Biomedical subjects

Siripen Kalayanarooj

Publications and source records attributed to Siripen Kalayanarooj.

At least 19 recordsLinked to original sources

PubMed2006

Virus-induced decline in soluble vascular endothelial growth receptor 2 is associated with plasma leakage in dengue hemorrhagic Fever.

Some individuals infected with dengue virus develop dengue hemorrhagic fever (DHF), a viral hemorrhagic disease characterized by a transient period of localized plasma leakage. To determine the importance of vascular endothelial growth factor A (VEGF-A) in this syndrome, we compared plasma levels of VEGF-A and the soluble forms of its receptors in patients with DHF to patients with dengue fever (DF), a milder form of dengue virus infection without plasma leakage. We observed a rise in the plasma levels of free, but not total VEGF-A in DHF patients at the time of plasma leakage. This was associated with a decline in the soluble form of VEGF receptor 2 (VEGFR2) and VEGF-soluble VEGFR2 complexes, but not the soluble form of VEGFR1. The severity of plasma leakage in patients inversely correlated with plasma levels of soluble VEGFR2. In vitro, dengue virus suppressed soluble VEGFR2 production by endothelial cells but up-regulated surface VEGFR2 expression and promoted response to VEGF stimulation. In vivo, plasma viral load correlated with the degree of decline in plasma soluble VEGFR2. These results suggest that VEGF regulates vascular permeability and its activity is controlled by binding to soluble VEGFR2. Dengue virus-induced changes in surface and soluble VEGFR2 expression may be an important mechanism of plasma leakage in DHF.

Capillary Permeability↗

PubMed2006

Cellular immune activation in children with acute dengue virus infections is modulated by apoptosis.

Apoptosis is an important modulator of cellular immune responses during systemic viral infections. Peripheral-blood mononuclear cell (PBMC) apoptosis and plasma soluble levels of CD95, a mediator of apoptosis, were determined in sequential samples from children participating in a prospective study of dengue virus (DV) infections. During the period of defervescence, levels of PBMC apoptosis were higher in children developing dengue hemorrhagic fever (DHF), the most severe form of illness, than in those with dengue fever (DF) and other, nondengue, febrile illnesses. CD8(+) T lymphocytes made up approximately half of the peak circulating apoptotic PBMCs in DHF and DF. Maximum plasma levels of soluble CD95 were also higher in children with DHF than in those with DF. The level of PBMC apoptosis correlated with dengue disease severity. Apoptosis appears to be involved in modulation of the innate and adaptive immune responses to DV infection and is likely involved in the evolution of immune responses in other viral hemorrhagic fevers.

Adolescent↗

PubMed2006

Structure and age of genetic diversity of dengue virus type 2 in Thailand.

Dengue virus type 2 (DENV-2) is a common viral infection and an important health concern in South-East Asia. To determine the molecular evolution of DENV-2 in Thailand, 105 isolates of the E (envelope) gene and 10 complete genomes sampled over a 27 year period were sequenced. Phylogenetic analysis of these data revealed that three genotypes of DENV-2 have circulated in Thailand, although, since 1991, only viruses assigned to Asian genotype I have been sampled from the population. A broader analysis of 35 complete genomes of DENV-2 revealed that most amino acids are subject to strong selective constraints, indicative of widespread purifying selection against deleterious mutations. This was further supported by an analysis of genome-wide substitution rates, which indicated that DENV-2 fixes approximately 10 mutations per genome per year, far lower than expected from its mutational dynamics. Finally, estimates of the age of DENV-2 were remarkably consistent among genes, indicating that the current genetic diversity in this virus probably arose within the last 120 years, concordant with the first determination of the aetiology of dengue disease.

Adolescent↗

PubMed2006

Comparative analysis reveals no consistent association between the secondary structure of the 3'-untranslated region of dengue viruses and disease syndrome.

A comparative analysis was performed of the 3'-untranslated region (UTR) of Dengue virus (DENV) sampled from Bangkok, Thailand, over a 30 year period and representing all four serotypes. Considerable genetic variation was observed both within and among serotypes. Notably, a full-length version of the critical 3'-long stable hairpin structure was absent from some isolates, suggesting the occurrence of complex structural interactions within the 3'-UTR, including the influence of upstream mutations. The Thai sequences were then combined with 61 globally sampled isolates of DENV taken from patients with either dengue fever or severe dengue disease. No consistent association was found between 3'-UTR secondary structure and the clinical outcome of DENV infection, although some evidence for a trend in this direction was observed in DENV-2. It was concluded that the 3'-UTR is not the sole determinant of DENV virulence in nature, although variation in secondary structure may greatly influence viral fitness.

