Dengue Illness Research Articles

Clinical evaluation of dengue and identification of risk factors for severe disease: protocol for a multicentre study in 8 countries.

BackgroundThe burden of dengue continues to increase globally, with an estimated 100 million clinically apparent infections occurring each year. Although most dengue infections are asymptomatic, patients can present with a wide spectrum of clinical symptoms ranging from mild febrile illness through to severe manifestations of bleeding, organ impairment, and hypovolaemic shock due to a systemic vascular leak syndrome. Clinical diagnosis of dengue and identification of which patients are likely to develop severe disease remain challenging. This study aims to improve diagnosis and clinical management through approaches designed a) to differentiate between dengue and other common febrile illness within 72 h of fever onset, and b) among patients with dengue to identify markers that are predictive of the likelihood of evolving to a more severe disease course.Method/DesignThis is a prospective multi-centre observational study aiming to enrol 7–8000 participants aged ≥ 5 years presenting with a febrile illness consistent with dengue to outpatient health facilities in 8 countries across Asia and Latin America. Patients presenting within 72 h of fever onset who do not exhibit signs of severe disease are eligible for the study. A broad range of clinical and laboratory parameters are assessed daily for up to 6 days during the acute illness, and also at a follow up visit 1 week later.DiscussionData from this large cohort of patients, enrolled early with undifferentiated fever, will be used to develop a practical diagnostic algorithm and a robust clinical case definition for dengue. Additionally, among patients with confirmed dengue we aim to identify simple clinical and laboratory parameters associated with progression to a more severe disease course. We will also investigate early virological and serological correlates of severe disease, and examine genetic associations in this large heterogeneous cohort. In addition the results will be used to assess the new World Health Organization classification scheme for dengue in practice, and to update the guidelines for “Integrated Management of Childhood Illness” used in dengue-endemic countries.Trial registrationNCT01550016. Registration Date: March 7, 2012

Elevated levels of vascular endothelial growth factor in adults with severe dengue infection.

The immune pathogenesis of dengue involves antibody production, B cell and T cell response and various pro-inflammatory and anti-inflammatory cytokines. VEGF, a potent permeability enhancing cytokine, is thought to play a pivotal role in mediating plasma leakage in DHF. It is a member of growing family of related proteins that includes VEGF B, VEGF C, VEGF D and placental growth factor. It promotes angiogenesis and vascular integrity. In addition to its role in promoting endothelial permeability & proliferation, it may contribute to inflammation and coagulation. This study was undertaken to investigate the role of VEGF in the patients with dengue infection. Sera were collected from 106 patients with various grades of dengue illness and 40 healthy controls and tested for VEGF levels using commercial ELISA kits. Viral serotypes were detected using specific primers. The results showed very low levels of VEGF (3.493±1.982pg/ml) in healthy controls. Levels of VEGF were higher in patients with severe dengue (428.170±224.61pg/ml) as compared to patients with non severe dengue with and without warning signs (290.407±167.17pg/ml). Significant correlation (p<0.001) was found between raised VEGF levels and thrombocytopenia and raised haematocrit levels. The VEGF profile patterns discovered between the different phases of illness indicate an essential role in dengue pathogenesis and with further studies may serve as predictive markers for progression of dengue fever to severe dengue infection.

Characterization of two anti-dengue human monoclonal antibodies prepared from PBMCs of patients with dengue illness in Thailand.

The global spread of the four dengue virus (DENV) serotypes (dengue-1 to -4) has made this virus a major and growing public health concern. Generally, pre-existing neutralizing antibodies derived from primary infection play a significant role in protecting against subsequent infection with the same serotype. By contrast, these pre-existing antibodies are believed to mediate a non-protective response to subsequent heterotypic DENV infections, leading to the onset of dengue illness. In this study, two monoclonal antibodies prepared by using peripheral blood mononuclear cells (PBMCs) from patients with dengue fever were characterized. Epitope mapping revealed that amino acid residues 254-278 in domain II of the viral envelope protein E were the target region of these antibodies. A database search revealed that certain sequences in this epitope region showed high conservation among the four serotypes of DENV. These two human monoclonal antibodies could neutralize DENV-2,-4 more effectively than DENV-1,-3. The amino acid sequences could not explain this difference in neutralizing activity. However, the 3D structure results showed that amino acid 274 could be the critical residue for the difference in neutralization. These results may provide basic information for the development of a dengue vaccine.

