiating a cascade of events, resulting in the entry of the virus into permissive cells. This phase is termed the pre-acute or the intrinsic incubation phase. The virus utilizes the cellular components of the innate immune system to enter into circulation and reach primary sites of infection such as the lymph nodes, spleen, and liver. Also, at this point, antigen-presenting cells (APCs) present the viral antigens to the T cells thereby activating and initiating adaptive immune responses. This phase is marked by the exhibition of clinical symptoms such as fever, rashes, arthralgia, and myalgia and is termed the acute phase of the disease. Viremia reaches its peak during this phase, thereby enhancing the antigen-specific host immune response. Simultaneously, T cell-mediated activation of B cells leads to the formation of CHIKV specific antibodies. Increase in titres of neutralizing IgG/IgM antibodies results in the clearance of virus from the bloodstream and marks the initiation of the post-acute phase. Immune responses mounted during this phase of the infection determine the degree of disease progression or its resolution. Some patients may progress to a chronic arthritic phase of the disease that may last from a few months to several years, owing to a compromised disease resolution. The present review discusses the immunopathology of CHIKD and the factors that dictate disease progression and its resolution.
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Affiliation(s)
- Priyanshu Srivastava
- Vector-Borne Diseases Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India
| | - Ankit Kumar
- Vector-Borne Diseases Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India
| | - Abdul Hasan
- Vector-Borne Diseases Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India
| | - Divya Mehta
- Vector-Borne Diseases Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India
| | - Ramesh Kumar
- Vector-Borne Diseases Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India
| | - Chetan Sharma
- Vector-Borne Diseases Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India
| | - Sujatha Sunil
- Vector-Borne Diseases Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India
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44
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Vairo F, Haider N, Kock R, Ntoumi F, Ippolito G, Zumla A. Chikungunya: Epidemiology, Pathogenesis, Clinical Features, Management, and Prevention. Infect Dis Clin North Am 2020; 33:1003-1025. [PMID: 31668189 DOI: 10.1016/j.idc.2019.08.006] [Citation(s) in RCA: 100] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Chikungunya, a zoonotic disease caused by the Chikungunya virus (CHIKV), is transmitted by infected Aedes spp mosquitoes. CHIKV has now spread to more than 100 countries and is listed on the WHO Blueprint priority pathogens. After an incubation period of 1 to 12 days, symptoms similar to other febrile infections appear, with a sudden onset of high fever, nausea, polyarthralgia, myalgia, widespread skin rash, and conjunctivitis. Serious complications include myocarditis, uveitis, retinitis, hepatitis, acute renal disease, severe bullous lesions, meningoencephalitis, Guillain-Barré syndrome, myelitis, and cranial nerve palsies. Treatment is supportive; there is no specific antiviral treatment and no effective vaccine.
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Affiliation(s)
- Francesco Vairo
- National Institute for Infectious Diseases, "Lazzaro Spallanzani"Istituto di ricovero e cura a carattere scientifico - IRCCS, Via Portuense 292, 00149, Rome, Italy.
