Last data update: Apr 18, 2025. (Total: 49119 publications since 2009)
Records 1-15 (of 15 Records) |
Query Trace: Halstead M[original query] |
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Lactic acid salts of nicotine potentiate the transfer of toxic metals into electronic cigarette aerosols
Pappas RS , Gray N , Halstead M , Watson CH . Toxics 2024 12 (1) The designs and liquid formulations of Electronic Nicotine Delivery System (ENDS) devices continue to rapidly evolve. Thus, it is important to monitor and characterize ENDS aerosols for changes in toxic constituents. Many ENDS liquid formulations now include the addition of organic acids in a 1 to 1 molar ratio with nicotine. Metal concentrations in aerosols produced by ENDS devices with different nicotine salt formulations were analyzed. Aerosols from devices containing lactic acid had higher nickel, zinc, copper, and chromium concentrations than aerosols produced by devices containing benzoic acid or levulinic acid. Our scanning electron microscope with energy dispersive X-ray analytical findings showed that the metals determined in the inductively coupled plasma-mass spectrometry analytical results were consistent with the metal compositions of the ENDS device components that were exposed to the liquids and that nickel is a major constituent in many ENDS internal components. As a result of the exposure of the nickel-containing components to the ENDS liquids, resulting aerosol nickel concentrations per puff were higher from devices that contained lactic acid in comparison to devices with benzoic or levulinic acid. The aerosol nickel concentrations in 10 puffs from ENDS-containing lactic acid were, in some cases, hundreds of times higher than cigarette mainstream smoke nickel deliveries. Thus, the design of an ENDS device in terms of both physical construction components and the liquid chemical formulations could directly impact potential exposures to toxic constituents such as metals. |
Analysis of Toxic Metals in Aerosols from Devices Associated with Electronic Cigarette, or Vaping, Product Use Associated Lung Injury
Gonzalez-Jimenez N , Gray N , Pappas RS , Halstead M , Lewis E , Valentin-Blasini L , Watson C , Blount B . Toxics 2021 9 (10) Research gaps exist in toxic metals characterization in e-cigarette, or vaping, products (EVPs) as these analytes typically have low concentrations and most standard aerosol trapping techniques have high metals background. An additional complication arises from differences in the EVP liquid formulations with nicotine products having polar properties and non-nicotine products often being non-polar. Differences in polar and non-polar matrices and the subsequent aerosol chemistries from various EVPs required modifications of our previously reported nicotine-based EVP aerosol method. Validation and application of the expanded method, suitable for both hydrophobic and hydrophilic aerosols, are reported here. The metals analyzed for this study were Al, Cr, Fe, Co, Ni, Cu, Cd, Sn, Ba, and Pb. The method limits of detection for the modified method ranged from 0.120 ng/10 puffs for Cd to 29.3 ng/10 puffs for Al and were higher than reported for the previous method. Results of the analyses for metals in aerosols obtained from 50 EVP products are reported. Cannabinoid based EVP aerosols were below reportable levels, except for one sample with 16.08 ng/10 puffs for Cu. Nicotine-based EVP results ranged from 6.72 ng/10 puffs for Pb to 203 ng/10 puffs for Sn. Results of the analyses for these metals showed that aerosols from only 5 of the 50 devices tested had detectable metal concentrations. Concentrations of toxic elements in the aerosols for nicotine-based EVP aerosol metal concentration ranges were consistent with previously published results of aerosol analyses from this class of devices. |
Return to learn ECHO: Telementoring for school personnel to help children return to school and learning after mild traumatic brain injury
McAvoy K , Halstead M , Radecki L , Shah A , Emanuel A , Domain S , Daugherty J , Waltzman D . J Sch Health 2022 92 (12) 1194-1201 BACKGROUND: Return to learn (RTL) after mild traumatic brain injury (mTBI) presents unique challenges for school professionals. A multidisciplinary team approach is necessary yet training school professionals is logistically difficult. This paper describes an innovative pilot RTL program and its evaluation. METHODS: Utilizing the telehealth/telementoring program Project ECHO® (Extension for Community Healthcare Outcomes), this study utilized a multidisciplinary team of subject matter experts to deliver five 1-hour sessions across 5 cohorts of school-based professionals (total of 133 participants). The evaluation used a mixed-methods approach of post-session and post-program participant surveys and post-program participant focus groups. RESULTS: Participants who completed a post-program survey reported