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Lo SH, Chen TC, Lin CY, Hsieh HC, Lai PC, Lien WL, Yeh YC, Lee IK, Chen YH, Lu PL, Chang K. Comparison of clinical and laboratory data between hantavirus infection and leptospirosis: a retrospective case series study in southern Taiwan. Trans R Soc Trop Med Hyg 2025; 119:464-471. [PMID: 39657123 DOI: 10.1093/trstmh/trae121] [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: 09/09/2024] [Revised: 10/28/2024] [Accepted: 11/07/2024] [Indexed: 12/17/2024] Open
Abstract
BACKGROUND Leptospirosis (LS) and hantavirus (HV) are rodent-borne diseases and share similar clinical manifestations, posing diagnostic challenges. METHODS This retrospective study compared clinical characteristics, laboratory data, complications and outcomes of 33 LS and nine HV cases in Kaohsiung, Taiwan, from 2006 to 2021. RESULTS Both LS and HV diseases had high rates of acute kidney injury (84.8% vs 66.7%) and hepatitis (65.6% vs 88.9%); LS showed more hyperbilirubinemia (70% vs 12.5% in HV, p=0.005), higher initial creatinine levels (2.9 vs 1.37, p=0.018) and elevated initial C-reactive protein (218.3 vs 28.6 mg/dl, p<0.001), but lower initial lymphocyte percentage (6.63% vs 14.2%, p=0.005) and platelets (138.7/mm3 vs 68.9, p=0.016) compared with HV. Microscopic hematuria was significantly more prevalent in LS (80% vs 28.65% in HV, p=0.016). Notably, the LS and HV groups exhibited statistically significant differences in thrombocytopenia (57.5% vs 100%, p=0.019), hyperbilirubinemia (70% vs 12.5%, p=0.005), shock (45.5% vs 0%, p=0.016) and hematuria (80% vs 28.6%, p=0.016). Neither group experienced fatalities. CONCLUSIONS Fever, thrombocytopenia and acute kidney injury alert physicians to consider LS and HV for differential diagnosis. Elevated bilirubin, along with hematuria or shock, suggests a preferred diagnosis for LS.
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Affiliation(s)
- Shih-Hao Lo
- School of Medicine, Institute of Graduate, Center for Tropical Medicine and Infectious Disease Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siao-gang Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tun-Chieh Chen
- School of Medicine, Institute of Graduate, Center for Tropical Medicine and Infectious Disease Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Kaohsiung Municipal Ta-tung Hospital, Kaohsiung, Taiwan
| | - Chun-Yu Lin
- School of Medicine, Institute of Graduate, Center for Tropical Medicine and Infectious Disease Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
| | | | | | - Wei-Li Lien
- Kaohsiung Municipal United Hospital, Kaohsiung, Taiwan
| | | | - Ing-Kit Lee
- Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Yen-Hsu Chen
- School of Medicine, Institute of Graduate, Center for Tropical Medicine and Infectious Disease Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - Po-Liang Lu
- School of Medicine, Institute of Graduate, Center for Tropical Medicine and Infectious Disease Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ko Chang
- School of Medicine, Institute of Graduate, Center for Tropical Medicine and Infectious Disease Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siao-gang Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
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Eng S, Frishman WH, Aronow WS. Cardiovascular Complications of Dengue Virus. Cardiol Rev 2025:00045415-990000000-00470. [PMID: 40249185 DOI: 10.1097/crd.0000000000000935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/19/2025]
Abstract
Dengue virus is an arbovirus primarily transmitted by Aedes aegypti and Aedes albopictus mosquitoes and can cause a range of symptoms from mild febrile illness to severe dengue hemorrhagic fever and shock leading to cardiovascular collapse. The incidence of dengue globally has been on the rise, partially due to higher travel volumes to dengue-endemic regions and climate change allowing for an expanded range of Aedes mosquito vectors. As the incidence of dengue rises, atypical presentations of dengue are reported with increasing frequency and cardiac manifestations such as electrocardiographic abnormalities, myocarditis, and pericarditis warrant further investigation. This review will discuss our current understanding of the cardiovascular manifestations of dengue and management, explore its proposed pathogenesis, and conclude with a discussion of possible future research directions.
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Affiliation(s)
- Shirley Eng
- From the Department of Medicine, New York Medical College, Valhalla, NY
| | | | - Wilbert S Aronow
- Departments of Cardiology and Medicine, Westchester Medical Center and New York Medical College, Valhalla, NY
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Li Y, Hu H, Chu C, Yang J. Mitochondrial calcium uniporter complex: An emerging therapeutic target for cardiovascular diseases (Review). Int J Mol Med 2025; 55:40. [PMID: 39749702 PMCID: PMC11758895 DOI: 10.3892/ijmm.2024.5481] [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: 08/14/2024] [Accepted: 11/27/2024] [Indexed: 01/04/2025] Open
Abstract
Cardiovascular disease (CVD) is currently a major factor affecting human physical and mental health. In recent years, the relationship between intracellular Ca2+ and CVD has been extensively studied. Ca2+ movement across the mitochondrial inner membrane plays a vital role as an intracellular messenger, regulating energy metabolism and calcium homeostasis. It is also involved in pathological processes such as cardiomyocyte apoptosis, hypertrophy and fibrosis in CVD. The selective mitochondrial calcium uniporter complex (MCU complex) located in the inner membrane is essential for mitochondrial Ca2+ uptake. Therefore, the MCU complex is a potential therapeutic target for CVD. In this review, recent research progress on the pathophysiological mechanisms and therapeutic potential of the MCU complex in various CVDs was summarized, including myocardial ischemia‑reperfusion injury, pulmonary arterial hypertension, other peripheral vascular diseases, myocardial remodeling and arrhythmias. This review contributes to a deeper understanding of these mechanisms at the molecular level and highlights potential intervention targets for CVD treatment in clinical practice.
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Affiliation(s)
- Yaling Li
- Department of Cardiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421000, P.R. China
| | - Hongmin Hu
- Department of Cardiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421000, P.R. China
| | - Chun Chu
- Department of Pharmacy, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421000, P.R. China
| | - Jun Yang
- Department of Cardiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421000, P.R. China
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Francis N, Asapu P, Qazi MU, Jaiganesh T. The Ultimate Buzzkill: When Dengue Hits Hard. Cureus 2025; 17:e80761. [PMID: 40248563 PMCID: PMC12005061 DOI: 10.7759/cureus.80761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/18/2025] [Indexed: 04/19/2025] Open
Abstract
Dengue cases have been rising globally in recent years. In the United Arab Emirates (UAE) specifically, weather conditions have created an ideal breeding ground for the Aedes aegypti mosquito, the primary vector of the disease. We report the case of a 62-year-old South Asian male residing in the UAE who initially experienced vague flu-like symptoms. His condition progressively worsened, ultimately resulting in an unexpected out-of-hospital cardiac arrest and, tragically, death.
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Affiliation(s)
| | | | - Mashhood U Qazi
- Emergency Medicine, Tawam Hospital, Al Ain, ARE
- Emergency Medicine, Sheikh Tahnoon Bin Mohammed Medical City, Al Ain, ARE
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Moragas LJ, Arruda LV, Oliveira LDLS, Alves FDAV, Salomão NG, da Silva JFR, Basílio-de-Oliveira CA, Basílio-de-Oliveira RP, Mohana-Borges R, Azevedo CG, de Oliveira GX, de Carvalho JJ, Rosman FC, Paes MV, Rabelo K. Detection of viral antigen and inflammatory mediators in fatal pediatric dengue: a study on lung immunopathogenesis. Front Immunol 2025; 16:1487284. [PMID: 39967674 PMCID: PMC11832654 DOI: 10.3389/fimmu.2025.1487284] [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: 08/27/2024] [Accepted: 01/13/2025] [Indexed: 02/20/2025] Open
Abstract
Introduction The dengue virus (DENV) is the etiological agent that causes dengue fever illness, an arbovirus with a major endemic potential that has become increasingly prevalent in Brazil and has already been associated with fatal cases in children. DENV has tropism for several organs, including lungs causing pulmonary complications. The aim of this article was to evaluate the inflammatory and histopathological profile of the lung tissue of three fatal cases of children infected with DENV, which represents a group more susceptible to fatality due to its incomplete development. Methods Histopathological analysis was carried out using Hematoxylin and Eosin staining and special stains. While the characterization of the inflammatory response and cellular expression was done by marking the viral protein, macrophages, lymphocytes and pro-inflammatory cytokines. Results and discussion The results confirm that vascular dysfunctions such as hemorrhage, vascular congestion and edema associated with a mononuclear infiltrate were observed in all three cases. In addition, the presence of viral replication and increased expression of inflammatory markers were also observed. Such findings contribute to the study and description of dengue, especially its effects on lung tissue.
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Affiliation(s)
- Leandro Junqueira Moragas
- Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Laíza Vianna Arruda
- Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
- Laboratório de Ultraestrutura e Biologia Tecidual, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | | | - Felipe de Andrade Vieira Alves
- Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
- Laboratório de Ultraestrutura e Biologia Tecidual, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Natália Gedeão Salomão
- Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
- Laboratório das Interações Vírus-Hospedeiros, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | | | | | | | - Ronaldo Mohana-Borges
- Laboratório de Genômica Estrutural, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Caio Gonçalves Azevedo
- Laboratório de Ultraestrutura e Biologia Tecidual, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Gabriela Xavier de Oliveira
- Laboratório de Ultraestrutura e Biologia Tecidual, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Jorge José de Carvalho
- Laboratório de Ultraestrutura e Biologia Tecidual, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Fernando Colonna Rosman
- Departamento de Patologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
- Serviço de Anatomia Patológica, Hospital Municipal Jesus, Rio de Janeiro, Brazil
| | - Marciano Viana Paes
- Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Kíssila Rabelo
- Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
- Laboratório de Ultraestrutura e Biologia Tecidual, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
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Kang MS, Kim JM, Jo HJ, Heo HJ, Kim YH, Park KM, Han DW. 3D bioprintable Mg 2+-incorporated hydrogels tailored for regeneration of volumetric muscle loss. Theranostics 2025; 15:2185-2200. [PMID: 39990217 PMCID: PMC11840723 DOI: 10.7150/thno.103677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Accepted: 01/06/2025] [Indexed: 02/25/2025] Open
Abstract
Rationale: Current therapeutic approaches for volumetric muscle loss (VML) face challenges owing to limited graft availability and insufficient bioactivity. Three-dimensional (3D) bioprinting has become an alternative technology for fabricating native tissue-mimetic grafts, allowing for tailored structures and complex designs. Methods: We developed an Mg2+-incorporated bioink composed of thiolated gelatin (GtnSH) and maleimide-conjugated gelatin (GtnMI) decorated with magnesium peroxide (MgO2), referred to as a GtnSH/GtnMI/MgO2 bioink. We designed in situ crosslinking between GtnSH and GtnMI to prepare cytocompatible bioink for 3D bioprinting of muscle mimetics. Results: The incorporated MgO2 particles provided oxygen supplementation and myogenic cues. In vitro assays demonstrated that C2C12 myoblasts encapsulated in the GtnSH/GtnMI/MgO2 bioink exhibited high viability, intrinsic proliferation rate, and increased expression of key myogenic markers. In vivo transplantation of the 3D bioprinted GtnSH/GtnMI/MgO2 constructs facilitated muscle mass restoration and M2 macrophage polarization. Additionally, they downregulate the activities of CD4+ and CD8+ lymphocytes, inducing a transition from the initial inflammatory to the restoration phase. Conclusion: The GtnSH/GtnMI/MgO2 bioink is a potential therapeutic strategy for enhancing myogenesis and skeletal muscle tissue regeneration.
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Affiliation(s)
- Moon Sung Kang
- Department of Cogno-mechatronics Engineering, Pusan National University, Busan 46241, Republic of Korea
| | - Jeong Min Kim
- Department of Bioengineering and Nano-bioengineering, Incheon National University, Incheon 22012, Republic of Korea
| | - Hyo Jung Jo
- Department of Cogno-mechatronics Engineering, Pusan National University, Busan 46241, Republic of Korea
| | - Hye Jin Heo
- Department of Anatomy, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea
| | - Yun Hak Kim
- Department of Anatomy, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea
- Department of Biomedical Informatics, Pusan National University, Yangsan 50612, Republic of Korea
- Medical Research Institute, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea
- Periodontal Disease Signaling Network Research Center and Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea
| | - Kyung Min Park
- Department of Bioengineering and Nano-bioengineering, Incheon National University, Incheon 22012, Republic of Korea
- Research Center for Bio Materials & Process Development, Incheon National University, Incheon 22012, Republic of Korea
| | - Dong-Wook Han
- Department of Cogno-mechatronics Engineering, Pusan National University, Busan 46241, Republic of Korea
- Institute of Nano-Bio Convergence, Pusan National University, Busan 46241, Republic of Korea
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Parepalli A, Saboo K, Acharya S, Kota V, Nelakuditi M. Dengue Hemorrhagic Fever Presenting With Pericardial Effusion and Cardiac Tamponade: A Case Report. Cureus 2025; 17:e76836. [PMID: 39897308 PMCID: PMC11787622 DOI: 10.7759/cureus.76836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Accepted: 01/03/2025] [Indexed: 02/04/2025] Open
Abstract
Dengue fever encompasses a spectrum of illnesses, ranging from mild dengue fever to more severe forms, including dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Cardiogenic shock and multi-organ failure are among the complications that can arise from the syndrome, which is considered to be caused by endothelial cell loss and increased capillary permeability. Its incidence is especially significant during monsoon seasons. A 45-year-old woman required intubation after presenting with hypotension and changed mental status after suffering from a high-grade fever, severe headache, myalgias, and progressive respiratory distress for seven days. An emergency was called when imaging indicated a considerable pericardial effusion, which echocardiography verified. Pericardiocentesis was carried out, and 300 mL of hemorrhagic fluid was collected. She then required inotropic therapy to avoid cardiogenic shock. After receiving empirical antibiotics, platelet transfusions, and close supervision, the patient's health improved, and the pericardial drain was removed on the fifth day of hospitalization. Since myocarditis and pericardial effusion are uncommon but hazardous cardiac symptoms in dengue fever, it is critical to detect and treat these disorders in patients with severe dengue fever to limit the illness's morbidity and mortality.
