Showing papers on "Dengue fever published in 1999"

Dengue Virus Structural Differences That Correlate with Pathogenesis

Abstract: The understanding of dengue virus pathogenesis has been hampered by the lack of in vitro and in vivo models of disease. The study of viral factors involved in the production of severe dengue, dengue hemorrhagic fever (DHF), versus the more common dengue fever (DF), have been limited to indirect clinical and epidemiologic associations. In an effort to identify viral determinants of DHF, we have developed a method for comparing dengue type 2 genomes (reverse transcriptase PCR in six fragments) directly from patient plasma. Samples for comparison were selected from two previously described dengue type 2 genotypes which had been shown to be the cause of DF or DHF. When full genome sequences of 11 dengue viruses were analyzed, several structural differences were seen consistently between those associated with DF only and those with the potential to cause DHF: a total of six encoded amino acid charge differences were seen in the prM, E, NS4b, and NS5 genes, while sequence differences observed within the 5′ nontranslated region (NTR) and 3′ NTR were predicted to change RNA secondary structures. We hypothesize that the primary determinants of DHF reside in (i) amino acid 390 of the E protein, which purportedly alters virion binding to host cells; (ii) in the downstream loop (nucleotides 68 to 80) of the 5′ NTR, which may be involved in translation initiation; and (iii) in the upstream 300 nucleotides of the 3′ NTR, which may regulate viral replication via the formation of replicative intermediates. The significance of four amino acid differences in the nonstructural proteins NS4b and NS5, a presumed transport protein and the viral RNA polymerase, respectively, remains unknown. This new approach to the study of dengue virus genome differences should better reflect the true composition of viral RNA populations in the natural host and permit their association with pathogenesis.

Phylogenetic evidence for recombination in dengue virus.

Abstract: A split decomposition analysis of dengue (DEN) virus gene sequences revealed extensive networked evolution, indicative of recombination, among DEN-1 strains but not within serotypes DEN-2, DEN-3, or DEN-4. Within DEN-1, two viruses sampled from South America in the last 10 years were identified as recombinants. To map the breakpoints and test their statistical support, we developed a novel maximum likelihood method. In both recombinants, the breakpoints were found to be in similar positions, within the fusion peptide of the envelope protein, demonstrating that a single recombination event occurred prior to the divergence of these two strains. This is the first report of recombination in natural populations of dengue virus.

Early Immune Activation in Acute Dengue Illness Is Related to Development of Plasma Leakage and Disease Severity

Abstract: T lymphocyte activation and increased cytokine levels have been described in retrospective studies of children presenting with dengue hemorrhagic fever (DHF). Serial plasma samples obtained in a prospective study of Thai children presenting with <72 h of fever were studied. Plasma levels of 80-kDa soluble tumor necrosis factor receptors (sTNFRs) were higher in children who developed DHF than in those with dengue fever (DF) or other nondengue febrile illnesses (OFIs) and were correlated with the degree of subsequent plasma leakage. Soluble CD8 and soluble interleukin-2 receptor levels were also elevated in children with DHF compared with those with DF. Interferon-gamma and sTNFR 60-kDa levels were higher in children with dengue than in those with OFIs. TNF-alpha was detectable more often in DHF than in DF or OFIs (P<.05). These results support the hypothesis that immune activation contributes to the pathogenesis of DHF. Further studies evaluating the predictive value of sTNFR80 for DHF are warranted.

New Mouse Model for Dengue Virus Vaccine Testing

Abstract: Several dengue (DEN) virus vaccines are in development; however, the lack of a reliable small animal model in which to test them is a major obstacle. Because evidence suggests that interferon (IFN) is involved in the human anti-DEN virus response, we tested mice deficient in their IFN functions as potential models. Intraperitoneally administered mouse-adapted DEN 2 virus was uniformly lethal in AG129 mice (which lack alpha/beta IFN and gamma IFN receptor genes), regardless of age. Immunized mice were protected from virus challenge, and survival times increased following passive transfer of anti-DEN polyclonal antibody. These results demonstrate that AG129 mice are a promising small animal model for DEN virus vaccine trials.

