Eduardo Gotuzzo is Principal Professor of Medicine and Director of the Instituto de Medicina Tropical "Alexander von Humboldt" at the Universidad Peruana Cayetano Heredia in Lima, Peru. Dr. Gotuzzo is also Head of the Department of Infectious Diseases and Tropical Medicine of the Hospital Nacional Cayetano Heredia.

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HTLV-I: a New Problem for Latin America?

This human retrovirus has been out of the limelight for some time now, but it poses a major public health threat in some parts of the world

Eduardo Gotuzzo

Human T-cell lymphotropic virus type I (HTLV-I), which infects human lymphocytes, became in 1980 the first human retrovirus to be isolated. Experts now realize that this virus is endemic in several Latin American countries, where some consider HTLV-I infections an emerging disease and are concerned over the increasing impact of those infections on public health.

Although many HTLV-I-infected individuals develop no outward symptoms, they become seropositive and remain infected indefinitely, presumably for the rest of their lives. There is no effective therapy for treating such infections, and the development of candidate vaccines to protect against HTLV-I infections has barely begun.

Even though most infected individuals are asymptomatic, small numbers of them develop serious medical problems, including between 1-4% who develop tropical spastic paraparesia, a bilateral form of neurologic disease, and another 1-4% develop acute leukemia/lymphomas, a type of malignancy with a poor prognosis. Other, even less-common diseases, including Norwegian scabies and recurrent uveitis, are also associated with this infection. Further, individuals who happen to be infected with HTLV-I appear to develop more severe disease when they become parasitized by the roundworm Strongyloides stercoralis.

HTLV-I infections typically occur among individuals with low economic resources. In Latin America, the virus often infects members of local ethnic groups, including indigenous peoples with Quechuan Indian origins, and also individuals whose families came from Africa or southern Japan. The virus appears to be sexually transmitted, and breastfeeding is an important risk factor for its acquisition by newborns as a bloodborne disease.

HTLV-I infections occur at high rates in several regions, notably the South of Japan (Okinawa and Kiuchu), where 12-16% of the population is affected; in parts of Africa; in several Latin American countries, including Peru, Colombia, and Brazil; and in several Caribbean countries, including Martinique, Trinidad-Tobago, and Jamaica, where the infection rates range between 2 and 6%.

HTLV-I can be transmitted between individuals by several different means, including vertically between mothers and their newborn children, by blood transfusions, and as a sexually transmitted disease (STD). Small-scale studies have helped to document these routes of transmission.

HTLV-I Is a Major STD in Some Regions

In Latin America and the Caribbean, infections are prevalent among female sex workers, who are seropositive for the virus at rates ranging from 7-25%, and among men who came to STD clinics, for whom the rates were between 5-10%. The prevalence patterns of HTLV-I infections resemble those of other, more common STDs—it typically occurs more frequently among people living in cities than those living in rural villages, and is especially more common among low socioeconomic classes.

There is no doubt that HTLV-I is an STD in Latin America. The virus is found in semen and cervical secretions and is more effectively transmitted from males to females than from females to males. Seropositivity is more frequently observed in groups of high sexual risk such as female sex workers and promiscuous men who have sex with men. The likelihood of transmission is higher for those with a high number of sexual partners, who spend a great deal of time visiting prostitutes, or who have other STDs or other signs of being promiscuous. Most importantly, sexual transmission is significantly reduced by consistent use of condoms.

Two studies, conducted in Lima in female sex workers, showed that the rate of HTLV-I infection among clandestine prostitutes when using condoms was only 1.7%, compared with 10.3% of HTLV-I infection when not using condoms. In other studies among Peruvian registered female sex workers, the infection rate for the use of condoms demonstrated them to be protective.

My colleagues and I studied a group of 83 HTLV-I infected Peruvian women and their offspring to determine whether and how the mothers transmit the virus to their young children. We found the infection in only 1 of 10 (10%) newborns who were not breast-fed, in 5 of 52 (10%) of those who were breast-fed for less than 6 months, and in 43 of 134 (32%) of those breast-fed for more than 6 months.