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Affiliation(s)
- Avinash Parepalli
- Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Keyur Saboo
- Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Sourya Acharya
- Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Vijay Kota
- Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Manikanta Nelakuditi
- Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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Pramudyo M, Putra ICS, Iqbal M, Prameswari HS, Karwiky G, Dewi TI, Raharjo P, Kamarullah W, Sukmadi N. Clinically suspected acute right ventricular fulminant dengue myocarditis masquerading with dual lethal arrhythmias: a case report. J Med Case Rep 2024; 18:554. [PMID: 39548493 PMCID: PMC11566477 DOI: 10.1186/s13256-024-04792-w] [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: 08/11/2024] [Accepted: 08/30/2024] [Indexed: 11/18/2024] Open
Abstract
BACKGROUND Acute right ventricular myocarditis is rare, comprising only 18% of myocarditis cases. Despite being relatively infrequent at 12.4%, dengue-induced myocarditis has a high mortality risk of 26.4%. This report presents a novel case of acute fulminant right ventricular myocarditis due to severe dengue infection, complicated by dual electrical disturbances: complete heart block and ventricular tachycardia. CASE REPORT A 49-year-old Asian male patient was referred to our hospital with a temporary pacemaker due to a complete heart block. He had a history of recurrent syncope over three days and a fever five days before admission. Initial electrocardiography showed a total atrioventricular nodal block progressing to a high-degree atrioventricular block with a left bundle branch block, indicating an infra-Hisian block. Laboratory findings included thrombocytopenia, elevated troponin, high creatinine, increased liver transaminases, and a positive dengue nonstructural protein 1 test, confirming a diagnosis of dengue infection. Echocardiography showed reduced right ventricular systolic function, normal left ventricular systolic function (ejection fraction: 50%), and dyskinetic intraventricular septum. Coronary angiography revealed normal coronary anatomy. An endomyocardial biopsy was deferred due to severe thrombocytopenia. On the third day, the patient's condition worsened, developing cardiogenic shock and left ventricular systolic dysfunction (ejection fraction: 35%). He subsequently experienced a seizure and slow ventricular tachycardia originating from the right coronary cusp, followed by cardiac arrest. The patient's family claimed not to resuscitate the patient. Furthermore, the patient died shortly after. CONCLUSION This case underscores the critical need for prompt diagnosis and aggressive management of clinically suspected acute fulminant right ventricular myocarditis because complications can rapidly progress to left ventricular systolic dysfunction, leading to cardiogenic shock and sudden cardiac death.
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Affiliation(s)
- Miftah Pramudyo
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Padjadjaran, Pasteur Street Number 38, Bandung, Jawa Barat, 40161, Indonesia
| | - Iwan C S Putra
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Padjadjaran, Pasteur Street Number 38, Bandung, Jawa Barat, 40161, Indonesia.
| | - Mohammad Iqbal
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Padjadjaran, Pasteur Street Number 38, Bandung, Jawa Barat, 40161, Indonesia
| | - Hawani S Prameswari
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Padjadjaran, Pasteur Street Number 38, Bandung, Jawa Barat, 40161, Indonesia
| | - Giky Karwiky
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Padjadjaran, Pasteur Street Number 38, Bandung, Jawa Barat, 40161, Indonesia
| | - Triwedya I Dewi
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Padjadjaran, Pasteur Street Number 38, Bandung, Jawa Barat, 40161, Indonesia
| | - Pradana Raharjo
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Padjadjaran, Pasteur Street Number 38, Bandung, Jawa Barat, 40161, Indonesia
| | - William Kamarullah
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Padjadjaran, Pasteur Street Number 38, Bandung, Jawa Barat, 40161, Indonesia
| | - Norman Sukmadi
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Padjadjaran, Pasteur Street Number 38, Bandung, Jawa Barat, 40161, Indonesia
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Putri A, Arunsodsai W, Hattasingh W, Sirinam S. DENV-1 infection with rhabdomyolysis in an adolescent: A case report and review of challenge in early diagnosis and treatment. Heliyon 2024; 10:e36379. [PMID: 39263171 PMCID: PMC11387269 DOI: 10.1016/j.heliyon.2024.e36379] [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: 02/14/2024] [Revised: 08/14/2024] [Accepted: 08/14/2024] [Indexed: 09/13/2024] Open
Abstract
Dengue infection is a well-known tropical disease that has become a global health issue. The clinical characteristics of dengue range from asymptomatic to severe, which can involve multiple organs and challenge management. Rhabdomyolysis in dengue infection is a rare condition described in children and adolescents. Herein, we present the case of a young adolescent with autism spectrum disorder who had a dengue virus serotype 1 infection complicated by rhabdomyolysis, which was not detected based on its typical manifestations. Rhabdomyolysis is recognized as one of the manifestations of expanded dengue syndrome and is associated with significant morbidity and mortality, especially if acute kidney injury develops. These coexisting conditions should be carefully considered, particularly in patients with underlying medical issues that may contribute to a worse prognosis. The early diagnosis and management of patients with dengue complicated by rhabdomyolysis is challenging and should be widely acknowledged. The detection of potential complications and appropriate fluid balance are essential to achieve a better prognosis.
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Affiliation(s)
- Anastasia Putri
- Thai Travel Clinic, Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
| | - Watcharee Arunsodsai
- Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
| | - Weerawan Hattasingh
- Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
| | - Salin Sirinam
- Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
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Sánchez JL, Salgado DM, Vega MR, Castro-Trujillo S, Narváez CF. Utility of the WHO dengue guidelines in pediatric immunological studies. J Trop Pediatr 2024; 70:fmae014. [PMID: 39002166 DOI: 10.1093/tropej/fmae014] [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] [Indexed: 07/15/2024]
Abstract
Dengue is a significant health problem due to the high burden of critical infections during outbreaks. In 1997, the World Health Organization (WHO) classified dengue as dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). It was revised in 2009 (updated in 2015), and the new guidelines recommended classifying patients as dengue without warning signs (DNS), dengue with warning signs (DWS), and severe dengue (SD). Although the utility of the revised 2009 classification for clinical studies is accepted, for immunological studies it needs to be clarified. We determined the usefulness of the 2009 classification for pediatric studies that analyze the circulating interleukin (IL)-6 and IL-8, two inflammatory cytokines. Plasma levels of IL-6 and IL-8 were evaluated in the acute and convalescent phases by flow cytometry in children with dengue classified using the 1997 and 2009 WHO guidelines. The plasma levels of IL-6 and IL-8 were elevated during the acute and decreased during convalescence, and both cytokines served as a good marker of acute dengue illness compared to convalescence. There were no differences in the plasma level of the evaluated cytokines among children with different clinical severity with any classification, except for the IL-8, which was higher in DWS than DNS. Based on the levels of IL-8, the 2009 classification identified DWS plus SD (hospital-treated children) compared to the DNS group [area under the curve (AUC): 0.7, p = 0.028]. These results support the utility of the revised 2009 (updated in 2015) classification in studies of immune markers in pediatric dengue.
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Affiliation(s)
- Jorge L Sánchez
- División de Inmunología, Programa de Medicina, Facultad de Ciencias de la Salud, Universidad Surcolombiana, Neiva 41001, Colombia
- Departamento de Pediatría, Universidad Surcolombiana, Hospital Universitario de Neiva, Neiva 41001, Colombia
| | - Doris M Salgado
- División de Inmunología, Programa de Medicina, Facultad de Ciencias de la Salud, Universidad Surcolombiana, Neiva 41001, Colombia
- Departamento de Pediatría, Universidad Surcolombiana, Hospital Universitario de Neiva, Neiva 41001, Colombia
| | - Martha Rocío Vega
- División de Inmunología, Programa de Medicina, Facultad de Ciencias de la Salud, Universidad Surcolombiana, Neiva 41001, Colombia
- Departamento de Pediatría, Universidad Surcolombiana, Hospital Universitario de Neiva, Neiva 41001, Colombia
| | - Sebastián Castro-Trujillo
- División de Inmunología, Programa de Medicina, Facultad de Ciencias de la Salud, Universidad Surcolombiana, Neiva 41001, Colombia
- Departamento de Pediatría, Universidad Surcolombiana, Hospital Universitario de Neiva, Neiva 41001, Colombia
| | - Carlos F Narváez
- División de Inmunología, Programa de Medicina, Facultad de Ciencias de la Salud, Universidad Surcolombiana, Neiva 41001, Colombia
- Departamento de Pediatría, Universidad Surcolombiana, Hospital Universitario de Neiva, Neiva 41001, Colombia
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Modak A, Mishra SR, Awasthi M, Aravind A, Singh S, Sreekumar E. Fingolimod (FTY720), an FDA-approved sphingosine 1-phosphate (S1P) receptor agonist, restores endothelial hyperpermeability in cellular and animal models of dengue virus serotype 2 infection. IUBMB Life 2024; 76:267-285. [PMID: 38031996 DOI: 10.1002/iub.2795] [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: 04/07/2023] [Accepted: 10/24/2023] [Indexed: 12/01/2023]
Abstract
Extensive vascular leakage and shock is a major cause of dengue-associated mortality. At present, there are no specific treatments available. Sphingolipid pathway is a key player in the endothelial barrier integrity; and is mediated through the five sphingosine-1-phosphate receptors (S1PR1-S1PR5). Signaling through S1PR2 promotes barrier disruption; and in Dengue virus (DENV)-infection, there is overexpression of this receptor. Fingolimod (FTY720) is a specific agonist that targets the remaining barrier-protective S1P receptors, without targeting S1PR2. In the present study, we explored whether FTY720 treatment can alleviate DENV-induced endothelial hyperpermeability. In functional assays, in both in vitro systems and in AG129 animal models, FTY720 treatment was found effective. Upon treatment, there was complete restoration of the monolayer integrity in DENV serotype 2-infected human microvascular endothelial cells (HMEC-1). At the molecular level, the treatment reversed activation of the S1P pathway. It significantly reduced the phosphorylation of the key molecules such as PTEN, RhoA, and VE-Cadherin; and also, the expression levels of S1PR2. In DENV2-infected AG129 mice treated with FTY720, there was significant improvement in weight gain, in overall clinical symptoms, and in survival. Whereas 100% of the DENV2-infected, untreated animals died by day-10 post-infection, 70% of the FTY720-treated animals were alive; and at the end of the 15-day post-infection observation period, 30% of them were still surviving. There was a significant reduction in the Evan's-blue dye permeability in the organs of FTY720-treated, DENV-2 infected animals; and also improvement in the hemogram, with complete restoration of thrombocytopenia and hepatic function. Our results show that the FDA-approved molecule Fingolimod (FTY720) is a promising therapeutic intervention in severe dengue.
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Affiliation(s)
- Ayan Modak
- Molecular Virology Laboratory, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, India
- Regional Centre for Biotechnology (RCB), NCR Biotech Science Cluster, Faridabad, Haryana (NCR Delhi), India
| | - Srishti Rajkumar Mishra
- Molecular Virology Laboratory, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, India
- Regional Centre for Biotechnology (RCB), NCR Biotech Science Cluster, Faridabad, Haryana (NCR Delhi), India
| | - Mansi Awasthi
- Molecular Virology Laboratory, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, India
- Regional Centre for Biotechnology (RCB), NCR Biotech Science Cluster, Faridabad, Haryana (NCR Delhi), India
| | - Arya Aravind
- Animal Research Facility, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, Kerala, India
| | - Sneha Singh
- Molecular Virology Laboratory, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, India
| | - Easwaran Sreekumar
- Molecular Virology Laboratory, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, India
- Molecular Bioassay Laboratory, Institute of Advanced Virology (IAV), Thiruvananthapuram, Kerala, India
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12
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Gomes Z, Lee GS, Mesfin S, Rocha R, Vervoort D. Viral cardiovascular surgical diseases: global burdens, challenges and opportunities. Future Cardiol 2024; 20:229-239. [PMID: 39049768 DOI: 10.1080/14796678.2024.2348382] [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: 10/20/2023] [Accepted: 04/24/2024] [Indexed: 07/27/2024] Open
Abstract
Globally, more than one billion people are vulnerable to neglected tropical diseases, many of which have viral origins and cardiovascular implications. Access to cardiovascular care is limited in countries where these conditions are endemic. Six billion people lack access to safe, timely and affordable cardiac surgical care, whereby over 100 countries and territories lack a single cardiac surgeon. Moreover, while clinically unique, the surgical consequences of neglected cardiovascular diseases with viral origins have been poorly described in the current literature. This review provides an overview of the global burden of viral cardiovascular disease, describes access to cardiac surgical care in regions where these conditions are endemic, and further highlights surgical consequences and considerations to manage patients requiring cardiac surgical care.
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Affiliation(s)
- Zoya Gomes
- Faculty of Medicine, Dalhousie University, Halifax, Nova B3H 4R2, Scotia, B3H 4R2, Canada
| | - Grace S Lee
- Temerty Faculty of Medicine, University of Toronto, Toronto, M5S 1A1, Ontario, M5S 1A1, Canada
| | - Samuel Mesfin
- College of Health Sciences, Addis Ababa University, Addis NBH1, Ababa, NBH1, Ethiopia
| | - Rodolfo Rocha
- Division of Cardiac Surgery, University of Toronto, Toronto, M5S 1A1, Ontario, M5S 1A1, Canada
| | - Dominique Vervoort
- Division of Cardiac Surgery, University of Toronto, Toronto, M5S 1A1, Ontario, M5S 1A1, Canada
- Institute of Health Policy, Management & Evaluation, University of Toronto, Toronto, M5T 3M6, M5T 3M6, Ontario,Canada
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13
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Yang TH, Gao WC, Ma X, Liu Q, Pang PP, Zheng YT, Jia Y, Zheng CB. A Review on The Pathogenesis of Cardiovascular Disease of Flaviviridea Viruses Infection. Viruses 2024; 16:365. [PMID: 38543730 PMCID: PMC10974792 DOI: 10.3390/v16030365] [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: 01/13/2024] [Revised: 02/20/2024] [Accepted: 02/25/2024] [Indexed: 05/23/2024] Open
Abstract
Members of the Flaviviridae family, encompassing the Flavivirus and Hepacivirus genera, are implicated in a spectrum of severe human pathologies. These diseases span a diverse spectrum, including hepatitis, vascular shock syndrome, encephalitis, acute flaccid paralysis, and adverse fetal outcomes, such as congenital heart defects and increased mortality rates. Notably, infections by Flaviviridae viruses have been associated with substantial cardiovascular compromise, yet the exploration into the attendant cardiovascular sequelae and underlying mechanisms remains relatively underexplored. This review aims to explore the epidemiology of Flaviviridae virus infections and synthesize their cardiovascular morbidities. Leveraging current research trajectories and our investigative contributions, we aspire to construct a cogent theoretical framework elucidating the pathogenesis of Flaviviridae-induced cardiovascular injury and illuminate prospective therapeutic avenues.
