Role of cognitive parameters in dengue hemorrhagic fever and dengue shock syndrome
© Tsai et al.; licensee BioMed Central Ltd. 2013
Received: 24 September 2013
Accepted: 26 November 2013
Published: 5 December 2013
Dengue is becoming recognized as one of the most important vector-borne human diseases. It is predominant in tropical and subtropical zones but its geographical distribution is progressively expanding, making it an escalating global health problem of today. Dengue presents with spectrum of clinical manifestations, ranging from asymptomatic, undifferentiated mild fever, dengue fever (DF), to dengue hemorrhagic fever (DHF) with or without shock (DSS), a life-threatening illness characterized by plasma leakage due to increased vascular permeability. Currently, there are no antiviral modalities or vaccines available to treat and prevent dengue. Supportive care with close monitoring is the standard clinical practice. The mechanisms leading to DHF/DSS remains poorly understood. Multiple factors have been attributed to the pathological mechanism, but only a couple of these hypotheses are popular in scientific circles. The current discussion focuses on underappreciated factors, temperature, natural IgM, and endotoxin, which may be critical components playing roles in dengue pathogenesis.
Dengue, a vector-borne human disease, has been recognized recently as one of the most significant public health threats, causing high morbidity and mortality worldwide. The disease is caused by the infection of dengue virus that is transmitted to human beings by the bite of a mosquito– domestic Aedes aegypti being the principal vector– although some other species, such as Aedes albopictus, are of importance. There are four serotypes (DENV1, DENV2, DENV3, and DENV4), each being capable of inducing typical dengue manifestations. The spectrum of illness is wide, ranging from inapparent or asymptomatic, mild febrile with varying degrees of thrombocytopenia, hemorrhaging and increased vascular permeability typical of dengue hemorrhagic fever (DHF), to plasma leakage and severe shock syndrome. The resurgence of dengue endemicity has resulted from numerous oscillating environmental, social and economical factors. It is estimated that about 40% of the world’s population is at risk of dengue virus infection, with approximately 25 million of these requiring hospitalization and about 25,000 resulting in death . Currently, there are no antiviral modalities or preventive vaccines available to alter disease outcomes. The mortality rate is varying, ranging from 1 to 5%, dependent upon the country and region. The exact mechanism by which dengue virus induces plasma leakage or disease severity remains poorly understood.
A large majority of the dengue infections occur in humans without any noticeable illness. However there are many incidences of symptomatic disease; they can be partitioned into two syndromes: dengue fever (DF) and DHF/dengue shock syndrome (DSS). While DF is a simple, self-limited febrile illness, DHF is a severe and potentially life-threatening condition. DHF/DSS is characterized by thrombocytopenia and hemorrhagic manifestations; additionally, there is increased vascular permeability that leads to depleted intravascular volume and shock. Severe, profound shock, as well as multiorgan failure, is known to occur in extreme cases and is associated with high mortality.
There are many excellent reviews on dengue pathogenesis, including the topics of dengue viral biology, the immune-mediated hypothesis, intervention strategies, and dengue diagnostic issues [2–7]. These aspects will not be included in the focus of the current article; readers who are interested in these details are encouraged to refer to the literature. The current article highlights other recent knowledge and developments in the field, and proposes a new mechanism for biological enhancement to dengue pathogenesis.
Initially, dengue disease predominantly affected the people living in tropical and subtropical zones. However the regions of the world that are endemic has spread and the incidence in dengue disease has climbed due to a number of contributing factors. Increased human migration is one culprit; individuals often travel between rural areas and city dwellings and even to other countries via air travel for the purpose of making money or personal enjoyment. A person carrying dengue virus acquired in one location can be bitten again by a mosquito and introduce it into new areas . Another factor is the weather; global warming and climate change has lead to the augmentation of zones hospitable for mosquito survival. Issues with unplanned urban development (including inadequate vector control and poor waste management) have resulted in the presence of many vesicles for the accumulation of water, which are exploited by Aedes aegypti for breeding and larvae/pupae production [9, 10]. All these factors have contributed to the spread of dengue virus in endemic regions.
Recently, dengue has even been spotted in the US territories . In order to avoid a significant impact on the world’s economy and avert potentially extensive burdens to society and the public health sector, a greater amount of research has focused on dengue virus surveillance [12, 13]. Consequently, as of today, dengue has been documented in over 100 countries, increasing the number of people at risk for an infection to 2.5 billion people. It is estimated that 50–100 million cases of dengue occur annually, resulting in 250,000 -500,000 cases of dengue hemorrhagic fever (DHF) and 25,000 deaths, depending on epidemic activity. However, these figures are reliant on a number of assumptions and the true incidence is unknown [14–16].
Diagnosis and clinical presentation
Accurate diagnosis of dengue requires serological testing and identification of viral material in the blood, which is dominantly performed in the clinic. Symptomatology cannot be relied upon because the early symptoms experienced by dengue patients are very similar to most other tropical pathogens and common febrile illnesses. Thus, it is very difficult for attending physicians to attribute the correct pathogen to each clinical presentation when they are often highly variable. Once the physicians determine the differential diagnosis, the second layer of difficulty is to distinguish whether the patient has dengue fever or dengue hemorrhagic fever. The former is likely a self-limited illness and patients normally recover without having noticeable sequelae; in contrast, the latter, if treatment is not instituted immediately, the progression of the condition can quickly escalate and result in life-threatening situations, including death. According to the old WHO guidelines , the initial phase of clinical manifestations for DF and DHF were quite similar. In general, the onset of DF and DHF are both very abrupt, beginning with fever. The common initial symptoms at the febrile stage are headache, malaise, weakness, chills, aches and pains, and gastrointestinal symptoms. Physical examination often reveals flushing of the face, lethargy, irritability (in young children), abdominal pain, hepatomegaly, and the presence of petechial hemorrhages or other bleeding manifestations. Initial complete blood counts reveal leucopenia, and after 2–5 days of fever, thrombocytopenia and depletion of coagulation factors often develop.
In DF, the fever abates after 3–7 days and the patients recover. In DHF, signs of progressive intravascular fluid leakage, such as petechiae, ecchymosis, epistaxis, gingival or gastrointestinal bleeding, occur after 3–5 days of fever. Frequently, confluent petechial convalescent rashes with scattered sparing spots develop in patients that undergo plasma leakage, allowing doctors a way to differentiate between DHF and typical DF. Conditions arising from plasma leakage, including pleural effusion, ascites, and hypoproteinaemia, are common in severe dengue. This is the so-called critical stage, when the fever typically begins to dissipate but the patients’ condition may worsen. At this point many patients may develop shock from depletion of intravascular volume and bleeding. Some patients deteriorate rapidly from circulatory failure, experiencing a condition called dengue shock syndrome (DSS), presenting with a rapid and weak pulse, narrow pulse pressure or hypotension, cold clammy skin, and altered mental status. Disease severity is classified as either mild (grades I and II) or severe (grades III and IV), the presence of shock being the main difference. This stage lasts no more than 48 hours, after which the patients usually recover .
