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Clinical Manifestations and Pathology

Dengue is characterized by sudden onset of high fe­ver, headache, prostration, joint and muscle pain, Iymphadenopathy, and a rash that appears simulta­neously with a second temperature rise following an afebrile period (saddle-back fever).

However, classi­cal saddle-back fever occurs in only 50 percent of cases; Iymphadenopathy is not an invariable finding; and the rash may either never develop at all or else not develop until the fourth or fifth day, or during the second phase if the fever is saddle-backed.

An outbreak of dengue fever occurred at Clark Air Force Base, a large U.S. military installation located about 70 kilometers north of Manila on Luzon Island, Republic of the Philippines, between June and Sep­tember 1984. Of 119 persons suspected of having dengue, 42 cases were confirmed by hemaggluti­nation-inhibition (HI) antibody seroconversion or by virus isolation. Seroconversion implies that HI anti­body was lacking in the serum of patients at an early stage of their illness, but could be detected subse­quently, usually during convalescence, providing in­direct evidence of the cause of the illness. Virus isola­tion from the blood of dengue-infected persons is the most accurate diagnostic test for dengue, but it is impracticable for widespread use because the vast majority of cases of dengue infection occur in parts of the world where sophisticated medical facilities are simply not available. A further nine cases were con­sidered to be probable dengue, as HI antibody was detectable in serum obtained from patients during the acute phase of their illness.

The most frequent clinical findings were fever (97 percent), headache (80 percent), and muscle and joint pain (80 percent). Other signs and symptoms frequently reported were malaise, chills, anorexia, nausea, vomiting, diarrhea, and maculopapular skin eruption (blotchy, raised, red rash).

Dizziness, un­usual taste sensation, and itching/scaling of the palms were less frequently reported. Hemorrhagic signs occurred in 18 patients and consisted of petech- iae (pinpoint hemorrhages into skin and mucous membranes) in 13 patients, gastrointestinal bleed­ing in 4 patients, and gum bleeding in 1 patient.

Common laboratory findings in 29 patients admit­ted to hospitals were low white blood cell count, relative lymphocytosis (71 percent), and a reduced platelet count. All four dengue serotypes were iso­lated (12 cases of dengue 1, 4 cases of dengue 2, 5 of dengue 3, and 1 of dengue 4). All patients survived their illness and returned to normal health. This outbreak of mixed classical benign dengue fever and dengue hemorrhagic fever of multiple serotype is typical of current dengue epidemics.

Severe dengue disease - dengue hemorrhagic fe­ver and dengue shock syndrome - proceeds through two stages. The first is similar to that of benign dengue; however, patients deteriorate during or shortly after the fall in temperature. Ifhypovolemic shock supervenes (because of a greatly reduced vol­ume of plasma), untreated patients may expire within 6 hours. The clinical evidence of disturbances of blood coagulation is accompanied by abnormal laboratory tests. Hemoconcentration and reduced platelet count are invariable findings. Reduced lev­els of serum albumin, elevations of serum trans­aminases and blood urea nitrogen, prolonged pro­thrombin time, and reduced serum levels of factors II, V, VI, IX, and XII are common. Hypofibrino­genemia is a frequent finding, and the condition is best described as an acute vascular permeability syndrome accompanied by activation of the blood clotting and complement systems.

The World Health Organization has developed di­agnostic criteria for dengue hemorrhagic fever and dengue shock syndrome:

Clinical

a. Fever - acute onset, high, continuous, and lasting for 2 to 7 days

b. Hemorrhagic manifestations including at least a positive tourniquet test and any of:

petechiae, purpura, ecchymosis (skin eruptions) nose or gum bleeding

hematemesis and/or melena (passing of black stools)

c. Enlargement of liver

d. Shock - manifested by rapid and weak pulse with narrowing of the range of pulse pressure (20 mmHg/2.7 kPa or less) or hypotension, with cold, clammy skin, and restlessness

Laboratory

a. Thrombocytopenia (0.10 ? 1012/L or less)

b. Hemoconcentration - hematocrit increased by 20 percent or more

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Source: Kiple Kenneth F. (Editor). The Cambridge World History of Human Disease. Cambridge University Press,1993. — 1200 p.. 1993

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