statistically significant improvements in essential aspects of RTL knowledge and self-efficacy. This included improvements in how to manage a student with an mTBI (44.8% to 86.9%), benefits of early return to school for students following mTBI (31.8% to 86.9%), and the importance of written RTL policies/procedures (55.1% to 97.1%). CONCLUSIONS: This study demonstrates that RTL training via a telementoring approach may be a positive and effective way to train school-based professionals and improve knowledge and self-efficacy, especially when attending face-to-face trainings are difficult. This model has the potential to produce programmatic and systematic improvements for RTL education. © 2022 The Authors. Journal of School Health published by Wiley Periodicals LLC on behalf of American School Health Association. |
Toxic metals in liquid and aerosol from pod-type electronic cigarettes
Gray N , Halstead M , Valentin-Blasini L , Watson C , Pappas RS . J Anal Toxicol 2020 46 (1) 69-75 High quality, accurate data on liquid contents and aerosol emissions from electronic nicotine delivery systems (ENDS, e.g. e-cigarettes) are crucial to address potential health concerns as these devices evolve and mature. Metals are an important class of ENDS constituents that merit attention as they have various health implications. Proper sampling, handling, and aerosol trapping materials are essential to generate accurate quantitative metals data and to reduce the likelihood of inaccurate results originating from inappropriate collection vessels and materials that contribute to high background levels. Published methods that meet these criteria were applied to the analyses of chromium, nickel, copper, zinc, cadmium, tin, and lead in liquid and aerosol from mint/menthol and tobacco flavors of currently popular pod-based devices from 3 manufacturers. Metal concentrations from pods that had not been used for generating aerosol ranged from below our lowest reportable level to 0.164 µg/g for Cr, 61.3 µg/g for Ni, 927 µg/g for Cu, 14.9 µg/g for Zn, 58.2 µg/g for Sn, and 2.56 µg/g for Pb. Cadmium was included in our analyte panel and was not present above detection limits in liquid or aerosol. Aerosol metal concentrations (using a 55 mL puff) ranged from below our lowest reportable level to 29.9 ng/10 puffs for Cr, 373 ng/10 puffs for Ni, 209 ng/10 puffs for Cu, 4,580 ng/10 puffs for Zn, 127 ng/10 puffs for Sn, and 463 ng/10 puffs for Pb. Our results showed some metals delivery from all the products examined and highly variable metal levels between manufacturer, brand, and package. |
Toxic metal-containing particles in aerosols from pod-type electronic cigarettes
Pappas RS , Gray N , Halstead M , Valentin-Blasini L , Watson C . J Anal Toxicol 2020 45 (4) 337-347 The popularity of electronic cigarettes (electronic nicotine delivery systems or ENDS) has grown rapidly over the past decade. With the continued evolution of ENDS, and the arrival of newer replaceable pod devices on the market, it is prudent to examine their emissions to help determine potential health risks to the user. Metal containing particles were examined in aerosol from several pod-based devices from three manufacturers that offer flavored liquids in their respective products. Previous ENDS metal emissions studies focused on the total toxic metal concentrations in aerosols and have suggested that the principal sources are oxidized internal metal components that are in contact with the liquid. Most metal oxides have limited solubility and it is likely that some metal content in ENDS aerosol may present as particles rather than dissolved forms. Examining the composition and number of particles in the ENDS aerosols is important because inhaled metal oxide particles cause pulmonary inflammation. Chronic inhalation of ENDS aerosol may lead to inflammatory cell activation in the lungs. Therefore, this study was designed to measure metal oxide particle concentrations and sizes in ENDS aerosols from select pod-based systems. Aerosol samples were generated with pod liquids (tobacco, mint or menthol) from devices produced by three manufacturers using CORESTA Recommended Method 81 parameters with a high purity fluoropolymer aerosol trap. Particle sizes for chromium, iron, nickel, copper, zinc, tin, and lead oxides were measured in triplicate using single particle inductively coupled plasma-mass spectrometry and dynamic light scattering. A novel aspect of these measurements included using dual element particle analysis to infer particle source component material. Particle concentrations in aerosols from the devices were variable between devices and from pod to pod, ranging from no detectable chromium and zinc containing particles in aerosol from some pods to 222,000 lead containing particles per 10 puffs from individual pods. |
Identifying Vaccine-associated Rash Illness Amidst a Large Measles Outbreak: Minnesota, 2017.
