Zidovudine treatment is not associated with HTLV-1 reverse transcriptase gene mutations in HTLV-I/HIV-1 co-infected patients.

Zidovudine treatment of human immunodeficiency virus (HIV) infection induces drug-resistant viral strains harbouring specific amino acid substitutions in the reverse transcriptase (RT). To investigate whether this phenomenon could be observed in the case of human T lymphotropic virus type I (HTLV-I) infection, we analysed the HTLV-I RT proviral gene sequence in five HTLV-I/HIV-1 co-infected patients treated with zidovudine for HIV-1 infection and in one untreated co-infected subject. In the 816 bp of HTLV-I pol gene sequence determined, no particular nucleotide mutation associated with zidovudine therapy could be identified in the treated subjects. Moreover, the dominant HTLV-1 deduced amino acid sequences determined in treated subjects were identical to that from the untreated subject. Our data show that in the co-infected patients already presenting well-defined mutations associated with zidovudine resistance in HIV-1, no mutations were observed in a part of the pol gene coding for the RT activity of HTLV-I.

HIV/HTLV-I coinfection and clinical grade at diagnosis.

A total of 963 HIV-infected patients have been identified or followed up in Martinique since 1985. Medical files were used to retrieve information about age, sex, circumstances of diagnosis, HTLV-I status, and HIV clinical grade at first examination according to CDC criteria from 1987. Complete information was available for 774 patients. At the first clinical examination, the clinical grade of 65 coinfected patients was more severe than that of the monoinfected patients (GIV versus GII, OR = 2.60, p < 0.01), but after adjustment for age and sex, this odds ratio was reduced 1.57. Although this study cannot invalidate the hypothesis of a faster progression toward AIDS of coinfected than of monoinfected patients, it shows that one or several other mechanisms contribute to the different grades of severity at the first clinical examination observed between these two categories of patients. We believe that HTLV-I infection acquired during adulthood is a marker of high-risk behavior and that it might be associated with early or multiple HIV infections.

[Vasculitis and neurologic manifestations related to HTLV-1]. / Vascularites et manifestations neurologiques liées au HTLV-1.

OBJECTIVES: The most common neurological picture associated with HTLV-1 infection is a slowly progressive spastic paraplegia often involving nerve and muscle inflammation. We report here six cases of inflammatory vasculitis of the nervous system observed among HTLV-1 infected patients. METHODS: HTLV-1 infection was diagnosed in 6 female patients, mean age 58 years (range 40-77 years) using ELISA, Western blot or polymerase chain reaction. RESULTS: All 6 patients presented a pyramidal syndrome which was associated with peripheral neuropathy in 3, myositis in 1 and a sicca syndrome in 3. Two groups of patients could be identified. In 3 patients, the neurological picture was typical of HTLV infection; pathology examination of biopsy material revealed necrozing vasculitis. In 3 other patients, the clinical course was particularly rapid, highly suggestive of anterior spinal artery infarction, associated, in 2, with a major inflammatory syndrome. CONCLUSION: These 6 cases demonstrate that vasculitis can be associated with HTLV-1 infection as has been observed in HIV-infected patients. In certain cases, clinical signs of vasculitis may be lacking while in others they may dominate the clinical manifestations.

HTLV-I maternal transmission in Martinique, using serology and polymerase chain reaction.

We have investigated HTLV-I and HTLV-II infection in children born to HTLV-I-seropositive or indeterminate Western blot mothers in Martinique by using the polymerase chain reaction (PCR). Only HTLV-I and no HTLV-II-positive samples were found in this study. All the samples from HTLV-I-seropositive children and adults were PCR positive, whereas the four HIV-I-seropositive and Western blot HTLV-I-negative mothers and their eight children were all PCR negative. Therefore, PCR and serology were in complete agreement in these patients. However, two of the six mothers who were first indeterminate by Western blot, and who later became seronegative, were found positive by PCR. Of the 27 children (ages 2-12 years), born to HTLV-I-seropositive and PCR-positive mothers, 2 were seropositive and PCR positive, 5 were seronegative and PCR positive with 2 primer pairs in gag and pol, and 4 were seronegative and PCR positive with only 1 of the primer pairs. In contrast to an initial rate of transmission of 7% estimated by serology we found a rate of transmission of 28 to 41% (whether or not children who were positive with only one of the primer pairs were included). Thus, our study confirms that PCR is useful in detecting HTLV-I infection in children before seroconversion and underlines the potential lack of sensitivity of serology to detect contaminating HTLV-I blood units in endemic areas.

[Epidemiological characteristics of HIV infection in Martinique]. / Caractéristiques épidémiologiques de l'infection à VIH en Martinique.

The epidemiologic study of HIV infected patients in Martinique from 1985 to 1992 allowed to point out a stability of new cases by year, and confirm the heterosexual transmission in this area. The sexual comportment of Martinicans seems to be different of the continental French people and different between men and women. This constation is important to know for the preventive strategy of the infection.

HTLV-I infection in French West Indies: a case-control study.