| | - Najmul Haider
- The Royal Veterinary College, University of London, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire AL9 7TA, UK
| | - Richard Kock
- The Royal Veterinary College, University of London, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire AL9 7TA, UK
| | - Francine Ntoumi
- Fondation Congolaise pour la Recherche Médicale (FCRM), Brazzaville, Congo; Faculty of Sciences and Techniques, University Marien Ngouabi, PO Box 69, Brazzaville, Congo; Institute for Tropical Medicine, University of Tübingen, Wilhelmstraße 27 72074, Tübingen, Germany
| | - Giuseppe Ippolito
- National Institute for Infectious Diseases, "Lazzaro Spallanzani"Istituto di ricovero e cura a carattere scientifico - IRCCS, Via Portuense 292, 00149, Rome, Italy
| | - Alimuddin Zumla
- Center for Clinical Microbiology, University College London, Royal Free Campus 2nd Floor, Rowland Hill Street, London NW3 2PF, United Kingdom
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45
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Broeders S, Garlant L, Fraiture MA, Vandermassen E, Suin V, Vanhomwegen J, Dupont-Rouzeyrol M, Rousset D, Van Gucht S, Roosens N. A new multiplex RT-qPCR method for the simultaneous detection and discrimination of Zika and chikungunya viruses. Int J Infect Dis 2020; 92:160-170. [PMID: 31884173 PMCID: PMC7129992 DOI: 10.1016/j.ijid.2019.12.028] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 12/11/2019] [Accepted: 12/20/2019] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVE The re-emergence and spread of tropical viruses to new areas has raised a wave of concern worldwide. In order to treat patients at an early stage and prevent the diffusion of an outbreak, early diagnosis, and therefore fast and adequate detection, is needed. To this end, a multiplex reverse transcription real-time polymerase chain reaction TaqMan method was designed to detect Zika (ZIKV) and chikungunya (CHIKV) viruses simultaneously. METHODS Two methods targeting different genome segments were selected from the literature for each virus. These were adapted for high genome coverage and combined in a four-plex assay that was thoroughly validated in-house. The SCREENED tool was used to evaluate the sequence coverage of the method. RESULTS The full validation approach showed that the new four-plex method allows the specific and sensitive identification and discrimination of ZIKV and CHIKV in routine samples. The combination of two targets per virus allowing almost 100% coverage of about 500 genomes is shown for the first time. CONCLUSIONS PCR is a reliable user-friendly technique that can be applied in remote areas. Such multiplex methods enable early and efficient diagnosis, leading to rapid treatment and effective confinement in outbreak cases. They may also serve as an aid for surveillance, and the full validation permits easy method-transfer allowing worldwide harmonization.
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Affiliation(s)
- Sylvia Broeders
- Sciensano, Transversal Activities in Applied Genomics, J. Wytsmanstraat 14, 1050 Brussels, Belgium.
| | - Linda Garlant
- Sciensano, Transversal Activities in Applied Genomics, J. Wytsmanstraat 14, 1050 Brussels, Belgium.
| | - Marie-Alice Fraiture
- Sciensano, Transversal Activities in Applied Genomics, J. Wytsmanstraat 14, 1050 Brussels, Belgium.
| | - Els Vandermassen
- Sciensano, Transversal Activities in Applied Genomics, J. Wytsmanstraat 14, 1050 Brussels, Belgium.
| | - Vanessa Suin
- Sciensano, Viral Diseases, J. Wytsmanstraat 14, 1050 Brussels, Belgium.
| | - Jessica Vanhomwegen
- Institut Pasteur France, Cellule d'Intervention Biologique d'Urgence (CIBU), 25-28 rue du docteur Roux, 75724 Paris Cedex 15, France.
| | - Myrielle Dupont-Rouzeyrol
- Institut Pasteur de Nouvelle-Calédonie, URE Dengue et Arboviroses, 11 ave P. Doumer, BP 61, 98845 Nouméa Cedex, New Caledonia.
| | - Dominique Rousset
- Institut Pasteur de la Guyane, Laboratoire de Virologie, 23 avenue Pasteur - BP 6010, 97306 Cayenne Cedex, Guyana.
| | - Steven Van Gucht
- Sciensano, Viral Diseases, J. Wytsmanstraat 14, 1050 Brussels, Belgium.
| | - Nancy Roosens
- Sciensano, Transversal Activities in Applied Genomics, J. Wytsmanstraat 14, 1050 Brussels, Belgium.