Dengue Outbreak in Martin County, Florida in 2013

Following a 2013 outbreak of dengue serotype 1 in Martin County, Florida, plasma samples from individuals with suspected dengue illness were tested for serotypespecific neutralization of dengue viruses 1-4. Titers and seroprevalence in these suspected cases from Florida were compared to those from (1) healthy donors from the U.S. and (2) dengue-suspected and dengue-confirmed samples collected from dengue-endemic regions during outbreaks in Puerto Rico in 2010 and Brazil in 2014. By dengue plaque reduction neutralization titer assays, we confirmed that four of the nine suspected individuals from Martin County Florida had been exposed to dengue virus serotype 1, and that these were primary dengue viral infections. Furthermore, primary and secondary dengue viral infections were observed in the Brazilian cohort, and a high incidence of secondary infections was observed in the Puerto Rican samples. Routine serotype-specific surveillance may be needed to continue monitoring establishment of dengue serotype 1 and

Health Seeking Behaviour and Treatment Intentions of Dengue and Fever: A Household Survey of Children and Adults in Venezuela.

BackgroundDengue in Venezuela is a major public health problem with an increasing incidence of severe cases. Early diagnosis and timely treatment influences the outcome of dengue illness, as delay in care-seeking is significantly associated with complications leading to severe dengue. We aimed to understand patterns of health seeking behaviour (HSB) in individuals exposed to high dengue incidence in order to improve early attendance to health centres.MethodsBetween September 2013 and February 2014 a cross-sectional household survey was performed in Maracay, Venezuela. Intended HSB of adults and children’s parents/guardians was assessed with respect to fever or suspected dengue. Data was collected through structured questionnaires from 105 individuals.ResultsMost individuals felt at risk of dengue and believed it could be a deadly disease. In the case of suspected dengue, the majority (60%) would choose to first seek medical help versus first treating at home, in contrast to 11% in the case of fever. Amongst those who decided to visit a doctor, a suspected dengue infection would prompt them to search medical help earlier than if having only fever (p<0.001). Multivariate analysis modelling showed that the independent factors associated with the intention to firstly visit a doctor versus treating at home in the case of dengue were feeling at risk (OR = 3.29; p = 0.042) and being an adult (as opposed to caring for a child as a parent/guardian; OR = 3.33, p = 0.021), while having had a previous dengue infection (OR = 0.29; p = 0.031) and living in the neighbourhood Caña de Azúcar (OR = 0.28, p = 0.038) were negatively associated with seeking medical care as their first action.ConclusionKnowledge of HSB related to dengue is scarce in the Americas, our study attempts to contribute to a better understanding of HSB in this region. Improving early dengue disease recognition and awareness may enhance prompt attendance to medical care in affected populations and thereby reduce mortality and severity of dengue. Especially for those with a previous dengue infection, efforts have to be made to promote prompt health centre attendance.

Dengue Infection: Challenges and Way Forward.