Martin KG , Banerjee E , McMahon M , Kenyon C , Strain A , Muscoplat MH , Gastanaduy PA , Rota PA , Mody RK , Ehresmann K . Clin Infect Dis 2020 71 (9) e517-e519 ![]() Characteristics of vaccine-associated rash illness (VARI) and confirmed measles cases were compared during a measles outbreak. Although some clinical differences were noted, having a measles exposure and identification of the vaccine strain were helpful for public health decision-making. Rapid, vaccine strain-specific diagnostic assays will more efficiently distinguish VARI from measles. |
Analysis of toxic metals in liquid from electronic cigarettes
Gray N , Halstead M , Gonzalez-Jimenez N , Valentin-Blasini L , Watson C , Pappas RS . Int J Environ Res Public Health 2019 16 (22) As the technology of electronic nicotine delivery systems (ENDS), including e-cigarettes, evolves, assessing metal concentrations in liquids among brands over time becomes challenging. A method for quantification of chromium, nickel, copper, zinc, cadmium, tin, and lead in ENDS liquids using triple quadrupole inductively coupled plasma mass spectrometry was developed. The method's limits of detection (LODs) were 0.031, 0.032, 3.15, 1.27, 0.108, 0.099, 0.066 microg/g for Cr, Ni, Cu, Zn, Cd, Sn, and Pb respectively. Liquids analyzed were from different brands and flavors of refill bottles or single-use, rechargeable, and pod devices from different years. Scanning electron microscopy with energy dispersive spectroscopy further evaluated the device components' compositions. Refill liquids before contacting a device were below lowest reportable levels (LRL) for all metals. Copper and zinc were elevated in liquids from devices containing brass. Cadmium was <LRL in all liquids and was not observed in device components. Cr, Ni, Cu, Zn, Sn, and Pb, reported in microg/g, ranged from <LRL to 0.396, 4.04, 903, 454, 0.898, and 13.5 respectively. Elevated metal concentrations in the liquid were also elevated in aerosol from the corresponding device. The data demonstrates the impact of device design and materials on toxic metals in ENDS liquid. |
Analysis of toxic metals in electronic cigarette aerosols using a novel trap design
Halstead M , Gray N , Gonzalez-Jimenez N , Fresquez M , Valentin-Blasini L , Watson C , Pappas RS . J Anal Toxicol 2019 44 (2) 149-155 Since 2006 the domestic popularity and sales of electronic cigarettes (i.e., electronic nicotine delivery systems or ENDS) have grown rapidly. Although the constituents of the aerosol produced by ENDS have been previously investigated, differences in puff regimens and aerosol trapping schema in published literature often complicate result comparisons and data interpretation. As the ENDS product designs continue to evolve, there is a critical need to develop and validate robust methodologies for laboratory testing, appropriate aerosol generation and trapping media required for accurate determinations of ENDS aerosol metals deliveries. A simple, high metals purity, fluoropolymer trap was developed and validated that meets standard machine puffing regimen (CORESTA Recommended Method 81) specifications and exhibits negligible acid extractable metal backgrounds. Using a standard machine puffing regimen in combination with a fluoropolymer condensation trap, aerosol was generated and collected from select ENDS devices for analysis of chromium, nickel, copper, zinc, cadmium, tin, and lead with triple quadrupole inductively coupled plasma mass spectrometry. Devices tested spanned a range of commercial products, including flavored variants of JUUL pods, refillable tank systems, rechargeable cartridges, and single-use ENDs devices. Results showed that for aerosols generated under a fixed puffing regimen (50 puffs/collection), metal concentrations ranged from below the detection limits (LOD) to 614 ng copper and 339 ng zinc per 10 puffs. Cadmium concentrations were below LOD for all devices tested. Device specific aerosol levels of Sn and Pb ranged from below LOD to low nanogram levels. Cr and Ni were transported in aerosols at levels equivalent to, or slightly higher than in mainstream cigarette smoke using a standard smoking regimen. The generally lower levels of specific metals, Cd and Pb, transmitted in ENDS aerosols compared to mainstream cigarette smoke reflect possible reduction of harm for smokers who substitute the use of ENDS as cessation devices in place of smoking cigarettes. |
