pharyngeal injection); (ii) hypotensive phase (may range from mild hypotension to shock and
hemorrhage lasting for one to two days); (iii) oliguric phase (associated with hypertension,
renal failure, pulmonary edema, confusion); (iv) diuretic phase (may last several months); and
(v) convalescence. Patients typically have thrombocytopenia, leukocytosis, hemoconcentration,
abnormal clotting profile, and proteinuria. Mortality is from 1% to 15%.
Hantavirus pulmonary syndromepresents with a prodromal stage (three to five days—
range: 1–10 days) followed by a sudden onset of fever, myalgia, malaise, chills, anorexia, and
headache. Patients go on to develop prostration, nausea, vomiting, abdominal pain, and
diarrhea. This progresses to cardiopulmonary compromise with a nonproductive cough,
tachypnea, fever, mild hypotension, and hypoxia. Chest X rays are initially normal but
progress to pulmonary edema and acute respiratory distress syndrome. Patients have
thrombocytopenia, leukocytosis, elevated partial thromboplastin times, and serum lactic acid
and lactate dehydrogenase. Few patients develop DIC.
Patients infected withEbola virushave a sudden onset of fever, headache, myalgia,
abdominal pain, diarrhea, pharyngitis, herpetic lesions of the mouth and pharynx, conjunctival
injection, and bleeding from the gums. The initial faint maculopapular rash that may be missed
in dark-skinned individuals evolves into petechiae, ecchymosis, and bleeding from
venepuncture sites and mucosa. Hemiplegia, psychosis, coma, and seizures are common.
Mortality rates are 60% to 90%.
Marburg hemorrhagic feveris similar with a sudden onset of symptoms progressing to
multiorgan failure and hemorrhagic fever syndrome. Some but not all of these patients may
present with a maculopapular rash. Mortality is 25% to 90% (average 25% to 30%).
Half of the patients withdengue hemorrhagic feverand classical dengue have a transient
rash. Two to five days after classical dengue fever, patients go into shock, develop
hepatomegaly, liver enzyme elevations, and hemorrhagic manifestations. Patients develop
respiratory and renal failure. Mortality is 10% but may be reduced to<1% with aggressive
supportive care.
Differential diagnosis: Malaria, typhoid, gastroenteritis, meningococcemia, etc.
Treatmentis supportive for all infections. Ribavirin has been used for prophylaxis and
treatment of Lassa fever, Sabia virus hemorrhagic fever, Argentine hemorrhagic fever, Bolivian
hemorrhagic fever, Rift Valley fever, Crimean-Congo hemorrhagic fever, and Venezuelan
hemorrhagic fever. Convalescent serum therapy has been used for Venezuelan hemorrhagic
fever. Ribavirin has been used to treat Hantavirus hemorrhagic fever with renal syndrome but
does not appear effective in treating Hantavirus pulmonary syndrome. There is no specific
therapy for yellow fever, Ebola, or Marburg virus infections. Ribavirin has not shown promise
in nonhuman primates (118). Ampligen (polyI:polyC12U) induces interferon production and is
being investigated as a treatment modality for dengue, chronic fatigue syndrome, HIV,
Epstein-Barr virus-positive Hodgkin’s lymphoma, and other entities.
Intravenous ribavirin is twice as effective as oral medication. The intravenous regimen
recommended for the viral hemorrhagic fevers is as follows: 2 g loading dose, followed by 1 g
every six hours for four days, followed by 0.5 g every eight hours for six days. Another
intravenous regimen: 30 mg/kg loading dose, followed by 15 mg/kg every six hours for four
days; followed by 7.5 mg/kg every eight hours for six days. Oral regimen: 2 g loading dose,
followed by 4 g/day in four divided doses for four days; followed by 2 g/day for six days.
Smallpox (11)
Humans are the only natural reservoir for smallpox virus (Poxvirus variolae,genus
Orthopoxvirus—a linear, double-stranded DNA virus). Infection is naturally acquired by
inhalation. Aerosolized virus is inactivated in 48 hours, but may remain viable in house dust
for up to two years. Exposure to contaminated materials, clothing, and blankets can spread
infection, and although rare, infection over long distances has been reported.
Incubation period: 10 to 12 days; range: 6 to 22 days.
Contagious period: Patients are not contagious during the incubation period but one to two
days before the onset of symptoms or when the oral enanthema appears (24 hours prior to the
rash). Viral shedding is greatest during the first 10 days of the rash, but persists until all scabs
and crusts are shed. Infection rates for close contacts are 37% to 88%.
476 Cleri et al.