Dengue is the commonest mosquito-borne viral infection with nearly half of the world population at risk. There is a significant difference between the reported and estimated number of cases of dengue infection indicating under-reporting of dengue infections. In the year 2010, a total of 2.4 million episodes of dengue illnesses were reported by the member states to the World Health Organization [1]; while Bhatt et al. estimated that there are nearly 390million dengue infections annually, of which 96 million manifest clinically [2]. In India, dengue is endemic and has been reported from almost all parts of the country. All 4 serotypes of dengue virus have been reported from India. Most regions of India have an environment that is optimal for the mosquito to breed, placing a huge population at risk of dengue. To complete its life cycle, Aedesmosquitos needs appropriate temperature and humidity. A recently published meta-analysis suggests association of mean temperature between 23.2–27.7 °C and incidence of dengue fever. The odds ratio (OR) of incidence of dengue fever has been reported to increase steeply from 22 °C to 29 °C [3]. Every year there are reports of outbreaks from different parts of the country and there is always a debate about the exact number of cases with a conflict between the numbers reported by the health agencies and the lay press. Though dengue is reportable disease in some states, the processes of collecting data on dengue cases are not standardized. The issue of under-reporting of dengue cases in the country has also been highlighted [4]. Delhi had an out break of dengue infection this year. Though no official data regarding total number of cases and deaths due to dengue in this season are available in public domain, lay press reports more than 12 thousand affected and 32 deaths till now (http://indianexpress.com/ article/cities/delhi/dengue-in-delhi-over-12000-affected-so-fardeath-toll-rises-to-32/). The government is trying to control dengue infection by enhancing vector control, creating more beds in all government and private hospitals and providing free diagnostic investigations for dengue infection in selected health care facilties. Dengue infection has been occurring for decades and initially was associated with morbidity but no significant mortality. However, since 1950s it is associated with significant morbidity and mortality including hemorrhagic manifestations and shock. The reasons for change in manifestations are not clear. Two hypotheses have been suggested to explain the pathogenesis of severe disease. First hypothesis suggests that second infection with different serotype may get enhanced due to the presence of non-neutralizing antibodies generated after the first infection. Alternative hypothesis include enhanced virulence of the viruses due to frequent transmission of infection [5]. Recently, research has been focused on the response of different components of the immune system to dengue infection. From the earlier focus on humoral immunity, new insights have been obtained for the cellular immune response [6]. Two recently published articles based on in vitro and animal studies suggest a potential role of dengue virus non-structural protein (NS1) in enhanced endothelial permeability and vascular leak [7, 8]. Modhiran et al. also showed that NS1 induced vascular leak was inhibited by antiTLR4 antibody treatment in mouse model of dengue [7], while Beatty et al. reported that the vascular leak could be blocked by anti NS1-immune polyclonal mouse serum or monoclonal antibodies to NS1 [8]. In the same study, authors demonstrated that immunization of mice with NS1 from * Rakesh Lodha rakesh_lodha@hotmail.com

Mouse models of dengue virus infection for vaccine testing

Dengue is a mosquito-borne disease caused by four serologically and genetically related viruses termed DENV-1 to DENV-4. With an annual global burden of approximately 390 million infections occurring in the tropics and subtropics worldwide, an effective vaccine to combat dengue is urgently needed. Historically, a major impediment to dengue research has been development of a suitable small animal infection model that mimics the features of human illness in the absence of neurologic disease that was the hallmark of earlier mouse models. Recent advances in immunocompromised murine infection models have resulted in development of lethal DENV-2, DENV-3 and DENV-4 models in AG129 mice that are deficient in both the interferon-α/β receptor (IFN-α/β R) and the interferon-γ receptor (IFN-γR). These models mimic many hallmark features of dengue disease in humans, such as viremia, thrombocytopenia, vascular leakage, and cytokine storm. Importantly AG129 mice develop lethal, acute, disseminated infection with systemic viral loads, which is characteristic of typical dengue illness. Infected AG129 mice generate an antibody response to DENV, and antibody-dependent enhancement (ADE) models have been established by both passive and maternal transfer of DENV-immune sera. Several steps have been taken to refine DENV mouse models. Viruses generated by peripheral in vivo passages incur substitutions that provide a virulent phenotype using smaller inocula. Because IFN signaling has a major role in immunity to DENV, mice that generate a cellular immune response are desired, but striking the balance between susceptibility to DENV and intact immunity is complicated. Great strides have been made using single-deficient IFN-α/βR mice for DENV-2 infection, and conditional knockdowns may offer additional approaches to provide a panoramic view that includes viral virulence and host immunity. Ultimately, the DENV AG129 mouse models result in reproducible lethality and offer multiple disease parameters to evaluate protection by candidate vaccines.