Among the general population in Caribbean and South American countries, the prevalence of HTLV-I seropositivity increases significantly with age. Moreover, it is higher among women, specifically those in low socioeconomic strata, and correlates with a history of blood transfusion. Peru is the only country in the region that routinely screens donated blood samples for this virus, a safety procedure that should be adopted in other neighboring countries. In several studies with patients with tropical spastic paraparesia (TSP) associated with HTLV-I, between 20% to 40% had antecedents of blood transfusion.

HTLV-I is found among members of major subpopulations among the Native Americans who populated pre-Hispanic America. The virus is found among Northern Amerindians from British Columbia in Canada, and in members of the Paez, Embera, Chachi, and Inga tribes from Colombia in South America. Moreover, the virus is found among peoples in other South American tribes, including Quechuas from Cuzco and Ayacucho, the Mapuches and Huiliches in Chile, in Tobas from Argentina, and among other members of the Andean subfamily.

In several regions of South America there are large populations whose ancestors came from Africa, including Tumaco along the Pacific Coast of Colombia, Bahia in Brazil, and Chincha in Peru. Among these groups, the prevalence of HTLV-I ranges from 2 to 5% among healthy adult populations.

Some researchers believe that HTLV-I was introduced into Latin America by individuals of African descent on several occasions and then spread to closely associated Andean or other groups several centuries ago. Recently, however, this explanation became controversial, following the detection of HTLV-I in a pre-Columbian mummy in Chile, results reported by A. Vandamme and others.

Meanwhile, HTLV-I also is found frequently among Latin Americans of Japanese descent. For example, in Bolivia 17% of the older Japanese immigrants are positive for HTLV-I, according to analysis of blood samples from this population group. In Peru, according to a survey of 407 healthy volunteers with Japanese ancestors, HTLV-I infection rates were 15.8% for those born in Japan, 4% for the first generation born in Peru, and 0% for the second generation. The virus responsible for infecting this Japanese immigrant population group is different from the major strains that are found disseminated throughout Latin America.

Several Diseases Are Found at Higher Frequencies among the HTLV-I Infected

The two most important diseases associated with HLTV-I are acute T-cell leukemia/lymphoma (ATLL) and tropical spastic paraparesia (TSP).

Although the factors responsible for triggering the development of tropical spastic paraparesia or adult T-cell leukemia/lymphoma in HTLV-I infected individuals are unknown, several genetic factors are believed to play a part. Surely at least two different mechanisms are involved, because TSP seems to be an autoimmune process whereas ATLL depends on the virus playing a part in a malignant process.

TSP is a myelopathy characterized by a chronic, progressive, low-grade inflammatory process that involves the gray and white matter of the spinal cord. The clinical pattern includes progressive spasticity in both legs with hypereflexy, urinary incontinence, and constipation. In 1985, Gessain and coworkers at Pasteur Institute found that patients in Martinique typically also had antibodies to HTLV-I in their sera. TSP is a disease predominantly found in Southern Japan, the Caribbean, and South America, mainly from countries such as Brazil, Colombia, Chile, and Peru, and to a lesser extent in Panama, Ecuador, Argentina, the Dominican Republic, Paraguay, and several Caribbean countries. Only a small proportion of HTLV-I- infected individuals develop TSP—about 1 to 4%. Typically, there is a slow onset of symptoms, with steady progression. However, about 10 to 15% of recently diagnosed patients with TSP in Brazil and Peru are developing a very rapid course of symptoms.

During the 1970s, Japan experienced an epidemic of ATLL. By 1980, two research groups isolated the oncogenic virus HTLV-I from patients with this disease. Meanwhile, in Latin America, several investigators, including Pombo in Brazil, Blank in Colombia, and Remondegui in Argentina, also recognized that HTLV-I infections appear to lead to ATLL.

