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Biomedical subjects

S Nimmannitya

Publications and source records attributed to S Nimmannitya.

At least 37 records · Page 2Linked to original sources

IgM capture ELISA for detection of IgM antibodies to dengue virus: comparison of 2 formats using hemagglutinins and cell culture derived antigens.

The highly sensitive AFRIMS format IgM capture ELISA for the diagnosis of dengue virus infections requires the use of mouse brain derived hemagglutinins and consequently also the use of 20% acetone extracted normal human serum to eliminate high background. These reagents are not always easily available and we have thus compared the AFRIMS format with another published format which uses cell culture derived antigens (culture fluid, CF, format) in order to determine if it is reasonable to use cell culture derived antigens in situations where hemagglutinins and normal human serum are difficult to obtain. The study shows that using AFRIMS results as the reference point, the CF format described here has a sensitivity of 90% and a specificity of 96%.

Antibodies, Viral↗

Activation of T lymphocytes in dengue virus infections. High levels of soluble interleukin 2 receptor, soluble CD4, soluble CD8, interleukin 2, and interferon-gamma in sera of children with dengue.

It has been reported that the severe complication of dengue virus infection, dengue hemorrhagic fever (DHF) is much more commonly observed during secondary dengue virus infections than primary infections. In order to elucidate the role of T lymphocytes in the pathogenesis of DHF, we attempted to determine whether T lymphocytes are activated in vivo during dengue virus infections, by examining the levels of soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4), soluble CD8 (sCD8), interleukin-2 (IL-2) and interferon-gamma (IFN gamma) in the sera of 59 patients with DHF and 41 patients with dengue fever (DF). The levels of sIL-2R, sCD4, sCD8, IL-2, and IFN gamma were significantly higher in the acute sera of patients with DHF than in the sera of healthy children (P less than 0.001 for all markers). The acute sera of patients with DF contained higher levels of sIL-2R, sCD4, IL-2, and IFN gamma than the sera of healthy children (P less than 0.001 for sIL-2R, IL-2, and IFN gamma; P less than 0.05 for sCD4), but did not have elevated levels of sCD8. The levels of sIL-2R (P less than 0.05), sCD4 (P less than 0.001), and sCD8 (P less than 0.001) were higher in DHF than in DF on days 3-4 after the onset of fever. The levels of IL-2 and IFN gamma in patients with DHF were highest 1 d before defervescence. There were no significant differences in the levels of sIL-2R, sCD4, sCD8, IL-2, and IFN gamma among grades 1, 2, and 3 of DHF. These results indicate (a) T lymphocytes are activated and produce IL-2 and IFN gamma in vivo during DHF and DF, (b) CD4+ T lymphocytes are activated in DHF and DF, and the level of activation is higher in DHF than in DF, and (c) activation of CD8+ T lymphocytes is evident in DHF, but not in DF.

Adolescent↗

Human immune responses to dengue viruses.

Dengue fever (DF) and dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) are major public health problems in many areas of the world. We are analyzing the human immune responses to dengue viruses, in order to understand the mechanism of recovery from dengue virus infections and the pathogenesis of DHF/DSS. Human natural killer (NK) cells lyse dengue virus-infected cells to a greater degree than uninfected cells. Antibodies to dengue viruses augment the lysis of dengue virus-infected cells by NK cells. Dengue virus-infected monocytes produce high levels of interferon alpha (IFN alpha). DR+ lymphocytes also produce high levels of IFN alpha after contact with dengue virus-infected monocytes. The IFN alpha produced protects uninfected monocytes from dengue virus infection. These results suggest that NK cells and IFN alpha may play an important role in controlling primary dengue virus infection. Dengue virus-specific CD4+CD8(-)T lymphocytes and CD4(-)CD8+T lymphocytes are present in the peripheral blood mononuclear cell population from donors who were infected with dengue virus. Most of CD4+T lymphocytes are dengue serotype-crossreactive. They lyse dengue virus-infected autologous cells in an HLA class II-restricted fashion, and produce interferon gamma (IFN gamma). IFN gamma augments dengue virus infection of monocytic cells in the presence of antidengue virus antibodies by increasing the number of Fc gamma receptors. Dengue virus-specific CD8+T lymphocytes lyse dengue virus-infected autologous cells in an HLA class I-restricted fashion. These CD8+T lymphocytes are also dengue serotype-crossreactive.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Differentiation, T-Lymphocyte↗

[Clinical observation of 15 Thai children with dengue hemorrhagic fever].