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46
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Ngwe Tun MM, Muthugala R, Kyaw Kyaw A, Shimada S, Morita K, Hayasaka D. Pathogenetic Potential Relating to Metabolic Activity in a Mouse Model of Infection with the Chikungunya Virus East/Central/South African Genotype. Viruses 2020; 12:v12020169. [PMID: 32028555 PMCID: PMC7077324 DOI: 10.3390/v12020169] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Revised: 01/17/2020] [Accepted: 01/30/2020] [Indexed: 12/13/2022] Open
Abstract
Epidemics of the Chikungunya virus (CHIKV) from 2004 onwards were caused by the East/Central/South African (ECSA) genotype. However, the pathogenesis of the genotype infection has not been fully explained. In this study, we examined the pathogenic potential of CHIKV ECSA genotype M-30 (M-30) by comparing it with that of African genotype S-27 (S-27) in mice. Following low titer infections in type-I IFN receptor KO (A129) mice, we found that the M-30 infection caused high and acute fatality compared with the S-27 infection. M-30-infected A129 mice showed higher viral loads in their central nervous systems and peripheral organs, and increased levels of IFN-γ responses in their brains. Interestingly, M-30-infected mice did not show the hypophagia and reductions in weight which were observed in S-27-infected mice. Our observations provide a novel explanation of the pathogenic mechanisms attributed to virus proliferation, anti-type-II IFN response and metabolic activity in the CHIKV ECSA virus in mice.
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Affiliation(s)
- Mya Myat Ngwe Tun
- Department of Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan; (M.M.N.T.); (R.M.); (S.S.); (K.M.)
| | - Rohitha Muthugala
- Department of Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan; (M.M.N.T.); (R.M.); (S.S.); (K.M.)
| | - Aung Kyaw Kyaw
- Department of Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan; (M.M.N.T.); (R.M.); (S.S.); (K.M.)
- Leading Graduate School Program, Nagasaki University, Nagasaki 852-8523, Japan
| | - Satoshi Shimada
- Department of Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan; (M.M.N.T.); (R.M.); (S.S.); (K.M.)
- Leading Graduate School Program, Nagasaki University, Nagasaki 852-8523, Japan
| | - Kouichi Morita
- Department of Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan; (M.M.N.T.); (R.M.); (S.S.); (K.M.)
- Leading Graduate School Program, Nagasaki University, Nagasaki 852-8523, Japan
| | - Daisuke Hayasaka
- Department of Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan; (M.M.N.T.); (R.M.); (S.S.); (K.M.)
- Laboratory of Veterinary Microbiology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi 753-8515, Japan
- Correspondence: ; Tel.: +81-83-933-5887
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47
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Corrêa DG, Freddi TAL, Werner H, Lopes FPPL, Moreira MEL, de Almeida Di Maio Ferreira FCP, de Andrade Lopes JM, Rueda-Lopes FC, da Cruz LCH. Brain MR Imaging of Patients with Perinatal Chikungunya Virus Infection. AJNR Am J Neuroradiol 2019; 41:174-177. [PMID: 31806601 DOI: 10.3174/ajnr.a6339] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Accepted: 10/02/2019] [Indexed: 11/07/2022]
Abstract
Since 2005, it has been known that mother-to-child transmission of the chikungunya virus is possible. Transmission generally occurs in the perinatal period. In the present study, we describe the brain lesions seen on MR imaging of 6 cases of perinatal chikungunya infection. Patients who underwent brain MR imaging in the acute phase presented with areas of restricted diffusion in the white matter, suggesting a perivascular distribution, whereas those in the subacute/late phase showed cystic lesions, also with a perivascular distribution, with or without brain atrophy. One patient also presented with scattered hemorrhages in the frontal and parietal lobes. Important differential diagnoses include rotavirus, Parechovirus, herpes simplex infection, and hypoxic-ischemic encephalopathy, depending on the disease phase.
