Viral Diseases of the Cardiovascular and Lymphatic Systems
Yellow fever. Yellow fever is a viral disease of the bloodstream transmitted by themosquito Aedes aegypti. The virus is an RNA-containing particle that is icosahedral. After injection by the mosquito, the virus spreads to the lymph nodes and blood, where it persists in the bloodrich organs such as the liver. Very high fever, nausea, and jaundice accompany the disease. The mortality rate is high. Two vaccines are available for preventing yellow fever.
Dengue fever. Dengue fever is transmitted by the Aedes aegypti mosquito and caused by an RNA virus. The viruses enter the bloodstream, where they cause fever and severe muscle, bone, and joint pains, leading to breakbone fever. Successive exposures to the virus may result in dengue hemorrhagic fever, in which extensive hemorrhaging occurs in the blood-rich organs.
Infectious mononucleosis. Infectious mononucleosis is caused by a herpes virus believed to be the Epstein-Barr virus. This virus has DNA and an envelope and the ability to remain latent in the B-lymphocytes. Symptoms of infectious mononucleosis include sore throat, mild fever, enlarged spleen, and an elevation of infected B-lymphocytes known as Downey cells. The viruses are often transmitted by saliva. Treatment usually consists of extensive bed rest, and recurrences are possible.
The virus of infectious mononucleosis is related to a type of tumor of the jaw tissues known as Burkitt's lymphoma. Most often seen in Africa, the condition is related to mononucleosis because of its etiologic agent. The Epstein-Barr virus is also related to cases of Epstein-Barr virus disease, known on occasion as chronic fatigue syndrome.
Acquired immune deficiency syndrome (AIDS). The AIDS epidemic was first recognized in the United States in 1981, when physicians in Los Angeles and other cities noted an unusually large number of opportunistic microbial infections. Destruction of T-lymphocytes of the immune system was associated with these infections. By 1984, the responsible virus had been identified, and in 1986, it was given the name human immunodeficiency virus (HIV).
HIV is a very fragile virus, and for this reason, it does not survive long periods of exposure outside the body. Most cases are transmitted directly from person to person via transfer of blood or semen. The disease is associated with intravenous drug users who use contaminated needles and with individuals who perform anal intercourse, since bleeding is often associated with this practice. Heterosexual intercourse can also be a mode of transmission, especially if lesions occur on the reproductive organs.
In the infected individual, HIV infects T-lymphocytes by combining its spike glycoproteins with the CD4 receptor sites of T-lymphocytes. The nucleocapsid enters the cytoplasm of the T-lymphocyte, and the viral enzyme reverse transcriptase synthesizes DNA molecules using the RNA of HIV as a template (for this reason, the virus is called aretrovirus).
The DNA molecule, known as a provirus, assumes a relationship with the DNA of the T-lymphocyte and enters the state of lysogeny. From this point, the provirus encodes new HIV particles. The human body attempts to keep up with the mass of new viral particles, but eventually, the newly emerging strains of HIV overwhelm the body defenses and the T-lymphocyte count begins to drop. Normally, the count is approximately 800 T-lymphocytes per cubic millimeter of blood, but as the disease progresses, it drops into the low hundreds and tens. This drop may occur as soon as six months after infection or as long as 12 years or longer after infection.
While the T-lymphocytes are infected, and so long as the T-lymphocyte level remains close to normal, the patient is said to have HIV infection. The patient occasionally will suffer swollen lymph nodes, mild prolonged fever, diarrhea, malaise, or other nonspecific symptoms. AIDS is the end stage of the disease. It is signaled by the appearance of opportunistic infections such as candidiasis, an excessively low T-lymphocyte count, a wasting syndrome, or deterioration of the mental faculties.
When a person has progressed to AIDS, an opportunistic infection is usually present. This infection may be Pneumocystis carinii pneumonia; Cryptosporidium diarrhea; encephalitis due to Toxoplasma gondii; severe eye infection and blindness due to cytomegalovirus; candidiasis of the mucous membranes and esophagus due to Candida albicans; meningitis due to Cryptococcus neoformans; or herpes simplex, tuberculosis, or cancer of the skin known as Kaposi's sarcoma. These opportunistic infections are treatable with various drugs, but the AIDS patient is constantly fighting one or the other, and it is difficult to retain the will to continue resisting. As of 1996, close to 600,000 cases of AIDS had been recognized in the United States, and approximately 400,000 patients had died.
Also as of 1996, two types of drugs were available to inhibit the multiplication of HIV. One group is the chain terminators, such as azidothymidine (AZT), dideoxycytidine (ddC), and dideoxyinosine (ddI). These drugs interfere with the synthesis of the DNA molecule using the viral RNA as a template. They effectively interfere with the activity of the reverse transcriptase. The second group consists ofprotease inhibitors. These drugs include saquinivir and indivir. They prevent the synthesis of the viral capsid by interfering with the last steps in preparation of the protein.
Diagnostic tests for AIDS are usually antibody-based tests. These tests seek to determine the presence of antibodies produced by the body on entry of HIV. It takes approximately six weeks for the body to produce sufficient antibodies for a positive test. Other tests called antigen-based tests are designed to detect the virus itself. These tests use gene probes that unite with and signal the presence of the viral DNA if it is present in the T-lymphocytes. Counts of the T-lymphocytes are performed by a process called flow cytometry.
Thus far, vaccines are not available against HIV. There is question, for example, whether whole viruses or viral fragments are preferred for the vaccine. Two glycoproteins called gp 120 and gp41 from the envelope spikes are being investigated as possible vaccines. Tests are hampered however, since animal models are not available for vaccine testing, and it is difficult to find volunteers, who would then be antibody-positive and could suffer discrimination as a result. Nevertheless, candidate vaccines have been prepared not only with gp 120 and gp41, but also with simian immunodeficiency virus (SIV), which infects primates, and viruses mutated so as to have no envelopes. Many candidate vaccines are now in the testing stage, and it is hoped that one will soon be available for the general population.