This WHO classification has been mostly adequate and used for many decades; however there have been occasional difficulties in classifying patients who present with unusual manifestations. Atypical or abnormal clinical presentations have been reported such as encephalopathy, severe hepatitis, and myocarditis, in which the patients have severe disease but do not fit the DHF definition. In 2009, WHO published another case classification system for guiding dengue management . This new classification includes dengue without warning signs, dengue with warning signs, and severe dengue, which improved sensitivity for detection but reduced specificity [18, 19]. To improve upon the specificity of the 2009 dengue classification system, in 2011 WHO SEARO published an amendment, which expanded case definitions based on the previous DF/DHF (WHO 1997 ) description to include unusual manifestations . Both WHO guidelines, the 2009 and SEARO 2011 versions, are in use in several countries. However, this is dependent upon the country’s public health administrative leaders; some advocate classifying disease according to the new guidelines, while others still triage patients according to the expanded older classification of DF and DHF.
Due to the nonspecificity and complexity of dengue patient clinical manifestations, it is imperative to confirm the clinical diagnosis with biological and/or laboratory assays. Since dengue disease management is time sensitive, onsite rapid screening tests at the point-of-care is a critical component in assisting decision-making. Unfortunately these rapid screening tests perform poorly, having low specificities and sensitivities. Other diagnostic tools, such as virus isolation or dengue virus genome, antigen or specific IgM/IgG detection, are more informative but are also very time consuming and expensive to perform. Even though these results do not directly contribute to decisions for the patients in real time, the confirmatory information can provide a guideline for future decision making on patient care in general, as well as lead to improved precision on diagnostic rapid screening tests under development. In addition, the results obtained with confirmatory assays can serve to advance our understanding of human dengue virus pathogenesis and guide the development of preventive modalities.
Parameters associated with DHF/DSS
Although the majority of dengue-infected individuals are asymptomatic, a small percentage of the subjects will progress to apparent clinical illness including life-threatening DHF/DSS. The available information suggests that multiple factors, including the presence of cross-reactive, sub- or non-neutralizing antibodies, viral virulence, genetic predisposition, age, nutritional status and underlying chronic disease, can all be a risk and/or contributive factor to the pathogenesis of DHF/DSS [21–23]. However none of these factors has been substantiated because there are no reliable in vivo model systems to perform the necessary side-by-side comparisons. Consequently, the causes of dengue disease remain poorly understood in spite of many decades of intensive investigations. Some known but under-appreciated factors are briefly discussed here.
Temperature has captured the attention of the media, owing to growing concerns about the environment and global warming. In line with this, the change in theglobal climate has significantly impacted the geographic distribution of the mosquito vector and thus dengue disease. Accordingly, WHO has reported that a temperature rise of only 1–2°C could increase the risk of dengue virus infection to the population by several hundred million, potentially resulting in 20,000–30,000 more fatal cases annually . Additionally, the biological importance of temperature, particularly in the form of fever, and its role in medical science has not received the appropriate attention . Dengue fever, as the name indicates, has fever as one of its most salient clinical features. This is also the case for many other common febrile illnesses. The increase in body temperature during infection is commonly viewed of as one way to interfere with pathogen replication directly. Additionally this biological alteration may also promote the production of the appropriate host transcriptional and translational profiles, which may work to eradicate some microorganisms. Despite these known phenomena, the contribution of fever to pathogenesis has not been investigated. Researchers more frequently attribute the symptoms as directly or indirectly caused by the pathogen rather than a direct result of the fever. Refocusing the interpretation of the clinical data in light of the degree of fever may allow for a better understanding of disease presentation.
Escalating problems of opportunistic pathogen infections in dengue patients
Day of fever
Staphylococcus aureus, Haemophilus influenzae, Coagulase-negative staphylococcus
Burkholderia pseudomallei, Varicella zoster, Salmonella, Shigella, Escherichia coli, Herpes simplex, Mycobacterium tuberculosis, Streptococcus pneumoniae, Mycoplasma pneumoniae
Rosemonas species, Klebisella pneumoniae, Moraxella lacunata, Klebisella ozaenae, Enterococcus faecalis
Enterococcus faecalis, Klebisella pneumoniae
Plasmodium vivax, Plasmodium falciparum
Natural IgM is high avidity of polymeric antibody, which may contribute to the initial immune defense and to the control of invading pathogens until immune system has time to launch a specific adaptive response . Importantly, natural IgM antibody has been shown to directly neutralize or inhibit pathogens as well as aid the initiation of adaptive immune response from follicular B cells, which together play critical roles in protection against bacterial and viral infection [67, 69, 74–76]. Consequently, despite with limited number of specimens, we feel confident that the levels of the IgM in acute dengue patients could be lower than that of healthy subjects. Interestingly, recent evidence also suggests that lipopolysaccharide levels are elevated in dengue virus infected patients and correlate with disease severity .
One of the alternative contributing factors is the amount of platelets. Dysfunctional platelets and thrombocytopenia are a salient clinical finding in dengue patients and are correlated with the severity of disease . A platelet-endotoxin interaction is a necessary step for the final removal of LPS by the reticuloendothelial system . The evidence also suggests that the levels of detectable endotoxin in patients may be inversely correlated with the platelet counts. Some percentage of dengue shock cases may result from increased gut mucosa permeability, which could lead to abnormally high endotoxin levels in the peripheral blood. This phenomenon in combination with reduced platelet counts and reduced IgM specific to LPS could lead to inefficient clearance of endotoxin and consequently another mechanism will need to be induced to promote its removal from the bloodstream.
Scientifically, it has been known that phagocytic cells such as primary monocytes and macrophages are very difficult to get infected by dengue virus . But, if these cells are pretreated with endotoxin (LPS) , the infectivity rate increases significantly, likely as a result of enhanced phagocytic activity . Monocytes potentially acquire the virus when they engulf dengue-containing platelets, a frequent occurrence in dengue patients on days 6–8 after the onset of fever [81, 82]. In addition, LPS is known to bind to the CD14 receptor of macrophages and B cells and promote the secretion of pro-inflammatory cytokines [83, 84]. Interestingly, it has been suggested that activated macrophages from secondary DENV infected patients display enhanced phagocytic behavior of opsonized platelets, through a mechanism involving milk fat globule-epidermal growth factor 8 . Taken together, a hypothetical scenario can be drawn; endotoxin, usually kept at a low frequency in the circulation by functioning platelets, may leak into the periphery through a damaged gut-endothelial barrier in dengue patients, whom likely have dysfunctional platelets, thrombocytopenia, or low natural IgM and are unable to clear off the endotoxin in a timely manner. This combination of events may result in the induction of activated macrophages or monocytes, enhancing their engulfment activities and triggering a tsunami of inflammatory cytokine production and inciting septic shock. However this alternative hypothesis requires further investigation.