A case-control study was performed in Martinique, French West Indies, comparing 66 anti-p24 antibody carriers to 91 seronegative subjects for HTLV-I, matched for age and place of residence. The aim of our study was to identify factors associated with HTLV-I infection and to observe whether clinical examination and biological measurements would reveal any abnormalities among the seropositive subjects. We observed a predominance of females among seropositive subjects (74% compared to 59%, p less than 0.05), and a greater risk due to earlier blood transfusions (p less than 0.001). This survey revealed important differences between cases and controls regarding socioeconomic factors: cases had fewer luxuries or advantages (i.e. bathroom, toilets, refrigerator, telephone, p less than 0.01), were more corpulent (p less than 0.05), and more often widowed, divorced or separated (p less than 0.01) than the controls. Although the differences were not significant, the seropositive donors seemed to be less educated, and were from a lower socioprofessional class than the seronegative donors. With regard to clinical symptoms (infections, adenopathies, splenomegaly, hepatomegaly) and biological parameters (blood count; T-cell subsets, electrophoresis of protids, immunoglobulins, calcemia, antischistosomal antibody), seropositive subjects appeared to be healthy; no parameters, except for alpha 1 globulin (p less than 0.05) and monocytes (p less than 0.05), were found to be correlated with seropositivity; but these two parameters remained within their normal ranges. This study confirms blood transfusion as a risk factor. It underscored the importance of socioeconomic factors for seropositivity.

[Malignant strongyloidiasis and the HTLV-I virus]. / Anguillulose "maligne" et virus HTLV-I.

A significant association between Strongyloides stercoralis and HTLV-1 infections has been demonstrated in areas (such as southern Japan and the Caribbean) where HTLV-1 is endemic. Due to the immunomodulating effects of the virus and the parasite, patients with both infections would be at risk for overwhelming strongyloidiasis as well as for T-lymphocyte haemopathy. S. stercoralis is thought to be a cofactor for viral replication and leukaemogenic power.

Diagnosis of HTLV-I infected seronegative neurological patients by polymerase chain reaction amplification in Martinique.

HTLV-I is a type C human retrovirus, endemic in Japan, central Africa, South America and the Caribbean, which causes adult T cell leukemia/lymphoma and chronic progressive paraparesis. Some neurological patients with chronic progressive myelopathies, but seronegative for HTLV-I have been reported in Martinique. We performed polymerase chain reaction (PCR), to look for the presence of HTLV-I genomic sequences in those patients. Two primers were chosen for gag and tax genes. Liquid hybridization was performed on the amplified products using an internal 32p labelled oligonucleotide as a probe. The hybridized material was run on a 6% polyacrylamide gel. Forty-three of forty-four seropositive subjects analysed as "positive controls" were positive for gag, but only 16/29 for tax. Twenty HTLV-I seronegative neurological patients with a symptomatology suggesting HAM/TSP were tested: 18 were found positive for at least one of the 2 oligonucleotide pairs. Two "negative controls": Moya-Moya and vascular brain failure were found negative. 8/9 subjects with uninterpretable WB were also studied by PCR, and 8 were found positive for at least one oligo pair. Our conclusion is that PCR methodology is able to detect genetic information related to HTLV-I in a number of cases where classical serology is negative.

[Sero-epidemiology of viral hepatitis A, B and delta in Martinique]. / Séro-épidémiologie des hépatites virales A, B et delta en Martinique.

In view of the ethnic and geographical peculiarities of the French department of Martinique and of the endemic character of hepatitis in tropical countries, we studied the prevalence of infections with hepatitis A, B and delta viruses in that region. A group of 10,109 blood donors and a group of about 100 patients were selected on account of their liver symptoms. As regards hepatitis A, the study of the 2 groups was completed by a sero-epidemiological survey of 509 children and teenagers aged from 1 to 18 years. The prevalence of the HB antigen among blood donors was 1.3 per cent, i.e. about 10 times higher than in Europe and 7 times lower than in hyperendemic tropical areas. It was 2.5 times higher in the male than in the female population; 84 per cent of HBs-positive donors had anti-HBe antibodies, 9 per cent had HBe antigen and 7 per cent had neither one nor the other. This distribution is coherent with a population of symptomless carriers. The prevalence of anti-HBs-positive sera was 34 per cent as against 70-95 per cent in highly endemic countries and 4-20 per cent in Europe; 1.9 per cent of the HBs donors studied and 8.8 per cent of the patients had anti-delta antibodies; 11 of the 13 anti-delta-positive subjects had anti-HBe antibodies and 2 had neither HBe nor anti-HBe. Between the ages of 1 and 3 years very few anti-HAV-positive subjects were observed. From 3 to 10 years, the percentage of seroconversions increased moderately. Between 10 and 20 years, the number of positive cases increased considerably reaching 67 per cent at 20 years and 100 per cent at and above 45 years. Among the patients, 97 were positive for IgG (96 per cent) and only 5 for IgM (4 per cent).

HTLV-I-associated tropical spastic paraparesis in Martinique: a reappraisal.

Human T-lymphotropic virus type I (HTLV-I)-associated tropical spastic paraparesis in Martinique has been identified in 54 patients, 49 women and 5 men. This myelopathy represents an endemic problem on this island and the earliest documented case dates from 1952. A blood transfusion history was obtained in 7 of the 54 patients (13%). There was a preponderance of cases from the northern Atlantic coast of Martinique, the most humid region on the island. The prevalence in this region reached 49.5 per 100,000, compared with the global prevalence of 11.9 cases per 100,000 for the island. An immune-mediated mechanism may be important in the pathogenesis of HTLV-I-associated tropical spastic paraparesis.