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Pulock OS, Mannan A, Chowdhury AFMN, Tousif G, Majumder K, Monsur S, Mehedi HMH, Kaiser E, Sultana A, Sagar MAH, Etu SN, Alam N, Mazid AHMT, Sattar MA. Clinical spectrum and risk factors of severe dengue infection: findings from the 2023 dengue outbreak in Bangladesh. BMC Infect Dis 2025; 25:469. [PMID: 40189546 PMCID: PMC11974146 DOI: 10.1186/s12879-025-10792-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Accepted: 03/13/2025] [Indexed: 04/09/2025] Open
Abstract
BACKGROUND Since the first detection of dengue in 2000, Bangladesh has been facing an increasing number of dengue patients and related deaths every year. This situation warrants the importance of quickly identifying severe dengue patients to expedite necessary medical interventions which could potentially reduce the adverse consequences. The aim of this study was to identify clinical features and laboratory parameters of the severe dengue patients in the 2023 dengue outbreak in Bangladesh. METHODS This hospital based cross-sectional study included the demographic, clinical and laboratory data of 1313 Dengue patients from several secondary and tertiary hospitals across Bangladesh from August 2023 to December 2023. According to the 2009 WHO classification, dengue cases were classified into severe dengue and non-severe dengue (with and without warning signs). Chi-square test, Fischer's exact test and multiple logistic regression analyses were conducted to identify potential risk factors associated with severe dengue cases. RESULTS Of the 1313 patients included in this study, nearly 20% had severe dengue, 36.71% of them were from the 16-25 year age bracket and nearly two-thirds were male. Fever (99.54%) was the most common clinical symptom followed by anorexia (69.54%) and severe headache (66.03%); whereas most common warning signs were severe lethargy (43.64%), persistent vomiting (27.57%), and severe abdominal pain and tenderness (20.03%) across all patients. Gastrointestinal symptoms such as nausea, vomiting, and diarrhea are significantly more common in severe dengue cases compared to non-severe ones. Among the laboratory parameters, decrease of platelet level and increased ALT level was more prominent in severe patients. Multiple logistic regression analysis found that severe abdominal pain, severe lethargy, respiratory distress, altered mental status, decreased urine output, pleural effusion and ascites were positively associated with the development of severe dengue. CONCLUSION This study presents warning signs, clinical symptoms and trends of laboratory parameters associated with severe cases of dengue in Bangladesh that can be used in improving patient management in the future.
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Affiliation(s)
- Orindom Shing Pulock
- Disease Biology and Molecular Epidemiology Research Group, Chattogram, Bangladesh
| | - Adnan Mannan
- Disease Biology and Molecular Epidemiology Research Group, Chattogram, Bangladesh.
- Department of Genetic Engineering & Biotechnology, University of Chittagong, Chattogram, Bangladesh.
| | | | - Golam Tousif
- Department of Medicine, Shaheed Syed Nazrul Islam Medical College, Kishoreganj, Bangladesh
| | - Koushik Majumder
- Disease Biology and Molecular Epidemiology Research Group, Chattogram, Bangladesh
- Department of Medicine, Chittagong Medical College, Chattogram, 4203, Bangladesh
| | - Sabrina Monsur
- Department of Medicine, Dhaka Medical College, Dhaka, Bangladesh
| | | | - Emrul Kaiser
- Department of Medicine, Fatikchari Health Complex, Chattogram, Bangladesh
| | - Afreen Sultana
- Department of Microbiology, Chittagong Medical College, Chattogram, 4203, Bangladesh
| | - Md Abdul Hamid Sagar
- Department of Medicine, Chittagong Medical College, Chattogram, 4203, Bangladesh
| | - Silvia Naznin Etu
- Disease Biology and Molecular Epidemiology Research Group, Chattogram, Bangladesh
- Department of Genetic Engineering & Biotechnology, University of Chittagong, Chattogram, Bangladesh
| | - Nazmul Alam
- Department of Public Health, Asian University for Women, Chattogram, 4000, Bangladesh
| | | | - M A Sattar
- Department of Medicine, Chittagong Medical College, Chattogram, 4203, Bangladesh
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Nguyen RN, Lam HT, Phan HV, Bui NQ. Machine Learning Nomogram for Predicting Dengue Shock Syndrome in Pediatric Patients With Dengue Fever in Vietnam. Cureus 2025; 17:e81819. [PMID: 40337565 PMCID: PMC12056676 DOI: 10.7759/cureus.81819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/06/2025] [Indexed: 05/09/2025] Open
Abstract
Background Early identification of pediatric patients at high risk for dengue shock syndrome (DSS) is crucial to enable timely and appropriate clinical interventions. However, the application of machine learning (ML) models for predicting DSS risk remains underexplored. Objective This study aimed to develop and validate a ML-based nomogram for predicting DSS risk in pediatric patients with dengue fever, supporting clinical decision-making. Methods A prospective study was conducted on 230 children with dengue fever admitted to Can Tho Children's Hospital, Vietnam, from January 2020 to December 2022. Clinical and laboratory data were collected and analyzed using R software (version 4.4.1). Six ML algorithms were used to develop risk prediction models for hospitalized pediatric patients with dengue, and their predictive performances were compared. The best-performing model was used to construct a nomogram for DSS prediction. Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC), and the calibration of the nomogram was assessed using a calibration curve. Results Among the 230 dengue patients enrolled, 124 (53.9%) were male, with a median age of 11 years (IQR: 8-13 years). The cohort was randomly divided into a training set (n = 173) and a test set (n = 57). Five key predictors selected for the nomogram were albumin, activated partial thromboplastin time (APTT), fibrinogen, aspartate aminotransferase (AST), and platelet count. In the test set, the AUROC for the six models ranged from 0.888 to 0.945. The random forest model demonstrated the best performance, with an AUROC of 0.945 (95% CI: 0.886-1.000), an accuracy of 0.951 (95% CI: 0.865-0.989), sensitivity of 0.894, specificity of 0.976, and a Kappa score of 0.884. Conclusions ML-based models can be established and potentially help identify hospitalized pediatric patients with dengue who are at high risk of progressing to DSS. The proposed nomogram may be a valuable tool for predicting DSS in clinical practice.
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Affiliation(s)
- Rang N Nguyen
- Pediatrics, Can Tho University of Medicine and Pharmacy, Can Tho, VNM
| | - Hue T Lam
- Pediatrics, Bac Lieu General Hospital, Bac Lieu, VNM
| | - Hung V Phan
- Pediatrics, Can Tho University of Medicine and Pharmacy, Can Tho, VNM
| | - Nghia Q Bui
- Pediatrics, Can Tho University of Medicine and Pharmacy, Can Tho, VNM
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Heydarifard Z, Heydarifard F, Mousavi FS, Zandi M. Dengue fever: a decade of burden in Iran. Front Public Health 2024; 12:1484594. [PMID: 39507666 PMCID: PMC11537875 DOI: 10.3389/fpubh.2024.1484594] [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: 08/22/2024] [Accepted: 10/09/2024] [Indexed: 11/08/2024] Open
Abstract
Since the first reported traveler case of Dengue in Tehran in 2008, the virus has gradually spread across Iran, driven by factors including international travel, climate change, and Aedes mosquito vectors. The disease has manifested in various forms, ranging from mild fever to severe dengue, with notable cases identified in Sistan and Baluchistan Province. Despite the increasing prevalence, Iran faces significant challenges in surveillance, diagnosis, and vector control. This perspective comprehensively analyzes dengue virus epidemiology in Iran, emphasizing the need for enhanced public health strategies, including genomic surveillance, targeted interventions, and health education. The findings highlight the critical importance of addressing these challenges to mitigate the potential for large-scale dengue epidemics and protect public health.
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Affiliation(s)
- Zahra Heydarifard
- Department of Virology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Fatemeh Heydarifard
- Department of Veterinary, Faculty of Veterinary Medicine, Lorestan University, Khorramabad, Iran
| | - Fatemeh Sadat Mousavi
- Department of Microbiology and Immunology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Milad Zandi
- Department of Microbiology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran
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Guzman MG, Martinez E. Central and Peripheral Nervous System Manifestations Associated with Dengue Illness. Viruses 2024; 16:1367. [PMID: 39339843 PMCID: PMC11435791 DOI: 10.3390/v16091367] [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: 06/07/2024] [Revised: 08/09/2024] [Accepted: 08/19/2024] [Indexed: 09/30/2024] Open
Abstract
Dengue illness, caused by the dengue viruses, continues to be a major global health concern, with increasing incidence and the emergence of severe manifestations such as neurological complications. An overview of the current understanding of dengue epidemiology, clinical manifestations, and research priorities is presented here. Dengue transmission has escalated in recent years, exacerbated by factors such as vector expansion, climate change, and socioeconomic challenges. The clinical spectrum of dengue ranges from mild febrile illness to severe manifestations, including hemorrhagic fever and neurological complications. Neurological manifestations of dengue, once considered rare, are now increasingly reported, encompassing encephalitis, myelitis, and Guillain-Barré Syndrome, among others. Diagnosis primarily relies on laboratory methods such as RT/PCR, NS1 antigen detection, and serological assays. Despite advancements in understanding the dengue pathogenesis, there remains a critical need for effective vaccines, antiviral drugs, improved surveillance methods, predictive models for disease severity, and long-term studies on post-Dengue sequelae. Integrated programs and holistic approaches to dengue control are essential for mitigating its impact. Addressing these research priorities will be pivotal in combating dengue and reducing its global burden.
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Affiliation(s)
- Maria G Guzman
- Institute of Tropical Medicine "Pedro Kouri", WHO/PAHO Collaborating Center for the Study of Dengue and Its Control, Autopista Novia del Mediodia, km 6 1/2, La Lisa 17100, Cuba
| | - Eric Martinez
- Institute of Tropical Medicine "Pedro Kouri", WHO/PAHO Collaborating Center for the Study of Dengue and Its Control, Autopista Novia del Mediodia, km 6 1/2, La Lisa 17100, Cuba
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Goyal PK, Hissaria K, Shekhawat C. Role of Serum Ferritin as a Predictor of Dengue Severity: A Prospective Observational Study From India. Cureus 2024; 16:e63503. [PMID: 39081444 PMCID: PMC11288214 DOI: 10.7759/cureus.63503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/29/2024] [Indexed: 08/02/2024] Open
Abstract
BACKGROUND Early detection of dengue fever progression to severe form using simple measurable tests is crucial for initiating appropriate supportive therapy. This study aimed to assess whether serum ferritin is an indicator of severity in dengue patients. MATERIAL AND METHODS This hospital-based prospective observational study was done on 70 patients admitted in wards and intensive care unit (ICU) of Aditya Birla Memorial Hospital, Pune, India, and Jaipur Golden Hospital, Delhi, India, satisfying inclusion criteria during the study period. Dengue cases were classified as those who had non-structural protein 1 (NS1) positivity on days 2-8 and/or positive immunoglobulin M (IgM) on days 6-10, while those with other confirmed diagnoses were considered as other febrile illnesses. The outcome of this study was to see an association between serum ferritin levels and severity of illness, condition at the time of discharge/death, and the length of hospitalization. RESULTS Mean serum ferritin (ng/mL), platelet count (cells/mm3), and hospital stay (in days) were 1469.43±297.53, 17289.29±8254.47, and 6.01±3.90, respectively. Subjects with severe dengue had significantly higher mean serum ferritin levels and median hospital stays compared to those with non-severe dengue (p<0.05). A moderate (Pearson correlation coefficient ρ=-0.35, p=0.0027) negative correlation was found between serum ferritin level and platelet count whereas a moderate (ρ=0.50, p=0.0000) positive correlation was found between serum ferritin level and hospital stay. CONCLUSION Serum ferritin levels can be used as a tool to help differentiate between severe and non-severe dengue.
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Masyeni S, Wardhana IMW, Nainu F. Cytokine profiles in dengue fever and dengue hemorrhagic fever: A study from Indonesia. NARRA J 2024; 4:e309. [PMID: 38798833 PMCID: PMC11125316 DOI: 10.52225/narra.v4i1.309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 02/27/2024] [Indexed: 05/29/2024]
Abstract
Recent studies have demonstrated that cytokine dysregulation has a critical role in the pathogenesis of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The aim of this study was to investigate the association between tumor necrosis factor (TNF- α), interleukin 6 (IL-6), interleukin 10 (IL-10), and interleukin 17 (IL-17) with infection status, and severity of dengue. A prospective cross-sectional study was conducted at three hospitals in Gianyar regency and Denpasar municipality, Bali, Indonesia, from June to December 2022. Sixty-four dengue infected patients were involved. Patients' serum was tested for dengue infection using NS1 antigen rapid test, dengue virus immunoglobulin M (IgM) and immunoglobulin G (IgG) test, and reverse transcription polymerase chain reaction (RT-PCR). Cytokine levels (TNF-α, IL-6, IL-10, and IL-17) were measured using enzyme-linked immunosorbent assay (ELISA). Infection status was determined by combining serological and RT-PCR results, categorizing patients into primary and secondary infections. The present study found that DF patients had lower TNF-α, IL-6, and IL-17 but higher IL-10 levels compared to DHF patients (p<0.001). Elevated TNF-α, IL-6, and IL-17 levels were higher in secondary infection, while IL-10 level was higher in primary infection (p<0.001). In conclusion, cytokines play a crucial role in the interplay between cytokine dysregulation and dengue infection dynamics.