The pathophysiology of severe dengue is very complex and may involve multiple factors. Epidemiological data tabulated from dengue endemic locales suggest that serologically defined primary dengue virus infection and/or subsequent homologous serotype infection is known to be associated with less severe disease as compared with secondary subsequent heterologous serotype infection, a term has been coined as antibody dependent enhancement . However, our understanding of these interacting components that contribute to the development of dengue disease is obstructed by the lack of suitable animal models that can recapitulate the cardinal features of human dengue. As a result, the exact mechanism(s) leading to the development of DHF/DSS remains poorly understood, in spite of several decades of intensive investigations. One of the factors believed to play a role in pathogenesis is pre-exposure. Results available from dengue epidemic countries have indicated that severe disease more frequently occurs not with the primary but during subsequent viral infections [87, 88]. Without experimentation with the appropriate comparison groups and controls, it became assumed that pre-existing immunity following a challenge with a heterogeneous serotype is a risk for DHF/DSS. Consequently, the hypothesis suggests that DHF/DSS results from an abnormal or exaggerated host immune response -– particularly due to the cross-reactive antibodies, which bind similar epitopes on other dengue viral strains – that augments the rate of virus uptake [4, 71, 89]. However, recent results accumulated from non-dengue endemic regions  and from travelers suggest that the frequency of DHF in primary infections in naive individuals is similar to that of secondary infection . Also, Libraty et al’s cohort study reveals no association between maternal antibodies and development of severe dengue in infants . Collectively, multiple causes may play a critical role in dengue pathogenesis. The cause of pathology in naïve individuals and in infants infected by dengue virus may be distinctively distinguishable from that of primary and secondary infection, respectively, in dengue epidemic zones.
As a whole, evidence for the role of pre-existing immunity in human disease is still by and large circumstantial [23, 97, 98]. Thus, in order to further advance the understanding of the causes of DHF/DSS, reported disease should be divided into three major categories (naïve primary infection, defined primary infection in endemic zones, and secondary infection) and considered separately . With a clearer definition of the virus pre-exposure history, the search for the identity of the pathogenic cause for DHF/DSS may be much simpler to assess and faster to acquire and likely make much more sense.
The occurrence of DHF/DSS in primary naïve individuals and the high frequency of asymptomatic secondary infections implicates that the immune-enhancement hypothesis alone is inadequate to explain dengue pathogenesis. An alternative explanation for the pathogenesis of DHF/DSS is the virulence of different viral strains . Although the in vivo scientific data on the topic is quite sparse, it can be interpreted that some dengue viral strains are more virulent for man than others. Reports based upon the epidemiological data advocate that particular serotypes appear to be more virulent than others with certain ethnic groups [101–106]. In addition, experimental results also suggest that certain genotypes within a serotype encode determinants for virulence, attenuation, and tissue tropism [107–111]. However, substantiation of the virulent strain hypothesis of dengue pathogenesis still awaits the availability of an adequate disease model for validation [112, 113].
As aforementioned, the factors that place patients at higher risk of developing DHF/DSS are not clearly identified yet. Multiple factors have been correlated with DHF/DSS: age, sex, underlying disease, nutritional status, ordering of serotype pre-exposure, individual genetic background including HLA type and ethnic variation [114–119]. These factors have yet to be further evaluated.
Treatment and prevention
Currently, there is not a specific antiviral treatment for dengue. Even if there were a drug available that could reduce viral replication or entry it would have limited usage. Treatment of dengue disease is time-sensitive; in other words, as time progresses, the presence of the virus and the ability to accurately detect it decreases, while the risk of severe immune-mediated disease increases. The best treatment currently available is immediate supportive or palliative care with vigilant monitoring by the professional healthcare staff. Patients usually recover after fluid and electrolyte supportive therapy. Early recognition of DHF and immediate treatment are of utmost importance to reduce the case fatality rate.
Since there is no antiviral therapeutic modality or vaccine against dengue available, the only possible preventive method that can be instituted is mosquito control. However, the effectiveness of current insecticides is diminishing and the successfulness of this strategy is compromised by its high cost. Thus, a dengue vaccine is urgently needed to prevent the virus from further spreading.
Dengue has been associated with human beings for more than two centuries and yet its pathogenic cause(s) remain poorly defined. Lack of a suitable animal model recapitulating the cardinal features of human dengue further hinders the progress of our understanding. Numerous factors and hypotheses have been associated with or attributed to the pathogenesis of dengue. There are only limited results suggestive that some of these theories may be the primal instigator of severe disease; however they remain to be circumstantial and require further verification. Complexity of severe dengue suggests that other factors, such as fever and endotoxin, are important as well. These factors are often underappreciated and may not only provide the critical link in understanding the cause(s) of dengue pathogenesis, but offer a new strategy for the amelioration and/or prevention of dengue.
We would like to thank the clinical staffs at the Tropical Medicine Center and Division of Infectious Diseases of Kaohsiung Medical University Hospital, and at the Division of Infectious Diseases in the Department of Pediatrics at the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. This study was partially supported by a startup grant from the National Science Council (NSC99-2321-B006-008) (GCP) with the Center of Infectious Disease and Signaling Research, NCKU, Taiwan, National Health Research Institutes (NHRI-EX102-10129SC) and National Science Council (NSC 101-2311-B-006-008-MY3) (YCL), and Grants from Taiwan National Science Council (NSC 99-2745-B-037-002) (JJT).