3' Untranslated Regions↗

PubMed2006

Relationship between body size and severity of dengue hemorrhagic fever among children aged 0-14 years.

A hospital based case-control study was conducted from October 2002 to November 2003 among children aged 0-14 years at Queen Sirikit National Institute of Child Health (Children's Hospital), Bangkok, Thailand. This study focused on body size and severity of dengue hemorrhagic fever (DHF) in children. One hundred five patients diagnosed as having DHF grade III or IV were the cases and 105 diagnosed as having DHF grade I or II were controls. They were matched at a ratio of 1:1 by their gender and age (within 5 years). Normal growth charts were used to differentiate child body size into normal, thin and obese. Data were collected using face to face interviews with caregivers, questionnaires, laboratory and physical examination reports as research tools. Multiple logistic regression analysis revealed that only two variables were related to severity of DHF: obesity (OR = 3.00, 95 % CI = 1.20-7.48) and dengue virus type II (OR = 4.94, 95 % CI = 2.57-9.47), respectively. Other variables were childhood factors: duration of breast-feeding, education, and parity; caregivers factors: age, gender, marital status, education, occupation, family income, knowledge of DHF, antipyretic type, treatment before hospitalization, and duration of fever; environmental factors: history of DHF patients in house, house pattern, time from house to hospital, and residence; and etiological factors: type of infection and history of DHF among children. These factors showed no significant association (p > 0.05). This result can be utilized in a preventive and control program, particularly in more aggressive management of overweight children. Health personnel should continue to provide health education, particularly, signs and symptoms of shock, to the community and private sectors. Government and Non-Government Protective Projects in primary schools (5-9 years children) should be continued in the high risk groups.

Adolescent↗

PubMed2005

Clade replacements in dengue virus serotypes 1 and 3 are associated with changing serotype prevalence.

The evolution of dengue virus (DENV) is characterized by phylogenetic trees that have a strong temporal structure punctuated by dramatic changes in clade frequency. To determine the cause of these large-scale phylogenetic patterns, we examined the evolutionary history of DENV serotype 1 (DENV-1) and DENV-3 in Thailand, where gene sequence and epidemiological data are relatively abundant over a 30-year period. We found evidence for the turnover of viral clades in both serotypes, most notably in DENV-1, where a major clade replacement event took place in genotype I during the mid-1990s. Further, when this clade replacement event was placed in the context of changes in serotype prevalence in Thailand, a striking pattern emerged; an increase in DENV-1 clade diversity was associated with an increase in the abundance of this serotype and a concomitant decrease in DENV-4 prevalence, while clade replacement was associated with a decline in DENV-1 prevalence and a rise of DENV-4. We postulate that intraserotypic genetic diversification proceeds at times of relative serotype abundance and that replacement events can result from differential susceptibility to cross-reactive immune responses.

Dengue↗

PubMed2005

Is dengue severity related to nutritional status?

A retrospective review of dengue patients admitted to Queen Sirikit National Institute of Child Health (previously known as Children's Hospital) from 1995 to 1999 revealed 4,532 confirmed cases of dengue infection; 80.9% were dengue hemorrhagic fever (DHF) and 19.1% were dengue fever cases (DF). Among the DHF patients; 30.6% had shock. The majority of them, 66.6%, had a normal nutritional status, while 9.3% were malnourished and 24.2% had obesity as classified by weight for age. Compared with control patients with other diagnoses (excluding HIV/AIDS patients), malnourished children had a lower risk of contracting dengue infection (odds ratio = 0.48, 95% Cl = 0.39-0.60, p = 0.000) while obese children had a greater risk of infection with dengue viruses (odds ratio = 1.96, 95% Cl = 1.55-2.5, p = 0.000). The clinical signs, symptoms and laboratory findings of dengue were almost the same among the 3 groups of malnourished, normal, and obese patients. The minor differences observed were that in obese children liver enlargement was found less often; maculopapular/convalescence rash and elevations of alanine aminotransferase were found more often. Malnourished patients had a higher risk of developing shock (37.8%) than normal (29.9%) and obese patients (30.2%) (p = 0.000). Obese patients had more unusual presentations: encephalopathy (1.3%) and associated infections (4.8%), than normal (0.5% and 2.7%) and malnourished patients (1.2% and 3.1%). Complications of fluid overload were found more in obese patients (6.5%) compared to normal (3.2%) and malnourished patients (2.1%) (p = 0.000). The case-fatality rates (CFR) in malnourished patients and obese patients were 0.5% and 0.4%, respectively, while in normal patients the CFR was 0.07%. Under and over nutrition DHF patients had either a greater risk of shock or unusual presentations and complications, which can lead to severe disease or complications and probably a higher CFR.