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Affiliation(s)
- Tie-Hua Yang
- School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, China; (T.-H.Y.); (P.-P.P.)
- Key Laboratory of Animal Models and Human Diseases Mechanisms of Chinese Academy of Sciences, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, China; (X.M.); (Y.-T.Z.)
- Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
| | - Wen-Cong Gao
- School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China;
| | - Xin Ma
- Key Laboratory of Animal Models and Human Diseases Mechanisms of Chinese Academy of Sciences, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, China; (X.M.); (Y.-T.Z.)
- College of Modern Biomedical Industry, Kunming Medical University, Kunming 650500, China
| | - Qian Liu
- School of Pharmacy, Chongqing Medical University, Chongqing 400016, China;
| | - Pan-Pan Pang
- School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, China; (T.-H.Y.); (P.-P.P.)
- Key Laboratory of Animal Models and Human Diseases Mechanisms of Chinese Academy of Sciences, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, China; (X.M.); (Y.-T.Z.)
| | - Yong-Tang Zheng
- Key Laboratory of Animal Models and Human Diseases Mechanisms of Chinese Academy of Sciences, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, China; (X.M.); (Y.-T.Z.)
- Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
| | - Yinnong Jia
- School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China;
| | - Chang-Bo Zheng
- School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China;
- College of Modern Biomedical Industry, Kunming Medical University, Kunming 650500, China
- Yunnan Vaccine Laboratory, Kunming 650500, China
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14
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Schneider CA, Leung JM, Valenzuela-Leon PC, Golviznina NA, Toso EA, Bosnakovski D, Kyba M, Calvo E, Peterson KE. Skin muscle is the initial site of viral replication for arboviral bunyavirus infection. Nat Commun 2024; 15:1121. [PMID: 38321047 PMCID: PMC10847502 DOI: 10.1038/s41467-024-45304-0] [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: 04/14/2023] [Accepted: 01/19/2024] [Indexed: 02/08/2024] Open
Abstract
The first step in disease pathogenesis for arboviruses is the establishment of infection following vector transmission. For La Crosse virus (LACV), the leading cause of pediatric arboviral encephalitis in North America, and other orthobunyaviruses, the initial course of infection in the skin is not well understood. Using an intradermal (ID) model of LACV infection in mice, we find that the virus infects and replicates nearly exclusively within skin-associated muscle cells of the panniculus carnosus (PC) and not in epidermal or dermal cells like most other arbovirus families. LACV is widely myotropic, infecting distal muscle cells of the peritoneum and heart, with limited infection of draining lymph nodes. Surprisingly, muscle cells are resistant to virus-induced cell death, with long term low levels of virus release progressing through the Golgi apparatus. Thus, skin muscle may be a key cell type for the initial infection and spread of arboviral orthobunyaviruses.
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Affiliation(s)
- Christine A Schneider
- Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
| | - Jacqueline M Leung
- Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
| | - Paola Carolina Valenzuela-Leon
- Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA
| | | | - Erik A Toso
- Lillehei Heart Institute, University of Minnesota, Minneapolis, MN, USA
| | - Darko Bosnakovski
- Lillehei Heart Institute, University of Minnesota, Minneapolis, MN, USA
| | - Michael Kyba
- Lillehei Heart Institute, University of Minnesota, Minneapolis, MN, USA
| | - Eric Calvo
- Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA
| | - Karin E Peterson
- Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
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15
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Farrukh AM, Ganipineni VDP, Jindal U, Chaudhary A, Puar RK, Ghazarian K, Corrales VV, Alarcón SE, Remala K, Thota N, Vijayan S, Rathore SS. Unveiling the Dual Threat: Myocarditis in the Spectrum of Dengue Fever. Curr Probl Cardiol 2024; 49:102029. [PMID: 37567490 DOI: 10.1016/j.cpcardiol.2023.102029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Accepted: 08/07/2023] [Indexed: 08/13/2023]
Abstract
This meta-analysis aims to systematically review and analyze available studies on the association between myocarditis and dengue viral fever. A comprehensive literature search was carried out using several databases. Mantel-Haenszel odds ratios and associated 95% confidence intervals were produced to report the overall effect size using random effect models. Besides, random effects models were used to calculate the overall pooled prevalence. Data from 26 articles (6622 dengue patients) showed that pooled estimate of myocarditis in dengue fever was 12.4% (95% CI, 8.41-17.08). Higher prevalence was seen in reports from Asia (15.2%) compared to that from Latin America (3.6%). Besides, the pooled prevalence of severity and mortality was 34% (95% CI, 20.49-49.04) and 26.44% (95% CI, 18.07-35.78) respectively. Significantly higher prevalence rates of severe disease in the pediatric population (52.4%) and studies with a higher percentage of females (52.1%) were also observed. However, higher mortality rates were seen in the adult population (34.8%) compared with the pediatric age group. Further, myocarditis in dengue patients was associated with increased risk of severity (RR = 2.44, 95% CI 1.007-5.93, P = 0.048) and mortality (RR = 19.41, 95% CI 7.19-52.38, P < 0.001) compared with dengue patients without myocarditis. No significant publication bias was evident in the meta-analysis. The findings highlight the clinical significance of early identification and management of myocarditis in patients with dengue fever.
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Affiliation(s)
| | | | - Urmi Jindal
- KJ Somaiya Medical College and Research Centre, Mumbai, Maharashtra, India
| | | | | | | | | | | | - Kavya Remala
- Konaseema Institute of Medical Sciences, Amalapuram, Andhra Pradesh, India
| | - Naganath Thota
- Department of Internal Medicine, Baptist Memorial Hospital, Memphis, TN
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16
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Puccioni-Sohler M, Nascimento Soares C, Christo PP, Almeida SMD. Review of dengue, zika and chikungunya infections in nervous system in endemic areas. ARQUIVOS DE NEURO-PSIQUIATRIA 2023; 81:1112-1124. [PMID: 38157877 PMCID: PMC10756841 DOI: 10.1055/s-0043-1777104] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Accepted: 10/15/2023] [Indexed: 01/03/2024]
Abstract
Dengue, zika, and chikungunya are arboviruses of great epidemiological relevance worldwide. The emergence and re-emergence of viral infections transmitted by mosquitoes constitute a serious human public health problem. The neurological manifestations caused by these viruses have a high potential for death or sequelae. The complications that occur in the nervous system associated with arboviruses can be a challenge for diagnosis and treatment. In endemic areas, suspected cases should include acute encephalitis, myelitis, encephalomyelitis, polyradiculoneuritis, and/or other syndromes of the central or peripheral nervous system, in the absence of a known explanation. The confirmation diagnosis is based on viral (isolation or RT-PCR) or antigens detection in tissues, blood, cerebrospinal fluid, or other body fluids, increase in IgG antibody titers between paired serum samples, specific IgM antibody in cerebrospinal fluid and serological conversion to IgM between paired serum samples (non-reactive in the acute phase and reactive in the convalescent). The cerebrospinal fluid examination can demonstrate: 1. etiological agent; 2. inflammatory reaction or protein-cytological dissociation depending on the neurological condition; 3. specific IgM, 4. intrathecal synthesis of specific IgG (dengue and chikungunya); 5. exclusion of other infectious agents. The treatment of neurological complications aims to improve the symptoms, while the vaccine represents the great hope for the control and prevention of neuroinvasive arboviruses. This narrative review summarizes the updated epidemiology, general features, neuropathogenesis, and neurological manifestations associated with dengue, zika, and chikungunya infection.
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Affiliation(s)
- Marzia Puccioni-Sohler
- Universidade Federal do Estado do Rio de Janeiro, Escola de Medicina e Cirurgia, Departamento de Medicina Geral, Rio de Janeiro RJ, Brazil.
- Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Programa de Pós-Graduação em Doenças Infecciosas e Parasitárias, Rio de Janeiro RJ, Brazil.
| | | | - Paulo Pereira Christo
- Santa Casa BH, Faculdade de Saúde, Programa de Pós-Graduação Stricto Sensu em Medicina-Biomedicina, Belo Horizonte MG, Brazil.
- Universidade Federal de Minas Gerais, Faculdade de Medicina, Departamento de Neurologia, Belo Horizonte MG, Brazil.
| | - Sérgio Monteiro de Almeida
- Universidade Federal do Paraná, Faculdade de Medicina, Departamento de Patologia Médica, Curitiba PR, Brazil.
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17
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Sandeep M, Padhi BK, Yella SST, Sruthi KG, Venkatesan RG, Krishna Sasanka KBS, Satapathy P, Mohanty A, Al-Tawfiq JA, Iqhrammullah M, Rabaan AA, Kabi A, Sah S, Rustagi S, Al-Qaim ZH, Barboza JJ, Waheed Y, Harapan H, Sah R. Myocarditis manifestations in dengue cases: A systematic review and meta-analysis. J Infect Public Health 2023; 16:1761-1768. [PMID: 37738692 DOI: 10.1016/j.jiph.2023.08.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 07/25/2023] [Accepted: 08/08/2023] [Indexed: 09/24/2023] Open
Abstract
BACKGROUND Dengue fever is a zoonotic viral infection that raises a global alarm in the tropics and subtropics, with the potentially escalating into newer geographical regions. Severe dengue may be associated with fatal complications such as myocarditis. There is a paucity of available data on the prevalence of dengue-associated myocarditis. The objective of this systematic review and meta-analysis was to estimate the global prevalence of dengue-associated myocarditis. METHODS A systematic search was conducted utilizing the Cochrane library, PubMed, Scopus, ProQuest, Web of Science, and Preprint servers such as arXiv, medRxiv, bioRxiv, BioRN, ChiRN, ChiRxiv, and SSRN as of November 25, 2022. All primary studies (case series, cross-sectional, retrospective, and prospective) that reported confirmed cases of dengue myocarditis were included. The I2 statistic test assessed the heterogenic characteristics and publication bias was evaluated using Doi plot and Egger regression tests. RESULTS A total of 12 studies conducted between 2007 and 2022 with 2795 laboratory-confirmed dengue patients were included. Of the included cases, 502 were positive for myocarditis, with a prevalence of 2.4-78%. The pooled prevalence of dengue-induced myocarditis in the studied population was 21.0% (95% CI, 9 - 38%). The prediction interval was estimated to be 0.00 - 0.81. CONCLUSION Myocarditis in dengue patients is a significant and understudied complication in many aspects. To prevent dengue-associated myocarditis, appropriate measures such as early detection of cases and signs, symptoms-based diagnosis via electrocardiography and echocardiography, as well as relevant vector control policies must be implemented.
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Affiliation(s)
| | - Bijaya K Padhi
- Department of Community Medicine and School of Public Health, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | | | - K G Sruthi
- Department of Oral Medicine and Radiology, KLE VK Institute of Dental Sciences, Hyderabad, India
| | | | | | - Prakasini Satapathy
- Department of Virology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Aroop Mohanty
- Department of Clinical Microbiology, All India Institute of Medical Sciences, Gorakhpur, India
| | - Jaffar A Al-Tawfiq
- Infectious Disease Unit, Specialty Internal Medicine, and Quality and Patient Safety Department, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia; Division of Infectious Diseases, Indiana University School of Medicine, Indianapolis, IN, USA; Division of Infectious Diseases, Johns Hopkins University, Baltimore, MD, USA
| | - Muhammad Iqhrammullah
- Faculty of Public Health, Universitas Muhammadiyah Aceh, Banda Aceh 23245, Indonesia; Innovative Sustainability Lab, PT. Biham Riset dan Edukasi, Banda Aceh 23243, Indonesia
| | - Ali A Rabaan
- Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia; College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; Department of Public Health and Nutrition, The University of Haripur, Haripur 22610, Pakistan
| | - Ankita Kabi
- Department of Anaesthesia and Critical Care, AIIMS Gorakhpur, Uttar Pradesh 273008, India
| | - Sanjit Sah
- Research Scientist, Global Consortium for Public Health and Research, Datta Meghe Institute of Higher Education and Research, Jawaharlal Nehru Medical College, Wardha 442001, India; SR Sanjeevani Hospital, Kalyanpur-11, Siraha, Nepal
| | - Sarvesh Rustagi
- School of Applied and Life Sciences, Uttaranchal University, Dehradun, Uttarakhand, India
| | - Zahraa Haleem Al-Qaim
- Department of Anesthesia Techniques, Al-Mustaqbal University College, 51001 Hilla, Babylon, Iraq
| | - Joshuan J Barboza
- Escuela de Medicina, Universidad César Vallejo, Trujillo 13007, Peru.
| | - Yasir Waheed
- Office of Research, Innovation, and Commercialization (ORIC), Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad 44000, Pakistan; Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos 1401, Lebanon
| | - Harapan Harapan
- Medical Research Unit, School of Medicine, Universitas Syiah Kuala, Banda Aceh 23111, Indonesia; Tropical Disease Centre, School of Medicine, Universitas Syiah Kuala, Banda Aceh 23111, Indonesia; Department of Microbiology, School of Medicine, Universitas Syiah Kuala, Banda Aceh 23111, Indonesia; Tsunami and Disaster Mitigation Research Center (TDMRC), Universitas Syiah Kuala, Banda Aceh 23111, Indonesia
| | - Ranjit Sah
- Department of Clinical Microbiology, Institute of Medicine, Tribhuvan University Teaching Hospital, Kathmandu 44600, Nepal; Department of Clinical Microbiology, Dr.D.Y Patil Medical College, Hospital and Research Centre, D.Y Patil Vidyapeeth, Pune 411000, India; Department of Public Health Dentistry, Dr. D.Y. Patil Dental College and Hospital, Dr. D.Y. Patil Vidyapeeth, Pune 411018, Maharashtra, India.