- WHO: Dengue Vaccine Development: The role of the WHO South-East Asia Regional Office. 2010, Geneva: World Health OrganizationGoogle Scholar
- Clark KB, Onlamoon N, Hsiao HM, Perng GC, Villinger F: Can non-human primates serve as models for investigating dengue disease pathogenesis?. Front in microbiol. 2013, 4: 305-Google Scholar
- Gusman MG: Dengue vaccines: new developments. Drugs Future. 2011, 36: 45-62.View ArticleGoogle Scholar
- Halstead SB: Dengue. Lancet. 2007, 370 (9599): 1644-1652. 10.1016/S0140-6736(07)61687-0.PubMedView ArticleGoogle Scholar
- Murphy BR, Whitehead SS: Immune response to dengue virus and prospects for a vaccine. Annu Rev Immunol. 2011, 29: 587-619. 10.1146/annurev-immunol-031210-101315.PubMedView ArticleGoogle Scholar
- Peeling RW, Artsob H, Pelegrino JL, Buchy P, Cardosa MJ, Devi S, Enria DA, Farrar J, Gubler DJ, Guzman MG, Halstead SB, Hunsperger E, Kliks S, Margolis HS, Nathanson CM, Nguyen VC, Rizzo N, Vazquez S, Yoksan S: Evaluation of diagnostic tests: dengue. Nat Rev Microbiol. 2010, 8 (12 Suppl): S30-S38.PubMedView ArticleGoogle Scholar
- Rothman AL: Immunity to dengue virus: a tale of original antigenic sin and tropical cytokine storms. Nat Rev Immunol. 2011, 11 (8): 532-543. 10.1038/nri3014.PubMedView ArticleGoogle Scholar
- Chastel C: Eventual role of asymptomatic cases of dengue for the introduction and spread of dengue viruses in non-endemic regions. Front in physiol. 2012, 3: 70-View ArticleGoogle Scholar
- Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, Drake JM, Brownstein JS, Hoen AG, Sankoh O, Myers MF, George DB, Jaenisch T, Wint GR, Simmons CP, Scott TW, Farrar JJ, Hay SI: The global distribution and burden of dengue. Nature. 2013, 496 (7446): 504-507. 10.1038/nature12060.PubMed CentralPubMedView ArticleGoogle Scholar
- Ramasamy R, Surendran SN: Global climate change and its potential impact on disease transmission by salinity-tolerant mosquito vectors in coastal zones. Front in physiol. 2012, 3: 198-View ArticleGoogle Scholar
- CDC: Locally acquired dengue--Key West, Florida, 2009–2010. MMWR. 2010, 59 (19): 577-581.Google Scholar
- Laughlin CA, Morens DM, Cassetti MC, Costero-Saint Denis A, San Martin JL, Whitehead SS, Fauci AS: Dengue research opportunities in the Americas. J Infect Dis. 2012, 206 (7): 1121-1127. 10.1093/infdis/jis351.PubMed CentralPubMedView ArticleGoogle Scholar
- Morens DM, Fauci AS: Dengue and hemorrhagic fever: a potential threat to public health in the United States. Jama. 2008, 299 (2): 214-216.PubMedView ArticleGoogle Scholar
- Pinheiro FP, Corber SJ: Global situation of dengue and dengue haemorrhagic fever, and its emergence in the Americas. World Health Stat Q. 1997, 50 (3–4): 161-169.PubMedGoogle Scholar
- Rigau-Perez JG, Clark GG, Gubler DJ, Reiter P, Sanders EJ, Vorndam AV: Dengue and dengue haemorrhagic fever. Lancet. 1998, 352 (9132): 971-977. 10.1016/S0140-6736(97)12483-7.PubMedView ArticleGoogle Scholar
- WHO: Dengue guidelines for diagnosis, treatment, prevention and control. 2009, Geneva: World Health OrganizationGoogle Scholar
- WHO: Dengue Haemorrhagic fever: diagnosis, treatment, prevention and control. 1997, Geneva: World Health Organization, 2Google Scholar
- Barniol J, Gaczkowski R, Barbato EV, da Cunha RV, Salgado D, Martinez E, Segarra CS, Pleites Sandoval EB, Mishra A, Laksono IS, Lum LC, Martinez JG, Nunez A, Balsameda A, Allende I, Ramirez G, Dimaano E, Thomacheck K, Akbar NA, Ooi EE, Villegas E, Hien TT, Farrar J, Horstick O, Kroeger A, Jaenisch T: Usefulness and applicability of the revised dengue case classification by disease: multi-centre study in 18 countries. BMC Infect Dis. 2011, 11: 106-10.1186/1471-2334-11-106.PubMed CentralPubMedView ArticleGoogle Scholar
- Basuki PS, Budiyanto , Puspitasari D, Husada D, Darmowandowo W, Ismoedijanto , Soegijanto S, Yamanaka A: Application of revised dengue classification criteria as a severity marker of dengue viral infection in Indonesia. Southeast Asian J Trop Med Public Health. 2010, 41 (5): 1088-1094.PubMedGoogle Scholar
- WHO: Revised and expanded edition. Comprehensive Guidelines for Prevention and Control of Dengue and Dengue Haemorrhagic Fever. 2011, Geneva: SEARO Technical Publication Series, 60:Google Scholar
- Guzman MG, Halstead SB, Artsob H, Buchy P, Farrar J, Gubler DJ, Hunsperger E, Kroeger A, Margolis HS, Martinez E, Nathan MB, Pelegrino JL, Simmons C, Yoksan S, Peeling RW: Dengue: a continuing global threat. Nat Rev Microbiol. 2010, 8 (12 Suppl): S7-S16.PubMed CentralPubMedView ArticleGoogle Scholar
- Halstead SB: Epidemiology of dengue and dengue haemorrhagic fever. Dengue and Dengue Haemorrhagic Fever. Edited by: Gubler D.J.a.K. G. 1997, Wallingford, England: CAB International, 23-44.Google Scholar
- Rothman AL: Dengue: defining protective versus pathologic immunity. J Clin Invest. 2004, 113 (7): 946-951.PubMed CentralPubMedView ArticleGoogle Scholar
- WHO: A vision for all. The World Health Report. 1998, Geneva: Life in the 21st centuryGoogle Scholar
- Chokephaibulkit K, Perng GC: The importance of temperature for medical science. Curr Top in Virol. 2011, 9: 43-49.Google Scholar
- Vaughn DW, Green S, Kalayanarooj S, Innis BL, Nimmannitya S, Suntayakorn S, Rothman AL, Ennis FA, Nisalak A: Dengue in the early febrile phase: Viremia and antibody responses. J Infect Dis. 1997, 176 (2): 322-330. 10.1086/514048.PubMedView ArticleGoogle Scholar