Child↗

PubMed2005

Genetic variations and relationship among dengue virus type 3 strains isolated from patients with mild or severe form of dengue disease in Indonesia and Thailand.

Sequence analysis was conducted on structural and non-structural genes of 7 strains of dengue virus type-3 (DENV-3 virus) isolated in Indonesia and Thailand in the year 1973, 1994, and 1998 from patients with different clinical manifestations. In general, sequence similarity among isolates was greater than 93%, indicating that the mutation rate of DENV-3 circulating in this region was not more than 7% in the last 3 decades and suggesting that sequences that may responsible for viral architectures and/or biological function were strictly conserved. Mutations unique to viral strains associated with specific clinical manifestations were not found. Alignment of PrM/M and E nucleic acid sequences followed by parsimony analysis of sequences obtained in this study and published elsewhere allowed generation of phylogenetic trees, demonstrating that DENV-3 strains isolated in Indonesia in 1998 belonged to a separate cluster (subtype 2) from those isolated between 1973-1985 (subtype 1).

Amino Acid Sequence↗

PubMed2004

Severity of measles: a study at the Queen Sirikit National Institute of Child Health.

INTRODUCTION: Thousands of measles cases are reported annually in Thailand even though measles vaccine has been introduced in the expanded program of immunization for every 9-month-old infant for nearly 20 years. Severe cases are admitted to the hospital, usually with complications, some cases lead to death. OBJECTIVES: To study the clinical presentations of severe cases of measles and its complications and find the correlations of severity of pneumonia with age, nutritional status and history of vaccination. MATERIAL AND METHOD: The hospital charts of measles patients admitted to the Queen Sirikit National Institute of Child Health (QSNICH) during 1998-2002 were retrospectively reviewed. Demographic data, history including history of measles vaccination, physical examinations, laboratory investigations, treatment and hospital course which were relevant were recorded. Paired t-test and Pearson's correlation were used for data analysis. RESULTS: There were 156 cases of measles admitted to the QSNICH. There were 95 boys and 61 girls and the male to female ratio was 1.56:1. The age range was 2 months to 14.8 years, median = 1.5 years, mode 8 months. Fifty-nine percent of the cases were under 2 years of age; 40% under one year and 23.9% were under 9 months. About 44% of the cases had one dose of previous measles vaccination, no history of measles vaccination in 91.4% of cases whose age was under 1 year in contrast to 80% of cases over 5 years that had a history of measles vaccination. Sixty-six percent of the cases had normal nutritional status while 12.4%, 4.8% and 2.1% had mild, moderate and severe protein calorie malnutrition. Fourteen cases (9%) had underlying diseases. At least 3 of the classical signs and symptoms of measles (rash, cough and coryza) were found in 92.3% of the cases. The mean duration of fever at the time of admission was 5.3 days. The common complications in admitted measles cases were pneumonia (62.2%) and diarrhea (38.1%). The likely causes of pneumonitis were measles viruses (52.6%) and bacteria (47.4%). There was one dead case with severe pneumonia, with ARDS and respiratory failure. Young infants had a higher incidence of diarrhea with dehydration (p = 0.000) but severity of pneumonia was not different from older children (p = 0.512). The severity of pneumonia was not correlated with the age (r = 0.087), nutritional status (r = 0122) or the history of receiving measles vaccine (r = 0.116). CONCLUSION: Measles is one of the important diseases of in-patients admitted to the QSNICH, because of the severity of the diseases due to pneumonia and diarrhea. One severe case died because of severe pneumonia that lead to ARDS and respiratory failure. Young infants had a higher incidence of diarrhea and dehydration, while there was no correlation between severe pneumonia with age, nutritional status and history of vaccination.