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18
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Jain S, Vimal N, Angmo N, Sengupta M, Thangaraj S. Dengue Vaccination: Towards a New Dawn of Curbing Dengue Infection. Immunol Invest 2023; 52:1096-1149. [PMID: 37962036 DOI: 10.1080/08820139.2023.2280698] [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] [Indexed: 11/15/2023]
Abstract
Dengue is an infectious disease caused by dengue virus (DENV) and is a serious global burden. Antibody-dependent enhancement and the ability of DENV to infect immune cells, along with other factors, lead to fatal Dengue Haemorrhagic Fever and Dengue Shock Syndrome. This necessitates the development of a robust and efficient vaccine but vaccine development faces a number of hurdles. In this review, we look at the epidemiology, genome structure and cellular targets of DENV and elaborate upon the immune responses generated by human immune system against DENV infection. The review further sheds light on various challenges in development of a potent vaccine against DENV which is followed by presenting a current account of different vaccines which are being developed or have been licensed.
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Affiliation(s)
- Sidhant Jain
- Independent Researcher, Institute for Globally Distributed Open Research and Education (IGDORE), Rewari, India
| | - Neha Vimal
- Bhaskaracharya College of Applied Sciences, University of Delhi, Delhi, India
| | - Nilza Angmo
- Maitreyi College, University of Delhi, Delhi, India
| | - Madhumita Sengupta
- Janki Devi Bajaj Government Girls College, University of Kota, Kota, India
| | - Suraj Thangaraj
- Swami Ramanand Teerth Rural Government Medical College, Maharashtra University of Health Sciences, Ambajogai, India
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19
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Rivera J, Rengifo AC, Alvarez-Díaz D, Parra E, Usme-Ciro J, Castellanos J, Velandia M, Laiton-Donato K, Rico A, Pardo L, Caldas ML. Multisystem Failure in Fatal Dengue: Associations between the Infectious Viral Serotype and Clinical and Histopathological Findings. Am J Trop Med Hyg 2023; 109:908-916. [PMID: 37604466 PMCID: PMC10551070 DOI: 10.4269/ajtmh.22-0587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 06/04/2023] [Indexed: 08/23/2023] Open
Abstract
Dengue is the most important arthropod-borne viral infection of humans. However, its viral pathogenesis is still unknown. The information collected from dengue fatal cases is crucial for understanding the complex interactions between virulence and host factors. This study aimed to establish possible associations between the clinical characteristics, histopathological changes, replication, and tissue location of viral serotypes in dengue fatal cases. Clinical and histopathological characterizations, antigen localization in tissue, and detection of the infecting serotype and replication using real-time polymerase chain reaction were all performed on the dengue fatal cases. The majority of the cases involved people under the age of 20. Bleeding (48.3%), abdominal pain (44.8%), myalgia (52.9%), and headache (48.3%) were the most common clinical manifestations in the cases. There was multiorgan pathology, with histopathological changes primarily in the liver, spleen, and lung. Similarly, the viral antigen was found primarily in these organs; however, there were no associations between tissue changes, viral location, infecting serotypes, and replication processes. Dengue infection should be considered a multiorgan disease, the outcome of which is possibly not associated with the infecting viral serotype.
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Affiliation(s)
- Jorge Rivera
- Grupo de Morfología Celular, Dirección de Investigación en Salud Pública, Instituto Nacional de Salud, Bogotá, Colombia
| | - Aura Caterine Rengifo
- Grupo de Morfología Celular, Dirección de Investigación en Salud Pública, Instituto Nacional de Salud, Bogotá, Colombia
| | - Diego Alvarez-Díaz
- Grupo de Morfología Celular, Dirección de Investigación en Salud Pública, Instituto Nacional de Salud, Bogotá, Colombia
| | - Edgar Parra
- Grupo de Patología, Dirección de Redes en Salud Pública, Instituto Nacional de Salud, Bogotá, Colombia
| | - José Usme-Ciro
- Centro de Investigación en Salud para el Trópico, Facultad de Medicina, Universidad Cooperativa de Colombia, Santa Marta, Colombia
| | - Jaime Castellanos
- Grupo Investigaciones Básicas y Aplicadas en Odontología (IBAPO), Facultad de Odontología, Universidad Nacional de Colombia, Bogotá, Colombia
| | - Myriam Velandia
- Instituto de Virología, Universidad El Bosque, Bogotá, Colombia
| | - Katherine Laiton-Donato
- Grupo de Virología, Dirección de Redes en Salud Pública, Instituto Nacional de Salud, Bogotá, Colombia
| | - Angélica Rico
- Grupo de Virología, Dirección de Redes en Salud Pública, Instituto Nacional de Salud, Bogotá, Colombia
| | - Lisseth Pardo
- Grupo de Virología, Dirección de Redes en Salud Pública, Instituto Nacional de Salud, Bogotá, Colombia
| | - María Leonor Caldas
- Grupo de Morfología Celular, Dirección de Investigación en Salud Pública, Instituto Nacional de Salud, Bogotá, Colombia
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20
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Nguyen RN, Lam HT, Phan HV. Liver Impairment and Elevated Aminotransferase Levels Predict Severe Dengue in Vietnamese Children. Cureus 2023; 15:e47606. [PMID: 37886653 PMCID: PMC10597804 DOI: 10.7759/cureus.47606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/28/2023] [Indexed: 10/28/2023] Open
Abstract
BACKGROUND The degree of liver impairment in children with dengue infection varies from mild to severe injury. Aminotransferase levels may be useful in predicting severe dengue. This study aimed to evaluate the degree of liver impairment and determine whether elevated aminotransferases could be used to discriminate between non-severe and severe dengue in Vietnamese children. METHODS This was a prospective cohort study of pediatric patients with confirmed dengue infection who were admitted to Can Tho Children's Hospital, Vietnam. The receiver operating characteristic (ROC) curve was used to discriminate the power of Aspartate transaminase (AST) or Alanine transaminase (ALT) to predict severe dengue. RESULTS Two hundred and thirty confirmed dengue patients were enrolled, including 70% (161) patients with non-severe dengue and 30% (69) with severe dengue. This study indicates that 73.9% of patients had abnormal AST (＞40 U/L), and 34.8% of patients had abnormal ALT (＞40 U/L). The incidence of dengue patients with hepatitis (AST or ALT ≥ 4×ULN) and severe hepatitis (AST or ALT ≥ 10×ULN) were 18.7% and 17.0%, respectively. At a cut-off point of 120 U/L, AST's AUROC, sensitivity, and specificity were 0.93 (95% CI: 0.90-0.96), 82.5%, and 87.3%, respectively. At a cut-off point of 80 U/L, ALT's AUROC, sensitivity, and specificity were 0.89 (95% CI: 0.84-0,93), 87.5%, and 85.2%, respectively, for predicting severe dengue. CONCLUSION Elevated aminotransferase levels were associated with severe dengue, and AST/ALT were good markers for predicting severe dengue in Vietnamese children.
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Affiliation(s)
- Rang N Nguyen
- Pediatrics, Can Tho University of Medicine and Pharmacy, Can Tho, VNM
| | - Hue T Lam
- Pediatrics, Can Tho University of Medicine and Pharmacy, Can Tho, VNM
| | - Hung V Phan
- Pediatrics, Can Tho University of Medicine and Pharmacy, Can Tho, VNM
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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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22
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Moragas LJ, Alves FDAV, Oliveira LDLS, Salomão NG, Azevedo CG, da Silva JFR, Basílio-de-Oliveira CA, Basílio-de-Oliveira R, Mohana-Borges R, de Carvalho JJ, Rosman FC, Paes MV, Rabelo K. Liver immunopathogenesis in fatal cases of dengue in children: detection of viral antigen, cytokine profile and inflammatory mediators. Front Immunol 2023; 14:1215730. [PMID: 37457689 PMCID: PMC10348746 DOI: 10.3389/fimmu.2023.1215730] [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: 05/02/2023] [Accepted: 06/16/2023] [Indexed: 07/18/2023] Open
Abstract
Introduction Dengue virus (DENV), the etiologic agent of dengue fever illness, represents a global public health concern, mainly in tropical and subtropical areas across the globe. It is well known that this acute viral disease can progress to severe hemorrhagic stages in some individuals, however, the immunopathogenic basis of the development of more severe forms by these patients is yet to be fully understood. Objective In this context, we investigated and characterized the histopathological features as well as the cytokine profile and cell subpopulations present in liver tissues from three fatal cases of DENV in children. Methods Hematoxylin and Eosin, Periodic Acid Schiff and Picro Sirius Red staining were utilized for the histopathological analysis. Immunohistochemistry assay was performed to characterize the inflammatory response and cell expression patterns. Results Vascular dysfunctions such as hemorrhage, vascular congestion and edema associated with a mononuclear infiltrate were observedin all three cases. Liver tissues exhibited increased presence of CD68+ and TCD8+ cells as well as high expression of MMP-9, TNF-a, RANTES, VEGFR-2 mediators. Viral replication was confirmed by the detection of NS3 protein. Conclusion Taken together, these results evidenced key factors that may be involved in the development of severe alterations in liver tissues of children in response to DENV infection.
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Affiliation(s)
- Leandro Junqueira Moragas
- Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Felipe de Andrade Vieira Alves
- Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
- Laboratório de Ultraestrutura e Biologia Tecidual, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | | | - Natália Gedeão Salomão
- Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Caio Gonçalves Azevedo
- Laboratório de Ultraestrutura e Biologia Tecidual, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | | | | | | | - Ronaldo Mohana-Borges
- Laboratório de Genômica Estrutural, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Jorge José de Carvalho
- Laboratório de Ultraestrutura e Biologia Tecidual, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Fernando Colonna Rosman
- Serviço de Anatomia Patológica, Hospital Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Marciano Viana Paes
- Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Kíssila Rabelo
- Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
- Laboratório de Ultraestrutura e Biologia Tecidual, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
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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: 5] [Impact Index Per Article: 2.5] [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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24
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Kaagaard MD, Wegener A, Gomes LC, Holm AE, Lima KO, Matos LO, Vieira IVM, de Souza RM, Vestergaard LS, Marinho CRF, Dos Santos FB, Biering-Sørensen T, Silvestre OM, Brainin P. Potential role of transthoracic echocardiography for screening LV systolic dysfunction in patients with a history of dengue infection. A cross-sectional and cohort study and review of the literature. PLoS One 2022; 17:e0276725. [PMCID: PMC9674131 DOI: 10.1371/journal.pone.0276725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Accepted: 10/12/2022] [Indexed: 11/19/2022] Open
Abstract
Background Dengue virus can affect the cardiovascular system and men may be at higher risk of severe complications than women. We hypothesized that clinical dengue virus (DENV) infection could induce myocardial alterations of the left ventricle (LV) and that these changes could be detected by transthoracic echocardiography. Methodology/Principal findings We examined individuals from Acre in the Amazon Basin of Brazil in 2020 as part of the Malaria Heart Study. By questionnaires we collected information on self-reported prior dengue infection. All individuals underwent transthoracic echocardiography, analysis of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). We included 521 persons (mean age 40±15 years, 39% men, 50% urban areas) of which 253 (49%) had a history of dengue infection. In multivariable models adjusted for clinical and sociodemographic data, a history of self-reported dengue was significantly associated with lower LVEF (β = -2.37, P < 0.01) and lower GLS (β = 1.08, P < 0.01) in men, whereas no significant associations were found in women (P > 0.05). In line with these findings, men with a history of dengue had higher rates of LV systolic dysfunction (LVEF < 50% = 20%; GLS < 16% = 17%) than those without a history of dengue (LVEF < 50% = 7%; GLS < 16% = 8%; P < 0.01 and 0.06, respectively). Conclusions/Significance The findings of this study suggest that a clinical infection by dengue virus could induce myocardial alterations, mainly in men and in the LV, which could be detected by conventional transthoracic echocardiography. Hence, these results highlight a potential role of echocardiography for screening LV dysfunction in participants with a history of dengue infection. Further larger studies are warranted to validate the findings of this study.
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Affiliation(s)
- Molly D. Kaagaard
- Multidisciplinary Center, Federal University of Acre, Cruzeiro do Sul, Acre, Brazil
- Department of Cardiology, Copenhagen University Hospital–Herlev and Gentofte, Herlev, Denmark
| | - Alma Wegener
- Multidisciplinary Center, Federal University of Acre, Cruzeiro do Sul, Acre, Brazil
- Department of Cardiology, Copenhagen University Hospital–Herlev and Gentofte, Herlev, Denmark
| | - Laura C. Gomes
- Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Anna E. Holm
- Multidisciplinary Center, Federal University of Acre, Cruzeiro do Sul, Acre, Brazil
- Department of Cardiology, Copenhagen University Hospital–Herlev and Gentofte, Herlev, Denmark
| | - Karine O. Lima
- Multidisciplinary Center, Federal University of Acre, Cruzeiro do Sul, Acre, Brazil
| | - Luan O. Matos
- Multidisciplinary Center, Federal University of Acre, Cruzeiro do Sul, Acre, Brazil
| | | | | | - Lasse S. Vestergaard
- National Malaria Reference Laboratory, Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark
| | | | | | - Tor Biering-Sørensen
- Department of Cardiology, Copenhagen University Hospital–Herlev and Gentofte, Herlev, Denmark
- Faculty of Biomedical Sciences, Copenhagen University, Copenhagen, Denmark
| | - Odilson M. Silvestre
- Health and Sport Science Center, Federal University of Acre, Rio Branco, Acre, Brazil
| | - Philip Brainin
- Multidisciplinary Center, Federal University of Acre, Cruzeiro do Sul, Acre, Brazil
- Department of Cardiology, Copenhagen University Hospital–Herlev and Gentofte, Herlev, Denmark
- * E-mail:
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25
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Rashid Z, Hussain T, Abdullah SN, Kumar J. Case of steroid refractory dengue myositis responsive to intravenous immunoglobulins. BMJ Case Rep 2022; 15:e250963. [PMID: 36216376 PMCID: PMC9557321 DOI: 10.1136/bcr-2022-250963] [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] [Accepted: 09/23/2022] [Indexed: 11/06/2022] Open
Abstract
Dengue is an arbovirus infection that usually presents with the symptoms of high-grade fever, myalgia and rash. Dengue is spread by the Aedes aegypti mosquito and frequent outbreaks are being reported in regions like Pakistan, India and Sri Lanka. Although muscle ache is quite common with dengue fever, overt myositis is of very rare occurrence. Here, we report a case of a young girl who presented to us with serologically confirmed dengue infection, and having bilateral upper and lower limb weakness. Her raised creatine kinase, along with her electromyography pattern was suggestive of myositis. Her condition was steroid-resistant and responded only to intravenous immunoglobulin. She was discharged in a stable condition.