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Affiliation(s)
- Sri Masyeni
- Department of Internal Medicine, Faculty of Medicine and Health Sciences, Universitas Warmadewa, Bali, Indonesia
| | - I Made W. Wardhana
- Department of Internal Medicine, Freeport Hospital, Irian Jaya, Indonesia
| | - Firzan Nainu
- Department of Pharmacy, Faculty of Pharmacy, Universitas Hasanuddin, Makassar, Indonesia
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Huits R, Angelo KM, Amatya B, Barkati S, Barnett ED, Bottieau E, Emetulu H, Epelboin L, Eperon G, Medebb L, Gobbi F, Grobusch MP, Itani O, Jordan S, Kelly P, Leder K, Díaz-Menéndez M, Okumura N, Rizwan A, Rothe C, Saio M, Waggoner J, Yoshimura Y, Libman M, Hamer DH, Schwartz E. Clinical Characteristics and Outcomes Among Travelers With Severe Dengue : A GeoSentinel Analysis. Ann Intern Med 2023; 176:940-948. [PMID: 37335991 PMCID: PMC10760980 DOI: 10.7326/m23-0721] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/21/2023] Open
Abstract
BACKGROUND Dengue virus is a flavivirus transmitted by Aedes mosquitoes and is an important cause of illness worldwide. Data on the severity of travel-associated dengue illness are limited. OBJECTIVE To describe the epidemiology, clinical characteristics, and outcomes among international travelers with severe dengue or dengue with warning signs as defined by the 2009 World Health Organization classification (that is, complicated dengue). DESIGN Retrospective chart review and analysis of travelers with complicated dengue reported to GeoSentinel from January 2007 through July 2022. SETTING 20 of 71 international GeoSentinel sites. PATIENTS Returning travelers with complicated dengue. MEASUREMENTS Routinely collected surveillance data plus chart review with abstraction of clinical information using predefined grading criteria to characterize the manifestations of complicated dengue. RESULTS Of 5958 patients with dengue, 95 (2%) had complicated dengue. Eighty-six (91%) patients had a supplemental questionnaire completed. Eighty-five of 86 (99%) patients had warning signs, and 27 (31%) were classified as severe. Median age was 34 years (range, 8 to 91 years); 48 (56%) were female. Patients acquired dengue most frequently in the Caribbean (n = 27 [31%]) and Southeast Asia (n = 21 [24%]). Frequent reasons for travel were tourism (46%) and visiting friends and relatives (32%). Twenty-one of 84 (25%) patients had comorbidities. Seventy-eight (91%) patients were hospitalized. One patient died of nondengue-related illnesses. Common laboratory findings and signs were thrombocytopenia (78%), elevated aminotransferase (62%), bleeding (52%), and plasma leakage (20%). Among severe cases, ophthalmologic pathology (n = 3), severe liver disease (n = 3), myocarditis (n = 2), and neurologic symptoms (n = 2) were reported. Of 44 patients with serologic data, 32 confirmed cases were classified as primary dengue (IgM+/IgG-) and 12 as secondary (IgM-/IgG+) dengue. LIMITATIONS Data for some variables could not be retrieved by chart review for some patients. The generalizability of our observations may be limited. CONCLUSION Complicated dengue is relatively rare in travelers. Clinicians should monitor patients with dengue closely for warning signs that may indicate progression to severe disease. Risk factors for developing complications of dengue in travelers need further prospective study. PRIMARY FUNDING SOURCE Centers for Disease Control and Prevention, International Society of Travel Medicine, Public Health Agency of Canada, and GeoSentinel Foundation.
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Affiliation(s)
- Ralph Huits
- Department of Infectious Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Verona, Italy (R.H.)
| | - Kristina M Angelo
- Division of Global Migration and Quarantine, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia (K.M.A.)
| | - Bhawana Amatya
- CIWEC Hospital and Travel Medicine Center, Kathmandu, Nepal (B.A.)
| | - Sapha Barkati
- J.D. MacLean Centre for Tropical Diseases, McGill University Health Centre, Montreal, Quebec, Canada (S.B.)
| | - Elizabeth D Barnett
- Section of Pediatric Infectious Diseases, Boston Medical Center, Boston, Massachusetts (E.D.B., M.L.)
| | - Emmanuel Bottieau
- Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium (E.B.)
| | - Hannah Emetulu
- International Society of Travel Medicine, Atlanta, Georgia (H.E., A.R.)
| | - Loïc Epelboin
- Infectious and Tropical Diseases Unit and CIC Inserm 1424, Centre Hospitalier de Cayenne, Cayenne, French Guiana (L.E.)
| | - Gilles Eperon
- Division of Tropical and Humanitarian Medicine, Geneva University Hospitals, Geneva, Switzerland (G.E.)
| | - Line Medebb
- Aix Marseille University, AP-HM, IHU-Méditerranée Infection, Marseille, France (L.M.)
| | - Federico Gobbi
- Department of Infectious Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Verona, and Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy (F.G.)
| | - Martin P Grobusch
- Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Amsterdam University Medical Center, Amsterdam, the Netherlands (M.P.G.)
| | - Oula Itani
- Institut Pasteur, Centre Médical, Centre d'Infectiologie Necker-Pasteur, Paris, France (O.I.)
| | - Sabine Jordan
- Division of Tropical Medicine, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, and Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany (S.J.)
| | - Paul Kelly
- BronxCare Hospital Center, Bronx, New York (P.K.)
| | - Karin Leder
- School of Public Health and Preventive Medicine, Monash University, and Victorian Infectious Diseases Service, The Royal Melbourne Hospital, Victoria, Australia (K.L.)
| | - Marta Díaz-Menéndez
- Tropical Medicine Department, Hospital Universitario La Paz-Carlos III, IdIPAz, and CIBERINFECT, Madrid, Spain (M.D.)
| | - Nobumasa Okumura
- Center Hospital of the National Center for Global Health and Medicine, Shinjuku City, Tokyo, Japan (N.O.)
| | - Aisha Rizwan
- International Society of Travel Medicine, Atlanta, Georgia (H.E., A.R.)
| | - Camilla Rothe
- Department of Infectious Diseases and Tropical Medicine, Ludwig-Maximilians-Universität München, Munich, Germany (C.R.)
| | - Mauro Saio
- Doctor's Plaza, Nairobi Hospital, Nairobi, Kenya (M.S.)
| | - Jesse Waggoner
- Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia (J.W.)
| | | | - Michael Libman
- Section of Pediatric Infectious Diseases, Boston Medical Center, Boston, Massachusetts (E.D.B., M.L.)
| | - Davidson H Hamer
- Department of Global Health, Boston University School of Public Health, Section of Infectious Diseases, Boston University School of Medicine, Center for Emerging Infectious Disease Policy and Research, Boston University, and National Emerging Infectious Disease Laboratory, Boston, Massachusetts (D.H.H.)
| | - Eli Schwartz
- The Center of Geographical Medicine and Tropical Diseases, Sheba Medical Center, Tel HaShomer, and Ramat Gan & Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.S.)
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Rathnakumar S, Kambhampati NSV, Saiswaroop R, Pradhan SS, Ramkumar G, Beeraka N, Muddu GK, Kumar S, Javvaji SK, Parangoankar A, Sivaramakrishnan V, Ramamurthy SS. Integrated clinical and metabolomic analysis of dengue infection shows molecular signatures associated with host-pathogen interaction in different phases of the disease. Metabolomics 2023; 19:47. [PMID: 37130982 DOI: 10.1007/s11306-023-02011-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 04/20/2023] [Indexed: 05/04/2023]
Abstract
PURPOSE Dengue is a mosquito vector-borne disease caused by the dengue virus, which affects 125 million people globally. The disease causes considerable morbidity. The disease, based on symptoms, is classified into three characteristic phases, which can further lead to complications in the second phase. Molecular signatures that are associated with the three phases have not been well characterized. We performed an integrated clinical and metabolomic analysis of our patient cohort and compared it with omics data from the literature to identify signatures unique to the different phases. METHODS The dengue patients are recruited by clinicians after standard-of-care diagnostic tests and evaluation of symptoms. Blood from the patients was collected. NS1 antigen, IgM, IgG antibodies, and cytokines in serum were analyzed using ELISA. Targeted metabolomics was performed using LC-MS triple quad. The results were compared with analyzed transcriptomic data from the GEO database and metabolomic data sets from the literature. RESULTS The dengue patients displayed characteristic features of the disease, including elevated NS1 levels. TNF-α was found to be elevated in all three phases compared to healthy controls. The metabolic pathways were found to be deregulated compared to healthy controls only in phases I and II of dengue patients. The pathways represent viral replication and host response mediated pathways. The major pathways include nucleotide metabolism of various amino acids and fatty acids, biotin, etc. CONCLUSION: The results show elevated TNF-α and metabolites that are characteristic of viral infection and host response. IL10 and IFN-γ were not significant, consistent with the absence of any complications.
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Affiliation(s)
- Sriram Rathnakumar
- Disease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Puttaparthi, Andhra Pradesh, 515134, India
| | - Naga Sai Visweswar Kambhampati
- STAR Laboratory, Central Research Instruments Facility, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Puttaparthi, Andhra Pradesh, 515134, India
| | - R Saiswaroop
- Disease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Puttaparthi, Andhra Pradesh, 515134, India
| | - Sai Sanwid Pradhan
- Disease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Puttaparthi, Andhra Pradesh, 515134, India
| | - G Ramkumar
- Department of General Medicine, Sri Sathya Sai General Hospital, Sri Sathya Sai Institute of Higher Medical Sciences Campus, Whitefield, Bengaluru, Karnataka, 560066, India
| | - Nirmala Beeraka
- Department of General Medicine, Sri Sathya Sai General Hospital, Sri Sathya Sai Institute of Higher Medical Sciences Campus, Whitefield, Bengaluru, Karnataka, 560066, India
| | - Gopi Krishna Muddu
- Department of Pediatrics, Sri Sathya Sai General Hospital, Puttaparthi, Andhra Pradesh, 515134, India
| | - Sandeep Kumar
- Department of General Medicine, Sri Sathya Sai General Hospital, Puttaparthi, Andhra Pradesh, 515134, India
| | - Sai Kiran Javvaji
- Department of Laboratory Medicine and Cardiology, Sri Sathya Sai Institute of Higher Medical Sciences, Whitefield, Bengaluru, Karnataka, 560066, India
| | | | - Venketesh Sivaramakrishnan
- Disease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Puttaparthi, Andhra Pradesh, 515134, India.
| | - Sai Sathish Ramamurthy
- STAR Laboratory, Central Research Instruments Facility, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Puttaparthi, Andhra Pradesh, 515134, India.
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Islam S, Khan MAS, Badal MFA, Khan MZI, Gozal D, Hasan MJ. Clinical and hematological profiles of children with dengue residing in a non-endemic zone of Bangladesh. PLoS Negl Trop Dis 2022; 16:e0010847. [PMID: 36215330 PMCID: PMC9584401 DOI: 10.1371/journal.pntd.0010847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 10/20/2022] [Accepted: 09/27/2022] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND The clinical and hematological parameters of children with dengue during an outbreak in a non-endemic region have not been well described. To delineate the clinical profile of pediatric cases from a tertiary care center located in a non-endemic zone (Tangail district) in Bangladesh was the objective of the study. METHODS A cross-sectional observational study was conducted in the Department of Pediatrics of a 250-bed general hospital in Tangail, Bangladesh, between June 2019 to September 2019. Data collection was done using a pre-structured case record form. All patients underwent detailed history taking, physical examination, and hematological profiling. A total of 123 confirmed dengue cases were analyzed. RESULTS The average age of patients was 7.3±4.1 (SD) years, with nearly two-thirds being male (61.8%) and the majority living in rural areas (76.4%). Fever (100%), body ache (57.7%), headache (56.9%), and rash (55.3%) were the four common clinical manifestations. NS1 antigen and anti-dengue IgM antibody tests were positive in 86% (102 out of 119) and 37.7% (20 out of 53) of cases, respectively. Thrombocytopenia was present in 42% of cases. The majority of the cases had dengue fever (73.2%), and the remaining cases were either dengue hemorrhagic fever or dengue shock syndrome (26.8%). Clinical and hematological parameters varied with the type of dengue. Particularly, rash (p = <0.001), bleeding manifestation (p = <0.001), vomiting (p = 0.012), hypotension (p = 0.018), pleural effusion (p = 0.018), ascites (p = 0.018), hepatomegaly (p = <0.001) and low platelet count (<150 x 103cells/μL) (p = 0.038) were significantly more common among dengue hemorrhagic fever or dengue shock syndrome cases. CONCLUSIONS The present study documented the clinical features of dengue in a pediatric group of patients from a non-endemic zone of Bangladesh. This vulnerable patient group requires earlier identification and keen attention during management.
