a) PREHEMORRHAGIC: ONSET is sudden and acute; lasts 1 to 7 days. SYMPTOMS: Fever, chills, headache; musculoskeletal, lumbar, and epigastric pain; nausea, repeated vomiting not associated with eating, diarrhea, weakness, and loss of appetite. SIGNS: Hyperemia of the face, neck, and chest; congested sclerae; conjunctivitis; slightly hyperemic pharynx; spotted enanthemas on the soft and hard palates; bradycardia (not in children), hypotension, and jaundice in some cases.
b) HEMORRHAGIC: Develops rapidly; usually begins on day 3 to 5. Characterized by bradycardia (not in children), muffled heart sounds, and hypotension. During this stage, the condition deteriorates rapidly; lasts 1 to 10 days or results in death. No relationship between degree of temperature and onset of hemorrhages. Hemorrhages range in size from petechiae to large ecchymoses/hematomas; often develop on mucous membranes and skin, especially along posterior axillary lines, in antecubital fossae, under women's breasts, and at injection and pressure sites. Gums, buccal mucosa, and nose bleed; intestinal and uterine hemorrhages occur, sometimes with bloody sputum and bleeding from conjunctivae and ears. In about 15% of patients, only a hemorrhagic rash appears. Patients may be pale and tachycardic with profuse hemorrhage. About 10% of patients develop hemorrhagic pneumonia. Palpation of the epigastric area is usually painful; liver and spleen are enlarged in about 33% of patients. Hypotension leading to shock and vascular collapse may occur. Fatalities due to massive hemorrhage (likely cause of death secondary to DIC), circulatory collapse, multiorgan failure and cardiac arrest; usually 7 to 16 days after onset of illness. Autopsy findings include numerous hemorrhages into all organs and tissues and copious quantities of blood in stomach and intestines.
c) CONVALESCENCE: Usually begins rapidly about day 15 to 20 of illness; no hemorrhagic relapse occurs. Most patients are discharged in 3 to 6 weeks. Characterized by prolonged, pronounced asthenia, labile pulse, and sometimes complete hair loss (replaced 4 to 5 months later) and pronounced mono- or polyneuritis. Common ongoing symptoms include: general weakness and rapid fatigability, sweating, headache, dizziness, nausea, poor appetite, xerostomia, labored breathing, tachycardia, poor vision and hearing (or complete hearing loss), and loss of memory. Symptoms may disappear rapidly or persist for a year or more.

a) Muffled heart sounds may be present during the hemorrhagic period though the reason for this is unclear (Hoogstraal, 1979).

a) Hypotension is expected following massive hemorrhage. Hemorrhage and cardiovascular collapse or shock are causes of death ((Anon, 2000); Peters, 2000; CDC, 1988; Suleiman et al, 1980).

a) Bleeding is one clinical feature of this disease and may manifest as hemoptysis. It may occur during the hemorrhagic period (Gear, 1989). Occurs on fourth or fifth day in over 75% of patients (WHO, 1985).

a) Hemorrhagic pneumonia develops in about 10% of patients during the hemorrhagic period (Hoogstraal, 1979).
b) Autopsy in 2 patients revealed intensely congested lungs with widespread intra-alveolar edema formation with fibrin deposition and small intra-alveolar hemorrhages (Baskerville, 1981).

a) Pulmonary edema is common in patients with hypotension and losses of intravascular volume through hemorrhage and increased vascular permeability. Pulmonary edema may be due to myocardial impairment and increased pulmonary vascular permeability ((Jahrling, 2000)).

a) Memory loss may occur during the convalescent period; it may disappear rapidly or persist for a year or more (Hoogstraal, 1979).

a) Headache may occur during the prehemorrhagic and convalescent periods; it may disappear rapidly or persist for a year or more (Hoogstraal, 1979).

a) Confusion may occur during the prehemorrhagic period; it may persist for 2 weeks (Swanepoel, 1987).

a) Dizziness may occur during the convalescent period; it may disappear rapidly or persist for a year or more (Hoogstraal, 1979).