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Affiliation(s)
- Zaraq Rashid
- Internal Medicine, Hayatabad Medical Complex, Peshawar, Pakistan
| | - Taimoor Hussain
- Neuroimmunology Division, Yale School of Medicine, New Haven, Connecticut, USA
- Neurology, Bolan Medical Complex Hospital, Quetta, Pakistan
| | | | - Jasvindar Kumar
- Medicine, Khyber Medical College, Peshawar, Khyber Pakhtunkhwa, Pakistan
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26
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Nicacio JM, Gomes OV, do Carmo RF, Nunes SLP, Rocha JRCF, de Souza CDF, Franca RFDO, Khouri R, Barral-Netto M, Armstrong ADC. Heart Disease and Arboviruses: A Systematic Review and Meta-Analysis. Viruses 2022; 14:v14091988. [PMID: 36146794 PMCID: PMC9502577 DOI: 10.3390/v14091988] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 08/27/2022] [Accepted: 09/06/2022] [Indexed: 11/28/2022] Open
Abstract
Dengue fever, chikungunya, and zika are highly prevalent arboviruses transmitted by hematophagous arthropods, with a widely neglected impact in developing countries. These diseases cause acute illness in diverse populations, as well as potential cardiovascular complications. A systematic review was carried out to investigate the burden of cardiac involvement related to these arboviruses. Multiple databases were searched for articles that investigated the association of cardiovascular diseases with arboviruses, published up to March 2022. Relevant articles were selected and rated by two independent reviewers. Proportion meta-analysis was applied to assess the frequency-weighted mean of the cardiovascular findings. A total of 42 articles were selected (n = 76,678 individuals), with 17 manuscripts on dengue and 6 manuscripts on chikungunya undergoing meta-analysis. The global pooled incidence of cardiac events in dengue fever using a meta-analysis was 27.21% (95% CI 20.21–34.83; I2 = 94%). The higher incidence of dengue-related myocarditis was found in the population younger than 20 years old (33.85%; 95% CI 0.00–89.20; I2 = 99%). Considering the studies on chikungunya (n = 372), the global pooled incidence of cardiac involvement using a meta-analysis was 32.81% (95% CI 09.58–61.49, I2 = 96%). Two Zika studies were included that examined cases of infection by vertical transmission in Brazil, finding everything from structural changes to changes in heart rate variability that increase the risk of sudden death. In conclusion, cardiac involvement in arboviruses is not uncommon, especially in dengue fever.
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Affiliation(s)
- Jandir Mendonça Nicacio
- Faculty of Medicine, Federal University of Vale do São Francisco—UNIVASF, Petrolina 56304-917, PE, Brazil
- Postgraduate Program in Human Ecology and Socio-Environmental Management, Bahia State University—UNEB, Juazeiro 48904-711, BA, Brazil
- Correspondence: (J.M.N.); (O.V.G.); (A.d.C.A.)
| | - Orlando Vieira Gomes
- Faculty of Medicine, Federal University of Vale do São Francisco—UNIVASF, Petrolina 56304-917, PE, Brazil
- Postgraduate Program in Human Ecology and Socio-Environmental Management, Bahia State University—UNEB, Juazeiro 48904-711, BA, Brazil
- Correspondence: (J.M.N.); (O.V.G.); (A.d.C.A.)
| | - Rodrigo Feliciano do Carmo
- College of Pharmaceutical Sciences, Federal University of Vale do São Francisco—UNIVASF, Petrolina 56304-917, PE, Brazil
- Postgraduate Program in Applied Cellular and Molecular Biology, University of Pernambuco—UPE, Recife 50100-010, PE, Brazil
| | - Sávio Luiz Pereira Nunes
- Postgraduate Program in Applied Cellular and Molecular Biology, University of Pernambuco—UPE, Recife 50100-010, PE, Brazil
| | | | - Carlos Dornels Freire de Souza
- Faculty of Medicine, Federal University of Vale do São Francisco—UNIVASF, Petrolina 56304-917, PE, Brazil
- Postgraduate Program in Human Ecology and Socio-Environmental Management, Bahia State University—UNEB, Juazeiro 48904-711, BA, Brazil
| | | | - Ricardo Khouri
- Oswaldo Cruz Foundation/Fiocruz, Institute Gonçalo Moniz, Salvador 40296-710, BA, Brazil
- Department of Medicine, Federal University of Bahia—UFBA, Salvador 40110-909, BA, Brazil
- Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium
| | - Manoel Barral-Netto
- Oswaldo Cruz Foundation/Fiocruz, Institute Gonçalo Moniz, Salvador 40296-710, BA, Brazil
- Department of Medicine, Federal University of Bahia—UFBA, Salvador 40110-909, BA, Brazil
- Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia, University of São Paulo, São Paulo 05347-902, SP, Brazil
| | - Anderson da Costa Armstrong
- Faculty of Medicine, Federal University of Vale do São Francisco—UNIVASF, Petrolina 56304-917, PE, Brazil
- Postgraduate Program in Human Ecology and Socio-Environmental Management, Bahia State University—UNEB, Juazeiro 48904-711, BA, Brazil
- Correspondence: (J.M.N.); (O.V.G.); (A.d.C.A.)
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27
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Verma P, Banerjee S, Baskey U, Dutta S, Bakshi S, Das R, Samanta S, Dutta S, Sadhukhan PC. Clinicopathological alteration of symptoms with serotype among dengue infected pediatric patients. J Med Virol 2022; 94:4348-4358. [PMID: 35578548 DOI: 10.1002/jmv.27862] [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: 09/20/2021] [Revised: 04/29/2022] [Accepted: 05/14/2022] [Indexed: 11/06/2022]
Abstract
Dengue fever is a self-limiting, acute febrile illness caused by an arbovirus. This infection may be asymptomatic or symptomatic with its potential life-threatening form as DHF/DSS. Severe dengue cases occur typically in children due to overproduction of pro-inflammatory and anti-inflammatory cytokines (called cytokines storm) as well as increased microvascular permeability in them. This study aimed to find prevalent circulating dengue serotype and their clinicopathological association among pediatric patients admitted to tertiary care hospitals in Kolkata, India. Overall, 210 patients were approached and among them, 170 dengue suspected children admitted to three tertiary care hospitals were included in this study. Dengue samples were screened for the presence of NS1 antigen and dengue IgM antibodies by ELISA. Viral RNA was extracted from NS1 seropositive serum samples and subjected to molecular serotyping by semi-nested RT-PCR. All patients were followed up for clinical manifestations and biochemical parameters associated with dengue. Co-circulation of all four serotypes was observed and DENV2 was the major circulating strain. Physiological classification of associated clinical symptoms was done and represented as a percentage variable. A multivariate logistic regression approach was used for making a regression model including dengue-associated clinical symptoms with dengue positivity and negativity as dependent variables. Thrombocytopenia was observed in 69% of patients and the commonest bleeding manifestation was petechia. Liver function profiles of infected patients were observed during follow-up and represented using a box plot. A significant change in trends of dengue-associated clinical manifestations and differential expression of liver functional profile with different phase transitions of dengue fever was obtained in the study population. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Priya Verma
- ndian Council of Medical Research-National Institute of Cholera and Enteric Diseases, P-33, Scheme XM, CIT Road, Beliaghata, Kolkata, 700010, West Bengal, India
| | - Sayan Banerjee
- R. G. Kar Medical College and Hospital, Khudiram Bose Sarani, Kolkata, 700004, West Bengal, India
| | - Upasana Baskey
- ndian Council of Medical Research-National Institute of Cholera and Enteric Diseases, P-33, Scheme XM, CIT Road, Beliaghata, Kolkata, 700010, West Bengal, India
| | - Supradip Dutta
- ndian Council of Medical Research-National Institute of Cholera and Enteric Diseases, P-33, Scheme XM, CIT Road, Beliaghata, Kolkata, 700010, West Bengal, India
| | - Sagnik Bakshi
- ndian Council of Medical Research-National Institute of Cholera and Enteric Diseases, P-33, Scheme XM, CIT Road, Beliaghata, Kolkata, 700010, West Bengal, India
| | - Raina Das
- ndian Council of Medical Research-National Institute of Cholera and Enteric Diseases, P-33, Scheme XM, CIT Road, Beliaghata, Kolkata, 700010, West Bengal, India
| | - Sandip Samanta
- Dr. B. C. Roy Post-Graduate Institute of Pediatric Sciences, 111, Narkeldanga Main Rd, Phool Bagan, Kankurgachi, Kolkata, 700054, West Bengal, India
| | - Shanta Dutta
- ndian Council of Medical Research-National Institute of Cholera and Enteric Diseases, P-33, Scheme XM, CIT Road, Beliaghata, Kolkata, 700010, West Bengal, India
| | - Provash Chandra Sadhukhan
- ndian Council of Medical Research-National Institute of Cholera and Enteric Diseases, P-33, Scheme XM, CIT Road, Beliaghata, Kolkata, 700010, West Bengal, India
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Wei KC, Sy CL, Wang WH, Wu CL, Chang SH, Huang YT. Major acute cardiovascular events after dengue infection-A population-based observational study. PLoS Negl Trop Dis 2022; 16:e0010134. [PMID: 35130277 PMCID: PMC8853534 DOI: 10.1371/journal.pntd.0010134] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 02/17/2022] [Accepted: 01/03/2022] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Dengue virus (DENV) infection may be associated with increased risks of major adverse cardiovascular effect (MACE), but a large-scale study evaluating the association between DENV infection and MACEs is still lacking. METHODS AND FINDINGS All laboratory confirmed dengue cases in Taiwan during 2009 and 2015 were included by CDC notifiable database. The self-controlled case-series design was used to evaluate the association between DENV infection and MACE (including acute myocardial infarction [AMI], heart failure and stroke). The "risk interval" was defined as the first 7 days after the diagnosis of DENV infection and the "control interval" as 1 year before and 1 year after the risk interval. The incidence rate ratio (IRR) and 95% confidence interval (CI) for MACE were estimated by conditional Poisson regression. Finally, the primary outcome of the incidence of MACEs within one year of dengue was observed in 1,247 patients. The IRR of MACEs was 17.9 (95% CI 15.80-20.37) during the first week after the onset of DENV infection observed from 1,244 eligible patients. IRR were significantly higher for hemorrhagic stroke (10.9, 95% CI 6.80-17.49), ischemic stroke (15.56, 95% CI 12.44-19.47), AMI (13.53, 95% CI 10.13-18.06), and heart failure (27.24, 95% CI 22.67-32.73). No increased IRR was observed after day 14. CONCLUSIONS The risks for MACEs are significantly higher in the immediate time period after dengue infection. Since dengue infection is potentially preventable by early recognition and vaccination, the dengue-associated MACE should be taken into consideration when making public health management policies.
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Affiliation(s)
- Kai-Che Wei
- Department of Dermatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Cheng-Len Sy
- Department of Internal Medicine, Division of Infectious Diseases, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Wen-Hwa Wang
- Department of Internal Medicine, Division of Cardiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Health Management Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- College of Management, I-Shou University, Kaohsiung, Taiwan
| | - Chia-Ling Wu
- Department of Medical Research and Development, Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital Linkou Main Branch, Taoyuan, Taiwan
| | - Shang-Hung Chang
- Department of Medical Research and Development, Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital Linkou Main Branch, Taoyuan, Taiwan
- Department of Internal Medicine, Division of Cardiology, Chang Gung Memorial Hospital Linkou Main Branch, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yu-Tung Huang
- Department of Medical Research and Development, Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital Linkou Main Branch, Taoyuan, Taiwan
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Riederer I, Mendes-da-Cruz DA, da Fonseca GC, González MN, Brustolini O, Rocha C, Loss G, de Carvalho JB, Menezes MT, Raphael LMS, Gerber A, Bonaldo MC, Butler-Browne G, Mouly V, Cotta-de-Almeida V, Savino W, Ribeiro de Vasconcelos AT. Zika virus disrupts gene expression in human myoblasts and myotubes: Relationship with susceptibility to infection. PLoS Negl Trop Dis 2022; 16:e0010166. [PMID: 35171909 PMCID: PMC8923442 DOI: 10.1371/journal.pntd.0010166] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 03/15/2022] [Accepted: 01/12/2022] [Indexed: 11/30/2022] Open
Abstract
The tropism of Zika virus (ZIKV) has been described in the nervous system, blood, placenta, thymus, and skeletal muscle. We investigated the mechanisms of skeletal muscle susceptibility to ZIKV using an in vitro model of human skeletal muscle myogenesis, in which myoblasts differentiate into myotubes. Myoblasts were permissive to ZIKV infection, generating productive viral particles, while myotubes controlled ZIKV replication. To investigate the underlying mechanisms, we used gene expression profiling. First, we assessed gene changes in myotubes compared with myoblasts in the model without infection. As expected, we observed an increase in genes and pathways related to the contractile muscle system in the myotubes, a reduction in processes linked to proliferation, migration and cytokine production, among others, confirming the myogenic capacity of our system in vitro. A comparison between non-infected and infected myoblasts revealed more than 500 differentially expressed genes (DEGs). In contrast, infected myotubes showed almost 2,000 DEGs, among which we detected genes and pathways highly or exclusively expressed in myotubes, including those related to antiviral and innate immune responses. Such gene modulation could explain our findings showing that ZIKV also invades myotubes but does not replicate in these differentiated cells. In conclusion, we showed that ZIKV largely (but differentially) disrupts gene expression in human myoblasts and myotubes. Identifying genes involved in myotube resistance can shed light on potential antiviral mechanisms against ZIKV infection.