An epidemiological study of dengue in Delhi, India

Delhi, the capital of India, is an important metropolitan hub for major financial and sociocultural exchanges, offering challenging threats to current public health infrastructure. In recent past, an upsurge of dengue cases in Delhi posed a significant menace to the existing dengue control policies. To reform the control strategies and take timely intervention to prevent future epidemics, an epidemiological study on the proportion of both asymptomatic and symptomatic dengue infections in selected population was conducted. The aim of the study was to investigate and assess the epidemiology of dengue infection and to estimate the proportion of asymptomatic and symptomatic dengue infections in Delhi. In this study, around 50 confirmed dengue cases, a total of 2125 individuals as household and neighbourhood contacts, with or without dengue febrile illness, were finger pricked and serologically detected as dengue positive or negative using SD Duo Bioline Rapid Diagnostic Test (SD Inc, Korea) with NS1, IgM & IgG combo test, which detected dengue virus antigen and antibodies to dengue virus in human blood. Out of 2125 individuals, 768 (36.1%) individuals showed positive dengue test with past (25.5%), primary (1.88%) or secondary (8.8%) dengue infections. Higher percentage of IgG was found in age groups 15–24 years and 25–50 years (36% each). Infants (<1 year) presented higher incidence of new infections (22% of NS1+IgM positives) as compared to adults. Further analysis revealed that out of the 226 newly infected cases (including NS1 and IgM positives), 142 (63%) were asymptomatic and 84 (37%) were symptomatic, as per WHO guidelines. Our findings also suggest that out of the total population screened, 10.6% dengue infection was either primary or secondary. On the basis of these results, it may be hypothesized that there are large number of asymptomatic dengue infections in the community as compared to reported symptomatic cases in Delhi. For the effective control of dengue transmission in such community like Delhi where dengue epidemics have frequently been encountered, it is essential to ascertain the proportion of asymptomatic dengue infections which may act as a reservoir for dengue transmission, as well as threat for developing dengue haemorrhagic fever (DHF).

Cost of Dengue Vector Control Activities in Malaysia.

Dengue fever, an arbovirus disease transmitted by Aedes mosquitoes, has recently spread rapidly, especially in the tropical countries of the Americas and Asia-Pacific regions. It is endemic in Malaysia, with an annual average of 37,937 reported dengue cases from 2007 to 2012. This study measured the overall economic impact of dengue in Malaysia, and estimated the costs of dengue prevention. In 2010, Malaysia spent US$73.5 million or 0.03% of the country's GDP on its National Dengue Vector Control Program. This spending represented US$1,591 per reported dengue case and US$2.68 per capita population. Most (92.2%) of this spending occurred in districts, primarily for fogging. A previous paper estimated the annual cost of dengue illness in the country at US$102.2 million. Thus, the inclusion of preventive activities increases the substantial estimated cost of dengue to US$175.7 million, or 72% above illness costs alone. If innovative technologies for dengue vector control prove efficacious, and a dengue vaccine was introduced, substantial existing spending could be rechanneled to fund them.

Serum levels of IFN-β are associated with days of evolution but not with severity of dengue.

The serum levels of beta interferon (IFN-β) were evaluated in clinical samples taken in the acute phase of dengue fever for 107 patients during the 2011 dengue outbreak in Yucatán, México. Dengue diagnoses were confirmed by NS1 or IgM/IgG serology in all patients. Average serum IFN-β levels in patients with dengue fever without warning signs (n = 53) were 140 pg/ml, and 105 pg/ml for patients with warning signs (n = 54). There was no statistically significant difference between IFN-β levels for the two groups (Mann-Whitney U Test P > 0.05) and no association with warning or mild signs (OR: 0.57; 95%CI: 0.26-1.22) was indicated. Thrombocytopenia was the most prevalent warning sign (91%) in one group of patients (49) with mean 113 pg/ml IFN-β levels. In contrast, the patients without thrombocytopenia (50) had 126 pg/ml of IFN-β, but this level was not statistically significant (Mann-Whitney U Test P > 0.05). The average levels of IFN-β were also found to have statistically similar results, using the 1997 WHO classification system. The amount of IFN-β at 1-3, 4-6, and 7-9 days after onset of illness, however, did show significant differences (ANOVA P = 0.038) between patients for the 1-3 and 4-6 days pair (Scheffe post-hoc P = 0.043). These results suggest that serum levels of IFN-β do not correlate well with the severity of dengue illness, but there is a clear association between changes in IFN-β levels and the days of evolution during the acute phase of the disease.