Impact of Dengue/Dengue Hemorrhagic Fever on The Developing World

Abstract: Publisher Summary This chapter focuses on the changing epidemiology of Dengue/Dengue Hemorrhagic Fever (DEN/DHF), estimates the global growth in the number of cases of DEN/DHF from 1955 to 1996, and uses these incidence data to estimate the global economic impact of this disease. Epidemic DEN/DHF has emerged as a global public health problem in the tropics in the past 20 years. This has been caused by the expanding geographic distribution of both the viruses and the principal mosquito vectors as a result of global demographic and societal changes. During this period, most tropical urban centers of the world have become hyperendemic, thus increasing the risk of epidemic transmission and the emergence of DHF. Despite this dramatic emergence of a new hemorrhagic disease, few estimates of the economic impact of DEN/DHF have been attempted. The lack of estimates of the economic impact of endemic DEN/DHF is important, because such estimates are needed by policy planners to help allocate limited resources for research, prevention, and control activities. Different model for evaluating the effect of the impact of DEN/DHF is provided in this chapter.

Transmission dynamics and epidemiology of dengue: insights from age-stratified sero-prevalence surveys.

Abstract: The relationship between infection with the four major serotypes of dengue virus and the occurrence of different forms of disease is complex and not fully understood. Interpreting longitudinal records of the incidence of serious disease to gain insight into the transmission dynamics and epidemiology of the virus is therefore complicated. Since age reflects duration of exposure, age–stratified, strain–specific serological surveys carried out at one point in time, or over a short time interval, can potentially provide a rich source of information on longitudinal patterns. This paper describes the development and application (to data collected in Thailand) of statistically rigorous methods designed to estimate time–varying, strain–specific forces of infection, and thus basic reproduction numbers, from cross–sectional serological data. The analyses provide support for the hypothesis that antibody– dependent enhancement of transmission influences observed epidemiological pattern. Age–stratified serological data also reveal evidence of a propensity for the annual incidence of infection to oscillate over time with a frequency of several years. The latter observation is consistent with the predictions of simple mathematical models of the transmission dynamics of the virus. The estimates of the basic reproduction numbers obtained are similar in magnitude for each dengue serotype, being in the range of four to six. Such values are higher than those obtained from earlier analyses, and the implications of this for dengue control are discussed.

Early CD69 expression on peripheral blood lymphocytes from children with dengue hemorrhagic fever.

Abstract: Recent reports have demonstrated immune activation in dengue hemorrhagic fever (DHF) by cytokine and soluble receptor detection in blood. The goal of this study was to determine which cell types are activated and likely to be responsible for cytokine production. Whole blood specimens from 51 Thai children presenting within 72 h of fever onset and with detectable plasma dengue viral RNA were studied by flow cytometry. Absolute CD4 T cell, CD8 T cell, NK cell, and gd T cell counts were decreased in children with DHF compared with those with dengue fever (DF) early in the course of illness. The percent of cells expressing CD69 was increased on CD8 T cells and NK cells in children who developed DHF more than in those with DF. These data directly demonstrate that cellular immune activation is present early in acute dengue and is related to disease severity.

A prospective seroepidemiologic study on dengue in children four to nine years of age in Yogyakarta, Indonesia I. studies in 1995-1996.

Abstract: A prospective study on dengue (DEN) viruses was initiated in October 1995 in Gondokusuman kecamatan, Yogyakarta, Indonesia. This report presents data from the first year of the study. The studied cohort included all children 4-9 years of age living in the kecamatan. Blood samples for serology were collected from 1,837 children in October 1995 and again in October 1996. Blood samples for virus isolation and serology were collected from cohort children who were seen in municipal health clinics with febrile syndromes or admitted to hospitals with a provisional diagnosis of dengue hemorrhagic fever. Dengue serotype antibody prevalence and 1995-1996 infection rates were calculated using a single dilution (1:60) 70% plaque reduction endpoint neutralization test. Prevalence of dengue antibody at the beginning of the study was DEN 1 = 12%, DEN 2 = 16%, DEN 3 = 2%, DEN 4 = 4%, and two or more dengue infections = 22%. Total dengue antibody prevalence increased from 38% in 4-year-old children to 69% in 9-year-old children. During the observation period, primary dengue infection rates were DEN 1 = 4.8%, DEN 2 = 7.7%, DEN 3 = 4.2%, and DEN 4 = 3.4%, while two or more dengue infections occurred in 6.7% of the study population. The secondary dengue infection rate was 19.0%. From febrile cases, all four dengue viruses were isolated with DEN 3 predominating. Seven children were hospitalized, including one fatal case with a hospital diagnosis of dengue shock syndrome. Based upon presence of antibody in the initial cohort bleeding and the serologic response both weeks and several months following illness, all had secondary dengue infections. Neutralizing antibody patterns in the initial cohort bleeding and in late convalescent serum samples permitted recognition of dengue infection sequence in five patients: DEN 2-DEN 1 (3), DEN 2-DEN 4 (1), DEN 1-DEN 3 (1), and none in the sequence DEN 1-DEN 2. In the total cohort 6.5% of the observed secondary infections were of the sequence DEN 2-DEN 1, while 4.9% were DEN 1-DEN 2, a highly pathogenic sequence in previous studies. Reduced pathogenic expression of secondary DEN 2 with enhanced pathogenic expression of secondary DEN 1 infections was an unexpected finding. Further studies will be required to understand the respective contributions to pathogenicity of antibody from initial dengue infections versus the biological attributes of the second infecting dengue viruses.