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Affiliation(s)
- Ingo Riederer
- Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM); Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- Rio de Janeiro Research Network on Neuroinflammation (RENEURIN), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, England, United Kingdom
| | - Daniella Arêas Mendes-da-Cruz
- Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM); Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- Rio de Janeiro Research Network on Neuroinflammation (RENEURIN), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, England, United Kingdom
| | | | - Mariela Natacha González
- Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM); Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Otavio Brustolini
- Bioinformatics Laboratory, National Laboratory for Scientific Computing, Petropolis, Rio de Janeiro, Brazil
| | - Cássia Rocha
- Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM); Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Guilherme Loss
- Bioinformatics Laboratory, National Laboratory for Scientific Computing, Petropolis, Rio de Janeiro, Brazil
| | - Joseane Biso de Carvalho
- Bioinformatics Laboratory, National Laboratory for Scientific Computing, Petropolis, Rio de Janeiro, Brazil
| | - Mariane Talon Menezes
- Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Lidiane Menezes Souza Raphael
- Laboratory of Molecular Biology of Flavivirus, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Alexandra Gerber
- Bioinformatics Laboratory, National Laboratory for Scientific Computing, Petropolis, Rio de Janeiro, Brazil
| | - Myrna Cristina Bonaldo
- Laboratory of Molecular Biology of Flavivirus, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Gillian Butler-Browne
- Sorbonne Université, Inserm, Institut de Myologie, Centre de Recherche en Myologie, Paris, France
| | - Vincent Mouly
- Sorbonne Université, Inserm, Institut de Myologie, Centre de Recherche en Myologie, Paris, France
| | - Vinicius Cotta-de-Almeida
- Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM); Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- Rio de Janeiro Research Network on Neuroinflammation (RENEURIN), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Wilson Savino
- Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM); Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- Rio de Janeiro Research Network on Neuroinflammation (RENEURIN), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
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Gupta S, Gupta M, Kashyap JR, Arora SK. Early cardiovascular involvement in dengue fever: A prospective study with two-dimensional speckle tracking echocardiography. Trop Doct 2022; 52:285-292. [DOI: 10.1177/00494755221076686] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Cardiac abnormalities in dengue infection have been conventionally identified by clinical manifestations. The primary objective of our prospective observational study was to assess true cardiovascular involvement and early myocarditis in 150 hospitalised, confirmed cases of dengue fever, through myocardial strain detection using two-dimensional speckle tracking echocardiography. Myocarditis was defined on the basis of European Society of Cardiology (ESC) 2013 criteria. Cardiac biomarkers, namely, creatine phosphokinase myocardial band was elevated in 28.6% and Troponin-T in 23.3% patients. Electrocardiography was abnormal in 64.6% while 6% patients had two-dimensional structural echocardiographic abnormalities. Myocardial dysfunction was suspected in 27.3% based on ESC criteria and strain analysis. The severe dengue group had lower longitudinal strain [−16.4 (6.3)] and circumferential strain [−15.7 (6.7)]. Two-dimensional speckle tracking echocardiography was found to be useful in improving the understanding of early myocardial mechanics in dengue fever.
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Affiliation(s)
- Samiksha Gupta
- Department of General Medicine, Government Medical College and Hospital, Chandigarh, India
| | - Monica Gupta
- Department of General Medicine, Government Medical College and Hospital, Chandigarh, India
| | - Jeet Ram Kashyap
- Department of Cardiology, Government Medical College and Hospital, Chandigarh, India
| | - Suraj Kumar Arora
- Department of Cardiology, All India Institute Medical Sciences, Bathinda, India
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Evaluating Dengue Virus Pathogenesis in Mice and Humans by Histological and Immunohistochemistry Approaches. Methods Mol Biol 2022; 2409:259-269. [PMID: 34709648 DOI: 10.1007/978-1-0716-1879-0_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The analysis of dengue virus (DENV) infected tissues in mice experimental model and in human biopsies/autopsies may support the pathogenesis studies. Through such models, it is possible to investigate possible histopathological changes caused by the infection and detections of different targets of interest, such as viral antigens, immune cells, and cytokines. In this chapter, we showed a brief review of how histological and immunohistochemistry approaches may improve the knowledge in this field.
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Jácome FC, Caldas GC, Rasinhas ADC, de Almeida ALT, de Souza DDC, Paulino AC, da Silva MAN, Bandeira DM, Barth OM, dos Santos FB, Barreto-Vieira DF. Immunocompetent Mice Infected by Two Lineages of Dengue Virus Type 2: Observations on the Pathology of the Lung, Heart and Skeletal Muscle. Microorganisms 2021; 9:microorganisms9122536. [PMID: 34946137 PMCID: PMC8704795 DOI: 10.3390/microorganisms9122536] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 09/27/2021] [Accepted: 09/28/2021] [Indexed: 11/16/2022] Open
Abstract
Dengue virus (DENV) infection by one of the four serotypes (DENV-1 to 4) may result in a wide spectrum of clinical manifestations, with unpredictable evolution and organ involvement. Due to its association with severe epidemics and clinical manifestations, DENV-2 has been substantially investigated. In fact, the first emergence of a new lineage of the DENV-2 Asian/American genotype in Brazil (Lineage II) in 2008 was associated with severe cases and increased mortality related to organ involvement. A major challenge for dengue pathogenesis studies has been a suitable animal model, but the use of immune-competent mice, although sometimes controversial, has proven to be useful, as histological observations in infected animals reveal tissue alterations consistent to those observed in dengue human cases. Here, we aimed to investigate the outcomes caused by two distinct lineages of the DENV-2 Asian/American genotype in the lung, heart and skeletal muscle tissues of infected BALB/c mice. Tissues were submitted to histopathology, immunohistochemistry, histomorphometry and transmission electron microscopy (TEM) analysis. The viral genome was detected in heart and skeletal muscle samples. The viral antigen was detected in cardiomyocytes and endothelial cells of heart tissue. Heart and lung tissue samples presented morphological alterations comparable to those seen in dengue human cases. Creatine kinase serum levels were higher in mice infected with both lineages of DENV-2. Additionally, statistically significant differences, concerning alveolar septa thickening and heart weight, were observed between BALB/c mice infected with both DENV-2 lineages, which was demonstrated to be an appropriate experimental model for dengue pathogenesis studies on lung, heart and skeletal muscle tissues.
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Affiliation(s)
- Fernanda Cunha Jácome
- Laboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, Brazil; (G.C.C.); (A.d.C.R.); (A.L.T.d.A.); (D.D.C.d.S.); (A.C.P.); (M.A.N.d.S.); (D.M.B.); (O.M.B.); (D.F.B.-V.)
- Correspondence:
| | - Gabriela Cardoso Caldas
- Laboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, Brazil; (G.C.C.); (A.d.C.R.); (A.L.T.d.A.); (D.D.C.d.S.); (A.C.P.); (M.A.N.d.S.); (D.M.B.); (O.M.B.); (D.F.B.-V.)
| | - Arthur da Costa Rasinhas
- Laboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, Brazil; (G.C.C.); (A.d.C.R.); (A.L.T.d.A.); (D.D.C.d.S.); (A.C.P.); (M.A.N.d.S.); (D.M.B.); (O.M.B.); (D.F.B.-V.)
| | - Ana Luisa Teixeira de Almeida
- Laboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, Brazil; (G.C.C.); (A.d.C.R.); (A.L.T.d.A.); (D.D.C.d.S.); (A.C.P.); (M.A.N.d.S.); (D.M.B.); (O.M.B.); (D.F.B.-V.)
| | - Daniel Dias Coutinho de Souza
- Laboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, Brazil; (G.C.C.); (A.d.C.R.); (A.L.T.d.A.); (D.D.C.d.S.); (A.C.P.); (M.A.N.d.S.); (D.M.B.); (O.M.B.); (D.F.B.-V.)
| | - Amanda Carlos Paulino
- Laboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, Brazil; (G.C.C.); (A.d.C.R.); (A.L.T.d.A.); (D.D.C.d.S.); (A.C.P.); (M.A.N.d.S.); (D.M.B.); (O.M.B.); (D.F.B.-V.)
| | - Marcos Alexandre Nunes da Silva
- Laboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, Brazil; (G.C.C.); (A.d.C.R.); (A.L.T.d.A.); (D.D.C.d.S.); (A.C.P.); (M.A.N.d.S.); (D.M.B.); (O.M.B.); (D.F.B.-V.)
| | - Derick Mendes Bandeira
- Laboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, Brazil; (G.C.C.); (A.d.C.R.); (A.L.T.d.A.); (D.D.C.d.S.); (A.C.P.); (M.A.N.d.S.); (D.M.B.); (O.M.B.); (D.F.B.-V.)
| | - Ortrud Monika Barth
- Laboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, Brazil; (G.C.C.); (A.d.C.R.); (A.L.T.d.A.); (D.D.C.d.S.); (A.C.P.); (M.A.N.d.S.); (D.M.B.); (O.M.B.); (D.F.B.-V.)
| | - Flavia Barreto dos Santos
- Laboratory of Viral Immunology, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, Brazil;
| | - Debora Ferreira Barreto-Vieira
- Laboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, Brazil; (G.C.C.); (A.d.C.R.); (A.L.T.d.A.); (D.D.C.d.S.); (A.C.P.); (M.A.N.d.S.); (D.M.B.); (O.M.B.); (D.F.B.-V.)
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Jose PMM, Paola ZS, Eduardo DG, Arturo SMMO, Fernando BG. A case of coinfection of a pediatric patient with acute SARS-COV-2 with MIS-C and severe DENV-2 in Mexico: a case report. BMC Infect Dis 2021; 21:1072. [PMID: 34663252 PMCID: PMC8521498 DOI: 10.1186/s12879-021-06765-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 06/01/2021] [Indexed: 11/27/2022] Open
Abstract
Background COVID-19 cases have been increasing since the epidemic started. One of the major concerns is how clinical symptomatology would behave after coinfection with another virus. Case presentation In this case report, a pediatric native patient from Estado de Mexico (EDOMEX), MEX had severe DENV-2 and acute SARS-CoV-2 at the same time. The clinical features were severe thrombocytopenia, secondary septic shock, cerebral edema, pericardial effusion, fluid overload that exhibited bipalpebral edema in all four extremities, hemophagocytic lymphohistiocytosis (HLH), coronary artery ectasia (CAE), multisystemic inflammatory syndrome in children (MIS-C), and probable COVID-19 pneumonia or acute respiratory distress syndrome (ARDS) that triggered patient intubation. The patient presented unusual symptomatology according to the literature. After 15 days of intubation and 15 more days under surveillance, he was released without respiratory sequelae and without treatment after major clinical improvement. Conclusion The aim of this manuscript is to present clinical challenges that coinfection may cause in pediatric patients, even though COVID-19 in children does not tend to be as severe as in other sectors of the population.
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Affiliation(s)
- Perez-Mendez Maria Jose
- Laboratorio de Medicina Traslacional, Escuela Superior de Medicina, Instituto Politecnico Nacional, Salvador Díaz Mirón esq. Plan de San Luis S/N, Miguel Hidalgo, Casco de Santo Tomas, 11340, Mexico, CDMX, Mexico.,Laboratorio de Biología Molecular, Laboratorio Estatal de Salud Pública del Estado de México, Tollocan S/N Colonia Moderna de la Cruz, 50180, Toluca,, Mexico
| | - Zarate-Segura Paola
- Laboratorio de Medicina Traslacional, Escuela Superior de Medicina, Instituto Politecnico Nacional, Salvador Díaz Mirón esq. Plan de San Luis S/N, Miguel Hidalgo, Casco de Santo Tomas, 11340, Mexico, CDMX, Mexico
| | - Davila-Gonzalez Eduardo
- Laboratorio de Biología Molecular, Laboratorio Estatal de Salud Pública del Estado de México, Tollocan S/N Colonia Moderna de la Cruz, 50180, Toluca,, Mexico
| | - Servin-Monroy Monroy Osvaldo Arturo
- Departamento de Epidemiología del Instituto de Seguridad Social del Estado de México y Municipios, ISSEMyM, Av. Hidalgo Pte. No. 600, Col. La Merced, 50080, Toluca, Estado de México, Mexico
| | - Bastida-Gonzalez Fernando
- Laboratorio de Biología Molecular, Laboratorio Estatal de Salud Pública del Estado de México, Tollocan S/N Colonia Moderna de la Cruz, 50180, Toluca,, Mexico.
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Morphological Aspects and Viremia Analysis of BALB/c Murine Model Experimentally Infected with Dengue Virus Serotype 4. Viruses 2021; 13:v13101954. [PMID: 34696384 PMCID: PMC8538460 DOI: 10.3390/v13101954] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 09/17/2021] [Accepted: 09/24/2021] [Indexed: 11/17/2022] Open
Abstract
Ever since its brief introduction in the Brazilian territory in 1981, dengue virus serotype 4 (DENV-4) remained absent from the national epidemiological scenario for almost 25 years. The emergence of DENV-4 in 2010 resulted in epidemics in most Brazilian states. DENV-4, however, remains one of the least studied among the four DENV serotypes. Despite being known as a mild serotype, DENV-4 is associated with severe cases and deaths and deserves to be investigated; however, the lack of suitable experimental animal models is a limiting factor for pathogenesis studies. Here, we aimed to investigate the susceptibility and potential tropism of DENV-4 for liver, lung and heart of an immunocompetent mice model, and to evaluate and investigate the resulting morphological and ultrastructural alterations upon viral infection. BALB/c mice were inoculated intravenously with non-neuroadapted doses of DENV-4 isolated from a human case. The histopathological analysis of liver revealed typical alterations of DENV, such as microsteatosis, edema and vascular congestion, while in lung, widespread areas of hemorrhage and interstitial pneumonia were observed. While milder alterations were present in heart, characterized by limited hemorrhage and discrete presence of inflammatory infiltrate, the disorganization of the structure of the intercalated disc is of particular interest. DENV-4 RNA was detected in liver, lung, heart and serum of BALB/c mice through qRT-PCR, while the NS3 viral protein was observed in all of the aforementioned organs through immunohistochemistry. These findings indicate the susceptibility of the model to the serotype and further reinforce the usefulness of BALB/c mice in studying the many alterations caused by DENV.