Centers for Disease Control and Prevention Guideline on the Diagnosis and Management of Mild Traumatic Brain Injury Among Children
Lumba-Brown A , Yeates KO , Sarmiento K , Breiding MJ , Haegerich TM , Gioia GA , Turner M , Benzel EC , Suskauer SJ , Giza CC , Joseph M , Broomand C , Weissman B , Gordon W , Wright DW , Moser RS , McAvoy K , Ewing-Cobbs L , Duhaime AC , Putukian M , Holshouser B , Paulk D , Wade SL , Herring SA , Halstead M , Keenan HT , Choe M , Christian CW , Guskiewicz K , Raksin PB , Gregory A , Mucha A , Taylor HG , Callahan JM , DeWitt J , Collins MW , Kirkwood MW , Ragheb J , Ellenbogen RG , Spinks TJ , Ganiats TG , Sabelhaus LJ , Altenhofen K , Hoffman R , Getchius T , Gronseth G , Donnell Z , O'Connor RE , Timmons SD . JAMA Pediatr 2018 172 (11) e182853 Importance: Mild traumatic brain injury (mTBI), or concussion, in children is a rapidly growing public health concern because epidemiologic data indicate a marked increase in the number of emergency department visits for mTBI over the past decade. However, no evidence-based clinical guidelines have been developed to date for diagnosing and managing pediatric mTBI in the United States. Objective: To provide a guideline based on a previous systematic review of the literature to obtain and assess evidence toward developing clinical recommendations for health care professionals related to the diagnosis, prognosis, and management/treatment of pediatric mTBI. Evidence Review: The Centers for Disease Control and Prevention (CDC) National Center for Injury Prevention and Control Board of Scientific Counselors, a federal advisory committee, established the Pediatric Mild Traumatic Brain Injury Guideline Workgroup. The workgroup drafted recommendations based on the evidence that was obtained and assessed within the systematic review, as well as related evidence, scientific principles, and expert inference. This information includes selected studies published since the evidence review was conducted that were deemed by the workgroup to be relevant to the recommendations. The dates of the initial literature search were January 1, 1990, to November 30, 2012, and the dates of the updated literature search were December 1, 2012, to July 31, 2015. Findings: The CDC guideline includes 19 sets of recommendations on the diagnosis, prognosis, and management/treatment of pediatric mTBI that were assigned a level of obligation (ie, must, should, or may) based on confidence in the evidence. Recommendations address imaging, symptom scales, cognitive testing, and standardized assessment for diagnosis; history and risk factor assessment, monitoring, and counseling for prognosis; and patient/family education, rest, support, return to school, and symptom management for treatment. Conclusions and Relevance: This guideline identifies the best practices for mTBI based on the current evidence; updates should be made as the body of evidence grows. In addition to the development of the guideline, CDC has created user-friendly guideline implementation materials that are concise and actionable. Evaluation of the guideline and implementation materials is crucial in understanding the influence of the recommendations. |
Diagnosis and management of mild traumatic brain injury in children: A systematic review