a) Generalized weakness may occur during the prehemorrhagic and convalescent periods; it may disappear rapidly or persist for a year or more. Prolonged, pronounced asthenia and/or rapid fatigability may occur during the convalescent period. Symptoms may disappear rapidly or persist for a year or more (Hoogstraal, 1979).

a) Intracranial hemorrhage may develop in patients with severe coagulopathy (Swanepoel et al, 1989).

a) Diarrhea is characteristic during the prehemorrhagic period (Hoogstraal, 1979).

a) Hematemesis may occur during the hemorrhagic period (Gear, 1989). Occurs on the fourth or fifth day in over 75% of patients (WHO, 1985).

a) Hematochezia and/or melena may occur during the hemorrhagic period (Hoogstraal, 1979; Suleiman et al, 1980). Bleeding may occur in the following descending order of frequency: from the nose, gums, buccal mucosa, stomach, uterus, intestines, and lungs (WHO, 1985).
b) Hemorrhages may be seen in the deeper parts of the mucosa and submucosa at autopsy (Baskerville, 1981).

a) Nausea may occur during the prehemorrhagic and convalescent periods; it may disappear rapidly or persist for a year or more (Hoogstraal, 1979). Nausea may begin abruptly after a 5- to 12-day incubation period.
b) Repeated vomiting not associated with eating may occur during the prehemorrhagic period. May begin abruptly after a 5- to 12-day incubation period (Hoogstraal, 1979).

a) Epigastric pain may occur during the prehemorrhagic and hemorrhagic periods (Hoogstraal, 1979). Abdominal pain may begin abruptly after a 5- to 12-day incubation period.

a) Splenomegaly occurs in about 33% of patients during the hemorrhagic period (Hoogstraal, 1979). Predominant features in histopathologic studies in 2 patients were extreme dilation of sinusoids, necrosis of red and white pulp, necrosis of marginal lymphocytes, and generalized lymphoid depletion (Baskerville, 1981).

a) Hepatomegaly occurs in about 33% of patients during the hemorrhagic period (Hoogstraal, 1979). Autopsy studies have shown widespread hepatocellular necrosis with a variable degree of hemorrhage in many sites and moderate fatty change (Baskerville, 1981).

a) Hepatic involvement is common; however, a clinical picture dominated by jaundice and other evidence of hepatic failure is seen in only a small number of patients ((Jahrling, 2000)). Aspartate aminotransferase may be elevated on the first day of illness. Values >1000 International Units/L associated with fatal outcome (Swanepoel, 1987).
b) Increased alanine aminotransferase may not be detected until day 5 of illness. Values >1000 International Units/L associated with fatal outcome (Swanepoel, 1987).
c) Increased bilirubin may be detected by day 9 of illness; both total and direct levels may be increased (Swanepoel, 1987).

a) Uterine hemorrhage may occur during the hemorrhagic period (Hoogstraal, 1979). Bleeding may occur in the following descending order of frequency: nose, gums, buccal mucosa, stomach, uterus, intestines, and lung (WHO, 1985).

a) Increased BUN may be detected by day 3 (Burney et al, 1980) Swanepoel, 1987). Renal failure is proportional to cardiovascular compromise ((Jahrling, 2000)).

a) Slight or pronounced albuminuria may be present in more than 50% of patients ((Jahrling, 2000); Hoogstraal, 1979).

a) One to 2 erythrocytes per microscope field are present in 50% of patients during the early prehemorrhagic period (Hoogstraal, 1979). Gross hematuria is common ((Jahrling, 2000)).

a) Patients in the acute, viremic phase of disease may bleed profusely ((Jahrling, 2000); Burney et al, 1980). Hemorrhages range in size from petechiae to large hematomas; develop on mucous membranes and skin, especially along posterior axillary lines, in antecubital fossae, under women's breasts, and at injection and pressure sites (Hoogstraal, 1979).
b) Gums, buccal mucosa, and nose bleed; intestinal and uterine hemorrhages occur, sometimes with bloody sputum and bleeding from conjunctivae and ears. In about 15% of patients, only a hemorrhagic rash appears (Hoogstraal, 1979).
c) Patients may be pale and tachycardic with profuse hemorrhage. About 10% of patients develop hemorrhagic pneumonia (Hoogstraal, 1979).
d) Autopsy findings include numerous hemorrhages into all organs and tissues and copious quantities of blood in stomach and intestines (Hoogstraal, 1979).