Some 300 new cases of non-Hodgkin's lymphoma are detected each year among patients at the National Institute of Cancer (INEN) in Lima, Peru. At least 30, or 10%, of these new cases occur among individuals who are infected with HTLV-I. In Jamaica, 55% of non-Hodgkin's lymphoma patients are also infected with HTLV-I, versus 5.4% in the general population.

By now, we have confirmed three pathogenic mechanisms associated with this infection: (i) oncogenesis (ATLL); (i) autoimmune disorders (TSP, uveitis, tiroiditis, etc.); and (iii) immunosuppresion (resulting in hyperinfection with Strongyloides stercoralis, Norwegian scabies, etc.). When individuals are colonized by the intestinal nematode Strongyloides stercoralis, they ordinarily develop mild diarrhea. However, it sometimes produces hyperinfections, involving the lungs and other organ systems, especially in patients undergoing chemotherapy, taking corticosteroid drugs, or with AIDS. Investigators in Japan and the Caribbean report that individuals who are infected with HTLV-I also have a high prevalence of S. stercoralis. Of our patients with S. stercoralis hyperinfection, 85.7% (18 of 21) also are infected with HTLV-I. Moreover, when treatment of parasitized patients with standard drugs, such as thiabendazole or ivermectin, fails, in those without known compromised immunity, there is a high risk that they are positive for HTLV-I.

Individuals who are infected with both retroviruses, HIV and HTLV-I, have a higher risk of developing AIDS than do those infected only with HIV. In 1990, in our Peruvian study of 50 patients who were not receiving any antiretroviral treatment, patients with dual infections survived for only 5 months, whereas patients infected with HIV alone survived for twice as long.

SUGGESTED READING

Arango, C., M. T. Rugeles, M. Concha, I. Borrero, H. Lai, S. Lai, C. Bernal, and E. Bernal. 1998. Risk factors for HTLV-I mother to child transmission: influence of genetic markers. Brazilian J. Infect. Dis. 2(3):1-6.

Araujo, A. Q. C., A. C. Leite, S. V. Dultra, et al. 1995. Progression of neurological disbility in HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). J. Neurol. Sci. 129:147.

Blattner, W. A. 1990. Epidemiology of HTLV-I and associated diseases. In W. A. Blattner (ed.), Human retrovirology: HTLV. Raven Press, New York.

Gotuzzo, E. 2000. Risk of transfusion-transmitted human T-cell lymphocyte virus-type I in Latin America (editorial). Int. J. Infect. Dis. 4(2):59-61.

Gotuzzo, E., C. Araujo, A. de Queiroz-Campos, and R. Isturiz. 2000. HTLV-I in Latin America. Infect. Dis. Clin. N. Amer., p. 211-240.

Gotuzzo, E., J. Sanchez, J. Escamilla, et al. 1994. Human T cell lymphotropic virus type I infection among female sex workers in Peru. J. Infect. Dis. 169:754-759.

Gotuzzo, E., A. Terashima, H. Alvarez, R. Tello, R. Infante, D. M. Watts, and D. O. Freedman. 1999. Strongyloides stercoralis hyperinfection associated with HTLV-I infection in Peru. Am. J. Trop. Med. Hyg. 60:146-149.

Gotuzzo, E., V. Yamamoto M. Kanna, G. Chauca, and D. Watts. 1996. Human T lymphotropic virus type I infection among Japanese immigrants in Peru. Int. J. Infect. Dis. 1(2):75-77.

Trujillo, L., D. Munoz, E. Gotuzzo, A. Yi, and D. M. Watts. 1999. Sexual practices and prevalence of HIV, HTLV-I/II and Treponema pallidum among clandestine female sex workers in Lima, Peru. J. Sex. Transm. Dis. 26(2):115-118.

Van Dooren S., E. Gotuzzo, M. Salemi, D. Watts, E. Audenaert, S. Duwe, H. Ellerbrok, R. Grassmann, E. Hagelberg, J. Desmyter, and A. M. Vandamme. 1998. Evidence for a post-Columbian introduction of HTLV-I in Latin America. J. Gen. Virol. 79:2695-2708.