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Risk Factors for HTLV-I Mother to Child Transmission: Influence of Genetic Markers.

This study was designed to evaluate the influence of genetic markers on the seropositivity of offspring of HTLV-I positive mothers in Tumaco, Colombia, an endemic area for HTLV-I infection and a site where there exists a racially mixed population of Black and Caucasian ancestors. 33 HTLV-I seropositive women with at least one offspring were studied. A total of 111 offspring were tested using hemaglutination-inhibition for testing sera for the allotypic markers G1m (1, 2, 3, 17) and G3m (5, 6, 13, 21). Potential risk factors such as mother s age at child's birth, mother's age at the time of the study, breastfeeding months, TSP vs. asymptomatic HTLV-I carrier, sibship's size, children's age and sex, were not found to be associated with mother to child transmission. Mother's Negroid genetic marker genotype (1, 17, 5, 13/1, 17, 5, +/- 13) was marginally associated with mother to child transmission of HTLV-I (P=0.0057; OR=11.97; CI=0.92-155.96)

Surgical combination therapy for vitiligo and piebaldism.

BACKGROUND: Refractory and stable defects of vitiligo and piebaldism may be unresponsive to medical therapy. Melanocyte transplantation can restore the normal pigmentation in some selected patients. OBJECTIVES: To evaluate the efficacy of additional mini-grafting with 1.0-1.2-mm punch grafts to complete the restoration of achromic defects when performing surgical correction of leukoderma. METHODS: Eight patients with refractory stable leukoderma were treated with melanocyte transplantation; three with segmental vitiligo had epidermal shave, by removing the hyperpigmented macules at the periphery of achromic lesions; two others received suction epidermal grafts; and three subjects were treated by in vitro cultured epidermal autografts. All patients received additional mini-grafts in areas of residual achromia. RESULTS: The depigmented defects were 100% restored in seven patients, and in one subject 80% improvement was observed. CONCLUSION: Surgical methods, followed by additional mini-grafting, may be helpful to restore completely the depigmented defects when residual achromia, after treatment with the methods described above, is still present.

Tax mutation associated with tropical spastic paraparesis/human T-cell leukemia virus type I-associated myelopathy.

Tumaco, Colombia, is an area with elevated rates of tropical spastic paraparesis/human T-cell leukemia virus type I (HTLV-I)-associated myelopathy (TSP/HAM). We have identified a mutation in nucleotide 7959 of the tax gene of 14 Tumaco HTLV-I isolates (14 positive of 14 tested) that was present in 5 of 14 (35%) TSP/HAM patients from Japan and in 8 of 11 (72%) TSP/HAM patients from other geographic locations. In contrast, this mutation was found in only 2 of 21 (9.5%) HTLV-I-infected subjects outside of Tumaco who did not have TSP/HAM. tax clones with nucleotide mutations including one at nucleotide 7959 showed a greater ability to transactivate the HTLV-I U3 promoter. However, this effect was not observed when two clones that differed only in nucleotide 7959 were compared. These results suggest that HTLV-I-infected individuals carrying isolates with this tax mutation are at higher risk for developing TSP/HAM.

Nucleotide sequences of human T-lymphotropic virus type I (HTLV-I) from a family cluster with tropical spastic paraparesis/HTLV-I-associated myelopathy.

We describe nucleotide sequences of human T-lymphotropic virus type I (HTLV-I) proviruses from three symptomatic family members with tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) from Tumaco, Colombia. Polymerase chain reaction was used to clone the U3 region, envelope and tax/rex genes of these HTLV-I proviruses from fresh peripheral blood lymphocytes. Sequences in U3, env and tax/rex showed 96.9-99.5% conservation when compared with sequences from HTLV-I clone ATK, and 96.6-100% when compared with each other. The range of sequence divergence within the family was similar to that described between unrelated TSP/HAM patients of the same geographical origin. Certain mutations were present in all three family members, supporting a geographic and/or familial segregation of mutations.

Human T-lymphotropic virus type I (HTLV-I)-specific antibodies and cell-free RNA in crevicular fluid-rich saliva from patients with tropical spastic paraparesis/HTLV-I-associated myelopathy.