- Pratten MK, Lloyd JB: Effects of temperature, metabolic inhibitors and some other factors on fluid-phase and adsorptive pinocytosis by rat peritoneal macrophages. Biochem J. 1979, 180 (3): 567-571.PubMed CentralPubMedView ArticleGoogle Scholar
- Weigel PH, Oka JA: Temperature dependence of endocytosis mediated by the asialoglycoprotein receptor in isolated rat hepatocytes. Evidence for two potentially rate-limiting steps. J Biol Chem. 1981, 256 (6): 2615-2617.PubMedGoogle Scholar
- Kuno G, Oliver A: Maintaining mosquito cell lines at high temperatures: effects on the replication of flaviviruses. In Vitr Cell Dev Biol. 1989, 25 (2): 193-196. 10.1007/BF02626177.View ArticleGoogle Scholar
- Paranjape SP, Kadam VD, Deolankar RP: Increased yields of Japanese encephalitis virus in heat shocked cell cultures. Acta Virol. 1994, 38 (6): 333-337.PubMedGoogle Scholar
- Noisakran S, Onlamoon N, Hsiao HM, Clark KB, Villinger F, Ansari AA, Perng GC: Infection of bone marrow cells by dengue virus in vivo. Exp Hematol. 2012, 40 (3): 250-259. 10.1016/j.exphem.2011.11.011. e254PubMed CentralPubMedView ArticleGoogle Scholar
- Chiu YC, Wu KL, Kuo CH, Hu TH, Chou YP, Chuah SK, Kuo CM, Kee KM, Changchien CS, Liu JW, Chiu KW: Endoscopic findings and management of dengue patients with upper gastrointestinal bleeding. Am J Trop Med Hyg. 2005, 73 (2): 441-444.PubMedGoogle Scholar
- Sandler NG, Douek DC: Microbial translocation in HIV infection: causes, consequences and treatment opportunities. Nat Rev Microbiol. 2012, 10 (9): 655-666. 10.1038/nrmicro2848.PubMedView ArticleGoogle Scholar
- Tan PS: Clinical correlates with immunopathogenesis in dengue haemorrhagic fever/dengue shock syndrome. Malays J Pathol. 1993, 15 (1): 41-47.PubMedGoogle Scholar
- Swank GM, Deitch EA: Role of the gut in multiple organ failure: bacterial translocation and permeability changes. World j of surg. 1996, 20 (4): 411-417. 10.1007/s002689900065.View ArticleGoogle Scholar
- Vejchapipat P, Theamboonlers A, Chongsrisawat V, Poovorawan Y: An evidence of intestinal mucosal injury in dengue infection. Southeast Asian J Trop Med Public Health. 2006, 37 (1): 79-82.PubMedGoogle Scholar
- Meltzer E, Heyman Z, Bin H, Schwartz E: Capillary leakage in travelers with dengue infection: implications for pathogenesis. Am J Trop Med Hyg. 2012, 86 (3): 536-539. 10.4269/ajtmh.2012.10-0670.PubMed CentralPubMedView ArticleGoogle Scholar
- Ruiz N, Kahne D, Silhavy TJ: Transport of lipopolysaccharide across the cell envelope: the long road of discovery. Nat Rev Microbiol. 2009, 7 (9): 677-683. 10.1038/nrmicro2184.PubMed CentralPubMedView ArticleGoogle Scholar
- Usawattanakul W, Nimmannitya S, Sarabenjawong K, Tharavanij S: Endotoxin and dengue haemorrhagic fever. Southeast Asian J Trop Med Public Health. 1986, 17 (1): 8-12.PubMedGoogle Scholar
- van de Weg CA, Koraka P, van Gorp EC, Mairuhu AT, Supriatna M, Soemantri A, van de Vijver DA, Osterhaus AD, Martina BE: Lipopolysaccharide levels are elevated in dengue virus infected patients and correlate with disease severity. J Clin Virol. 2012, 53 (1): 38-42. 10.1016/j.jcv.2011.09.028.PubMedView ArticleGoogle Scholar
- Halstead SB, Udomsakdi S, Singharaj P, Nisalak A: Dengue chikungunya virus infection in man in Thailand, 1962–1964. 3. Clinical, epidemiologic, and virologic observations on disease in non-indigenous white persons. Am J Trop Med Hyg. 1969, 18 (6): 984-996.PubMedGoogle Scholar
- Tsai CJ, Kuo CH, Chen PC, Changcheng CS: Upper gastrointestinal bleeding in dengue fever. Am J Gastroenterol. 1991, 86 (1): 33-35.PubMedGoogle Scholar
- Noisakran S, Gibbons RV, Songprakhon P, Jairungsri A, Ajariyakhajorn C, Nisalak A, Jarman RG, Malasit P, Chokephaibulkit K, Perng GC: Detection of dengue virus in platelets isolated from dengue patients. Southeast Asian J Trop Med Public Health. 2009, 40 (2): 253-262.PubMedGoogle Scholar
- Tsai JJ, Jen YH, Chang JS, Hsiao HM, Noisakran S, Perng GC: Frequency alterations in key innate immune cell components in the peripheral blood of dengue patients detected by FACS analysis. J Innate Immun. 2011, 3 (5): 530-540. 10.1159/000322904.PubMedView ArticleGoogle Scholar
- Chai LY, Lim PL, Lee CC, Hsu LY, Teoh YL, Lye DC, Krishnan P, Leo YS: Cluster of staphylococcus aureus and dengue co-infection in Singapore. Ann Acad Med Singapore. 2007, 36 (10): 847-850.PubMedGoogle Scholar
- Hongsiriwon S: Dengue hemorrhagic fever in infants. Southeast Asian J Trop Med Public Health. 2002, 33 (1): 49-55.PubMedGoogle Scholar
- Pancharoen C, Thisyakorn U: Coinfections in dengue patients. Pediatr Infect Dis J. 1998, 17 (1): 81-82. 10.1097/00006454-199801000-00019.PubMedView ArticleGoogle Scholar
- Sudjana P, Jusuf H: Concurrent dengue hemorrhagic fever and typhoid fever infection in adult: case report. Southeast Asian J Trop Med Public Health. 1998, 29 (2): 370-372.PubMedGoogle Scholar
- Charrel RN, Abboud M, Durand JP, Brouqui P, De Lamballerie X: Dual infection by dengue virus and Shigella sonnei in patient returning from India. Emerg Infect Dis. 2003, 9 (2): 271-PubMed CentralPubMedView ArticleGoogle Scholar
- Lee IK, Liu JW, Yang KD: Clinical characteristics and risk factors for concurrent bacteremia in adults with dengue hemorrhagic fever. Am J Trop Med Hyg. 2005, 72 (2): 221-226.PubMedGoogle Scholar
