The respiratory tract infections caused by HPIV-1 and HPIV-3 may be limited to the upper respiratory tract, causing colds, or may also involve the lower respiratory tract, causing bronchopneumonia, bronchiolitis, or bronchitis. These viruses are widespread around the world and are an important cause of lower respiratory tract disease in young children. Serological studies have shown that most children are infected by HPIV-3 by 2-4 years of age, and that the incidence of infection can be as high as 67 out of 100 children per year during the first 2 years of life (that is, reinfections are common). Thus, immunity is incomplete and the viruses continue to reinfect older children and adults. However, subsequent infections are normally less severe and there is a reduction in the incidence of lower respiratory tract disease (which is more serious than infection of the upper respiratory tract). The viruses, as is common for respiratory tract infections, are spread by respiratory droplets.
Attempts to develop vaccines against the HPIVs have not met with success. Because of incomplete immunity produced by natural infections, the primary purpose of a vaccine would be to decrease the severity of natural infection by the virus. Even so, results to date have been disappointing. Inactivated virus vaccines developed for HPIV-1 and -3, as well as for HPIV-2, a rubulavirus, were antigenic but failed to induce resistance to the viruses. This could have resulted from failure to develop IgA following a par-enterally administered vaccine (Chapter 8), and attempts to develop effective vaccines are continuing.
The genus Rubulavirus gets its name from an old name for mumps, which is the disease produced in humans by mumps virus. The only natural host for mumps virus is humans and the virus is transmitted from person to person by contact. The disease has been known since the 5th century b.c. The incubation period, that is, the period of time between infection by the virus and the development of symptoms, is about 18 days. During the last 7 days of the incubation period, a person sheds virus and is capable of infecting others. Infection of children is usually not serious, but mumps virus infection can cause serious illness, particularly in adults. Infection begins in the upper respiratory tract but becomes systemic with the virus infecting many organs, where it replicates in epithelial cells. It is best known for infection of the parotid salivary glands leading to painful swelling of these glands. More serious disease can result from the replication of the virus in other organs, however. The central nervous system (CNS) is a common target for the virus and 0.5-2.3% cases of mumps encephalitis are fatal. Infection of the pancreas can occur, and it has been suggested that mumps may be associated with sudden onset insulin-dependent diabetes. The heart is sometimes infected, resulting in myocarditis. Infection of the testes in adult males can lead to orchitis and, in rare cases, to sterility. Infection of the fetus can result in spontaneous abortion.
At one time, mumps was one of the common childhood diseases that was contracted by almost everyone. It is now controlled in developed countries by an effective attenuated virus vaccine that was selected by passage of the virus in embryonated eggs. This mumps vaccine is given as part of the MMR (measles-mumps- rubella) combination vaccine. The dramatic decline in cases of mumps in the United
States after introduction of this vaccine is shown in Fig. 4.8. Because mumps is exclusively a human virus that induces effective immunity following infection, and infection of an individual requires direct contact with a person actively shedding the virus, the virus requires a population of about 200,000 people to sustain it. Such a population density was first attained 4000 or 5000 years ago, before which mumps could not have existed, at least in its current form.
Other human rubulaviruses include HPIV-2 and HPIV-4. They are named human parainfluenza viruses because the disease they cause is similar to that caused by HPIV-1 and HPIV-3. However, they are genetically related to the rubulaviruses rather than to the respiroviruses (Fig. 4.5). Other members of the rubulavirus genus infect many mammals and birds. One of the most intensively studied rubulaviruses (studied as a model system for replication of members of the family) has been SV-5 (simian virus 5). During the development of the polio vaccine, Rhesus monkey kidney cells were used for replication of poliovirus in culture, and these cultures were often contaminated with monkey viruses. These simian viruses (SVs) were simply numbered as they were isolated, and any particular SV may be totally unrelated to any other. Two of the most widely studied are SV-5 and SV-40, which are not related to one another: SV-5 is an RNA-containing paramyxovirus and SV-40 is a DNA-containing polyomavirus (Chapter 6).
The avian viruses include nine serologically distinct paramyxoviruses. These viruses form a distinct lineage, but clearly group with the rubulaviruses (Fig. 4.5). APMV-1 is also known as Newcastle disease virus (NDV), which causes a highly contagious and fatal disease of birds. NDV has serious economic consequences because it infects chickens, among other avian hosts. When epidemics break out, and they do with some regularity, many birds die, causing economic losses. Quarantines are placed on the movement of birds during epidemics in an effort to curtail the spread of the virus, which could have further economic consequences.
The genus Morbillivirus contains measles virus as well as a number of nonhuman pathogens that include rinderpest virus, which infects cattle and pigs, and distemper viruses of dogs, dolphins, and porpoises. The relationships among these viruses are illustrated in Fig. 4.5.
Measles virus causes serious illness in man. Infection begins in the upper respiratory tract but becomes systemic, and many organs become infected. Lymphoid organs and
Mumps vaccine licensed in 1967 ^ 7- -
Mumps vaccine licensed in 1967 ^ 7- -
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