Answers to these questions reveal a story that raises some serious questions about government policy on infectious disease.
The story starts in the 1970s, when Gallo's lab had been pursuing the conviction that viruses cause human cancers, especially leukemias and lymphomas, which are blood cancers originating in the bone marrow or lymphatic tissues. Scientists already knew that a specific genus, the retroviruses, caused leukemias in some animals -- notably primates and domestic cats. Retroviruses are a unique family because their mode of invading cells and reproducing -- the way in which they process their RNA into DNA of the host cell -- is different from that of most other viruses.
A Tangled Web of Discoveries
In 1978, Gallo's people found the first-in-history human retrovirus in a human patient with lymphoma. By 1981 Gallo had named it HTLV-1, but he couldn't prove that the retrovirus actually caused lymphoma. That breakthrough was made by Japanese researchers, who nailed HTLV-1 as the cause of adult T-cell leukemia, which was first noted in Japan and was becoming endemic there. HTLV-1 was later linked to both lymphoma and leukemia, as well as certain crippling disorders of the central nervous system, and possibly multiple sclerosis.
In 1982 Gallo discovered a related retrovirus that he named HTLV-2. Eventually a few studies linked it to a specific disorder -- hairy-cell leukemia. Meanwhile, in 1986 a second sub-type of HIV was identified in West Africa. So far, that region is mainly where the variant is found. The NIH refers to this one as both HIV-2 and HTLV-4.
Scientists have noted differences -- and also similarities -- between HTLV-1/2 and HTLV-3/4. Authors George W. Lowis, Edwin Van Teulingen and William Sheremata discuss these in their article "AIDS in Developing Countries: A Comparative Epidemiologic Analysis." According to them, HTLV-III and IV "were renamed human immunodeficiency virus (HIV) since they differ significantly in their structure and in the pathology of the diseases they cause. ...Despite these important differences, the four members of the HTLV family have sole common epidemiologic features in that: (a) they are exogenous human infecting viruses and (b) their transmission occurs by whole blood or its derivatives and through sexual intercourse." HIV-2/HTLV-4 is an oddball member of the family, because it shares two proteins with HTLV-1 and -2.
Science did note that HTLV-1 progresses to full-blown disease much more slowly than HIV does. Sometimes 10 or 20 years can go by before T-cell leukemia or lymphoma actually develops --and it does this in perhaps 1 out of every 20 carriers. But healthy carriers are able to transmit the HTLV viruses to others, by the same routes as HIV is said to be transmitted, including blood transfusion. By 1983, the CDC even knew that a certain percentage of HIV-positive persons were co-infected with HTLV-1 and -2.
Today, HTLV-1 is described as endemic in Japan, parts of Africa, the Caribbean and South America. But according to Journal of Clinical Virology, "HTLV-2 has a worldwide distribution and is epidemic among injection drug users." This means that many drug-users can be co-infected with HTLV-2. In the U.S., statistics on the incidence of both viruses are hard to find. Yet with all the immigration both legal and illegal that is streaming into the U.S., and the drug-using risk groups being so numerous in our crowded prisons, where infectious organisms are spreading like wildfire, it's possible that there are way more HTLV-1 and HTLV-2 carriers than our government knows.
Yet a decision was evidently made, at the highest levels of government, to soft-pedal the public positioning on HTLV-1 and -2. I've been wondering why.
The Question of Treatments
The search for HIV treatments has constituted high drama for the medical and media worlds. AZT had been developed in 1964 as a type of chemotherapy for cancer, but was shelved because of its high toxicity. But when AIDS came along and there was an outcry for treatment, AZT was hauled off the shelf and fast-tracked to market by the FDA. Next came a whole spate of different groups of new drugs, many of which are also problematical as to side effects. A parallel effort has been the work by various researchers to develop an AIDS vaccine.
But what of treatment for the diseases caused by these two HTLV viruses?