Association of FcγRIIa Polymorphism with Clinical Outcome of Dengue Infection: First Insight from Pakistan.

Dengue illness has been a major health concern in Pakistan during the last decade. Dengue infection can result in a spectrum of clinically distinct outcomes, ranging from asymptomatic infection to potentially life-threatening forms of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). A single-nucleotide polymorphism in FcγRIIa (rs1801274) results in altered affinity of the receptor for different subclasses of immunoglobulin G, and is a key player in determining the susceptibility to or protection from severe clinical infection of dengue. In this study, we analyzed the allelic and genotypic distribution of rs1801274 in subjects of Pakistani origin with subclinical dengue infection (n = 40), dengue fever (DF) (n = 40), and DHF/DSS (n = 30). We found that HH homozygotes and heterozygotes were significantly more likely to develop clinical dengue (odds ratio [OR] = 3.21, 95% confidence interval [CI] = 1.29-7.97, P = 0.009), either DF (OR = 2.82, 95% CI = 1.00-7.97, P = 0.045) or DHF/DSS (OR = 3.90, 95% CI = 1.13-13.07, P = 0.024) than the asymptomatic dengue infection. Results of allelic distribution comparisons and logistic regression analysis also supported the same relationship. The results suggest complex nature of interacting factors in determining the course for severe dengue illness.

Changing clinical profile of Dengue infection: A newer perspective in the pediatric population

Background: Traditionally complications of Dengue infection is limited to vascular and haematological system. The present study describes the changing clinico-epidemiological and laboratory profile of children hospitalized with dengue infec- tion. Methods: Prospective observational study of children hospitalized with a diagnosis of dengue illness from October to December, 2010 at a tertiary care centre in Kolkata. Results: Of 50 children admitted with dengue infection, 24 had dengue fever (DF), 18 dengue hemorrhagic fever (DHF) and 8 had dengue shock syndrome (DSS). The mean age of affected children was 6.25 ± 3.34 years, mostly being males from rural areas. The common clinical manifestations were fever, rash, body ache, hemorrhagic manifestations and oedema. While headache and body ache was commoner among DF cases, rash and hemorrhagic manifesta- tions were significantly more among DHF group. Incidence of altered sensorium, neck rigidity, fulminant hepatitis, and sple- nomegaly were significantly higher among the DHF/DSS group. 12% case fatality rate was found. Conclusion: Clinical mani- festations of dengue seem to be changing. Fever, rash and bodyache are not the only clinical presentations. Encephalopathy, encephalitis, 6 th cranial nerve palsy, fulminant hepatic failure, acute acalculous cholecystitis, myocarditis, myelitis, spleno- megaly are some unusual but novel presentations of dengue in pediatric population that clinician in endemic area should be aware of though they are not mentioned in conventional guidelines Dengue is no longer restricted to urban areas but has propensity to spread to rural areas also.

Economic Burden of Dengue Virus Infection at the Household Level Among Residents of Puerto Maldonado, Peru.

Dengue virus (DENV) was reintroduced to Peru in the 1990s and has been reported in Puerto Maldonado (population ~65,000) in the Peruvian southern Amazon basin since 2000. This region also has the highest human migration rate in the country, mainly from areas not endemic for DENV. The objective of this study was to assess the proportion of household income that is diverted to costs incurred because of dengue illness and to compare these expenses between recent migrants (RMs) and long-term residents (LTRs). We administered a standardized questionnaire to persons diagnosed with dengue illness at Hospital Santa Rosa in Puerto Maldonado from December 2012 to March 2013. We compared direct and indirect medical costs between RMs and LTRs. A total of 80 participants completed the survey, of whom 28 (35%) were RMs and 52 (65%) were LTRs. Each dengue illness episode cost the household an average of US$105 (standard deviation [SD] = 107), representing 24% of their monthly income. Indirect costs were the greatest expense (US$56, SD = 87), especially lost wages. The proportion of household income diverted to dengue illness did not differ significantly between RM and LTR households. The study highlights the significant financial burden incurred by households when a family member suffers dengue illness.