Adolescent↗

PubMed2003

A blunted blood plasmacytoid dendritic cell response to an acute systemic viral infection is associated with increased disease severity.

At least two distinct human dendritic cell (DC) subsets are produced in the bone marrow and circulate in the peripheral blood-precursor myeloid DCs (pre-mDCs) and plasmacytoid DCs (PDCs). Both lineages of DCs are instrumental in antiviral innate immunity and shaping Th1 adaptive immune responses. PDCs are the most potent IFN-alpha-producing cells to viral pathogens. Dengue, an acute flavivirus disease, provides a model to study DC responses to a self-limited human viral infection. We analyzed circulating DC subsets in a prospective study of children with dengue across a broad range of illness severities: healthy controls; mild, nondengue, presumed viral infections; moderately ill dengue fever; and, the most severe form of illness, dengue hemorrhagic fever. We also examined PDC responses in monkeys with asymptomatic dengue viremia and to dengue virus exposure in vitro. The absolute number and frequency of circulating pre-mDCs early in acute viral illness decreased as illness severity increased. Depressed pre-mDC blood levels appeared to be part of the typical innate immune response to acute viral infection. The frequency of circulating PDCs trended upward and the absolute number of circulating PDCs remained stable early in moderately ill children with dengue fever, mild other, nondengue, febrile illness, and monkeys with asymptomatic dengue viremia. However, there was an early decrease in circulating PDC levels in children who subsequently developed dengue hemorrhagic fever. A blunted blood PDC response to dengue virus infection was associated with higher viremia levels, and was part of an altered innate immune response and pathogenetic cascade leading to severe disease.

Acute Disease↗

PubMed2003

Serotype-specific dengue virus circulation and dengue disease in Bangkok, Thailand from 1973 to 1999.

Dengue virus circulation and association with epidemics and severe dengue disease were studied in hospitalized children with suspected dengue at the Queen Sirikit National Institute of Child Health in Bangkok, Thailand, from 1973 to 1999. Dengue serology was performed on all patients and viral isolation attempted on laboratory-confirmed patients. Acute dengue was diagnosed in 15,569 children and virus isolated from 4,846. DEN-3 was the most frequent serotype in primary dengue (49% of all isolates), DEN-2 in secondary and in dengue hemorrhagic fever (37% and 35%, respectively). The predominant dengue serotype varied by year: DEN-1 from 1990-92, DEN-2 from 1973-86 and 1988-89; DEN-3 in 1987 and 1995-99; and DEN-4 from 1993-94. Only DEN-3 was associated with severe outbreak years. Our findings illustrate the uniqueness of each serotype in producing epidemics and severe disease and underscore the importance of long-term surveillance of dengue serotypes in understanding the epidemiology of these viruses.

Adolescent↗

PubMed2003

Vertical transmission of dengue infection in Thai infants: two case reports.

Dengue infection is hyperendemic in tropical countries especially in Thailand. Most dengue infections occur during childhood but some adults may remain susceptible to infection. About 30 per cent of dengue infection are reported in patients > 15 years old. Some pregnant women may also be susceptible to dengue and if they experience dengue infection, they can transmit the dengue viruses to their babies. The authors report two babies who developed mild dengue illness, dengue hemorrhagic fever (DHF) grade II, beginning on their 6th day of life. Both of them had low grade fever, hepatomegaly and generalized petechial rash. The first baby had Hct ranging from 46 to 40 per cent with minimal right pleural effusion. The lowest platelet count was 19,000 cells/mm3. His mother had dengue shock syndrome with masssive post partum bleeding. The second baby had dengue 2 infection while his mother had dengue fever. His Hct had also risen from 52 per cent to 61 per cent with right pleural effusion. His lowest platelet count was 7,000 cells/mm3. Both mothers and their babies had a complete recovery although the first baby had prolonged thrombocytopenia for two months.

Adult↗

PubMed2003

Clinical presentations of dengue hemorrhagic fever in infants compared to children.

