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Coltiviruses and orbiviruses cause fever. Table 63-1 shows the four human pathogens, their diseases, vectors, and geographic distribution. The most serious of these is Colorado tick fever virus, which will be emphasized in the rest of this chapter. Colorado tick fever virus causes diphasic fever in about half the infected individuals. Colorado tick fever is manifested by headache, chills, muscle pain (especially in the back and legs), and photophobia. Children may have hemorrhagic illness or encephalitic signs (including disorientation and stiff neck). Pericarditis has been reported. The case fatality rate is estimated at 0.2 percent. Most patients recover within 2 weeks, but occasionally convalescence is prolonged.
Kemerovo virus is a tick-borne virus that was isolated from cerebrospinal fluid of two patients in western Siberia in 1962 during a small outbreak of febrile disease. Orungo virus was found in the blood of febrile patients in tropical Africa and is believed to cause small epidemics. Changuinola virus was isolated from a patient with fever in Panama. Little more is known about the disease potential of these three orbiviruses.
Orbiviruses contain 10 segments of double-stranded RNA, exhibit icosahedral symmetry, and are spherical with a diameter of 60 to 80 nm. The total molecular weight is about 12 × 106. Their infectivity is destroyed at pH 3.0. Orbiviruses have at least seven structural and two nonstructural polypeptides.
The genera Orbivirus and Coltivirus consist of at least 109 serotypes of arthropod-borne viruses. They form 13 serogroups and at least 6 ungrouped viruses. The major group-reactive polypeptide is P7, which reacts broadly by the complement fixation test. The major type-specific polypeptide is P2, a surface component principally responsible for the neutralization reaction.
Orbiviruses and Coltivirus replicate in the cytoplasm. They replicate in arthropods as well as in vertebrates and are transmitted by arthropods, thus differing from rotaviruses and reoviruses. The virion outer shell must be removed to activate the RNA-dependent RNA polymerase. RNA segment reassortment between closely related orbiviruses accounts for genetic diversity and may lead to rapid changes in properties of viruses.
Colorado tick fever virus replicates in Dermacentor andersoni ticks that are infected in the larval stage when they feed on blood of the golden-mantled ground squirrel or other rodents (Fig.63-4
). After a period of days or weeks, the virus appears in the tick's saliva. The tick, which remains infectious for life, feeds on humans during its adult stage. The virus does not pass transovarially in the tick.
In humans, Colorado tick fever virus, possibly after infecting the regional lymph nodes, replicates in the bone marrow cells, arresting the maturation of the polymorphonuclear leukocytes, eosinophils, and basophils and sometimes causing severe thrombocytopenia. Erythrocytes presumably are infected as erythroblasts and are later detected in large numbers as antigen-containing red blood cells in the peripheral blood. The virus is found only briefly in serum. Antibody appears about 2 weeks after the onset of symptoms, but virus can still be isolated from peripheral blood cells for up to 6 weeks.
In 3 to 15 percent of infected children under 10 years of age, Colorado tick fever virus invades the central nervous system and causes encephalitis. Virus has been isolated from the cerebrospinal fluid of some of these patients.
There have been very few studies of the host defenses against Colorado tick fever virus. Nonimmune persons appear to be uniformly susceptible. Symptoms subside when humoral antibody appears, although exacerbations are reported; the role of cell-mediated immunity is not known. The virus induces interferon, but it is not known whether interferon is important in host defense.
The distribution of Colorado tick fever is the same as that of its principal tick vector, D andersoni. The disease is found in California, Colorado, Idaho, Montana, Nevada, Oregon, Utah, Washington, Wyoming, British Columbia, and Alberta; 200 to 400 cases are reported each year. Campers, hikers, and foresters are commonly infected. Infections occur mainly in April, May, and June, when adult ticks are abundant. The virus overwinters in nymphal ticks, which feed on and infect small rodents in the spring. The rodents become viremic and in turn infect larval ticks. The larvae metamorphose during the summer; they overwinter as infected nymphs and do not transmit virus to humans until reaching the adult stage, which may be 1 or 2 years after infection. Foci of infected ticks occur primarily in ecologic zones favorable to large populations of ground squirrels and other small rodents.
Colorado tick fever should be suspected in individuals in western North America with diphasic fever, leukopenia, and a history of exposure to ticks 3 to 6 days before onset of disease. Diagnosis depends on isolation of the virus, demonstration of antigen in the red blood cells, or demonstration of a fourfold rise or fall in antibody titer from the acute to the convalescent phase. Virus is readily isolated from erythrocytes by inoculating them into tissue culture or intracerebrally into baby mice. Antibody is washed from red cells or removed by trypsin treatment to enhance the chance of isolation. Red cells may still be positive up to 6 weeks after infection. Antigen also can be detected in red cells by the immunofluorescence technique. Within 1 week of onset of symptoms, antibody appears in the serum as determined by indirect immunofluorescence. Neutralizing antibody appears somewhat later. The complement fixation test does not become positive until about 3 weeks after onset of illness. A travel history can aid the physician and the laboratory in diagnosis. Because of the long duration of viremia, definitive diagnosis of Colorado tick fever has been made in persons returning home far from the endemic area where the infection was acquired.
Colorado tick fever can be prevented by avoiding tick-infested areas, by wearing long-sleeved tightfitting clothing, by checking the body for ticks every 3 hours while camping or hiking and removing them, and by using tick repellents such as diethyltoluamide. Theoretically, campgrounds should be located away from the habitat of the golden-mantled ground squirrel and other rodents; however, these creatures are favorites of campers, and such a measure would not be popular. No vaccine or specific treatment for the disease is available, although the nucleoside analog, 3′-fluors-3′-deoxyadanosine, inhibits replication in vitro.