Evidence based community mobilization for dengue prevention in Nicaragua and Mexico (Camino Verde, the Green Way): cluster randomized controlled trial

Objective To test whether community mobilization adds effectiveness to conventional dengue control.Design Pragmatic open label parallel group cluster randomized controlled trial. Those assessing the outcomes and analyzing the data were...

Spleen Tyrosine Kinase (Syk) Mediates IL-1β Induction by Primary Human Monocytes during Antibody-enhanced Dengue Virus Infection

Approximately 500,000 people are hospitalized with severe dengue illness annually. Antibody-dependent enhancement (ADE) of dengue virus (DENV) infection is believed to contribute to the pathogenic cytokine storm described in severe dengue patients, but the precise signaling pathways contributing to elevated cytokine production are not elucidated. IL-1β is a potent inflammatory cytokine that is frequently elevated during severe dengue, and the unique dual regulation of IL-1β provides an informative model to study ADE-induced cytokines. This work utilizes patient-derived anti-DENV mAbs and primary human monocytes to study ADE-induced IL-1β and other cytokines. ADE of DENV serotype 2 (DENV-2) elevates mature IL-1β secretion by monocytes independent of DENV replication by 4 h postinoculation (hpi). Prior to this, DENV immune complexes activate spleen tyrosine kinase (Syk) within 1 hpi. Syk induces elevated IL1B, TNF, and IL6 mRNA by 2 hpi. Syk mediates elevated IL-1β secretion by activating ERK1/2, and both Syk and ERK1/2 inhibitors ablated ADE-induced IL-1β secretion. Maturation of pro-IL-1β during ADE requires caspase-1 and NLRP3, but caspase-1 is suboptimally increased by ADE and can be significantly enhanced by a typical inflammasome agonist, ATP. Importantly, this inflammatory Syk-ERK signaling axis requires DENV immune complexes, because DENV-2 in the presence of serotype-matched anti-DENV-2 mAb, but not anti-DENV-1 mAb, activates Syk, ERK, and IL-1β secretion. This study provides evidence that DENV-2 immune complexes activate Syk to mediate elevated expression of inflammatory cytokines. Syk and ERK may serve as new therapeutic targets for interfering with ADE-induced cytokine expression during severe dengue.

Clinical profile of dengue infection in a tertiary care hospital

Background: Dengue is a major international health concern that is prevalent in tropical and sub-tropical countries. The total burden of febrile illnesses that presents to primary health facilities due to dengue in different parts of Karnataka is largely unknown. Objective: The objective was to study the different clinical manifestations, trend, and outcome of dengue cases admitted in a tertiary care hospital. Materialsand Methods: Prospective study conducted over a period of 6 months (July-December 2013) in a tertiary care hospital at Bangalore. Dengue serology was done for all suspected subjects by enzyme-linked immunosorbent assay method. Detailed clinical and demographic details were taken at admission and serial close monitoring for signs and symptoms was done to watch for the progression of the disease. Results: Of the 100 children admitted with probable dengue fever, 57 had confirmed dengue illness. Of these 57 cases, most of the cases were male, and 34 (60%)cases were in age group of 5 months to 15 years with mean age of 7.5±4.7 years. Among the serology confirmed cases, the most common presentation was fever in 57 (100%), followed by abdominal pain in 37 (65%), rashes in 31 (54%), myalgia in 26 (46%), and vomiting in 23 (40%) cases. The most common hemorrhagic manifestation was cutaneous bleeding manifestations like petechiae. Of 57 cases, 46 patients had dengue with no warning signs, 8 had dengue fever with warning signs, and 3 had severe dengue. Conclusion: Clinical manifestations of dengue seem to be changing. Fever, rash, and body ache are still the common manifestations; however, clinicians in the endemic areas should be aware of unusual and novel presentations such as fulminant hepatic failure, splenomegaly, and myocarditis also.