According to the Johns Hopkins HIV Guide, which has a section on the two HTLV viruses, there is "no evidence for benefit of antiviral therapy" for those who have asymptomatic infections. Says the Guide: "HTLV genome [is] integrated into host DNA; therefore, eradication [is] probably not possible." This is radically different advice than given to HIV+ people who are still asymptomatic, for whom early treatment -- HAART -- has been advised.
For those who do develop disease, treatment for adult T-cell leukemia and lymphoma is iffy. These are aggressive and fast-moving malignant disorders -- most patients survive less than a year. Researchers do report some cases of patients who successfully undergo standard chemotherapy and bone-marrow transplants, and who were able to go on living in complete recession.
But the outlook for treating hairy-cell leukemia is apparently more optimistic. New England Journal of Medicine has reported "lasting remissions in hairy-cell leukemia induced by a single infusion of 2-chlorodeoxyadenosine." This infusion is intravenous, and lasts one week. The drug, approved by FDA in 1993 under the brand name Leustatin, was developed by Ortho Biotech.
Leustatin is also being used for treating other leukemias and MS. However, with its cost running at perhaps $800 a month, this is not likely a drug that will handily be available for at-risk demographics in the U.S. (since injection drug-users are often low-income or homeless people). Nor would it be easily affordable in developing parts of the world, where a poor family might earn way less than $800 a year.
Though many scientists agree that serious diseases are caused by HTLV-1 and -2, you have to look hard to find mention of them at the CDC website. Even T-cell leukemia and lymphoma are not listed in the CDC's prominent alphabetical index of infectious diseases, though they are caused by infectious organisms.
Instead, T-cell lymphoma/leukemia and these two viruses are buried in CDC's "search results." But if you look there, you do find a healthy literature on both viruses. There's a 2006 article by Siobhán M. O'Connor, Christopher E. Taylor, and James M. Hughes, who tell us, "Evidence now confirms that noncommunicable chronic diseases can stem from infectious agents." The authors mention "three very different outcomes of human T-cell lymphotropic virus type 1 (HTLV-1) infection: acute T-leukemia/lymphoma, tropical spastic paraparesis/HTLV-1-associated myelopathy, and chronic arthropathy."
Tropical spastic paraparesis/HAM is one of the neurological disorders associated with -1 -- it results in progressive crippling weakness of the lower limbs.
Also buried there is an article stating, "HTLV-1 infection in the United States appears to be rare. Although little serologic data exist, prevalence of infection is thought to be highest among blacks living in the Southeast." Yet the article goes on to say, " A prevalence rate of 30% has been found among black intravenous drug abusers in New Jersey, and a rate of 49% has been found in a similar group in New Orleans (8). It is possible that prevalence of infection is increasing in this risk group." Forty-nine and 30 percent are pretty hefty percentages for a virus that is supposedly "rare."
Another CDC abstract says, "Researchers found that 6.7 percent of 1,305 prostitutes surveyed in eight cities between 1986 and 1988 were infected with HTLV-1 or HTLV-2, a related virus. Public health authorities are increasingly concerned with the prevalence of HTLV-1, which is probably transmitted to prostitutes via sex with IV drug users."
Elsewhere, the American Cancer Society sheds a bit more light -- but not much. For 2007 in the U.S., they reported 19,730 lymphoma deaths in 2006, along with 21,790 deaths from leukemia. But all the different forms of leukemia and lymphoma are lumped together, making it difficult to get a profile on the numbers of HTLV-1 caused deaths. The ACS explains that often it is difficult to get exact information on a cancer casualty's cause of death.
But if we posit that the 1 in 20 figure is correct, and that 10,000 of those 21,790 annual deaths are due to the adult T-cell variety, that means that possibly 200,000 Americans would be HTLV-1 positives.