a) Coagulation cascades are activated and commonly result in profound disseminated intravascular coagulation (DIC) ((Anon, 2000); (Jahrling, 2000); Peters, 2000). Hemorrhage can also be enhanced by specific end-organ failures. The final pathway of hemorrhagic fever is damage to the vascular endothelium. Evidence of DIC has serious prognostic implications (Joubert et al, 1985).

a) Leukocyte count may decrease to 2000 to 3000/mm(3) (possibly to 800/mm(3)) during the early prehemorrhagic period. Diagnosis of a viral hemorrhagic fever should be strongly considered when accompanied by clinical evidence (Hoogstraal, 1979; Burney et al, 1980) Van Eeden, 1985; (Joubert et al, 1985).
b) Leukopenia may disappear by day 14 to 17 in patients with mild disease, after 3 to 4 weeks in those with moderately severe disease, and after 5 to 6 weeks in those with severe disease. This is less pronounced in children (Hoogstraal, 1979) Van Eeden, 1985).

a) Platelet count may decrease to 50,000/mm(3) during the early prehemorrhagic period. Diagnosis of a viral hemorrhagic fever should be strongly considered when accompanied by clinical evidence (Hoogstraal, 1979; Burney et al, 1980; Joubert et al, 1985).
b) Thrombocytopenia may be moderate in patients with mild disease and 70,000 to 90,000/mm(3) in those with moderately severe disease (Hoogstraal, 1979). Death occurred in patient with hemorrhages and a reported platelet count of 95,000/mm(3) (Burney et al, 1980).
c) Values become normal after 3 to 4 weeks in patients with moderately severe disease and after 5 to 6 weeks in those with severe disease (Hoogstraal, 1979).

a) Diagnosis is difficult; tick bite is often painless. Many patients are not aware of a bite until symptoms develop.

a) Diaphoresis may occur during the convalescent period; it may disappear rapidly or persist for a year or more (Hoogstraal, 1979).

a) Hemorrhages range in size from petechiae to large hematomas; develop on mucous membranes and skin, especially along posterior axillary lines, in antecubital fossae, under women's breasts, and at injection and pressure sites (Hoogstraal, 1979).

a) Hyperemia may occur on face, neck, and chest during prehemorrhagic period. Hemorrhagic rash is the only sign during hemorrhagic period in about 15% of patients. Hemorrhages range in size from petechiae to large hematomas (Hoogstraal, 1979). Large purpuric areas caused by subcutaneous extravasation of blood may be noted ((Anon, 2000)).

a) Patients may be pale with profuse hemorrhage (Hoogstraal, 1979).

a) Complete hair loss may occur during convalescent period (replaced 4 to 5 months later) (Hoogstraal, 1979).

a) Muscle pain is characteristic during prehemorrhagic period (Hoogstraal, 1979).

a) Lumbar pain may occur during prehemorrhagic period (Hoogstraal, 1979).

a) Creatine phosphokinase may not be elevated during first week but may be markedly elevated the second (Swanepoel, 1987).

a) Definitive diagnosis of Crimean-Congo hemorrhagic fever may be accomplished by isolation of the Bunyavirus from blood during the first week of illness or detecting rising antibody titer by IRA, complement fixation, or one of several other methods. No data is yet available on evaluation of IgM antibody response (CDC, 1988; Shepherd et al, 1985). In 2 fatalities, no demonstrable IF antibodies were detected at the time of death. In survivors, antibodies have been detected on days 7-8 after onset of illness (Shepherd et al, 1985).
b) Clinical specimens from potentially infected persons should be submitted to a Biosafety Level 4 containment facility ((Anon, 2000); (Anon, 2000a)).

1) High risk contacts with exposure to the virus, should receive postexposure chemoprophylaxis (ribavirin 500 mg orally every 6 hours for 7 days) ((Anon, 2000)).