Fifteen Thai children, diagnosed with dengue hemorrhagic fever and admitted to the Children's Hospital in Bangkok, were studied. All cases were serologically proved to be secondary dengue infections. The clinical signs and symptoms in the first few days of the acute febrile phase were similar to those observed in cases with classical dengue fever, and included continuously high fever, headache, muscle pain, nausea, vomiting and abdominal pain, etc. In the laboratory findings we noted hypoalbuminemia and mild elevation of the GOT and GPT. The hemogram showed an increasing atypical lymphocyte count during the acute febrile period. Prolongations of the partial thromboplastin time and thrombin time were also found, especially in the severe shock cases. All patients had varying degrees of hepatomegaly and pleural effusion from their chest x-rays accompanied by a rapid increase in the hematocrit of more than 20% and a fall in the platelet count to less than 100000/microliters. During the plasma leakage period the patients easily developed shock, even leading to death, unless adequate fluid supplies were given. This is also the major pathophysiological difference between dengue hemorrhagic fever and classical dengue fever. Although some studies concerning the pathogenesis of dengue hemorrhagic fever have been reported, but the exact mechanisms need further investigation.

Adolescent↗

Human T cell responses to dengue virus antigens. Proliferative responses and interferon gamma production.

The severe complications of dengue virus infections, hemorrhagic manifestations and shock, are more commonly observed during secondary dengue virus infections than during primary infections. It has been speculated that these complications are mediated by cross-reactive host-immune responses. We have begun to analyze human T cell responses to dengue antigens in vitro to explain the possible role of T lymphocytes in the pathogenesis of these complications. Dengue antigens induce proliferative responses of PBMC from dengue antibody-positive donors, but do not induce specific proliferative responses of PBMC from dengue antibody-negative donors. IFN gamma is detected in the culture fluids of dengue-immune PBMC stimulated with dengue antigens. The cells that proliferate in the dengue antigen-stimulated bulk cultures have CD3+, CD4+, CD8-, CD16-, and CD20- phenotypes. Dengue-specific T cell lines were established using limiting dilution techniques. They have CD3+, CD4+, and CD8- phenotypes, and produce IFN gamma in response to dengue antigens. Culture fluids from dengue-immune PBMC stimulated with dengue antigens, which contain IFN gamma, augment dengue virus infection of human monocytes by dengue virus-antibody complexes. These results indicate that PBMC from dengue-immune donors contain CD4+ T cells that proliferate and produce IFN gamma after stimulation with dengue antigens, and suggest that the IFN gamma that is produced by these stimulated dengue-specific T cells may contribute to the pathogenesis of dengue hemorrhagic fever and dengue shock syndrome by increasing the number of dengue virus-infected monocytes in the presence of cross-reactive anti-dengue antibodies.

Antigens, Differentiation, T-Lymphocyte↗

An enzyme-linked immunosorbent assay to characterize dengue infections where dengue and Japanese encephalitis co-circulate.

