Correlation of disease spectrum among four Dengue serotypes: a five years hospital based study from India

The recognition of DF (DHF Dengue Hemorrhagic Fever) is very complicated due to occurrence of a wide spectrum of clinical signs and symptoms during acute phase of illness. Moreover, presence of four serotypes further complicates the prognosis. To investigate the predictors of disease severity and elucidate the prognostic markers among four dengue serotypes, this study was conducted on 320 inpatients having acute febrile illness clinically suspected as DI, over a period of five years. Dengue serotypes were confirmed by multiplex reverse transcriptase (RT)-PCR. Eighty patients were positive for DI with presence of Den-1, Den-2, Den-3, and Den-4 in 8, 35, 27 and 10 patients, respectively. The severe clinical manifestations, abdominal pain and hepatomegaly, were comparatively higher in Den-2 patients. Liver aminotransferases levels were also higher in Den-2 patients (app. 5 fold). This study clearly indicates the hyperendemicity of all dengue serotypes. Nucleotide sequencing of Envelope region revealed that the presently emerged Den-3 belongs to type III, having high homology with genotype responsible for number of outbreaks in 1980s. The re-emergence of this deadly type can be suspected to cause more outbreaks in future and is a matter of great concern.

Circulating levels of tumour necrosis factor-alpha & interferon-gamma in patients with dengue & dengue haemorrhagic fever during an outbreak.

BACKGROUND & OBJECTIVE: Dengue haemorrhagic fever (DHF) is a severe illness caused by dengue viruses, the pathogenesis of which is not fully understood. Immune enhancement caused by cytokines, interferon and activated complement system is one of the hypotheses proposed to explain the haemorrhagic form of disease. This study was undertaken to investigate the role of pro-inflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) in dengue infection, and their possible association with disease severity. METHODS: Blood samples were collected from 60 patients; 28 patients of DF and 32 of DHF (clinically categorized into DF or DHF as per WHO criteria) from September to November 2003 at Delhi. Fifteen healthy individuals were included as control. All the patients were confirmed positive for dengue infection by serology or by reverse transcriptase-polymerase chain reaction (RT-PCR). Serum levels of TNF-alpha and IFN-gamma were determined by ELISA. RESULTS: The levels of both the cytokines were significantly elevated in the disease group as compared to the control group. Significantly higher levels of TNF-alpha; 258.02 pg/ml (P<0.005) were seen in patients having secondary infection, while patients with primary infection had higher level of IFN-gamma; 29.47 pg/ml (P<0.005). TNF-alpha was elevated in the later phase of illness, while IFN-gamma was elevated in early phase also. INTERPRETATION & CONCLUSION: Overproduction of TNF-alpha during secondary infection may have a role in immunopathogenesis of DHF, however, study of other cytokines produced along with IFN-gamma;, during the course of dengue infection is required to know the specific role of IFN-gamma in DI.