Motive for a Blood Test
Alarming risk-group statistics like these may have motivated the U.S. to quietly develop an antibody test for both viruses. In 1988, just as quietly, the government began screening its blood supply for HTLV-1 and -2. The government also barred organ donations by people infected with the two HTLVs. So we have to wonder -- why the apparent choice of a low profile on viruses that the U.S. considers enough of a threat to screen blood for? Especially in the case of HTLV-2, whose link to disease is questioned by some?
The government's official position was that both viruses were "rare" in the U.S. Yet just a year later, in 1989, the New York Times published a story about some new surveys that were termed "frightening" by David Golde, who worked with Gallo on discovering HTLV-2 in 1982. The story was headlined VIRUS THAT MAY CAUSE LEUKEMIA IS SPREADING AMONG DRUG ADDICTS.
In the article, the Times said: "The virus, HTLV-II, ... has been found in about 20 percent of a group of drug addicts in New Orleans, from 4 percent to 10 percent of a group of drug users in New York, and 20 percent of a group of New York drug addicts who were also suffering from AIDS. A preliminary survey of blood donors in the San Francisco area found that the virus, though very rare, was more widespread than the AIDS virus. Another survey found HTLV-II more prevalent in blood donors in Los Angeles and New Orleans than the results reported from San Francisco."
This Times story about a "rare" virus infecting hundreds of addicts and blood donors, produced only a ripple -- compared to the tidal wave of national panic that had been set off by the Times's now-famous 1981 story headlined RARE CANCER SEEN IN 41 HOMOSEXUALS.
Today the U.S.'s low profile on HTLV-1 and -2 extends to its global views. The National Institute of Allergy and Infectious Diseases (NIAID) maintains a detailed list of emerging and re-emerging diseases that have global implications for us because of immigration, trade, tourism and terrorism. NIAID's list can be found online -- but it doesn't mention either HTLV-1 or -2.
Outside of the U.S., however, HTLV-1 and 2 are taken more seriously. They have gotten a high profile on the World Health Organization's global list of dozens of emerging infectious diseases that have been recognized since 1973, when the list was first developed. The global list has lengthened to 36, with SARS and swine flu being recent additions. The two "cousin retroviruses" were right there on the WHO list in company with pathogens that cause scary things like Ebola, Lassa fever and hemorrhagic fever. As I write this, the list is headlined in the UN Chronicle
According to Blood Magazine, "Currently, the estimated number of people infected with HTLV-I worldwide is between 15 and 25 million."
Fifteen to 25 million is a lot of people who are capable of transmitting the virus to others -- and those others then have no idea that they might be among those 1-in-20s who will develop a devastating, possibly fatal illness. So...since there is global cause for concern, why didn't the U.S. public get told more about HTLV-1 and -2 over the years?
A Look at Co-Infected PWAs
Did the government soft-pedal HTLV-1 and -2 because it was reacting rapidly to the panic caused by the emergence of AIDS? Because it didn't want to rock the boat by mentioning other retroviruses that are related to HIV?
Eventually the CDC did publish guidelines for the HTLVs, in which the government's schizoid position on the HTLVs is visible. The guidelines are very emphatic that blood donors who test positive for either retrovirus "should be told that [it] is not the AIDS virus, that it does not cause AIDS, and that AIDS is caused by a different virus called HIV." Nevertheless CDC recommendations for HTLVs are almost as stringent as those for HIV -- positives should use condoms, refrain from donating semen and breastfeeding, etc. So the agency is clearly anxious that these retroviruses not be transmitted. Yet the guidelines insist that no link between HTLV-2 and any infectious disease has been proven. So...if there is no proof, why the need for a CDC dictum on HTLV-2?
Today it's still hard to find official estimates of how many Americans are carriers of the HTLVs, or co-infected with HIV.
It's true that CDC, NIAID and NIH have talked a great deal about "co-factors" in AIDS -- especially those that are caused by unrelated organisms, such as tuberculosis, syphilis, Kaposi's sarcoma -- pathogens whose activity in the body could make the HIV+ person more vulnerable to the development of full-blown AIDS. But co-factors that are caused by retroviruses related to HIV might have been a different matter. Was the government concerned that the public would become confused about which organism was actually killing people?
