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HTLV-I: a new AIDS-like threat.

Both are devastating and fatal diseases that have no known cures. The causative agent of both is a virus that can be transmitted through sexual contact, intravenous drug abuse, or blood transfusions, or from mother to child by breastfeeding-and perhaps by intrauterine transmission. Although it all sounds alarmingly familiar, neither of the diseases is AIDS.

One of the diseases is adult T-cell leukemia (ATL), a malignancy with a particularly poor prognosis: frequently death results within six months after diagnosis. ATL in its classic acute form is characterized by large lymph nodes, malignant circulating white blood cells, and significant involvement of the skin, exemplified by numerous skin lesions. It has been postulated that cells infected by the virus also release an agent that causes calcium to be leached from the bones. Hypercalcemia results. The disease is also known to exist in a chronic or smoldering" form. Thus far ATL has been found almost equally distributed between males and females, and the peak occurrences have been in persons between 40 and 60 years old.

The other disease is tropical spastic paraparesis (TSP), a neurological disorder similar to multi le sclerosis characterized by progressive difficulty in walking, lower extremity weakness, sensory disturbances, and urinary incontinence. Eventually the central nervous system and the brain are ravaged by the infectious agent, leading to dementia and death. The disease has been observed more frequently in females than in males. No age group is at particular risk, although peak incidences are in the range of 40 to 49 years of age.

Although there is no requirement in the United States to systematically register ATL with federal authorities, at least 74 cases of ATL were reported to the National Institutes of Health through 1987. To date, most ATL cases reported in the United States have occurred in individuals born outside the United States in areas known to be highly endemic for the causative agent. Of ATL patients born within U.S. borders, most were born in the southeastern portion of the country. The disease is widely recognized in Japan, parts of Africa, and the Caribbean. TSP has also been observed in the same parts of the world as ATL; the number of cases reported in the United States is on the upswing.

The suspected causative agent of both ATL and TSP is a virus known as the human T-cell lymphotropic virus type I HTLV-I). Although it was the first human retrovirus discovered, its kissing cousin," the human immunodeficiency virus HIV-l)-the causative agent of AIDS and the third human retrovirus discovered-has received most of the attention of the media, as well as the funds of the various government tal research-supporting agencies. At least two other human retroviruses are known; still others are suspected. Because the modes of transmission of the known retroviruses are similar and the diseases they cause are, catastrophic, public informa- tion regarding their characteris tics and modes of transmission, along with appropriate preventive actions, is imperative.

Retroviruses as a family first became a scientific curiosity in 1910, when Dr. Peyton Rous discovered the Rous sarcome virus, a cancer-causing virus in chickens. Rous' discovery pre cipitated the emergence of the field of retrovirology. Although other animal retroviruses were discovered that invariably were linked to animal malignancies.. the birth of human retrovirol. ogy was stalled for more than 70 years as scientists through. out the world unsuccessfully searched for evidence of retroviral infections within the human population. That search was culminated in the late 1970s at the National Cancer Institute, where a team of scientists including Drs. Bernard Poiesz, Francis Ruscetti, and Robert Gallo, isolated and characterized the firs human retrovirus and linked it to human malignancy. It was initially referred to as the human T-cell leukemia virus, but now it is named the human T-cell lymphotropic virus type I HTLV-I). Within a year, a second human retrovirus HTLV-II), also linked to a human malignancy, was reported by the same research team. Approximately five years later, the "AIDS" virus, which causes an immunodeficiency, became the third human retrovirus discovered. Its original name, HTLV-III, was changed, however, to the human immunodeficiency virus (HIV-1), because, by convention, viruses are named for the diseases they cause. A fourth human retrovirus, HIV-2, an- has been isolated in patients from West Africa and portions of Europe.

All viruses, whether -.or not they are of the retroviral variety, are among the most highly specialized life forms known to man. Viruses are sophisticated packages of genetic informa- tion surrounded by a variety of protective protein coatings, depending upon the particular virus. Unlike other life forms, they are not compe- tent to survive on their own, because they lack all other life-supporting capabilities. Their only means of survival is to take over the components of the cells they infect and thus commandeer their host's own "cellular machinery" to perform the necessary life-supporting functions.

The genetic information of retroviruses, as well as all other life forms, may be compared to computer software. Just as computer software is needed to direct the activities of the modern computer, genetic information is responsible in an analogous manner for directing all activities of living organisms. Without the required genetic information, all cellular machinery present in living cells would be as useless and as silent as a computer lacking software.