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Affiliation(s)
- D G Corrêa
- From the Clínica de Diagnóstico por Imagem/Diagnósticos da América (D.G.C., H.W., F.P.P.L.L., F.C.R.-L., L.C.H.d.C.)
| | - T A L Freddi
- Rio de Janeiro, RJ, Brazil; Department of Radiology (T.A.L.F.), Hospital do Coração, São Paulo, SP, Brazil
| | - H Werner
- From the Clínica de Diagnóstico por Imagem/Diagnósticos da América (D.G.C., H.W., F.P.P.L.L., F.C.R.-L., L.C.H.d.C.)
| | - F P P L Lopes
- From the Clínica de Diagnóstico por Imagem/Diagnósticos da América (D.G.C., H.W., F.P.P.L.L., F.C.R.-L., L.C.H.d.C.)
| | - M E L Moreira
- Clínica Perinatal (M.E.L.M., F.C.P.d.A.D.M.F., J.M.d.A.L.), Rio de Janeiro, RJ, Brazil
| | | | - J M de Andrade Lopes
- Clínica Perinatal (M.E.L.M., F.C.P.d.A.D.M.F., J.M.d.A.L.), Rio de Janeiro, RJ, Brazil
| | - F C Rueda-Lopes
- From the Clínica de Diagnóstico por Imagem/Diagnósticos da América (D.G.C., H.W., F.P.P.L.L., F.C.R.-L., L.C.H.d.C.)
| | - L C H da Cruz
- From the Clínica de Diagnóstico por Imagem/Diagnósticos da América (D.G.C., H.W., F.P.P.L.L., F.C.R.-L., L.C.H.d.C.)
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48
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Abstract
This review includes the congenital infections best known by the acronym TORCH (Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes virus), as well as Zika virus infection and perinatally acquired infections (enterovirus, parechovirus, rotavirus, parvovirus). Congenital infections are due to pathogens that can cross the placenta and are more likely to injure the brain when the infection occurs early in pregnancy. There are many similarities, with regards to brain lesions, for congenital Zika syndrome and congenital cytomegalovirus infection. Perinatally acquired viral infections tend to injure the white matter, with cystic evolution being more likely in the (late) preterm infant compared to the full-term infant. Congenital and perinatally acquired viral infections can be associated with adverse neurological outcomes. Prevention is important, especially as therapeutic options are limited. In this review both congenital as well as perinatally acquired viral infections will be discussed with a focus on neuro-imaging findings.
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Affiliation(s)
- Linda S de Vries
- Department of Neonatology, University Medical Center, Utrecht University, Utrecht, the Netherlands.
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49
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Young AR, Locke MC, Cook LE, Hiller BE, Zhang R, Hedberg ML, Monte KJ, Veis DJ, Diamond MS, Lenschow DJ. Dermal and muscle fibroblasts and skeletal myofibers survive chikungunya virus infection and harbor persistent RNA. PLoS Pathog 2019; 15:e1007993. [PMID: 31465513 PMCID: PMC6715174 DOI: 10.1371/journal.ppat.1007993] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Accepted: 07/21/2019] [Indexed: 12/23/2022] Open
Abstract
Chikungunya virus (CHIKV) is an arthritogenic alphavirus that acutely causes fever as well as severe joint and muscle pain. Chronic musculoskeletal pain persists in a substantial fraction of patients for months to years after the initial infection, yet we still have a poor understanding of what promotes chronic disease. While replicating virus has not been detected in joint-associated tissues of patients with persistent arthritis nor in various animal models at convalescent time points, viral RNA is detected months after acute infection. To identify the cells that might contribute to pathogenesis during this chronic phase, we developed a recombinant CHIKV that expresses Cre recombinase (CHIKV-3'-Cre). CHIKV-3'-Cre replicated in myoblasts and fibroblasts, and it induced arthritis during the acute phase in mice. Importantly, it also induced chronic disease, including persistent viral RNA and chronic myositis and synovitis similar to wild-type virus. CHIKV-3'-Cre infection of tdTomato reporter mice resulted in a population of tdTomato+ cells that persisted for at least 112 days. Immunofluorescence and flow cytometric profiling revealed that these tdTomato+ cells predominantly were myofibers and dermal and muscle fibroblasts. Treatment with an antibody against Mxra8, a recently defined host receptor for CHIKV, reduced the number of tdTomato+ cells in the chronic phase and diminished the levels of chronic viral RNA, implicating these tdTomato+ cells as the reservoir of chronic viral RNA. Finally, isolation and flow cytometry-based sorting of the tdTomato+ fibroblasts from the skin and ankle and analysis for viral RNA revealed that the tdTomato+ cells harbor most of the persistent CHIKV RNA at chronic time points. Therefore, this CHIKV-3'-Cre and tdTomato reporter mouse system identifies the cells that survive CHIKV infection in vivo and are enriched for persistent CHIKV RNA. This model represents a useful tool for studying CHIKV pathogenesis in the acute and chronic stages of disease.
