The host

00000000 In humans, each of the four dengue virus serotypes has been associated with DF and with DHF. Studies in Cuba and Thailand have shown a consistently high asociation between DEN-2 infection and DHF/DSS, but in the 1976 - 1978 Indonesia, 1980 - 1982 Malaysia, and 1989 - 90 Tahiti epidemics, and from 1983 onwards in Thailand, DEN-3 was the predominant serotype recovered from patients with severe disease. In the 1984 Mexico, the 1986 Puerto Rico, and the 1989 El Salvador outbreads, DEN-4 was most often isolated from DHF patients. DSS occurs with higher frequency in two immunologically difined groups: children who have experienced a previous dengue infection, and infants with waning levels of maternal dengue antibody. The acute phase of infection, following an incubation of 3 - 14 days, lasts about 5 - 7 days and is followed by an immune response. The first infection produces life-long immunity to the infecting serotype but only temporary and partial protection against the other three serotypes, and secondary or sequential infections are possible after a short time. Transmission of dengue virus from infected humans to feeding mosquitos is determined by the magnitude and duration of viraemia in the human host; persons with high viraemia provide a higher infectious dose of virus to the feeding mosquito, normally leading to a greater percentage of feeding mosquitos becoming infected, although even very low levels of virus in blood may be infectious to some vector mosquitos.

Pathology

00000000 At autopsy, all patients who have died of DHF show some degree of haemorrhage; in order of frequency, haemorrhage is found in the skin and subcutaneous tissue, in the mucosa of the gatrointestinal tract, and in the heart and liver. Gastrointestinal haemorrhage may be severe, but subarachnoid or cerebral haemorrhage is rarely seen. Serous effusion with a high protein content (mostly ablumin) is commonly present in the pleural and abdominal cavities, but is less common in the pericardial cavity.

00000000 Light microscopy of blood vessels shows no significant changes in vascular walls. Capillaries and venules in the affected organ systems may show extravascular bleeding by diapedesis and perivascular haemorrhage, with perivascular infiltration by lymphocytes and mononuclear cells. Morphological evidence of intravascular clot formation in small vessels has been recognized in patients with severe haemorrhage.

00000000 In most fatal cases, lymphocyte tissue shows an increased activity of the B-lymphocyte system, with active proliferation of plasma cells and lymphoblastoid cells, and active germinal centres. There is evidence indicating that proliferation of large immunoblasts and considerable turnover of the lymphocytes occur. The latter is manifested by a reduction of white spoenic pulps, lymphocytolysis, and marked lymphocytic phagocytosis.
In the liver, there is focal necrosis of hepatic cells, swelling, appearance of Councilman bodies and hyaline nicrosis of Kupffer cells. Proliferation of mononuclear ceukocytes, and less frequently polymorphonuclear leukocytes, occurs in the sinusoids and occasionally in the portal areas. Lesions in the liver typically resemble those 72 - 96 hours after infection with yellow fever virus, when parenchymal cell damage is limited.

00000000 At autopsy, dengue virus antigen has been found predominantly in liver, spleen, thymus, lymph node, and lung cells. The virus has also been isolated at autopsy from the bone marrow, brain, heart, kidney, liver, lungs, lymph nodes, and the gastrointestinal tract.

00000000 Pathological studies of the bone marrow, kidneys and skin have been made in patients who had non-fatal DHF. In the bone marrow, depression of all haematopoietic cells was observed, which would rapidly improve as fever subsided. Studies in kidneys have shown a mild immune-complex type of glomerulonephritis, which would resolve after about 3 weeds with no residual change. Biopsies of skin rashes have revealed perivascular oedema of the terminal microvasculature of dermal papillae and infeltration of lymphocytes and monocytes. Antigen-bearing mononuclear phagocytes have been found in the vicinity of this oedema. Deposition of serum complement, immunoglobulin and fibrinogen on vessel walls has also been described.