The diagnostic sensitivity and specificity of detection of anti-dengue IgM by antibody capture enzyme-linked immunosorbent assay (ELISA) was investigated in dengue infections in a variety of clinical settings. Sera from uninfected controls were uniformly negative. Serial specimens from experimental and natural infections showed that viremia and fever terminated as anti-dengue IgM became detectable. Anti-dengue IgM appeared in most cases by the 3rd afebrile day of illness and declined to undetectable levels after 30-60 days. Assay sensitivity was 78% in admission sera (924/1,183; 95% CI = 75-81%) and 97% in paired sera (1,030/1,062; 95% CI = 96-98%) thus exceeding or matching the performance of the hemagglutination-inhibition assay. Measurement of the anti-dengue IgM to anti-Japanese encephalitis IgM ratio correctly identified all sera from 112 patients with strictly defined Japanese encephalitis and 98% (307/312; 95% CI = 96-99%) of sera from patients whose dengue infections were confirmed by virus isolation. Dengue infections could be classified as primary or secondary by determining the ratio of units of dengue IgM to IgG antibody. We propose that measurement of dengue and Japanese encephalitis IgM and IgG antibodies upon admission and discharge from hospital care should replace the hemagglutination inhibition assay as the standard dengue serologic technique in regions where these 2 viruses co-circulate.

Acute Disease↗

A study of erythrocyte sedimentation rate in dengue hemorrhagic fever.

Erythrocyte sedimentation rate (ESR) was determined in 180 DHF patients and 70 patients with various viral and bacterial infections using the Winthrobe method. Seventy-seven percent of DHF patients had normal ESR (less than 20 mm/hour) and 15% had slightly elevated ESR value (between 21-30 mm/hour). The other 8% had ESR in the range of 31-49 mm/hour. Among 7 patients in the latter group, one had definite evidence of complicating urinary tract infection while the other 6 cases had anemia and severe bleeding. The mean ESR in DHF patients (10.71 mm/hour) was significantly lower than the mean values in other groups of patients with viral infection (20.46 mm/hour), bacterial infection (34.81 mm/hour) and miscellaneous illnesses (35.29 mm/hour). The mean ESR in shock cases was 7.63 mm/hour while in non-shock cases it was 13.87 mm/hour and they are statistically different (p less than 0.05). The mean ESR during the time of shock was lower than in the pre-shock and post-shock period. Hemoconcentration, low level of albumin and fibrinogen and the presence of disseminated intravascular clotting (DIC) in a majority of DHF patients are most likely responsible to this observed lower ESR especially during shock period. The determination of ESR, which is simple, is therefore useful in differentiating DHF from bacterial infections and dengue shock syndrome from septic shock.

Bacterial Infections↗

Platelet function during the acute phase of dengue hemorrhagic fever.

Platelet aggregation, plasma betathromboglobulin (BTG) and platelet factor 4 (PF4) were studied in 35 children with dengue hemorrhagic fever. The suppression of platelet aggregation was demonstrated during acute phase of DHF in both shock and non-shock patients. Simultaneous with abnormal platelet aggregation, there was increased release of BTG and PF4 from platelets into plasma during the acute phase which lasted only 3-4 days after shock or subsidence of fever. Acute phase plasma during DHF infection was also shown to have a stimulatory effect on the aggregation of autologous platelets. In this study we showed that there was an increase in platelet secretory activity of BTG and PF4 along with an impairment of the platelet aggregation during acute phase of DHF.

Adolescent↗

Protective efficacy of plasma-derived hepatitis beta vaccine in preventing perinatal transmission of HBV infection in infants of HBsAg/HBeAg positive mothers.

Two hundred and four newborn infants of HBsAg/HBeAg carrier mothers were randomly assigned into three groups. Group A (69 infants) received full-dose HB vaccine, group B (70 infants) received half-dose HB vaccine at birth, 1 month, 3 months and group C (65 infants) were untreated control group. After twelve months follow-up the cumulative incidence of HBs antigenemia was 17.2%, 30% in group A, B respectively as compared with 78.4% in group C (p less than 0.001). The protective efficacy rates (PER) of group A and B were 78.1% and 61.7% respectively (p less than 0.05). The vaccine was also effective in preventing persistent HBsAg carriers (HBsAg positive for at least 6 months). The PER of group A and B were at least 74.9% and 49.2% respectively (p less than 0.001) at 1 year follow-up. From the practical point of view and economic reasons administration of full-dose HB vaccine give better protection to high risk infants.

