NK cells, displaying early activation, cytotoxicity and adhesion molecules, are associated with mild dengue disease.

During the innate immune response against infections, Natural Killer (NK) cells are as important effector cells as are Cytotoxic T lymphocytes (CTL) generated after antigenic stimulation in the adaptative response. NK cells increase in numbers, after viral infection or vaccination. We investigated the NK cell and CD8 T lymphocyte status in 55 dengue infected patients. The NK (CD56+CD3-) and CD56+ T cell (CD56+CD3+) rates rise during the acute phase of disease. The majority of NK cells from dengue patients display early markers for activation (CD69, HLA-DR, and CD38) and cell adhesion molecules (CD44, CD11a) during the acute phase of disease. The intracellular cytotoxic granule, TIA-1, is also up-regulated early in NK cells. Most of these markers appear also on CD8+ T lymphocytes but during the late acute phase. Circulating IL-15 is elevated in a significant number of patients during early acute infection and its values were statistically correlated with NK frequencies and cytotoxic markers on NKs. We have therefore shown that dengue virus infection is very likely stimulating a cytotoxic response that may be efficient in controlling the virus in synergism with CD8+ T lymphocytes. Interestingly, the heightened CD56+CD3-, CD56+CD3+, CD56+TIA-1+ and CD56+CD11a+ cell rates are associated with mild dengue clinical manifestations and might indicate a good prognosis of the disease.

Characterisation of lymphocyte response and cytokine patterns in patients with dengue fever.

It is believed that the pathogenesis of dengue is generated by a deregulation of the immunological response. Dengue virus-infected monocytes/macrophages are likely to secrete monokines, which play a role in clinical features observed in patients with dengue haemorrhagic fever or dengue shock syndrome. This is a report on a study on 45 individuals presenting clinical and laboratory characteristics of dengue virus infection. During the acute phase of infection, immunophenotyping of peripheral mononuclear leukocytes was carried out in 19 patients and demonstrated a reduced frequency of CD2+ lymphocytes and their CD4+ and CD8+ subsets. Normal ratios were recovered during convalescence. Also, during the acute phase, mononuclear cells proliferated poorly in response to mitogens and dengue antigens as detected by incorporation of radiolabeled thymidine. During convalescence the lymphoproliferative response was re-established. In addition, the presence of circulating cytokines was investigated in the plasma of the same 45 patients. Concentrations of tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-10 (IL-10) and soluble tumor necrosis factor receptor (sTNF-Rp75) were found to be significantly elevated in patients when compared to normal controls. The increase in TNF-alpha was correlated with haemorrhagic manifestations and the increase in IL-10 with platelet decay. The data demonstrate that during the acute phase of dengue infection subsets of T lymphocytes are depressed in terms of both rate and function and provide evidence that circulating pro-inflammatory cytokines, such as TNF-alpha, are important in the pathogenesis and severity of dengue. IL-10 may be downregulating lymphocyte and platelet function.

Dengue in the State of Rio de Janeiro, Brazil, 1986-1998.

This paper presents epidemiological, laboratory, and clinical data on 12 years of dengue virus activity in the State of Rio de Janeiro from the time the disease was first confirmed virologically in April 1986 through April 1998. DEN-1 and DEN-2 viruses are the serotypes circulating in the state and were responsible for the epidemics reported during the last 12 years. The results published here show both the impact of dengue virus infections on the population and laboratory advances that have improved dengue diagnosis.

Dengue haemorrhagic fever in the state of Rio de Janeiro, Brazil: a study of 56 confirmed cases.

We studied 56 cases of serologically confirmed dengue haemorrhagic fever living in the metropolitan area of Niterói and surrounding cities in the state of Rio de Janeiro, Brazil. The most frequent findings were fever and myalgia. Spontaneous haemorrhagic manifestations occurred in 46 patients, and 23 of these had more than one kind of bleeding; petechiae and bleeding gums were the most frequent association. The distribution according to the World Health Organization's criteria of severity was 6 in grade I, 23 in grade II, 24 in grade III and 3 in grade IV.

Dengue epidemic in the stage of Rio de Janeiro, Brazil, 1990-1: co-circulation of dengue 1 and dengue 2 serotypes.

During 1990 and 1991, dengue fever was detected in the State of Rio de Janeiro, Brazil. It occurred in two epidemic waves; one, from January to August 1990, caused predominantly by dengue virus type 1 (DEN-1) the other from October 1990 to May 1991 caused by type 2 virus (DEN-2). Dengue was confirmed by virus isolation and/or IgM capture enzyme-linked immunosorbent assay (MAC-ELISA) in 2109/5964 (35.4%) of the cases. DEN-2 virus was isolated from 180 patients. HAI tests indicated that of these previous infection with DEN-1 had occurred in 130 (72%). The epidemic was classified as dengue fever, but severe and even fatal cases occurred in association with secondary infection.