BACKGROUND: Dengue infections are endemic in Thailand. Infants are at risk of developing dengue fever (DF) and dengue hemorrhagic fever (DHF). Many infants have severe DHF with unusual manifestations and may suffer from complications and even death because of difficulties in early diagnosis and improper management. OBJECTIVE: To study the incidence of infants DHF and to compare clinical and laboratory findings of DHF between infants and children in order to improve diagnosis and management of infants with DHF. MATERIAL AND METHOD: A retrospective review of hospital charts of DHF patients who were admitted to the Children's Hospital between 1995-1999 was carried out. Only confirmed DHF cases, either by serologic or virologic studies were included. Clinical and laboratory findings were compared using the standard software package SPSS. RESULTS: There were 4,595 confirmed dengue patients admitted to the Children's Hospital during this 5-year period and among these 245 infants were under one year old (5.3%). Unusual presentations of DHF including upper respiratory tract infection (URI) symptoms, diarrhea, convulsions and encephalopathy were found more in the infants (4.5%, 13.1%, 12.7% and 4.1%) than in the children (1.7%, 2.0%, 2.0% and 0.6%) but shock was found less in the infants (25%) than in the children (30.9%). The percentages of Tourniquet test positive and low WBC (< or = 5,000 cells/mm3) which help in the early diagnosis of dengue were less in the infants (50.2% and 26.8%) than in the children (92.2% and 71.9%). Liver involvement and/or dysfunction were found more in the infants as shown by mean aspartate aminotransferase/alanine aminotransferase (AST/ALT) elevation and prolonged prothrombin time. Duration of i.v. fluid was shorter in the infants than in the children (21.9 vs 38.2 hours). Complications of fluid overload were found more often in the infants than in the children (9% vs 3.6%). The case fatality rate was 1.2 in the infants and 0.3 in the children. CONCLUSION: Management of infants with DHF is critical because early diagnosis is rather difficult and they sometimes present with unusual manifestations (convulsions, encephalopathy and associated infections). Complications such as hepatic dysfunction and fluid overload are more commonly found in infants than in children and adults and also the case fatality rate is higher. Judicious i.v. fluid resuscitation and replacement is critical to the outcome of infants with DHF. It seems that the degree of plasma leakage is less in infants and the duration of plasma leakage is shorter in infants than in children.

Adolescent↗

PubMed2003

Antibody response after measles immunization.

RATIONALE: Measles is still an important public health problem in Thailand despite measles vaccination being practiced since 1984. Vaccine failure is one of the suspected reasons for the high incidence of measles. OBJECTIVE: To study the seroconversion rate of 9-month-old infants and to study the antibody level in 18 month-old and 4 year-old children who had measles vaccination at 9 months of age. MATERIAL AND METHOD: Enrolled infants and children who attended the child health clinic for routine immunization at the Queen Sirikit National Institute of Child Health from March 1, 1994 to May 31, 1995. They were divided into 3 groups. Group A, 9 month-old infants who came for measles vaccination. Blood samples were drawn twice from these infants, before measles vaccination and 3 months later for measles antibody level. Group B and C were 18 month-old and 4-year-old children who came for their first and second DTP (Diphtheria, Tetanus, Pertussis vaccine) booster. One blood sample for measles antibody was drawn from the latter group of children. Measles antibody was determined by micro-neutralization technic at the National Institute of Health (NIH). The geometric mean antibody titer before and after measles vaccination was compared by using the paired t-test. RESULTS: There were 30, 31 and 34 infants/children in group A, B and C respectively. No significant measles antibody (NT antibody was less than 1:4) was detected in 93.5 per cent of 9-month-old infants. The seroconversion rate at 3 months after vaccination in group A children was 68.75 per cent while in group B, 9 months after vaccination it was 53.3 per cent. Ninety seven per cent of children in group C had NT antibody above 1:4. The geometric mean titer (GMT) of measles antibody in 9-month (before vaccination), 12-month, 18-month infants and 4 year old children was 1:2.5; 1:14.8, 1:8.2 and 1:73.8, respectively (p < 0.05). CONCLUSION: Almost 70 per cent of vaccinees at 9 months of age had seroconversion to measles vaccine with GMT of 1:14.8 while fifty three per cent of 18 month old children had an average GMT of 1:8.2. The GMT of the two groups was significantly different (p < 0.05). At 4 years of age almost all the children had NT antibody to measles with a GMT of 1:73.8 (p < 0.05) Vaccine failure is likely to be one factor responsible for the high incidence of measles after the introduction of measles vaccine into the Expanded Program of Immunization (EPI). The authors suggest giving a booster dose of measles at 15 months of age to boost the antibody level before waning of measles antibody at 18 months old, in order to protect this group of children from contracting measles.