El Niño and the dynamics of vectorborne disease transmission.

Abstract: The objective of the study was to investigate the relationship between reported incidence of dengue fever and El Nino southern oscillation (ENSO) in 14 island nations of the South Pacific. Using a mixed ecological study design, we calculated correlations between annual averages of the southern oscillation index (SOI), local temperature and rainfall, and dengue fever. We also calculated temporal correlations between monthly reports of dengue fever cases on different islands. There were positive correlations between SOI and dengue in 10 countries. In five of these (including all of the larger islands) there were also positive correlations between SOI and estimates of local temperature and/or rainfall. There were temporal correlations between monthly reports of dengue cases within two groups of countries. Climate changes associated with ENSO may trigger an increase in dengue fever transmission in larger, more populated islands where the disease is endemic. There was also evidence of propagation of infection from larger islands to smaller neighbors. Unlike the initiation of epidemics, this transfer between islands appears to be independent of interannual climate variations, pointing to the importance of modulating factors in dengue transmission such as population density and travel. In the future, models of the impact of climate change must attempt to account for these factors.

Detection of Dengue Virus RNA in Patients after Primary or Secondary Dengue Infection by Using the TaqMan Automated Amplification System

Abstract: In consecutive serum samples from 25 tourists with acute dengue fever, virus-specific RNA was detected by using fully automated TaqMan reverse transcriptase PCR. For this amplification technique new primers and special fluorochrome-labeled probes had to be synthesized. During amplification the increasing amount of viral DNA could simultaneously be measured in the tightly sealed tubes. Dengue virus RNA was found in almost all patients (17 of 18), if the samples had been taken soon after the onset of symptoms and before anti-dengue virus antibody had been produced. RNA was detectable in only one of five persons who had anti-dengue virus immunoglobulin M (IgM) antibodies but not yet IgG antibodies. In 30 late samples with both IgG and IgM antibodies viral RNA was no longer demonstrable. In two early samples from two frequent travelers obtained 1 and 2 days after the onset of symptoms significant IgG antibody titers were present but there were no anti-dengue virus IgM antibodies. In these samples a viral load of >5 x 10(6) dengue virus RNA copies (dengue types 1 and 2) was detectable. These findings of a high viral load in the presence of anti-dengue virus IgG antibody are suggestive of a secondary dengue virus infection. In the 20 tourists (17 plus 1 plus 2) in whom viral RNA was found, the dengue virus serotype could be related to the area where the infection had taken place. Most of our patients came from southeast Asia and most frequently had dengue virus type 1 infections (8 of 20).

Elevated plasma interleukin-10 levels in acute dengue correlate with disease severity.

Abstract: Dengue viruses, of which there are four serotypes,are the most important arthropod-borne viral infec-tions in the world, accounting for more than 250,000cases of dengue hemorrhagic fever (DHF) and 10,000deaths annually [Monath, 1994]. Infection with dengueviruses can yield different clinical syndromes, includ-ing (1) undifferentiated febrile illness, seen more com-monly in children; (2) dengue fever (DF), a flu-like syn-drome characterized by high fever, headache, retro-orbital pain, myalgias, abdominal pain, nausea, andvomiting; and (3) dengue hemorrhagic fever (DHF), aplasma leak syndrome that, in its most severe form,can be life-threatening [Nimmannitya, 1987].Plasma leakage is a major clinical feature of DHFand tends to occur around the time of defervescence.We have been interested in the events that precede theperiod of plasma leakage to better define its etiology.We have found that dengue virus-specific CD4

Rapid serologic diagnosis of dengue virus infection using a commercial capture ELISA that distinguishes primary and secondary infections.