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Affiliation(s)
- Saiful Islam
- 250 Bedded General Hospital, Tangail, Bangladesh
| | | | | | | | - David Gozal
- University of Missouri School of Medicine, Columbia, Missouri, United States of America
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Leowattana W, Leowattana T. Dengue hemorrhagic fever and the liver. World J Hepatol 2021; 13:1968-1976. [PMID: 35070001 PMCID: PMC8727196 DOI: 10.4254/wjh.v13.i12.1968] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 03/30/2021] [Accepted: 11/13/2021] [Indexed: 02/06/2023] Open
Abstract
Dengue hemorrhagic fever (DHF) is one of the most rapidly emerging infections of tropical and subtropical regions worldwide. It affects more rural and urban areas due to many factors, including climate change. Although most people with dengue viral infection are asymptomatic, approximately 25% experience a self-limited febrile illness with mild to moderate biochemical abnormalities. Severe dengue diseases develop in a small proportion of these patients, and the common organ involvement is the liver. The hepatocellular injury was found in 60%-90% of DHF patients manifested as hepatomegaly, jaundice, elevated aminotransferase enzymes, and critical condition as an acute liver failure (ALF). Even the incidence of ALF in DHF is very low (0.31%-1.1%), but it is associated with a relatively high mortality rate (20%-68.3%). The pathophysiology of liver injury in DHF included the direct cytopathic effect of the DENV causing hepatocytes apoptosis, immune-mediated hepatocyte injury induced hepatitis, and cytokine storm. Hepatic hypoperfusion is another contributing factor in dengue shock syndrome. The reduction of morbidity and mortality in DHF with liver involvement is dependent on the early detection of warning signs before the development of ALF.
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Affiliation(s)
- Wattana Leowattana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Bangkok, Thailand.
| | - Tawithep Leowattana
- Department of Medicine, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Bangkok, Thailand
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Successful Outpatient Management of Children at a Secondary Care Hospital in Pakistan in a Dengue Fever Epidemic and Their Clinical Outcomes. J Trop Med 2021; 2021:3296448. [PMID: 34764996 PMCID: PMC8577943 DOI: 10.1155/2021/3296448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 09/27/2021] [Accepted: 10/09/2021] [Indexed: 11/17/2022] Open
Abstract
Background There is limited published literature on the feasibility of WHO 2009 guidelines for the management of dengue fever (DF) in Pakistani children. This study aimed to assess the outcome of children with DF who received outpatient treatment according to these guidelines during a DF epidemic. Method This was a prospective cohort study conducted at Federal General Hospital, a secondary care hospital, Islamabad, Pakistan, from 1st August to 31st October 2019. Using WHO DF 2009 guidelines, children ≤13 years, diagnosed as confirmed DF (NS1 Ag +), were classified into the outpatient (DF) or the inpatient group (DF with warning signs or severe dengue (SD)). The inpatient group was admitted to the Pakistan Institute of Medical Sciences, a tertiary care hospital, and discharged on recovery. These children were followed for the primary outcome, i.e., recovery or hospitalization by day 14 of enrollment. Additionally, clinical and laboratory features (Hb, HCT, TLC, PLT, and ALT) of the patients in the outpatient who remained stable with those who progressed to inpatient care during follow-up were compared; also, time of recovery of blood counts was assessed. Results Of 93 children with DF, 87 (93.5%) received outpatient care at enrollment. Of these, 6 (7.8%) deteriorated by day 7 and were admitted to inpatient care. SD was present in 6/93 (6.4%) patients at presentation and were admitted. All children showed signs of recovery until day 14. Male gender (p=0.049), lower normal mean platelet (p=0.02), and high mean hematocrit (p=0.001) were associated with disease progression. Conclusion The majority of children with confirmed DF who received outpatient treatment according to WHO 2009 guidelines were successfully managed. Additionally, confirmed DF with warning signs or SD were admitted and recovered. Regular follow-ups according to the guidelines are pertinent. Thrombocytopenia and high HCT were associated with disease progression.
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Khan MAS, Al Mosabbir A, Raheem E, Ahmed A, Rouf RR, Hasan M, Alam FB, Hannan N, Yesmin S, Amin R, Ahsan N, Anwar S, Afroza S, Hossain MS. Clinical spectrum and predictors of severity of dengue among children in 2019 outbreak: a multicenter hospital-based study in Bangladesh. BMC Pediatr 2021; 21:478. [PMID: 34715835 PMCID: PMC8555185 DOI: 10.1186/s12887-021-02947-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 10/07/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND The mosquito-borne arboviral disease dengue has become a global public health concern. However, very few studies have reported atypical clinical features of dengue among children. Because an understanding of various spectrums of presentation of dengue is necessary for timely diagnosis and management, we aimed to document the typical and atypical clinical features along with predictors of severity among children with dengue during the largest outbreak in Bangladesh in 2019. METHODS We conducted a cross-sectional study between August 15 and September 30, 2019. in eight tertiary level hospitals in Dhaka city. Children (aged < 15 years) with serologically confirmed dengue were conveniently selected for data collection through a structured questionnaire. Descriptive, inferential statistics, and multivariable logistic regression were used to analyze data. RESULTS Among the 190 children (mean age 8.8 years, and male-female ratio 1.22:1) included in the analysis, respectively 71.1 and 28.9% children had non-severe and severe dengue. All children had fever with an average temperature of 103.3 ± 1.2 F (SD). Gastrointestinal symptoms were the most common associated feature, including mostly vomiting (80.4%), decreased appetite (79.5%), constipation (72.7%), and abdominal pain (64.9%). Mouth sore, a less reported feature besides constipation, was present in 28.3% of children. Atypical clinical features were mostly neurological, with confusion (21.3%) being the predominant symptom. Frequent laboratory abnormalities were thrombocytopenia (87.2%), leucopenia (40.4%), and increased hematocrit (13.4%). Age (AOR 0.86, 95%CI 0.75-0.98, p = 0.023), mouth sore (AOR 2.69, 95%CI 1.06-6.96, p = 0.038) and a decreased platelet count (< 50,000/mm3) with increased hematocrit (> 20%) (AOR 4.94, 95%CI 1.48-17.31, p = 0.01) were significant predictors of severity. CONCLUSIONS Dengue in children was characterized by a high severity, predominance of gastrointestinal symptoms, and atypical neurological presentations. Younger age, mouth sores, and a decreased platelet with increased hematocrit were significant predictors of severity. Our findings would contribute to the clinical management of dengue in children.
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Affiliation(s)
- Md Abdullah Saeed Khan
- Department of Emerging and Neglected Diseases, Biomedical Research Foundation, Dhaka, Bangladesh
| | - Abdullah Al Mosabbir
- Department of Emerging and Neglected Diseases, Biomedical Research Foundation, Dhaka, Bangladesh
| | - Enayetur Raheem
- Department of Emerging and Neglected Diseases, Biomedical Research Foundation, Dhaka, Bangladesh
| | - Ahsan Ahmed
- Department of Emerging and Neglected Diseases, Biomedical Research Foundation, Dhaka, Bangladesh
| | - Rashawan Raziur Rouf
- Department of Emerging and Neglected Diseases, Biomedical Research Foundation, Dhaka, Bangladesh
| | - Mahmudul Hasan
- Department of Emerging and Neglected Diseases, Biomedical Research Foundation, Dhaka, Bangladesh
| | - Fawzia Bente Alam
- Sir Salimullah Medical College and Mitford Hospital, Dhaka, Bangladesh
| | - Nahida Hannan
- Department of Emerging and Neglected Diseases, Biomedical Research Foundation, Dhaka, Bangladesh
| | | | - Robed Amin
- Department of Medicine, Dhaka Medical College & Hospital, Dhaka, Bangladesh
| | - Nazmul Ahsan
- Department of Medicine, Shaheed Suhrawardy Medical College & Hospital, Dhaka, Bangladesh
| | - Sayeeda Anwar
- Department of Paediatrics, Dhaka Medical College & Hospital, Dhaka, Bangladesh
| | - Syeda Afroza
- Department of Paediatrics, MH Samorita Hospital and Medical College, Dhaka, Bangladesh
| | - Mohammad Sorowar Hossain
- Department of Emerging and Neglected Diseases, Biomedical Research Foundation, Dhaka, Bangladesh.
- School of Environment and Life Sciences, Independent University, Dhaka, Bangladesh.
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Tsheten T, Clements ACA, Gray DJ, Adhikary RK, Furuya-Kanamori L, Wangdi K. Clinical predictors of severe dengue: a systematic review and meta-analysis. Infect Dis Poverty 2021; 10:123. [PMID: 34627388 PMCID: PMC8501593 DOI: 10.1186/s40249-021-00908-2] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 09/21/2021] [Indexed: 11/11/2022] Open
Abstract
Background Severe dengue is a life-threatening complication; rapid identification of these cases, followed by adequate management is crucial to improve the clinical prognosis. Therefore, this study aimed to identify risk factors and predictors of severe dengue.
Methods A literature search for studies reporting risk factors of severe dengue among individuals with dengue virus infection was conducted in PubMed, Scopus and Web of Science database from inception to December 31, 2020. Pooled odds ratios (ORs) for patients’ demographic characteristics, co-morbidities, and warning signs were estimated using an inverse variance heterogeneity model.
Results We included 143 articles in the meta-analysis from a total of 13 090 articles retrieved from the literature search. The risk factors of severe dengue were: being a child [OR = 1.96; 95% confidence interval (CI): 1.22–3.13], secondary infection (OR = 3.23; 95% CI: 2.28–4.57), and patients with pre-existing diabetes (OR = 2.88; 95% CI: 1.72–4.81) and renal disease (OR = 4.54; 95% CI: 1.55–13.31). Warning signs strongly associated with severe disease were increased haematocrit with a concurrent decrease in platelet count (OR = 5.13; 95% CI: 1.61–16.34), abdominal pain (OR = 2.00; 95% CI: 1.49–2.68), lethargy (OR = 2.73; 95% CI: 1.05–7.10), vomiting (OR = 1.80; 95% CI: 1.43–2.26), hepatomegaly (OR = 5.92; 95% CI: 3.29–10.66), ascites (OR = 6.30; 95% CI: 3.75–10.60), pleural effusion (OR = 5.72; 95% CI: 3.24–10.10) and melena (OR = 4.05; 95% CI: 1.64–10.00). Conclusions Our meta-analysis identified children, secondary infection, diabetes and renal disease(s) as important predictors of severe dengue. Our finding also supports the predictive ability of the WHO warning signs to identify severe dengue. These findings are useful for clinicians to identify severe dengue for management and timely interventions. ![]()
Supplementary Information The online version contains supplementary material available at 10.1186/s40249-021-00908-2.