Through the late 1980s and into the '90s, quite a few researchers looked at HIV+ persons who were co-infected with either or both of the HTLV viruses, trying to get a bead on exactly how the HTLVs might impact the history of HIV in each body. But different studies didn't always agree.
Italian researchers, in particular, did some significant study on this question. According to a 1991 article by Italian researchers on the NIH website, HTLV-1 "is known to accelerate progression of the HIV infection to AIDS." In a small Italian study published in Infection in 1995, the researchers claimed that they could find no influence of HTLV-2 on the natural history of HIV infection. But in another Italian study published in 1999, involving 1152 HIV-positive patients who were screened for HTLV-2 infection, patients "had an increased risk of developing peripheral neuropathy .... These results support the hypothesis that HTLV-2 plays a role in the development of neurologic abnormalities in HIV-1-infected patients."
Today the nagging questions of what these two viruses can do to a human system already infected with HIV are still not answered. Johns Hopkins finds "[the] effect of HTLV-I/II on HIV disease progression controversial, with different studies reaching opposite conclusions."
Emerging Patient Activism
As with AIDS, the HTLVs have their patient activists. But HTLV activism has been way slower to develop, given the low profile put on these two retroviruses.
A pioneer in this area is Richard Engnath, an older man who lives in New York State. In 2004, Richard tells me, he thought he was developing AIDS, but his HIV test was negative. Persistence of painful neurological symptoms led his doctor to do further study and testing, and Engnath came up positive on the HTLV-1 test. His doctor thinks that Engnath might be in the early stages of tropical spastic paraparesis/HAM. Engnath is an example of a case cropping up well outside the Southeastern area where U.S. infectious-disease authorities believed the HTLV-1 virus to be concentrated.
When Engnath started looking for information about his disease, he was shocked all over again. Though there were standard tests (ELISA, Western blot) for the infection he had, there was no specific patient-support organization for him to go to. Even the Leukemia & Lymphoma Society doesn't discuss the virally caused T-cell disorders, preferring to concentrate on the B-cell disorders that may have environmental, genetic or other causes. Outraged at the scarcity of information, Engnath started his own NGO and toiled to create printed materials and a poster about HTLV-1 and -2 at his own cost. Slowly but surely, in his home state, he's getting the attention of health-conscious politicians like New York's Congressman Maurice Hinchey.
Engnath's sense of shock is echoed by that of Robert Parete, chairman of the Health Services Committee for the Ulster County legislature in New York State. After he saw Engnath's documentation in summer 2009, Parete put out a memo to the local healthcare facilities, telling them about "a growing epidemic that almost all Committee Members were largely or entirely unaware of." Parete expressed his shock that all 50 state departments of health had known about the HTLVs since the mid-1980s but had never developed an information campaign. He urged them to display Engnath's poster as a measure of education/prevention.
Today the Web offers some informational resources for the HTLVs -- they even include Wikipedia articles -- but there is definitely room for improvement. Meanwhile, Engnath continues his patient activism to help publicize HTLV-1 and -2, and to encourage people to protect themselves and have themselves tested if they want to know their status. For more information, write or phone to:
HTLV National Registry
Richard R. Engnath, Founder
199 Wall Street
Kingston, NY 12401-4517
A last-but-not least-question: Even if the U.S. government were to decide to put a higher priority on HTLV research and prevention, how will its agencies get rolling on this issue in a time of economic crisis, when they are slashing HIV funding right and left? This is a question that might be tough to answer.
Note: For many years, I have written a monthly column on AIDS politics and public-health politics for A & U Magazine. An archive of my columns can be found at the A & U website. A shorter version of this article was published in my "Left Field" column in A & U's August 2009 issue.