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Parchani A, Krishnan Vs G, Kumar VKS. Electrocardiographic Changes in Dengue Fever: A Review of Literature. Int J Gen Med 2021; 14:5607-5614. [PMID: 34548812 PMCID: PMC8449644 DOI: 10.2147/ijgm.s328755] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 08/30/2021] [Indexed: 11/24/2022] Open
Abstract
Dengue fever is a prevalent viral disease that primarily affects tropical nations. Although most symptomatic infections have a relatively benign course, a small percentage of patients experience severe clinical symptoms, such as bleeding and endothelial dysfunction, which can lead to hypovolemic shock and cardiovascular collapse. Dengue fever is now known to involve the heart by inducing myocardial inflammation, arrhythmias, and, in rare cases, fulminant myocarditis, up to 13% in severe dengue. Conduction abnormalities can range from benign sinus bradycardia to fulminant tachyarrhythmias and atrioventricular blocks. Although most conduction disturbances are benign and transient, they can occasionally aggravate pre-existing conditions and even be fatal. Unlike other viral myocarditis like hepatitis C induced myocarditis, dengue causes mainly transient changes, and long-term complications like dilated cardiomyopathy are not noted. There is indeed a paucity of data on how to assess and treat individuals with conduction abnormalities. In this review, the authors have discussed the wide variety of conduction abnormalities seen in dengue, their pathophysiology, clinical consequences, and a method for evaluating and managing these individuals.
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Affiliation(s)
- Ashwin Parchani
- Department of Internal Medicine, All India Institute of Medical Sciences, Rishikesh, 249203, India
| | - Gokul Krishnan Vs
- Department of Internal Medicine, Kasturba Medical College, Manipal, 576104, India
| | - V K Sunil Kumar
- Consultant Cardiologist, V Care Polyclinic, Dubai, United Arab Emirates
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Mansanguan C, Hanboonkunupakarn B, Muangnoicharoen S, Huntrup A, Poolcharoen A, Mansanguan S, Piyaphanee W, Phumratanaprapin W. Cardiac evaluation in adults with dengue virus infection by serial echocardiography. BMC Infect Dis 2021; 21:940. [PMID: 34507547 PMCID: PMC8431916 DOI: 10.1186/s12879-021-06639-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Accepted: 08/31/2021] [Indexed: 01/01/2023] Open
Abstract
Background Dengue virus infection (DVI) is a major health problem in many parts of the world. Its manifestations range from asymptomatic infections to severe disease. Although cardiac involvement has been reported in DVI, its incidence has not yet been well established. Methods From July 2016 to January 2018, patients hospitalized at the Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Thailand, with dengue virus infection confirmed by positive NS1 or positive dengue immunoglobulin M findings, participated in the study. We characterized the incidence and change in cardiac function by serial echocardiography and levels of troponin-T and creatine kinase-myocardial band (CK-MB) on the day of admission, the day of defervescence, the first day of hypotension (if any), and at 2 week follow-up. Results Of the 81 patients evaluated, 6 (7.41%) exhibited elevated biomarker levels. There was no difference in clinical presentation amongst dengue fever, dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), except for the amount of bleeding. Cardiac involvement was found in 22.2% of patients: 3 (3.70%) had left ventricular systolic dysfunction, 3 (3.70%) had transient diastolic dysfunction, 6 (7.41%) had increased levels of at least one cardiac biomarker (troponin-T or CK-MB), and 6 (7.41%) had small pericardial effusion. Myocarditis was suspected in only two patients (with DHF); thus, myocarditis was uncommon in patients with dengue virus infection. Three patients developed DSS during admission and were transferred to the intensive care unit. Conclusion Cardiac involvement in adults with dengue infection was common, ranging from elevated cardiac biomarker to myocarditis. Abnormalities in cardiac function had resolved spontaneously by the day of follow-up, without specific treatment. We found that DHF was a significant risk factor for cardiac involvement. Echocardiography is the investigation of choice for evaluating the haemodynamic status of patients with DVI, especially in severe dengue. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-021-06639-x.
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Affiliation(s)
- Chayasin Mansanguan
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
| | - Borimas Hanboonkunupakarn
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Sant Muangnoicharoen
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Arun Huntrup
- Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | | | | | - Watcharapong Piyaphanee
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Weerapong Phumratanaprapin
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
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Insights Into the Emerging Role of Myocarditis in Dengue Fever. CURRENT TROPICAL MEDICINE REPORTS 2021. [DOI: 10.1007/s40475-021-00249-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Alagarasu K. Immunomodulatory effect of vitamin D on immune response to dengue virus infection. VITAMINS AND HORMONES 2021; 117:239-252. [PMID: 34420583 DOI: 10.1016/bs.vh.2021.06.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Dengue, an acute febrile illness which in some cases requires hospitalization and occasionally a fatal disease, caused by dengue virus is a potential threat to the public health systems throughout the world. Approved antivirals are not available for treating dengue. Immunomodulators, that can reduce inflammation which if not treated properly results in vascular leakage, are being attempted as therapeutics against severe dengue. Vitamin D, an immunomodulatory hormone, with both antiviral and immunomodulatory effects, is an appropriate choice for investigation as a potential drug against dengue. Investigations of vitamin D levels by many studies have suggested vitamin D levels as a potential marker for predicting severe dengue. In-vitro studies have shown that 1, 25 dihydroxy vitamin D3 (1,25(OH)2D3), active form of vitamin D, can reduce the expression of dengue virus entry receptors, restrict the viral replication and can modulate the expression of inflammatory cytokines in dengue virus infected cells. The results from in-vitro studies also have cautioned that insufficient levels of vitamin D supplementation might increase the virus replication. Available evidence suggests vitamin D based therapeutics against dengue and provides ray of light for treating dengue patients but, the available evidence needs to be supported by beneficial outcomes in clinical trials.
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Affiliation(s)
- K Alagarasu
- Dengue and Chikungunya Group, ICMR-National Institute of Virology, Pune, Maharashtra, India.
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Leowattana W, Leowattana T. Dengue hemorrhagic fever and cardiac involvement. World J Meta-Anal 2021; 9:286-296. [DOI: 10.13105/wjma.v9.i3.286] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2021] [Revised: 05/30/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023] Open
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Kangussu LM, Costa VV, Olivon VC, Queiroz-Junior CM, Gondim ANS, Melo MB, Reis D, Nóbrega N, Araújo N, Rachid MA, Souza RPD, Tirapelli CR, Santos RASD, Cruz JDS, Teixeira MM, Souza DDGD, Bonaventura D. Dengue virus infection induces inflammation and oxidative stress on the heart. Heart 2021; 108:388-396. [PMID: 34049953 DOI: 10.1136/heartjnl-2020-318912] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 05/07/2021] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE Dengue fever is one of the most important arboviral diseases in the world, and its severe forms are characterised by a broad spectrum of systemic and cardiovascular hallmarks. However, much remains to be elucidated regarding the pathogenesis triggered by Dengue virus (DENV) in the heart. Herein, we evaluated the cardiac outcomes unleashed by DENV infection and the possible mechanisms associated with these effects. METHODS A model of an adapted DENV-3 strain was used to infect male BALB/c mice to assess haemodynamic measurements and the functional, electrophysiological, inflammatory and oxidative parameters in the heart. RESULTS DENV-3 infection resulted in increased systemic inflammation and vascular permeability with consequent reduction of systolic blood pressure and increase in heart rate. These changes were accompanied by a decrease in the cardiac output and stroke volume, with a reduction trend in the left ventricular end-systolic and end-diastolic diameters and volumes. Also, there was a reduction trend in the calcium current density in the ventricular cardiomyocytes of DENV-3 infected mice. Indeed, DENV-3 infection led to leucocyte infiltration and production of inflammatory mediators in the heart, causing pericarditis and myocarditis. Moreover, increased reactive oxygen species generation and lipoperoxidation were also verified in the cardiac tissue of DENV-3 infected mice. CONCLUSIONS DENV-3 infection induced a marked cardiac dysfunction, which may be associated with inflammation, oxidative stress and electrophysiological changes in the heart. These findings provide new cardiac insights into the mechanisms involved in the pathogenesis triggered by DENV, contributing to the research of new therapeutic targets for clinical practice.
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Affiliation(s)
- Lucas Miranda Kangussu
- Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | | | - Vania Claudia Olivon
- Departamento de Fisiologia e Biofísica, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | | | - Antônio Nei Santana Gondim
- Departamento de Educação - Campus XII, Universidade do Estado da Bahia, Salvador, Bahia, Brazil.,Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | - Marcos Barrouin Melo
- Departamento de Fisiologia e Biofísica, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | - Daniela Reis
- Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | - Natália Nóbrega
- Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | - Natália Araújo
- Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | - Milene Alvarenga Rachid
- Departamento de Patologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | - Renan Pedra de Souza
- Departamento de Genética, Ecologia e Evolução, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | - Carlos Renato Tirapelli
- Laboratório de Farmacologia, DEPCH, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil
| | | | - Jader Dos Santos Cruz
- Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | - Mauro Martins Teixeira
- Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | | | - Daniella Bonaventura
- Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
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Abhinayaa J, James S, Jebaraj R, Vinoth PN. Incidence of Cardiac Manifestations in Children with Dengue Fever: A Cross-sectional Study. Rambam Maimonides Med J 2021; 12:RMMJ.10436. [PMID: 33938801 PMCID: PMC8092955 DOI: 10.5041/rmmj.10436] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
OBJECTIVE The aim of our study was to explore the incidence of cardiac involvement in children with dengue infection admitted in a tertiary care hospital and to evaluate the features of cardiac involvement with the severity of dengue fever. METHODS This was a cross-sectional study conducted from September 2014 to August 2016. A total of 130 patients with confirmed dengue NS1 antigen or IgM antibody positivity between the ages of 1 month and 18 years were evaluated. On the third day of admission, blood samples for cardiac markers were collected, and electrocardiograms (ECG) and echocardiograms were performed for each patient. RESULTS Of the 130 dengue patients in the study, 60 (46.2%) were males and 70 (53.8%) were females (male to female ratio, 1:1.16). Cardiac involvement was present in 60 (46.2%) children and was more prominent in children with severe dengue (72.7%), followed by dengue with warning symptoms (53.8%) and dengue fever (28.6%). There was no significant correlation between cardiac involvement and primary/secondary dengue. Both ECG and echocardiography changes were significantly correlated with dengue severity, as opposed to cardiac markers. CONCLUSIONS Cardiac involvement was present in children with dengue. Evaluation with ECG, echocardiography, and cardiac markers such as creatine phosphokinase-myocardial band (CPK-MB) are required for the management of cardiac complications in children with dengue. Our study showed an association between cardiac involvement and the severity of dengue. Further studies should be framed, and follow-up of dengue patients with cardiac involvement is necessary for therapeutic management.
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Affiliation(s)
- Janakiraman Abhinayaa
- Department of Pediatrics, Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu, India
| | - Saji James
- Department of Pediatrics, Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu, India
| | - Rathinasamy Jebaraj
- Department of Cardiology, Sri Ramachandra Medical Centre, Chennai, Tamil Nadu, India
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Chang K, Huang CH, Chen TC, Lin CY, Lu PL, Chen YH. Clinical characteristics and risk factors for intracranial hemorrhage or infarction in patients with dengue. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2021; 54:885-892. [PMID: 33840603 DOI: 10.1016/j.jmii.2021.03.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 02/15/2021] [Accepted: 03/07/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Intracranial hemorrhage (ICH) or infarction in dengue cases is rare but very challenging for clinicians. We report these uncommon complications of dengue patients and focused on the significant factors associated with ICH or infarction in dengue patients. METHODS This investigation was a retrospective study of 182 adult dengue patients who received brain computed tomography at three Taiwan hospitals during the 2014 and 2015 dengue outbreaks. This included 13 hemorrhage cases, 26 infarction cases and 143 cases without brain infarction or hemorrhage. RESULTS Among them, 13 (7.14%) suffered from ICH (6 had subdural hemorrhage, 3 had subarachnoid hemorrhage, 1 had subdural and subarachnoid hemorrhage, and 3 had intracerebral hemorrhage) and 26 (14.3%) had brain infarction. The overall mortality rate was 4/13 (30.8%) in the ICH group and 3/26 (11.5%) in the infarction group. The significant variables from the univariate analysis, including difference between 2014 and 2015, age, history of cerebrovascular accident, bone pain, arthralgia, dizziness, altered consciousness, and a higher Charlson comorbidity score. Multivariate analysis revealed that significant risk factors for ICH/infarction in dengue cases were the year of occurrence, 2014 vs. 2015 (p < 0.0001, OR = 25.027, 95% CI = 8.205-76.336), Charlson score >4 (p = 0.01, OR = 3.764, 95% CI = 1.364-10.386) and altered consciousness (p < 0.0001, OR = 6.3, 95% CI = 2.242-17.7). The factors physicians should notice in dengue endemic regions for brain infarction or ICH include altered consciousness and a Charlson score >4, especially in the year that a higher frequency of infarction/ICH was observed.
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Affiliation(s)
- Ko Chang
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Chung-Hao Huang
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
| | - Tun-Chieh Chen
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Chun-Yu Lin
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Po-Liang Lu
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Yen-Hsu Chen
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, Graduate Institute of Medicine, Sepsis Research Institute, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.
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Adams CD, Syro D, Llano JF, Betancur JF. Myocarditis: an uncommon manifestation of dengue fever infection. BMJ Case Rep 2021; 14:14/2/e241569. [PMID: 33541977 PMCID: PMC7868252 DOI: 10.1136/bcr-2021-241569] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
| | - Daniel Syro
- Department of Emergency Medicine, Clinica Medellin - Grupo Quirónsalud, Medellin, Colombia
| | - Juan Felipe Llano
- Department of Emergency Medicine, Clinica Medellin - Grupo Quirónsalud, Medellin, Colombia
| | - Juan Felipe Betancur
- Department of Internal Medicine, Clinica Medellin - Grupo Quirónsalud, Medellin, Colombia,Department of Internal Medicine, Salud Sura, Medellin, Colombia
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Tammineni ER, Hurtado-Monzón AM, García MC, Carrillo ED, Hernández A, María Del Ángel R, Sánchez JA. Dantrolene hinders dengue virus-induced upregulation and translocation of calmodulin to cardiac cell nuclei. Virology 2020; 553:81-93. [PMID: 33249258 DOI: 10.1016/j.virol.2020.11.005] [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: 08/12/2020] [Revised: 11/14/2020] [Accepted: 11/15/2020] [Indexed: 11/19/2022]
Abstract
Dengue virus (DENV) infection elevates intracellular Ca2+ concentration ([Ca2+]i), but it is unknown whether Ca2+ and calmodulin (CaM) are involved in DENV infection. We conducted immunofluorescence and western blot experiments and measured [Ca2+]i examining the effects of DENV infection and drugs that alter Ca2+/CaM functions on CaM translocation, DENV2 infection, protein expression, virus-inducible STAT2 protein abundance, and CREB phosphorylation in H9c2 cells. DENV infection increased CaM expression, its nuclear translocation and NS3 and E viral proteins expression and colocalization in a manner that could be blocked by the ryanodine receptor antagonist dantrolene. DENV infection also increased CREB phosphorylation, an effect inhibited by either dantrolene or the CaM inhibitor W7. Dantrolene substantially hindered infection as assessed by focus assays in Vero cells. These results suggest that Ca2+ and CaM play an important role in DENV infection of cardiac cells and that dantrolene may protect against severe DENV cardiac morbidity.