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Affiliation(s)
- Tsheten Tsheten
- Department of Global Health, Research School of Population Health, College of Health and Medicine, Australian National University, Canberra, Australia. .,Royal Centre for Disease Control, Ministry of Health, Thimphu, Bhutan.
| | - Archie C A Clements
- Telethon Kids Institute, Nedlands, Australia.,Curtin University, Perth, Australia
| | - Darren J Gray
- Department of Global Health, Research School of Population Health, College of Health and Medicine, Australian National University, Canberra, Australia
| | - Ripon K Adhikary
- Department of Global Health, Research School of Population Health, College of Health and Medicine, Australian National University, Canberra, Australia
| | - Luis Furuya-Kanamori
- UQ Centre for Clinical Research, The University of Queensland, Herston, QLD, Australia
| | - Kinley Wangdi
- Department of Global Health, Research School of Population Health, College of Health and Medicine, Australian National University, Canberra, Australia
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Thach TQ, Eisa HG, Hmeda AB, Faraj H, Thuan TM, Abdelrahman MM, Awadallah MG, Ha NX, Noeske M, Abdul Aziz JM, Nam NH, Nile ME, Dumre SP, Huy NT, Hirayama K. Predictive markers for the early prognosis of dengue severity: A systematic review and meta-analysis. PLoS Negl Trop Dis 2021; 15:e0009808. [PMID: 34610027 PMCID: PMC8519480 DOI: 10.1371/journal.pntd.0009808] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Revised: 10/15/2021] [Accepted: 09/10/2021] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Predictive markers represent a solution for the proactive management of severe dengue. Despite the low mortality rate resulting from severe cases, dengue requires constant examination and round-the-clock nursing care due to the unpredictable progression of complications, posing a burden on clinical triage and material resources. Accordingly, identifying markers that allow for predicting disease prognosis from the initial diagnosis is needed. Given the improved pathogenesis understanding, myriad candidates have been proposed to be associated with severe dengue progression. Thus, we aim to review the relationship between the available biomarkers and severe dengue. METHODOLOGY We performed a systematic review and meta-analysis to compare the differences in host data collected within 72 hours of fever onset amongst the different disease severity levels. We searched nine bibliographic databases without restrictive criteria of language and publication date. We assessed risk of bias and graded robustness of evidence using NHLBI quality assessments and GRADE, respectively. This study protocol is registered in PROSPERO (CRD42018104495). PRINCIPAL FINDINGS Of 4000 records found, 40 studies for qualitative synthesis, 19 for meta-analysis. We identified 108 host and viral markers collected within 72 hours of fever onset from 6160 laboratory-confirmed dengue cases, including hematopoietic parameters, biochemical substances, clinical symptoms, immune mediators, viral particles, and host genes. Overall, inconsistent case classifications explained substantial heterogeneity, and meta-analyses lacked statistical power. Still, moderate-certainty evidence indicated significantly lower platelet counts (SMD -0.65, 95% CI -0.97 to -0.32) and higher AST levels (SMD 0.87, 95% CI 0.36 to 1.38) in severe cases when compared to non-severe dengue during this time window. CONCLUSION The findings suggest that alterations of platelet count and AST level-in the first 72 hours of fever onset-are independent markers predicting the development of severe dengue.
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Affiliation(s)
- Tran Quang Thach
- Department of Immunogenetics, Nagasaki University, Nagasaki, Japan
| | - Heba Gamal Eisa
- Faculty of Medicine, Menoufia University, Shebin El-Koum, Egypt
| | | | - Hazem Faraj
- Faculty of Medicine, University of Tripoli, Tripoli, Libya
| | - Tieu Minh Thuan
- Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada
| | | | | | - Nam Xuan Ha
- Hue University of Medicine and Pharmacy, Hue, Vietnam
| | - Michael Noeske
- American University of the Caribbean School of Medicine, Cupecoy, Sint Maarten
| | | | - Nguyen Hai Nam
- Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | | | | | - Nguyen Tien Huy
- School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan
| | - Kenji Hirayama
- Department of Immunogenetics, Nagasaki University, Nagasaki, Japan
- School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan
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Sangkaew S, Ming D, Boonyasiri A, Honeyford K, Kalayanarooj S, Yacoub S, Dorigatti I, Holmes A. Risk predictors of progression to severe disease during the febrile phase of dengue: a systematic review and meta-analysis. THE LANCET. INFECTIOUS DISEASES 2021; 21:1014-1026. [PMID: 33640077 PMCID: PMC8240557 DOI: 10.1016/s1473-3099(20)30601-0] [Citation(s) in RCA: 119] [Impact Index Per Article: 29.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Revised: 05/01/2020] [Accepted: 06/30/2020] [Indexed: 01/12/2023]
Abstract
BACKGROUND The ability to accurately predict early progression of dengue to severe disease is crucial for patient triage and clinical management. Previous systematic reviews and meta-analyses have found significant heterogeneity in predictors of severe disease due to large variation in these factors during the time course of the illness. We aimed to identify factors associated with progression to severe dengue disease that are detectable specifically in the febrile phase. METHODS We did a systematic review and meta-analysis to identify predictors identifiable during the febrile phase associated with progression to severe disease defined according to WHO criteria. Eight medical databases were searched for studies published from Jan 1, 1997, to Jan 31, 2020. Original clinical studies in English assessing the association of factors detected during the febrile phase with progression to severe dengue were selected and assessed by three reviewers, with discrepancies resolved by consensus. Meta-analyses were done using random-effects models to estimate pooled effect sizes. Only predictors reported in at least four studies were included in the meta-analyses. Heterogeneity was assessed using the Cochrane Q and I2 statistics, and publication bias was assessed by Egger's test. We did subgroup analyses of studies with children and adults. The study is registered with PROSPERO, CRD42018093363. FINDINGS Of 6643 studies identified, 150 articles were included in the systematic review, and 122 articles comprising 25 potential predictors were included in the meta-analyses. Female patients had a higher risk of severe dengue than male patients in the main analysis (2674 [16·2%] of 16 481 vs 3052 [10·5%] of 29 142; odds ratio [OR] 1·13 [95% CI 1·01-1·26) but not in the subgroup analysis of studies with children. Pre-existing comorbidities associated with severe disease were diabetes (135 [31·3%] of 431 with vs 868 [16·0%] of 5421 without; crude OR 4·38 [2·58-7·43]), hypertension (240 [35·0%] of 685 vs 763 [20·6%] of 3695; 2·19 [1·36-3·53]), renal disease (44 [45·8%] of 96 vs 271 [16·0%] of 1690; 4·67 [2·21-9·88]), and cardiovascular disease (nine [23·1%] of 39 vs 155 [8·6%] of 1793; 2·79 [1·04-7·50]). Clinical features during the febrile phase associated with progression to severe disease were vomiting (329 [13·5%] of 2432 with vs 258 [6·8%] of 3797 without; 2·25 [1·87-2·71]), abdominal pain and tenderness (321 [17·7%] of 1814 vs 435 [8·1%] of 5357; 1·92 [1·35-2·74]), spontaneous or mucosal bleeding (147 [17·9%] of 822 vs 676 [10·8%] of 6235; 1·57 [1·13-2·19]), and the presence of clinical fluid accumulation (40 [42·1%] of 95 vs 212 [14·9%] of 1425; 4·61 [2·29-9·26]). During the first 4 days of illness, platelet count was lower (standardised mean difference -0·34 [95% CI -0·54 to -0·15]), serum albumin was lower (-0·5 [-0·86 to -0·15]), and aminotransferase concentrations were higher (aspartate aminotransferase [AST] 1·06 [0·54 to 1·57] and alanine aminotransferase [ALT] 0·73 [0·36 to 1·09]) among individuals who progressed to severe disease. Dengue virus serotype 2 was associated with severe disease in children. Secondary infections (vs primary infections) were also associated with severe disease (1682 [11·8%] of 14 252 with vs 507 [5·2%] of 9660 without; OR 2·26 [95% CI 1·65-3·09]). Although the included studies had a moderate to high risk of bias in terms of study confounding, the risk of bias was low to moderate in other domains. Heterogeneity of the pooled results varied from low to high on different factors. INTERPRETATION This analysis supports monitoring of the warning signs described in the 2009 WHO guidelines on dengue. In addition, testing for infecting serotype and monitoring platelet count and serum albumin, AST, and ALT concentrations during the febrile phase of illness could improve the early prediction of severe dengue. FUNDING Wellcome Trust, National Institute for Health Research, Collaborative Project to Increase Production of Rural Doctors, and Royal Thai Government.
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Affiliation(s)
- Sorawat Sangkaew
- Section of Adult Infectious Disease, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK; Department of Social Medicine, Hatyai Hospital, Songkhla, Thailand.
| | - Damien Ming
- Section of Adult Infectious Disease, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK
| | - Adhiratha Boonyasiri
- Section of Adult Infectious Disease, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK
| | - Kate Honeyford
- Global Digital Health Unit, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, UK
| | - Siripen Kalayanarooj
- Department of Pediatrics, Queen Sirikit National Institute of Child Health, Bangkok, Thailand
| | - Sophie Yacoub
- Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK
| | - Ilaria Dorigatti
- MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, UK
| | - Alison Holmes
- Section of Adult Infectious Disease, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK; Antimicrobial Resistance Collaborative, Imperial College London, London, UK
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Htun TP, Xiong Z, Pang J. Clinical signs and symptoms associated with WHO severe dengue classification: a systematic review and meta-analysis. Emerg Microbes Infect 2021; 10:1116-1128. [PMID: 34036893 PMCID: PMC8205005 DOI: 10.1080/22221751.2021.1935327] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
The World Health Organization (WHO) introduced the new dengue classification in 2009. We aimed to assess the association of clinical signs and symptoms with WHO severe dengue classification in clinical practice. A systematic literature search was performed using the databases of PubMed, Embase, and Scopus between 2009 and 2018 according to PRISMA guideline. Meta-analysis was performed with the RevMan software. A random or fixed-effect model was applied to pool odds ratios and 95% confidence intervals of important signs and symptoms across studies. Thirty nine articles from 1790 records were included in this review. In our meta-analysis, signs and symptoms associated with higher risk of severe dengue were comorbidity, vomiting, persistent vomiting, abdominal pain or tenderness, pleural effusion, ascites, epistaxis, gum bleeding, GI bleeding, skin bleeding, lethargy or restlessness, hepatomegaly (>2 cm), increased HCT with decreased platelets, shock, dyspnea, impaired consciousness, thrombocytopenia, elevated AST and ALT, gall bladder wall thickening and secondary infection. This review shows new factors comorbidity, epistaxis, GI and skin bleeding, dyspnea, gall bladder wall thickening and secondary infection may be useful to refine the 2009 classification to triage severe dengue patients.
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Affiliation(s)
- Tha Pyai Htun
- Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore
| | - Zhonghui Xiong
- Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore
| | - Junxiong Pang
- Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore
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Cytokine Signature of Dengue Patients at Different Severity of the Disease. Int J Mol Sci 2021; 22:ijms22062879. [PMID: 33809042 PMCID: PMC7999441 DOI: 10.3390/ijms22062879] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/07/2021] [Accepted: 03/09/2021] [Indexed: 12/18/2022] Open
Abstract
Clinical presentations of dengue fever (DF) are diverse and non-specific, causing unpredictable progression and outcomes. Its progression and severity have been associated with cytokine levels alteration. In this study, dengue patients were classified into groups following the 2009 WHO dengue classification scheme to investigate the cytokine signature at different severity of the disease: dengue without warning sign symptoms (A); dengue with warning signs (B); severe dengue (C); other fever (OF) and healthy (Healthy). We analyzed 23 different cytokines simultaneously, namely IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-33, CD14, CD54, CD62E, CD62L, CD62p, CD106, CD121b, CD154, CD178, GM-CSF, IFN-g, MIF, ST2 and TNF from patients admitted to National Cheng Kung University Hospital during the 2015 Taiwan dengue outbreak. Cytokines TNF, CD54, CD62E, CD62L, CD62P, GM-CSF, IL-1b, IL-2, IL-6, IL-8, IL-10, IL-12p70, IL-17A, INF-g and MIF were elevated while CD106, CD154, IL-4 and L-33 were decreased when compared to the control. IL-10 demonstrated to be a potential diagnostic marker for DF (H and A group; AUC = 0.944, H and OF group; AUC = 0.969). CD121b demonstrated to be predictive of the SD (A and B group; AUC = 0.744, B and C group; AUC = 0.775). Our results demonstrate the cytokine profile changes during the progression of dengue and highlight possible biomarkers for optimizing effective intervention strategies.