Abstract: A commercial capture ELISA for specific IgM and IgG antibodies produced during dengue infection (PanBio Dengue Duo) showed excellent sensitivity (99%, n = 78) using sera collected at hospital discharge compared with established ELISA and hemagglutination inhibition (HAI) assays. Furthermore, the ELISA was able to diagnose 79% of the dengue cases using sera collected at hospital admission. The ELISA also showed high specificity (92%) in paired sera from patients without flavivirus infection (n = 26), although 45% of the patients with Japanese encephalitis (n = 20) showed elevation of IgG but not IgM. The IgG capture ELISA showed good correlation with the HAI assay (r = 0.83, P < 0.0001), and IgG levels could be used to distinguish between primary and secondary infection, with 100% of primary infections and 96% of secondary infections being correctly classified. This ELISA should prove useful in the clinical diagnosis of dengue infections.

The first major outbreak of dengue hemorrhagic fever in Delhi, India.

Abstract: India An outbreak of dengue hemorrhagic fever/dengue shock syndrome (DHS/DSS) occurred in 1996 in India in and near Delhi. The cause was confirmed as dengue virus type 2, by virus cultivation and indirect immunofluorescence with type-specific monoclonal antibodies. This is the largest such outbreak reported from India, indicating a serious resurgence of dengue virus infection.

Value of a Single-Tube Widal Test in Diagnosis of Typhoid Fever in Vietnam

Abstract: The diagnostic value of an acute-phase single-tube Widal test for suspected typhoid fever was evaluated with 2,000 Vietnamese patients admitted to an infectious disease referral hospital between 1993 and 1998. Test patients had suspected typhoid fever and a blood culture positive for Salmonella typhi (n= 1,400) or Salmonella paratyphi A (n = 45). Control patients had a febrile illness for which another cause was confirmed (malaria [n = 103], dengue [n = 76], or bacteremia due to another microorganism [n = 156] or tetanus (n = 265). An O-agglutinin titer of ≥100 was found in 18% of the febrile controls and 7% of the tetanus patients. Corresponding values for H agglutinins were 8 and 1%, respectively. The O-agglutinin titer was ≥100 in 83% of the blood culture-positive typhoid fever cases, and the H-agglutinin titer was ≥100 in 67%. The disease prevalence in investigated patients in this hospital was 30.8% (95% confidence interval, 26.8 to 35.1%); at this prevalence, an elevated level of H agglutinins gave better positive predictive values for typhoid fever than did O agglutinins. With a cutoff titer of ≥200 for O agglutinin or ≥100 for H agglutinin, the Widal test would diagnose correctly 74% of the blood culture-positive cases of typhoid fever. However, 14% of the positive results would be false-positive, and 10% of the negative results would be false-negative. The Widal test can be helpful in the laboratory diagnosis of typhoid fever in Vietnam if interpreted with care.

Increase of leptospirosis in dengue-negative patients after a hurricane in Puerto Rico in 1996 [correction of 1966].

Abstract: Leptospirosis has rarely been reported in Puerto Rico, although in the period from 1948 to 1952, 208 cases of leptospirosis and an island-wide seroprevalence of antibody to Leptospira of 14% were documented. In Puerto Rico in October 1996, following rainfall and a period of flooding generated by Hurricane Hortense, serum specimens of 4 patients with suspected dengue fever that were negative for dengue tested positive for Leptospira-specific IgM antibodies in a dipstick assay. Subsequently, we used an island-wide dengue laboratory-based surveillance system to determine the increase in leptospirosis after hurricane-generated floods. All anti-dengue IgM-negative patients (n = 142) with disease onset from August 8 to October 6, 1996 from prehurricane and posthurricane groups were investigated for leptospirosis. Laboratory-confirmed leptospirosis cases were defined as microscopic agglutination test titers > or = 1 :400 to 1 or more serovars, or positive immunohistochemistry in autopsy tissues. Four (6%) of 72 prehurricane and 17 (24%) of 70 posthurricane patients had laboratory-confirmed cases of leptospirosis (relative risk [RR] = 4.4, 95% confidence interval [CI] = 1.6-12.4). The mean age of case-patients was 34 years (range = 13-64). Eighteen (86%) of 21 confirmed case-patients were males, including one patient who died (31 years old). Patients were located in 18 (38%) of 48 municipalities that submitted serum samples. Clinical features significantly associated with leptospirosis were eye pain (RR = 1.5, 95% CI = 1.3-1.9), joint pain (RR = 1.4, 95% CI = 1.1-1.6), diarrhea (RR = 1.7, 95% CI = 1.2-2.5), and jaundice (RR = 3.3, 95% CI = 1.5-7.2). This study demonstrates the utility of a dengue laboratory-based surveillance system for the detection of an increase of leptospirosis, which most likely would have gone unrecognized. Leptospirosis is treatable with antibacterial agents; knowledge of this diagnosis may significantly reduce morbidity and mortality.