All viruses are packages of genetic software searching for the appropriate and compatible hosts to infect and then control in order to survive and multiply. A retrovirus has the unique ability to actually insert its genetic information directly into the genetic information of the infected host cells. Therefore, when a retrovirus infects a cell, the genetic information present in the retrovirus' "software" permanently reprograms the infected cell's "hardware" to perform the functions desired by the virus.

This requirement for the insertion of retroviral genetic information into the infected individual's genetic in- formation is perhaps one of the most menacing features of retroviruses. Effective treatment would require either the selective elimination of retrovirally infected cells or the ability to discriminately eliminate or alter specific retroviral genetic information within the infected cells. Either procedure is technically difficult. Furthermore, unlike most other STDs (sexually transmitted diseases) that can be effectively controlled with modern antibiotics, a retroviral STD renders the infected individual "once infected-always infected. "

Unlike the AIDS virus, which can cause disease symptoms within a relatively short one to ten years after infection, the HTLV-L virus usually lies dormant for many years perhaps as long as three decades-before the disease manifests itself. This protracted latency period, coupled with the once infected-always infected" reality, poses one of the most dangerous threats of this virus: the capability of a seemingly healthy individual to transmit the virus to other unsuspecting individuals by any mechanism that permits the transfer of body fluids from one individual to another i.e. sexual contact, intravenous drug abuse, blood transfusion, or maternal transmission).

At the present, the highest level of HTLV-I infection is found in southwestern Japan, where infection rates of as high as 20 to 30 percent of the general population have been reported. Even within the highly infected areas of the world the actual rates of infection vary widely from one region to another.

In the course of studies during the mid-1970s to evaluate the potential health effects of the atomic bombs dropped on Japan during World War II, the ATL disease was originally recognized and characterized. The HTLV-I infect virtually all ATL patients evaluated, leading to the ultimate linkage between HTLV-L and ATL. Since those early studies, transmission of HTLV-I infection in Japan by transfusion has been well-documented. Many individuals receiving transfusions of HTLV-I-infected blood that includes cellular blood components show evidence of HTLV-I infection. The same study demonstrated, however, that the recipients of transfusions lacking cellular material (i.e., plasma transfusions) showed no evidence of HTLV-I infection. These data are consistent with laboratory findings which indicate that successful HTLV-I infection requires the contact of HTLV-I-infected cells with the target, non-infected cells-in marked contrast to HIV infection, in which a high incidence of cell-free transmission is observed.

Japan, as the apparent "hotbed" of HTLV-I infection, is the source of valuable information regarding the linkage between TSP and HTLV-I. Virtually all the TSP patients display evidence of infection with HTLV-I, and interestingly, more than a quarter information is available have histories of blood transfusions, with a mean interval between transfusion and the onset of neurologic symptoms of approximately four years.

Japanese data also suggest that for HTLV-I-infected individuals the lifelong risk of developing ATL is approximately 2.5 to 4.5 percent. A similar Jamaican study also suggests an overall risk of ATL disease among HTLV-I-infected individuals of approximately 4 percent. Scientists are currently uncertain of the lifelong risk for TSP among HTLV-I infected individuals, although the latency period between HTLV-I infection and manifestation of disease symptoms is considerably shorter for TSP than for ATL.

In the Caribbean islands, infection rates as high as 5 percent have been reported, and in portions of South America, particularly those areas bordering the Caribbean basin, elevated infection rates have been noted. Within the United States, intravenous drug abusers currently exhibit the highest HTLV-I infection rates, ranging from 7 percent to 49 percent depending upon geographical location. Various sources of clinical data suggest that homosexual men, although at high risk for HIV infection, rarely exhibit HTLV-I infection. Similarly, HTLV-I infection of the other major AIDS risk group, hemophiliacs, currently appears to be nonexistent.

Another major difference between HTLV-I and the AIDS virus is the extent of infections within families of patients. Family members of AIDS patients are generally not infected by the AIDS virus. The exceptions to the rule are either sexual contacts of an AIDS patient or children born to an infected mother. Various studies have indicated that as many as 40 percent of the family members, including parents, spouses, and siblings of ATL patients, are infected with HTLV-I.

At first this ominous fact incorrectly suggested the possibility of casual transmission of the infectious agent, a menacing thought indeed. It is now apparent, however, that intrafamilial transmissions are due to sexual transmission between spouses as well as transmission from mother to child either in utero or via breast-feeding. Accordingly, an infected male or female could sexually infect the other, and the infected female could transmit the virus to her children. Due to the long latency period associated with HTLV-I infection, the vast majority of infected adults may well succumb to other illnesses before the manifestation of HTLV-L disease symptoms. Tragically, infected children may represent the true innocent victims of HTLV-L infection, for their life expectancies are greater than the latency period of HTLV-I.