Lumba-Brown A , Yeates KO , Sarmiento K , Breiding MJ , Haegerich TM , Gioia GA , Turner M , Benzel EC , Suskauer SJ , Giza CC , Joseph M , Broomand C , Weissman B , Gordon W , Wright DW , Moser RS , McAvoy K , Ewing-Cobbs L , Duhaime AC , Putukian M , Holshouser B , Paulk D , Wade SL , Herring SA , Halstead M , Keenan HT , Choe M , Christian CW , Guskiewicz K , Raksin PB , Gregory A , Mucha A , Taylor HG , Callahan JM , DeWitt J , Collins MW , Kirkwood MW , Ragheb J , Ellenbogen RG , Spinks TJ , Ganiats TG , Sabelhaus LJ , Altenhofen K , Hoffman R , Getchius T , Gronseth G , Donnell Z , O'Connor RE , Timmons SD . JAMA Pediatr 2018 172 (11) e182847 Importance: In recent years, there has been an exponential increase in the research guiding pediatric mild traumatic brain injury (mTBI) clinical management, in large part because of heightened concerns about the consequences of mTBI, also known as concussion, in children. The CDC National Center for Injury Prevention and Control's (NCIPC) Board of Scientific Counselors (BSC), a federal advisory committee, established the Pediatric Mild TBI Guideline workgroup to complete this systematic review summarizing the first 25 years of literature in this field of study. Objective: To conduct a systematic review of the pediatric mTBI literature to serve as the foundation for an evidence-based guideline with clinical recommendations associated with the diagnosis and management of pediatric mTBI. Evidence Review: Using a modified Delphi process, the authors selected 6 clinical questions on diagnosis, prognosis, and management or treatment of pediatric mTBI. Two consecutive searches were conducted on PubMed, Embase, ERIC, CINAHL, and SportDiscus. The first included the dates January 1, 1990, to November 30, 2012, and an updated search included December 1, 2012, to July 31, 2015. The initial search was completed from December 2012 to January 2013; the updated search, from July 2015 to August 2015. Two authors worked in pairs to abstract study characteristics independently for each article selected for inclusion. A third author adjudicated disagreements. The risk of bias in each study was determined using the American Academy of Neurology Classification of Evidence Scheme. Conclusion statements were developed regarding the evidence within each clinical question, and a level of confidence in the evidence was assigned to each conclusion using a modified GRADE methodology. Data analysis was completed from October 2014 to May 2015 for the initial search and from November 2015 to April 2016 for the updated search. Findings: Validated tools are available to assist clinicians in the diagnosis and management of pediatric mTBI. A significant body of research exists to identify features that are associated with more serious TBI-associated intracranial injury, delayed recovery from mTBI, and long-term sequelae. However, high-quality studies of treatments meant to improve mTBI outcomes are currently lacking. Conclusions and Relevance: This systematic review was used to develop an evidence-based clinical guideline for the diagnosis and management of pediatric mTBI. While an increasing amount of research provides clinically useful information, this systematic review identified key gaps in diagnosis, prognosis, and management. |
Electron microscopic analysis of silicate and calcium particles in cigarette smoke tar
Pappas RS , Halstead MM , Watson CH . Int J Respir Pulm Med 2016 3 (1) Scanning electron microscopy with energy dispersive x-ray spectroscopy (SEM-EDS) supplies information that is complementary to those data traditionally obtained using inductively coupled plasma-mass spectrometry for analysis of inorganic tobacco and tobacco smoke constituents. The SEM-EDS approach was used to identify select inorganic constituents of mainstream cigarette smoke "tar." The nature of SEM-EDS instrumentation makes it an ideal choice for microstructural analyses as it provides information relevant to inorganic constituents that could result from exposure to combusted tobacco products. Our analyses show that aluminum silicates, silica, and calcium compounds were common constituents of cigarette mainstream smoke "tar." Identifying inorganic tobacco smoke constituents is important because inhalation of fine inorganic particles could lead to inflammatory responses in the lung and systemic inflammatory responses. As cigarette smoking causes chronic inflammation in the respiratory tract, information on inorganic particulate in mainstream smoke informs efforts to determine causative agents associated with increased morbidity and mortality from tobacco use. |