Serum levels of IL-8, IFNγ, IL-10, and TGF β and their gene expression levels in severe and non-severe cases of dengue virus infection

Increased serum and mRNA levels of cytokines in patients with dengue virus (DV) infection suggest that cytokines are one of the key factors in the pathogenesis of disease caused by this virus. Here, we tested 211 serum and 56 mRNA samples from an equal number of dengue cases to determine the levels of interleukin-8 (IL-8), interferon gamma (IFN-γ), interleukin-10 (IL-10) and transforming growth factor beta (TGF-β). A total 70 serum and 15 mRNA samples from healthy individual were also tested for cytokines and served as controls. Serum and mRNA levels of IL-8 were highest in the earlier days of dengue infection. IFNγ levels peaked one or two days before defervescence. Levels of IL-10 and TGF-β were highest later in dengue infection, and TGF-β levels peaked on the day of defervescence. Mean levels of IFNγ, TGF β and IL-10 were higher in samples from dengue cases, irrespective of severity, than in healthy controls. In contrast, the level of IL-8 was significantly higher in samples from severe dengue cases and lower in cases of dengue without warning signs than in healthy controls. Children (82.2 % of 101 paediatric cases) commonly had severe dengue illness. Samples that were positive for anti-DV IgG antibody had higher levels of IL-8 and TGF β. DV-2 infections were associated with severe dengue illness. IL-8 and IFNγ levels were higher in the presence of warning signs of severe dengue. Levels of IL-8, IL-10 and TGF β were independently associated with disease outcome. These data provide evidence of an association of IL-8, IFNγ, TGF β and IL-10 levels with the severity of dengue illness. Especially, IL-8 levels can be used as a predictor of severe DV infection.

HLA Class I Supertype Associations With Clinical Outcome of Secondary Dengue Virus Infections in Ethnic Thais.

Human leukocyte antigen (HLA) supertypes are groups of functionally related alleles that present structurally similar antigens to the immune system. To analyze HLA class I supertype associations with clinical outcome in hospitalized Thai children with acute dengue illness. Seven hundred sixty-two patients and population-matched controls recruited predominantly in Bangkok were HLA-A and -B typed. HLA supertype frequencies were compared and tested for significant dengue disease associations using logistic regression analyses. Multivariable models were built by conducting forward stepwise selection procedures. In the final logistic regression model, the HLA-B44 supertype was protective against dengue hemorrhagic fever (DHF) in secondary infections (odds ratio [OR] = 0.46, 95% confidence interval [CI], .30-.72), while the HLA-A02 supertype (OR = 1.92, 95% CI, 1.30-2.83) and the HLA-A01/03 supertype (OR = 3.01, 95% CI, 1.01-8.92) were associated with susceptibility to secondary dengue fever. The B07 supertype was associated with susceptibility to secondary DHF in the univariate analysis (OR = 1.60, 95% CI, 1.05-2.46), whereas that was not retained in the final model. As the HLA-B44 supertype is predicted to target conserved epitopes in dengue, our results suggest that B44 supertype-restricted immune responses to highly conserved regions of the dengue proteome may protect against secondary DHF.

Protective immune responses to dengue virus infection and vaccines: perspectives from the field to the bench.

Protective immune responses to dengue virus infection and vaccines: perspectives from the field to the bench.

English

The performance of a commercial rapid immunochromatographic dengue NS1, IgG/IgM assay device was evaluated against an in-place dengue IgM-capture ELISA in the KPC Medical College & Hospital, Jadavpur. Of the 932 serum samples from patients with clinical diagnosis of acute dengue illness, 542, 237 and 90 samples were tested positive respectively for NS1 ELISA, anti-dengue IgM (MAC ELISA) and anti-dengue IgG ELISA. Comparatively, 476, 205 and 79 samples were tested positive respectively by the immunochromatographic method, has less sensitivity of 13% and a relative specificity of 12% compared to the ELISA method. Though the rapid immunochromato graphic assay device has the advantages of rapid testing which simultaneously detects both IgG and IgM and can also be performed with whole blood, serum or plasma, the user has to exercise extreme caution with the interpretation of the test result.