Antibodies, Viral↗

PubMed2002

High circulating levels of the dengue virus nonstructural protein NS1 early in dengue illness correlate with the development of dengue hemorrhagic fever.

Infection with any 1 of 4 dengue viruses produces a spectrum of clinical illness ranging from a mild undifferentiated febrile illness to dengue fever (DF) to dengue hemorrhagic fever (DHF), a potentially life-threatening disease. The morbidity and mortality of DHF can be reduced by early hospitalization and careful supportive care. To determine its usefulness as a predictor of DHF, plasma levels of the secreted dengue virus nonstructural protein NS1 (sNS1) were measured daily in 32 children with dengue-2 virus infections participating in a prospective, hospital-based study. Free sNS1 levels in plasma correlated with viremia levels and were higher in patients with DHF than in those with DF. An elevated free sNS1 level (> or =600 ng/mL) within 72 h of illness onset identified patients at risk for developing DHF.

Adolescent↗

PubMed2002

T cell responses to an HLA-B*07-restricted epitope on the dengue NS3 protein correlate with disease severity.

Dengue hemorrhagic fever (DHF), the severe manifestation of dengue virus (DV) infection characterized by plasma leakage, is more common in secondary DV infections in previously infected individuals and is associated with high levels of immune activation. To determine the Ag specificity of this immune response, we studied the response to an HLA-B*07-restricted T cell epitope, residues 221-232 of the DV NS3 protein, in 10 HLA-B*07(+) Thai children who were studied during and after acute DV infections. Peptide-specific T cells were detected in 9 of 10 subjects. The frequency of peptide-specific T cells was higher in subjects who had experienced DHF than in those who had experienced DF. We also detected peptide-specific T cells in PBMC obtained at the time of the acute DV infection in 2 of 5 subjects. These data suggest that the NS3 (221-232) epitope is an important target of CD8(+) T cells in secondary DV infection and that the activation and expansion of DV-specific T cells is greater in subjects with DHF than in those with dengue fever. These findings support the hypothesis that activation of DV-specific CD8(+) T cells plays an important role in the pathogenesis of DHF.

Adolescent↗

PubMed2002

Differing influences of virus burden and immune activation on disease severity in secondary dengue-3 virus infections.

Dengue hemorrhagic fever (DHF), the most severe form of illness following infection with a dengue virus, is characterized by plasma leakage, thrombocytopenia, and hepatic inflammation. The interrelationships among virus burden, immune activation, and development of DHF were examined in 54 children with secondary dengue-3 virus infections participating in a prospective, hospital-based study. DHF was associated with higher mean plasma viremia early in illness and earlier peak plasma interferon-gamma levels. Maximum plasma viremia levels correlated with the degree of plasma leakage and thrombocytopenia. Maximum plasma levels of interleukin (IL)-10 and soluble tumor necrosis factor receptor-II correlated with the degree of thrombocytopenia, independently of viremia levels. Hepatic transaminase elevation correlated with plasma soluble IL-2 receptor levels and not with viremia levels. Quantitative differences in virus burden and host immune responses, and the timing of type 1 cytokine responses, have differing influences on the severity of disease manifestations during secondary dengue-3 virus infections.

Antigens, CD↗

PubMed2002

Cytokine gene expression and protein production in peripheral blood mononuclear cells of children with acute dengue virus infections.

Plasma leakage in dengue hemorrhagic fever (DHF) is associated with elevated plasma levels of cytokines. To define further the contribution of immune activation to DHF and the source of cytokines, we analyzed the production of cytokines in peripheral blood mononuclear cells (PBMC) obtained from children with dengue, using RT-PCR and immunostaining. Tumor necrosis factor-alpha (TNF-alpha) and TNF-beta expression was detected in all samples by PCR and in < 50% of samples by immunostaining. Interferon-gamma (IFN-gamma) expression was detected in < 50% of samples by either method. Interleukin-2 (IL-2) and IL-4 expression was detected in a few samples by immunostaining but was not detectable by PCR. We found greater expression of TNF-alpha and IL-4 in DHF than in dengue fever or other (non-dengue) febrile illnesses. These results support the model of immunopathogenesis of DHF. However, low levels of cytokine expression in PBMC suggest that cellular activation in tissues may contribute to high serum cytokine levels in DHF.

Acute Disease↗