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Epidemiology of dengue fever in Gabon: Results from a health facility-based fever surveillance in Lambaréné and its surroundings. PLoS Negl Trop Dis 2021; 15:e0008861. [PMID: 33566822 PMCID: PMC7875424 DOI: 10.1371/journal.pntd.0008861] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 10/08/2020] [Indexed: 11/19/2022] Open
Abstract
Background In Africa, information on dengue is limited to outbreak reports and focused on some countries with continuing transmission in West and East Africa. To estimate the proportion of dengue-positive cases among febrile patients and identify clinical indicators of dengue cases, we conducted passive facility-based fever surveillance in a catchment area population of 70,000 residents of Lambaréné and its surroundings in Gabon. Methods Non-malarial febrile patients with current fever or history of fever (≤7 days) between 1 and 55 years of age, were enrolled at Albert Schweitzer Hospital (ASH). Acute (visit 1, day of enrollment) and convalescent blood samples were collected between 10 and 21 days after enrollment. Acute/convalescent samples were tested with IgM/IgG ELISA, and a selected subset of acute samples with RT-PCR. Results Among 682 non-malarial febrile patients enrolled, 119 (17.4%) were identified as dengue-positive (94 dengue-confirmed and 25 dengue-probable cases). Of these dengue-positive cases, 14 were confirmed with PCR, and based on serotyping, two infections were identified to be DENV-2 and two were DENV-3. The majority of our enrolled patients were <25 years of age and close to 80% of our dengue-positive cases were <15 years of age. In adjusted analyses, retro-orbital pain and abdominal pain were 2.7 and 1.6 times more frequently found among dengue-positive cases, compared to non-dengue cases. Conclusion Lambaréné is not considered dengue-endemic. However, one in six non-malarial febrile episodes was found to be dengue-positive in the study period. Dengue should be considered more frequently in clinicians’ diagnosis among non-malarial febrile patients in Lambaréné. Given the lack of data on dengue in Gabon, additional prospective and longitudinal studies would help to further define the burden and patterns of dengue for improved case detection. In Africa, information on dengue is limited to outbreak reports focused on some countries in West and East Africa. To estimate the proportion of dengue-positive cases among febrile patients and identify clinical indicators of dengue cases, we conducted passive health facility-based fever surveillance in a catchment area population of 70,000 residents of Lambaréné and its surroundings, Gabon. Among the patients with negative malaria RDT results, those with current fever or history of fever (≤7 days) between 1 and 55 years of age were enrolled at Albert Schweitzer Hospital (ASH). Two samples were collected with an interval of 10 to 21 days after enrollment. Samples underwent different testing for dengue confirmation. Among 682 febrile patients enrolled, 17.4% were identified as dengue-positive. Of these dengue-positive cases, we found DENV-2 and DENV-3 serotypes. Close to 80% of our dengue-positive cases were < 15 years old. Retro-orbital pain and abdominal pain were more commonly found among dengue-positive cases, compared to non-dengue cases. Lambaréné is not considered dengue-endemic. However, one in six non-malarial febrile episodes was found to be dengue-positive in the study period. Clinicians should consider dengue more frequently among non-malarial febrile patients. Given the lack of data on dengue in Gabon, more data should be generated to understand the burden and patterns of dengue for improved case detection.
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Kazaura M. Knowledge, attitude and practices about dengue fever among adults living in Pwani Region, Tanzania in 2019. Afr Health Sci 2020; 20:1601-1609. [PMID: 34394220 PMCID: PMC8351831 DOI: 10.4314/ahs.v20i4.12] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Dengue fever (DF) is currently widespread in tropical and sub-tropical countries. Among the triggers of epidemic include urbanization and internal migrations. Within the past few years, there have been DF outbreaks in Tanzania. Although Pwani region is among the predicted risk areas for the DF, there is insufficient data about people's knowledge, attitude and practices towards prevention of DF in their settings. Therefore, the aim of this study was to assess knowledge, attitude and practices about DF among adults in Pwani region in Tanzania. METHODS The cross-sectional study conducted in Mkuranga District, Pwani region in Tanzania. We used face-to-face interviews to collect data. The main analytical procedure was descriptive using frequencies. RESULTS The majority, 97.7%, were aware of DF. Nevertheless, almost 80% had a low knowledge on symptoms, transmission and vector control measures. Furthermore, less than 20% had positive attitude towards dengue fever prevention, severity of the illness and health seeking behavior. CONCLUSION Lack of enough knowledge and positive attitude about disease transmission, symptoms and preventive measures put the population at high risk of contracting the disease. There is need to create and improve friendly, correct and simple information, education and education messages for the rural populations.
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Baiduri S, Husada D, Puspitasari D, Kartina L, Basuki PS, Ismoedijanto I. PROGNOSTIC FACTORS OF SEVERE DENGUE INFECTIONS IN CHILDREN. INDONESIAN JOURNAL OF TROPICAL AND INFECTIOUS DISEASE 2020. [DOI: 10.20473/ijtid.v8i1.10721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
The incidence of dengue fever increase annually and can increase morbidity and mortality. Dengue fever is mosquito-borne disease and caused by one of four serotype dengue viruses. Severe dengue is characterized either by plasma leakage, fluid accumulation, respiratory distress, severe bleeding, or organ impairment. Mortality and serious morbidity of dengue were caused by several factors including the late recognition of the disease and the changing of clinical signs and symptoms. Understanding the prognostic factors in severe dengue will give early warning to physician thus decreasing the morbidity and mortality, and also improving the treatment and disease management. The aim of this study was to analyze the prognostic factors of severe dengue infection in children. This study was observational cohort study in children (2 months-18 years) with dengue infection according to WHO 2009 criteria which admitted in Soetomo and Soewandhie Hospital Surabaya. Analysis with univariate, bivariate and multivariate with IBM SPSS Statistic 17. All patients were confirmed by serologic marker (NS-1 or IgM/IgG Dengue). Clinical and laboratory examination such as complete blood count, aspartate aminotrasnferase (AST), alanine aminotrasferase (ALT), albumin, and both partial trombocite time and activated partial trombosit time (PTT and aPPT) were analyzed comparing nonsevere dengue and severe dengue patients. There were 40 subjects innonsevere and 27 subjects with severe dengue infection. On bivariate analysis, there were significant differences of nutritional status, abdominal pain, petechiae, pleural effusion, leukopenia, thrombocytopenia, hypoalbuminemia, history of transfusion, increasing AST>3x, prolonged PPT and APTT between severe and nonsevere dengue group. After multivariate analyzed, the prognostic factors of severe dengue were overweight/obesity (p=0.003, RR 94), vomiting (p=0.02, RR 13.3), hepatomegaly (p=0.01, RR=69.4), and prolonged APTT (p=0.005, RR=43.25). In conclusion, overweight/obesity, vomiting, hepatomegaly, and prolonged APTT were prognostic factors in severe dengue infection in children.Those factors should be monitored closely in order to reduce the mortality and serious morbidity.
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21
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Lum FM, Lye DCB, Tan JJL, Lee B, Chia PY, Chua TK, Amrun SN, Kam YW, Yee WX, Ling WP, Lim VWX, Pang VJX, Lee LK, Mok EWH, Chong CY, Leo YS, Ng LFP. Longitudinal Study of Cellular and Systemic Cytokine Signatures to Define the Dynamics of a Balanced Immune Environment During Disease Manifestation in Zika Virus-Infected Patients. J Infect Dis 2019; 218:814-824. [PMID: 29672707 PMCID: PMC6057545 DOI: 10.1093/infdis/jiy225] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Accepted: 04/13/2018] [Indexed: 01/12/2023] Open
Abstract
Background Since its unexpected reemergence, Zika virus (ZIKV) has caused numerous outbreaks globally. This study characterized the host immune responses during ZIKV infection. Methods Patient samples were collected longitudinally during the acute, convalescence and recovery phases of ZIKV infection over 6 months during the Singapore outbreak in late 2016. Plasma immune mediators were profiled via multiplex microbead assay, while changes in blood cell numbers were determined with immunophenotyping. Results Data showed the involvement of various immune mediators during acute ZIKV infection accompanied by a general reduction in blood cell numbers for all immune subsets except CD14+ monocytes. Importantly, viremic patients experiencing moderate symptoms had significantly higher quantities of interferon γ–induced protein 10, monocyte chemotactic protein 1, interleukin 1 receptor antagonist, interleukin 8, and placental growth factor 1, accompanied by reduced numbers of peripheral CD8+ T cells, CD4+ T cells, and double-negative T cells. Levels of T-cell associated mediators, including interferon γ–induced protein 10, interferon γ, and interleukin 10, were high in recovery phases of ZIKV infection, suggesting a functional role for T cells. The identification of different markers at specific disease phases emphasizes the dynamics of a balanced cytokine environment in disease progression. Conclusions This is the first comprehensive study that highlights specific cellular changes and immune signatures during ZIKV disease progression, and it provides valuable insights into ZIKV immunopathogenesis.
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Affiliation(s)
- Fok-Moon Lum
- Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore
| | - David C B Lye
- Communicable Diseases Centre, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore.,Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.,Department of Medicine, Yong Loo Lin School of Medicine, Singapore
| | - Jeslin J L Tan
- Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore
| | - Bernett Lee
- Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore
| | - Po-Ying Chia
- Communicable Diseases Centre, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore
| | - Tze-Kwang Chua
- Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore
| | - Siti N Amrun
- Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore
| | - Yiu-Wing Kam
- Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore
| | - Wearn-Xin Yee
- Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore
| | - Wei-Ping Ling
- Communicable Diseases Centre, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore
| | - Vanessa W X Lim
- Communicable Diseases Centre, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore
| | - Vincent J X Pang
- Communicable Diseases Centre, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore.,Saw Swee Hock School of Public Health, National University of Singapore, Singapore
| | - Linda K Lee
- Communicable Diseases Centre, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore
| | - Esther W H Mok
- Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore
| | | | - Yee-Sin Leo
- Communicable Diseases Centre, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore.,Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.,Department of Medicine, Yong Loo Lin School of Medicine, Singapore.,Saw Swee Hock School of Public Health, National University of Singapore, Singapore
| | - Lisa F P Ng
- Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore.,Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.,National Institute of Health Research, Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, United Kingdom.,Institute of Infection and Global Health, University of Liverpool, United Kingdom
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22
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Douglas KO, Samuels TA, Gittens-St Hilaire M. Serum LPS Associated with Hantavirus and Dengue Disease Severity in Barbados. Viruses 2019; 11:v11090838. [PMID: 31505806 PMCID: PMC6783883 DOI: 10.3390/v11090838] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 09/04/2019] [Accepted: 09/05/2019] [Indexed: 12/25/2022] Open
Abstract
Hantavirus and dengue virus (DENV) infections are caused by RNA viruses which infect immune systems’ cells including monocytes, macrophages and dendritic cells and occur year-round in Barbados. A retrospective serological study (2008–2015) was conducted on hantavirus and dengue patient sera confirmed by IgM and IgG ELISA, NS1 and RT-PCR using Limulus amoebocyte lysate (LAL) kinetic turbidimetric method to determine serum endotoxin levels. Hantavirus patients were categorized into two groups, namely (a) hospitalized and (b) non-hospitalized. Dengue patients were categorized into 3 groups using 2009 WHO dengue guidelines (a) severe dengue (SD), (b) hospitalized non-severe dengue (non-SD) and (c) non-hospitalized non-SD. Statistical analyses were conducted to determine the association of endotoxin levels with hantavirus disease severity based on hospitalization and dengue disease severity. Serum endotoxin levels are associated with hantavirus disease severity and hospitalization and dengue disease severity (p < 0.01). Similar studies have found an association of serum endotoxin levels with dengue disease severity but never with hantavirus infection. Co-detection of hantavirus- and DENV-specific IgM in some patients were observed with elevated serum endotoxin levels. In addition, previous studies observed hantavirus replication in the gut of patients, gastrointestinal tract as a possible entry route of infection and evidence of microbial translocation and its impact on hantavirus disease severity. A significant correlation of serum endotoxin and hantavirus disease severity and hospitalization in hantavirus infected patients is reported for the first time ever. In addition, serum endotoxin levels correlated with dengue disease severity. This study adds further support to the role of endotoxin in both hantavirus and dengue virus infection and disease severity and its role as a possible therapeutic target for viral haemorrhagic fevers (VHFs).
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Affiliation(s)
- Kirk Osmond Douglas
- Faculty of Medical Sciences, University of the West Indies, Cave Hill, BB11000 St. Michael, Barbados.
| | - Thelma Alafia Samuels
- Faculty of Medical Sciences, University of the West Indies, Cave Hill, BB11000 St. Michael, Barbados.
- George Alleyne Chronic Disease Research Centre (GA-CDRC), University of the West Indies, Cave Hill, BB11000 St. Michael, Barbados.
| | - Marquita Gittens-St Hilaire
- Faculty of Medical Sciences, University of the West Indies, Cave Hill, BB11000 St. Michael, Barbados.
- Best-Dos Santos Public Health Laboratory, University of the West Indies, Cave Hill, BB11000 St. Michael, Barbados.
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Mariko R, Darwin E, Yanwirasti Y, Hadinegoro SR. The Difference of sVE-Cadherin Levels between Dengue Hemorrhagic Fever Patients with Shock and without Shock. Open Access Maced J Med Sci 2019; 7:2277-2281. [PMID: 31592274 PMCID: PMC6765090 DOI: 10.3889/oamjms.2019.602] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 06/06/2019] [Accepted: 06/07/2019] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Dengue virus infection is an infectious disease caused by the dengue virus and transmitted by the Aedes aegypti mosquito. Dengue virus (DEN-V) consists of 4 serotypes, namely DEN-1, DEN-2, DEN-3, and DEN-4. The most feared result of DHF is death. Death in children is caused by hypovolemic shock due to plasma leakage from intravascular to extravascular space due to endothelial dysfunction. AIM This study aims to analyse difference in sVE-Cadherin levels in Dengue Hemorrhagic Fever (DHF) with and without shock. MATERIAL AND METHODS The method of taking samples is consecutive sampling, namely the research subjects obtained based on the order of entry in the hospital with a comparative cross-sectional design. From the results of the calculation using the sample formula, the sample size for each group is set at 32 people. So that the total sample size used for both groups is 64 people. The serum sVE-Cadherin levels using the ELISA method. The statistical test used is the independent t-test. The value of p < 0.05 was said to be statistically significant. RESULTS The result showed that there was no difference in mean sVE-Cadherin levels between DHF patients with shock and without shock (p > 0.05). CONCLUSION This study concluded that there was no difference in mean of sVE-Cadherin level in DHF patients with shock and without shock.