Electron microscopic analysis of surface inorganic substances on oral and combustible tobacco products
Halstead MM , Watson CH , Pappas RS . J Anal Toxicol 2015 39 (9) 698-701 Although quantitative trace toxic metal analyses have been performed on tobacco products, little has been published on inorganic particulate constituents on and inside the products. We analyzed these constituents using scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS). The nature of SEM-EDS instrumentation makes it an ideal choice for inorganic particulate analyses and yields relevant information to potential exposures during consumption of oral tobacco products, and possibly as a consequence of smoking. Aluminum silicates, silica and calcium compounds were common inorganic particulate constituents of tobacco products. Aluminum silicates and silica from soil were found on external leaf surfaces. Phytolithic silica, found in the lumen of the plant leaf, is of biogenic origin. Calcium oxalate was also apparently of biogenic origin. Small mineral deposits on tobacco could have health implications. Minerals found on the surfaces of smokeless tobacco products could possibly abrade the oral mucosa and contribute to the oral inflammatory responses observed with smokeless tobacco product use. If micron and sub-micron size calcium particles on cigarette filler were transported in mainstream smoke, they could potentially induce a pulmonary irritant inflammation when inhaled. The transport of aluminum silicate and silica in smoke could potentially also contribute to chronic inflammatory disease. |
Evaluation of commercially available diagnostic tests for the detection of dengue virus NS1 antigen and anti-dengue virus IgM antibody
Hunsperger EA , Yoksan S , Buchy P , Nguyen VC , Sekaran SD , Enria DA , Vazquez S , Cartozian E , Pelegrino JL , Artsob H , Guzman MG , Olliaro P , Zwang J , Guillerm M , Kliks S , Halstead S , Peeling RW , Margolis HS . PLoS Negl Trop Dis 2014 8 (10) e3171 Commercially available diagnostic test kits for detection of dengue virus (DENV) non-structural protein 1 (NS1) and anti-DENV IgM were evaluated for their sensitivity and specificity and other performance characteristics by a diagnostic laboratory network developed by World Health Organization (WHO), the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) and the Pediatric Dengue Vaccine Initiative (PDVI). Each network laboratory contributed characterized serum specimens for the panels used in the evaluation. Microplate enzyme-linked immunosorbent assay (ELISA) and rapid diagnostic test (RDT formats) were represented by the kits. Each ELISA was evaluated by 2 laboratories and RDTs were evaluated by at least 3 laboratories. The reference tests for IgM anti-DENV were laboratory developed assays produced by the Armed Forces Research Institute for Medical Science (AFRIMS) and the Centers for Disease Control and Prevention (CDC), and the NS1 reference test was reverse transcriptase polymerase chain reaction (RT-PCR). Results were analyzed to determine sensitivity, specificity, inter-laboratory and inter-reader agreement, lot-to-lot variation and ease-of-use. NS1 ELISA sensitivity was 60-75% and specificity 71-80%; NS1 RDT sensitivity was 38-71% and specificity 76-80%; the IgM anti-DENV RDTs sensitivity was 30-96%, with a specificity of 86-92%, and IgM anti-DENV ELISA sensitivity was 96-98% and specificity 78-91%. NS1 tests were generally more sensitive in specimens from the acute phase of dengue and in primary DENV infection, whereas IgM anti-DENV tests were less sensitive in secondary DENV infections. The reproducibility of the NS1 RDTs ranged from 92-99% and the IgM anti-DENV RDTs from 88-94%. |
Dogma in classifying dengue disease