Carrier State↗

Dengue haemorrhagic fever with unusual manifestations.

A retrospective study on 18 cases of DHF presented with jaundice and neurological signs which were considered unusual manifestation of DHF reveals that the causes or contributing factors are multifactorial. Most commonly found associated conditions were prolonged shock with metabolic acidosis and severe DIC that lead to hypoxia/ischaemia and resulted in both hepatic and brain dysfunction. Gross haemorrhage in the brain was noted in 6 of the 10 fatal cases while brain oedema was noted in 3 cases. Electrolyte disturbance such as hyponatremia could be another cause of brain oedema. It is certain from this study that there is no pathological evidence of encephalitis. Hepatic dysfunction found in associated with jaundice and encephalopathy is possibly caused by toxic substances, drugs and/or associated with underlying liver conditions. Reye's or Reye's-like syndrome was postulated in one case.

Brain Diseases↗

Endotoxin and dengue haemorrhagic fever.

Limulus amoebocyte lysate test (LALT) was used to detect endotoxin-like substances in the plasma of 57 patients with dengue haemorrhagic fever and dengue shock syndrome (DHF/DSS), four patients with dengue fever and 20 control patients with other diseases. The LALT positivity rates in DHF/DSS and dengue fever patients were 43.9 and 25 per cent respectively, whereas all control patients were negative (p less than 0.0025). LALT positivity was highest on 5th and 6th days of admission with positive rates of 46 and 50 per cent respectively whereas the positive rates in those admitted on fourth and seventh days of admission were 29 and 33 per cent respectively. A follow-up in LALT positive patients showed a decline in the positive rates after admission. LALT positivity was observed in 48.8 per cent of DHF/DSS patients with shock and in 26.6 per cent of patients without shock.

Adolescent↗

Japanese encephalitis in Thai children, Bangkok, Thailand.

During a period of 5 years from May 1979 to April 1984, 121 encephalitis patients were admitted to Bangkok Children's Hospital. 79 were proved to be JE. 73.42% of JE patients came from outside Bangkok while the rest came from suburban areas of Bangkok. No distinction could be made between JE and encephalitis caused by other agents by clinical data and cerebrospinal fluid examination. Definite diagnosis of JE could be done by demonstration of specific IgM antibody against JEV in cerebrospinal fluid. Case fatality rate of JE was 25%.

Adolescent↗

Atypical lymphocyte in dengue hemorrhagic fever: its value in diagnosis.

Simple peripheral and buffy coat smear were studied in 40 serological confirmed dengue hemorrhagic fever patients, and in other patients with viral and bacterial infections. Atypical lymphocytosis was found in majority of dengue hemorrhagic fever both associated with secondary and also in dengue fever with primary infection as compared to other infections. The time course relationship of atypical lymphocytosis, platelet and hematocrit level were discussed, concerning their value as diagnostic and prognostic criteria in dengue hemorrhagic fever.

Dengue↗

Cold-reactive immunoglobulin M antilymphocyte antibodies directed against B cells in Thai children with dengue hemorrhagic fever.

Antilymphocyte antibodies were found in 51 of 83 serum specimens from Thai children with dengue hemorrhagic fever (DHF). The lymphocytotoxic activity was complement dependent, and cytotoxicity was detected in the 19S immunoglobulin M-associated serum fractions at a temperature optimum of 15 degrees C. Sera with lymphocytotoxic activity were cytotoxic to autologous as well as allogeneic lymphocytes from patients and healthy adult donors and were directed primarily against B cells, with some T cell cross-reactivity. This study suggests that infection with DHF induces predominately cold-reactive antilymphocyte antibodies in DHF patients that could potentially interact with peripheral blood cells of patients and modulate the humoral immune responses of patients during infection.

Autoantibodies↗