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Affiliation(s)
- Rinang Mariko
- Biomedical Science, Faculty of Medicine, Andalas University, Padang, Indonesia
- Department of Pediatrics, Faculty of Medicine, Andalas University, General Hospital of Dr M. Djamil, Padang, Indonesia
| | - Eryati Darwin
- Department of Histology, Faculty of Medicine, Andalas University, Padang, Indonesia
| | | | - Sri Rezeki Hadinegoro
- Department of Pediatrics, Faculty of Medicine, Indonesia University, Jakarta, Indonesia
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24
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May WL, Kyaw MP, Blacksell SD, Pukrittayakamee S, Chotivanich K, Hanboonkunupakarn B, Thein KN, Lim CS, Thaipadungpanit J, Althaus T, Jittamala P. Impact of glucose-6-phosphate dehydrogenase deficiency on dengue infection in Myanmar children. PLoS One 2019; 14:e0209204. [PMID: 30601843 PMCID: PMC6314580 DOI: 10.1371/journal.pone.0209204] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Accepted: 12/01/2018] [Indexed: 01/15/2023] Open
Abstract
Glucose-6-phosphate dehydrogenase (G6PD) deficiency may affect the clinical presentation of dengue due to the altered redox state in immune cells. We aimed to determine the association between G6PD deficiency and severity of dengue infection in paediatric patients in Myanmar. A cross-sectional study was conducted among paediatric patients aged 2–13 years with dengue in Yankin Children Hospital, Myanmar. One hundred and ninety-six patients positive for dengue infection, as determined via PCR or ELISA, were enrolled. Dengue severity was determined according to the 2009 WHO classification guidelines. Spectrophotometric assays determined G6PD levels. The adjusted median G6PD value of males in the study population was used to define various cut-off points according to the WHO classification guidelines. G6PD genotyping for Mahidol, Kaiping and Mediterranean mutations was performed for 128 out of 196 samples by real-time multiplex PCR. 51 of 196 (26.0%) patients had severe dengue. The prevalence of G6PD phenotype deficiency (< 60% activity) in paediatric patients was 14.8% (29/196), specifically, 13.6% (14/103) in males and 16.2% (15/93) in females. Severe deficiency (< 10% activity) accounted for 7.1% (14/196) of our cohort, occurring 11.7% (12/103) in males and 2.2% (2/93) in females. Among 128 samples genotyped, the G6PD gene mutations were detected in 19.5% (25/128) of patients, with 20.3% (13/ 64) in males and 18.8% (12/64) in females. The G6PD Mahidol mutation was 96.0% (24/25) while the G6PD Kaiping mutation was 4.0% (1/25). Severe dengue was not associated with G6PD enzyme deficiency or presence of the G6PD gene mutation. Thus, no association between G6PD deficiency and dengue severity could be detected. Trial registration: The study was registered following the WHO International Clinical Trials Registry Platform (WHO-ICTRP) on Thai Clinical Trials Registry (TCTR) website, registration number # TCTR20180720001
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Affiliation(s)
- Win Lai May
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Department of Medical Research, Yangon, Myanmar
| | | | - Stuart D. Blacksell
- Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Sasithon Pukrittayakamee
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Kesinee Chotivanich
- 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
| | - Khin Nyo Thein
- Department of Paediatrics, University of Medicine 2, Yangon, Myanmar
| | | | - Janjira Thaipadungpanit
- Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Thomas Althaus
- Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Podjanee Jittamala
- Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- * E-mail:
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Ren J, Ling F, Sun J, Gong Z, Liu Y, Shi X, Zhang R, Zhai Y, Chen E, Chen Z. Epidemiological profile of dengue in Zhejiang Province, southeast China. PLoS One 2018; 13:e0208810. [PMID: 30533054 PMCID: PMC6289432 DOI: 10.1371/journal.pone.0208810] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Accepted: 11/23/2018] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Dengue is one of the most important vector-bore infectious diseases in China because of its drastic increase in incidence, geographic extension and profound influence on China's economy. This study aims to retrospectively uncover the epidemiological profile of dengue in Zhejiang, one of the most developed provinces in China, and to find the problem existing in dengue control and prevention. METHODOLOGY Descriptive analyses on the dengue incidence and associated factors were performed. We also identified potential space-time cluster and generated the risk map of dengue. PRINCIPAL FINDINGS A total of 529 cases were reported in Zhejiang Province from 2005 to 2016, and 44.4% were imported. 67.7% of cases were 25~60 years old and the overall male-to-female sex ratio was 1.09:1. Dengue was reported all year round and 70.7% of cases occurred between August and October. Indigenous cases were only reported in the period between July to November and more than half occurred in September. Geographically, dengue was most distributed in Jinghua (3.62 per million), Shaoxing (1.00 per million) and Taizhou (0.81 per million) prefecture level cities. Outbreaks were confirmed in Yiwu, Keqiao and Huangyan counties in 2009, 2015, and 2016, respectively. 73.9% cases would seek medical advice within two days after onset and be confirmed within 9 days after onset. 75.6% would be recognized as dengue within 8 days after their first visit. The time intervals between onset and confirmation (median 7 vs 6 days; Wilcoxon rank sum test Z = -2.40, P = 0.016), first visit and confirmation (median 7 vs 6 days; Wilcoxon rank sum test Z = -2.59, P = 0.009) of indigenous cases were significantly longer than those of imported ones. However, the time intervals between onset and first visit for indigenous cases was shorter (median 0 vs 1 days; Wilcoxon rank sum test Z = -2.10, P = 0.036). Fever (99.1%), fatigue (81.9), rash (63.7%), headache (67.2%) and myalgia (52.60%) were the most frequently mentioned symptoms. CONCLUSIONS Zhejiang has recently witnessed an increase in incidence and geographic extension of dengue. Timely diagnosis is important to stop local transmission and outbreak.
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Affiliation(s)
- Jiangping Ren
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
- Key Laboratory of Vaccine, Prevention and Control of Infectious Disease of Zhejiang Province, Hangzhou, China
- Field Epidemiology Training Program of Zhejiang Province, Hangzhou, China
| | - Feng Ling
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
- Key Laboratory of Vaccine, Prevention and Control of Infectious Disease of Zhejiang Province, Hangzhou, China
| | - Jimin Sun
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
- Key Laboratory of Vaccine, Prevention and Control of Infectious Disease of Zhejiang Province, Hangzhou, China
| | - Zhenyu Gong
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
- Key Laboratory of Vaccine, Prevention and Control of Infectious Disease of Zhejiang Province, Hangzhou, China
| | - Ying Liu
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
| | - Xuguang Shi
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
| | - Rong Zhang
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
| | - Yujia Zhai
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
| | - Enfu Chen
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
- Key Laboratory of Vaccine, Prevention and Control of Infectious Disease of Zhejiang Province, Hangzhou, China
- * E-mail: (EC); (ZC)
| | - Zhiping Chen
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
- * E-mail: (EC); (ZC)
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Sreenivasan P, S G, K S. Development of a Prognostic Prediction Model to Determine Severe Dengue in Children. Indian J Pediatr 2018; 85:433-439. [PMID: 29344875 DOI: 10.1007/s12098-017-2591-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Accepted: 12/18/2017] [Indexed: 12/23/2022]
Abstract
OBJECTIVE To develop a prognostic prediction model using the seven warning signs highlighted by WHO revised Dengue fever classification 2009 to determine severe dengue in children. METHODS In this prospective analytical study conducted in a tertiary care centre, consecutive sampling of all children aged 1mo to 12y admitted with serologically confirmed Dengue was done from May 2015 through August 2016. After excluding 27 patients with co-infections and co-morbidities, 359 patients were followed up daily to assess clinical and laboratory progression till discharge/ death. Independent predictors were abdominal pain or tenderness, persistent vomiting, lethargy, mucosal bleed, clinical fluid accumulation, hepatomegaly >2 cm and rising hematocrit concurrent with platelet count <100 × 109/L. Outcome measure was severe dengue defined as per WHO guidelines 2009. RESULTS Among 359 children, 93 progressed to severe dengue. In univariate analysis, significant predictors were clinical fluid accumulation (OR 4.773, p = 0.000, 95%CI 2.511-9.075), persistent vomiting (OR 1.944, p = 0.010, 95%CI 1.170-3.225), mucosal bleed (OR 2.045, p = 0.019, 95%CI 1.127-3.711) and hematocrit ≥0.40 concurrent with platelet count <100 × 109/L (OR 2.985, p = 0.000, 95%CI 1.783-4.997). The final multivariable model included clinical fluid accumulation (aOR 3.717, p = 0.000, 95%CI 1.901-7.269), hematocrit ≥0.40 concurrent with platelet count <100 × 109/L (aOR 2.252, p = 0.004, 95%CI 1.302-3.894) and persistent vomiting (p = 0.056) as predictors of severe dengue. CONCLUSIONS Among seven WHO warning signs, predictors of severe dengue as suggested by the present multivariable prediction model include clinical fluid accumulation, persistent vomiting and hematocrit ≥0.40 concurrent with platelet count <100 × 109/L.
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Affiliation(s)
- Priya Sreenivasan
- Department of Pediatrics, Government Medical College, Thiruvananthapuram, Thiruvananthapuram District, Kerala, 695011, India.
| | - Geetha S
- Department of Pediatrics, Government Medical College, Thiruvananthapuram, Thiruvananthapuram District, Kerala, 695011, India
- Clinical Epidemiology Research & Training Centre (CERTC), Government Medical College, Thiruvananthapuram, Kerala, India
| | - Sasikala K
- Clinical Epidemiology Research & Training Centre (CERTC), Government Medical College, Thiruvananthapuram, Kerala, India
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Singhi SC. Severe Dengue: Developing a Universally Applicable Simple Prediction Model. Indian J Pediatr 2018; 85:413-414. [PMID: 29637462 DOI: 10.1007/s12098-018-2668-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Accepted: 03/19/2018] [Indexed: 10/17/2022]
Affiliation(s)
- Sunit C Singhi
- Division of Pediatrics, Medanta, The Medicity, Gurugram, NCR 122001, India.
- Department of Pediatrics & Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
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Temprasertrudee S, Thanachartwet V, Desakorn V, Keatkla J, Chantratita W, Kiertiburanakul S. A Multicenter Study of Clinical Presentations and Predictive Factors for Severe Manifestation of Dengue in Adults. Jpn J Infect Dis 2018; 71:239-243. [PMID: 29709965 DOI: 10.7883/yoken.jjid.2017.457] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
| | - Vipa Thanachartwet
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University
| | - Varunee Desakorn
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University
| | - Jiraporn Keatkla
- Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University
| | - Wasun Chantratita
- Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University
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Furlan NB, Tukasan C, Estofolete CF, Nogueira ML, da Silva NS. Low sensitivity of the tourniquet test for differential diagnosis of dengue: an analysis of 28,000 trials in patients. BMC Infect Dis 2016; 16:627. [PMID: 27809813 PMCID: PMC5095934 DOI: 10.1186/s12879-016-1947-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Accepted: 10/20/2016] [Indexed: 01/15/2023] Open
Abstract
Background The aim of this study was to evaluate the utility of the tourniquet test (TT) for dengue diagnosing. To our knowledge, no previous study with such a large sample, of this duration, with as many laboratory methods referenced, or relating the results of the TT to the 2009 WHO classification of severity has been conducted thus far. Methods In this study, we analyzed the records of 119,589 suspected dengue cases in a Brazilian city, with 30,670 confirmed cases. The Cohen’s Kappa test was applied to evaluate the degree of agreement between the tests, and the sensitivity and specificity was calculated for the TT. Results Twenty-eight thousand six hundred thirty-five TT were performed. No association between the outcome of the TT and greater severity of infection, according to the 2009 guideline, was observed (P = 0.28); furthermore, relevant agreement with the final diagnosis (κ = 0.01; 95 % CI = 0.00 to 0.02) or individually with the IgM enzyme-linked immunoassay was not observed (κ = 0.05; 95 % CI = 0.04 to 0.06), and was even lower with PCR (κ = 0.27; 95 % CI = 0.06 to 0.49). Most importance of the TT was shown in relation to specificity (88.9 %; 95 % CI = 0.88 to 0.89) and negative predictive value (70.3 %; CI 95 % = 0.70 to 0.71). Conclusions TT was more effective in detecting cases that were truly negative than positive. These results suggest that the TT should not be used as diagnosis of dengue.