Farrar JJ , Hien TT , Horstick O , Hung NT , Jaenisch T , Junghanns T , Kroeger A , Laksono IS , Lum L , Martinez E , Simmons CP , Tami A , Tomashek KM , Wills BA . Am J Trop Med Hyg 2013 89 (2) 198-201 In his recent perspective entitled Dengue: the Syndromic Basis to Pathogenesis Research, Inutility of the 2009 WHO Case Definition, Halstead expresses concern that adoption of the 2009 World Health Organization (WHO) classification scheme will compromise the “analytic clarity needed to understand mechanisms underlying dengue pathophysiology, pathogenesis, treatment, and therapeutics.”1 Leaving aside the important issue of how best to resolve the long running and convoluted debate on dengue case definitions and classification, two important misconceptions need to be addressed. | First, rather than being a research tool, the 2009 WHO dengue classification scheme is primarily intended to be used by clinicians and public health specialists engaged in dealing with the ever-expanding global pandemic of dengue disease.2,3 The main objectives of the classification scheme are to improve case management by timely identification of severe or potentially severe cases, and to ensure that scarce resources are directed towards those most in need. The simplicity and sensitivity of the classification scheme should enable the complete clinical spectrum of dengue to be captured by surveillance systems and enhance the comparability of epidemiologic data gathered over time from different countries and regions. If, in addition, the new system provides a valid framework for scientific research on dengue pathogenesis, this feature should be regarded as a bonus. |
Evaluation of diagnostic tests: dengue
Peeling RW , Artsob H , Pelegrino JL , Buchy P , Cardoso MJ , Devi S , Enria DA , Jeremy F , Gubler DJ , Guzman MC , Halstead SB , Hunsperger E , Kliks S , Margolis HS , Nathanson CM , Vinh CN , Rizzo N , Vazquez S , Yoksan S . Nat Rev Microbiol 2010 8 S30-8 Dengue is an arthropod-borne flavivirus that comprises four distinct serotypes (DEN-1, DEN-2, DEN-3 and DEN-4) that constitute an antigenic complex of the genus flavivirus, family Flaviviridae. Infection by one serotype induces life-long immunity against reinfection by the same serotype, but only transient and partial protection against infection with the other serotypes1,2. | Dengue virus infections can result in a range of clinical manifestations from asymptomatic infection to dengue fever (DF) and the severe disease dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). Most dengue infections are asymptomatic or cause mild symptoms, which are characterized by undifferentiated fever with or without rash. Typical DF is characterized by high fever, severe headache, myalgia, arthralgia, retro-orbital pain and maculopapular rash. Some patients show petechiae, bruising or thrombocytopenia. The clinical presentation of acute dengue infection is non-specific but 5–10% of patients progress to severe DHF/DSS, which can result in death if it is not managed appropriately. Plasma extravasation is the main pathophysiological finding of DHF/DSS, which differentiates it from DF. DHF/DSS is characterized by high fever, bleeding, thrombocytopenia and haemoconcentration (an increase in the concentration of blood cells as a result of fluid loss). Approximately 3–4 days after the onset of fever, patients can present with petechiae, rash, epistaxis, and gingival and gastrointestinal bleeding. Pleural effusion and ascites are common. Some patients develop circulatory failure (DSS), presenting with a weak and fast pulse, narrowing of pulse pressure or hypotension, cold and moist skin and altered mental state. Although there are no specific antiviral treatments for dengue infection, patients usually recover when the need for fluid management is identified early and electrolytes are administered3. It has been proposed that the classification of dengue disease should be simplified as severe and non-severe dengue. This simplified classification would make patient management and surveillance easier4. |
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