A clinical study of the patients with dengue hemorrhagic fever during the epidemic of 1996 at Lucknow, India

Abstract: This paper describes the clinical findings in 206 patients with dengue fever (DF) or with dengue hemorrhagic fever (DHF) during the epidemic of 1996 at Lucknow. The age group affected most was 11 to 30 years and 21% of the patients were less than 10 years old. The male:female ratio was 1.9:1. The onset was abrupt in all the patients, severe frontal headache was observed in 97%, myalgia in 90%, skin rash in 40%, vomiting in 29% and arthralgia in knee and hip joints in 9%. Anuria was seen in two patients. Lymphadenopathy was noted in 14%, hepatomegaly in 4%, being associated with mild jaundice in one patient, and splenomegaly in 2% of the patients. Involvement of the heart and lungs was seen in one patient each and no case with encephalitis was recorded. Hemorrhages from various sites were observed in 54% patients and 17 patients had profound shock. The commonest bleeding site was gums. Profound shock was preceded by various warning signs, the commonest being sudden hypotension. Among the patients with profound shock the mortality was 47% while the overall fatality rate was 3.8%. A number of the risk factors existed for a long time in this part of the world, but what precipitated the present epidemic at this time, is not known.

Mayaro Virus Disease: An Emerging Mosquito-Borne Zoonosis in Tropical South America

Abstract: This report describes the clinical, laboratory, and epidemiological findings on 27 cases of Mayaro virus (MV) disease, an emerging mosquito-borne viral illness that is endemic in rural areas of tropical South America. MV disease is a nonfatal, dengue-like illness characterized by fever, chills, headache, eye pain, generalized myalgia, arthralgia, diarrhea, vomiting, and rash of 3-5 days' duration. Severe joint pain is a prominent feature of this illness; the arthralgia sometimes persists for months and can be quite incapacitating. Cases of two visitors from the United States, who developed MV disease during visits to eastern Peru, are reported. MV disease and dengue are difficult to differentiate clinically.

Changing epidemiology of dengue hemorrhagic fever in Thailand.

Abstract: Dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) are reportable diseases, the third most common causes for hospitalization of children in Thailand. Data collected from the Ministry of Public Health were analysed for trends. Rates of DHF increased in Thailand until 1987 when the largest epidemic ever, 325/100000 population, was recorded. Whereas the disease used to be confined to large cities, the rate is now higher in rural (102.2 per 100000) than urban areas (95.4 per 100000 in 1997). The age of highest incidence has increased, and the age group most severely affected is now those 5-9 years old (679/100000 in 1997). The case fatality rate has decreased with improved treatment and is now only 0.28%.

Dengue haemorrhagic fever in children in the 1996 Delhi epidemic

Abstract: An epidemic of dengue haemorrhagic fever (DHF) occurred in Delhi in 1996. A total of 240 children between the age of 4 months to 13 years of either sex, admitted in one hospital, were evaluated. Two hundred and sixteen (90%) children were from Delhi. A clinical diagnosis of dengue fever (DF) was made in 25 (10%), dengue fever with unusual bleeding (DFB) in 22 (9%), DHF in 80 (33%) and dengue shock syndrome (DSS) in 113 (47%) of the children strictly according to the WHO classification. The age peaked at 8 years. There was no association between various grades of severity of illness and age-groups though girls suffered from more severe illness. No association between severity of malnutrition and severity of illness was observed. Tourniquet test was positive in 40% with DF, 18% with DFB, 62% with DHF and 64% with DSS. In DSS haematemesis was present in 55 (49%), epistaxis in 39 (35%), melaena in 27 (24%) and ecchymosis in 34 (30%) patients. Children diagnosed as DFB had haematemesis and epistaxis in 12 (55%) and 10 (45%) respectively. Intravenous fluid requirement was clearly less in DFB patients than in DHF/DSS patients. Unusual clinical features in the form of jaundice were present in 7 (6%), hepatic encephalopathy in 6 (5%) and dengue encephalopathy in 6 (5%) patients. Dengue 2 virus was isolated from 10 of the 50 patients for whom viral culture was done on C6/36 clone of Aedes albopictus cell line. Eighteen patients suffering from DSS died giving an overall case fatality of 7.5%. The mortality rate in DHF/DSS was 9.3%. It is further suggested that DFB is a distinct entity. Most patients could be classified by the WHO classification if a retrospective packed cell volume was used to assess haemoconcentration. We suggest that development of area-specific criteria for diagnosis and management is desirable.