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MESH Headings
- Animals
- Arthritis, Experimental/metabolism
- Arthritis, Experimental/pathology
- Arthritis, Experimental/virology
- Chikungunya Fever/metabolism
- Chikungunya Fever/virology
- Chikungunya virus/genetics
- Chikungunya virus/pathogenicity
- Dermis/metabolism
- Dermis/pathology
- Dermis/virology
- Disease Models, Animal
- Fibroblasts/metabolism
- Fibroblasts/pathology
- Fibroblasts/virology
- Mice
- Mice, Inbred C57BL
- Muscle Fibers, Skeletal/metabolism
- Muscle Fibers, Skeletal/pathology
- Muscle Fibers, Skeletal/virology
- Muscle, Skeletal/metabolism
- Muscle, Skeletal/pathology
- Muscle, Skeletal/virology
- RNA, Viral/genetics
- RNA, Viral/metabolism
- Virus Replication
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Affiliation(s)
- Alissa R. Young
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Marissa C. Locke
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Lindsey E. Cook
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Bradley E. Hiller
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Rong Zhang
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Matthew L. Hedberg
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Kristen J. Monte
- Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Deborah J. Veis
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America
- Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America
- Shriners Hospitals for Children–St. Louis, St. Louis, Missouri, United States of America
| | - Michael S. Diamond
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America
- Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Deborah J. Lenschow
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America
- Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America
- * E-mail:
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50
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Mendoza EJ, Robinson A, Dimitrova K, Mueller N, Holloway K, Makowski K, Wood H. Combining anti-IgM and IgG immunoassays for comprehensive chikungunya virus diagnostic testing. Zoonoses Public Health 2019; 66:909-917. [PMID: 31449360 DOI: 10.1111/zph.12641] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Revised: 07/10/2019] [Accepted: 07/29/2019] [Indexed: 11/29/2022]
Abstract
Chikungunya virus (CHIKV) is a mosquito-borne pathogen that causes CHIKV fever. Definitive diagnosis is crucial for patients experiencing symptoms similar to other arboviral diseases because they can vary in clinical consequences. An increasing number of patients experience long-term rheumatic effects of CHIKV infection, but these cases may not be optimally detected by molecular assays and anti-CHIKV IgM ELISAs (M-ELISAs) used for confirmation and screening, respectively. The subsequent confirmatory serological test, the plaque reduction neutralization test (PRNT), is laborious and time-consuming. In this study, we evaluated a new diagnostic algorithm in which the M-ELISA is conducted in parallel with an anti-CHIKV IgG ELISA (G-ELISA) and observed that the Euroimmun M-ELISA combined with the Euroimmun G-ELISA or the Abcam G-ELISA exhibited excellent sensitivity and specificity for CHIKV. The combinations demonstrated perfect and near perfect inter-rater agreement with the PRNT, respectively, suggesting their potential to be used as alternatives to the confirmatory serological PRNT assay for CHIKV.
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Affiliation(s)
- Emelissa J Mendoza
- Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada
| | - Alyssia Robinson
- Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada
| | - Kristina Dimitrova
- Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada
| | - Nicole Mueller
- Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada
| | - Kimberly Holloway
- Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada
| | - Kai Makowski
- Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada
| | - Heidi Wood
- Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada
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