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Affiliation(s)
- Eshwar Reddy Tammineni
- Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico
| | - Arianna Mahely Hurtado-Monzón
- Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico
| | - María Carmen García
- Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico
| | - Elba Dolores Carrillo
- Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico
| | - Ascención Hernández
- Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico
| | - Rosa María Del Ángel
- Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico
| | - Jorge Alberto Sánchez
- Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico.
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Shah C, Vijayaraghavan G, Kartha CC. Spectrum of cardiac involvement in patients with dengue fever. Int J Cardiol 2020; 324:180-185. [PMID: 32931859 DOI: 10.1016/j.ijcard.2020.09.034] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Revised: 08/27/2020] [Accepted: 09/10/2020] [Indexed: 01/22/2023]
Abstract
BACKGROUND Dengue fever (DF) is an infectious disease of viral origin common in the tropics. Studies on a large number of patients with dengue infection to assess associated cardiac involvement are rare. METHODS We analyzed the incidence and spectrum of cardiac abnormalities in 320 patients with dengue fever admitted to our hospital located in an endemic area for dengue infection. All patients were evaluated following the WHO guidelines. Those confirmed to have dengue infection by serology had detailed clinical evaluation, 12‑lead electrocardiography (ECG), assay for cardiac markers (troponin T, CK-MB, NT Pro BNP) and 2-D echocardiography. RESULTS Among the 320 patients selected for the study 112 (35%) had changes of cardiac involvement as detected by investigations. Changes in ECG were seen in all of them. Sinus bradycardia in spite of fever was the most common abnormality (n = 63;19.7%). Forty-two (13.1%) patients had left ventricular ejection fraction less than 40%. Forty-eight patients (15%) had increased serum levels of troponin-T. Serum levels of CK-MB were elevated in 34 (10.6%) and serum levels of NT-pro BNP was increased in 19 (5.9%). Fourteen patients died and all of them had abnormalities in electrocardiogram, echocardiogram and serum markers. CONCLUSION Our study reveals that cardiac involvement in patients with dengue infection is not uncommon. We found that ECHO or ECG abnormalities or elevated serum levels of markers of cardiac injury are predictors of risk for adverse outcome. Absence of these abnormalities has a 100% negative predictive value.
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Affiliation(s)
- Chintan Shah
- Department of Cardiology, Society for Continuing Medical Education & Research, Kerala Institute of Medical Sciences, Trivandrum 695029, Kerala, India
| | - Govindan Vijayaraghavan
- Department of Cardiology, Society for Continuing Medical Education & Research, Kerala Institute of Medical Sciences, Trivandrum 695029, Kerala, India.
| | - Chandrasekharan C Kartha
- Department of Cardiology, Society for Continuing Medical Education & Research, Kerala Institute of Medical Sciences, Trivandrum 695029, Kerala, India
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Illustrated histopathological features of fatal dengue cases in Colombia. ACTA ACUST UNITED AC 2020; 40:438-447. [PMID: 33030821 PMCID: PMC7666849 DOI: 10.7705/biomedica.5016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Indexed: 11/21/2022]
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Legros V, Jeannin P, Burlaud-Gaillard J, Chaze T, Gianetto QG, Butler-Browne G, Mouly V, Zoladek J, Afonso PV, Gonzàlez MN, Matondo M, Riederer I, Roingeard P, Gessain A, Choumet V, Ceccaldi PE. Differentiation-dependent susceptibility of human muscle cells to Zika virus infection. PLoS Negl Trop Dis 2020; 14:e0008282. [PMID: 32817655 PMCID: PMC7508361 DOI: 10.1371/journal.pntd.0008282] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 09/22/2020] [Accepted: 04/09/2020] [Indexed: 11/27/2022] Open
Abstract
Muscle cells are potential targets of many arboviruses, such as Ross River, Dengue, Sindbis, and chikungunya viruses, that may be involved in the physiopathological course of the infection. During the recent outbreak of Zika virus (ZIKV), myalgia was one of the most frequently reported symptoms. We investigated the susceptibility of human muscle cells to ZIKV infection. Using an in vitro model of human primary myoblasts that can be differentiated into myotubes, we found that myoblasts can be productively infected by ZIKV. In contrast, myotubes were shown to be resistant to ZIKV infection, suggesting a differentiation-dependent susceptibility. Infection was accompanied by a caspase-independent cytopathic effect, associated with paraptosis-like cytoplasmic vacuolization. Proteomic profiling was performed 24h and 48h post-infection in cells infected with two different isolates. Proteome changes indicate that ZIKV infection induces an upregulation of proteins involved in the activation of the Interferon type I pathway, and a downregulation of protein synthesis. This work constitutes the first observation of primary human muscle cells susceptibility to ZIKV infection, and differentiation-dependent restriction of infection from myoblasts to myotubes. Since myoblasts constitute the reservoir of stem cells involved in reparation/regeneration in muscle tissue, the infection of muscle cells and the viral-induced alterations observed here could have consequences in ZIKV infection pathogenesis. Muscle cells are potential targets of many arboviruses, such as Ross River, Dengue, Sindbis, and chikungunya viruses, and may be involved in the disease manifestation. During the recent outbreak of Zika virus (ZIKV), myalgia was one of the most frequently reported symptoms. We investigated the susceptibility of human muscle cells to ZIKV infection. Using an in vitro model of human muscle stem cells (myoblasts) that can be differentiated into differentiated muscle cells (myotubes), we found that myoblasts can be infected by ZIKV. In contrast, myotubes were shown to be resistant to ZIKV infection. Infection induced the death of infected cells. Protein levels 24h and 48h post-infection indicate that ZIKV infection induces an upregulation of proteins involved in the activation of the Interferon type I pathway, and a downregulation of protein synthesis. This work constitutes the first observation of primary human muscle cells susceptibility to ZIKV infection, muscle stem cells being susceptible while differentiated muscle cells are resistant. Since myoblasts constitute the reservoir of stem cells involved in reparation/regeneration in muscle tissue, the infection of muscle cells and the viral-induced alterations observed here could have consequences during ZIKV infection.
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Affiliation(s)
- Vincent Legros
- Unité Epidémiologie et Physiopathologie des Virus Oncogènes, Département de virologie, Institut Pasteur, Paris, France
- Université de Paris, Paris, France
- UMR CNRS 3569, Paris, France
| | - Patricia Jeannin
- Unité Epidémiologie et Physiopathologie des Virus Oncogènes, Département de virologie, Institut Pasteur, Paris, France
- Université de Paris, Paris, France
- UMR CNRS 3569, Paris, France
| | - Julien Burlaud-Gaillard
- INSERM U1259 & Plate Forme IBiSA de Microscopie Electronique, Université François Rabelais and CHRU, Tours, France
| | - Thibault Chaze
- Proteomics Platform, Mass Spectrometry for Biology Unit, USR 2000 IP CNRS, Institut Pasteur, Paris, France
| | - Quentin Giai Gianetto
- Proteomics Platform, Mass Spectrometry for Biology Unit, USR 2000 IP CNRS, Institut Pasteur, Paris, France
- Bioinformatics and Biostatistics Hub, C3BI, USR 3756 IP CNRS, Institut Pasteur, Paris, France
| | - Gillian Butler-Browne
- Sorbonne Université, Institut National de la Santé et de la Recherche Médicale, Association Institut de Myologie, Centre de Recherche en Myologie, UMRS974, Paris, France
| | - Vincent Mouly
- Sorbonne Université, Institut National de la Santé et de la Recherche Médicale, Association Institut de Myologie, Centre de Recherche en Myologie, UMRS974, Paris, France
| | - Jim Zoladek
- Unité Epidémiologie et Physiopathologie des Virus Oncogènes, Département de virologie, Institut Pasteur, Paris, France
- Université de Paris, Paris, France
- UMR CNRS 3569, Paris, France
| | - Philippe V. Afonso
- Unité Epidémiologie et Physiopathologie des Virus Oncogènes, Département de virologie, Institut Pasteur, Paris, France
- Université de Paris, Paris, France
- UMR CNRS 3569, Paris, France
| | - Mariela-Natacha Gonzàlez
- Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- Brazilian National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Rio de Janeiro, Brazil
| | - Mariette Matondo
- Proteomics Platform, Mass Spectrometry for Biology Unit, USR 2000 IP CNRS, Institut Pasteur, Paris, France
| | - Ingo Riederer
- Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- Brazilian National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Rio de Janeiro, Brazil
| | - Philippe Roingeard
- INSERM U1259 & Plate Forme IBiSA de Microscopie Electronique, Université François Rabelais and CHRU, Tours, France
| | - Antoine Gessain
- Unité Epidémiologie et Physiopathologie des Virus Oncogènes, Département de virologie, Institut Pasteur, Paris, France
- Université de Paris, Paris, France
- UMR CNRS 3569, Paris, France
| | - Valérie Choumet
- Unité Environnement et Risques Infectieux, Département de santé globale, Institut Pasteur, Paris, France
- * E-mail: (VC); (PEC)
| | - Pierre-Emmanuel Ceccaldi
- Unité Epidémiologie et Physiopathologie des Virus Oncogènes, Département de virologie, Institut Pasteur, Paris, France
- Université de Paris, Paris, France
- UMR CNRS 3569, Paris, France
- * E-mail: (VC); (PEC)
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Myocarditis in admitted patients with dengue fever. Infection 2020; 48:899-903. [PMID: 32780310 DOI: 10.1007/s15010-020-01500-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 08/03/2020] [Indexed: 02/06/2023]
Abstract
PURPOSE Cardiac involvement in dengue fever is underdiagnosed due to low index of clinical suspicion and its contribution to hemodynamic instability in severe dengue is not well known. METHODS A prospective observational study was conducted among admitted patients ≥ 14 years of age having confirmed dengue fever. Patients on medications affecting heart rhythm/rate, pre-existing heart disease and electrolyte abnormalities were excluded. A baseline electrocardiography (ECG), Trop-I and NT-proBNP were done for all patients. The biomarkers were measured using enzyme-linked fluorescent assay and recommended cut-off were used. Patients with elevated biomarkers underwent 2-dimensional echocardiography. Diagnosis of myocarditis was as per European Society of Cardiology (ESC) 2013 criteria. RESULTS A total of 182 patients were recruited with mean age of 30 ± 12.6 years and 31% were females. Dengue with warning signs was present in 85 (47%) and severe dengue in 60 (33%) patients. ECG abnormalities were observed in 44 (24%) patients, biomarkers were elevated in 27 (15%) patients and 11 (6%) patients had echocardiographic abnormalities. According to ESC 2013 criteria, dengue fever with myocarditis was diagnosed in 13 [7.1% (95% CI 3.4-10.9)] patients. The patients with myocarditis were more likely to have shortness of breath, bleeding manifestations and higher respiratory rate at baseline. Clinical features of fluid overload were more common (69% vs. 1.7%, p < 0.01) and the duration of hospital stay longer in myocarditis group (7 ± 4.3 vs. 4.8 ± 1.9 days, p < 0.01). CONCLUSION Myocarditis among admitted dengue patients is not uncommon and may lead to increased morbidity.
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Arboviruses and Muscle Disorders: From Disease to Cell Biology. Viruses 2020; 12:v12060616. [PMID: 32516914 PMCID: PMC7354517 DOI: 10.3390/v12060616] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 05/29/2020] [Accepted: 05/29/2020] [Indexed: 12/23/2022] Open
Abstract
Infections due to arboviruses (arthropod-borne viruses) have dramatically increased worldwide during the last few years. In humans, symptoms associated with acute infection of most arboviruses are often described as "dengue-like syndrome", including fever, rash, conjunctivitis, arthralgia, and muscular symptoms such as myalgia, myositis, or rhabdomyolysis. In some cases, muscular symptoms may persist over months, especially following flavivirus and alphavirus infections. However, in humans the cellular targets of infection in muscle have been rarely identified. Animal models provide insights to elucidate pathological mechanisms through studying viral tropism, viral-induced inflammation, or potential viral persistence in the muscle compartment. The tropism of arboviruses for muscle cells as well as the viral-induced cytopathic effect and cellular alterations can be confirmed in vitro using cellular models. This review describes the link between muscle alterations and arbovirus infection, and the underlying mechanisms.
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50
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Gulia M, Dalal P, Gupta M, Kaur D. Concurrent Guillain-Barré syndrome and myositis complicating dengue fever. BMJ Case Rep 2020; 13:13/2/e232940. [PMID: 32047085 DOI: 10.1136/bcr-2019-232940] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Dengue is an arboviral infection that classically presents with fever, headache, joint pain, skin flush and morbilliform rashes. Neurological manifestations are well recognised but their exact incidence is unknown. Though myalgias are common in dengue virus infection, myositis and/or elevated serum creatine kinase is an uncommon complication. Guillain-Barré syndrome is another rare neurological manifestation associated with dengue fever. Here, we report the case of a 21-year-old man with serologically confirmed dengue fever presenting with severe myalgia, bilateral lower and upper limb weakness with raised creatine kinase, MRI suggestive of myositis and myonecrosis and nerve conduction velocity showing bilateral lower limb and axillary sensory motor neuropathy. He was managed conservatively and made an uneventful recovery.
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Affiliation(s)
- Manisha Gulia
- Department of General Medicine, Government Medical College and Hospital, Chandigarh, India
| | - Preeti Dalal
- Department of General Medicine, Government Medical College and Hospital, Chandigarh, India
| | - Monica Gupta
- Department of General Medicine, Government Medical College and Hospital, Chandigarh, India
| | - Daljinderjit Kaur
- Department of General Medicine, Government Medical College and Hospital, Chandigarh, India
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