Common occurrence of concurrent infections by multiple dengue virus serotypes.

Abstract: The co-circulation of all 4 dengue virus serotypes in the same community, common since the 1950s in Southeast Asia, has now become a frequent occurrence in many Caribbean Islands, Mexico, and Central and South America in the past 20 years. As a consequence, the frequency of concurrent infections would be expected to increase in these areas. To assess this, using state of the art technology, we screened viremic serum samples and mosquitoes inoculated with serum samples collected during epidemics involving multiple dengue virus serotypes in Indonesia, Mexico, and Puerto Rico for virus isolation. Of 292 samples tested, 16 (5.5%) were found to contain 2 or more dengue viruses by an indirect immunofluorescence test and/or the reverse transcriptase-polymerase chain reaction.

Mayaro Virus Disease: An Emerging Mosquito-Borne Zoonosis in Tropical

Abstract: This report describes the clinical, laboratory, and epidemiological findings on 27 cases of Mayaro virus (MV) disease, an emerging mosquito-borne viral illness that is endemic in rural areas of tropical South America. MV disease is a nonfatal, dengue-like illness characterized by fever, chills, headache, eye pain, generalized myalgia, arthralgia, diarrhea, vomiting, and rash of 3 ‐ 5 days’ duration. Severe joint pain is a prominent feature of this illness; the arthralgia sometimes persists for months and can be quite incapacitating. Cases of two visitors from the United States, who developed MV disease during visits to eastern Peru, are reported. MV disease and dengue are difficult to differentiate clinically.

Infection of Primary Cultures of Human Kupffer Cells by Dengue Virus: No Viral Progeny Synthesis, but Cytokine Production Is Evident

Abstract: We investigated the ability of dengue virus to invade human primary Kupffer cells and to complete its life cycle The virus effectively penetrated Kupffer cells, but the infection did not result in any viral progeny Dengue virus-replicating Kupffer cells underwent apoptosis and were cleared by phagocytosis Infected Kupffer cells produced soluble mediators that could intervene in dengue virus pathogenesis

Sequential production of cytokines by dengue virus-infected human peripheral blood leukocyte cultures.

Abstract: The study was undertaken to elucidate the sequence of appearance of T helper (Th)1- and Th2-type cytokines in human peripheral blood leucocyte cultures infected in vitro with dengue type 2 virus. Commercial sandwich enzyme-linked immunosorbent assay kits were used to assay the levels of tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin (IL)-2, IL-4, IL-5, IL-6, and IL-10 in culture supernatants. Culture supernatants were also screened for the cytotoxic factor and the dengue virus titres determined. The cytokines that appeared in the culture supernatants on the first day post-infection (p.i.) were cytotoxic factor, TNF-alpha, IL-2, and IL-6; their levels were highest on the second day p.i. IFN-gamma appeared on the second day with a peak on the third day p.i. The levels of these cytokines declined quickly, except for human cytotoxic factor (hCF) and IL-2. The cytokines that appeared later were IL-10 and IL-5 on the fourth day and IL-4 on the sixth day p.i. Dengue virus replicated in the peripheral blood leucocyte (PBL) cultures and was present throughout the course of the study. The findings of the present study show that dengue virus induced a predominant Th1-type cytokine response during the first 3 days of infection of PBL cultures that was replaced by a Th2-type response later.

Detection of dengue virus RNA by reverse transcription-polymerase chain reaction in the liver and lymphoid organs but not in the brain in fatal human infection.

Abstract: Autopsy tissues from 18 children believed to have died of dengue hemorrhagic fever were tested for the presence of dengue virus RNA by reverse transcription-polymerase chain reaction (RT-PCR). Such RNA was found in 14 of 18 liver specimens, 13 of 18 spleen specimens and 7 of 16 mesenteric lymph node specimens. No dengue virus RNA was detected in 44 samples of brain tissue from 15 individuals, 1 or more of whose other tissues yielded such RNA. All tissues had been tested previously for dengue virus by mosquito inoculation. In those tests, virus was recovered from 5 of 18 liver and 2 of 18 spleen specimens. Thus, the RT-PCR is more sensitive than the most sensitive virus isolation technique for detecting dengue virus or its components in human tissue. Failure to isolate virus from most of spleen and all mesenteric lymph node specimens may indicate that those tissues contained primarily degraded virus undergoing inactivation.