- Lee IK, Liu JW, Yang KD: Fatal dengue hemorrhagic fever in adults: emphasizing the evolutionary Pre-fatal clinical and laboratory manifestations. PLoS Negl Trop Dis. 2012, 6 (2): e1532-10.1371/journal.pntd.0001532.PubMed CentralPubMedView ArticleGoogle Scholar
- Larbcharoensub N, Aroonroch R, Kanoksil W, Leopairut J, Nitiyanant P, Khositseth A, Tangnararatchakit K, Chuansumrit A, Yoksan S: Infection-associated hemophagocytic syndrome among patients with dengue shock syndrome and invasive aspergillosis: a case series and review of the literature. Southeast Asian J Trop Med Public Health. 2011, 42 (5): 1106-1112.PubMedGoogle Scholar
- Charrel RN, Brouqui P, Foucault C, de Lamballerie X: Concurrent dengue and malaria. Emerg Infect Dis. 2005, 11 (7): 1153-1154. 10.3201/eid1107.041352.PubMed CentralPubMedView ArticleGoogle Scholar
- Kaushik RM, Varma A, Kaushik R, Gaur KJ: Concurrent dengue and malaria due to Plasmodium falciparum and P. vivax. Trans R Soc Trop Med Hyg. 2007, 101 (10): 1048-1050. 10.1016/j.trstmh.2007.04.017.PubMedView ArticleGoogle Scholar
- Arya SC, M. LK, Nirmala A, Agarwal BK, George M, Arun M: Episodes of concurrent dengue and malaria. Dengue Bull. 2005, 29: 208-209.Google Scholar
- Thangaratham PS, Jeevan MK, Rajendran R, Samuel PP, Tyagi BK: Dual infection by dengue virus and Plasmodium vivax in Alappuzha District, Kerala, India. Jpn J Infect Dis. 2006, 59 (3): 211-212.PubMedGoogle Scholar
- Kaur H, John M: Mixed infection due to leptospira and dengue. Indian J Gastroenterol. 2002, 21 (5): 206-PubMedGoogle Scholar
- Rele MC, Rasal A, Despande SD, Koppikar GV, Lahiri KR: Mixed infection due to Leptospira and Dengue in a patient with pyrexia. Indian J Med Microbiol. 2001, 19 (4): 206-207.PubMedGoogle Scholar
- Suzuki S, Kitazawa T, Ota Y, Okugawa S, Tsukada K, Nukui Y, Hatakeyama S, Yamaguchi D, Matsuse S, Ishii T, Matsubara T, Yamauchi C, Ota S, Yahagi N, Fukayama M, Koike K: Dengue hemorrhagic shock and disseminated candidiasis. Intern Med. 2007, 46 (13): 1043-1046. 10.2169/internalmedicine.46.6354.PubMedView ArticleGoogle Scholar
- Hashimoto K, Handa H, Umehara K, Sasaki S: Germfree mice reared on an “antigen-free” diet. Lab Anim Sci. 1978, 28 (1): 38-45.PubMedGoogle Scholar
- Coutinho A, Kazatchkine MD, Avrameas S: Natural autoantibodies. Curr Opin Immunol. 1995, 7 (6): 812-818. 10.1016/0952-7915(95)80053-0.PubMedView ArticleGoogle Scholar
- Tlaskalova-Hogenova H, Mandel L, Stepankova R, Bartova J, Barot R, Leclerc M, Kovaru F, Trebichavsky I: Autoimmunity: from physiology to pathology. Natural antibodies, mucosal immunity and development of B cell repertoire. Folia Biol (Praha). 1992, 38 (3–4): 202-215.Google Scholar
- Brandlein S, Vollmers HP: Natural IgM antibodies, the ignored weapons in tumour immunity. Histol Histopathol. 2004, 19 (3): 897-905.PubMedGoogle Scholar
- Konishi E: Naturally occurring immunoglobulin M antibodies to Toxoplasma gondii in Japanese populations. Parasitology. 1991, 102 (Pt 2): 157-162.PubMedView ArticleGoogle Scholar
- Vollmers HP, Brandlein S: Natural IgM antibodies: from parias to parvenus. Histol Histopathol. 2006, 21 (12): 1355-1366.PubMedGoogle Scholar
- Kantor AB, Herzenberg LA: Origin of murine B cell lineages. Annu Rev Immunol. 1993, 11: 501-538. 10.1146/annurev.iy.11.040193.002441.PubMedView ArticleGoogle Scholar
- Baumgarth N, Herman OC, Jager GC, Brown LE, Herzenberg LA, Chen J: B-1 and B-2 cell-derived immunoglobulin M antibodies are nonredundant components of the protective response to influenza virus infection. J Exp Med. 2000, 192 (2): 271-280. 10.1084/jem.192.2.271.PubMed CentralPubMedView ArticleGoogle Scholar
- Ehrenstein MR, Notley CA: The importance of natural IgM: scavenger, protector and regulator. Nat Rev Immunol. 2010, 10 (11): 778-786. 10.1038/nri2849.PubMedView ArticleGoogle Scholar
- Ochsenbein AF, Fehr T, Lutz C, Suter M, Brombacher F, Hengartner H, Zinkernagel RM: Control of early viral and bacterial distribution and disease by natural antibodies. Science. 1999, 286 (5447): 2156-2159. 10.1126/science.286.5447.2156.PubMedView ArticleGoogle Scholar
- Reid RR, Prodeus AP, Khan W, Hsu T, Rosen FS, Carroll MC: Endotoxin shock in antibody-deficient mice: unraveling the role of natural antibody and complement in the clearance of lipopolysaccharide. J Immunol. 1997, 159 (2): 970-975.PubMedGoogle Scholar
- Kurane I, Ennis FA: Immunopathogenesis of dengue virus infections. Dengue and Dengue Hemorrhagic Fever. Edited by: Gubler DJ, Kuno G. 1997, Wallingford, UK: CAB International, 273-290.Google Scholar
- Hotta S: Newer problems of dengue research. 1984, The Eighth Tropical Medicine Seminar: Kanazawa Medical UniversityGoogle Scholar
- Baumgarth N, Tung JW, Herzenberg LA: Inherent specificities in natural antibodies: a key to immune defense against pathogen invasion. Springer Semin Immunopathol. 2005, 26 (4): 347-362. 10.1007/s00281-004-0182-2.PubMedView ArticleGoogle Scholar
- Boes M, Prodeus AP, Schmidt T, Carroll MC, Chen J: A critical role of natural immunoglobulin M in immediate defense against systemic bacterial infection. J Exp Med. 1998, 188 (12): 2381-2386. 10.1084/jem.188.12.2381.PubMed CentralPubMedView ArticleGoogle Scholar