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Affiliation(s)
- Nathália Barbosa Furlan
- Faculdade de Medicina, União das Faculdades dos Grandes Lagos, São José do Rio Preto, São Paulo, Brazil
| | - Caroline Tukasan
- Faculdade de Medicina, União das Faculdades dos Grandes Lagos, São José do Rio Preto, São Paulo, Brazil
| | - Cássia Fernanda Estofolete
- Faculdade de Medicina, União das Faculdades dos Grandes Lagos, São José do Rio Preto, São Paulo, Brazil.,Laboratório de Pesquisas em Virologia, Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil
| | - Maurício Lacerda Nogueira
- Laboratório de Pesquisas em Virologia, Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil
| | - Natal Santos da Silva
- Faculdade de Medicina, União das Faculdades dos Grandes Lagos, São José do Rio Preto, São Paulo, Brazil. .,Laboratório de Pesquisas em Virologia, Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil. .,Laboratório de Modelagens Matemática e Estatística em Medicina, União das Faculdades dos Grandes Lagos, São José do Rio Preto, São Paulo, Brazil. .,Laboratório de Modelagens Matemática e Estatística em Medicina, Faculdade de Medicina, União das Faculdades dos Grandes Lagos, Rua Dr. Eduardo Nielsem, 960 Jardim Novo Aeroporto, São Jose do Rio Preto, São Paulo, CEP 15030-070, Brazil.
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Tamibmaniam J, Hussin N, Cheah WK, Ng KS, Muninathan P. Proposal of a Clinical Decision Tree Algorithm Using Factors Associated with Severe Dengue Infection. PLoS One 2016; 11:e0161696. [PMID: 27551776 PMCID: PMC4994952 DOI: 10.1371/journal.pone.0161696] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Accepted: 08/10/2016] [Indexed: 11/18/2022] Open
Abstract
Background WHO’s new classification in 2009: dengue with or without warning signs and severe dengue, has necessitated large numbers of admissions to hospitals of dengue patients which in turn has been imposing a huge economical and physical burden on many hospitals around the globe, particularly South East Asia and Malaysia where the disease has seen a rapid surge in numbers in recent years. Lack of a simple tool to differentiate mild from life threatening infection has led to unnecessary hospitalization of dengue patients. Methods We conducted a single-centre, retrospective study involving serologically confirmed dengue fever patients, admitted in a single ward, in Hospital Kuala Lumpur, Malaysia. Data was collected for 4 months from February to May 2014. Socio demography, co-morbidity, days of illness before admission, symptoms, warning signs, vital signs and laboratory result were all recorded. Descriptive statistics was tabulated and simple and multiple logistic regression analysis was done to determine significant risk factors associated with severe dengue. Results 657 patients with confirmed dengue were analysed, of which 59 (9.0%) had severe dengue. Overall, the commonest warning sign were vomiting (36.1%) and abdominal pain (32.1%). Previous co-morbid, vomiting, diarrhoea, pleural effusion, low systolic blood pressure, high haematocrit, low albumin and high urea were found as significant risk factors for severe dengue using simple logistic regression. However the significant risk factors for severe dengue with multiple logistic regressions were only vomiting, pleural effusion, and low systolic blood pressure. Using those 3 risk factors, we plotted an algorithm for predicting severe dengue. When compared to the classification of severe dengue based on the WHO criteria, the decision tree algorithm had a sensitivity of 0.81, specificity of 0.54, positive predictive value of 0.16 and negative predictive of 0.96. Conclusion The decision tree algorithm proposed in this study showed high sensitivity and NPV in predicting patients with severe dengue that may warrant admission. This tool upon further validation study can be used to help clinicians decide on further managing a patient upon first encounter. It also will have a substantial impact on health resources as low risk patients can be managed as outpatients hence reserving the scarce hospital beds and medical resources for other patients in need.
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Affiliation(s)
| | - Narwani Hussin
- Clinical Research Centre, Taiping Hospital, Perak, Malaysia
- * E-mail: (JT); (NH)
| | - Wee Kooi Cheah
- Department of Medicine, Taiping Hospital, Perak, Malaysia
| | - Kee Sing Ng
- Department of Medicine, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia
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Soo KM, Khalid B, Ching SM, Chee HY. Meta-Analysis of Dengue Severity during Infection by Different Dengue Virus Serotypes in Primary and Secondary Infections. PLoS One 2016; 11:e0154760. [PMID: 27213782 PMCID: PMC4877104 DOI: 10.1371/journal.pone.0154760] [Citation(s) in RCA: 163] [Impact Index Per Article: 18.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Accepted: 04/19/2016] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION Dengue virus (DENV) infection is currently a major cause of morbidity and mortality in the world; it has become more common and virulent over the past half-century and has gained much attention. Thus, this review compared the percentage of severe cases of both primary and secondary infections with different serotypes of dengue virus. METHODS Data related to the number of cases involving dengue fever (DF), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) or severe dengue infections caused by different serotypes of dengue virus were obtained by using the SCOPUS, the PUBMED and the OVID search engines with the keywords "(dengue* OR dengue virus*) AND (severe dengue* OR severity of illness index* OR severity* OR DF* OR DHF* OR DSS*) AND (serotypes* OR serogroup*)", according to the MESH terms suggested by PUBMED and OVID. RESULTS Approximately 31 studies encompassing 15,741 cases reporting on the dengue serotypes together with their severity were obtained, and meta-analysis was carried out to analyze the data. This study found that DENV-3 from the Southeast Asia (SEA) region displayed the greatest percentage of severe cases in primary infection (95% confidence interval (CI), 31.22-53.67, 9 studies, n = 598, I2 = 71.53%), whereas DENV-2, DENV-3, and DENV-4 from the SEA region, as well as DENV-2 and DENV-3 from non-SEA regions, exhibited the greatest percentage of severe cases in secondary infection (95% CI, 11.64-80.89, 4-14 studies, n = 668-3,149, I2 = 14.77-96.20%). Moreover, DENV-2 and DENV-4 from the SEA region had been found to be more highly associated with dengue shock syndrome (DSS) (95% CI, 10.47-40.24, 5-8 studies, n = 642-2,530, I2 = 76.93-97.70%), while DENV-3 and DENV-4 from the SEA region were found to be more highly associated with dengue hemorrhagic fever (DHF) (95% CI, 31.86-54.58, 9 studies, n = 674-2,278, I2 = 55.74-88.47%), according to the 1997 WHO dengue classification. Finally, DENV-2 and DENV-4 from the SEA region were discovered to be more highly associated with secondary infection compared to other serotypes (95% CI, 72.01-96.32, 9-12 studies, n = 671-2,863, I2 = 25.01-96.75%). CONCLUSION This study provides evidence that the presence of certain serotypes, including primary infection with DENV-3 from the SEA region and secondary infection with DENV-2, DENV-3, and DENV-4 also from the SEA region, as well as DENV-2 and DENV-3 from non SEA regions, increased the risk of severe dengue infections. Thus, these serotypes are worthy of special consideration when making clinical predictions upon the severity of the infection. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42015026093 (http://www.crd.york.ac.uk/PROSPERO).
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Affiliation(s)
- Kuan-Meng Soo
- Department of Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
| | - Bahariah Khalid
- Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
| | - Siew-Mooi Ching
- Department of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
- Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang, Malaysia
| | - Hui-Yee Chee
- Department of Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
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Gupta BP, Adhikari A, Rauniyar R, Kurmi R, Upadhya BP, Jha BK, Pandey B, Manandhar KD. Dengue virus infection in a French traveller to the hilly region of Nepal in 2015: a case report. J Med Case Rep 2016; 10:65. [PMID: 26997343 PMCID: PMC4800766 DOI: 10.1186/s13256-016-0847-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Accepted: 02/23/2016] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Dengue viral infections are known to pose a significant risk during travel to tropical regions, but it is surprising to find dengue transmission in the hilly region of Nepal, which is over 1800mtr above sea level. CASE PRESENTATION A 43-year-old Caucasian female traveler from France presented with fever and abdominal pain following a diarrheal illness while visiting the central hilly region of Nepal. Over the course of 9 days, she developed fever, body aches, and joint pain, with hemorrhagic manifestation. She was hospitalized in India and treated with supportive care, with daily monitoring of her platelets. An assessment by enzyme-linked immunosorbent assay showed that she was positive for dengue non-structural protein 1. Upon her return to France, dengue virus was confirmed by reverse transcriptase-polymerase chain reaction. CONCLUSION The district where this dengue case was reported is in the hilly region of Nepal, neighboring the capital city Kathmandu. To the best of our knowledge, there has previously been no dengue cases reported from the district. This study is important because it aims to establish a potential region of dengue virus circulation not only in the tropics, but also in the subtropics as well, which in Nepal may exceed elevations of 1800mtr. This recent case report has raised alarm among concerned health personnel, researchers, and organizations that this infectious disease is now on the way to becoming established in a temperate climate.
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Affiliation(s)
- Birendra Prasad Gupta
- />Virology Unit, Central Department of Biotechnology, Tribhuvan University, Kritipur, Kathmandu, Nepal
| | - Anurag Adhikari
- />Asian Institute of Technology and Management, Purbanchal University, Lalitpur, Nepal
| | | | - Roshan Kurmi
- />Bhawani Hospital and Research Center, Birgunj, Nepal
| | | | | | - Basudev Pandey
- />Leprosy Division, Ministry of Health, Government of Nepal, Kathmandu, Nepal
| | - Krishna Das Manandhar
- />Virology Unit, Central Department of Biotechnology, Tribhuvan University, Kritipur, Kathmandu, Nepal
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Wong JGX, Thein TL, Leo YS, Pang J, Lye DC. Identifying Adult Dengue Patients at Low Risk for Clinically Significant Bleeding. PLoS One 2016; 11:e0148579. [PMID: 26849556 PMCID: PMC4743958 DOI: 10.1371/journal.pone.0148579] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Accepted: 01/19/2016] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Clinically significant bleeding is important for subsequent optimal case management in dengue patients, but most studies have focused on dengue severity as an outcome. Our study objective was to identify differences in admission parameters between patients who developed clinically significant bleeding and those that did not. We sought to develop a model for discriminating between these patients. METHODS We conducted a retrospective study of 4,383 adults aged >18 years who were hospitalized with dengue infection at Tan Tock Seng Hospital, Singapore from 2005 to 2008. Patients were divided into those with clinically significant bleeding (n = 188), and those without (n = 4,195). Demographic, clinical, and laboratory variables on admission were compared between groups to determine factors associated with clinically significant bleeding during hospitalization. RESULTS On admission, female gender (p<0.001); temperature >38°C (p<0.001); nausea/vomiting (p = 0.009) and abdominal pain/tenderness (p = 0.005); lower systolic blood pressure (p<0.001); higher pulse rate (p<0.001); increased absolute neutrophil count (ANC; p<0.001); reduced absolute lymphocyte count (ALC; p<0.001), haematocrit percentage (p<0.001) and platelet count (p = 0.04), and increased prothrombin time (p = 0.003) were significantly associated with clinically significant bleeding on univariate analysis. Multivariate analysis showed that independent variables in the final model were female gender (aOR 2.85; 95% CI: 1.9-4.33); temperature >38°C (aOR 1.81; 95% CI: 1.27-2.61), nausea/vomiting (aOR 1.39; 95% CI: 0.94-2.12), ANC (aOR 1.3; 95% CI: 1.15-1.46), ALC (aOR 0.4; 95% CI: 0.25-0.64), hematocrit percentage (aOR 0.96; 95% CI: 0.92-1.002) and platelet count (aOR 0.993; 95% CI: 0.988-0.998). At the cutoff of -3.919, the model achieved an AUC of 0.758 (sensitivity:0.87, specificity: 0.38, PPV: 0.06, NPV: 0.98). CONCLUSION Clinical risk factors associated with clinically significant bleeding were identified. This model may be useful to complement clinical judgement in triaging adult dengue patients given the dynamic nature of acute dengue, particularly in pre-identifying those less likely to develop clinically significant bleeding.