In a family study of a female adult T-cell leukemia patient, Drs. Lee Ratner and Bernard Poiesz that two sisters and the spouse of the patient have been infected with HTLV-I. One of the infected sisters suffers from chronic ATL, a "smoldering" form of ATL that may persist for many years or progress to acute ATL. The patient's husband and the other HTLV-I-infected sister are both free of disease symptoms. Although the data suggest that the siblings were maternally infected, unfortunately the mother of these individuals was not available for testing. It is also presumed that the husband was sexually infected by the HTLV-infected I-ATL patient. The patient and her husband have three children, none of whom displays any evidence of HTLVI infection or related disease.

Because of the long latency period between HTLV-L infection and the manifestation of HTLV-l disease, all modes of transmission could theoretically proceed in a "silent" manner, because only disease manifestations would lead an otherwise unsuspecting individual to seek medical treatment. A case in point is the death of an elderly, female U.S. ATL patient who, fit into none of the currently suspected risk groups. She was neither an intravenous drug user, nor the recipient of a blood, transfusion. Furthermore, she never had sexual contact with anyone other than her husband of some 40 years. One peculiar circumstance surrounding this case, however, is that although the patient never spent time in any HTLV-I endemic area of the world, her husband spent time in Okinawa, Japan, as a member of the U.S. occupation forces after World War Il. (Even by Japanese standards, Okinawa has an extremely high rate of HTLV-I infection among the general population.) Did her husband contract the virus there more than 40 years ago and subsequently sexually transmit it to her? Using a powerful new tool developed by Cetus Corporation capable of detecting minute quantities of the HTLV-I virus, the deceased ATL patient was found to be infected with HTLV-I. No evidence of HTLV-I infection, however, was detected in the woman's asymptomatic husband. If the husband was the source of the HTLV-I infection, why was the virus not found in his body? Years ago, did he possess transient levels of HTLV-I, sexually transmit the virus to his spouse, and then clear the virus from his own system? Unfortunately, the answers to these questions will probably never be obtained. These circumstances do point, however, to significant global implications of HTLV-I infection that must continue to be explored and evaluated.

The rates of infection of the general U.S. population have been estimated from a nationwide clinical study conducted by the national headquarter s of the American Red Cross. Approximately 40,000 blood donors from eight geographically distinct centers were evaluated for infection with HTLV-I using test kits developed by two different U.S. firms (Cellular Products, Inc., Buffalo, New York, and E.I. du Pont de Nemours & Co., Wilmington, Delaware). This study indicated that ten donors (0.025 percent) were infected with HTLV-I, the highest rates of infection being found in the southeastern United States. This is consistent with the findings that most native- born U.S. ATL patients were born in this quadrant of the country. These compelling data were presented at the American Association of Blood Bankers convention in Orlando, Florida, in November 1987. In a show of hands the assembled blood bankers concurred that, knowing what we know, it would be prudent to begin screening the blood supply for evidence of HTLV-I as soon as FDA-licensed test kits were available. Supportive data was provided to the AIDS Commission in May 1988 in testimony from the author of this article. That testimony also included a recommendation for nationwide blood screening, and the Presidential AIDS Commission made the recommendation in its report to the President on June 23, 1988.

The recommendations for nationwide screening of all blood donors were intended to short-circuit a potential problem one to three decades from now. After the completion of the required clinical studies and review of the clinical data by the U.S. Food and Drug Administration (FDA), diagnostic blood screening tests (manufactured by Abbott Laboratories, Cellular Products, and E.I. du Pont) were licensed on November 29, 1988, by the FDA. The Centers for Disease Control and the FDA simultaneously recommended that all blood donations in the United States intended for transfusion of cell-containing components be screened for evidence of HTLV-I infection.

The call for HTLV-I testing not only represents a major step forward but also is a manifestation of the lessons learned during the AIDS dilemma. By implementing testing today, we may very well ward off the occurrence of another serious retroviral epidemic.

Of perhaps even greater significance, as more information is obtained about retroviruses and their ability to insert their own genetic information into the infected cells' genetic information, the future holds not only hope for a cure for retroviral diseases but also the very real posibility that retroviruses themselves will become powerful scientific tools capable of inserting new genetic information into a diseased individual to correct genetic abnormalities. The ability to control these sinister life forms may very well lead to significant scientific breakthroughs.
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Title Annotation:human T-cell lymphotropic virus type I
Author:Montagna, Richard
Publication:Saturday Evening Post
Date:Jul 1, 1989
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