- Weerkamp F, de Haas EF, Naber BA, Comans-Bitter WM, Bogers AJ, van Dongen JJ, Staal FJ: Age-related changes in the cellular composition of the thymus in children. J Allergy Clin Immunol. 2005, 115 (4): 834-840. 10.1016/j.jaci.2004.10.031.PubMedView ArticleGoogle Scholar
- Xu G, Dong H, Shi N, Liu S, Zhou A, Cheng Z, Chen G, Liu J, Fang T, Zhang H, Gu C, Tan X, Ye J, Xie S, Cao G: An outbreak of dengue virus serotype 1 infection in Cixi, Ningbo, People’s Republic of China, 2004, associated with a traveler from Thailand and high density of Aedes albopictus. Am J Trop Med Hyg. 2007, 76 (6): 1182-1188.PubMedGoogle Scholar
- WHO: Pathogenetic mechanisms in dengue haemorrhagic fever: report of an international collaboratorive study. Bull WHO. 1973, 48: 117-133.Google Scholar
- Das J, Schwartz AA, Folkman J: Clearance of endotoxin by platelets: role in increasing the accuracy of the Limulus gelation test and in combating experimental endotoxemia. Surgery. 1973, 74 (2): 235-240.PubMedGoogle Scholar
- Kou Z, Lim JY, Beltramello M, Quinn M, Chen H, Liu S, Martinez-Sobrido L, Diamond MS, Schlesinger JJ, de Silva A, Sallusto F, Jin X: Human antibodies against dengue enhance dengue viral infectivity without suppressing type I interferon secretion in primary human monocytes. Virology. 2011, 410 (1): 240-247. 10.1016/j.virol.2010.11.007.PubMedView ArticleGoogle Scholar
- Hotta H, Hotta S: Dengue virus multiplication in cultures of mouse peritoneal macrophages: effects of macrophage activators. Microbiol Immunol. 1982, 26 (8): 665-676. 10.1111/j.1348-0421.1982.tb00210.x.PubMedView ArticleGoogle Scholar
- Noisakran S, Onlamoon N, Pattanapanyasat K, Hsiao HM, Songprakhon P, Angkasekwinai N, Chokephaibulkit K, Villinger F, Ansari AA, Perng GC: Role of CD61(+) cells in thrombocytopenia of dengue patients. Int J Hematol. 2012, 96 (5): 600-610. 10.1007/s12185-012-1175-x.PubMed CentralPubMedView ArticleGoogle Scholar
- Tsai J-J, Liu L-T, Chang K, Wang S-H, Hsiao H-M, Clark KB, Perng GC: The importance of hematopoietic progenitor cells in dengue. Ther Adv in Hematol. 2012, 3 (1): 59-71. 10.1177/2040620711417660.View ArticleGoogle Scholar
- Raetz CR, Whitfield C: Lipopolysaccharide endotoxins. Annu Rev Biochem. 2002, 71: 635-700. 10.1146/annurev.biochem.71.110601.135414.PubMed CentralPubMedView ArticleGoogle Scholar
- Rittig MG, Kaufmann A, Robins A, Shaw B, Sprenger H, Gemsa D, Foulongne V, Rouot B, Dornand J: Smooth and rough lipopolysaccharide phenotypes of Brucella induce different intracellular trafficking and cytokine/chemokine release in human monocytes. J Leukoc Biol. 2003, 74 (6): 1045-1055. 10.1189/jlb.0103015.PubMedView ArticleGoogle Scholar
- Alonzo MT, Lacuesta TL, Dimaano EM, Kurosu T, Suarez LA, Mapua CA, Akeda Y, Matias RR, Kuter DJ, Nagata S, Natividad FF, Oishi K: Platelet apoptosis and apoptotic platelet clearance by macrophages in secondary dengue virus infections. J Infect Dis. 2012, 205 (8): 1321-1329. 10.1093/infdis/jis180.PubMedView ArticleGoogle Scholar
- Halstead SB: Pathogenesis of dengue: challenges to molecular biology. Science. 1988, 239 (4839): 476-481. 10.1126/science.3277268.PubMedView ArticleGoogle Scholar
- Halstead SB, Nimmannitya S, Cohen SN: Observations related to pathogenesis of dengue hemorrhagic fever. IV. Relation of disease severity to antibody response and virus recovered. Yale J Biol Med. 1970, 42 (5): 311-328.PubMed CentralPubMedGoogle Scholar
- Sangkawibha N, Rojanasuphot S, Ahandrik S, Viriyapongse S, Jatanasen S, Salitul V, Phanthumachinda B, Halstead SB: Risk factors in dengue shock syndrome: a prospective epidemiologic study in Rayong, Thailand. I. The 1980 outbreak. Am J Epidemiol. 1984, 120 (5): 653-669.PubMedGoogle Scholar
- Green S, Rothman A: Immunopathological mechanisms in dengue and dengue hemorrhagic fever. Curr Opin Infect Dis. 2006, 19 (5): 429-436. 10.1097/01.qco.0000244047.31135.fa.PubMedView ArticleGoogle Scholar
- Chao DY, Lin TH, Hwang KP, Huang JH, Liu CC, King CC: 1998 dengue hemorrhagic fever epidemic in Taiwan. Emerg Infect Dis. 2004, 10 (3): 552-554. 10.3201/eid1003.020518.PubMed CentralPubMedView ArticleGoogle Scholar
- Meltzer E, Schwartz E: A travel medicine view of dengue and dengue hemorrhagic fever. Travel Med Infect Dis. 2009, 7 (5): 278-283. 10.1016/j.tmaid.2009.05.002.PubMedView ArticleGoogle Scholar
- Libraty DH, Acosta LP, Tallo V, Segubre-Mercado E, Bautista A, Potts JA, Jarman RG, Yoon IK, Gibbons RV, Brion JD, Capeding RZ: A prospective nested case–control study of Dengue in infants: rethinking and refining the antibody-dependent enhancement dengue hemorrhagic fever model. PLoS Med. 2009, 6 (10): e1000171-10.1371/journal.pmed.1000171.PubMed CentralPubMedView ArticleGoogle Scholar
- Balmaseda A, Hammond SN, Perez L, Tellez Y, Saborio SI, Mercado JC, Cuadra R, Rocha J, Perez MA, Silva S, Rocha C, Harris E: Serotype-specific differences in clinical manifestations of dengue. Am J Trop Med Hyg. 2006, 74 (3): 449-456.PubMedGoogle Scholar
- Thai KT, Binh TQ, Giao PT, Phuong HL, le Hung Q, Van Nam N, Nga TT, Groen J, Nagelkerke N, de Vries PJ: Seroprevalence of dengue antibodies, annual incidence and risk factors among children in southern Vietnam. Trop Med Int Health. 2005, 10 (4): 379-386. 10.1111/j.1365-3156.2005.01388.x.PubMedView ArticleGoogle Scholar
- Perng GC: Dengue vaccines: challenge and confrontation. World J of Vaccines. 2011, 01 (04): 109-130. 10.4236/wjv.2011.14012.View ArticleGoogle Scholar