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Affiliation(s)
- Joshua G. X. Wong
- Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore
- Department of Clinical Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore
| | - Tun Linn Thein
- Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore
| | - Yee-Sin Leo
- Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Junxiong Pang
- Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
| | - David C. Lye
- Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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Yi YX, Han JB, Zhao L, Fang Y, Zhang YF, Zhou GY. Tumor necrosis factor alpha gene polymorphism contributes to pulmonary tuberculosis susceptibility: evidence from a meta-analysis. Int J Clin Exp Med 2015; 8:20690-20700. [PMID: 26884992 PMCID: PMC4723837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2015] [Accepted: 11/02/2015] [Indexed: 06/05/2023]
Abstract
This study is to estimate the association between polymorphisms in the tumor necrosis factor alpha (TNF-α) gene and pulmonary tuberculosis susceptibility (pTB). Studies were identified by searching PubMed and ISI web of Knowledge. The strength of association between the TNF-α gene and pTB susceptibility was assessed by odds ratios. Totals of 18 studies including 2, 735 cases and 3, 177 controls were identified referring to four single-nucleotide polymorphisms: -308G>A, -863C>A, -857C>T and -238G>A. The significantly associations were found between -308G>A (Dominant model: OR 0.53, 95% CI 0.35-0.81, P=0.004; Homozygote model: OR 0.51, 95% CI 0.33-0.78, P=0.002), -238G>A (Dominant model: OR 0.33, 95% CI 0.18-0.57, P<0.001) and pTB susceptibility. The results showed that the variant genotype of TNF-α -308G>A was protective in pooled groups of patients with pTB in the dominant genetic model (OR 0.16, 95% CI 0.06-0.39, P<0.001), the homozygote comparison (OR 0.14, 95% CI 0.06-0.36, P<0.001) in African, while that was with -238G>A in the dominant genetic model (OR 0.31, 95% CI 0.18-0.56, P<0.001) in Asian. Our meta-analysis suggest TNF-α -308G>A and -238G>A polymorphisms increases the risk of pTB susceptibility regardless of ethnicity and HIV statue. In Asian population, the significantly association with pTB is TNF-α -238G>A, while TNF-α -308G>A is in African population.
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Affiliation(s)
- Yong-Xiang Yi
- Department of Hepatobiliary Surgery, The Second Hospital of Nanjing, Affiliated to Southeast UniversityNanjing 210003, China
| | - Jian-Bo Han
- Department of Hepatobiliary Surgery, The Second Hospital of Nanjing, Affiliated to Southeast UniversityNanjing 210003, China
| | - Liang Zhao
- Department of Hepatobiliary Surgery, The Second Hospital of Nanjing, Affiliated to Southeast UniversityNanjing 210003, China
| | - Yuan Fang
- Department of Immunotherapy, The Second Hospital of Nanjing, Affiliated to Southeast UniversityNanjing 210003, China
| | - Yu-Feng Zhang
- Department of Hepatobiliary Surgery, The Second Hospital of Nanjing, Affiliated to Southeast UniversityNanjing 210003, China
| | - Guang-Yao Zhou
- Department of Infectious Disease, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou 325027, China
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John DV, Lin YS, Perng GC. Biomarkers of severe dengue disease - a review. J Biomed Sci 2015; 22:83. [PMID: 26462910 PMCID: PMC4604634 DOI: 10.1186/s12929-015-0191-6] [Citation(s) in RCA: 72] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Accepted: 09/25/2015] [Indexed: 12/03/2022] Open
Abstract
Dengue virus infection presents a wide spectrum of manifestations including asymptomatic condition, dengue fever (DF), or severe forms, such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) in affected individuals. The early prediction of severe dengue in patients without any warning signs who may later develop severe DHF is very important to choose appropriate intensive supportive therapy since available vaccines for immunization are yet to be approved. Severe dengue responses include T and B cell activation and apoptosis, cytokine storm, hematologic disorders and complement activation. Cytokines, complement and other unidentified factors may transiently act on the endothelium and alter normal fluid barrier function of the endothelial cells and cause plasma leakage. In this review, the host factors such as activated immune and endothelial cells and their products which can be utilized as biomarkers for severe dengue disease are discussed.
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Affiliation(s)
- Daisy Vanitha John
- Biotechnology Research Institute, University Malaysia Sabah, Kota Kinabalu, Sabah, Malaysia.
| | - Yee-Shin Lin
- Center of Infectious Disease and Signaling Research, Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
| | - Guey Chuen Perng
- Center of Infectious Disease and Signaling Research, Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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Mallhi TH, Khan AH, Adnan AS, Sarriff A, Khan YH, Jummaat F. Clinico-laboratory spectrum of dengue viral infection and risk factors associated with dengue hemorrhagic fever: a retrospective study. BMC Infect Dis 2015; 15:399. [PMID: 26423145 PMCID: PMC4590689 DOI: 10.1186/s12879-015-1141-3] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2015] [Accepted: 09/22/2015] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The incidence of dengue is rising steadily in Malaysia since the first major outbreak in 1973. Despite aggressive measures taken by the relevant authorities, Malaysia is still facing worsening dengue crisis over the past few years. There is an urgent need to evaluate dengue cases for better understanding of clinic-laboratory spectrum in order to combat this disease. METHODS A retrospective analysis of dengue patients admitted to a tertiary care teaching hospital during the period of six years (2008 - 2013) was performed. Patient's demographics, clinical and laboratory findings were recorded via structured data collection form. Patients were categorized into dengue fever (DF) and dengue hemorrhagic fever (DHF). Appropriate statistical methods were used to compare these two groups in order to determine difference in clinico-laboratory characteristics and to identify independent risk factors of DHF. RESULTS A total 667 dengue patients (30.69 ± 16.13 years; Male: 56.7 %) were reviewed. Typical manifestations of dengue like fever, myalgia, arthralgia, headache, vomiting, abdominal pain and skin rash were observed in more than 40 % patients. DHF was observed in 79 (11.8 %) cases. Skin rash, dehydration, shortness of breath, pleural effusion and thick gall bladder were more significantly (P < 0.05) associated with DHF than DF. Multivariate regression analysis demonstrated presence of age > 40 years (OR: 4.1, P < 0.001), secondary infection (OR: 2.7, P = 0.042), diabetes mellitus (OR: 2.8, P = 0.041), lethargy (OR: 3.1, P = 0.005), thick gallbladder (OR: 1.7, P = 0.029) and delayed hospitalization (OR: 2.3, P = 0.037) as independent predictors of DHF. Overall mortality was 1.2 % in our study. CONCLUSIONS Current study demonstrated that DF and DHF present significantly different clinico-laboratory profile. Older age, secondary infection, diabetes mellitus, lethargy, thick gallbladder and delayed hospitalization significantly predict DHF. Prior knowledge of expected clinical profile and predictors of DHF/DSS development would provide information to identify individuals at higher risk and on the other hand, give sufficient time to clinicians for reducing dengue related morbidity and mortality.
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Affiliation(s)
- Tauqeer Hussain Mallhi
- Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, University Sains Malaysia, Penang, 11800, Malaysia. .,Chronic Kidney Disease Resource Centre, School of Medical Sciences, Health Campus, University Sains Malaysia, Kubang Kerain 16150, Kelantan, Malaysia.
| | - Amer Hayat Khan
- Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, University Sains Malaysia, Penang, 11800, Malaysia. .,Chronic Kidney Disease Resource Centre, School of Medical Sciences, Health Campus, University Sains Malaysia, Kubang Kerain 16150, Kelantan, Malaysia.
| | - Azreen Syazril Adnan
- Chronic Kidney Disease Resource Centre, School of Medical Sciences, Health Campus, University Sains Malaysia, Kubang Kerain 16150, Kelantan, Malaysia.
| | - Azmi Sarriff
- Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, University Sains Malaysia, Penang, 11800, Malaysia.
| | - Yusra Habib Khan
- Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, University Sains Malaysia, Penang, 11800, Malaysia. .,Chronic Kidney Disease Resource Centre, School of Medical Sciences, Health Campus, University Sains Malaysia, Kubang Kerain 16150, Kelantan, Malaysia.
| | - Fauziah Jummaat
- Department of Obstetrics and Gynecology, School of Medical Sciences, Health Campus, University Sains Malaysia, Kubang Kerain 16150, Kelantan, Malaysia.
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Zhu B, Zhu B, Xiao C, Zheng Z. Vitamin D deficiency is associated with the severity of COPD: a systematic review and meta-analysis. Int J Chron Obstruct Pulmon Dis 2015; 10:1907-16. [PMID: 26392765 PMCID: PMC4574800 DOI: 10.2147/copd.s89763] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Purpose To explore the association between host serum 25-hydroxyvitamin D (25(OH)D) and the susceptibility and severity of COPD. Methods Previous studies on the association between host 25(OH)D and the susceptibility and severity of COPD were collected on the basis of a systematic literature search of PubMed and Web of Science up to June 2015. Continuous variable data were presented as standard mean difference (SMD) or weighted mean difference with 95% confidence interval (CI). The dichotomous variable data were analyzed as relative ratio (RR) or odds ratio with 95% CI for cohort and case-control studies. A systematic review was conducted to understand the curative and side effects of vitamin D intake. Results A total of 18 studies including eight cohort, five case-control, and five randomized studies met the inclusion criteria. The serum level of 25(OH)D in COPD patients was comparable with controls with a pooled SMD of 0.191 (95% CI: −0.126 to 0.508, P=0.237) based on pooled analyses of cohort studies. However, the serum level of 25(OH)D in COPD patients was lower with a pooled SMD of 0.961 (95% CI: 0.476–1.446, P<0.001) compared with controls based on pooled analyses of case-control studies. The deficiency rates of 25(OH)D were comparable between controls and COPD patients with a pooled RR of 0.955 (95% CI: 0.754–1.211, P=0.705) based on analyses of cohort studies, and the same results were observed based on pooled analyses of case-control studies. Interestingly, the deficiency rate of 25(OH)D was significantly lower in moderate or severe COPD patients with a pooled RR of 0.723 (95% CI: 0.632–0.828, P<0.001) compared with that in mild COPD patients. The same results were obtained from the pooled analysis between moderate and severe COPD patients. The four randomized studies showed that vitamin D intake provided benefit for COPD patients. Conclusion Low serum levels of 25(OH)D were not associated with COPD susceptibility, but the high deficiency rate of 25(OH)D was associated with COPD severity. Vitamin D supplementation may prevent COPD exacerbation.
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Affiliation(s)
- Biyuan Zhu
- The Fifth Internal Medicine Department, Guangzhou University of Chinese Medicine, Dongguan City, People's Republic of China
| | - Biqing Zhu
- Department of Laboratory Medicine, Guangzhou University of Chinese Medicine, Dongguan City, People's Republic of China
| | - Chaolie Xiao
- Department of Intensive Care Unit, Dongguan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan City, People's Republic of China
| | - Zhiwen Zheng
- The Fifth Internal Medicine Department, Guangzhou University of Chinese Medicine, Dongguan City, People's Republic of China
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Zhang H, Zhou Y, Yuan G, Zhou G, Yang D, Zhou Y. Antiviral therapy improves the survival rate and decreases recurrences and fatalities in liver cancer patients following curative resection: A meta-analysis. Mol Clin Oncol 2015; 3:1239-1247. [PMID: 26807227 PMCID: PMC4665680 DOI: 10.3892/mco.2015.614] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2015] [Accepted: 06/11/2015] [Indexed: 02/07/2023] Open
Abstract
The present study aimed to investigate the impact of postoperative antiviral treatment on tumor recurrence, fatalities and survival of patients with chronic hepatitis B virus (HBV) infection-related primary hepatocellular carcinoma (HCC). A systematic meta-analysis was performed. All the studies comparing nucleos(t)ide analogues (NAs) versus placebo or no treatment were considered. The results were expressed as relative ratio (RR) for 1-, 3- and 5-year recurrence-free survival (RFS) and overall survival (OS), recurrence HCC and fatalities with 95% confidence intervals (CI) using STATA 11.0. In total, 15 trials with 7,619 patients were included. There were significant improvements for 1-, 3- and 5-year RFS (RR, 1.09; P=0.003; RR, 1.202; P<0.001; and RR, 1.219; P=0.02; respectively) and in 3- and 5-year OS (RR, 1.087, P=0.006; and RR, 1.186; P<0.001) in the NAs group compared with the control group. Sensitivity analyses confirmed the robustness of the results. In addition, the significantly high rate of recurrence HCC and fatalities existed in the control group (RR, 1.301; P=0.002; and RR, 1.816, P<0.001). One study was for an entecavir (ETV)-treated group compared with an adefovir (ADV)-treated group and lamivudine (LAM)-treated group. The 3-year disease-free survival rate for the ETV group was significantly better compared with the ADV and LAM groups [hazard ratio (HR), 0.810; P=0.049; and HR, 0.737; P=0.007]. The present study demonstrated the beneficial effects of NAs therapy following curative treatment of HBV-related HCC. ETV may be the superior choice compared to ADV or LAM for the antiviral treatment.
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Affiliation(s)
- Hao Zhang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Yuchen Zhou
- Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Guosheng Yuan
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Guangyao Zhou
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Dinghua Yang
- Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Yuanping Zhou
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
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