- Prince HE, Yeh C, Lape-Nixon M: Utility of IgM/IgG ratio and IgG avidity for distinguishing primary and secondary dengue virus infections using sera collected more than 30 days after disease onset. Clin Vaccine Immunol. 2011, 18 (11): 1951-1956. 10.1128/CVI.05278-11.PubMed CentralPubMedView ArticleGoogle Scholar
- Kurane I: Dengue hemorrhagic fever with special emphasis on immunopathogenesis. Comp Immunol Microbiol Infect Dis. 2007, 30 (5–6): 329-340.PubMedView ArticleGoogle Scholar
- Stephenson JR: Understanding dengue pathogenesis: implications for vaccine design. Bull World Health Organ. 2005, 83 (4): 308-314.PubMed CentralPubMedGoogle Scholar
- Perng GC, Chokephaibulkit K: Immunologic hypo- or non-responder in natural dengue virus infection. J Biomed Sci. 2013, 20 (1): 34-10.1186/1423-0127-20-34.PubMed CentralPubMedView ArticleGoogle Scholar
- Barnes WJ, Rosen L: Fatal hemorrhagic disease and shock associated with primary dengue infection on a Pacific island. Am J Trop Med Hyg. 1974, 23 (3): 495-506.PubMedGoogle Scholar
- Gubler DJ, Reed D, Rosen L, Hitchcock JR: Epidemiologic, clinical, and virologic observations on dengue in the Kingdom of Tonga. Am J Trop Med Hyg. 1978, 27 (3): 581-589.PubMedGoogle Scholar
- Dengue And Dengue Hemorrhagic Fever. Edited by: Gubler DJGK. 1997, Wallingford, UK: CABI, 1Google Scholar
- Mota J, Rico-Hesse R: Dengue virus tropism in humanized mice recapitulates human dengue Fever. PLoS One. 2011, 6 (6): e20762-10.1371/journal.pone.0020762.PubMed CentralPubMedView ArticleGoogle Scholar
- Rico-Hesse R: Dengue virus markers of virulence and pathogenicity. Future Virol. 2009, 4 (6): 581-10.2217/fvl.09.51.PubMed CentralPubMedView ArticleGoogle Scholar
- Rico-Hesse R, Harrison LM, Salas RA, Tovar D, Nisalak A, Ramos C, Boshell J, de Mesa MT, Nogueira RM, da Rosa AT: Origins of dengue type 2 viruses associated with increased pathogenicity in the Americas. Virology. 1997, 230 (2): 244-251. 10.1006/viro.1997.8504.PubMedView ArticleGoogle Scholar
- Watts DM, Porter KR, Putvatana P, Vasquez B, Calampa C, Hayes CG, Halstead SB: Failure of secondary infection with American genotype dengue 2 to cause dengue haemorrhagic fever. Lancet. 1999, 354 (9188): 1431-1434. 10.1016/S0140-6736(99)04015-5.PubMedView ArticleGoogle Scholar
- Messer WB, Gubler DJ, Harris E, Sivananthan K, de Silva AM: Emergence and global spread of a dengue serotype 3, subtype III virus. Emerg Infect Dis. 2003, 9 (7): 800-809. 10.3201/eid0907.030038.PubMed CentralPubMedView ArticleGoogle Scholar
- Puri B, Nelson WM, Henchal EA, Hoke CH, Eckels KH, Dubois DR, Porter KR, Hayes CG: Molecular analysis of dengue virus attenuation after serial passage in primary dog kidney cells. J Gen Virol. 1997, 78 (Pt 9): 2287-2291.PubMedView ArticleGoogle Scholar
- Rico-Hesse R: Microevolution and virulence of dengue viruses. Adv Virus Res. 2003, 59: 315-341.PubMed CentralPubMedView ArticleGoogle Scholar
- Rico-Hesse R: Molecular evolution and distribution of dengue viruses type 1 and 2 in nature. Virology. 1990, 174 (2): 479-493. 10.1016/0042-6822(90)90102-W.PubMedView ArticleGoogle Scholar
- Thant KZ, Morita K, Igarashi A: Detection of the disease severity-related molecular differences among new Thai dengue-2 isolates in 1993, based on their structural proteins and major non-structural protein NS1 sequences. Microbiol Immunol. 1996, 40 (3): 205-216. 10.1111/j.1348-0421.1996.tb03336.x.PubMedView ArticleGoogle Scholar
- Chen W, Kawano H, Men R, Clark D, Lai CJ: Construction of intertypic chimeric dengue viruses exhibiting type 3 antigenicity and neurovirulence for mice. J Virol. 1995, 69 (8): 5186-5190.PubMed CentralPubMedGoogle Scholar
- Cologna R, Rico-Hesse R: American genotype structures decrease dengue virus output from human monocytes and dendritic cells. J Virol. 2003, 77 (7): 3929-3938. 10.1128/JVI.77.7.3929-3938.2003.PubMed CentralPubMedView ArticleGoogle Scholar
- Guzman MG, Kouri G: Dengue: an update. Lancet Infect Dis. 2002, 2 (1): 33-42. 10.1016/S1473-3099(01)00171-2.PubMedView ArticleGoogle Scholar
- Guzman MG, Kouri G, Bravo J, Valdes L, Vazquez S, Halstead SB: Effect of age on outcome of secondary dengue 2 infections. Int J Infect Dis. 2002, 6 (2): 118-124. 10.1016/S1201-9712(02)90072-X.PubMedView ArticleGoogle Scholar
- Halstead SB, Streit TG, Lafontant JG, Putvatana R, Russell K, Sun W, Kanesa-Thasan N, Hayes CG, Watts DM: Haiti: absence of dengue hemorrhagic fever despite hyperendemic dengue virus transmission. Am J Trop Med Hyg. 2001, 65 (3): 180-183.PubMedGoogle Scholar
- Loke H, Bethell DB, Phuong CX, Dung M, Schneider J, White NJ, Day NP, Farrar J, Hill AV: Strong HLA class I–restricted T cell responses in dengue hemorrhagic fever: a double-edged sword?. J Infect Dis. 2001, 184 (11): 1369-1373. 10.1086/324320.PubMedView ArticleGoogle Scholar
- Malavige GN, Velathanthiri VG, Wijewickrama ES, Fernando S, Jayaratne SD, Aaskov J, Seneviratne SL: Patterns of disease among adults hospitalized with dengue infections. Qjm. 2006, 99 (5): 299-305. 10.1093/qjmed/hcl039.PubMedView ArticleGoogle Scholar
- Thisyakorn U, Nimmannitya S: Nutritional status of children with dengue hemorrhagic fever. Clin Infect Dis. 1993, 16 (2): 295-297. 10.1093/clind/16.2.295.PubMedView ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.