Despite the likely role of mucosae in human T cell leukemia virus type I (HTLV-I) transmission, little is known about the mucosal immune response to HTLV-I. The present study evaluated the antibody response to HTLV-I in oral mucosa and the value of crevicular fluid rich saliva (CFRS) for diagnosing HTLV-I infection. CFRS and sera from patients with tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM), asymptomatic carriers, and HTLV-I seronegative individuals from Tumaco, Colombia, were analyzed for HTLV-I specific IgG, IgA, and secretory IgA (sIgA). Detection of IgG in CFRS by enzyme-linked immunosorbent assay correlated with its presence in sera for TSP/HAM patients and asymptomatic carriers. IgA and sIgA were more frequently detected in CFRS and sera from TSP/HAM patients than in those from asymptomatic carriers. An HTLV-I pol fragment could be amplified from CFRS by reverse transcriptase-PCR in 3 TSP/HAM patients and one asymptomatic carrier, all of whom had an IgA response in CFRS but not in sera. The more frequent detection of IgA and sIgA in sera and CFRS of TSP/HAM patients suggests increased viral replication. Further, the association of viral RNA in CFRS with a local IgA response may signify rounds of viral replication in the oral cavity.

Seroprevalence and cofactors of HTLV-I infection in Tumaco, Colombia.

This study presents an analysis of the factors associated with HTLV-I seroprevalence in the endemic area of Tumaco, Colombia. During June to August 1988, 1,077 individuals were selected at random from a population of 45,594. The overall prevalence rate of HTLV-I antibodies was 2.8%. Among females prevalence was significantly higher (p less than 0.02) than among males. Rates increased substantially with age. HTLV-I prevalence among individuals with history of use of intravenous medications was significantly higher (p less than 0.001) than in those without such history. Logistic regression analysis included age in years, indicators for male gender, and for i.v. injections, and their interactions. Age was very strongly associated to HTLV-I infection among females. At early ages prevalence was not different between sexes, but females presented a significantly higher rate than males after age 42. History of i.v. administered medications was very strongly associated in the univariate analysis and, although significance was borderline in the multivariate analysis, it had the effect of doubling the odds of HTLV-I infection.

Treatment of refractory and stable vitiligo by transplantation of in vitro cultured epidermal autografts bearing melanocytes.

BACKGROUND: Previous reports demonstrated the usefulness of in vitro cultured epidermis for repigmenting vitiligo. OBJECTIVE: Our purpose was to determine the potential of in vitro cultured epidermal sheets to treat extensive areas of intractable vitiligo. METHODS: In nine patients with long-standing, stable, and refractory vitiligo, autologous epidermis was cultured in vitro in H-MEM but without growth enhancers or hormones and transplanted onto previously denuded achromic lesions. RESULTS: Repigmentation was achieved to almost 100% in three subjects, 60% improvement was seen in two patients, and 30% to 40% in three additional cases. Only one patient had almost no response. Long-term observations in these patients indicate that repigmentation obtained by this method is permanent. CONCLUSION: Transplantation of in vitro cultured epidermis bearing melanocytes is potentially effective to treat extensive areas of vitiligo, but this method is presently at an experimental stage.

Acute respiratory tract infections among a birth cohort of children from Cali, Colombia, who were studied through 17 months of age.

For this study, 340 children less than 18 months old from a low-income, urban neighborhood in Cali, Colombia, were observed from birth by means of weekly home visits to detect cases of acute respiratory tract infection. All suspected cases were confirmed by trained doctors in a special clinic. Information on symptoms, signs, and potential risk factors was documented prospectively. Etiologic agents were identified in cases of lower respiratory tract infection (LRI). The overall incidence of acute respiratory tract infection was 6.6 cases per child-year at risk. The incidence of upper respiratory tract infection was 4.9 cases per child-year at risk and that of LRI was 1.7 cases per child-year at risk. Crowding in the home was found to be significantly associated with an increased incidence of LRI. Respiratory syncytial virus was the viral agent most frequently isolated from cultures of nasopharyngeal aspirates of children with LRI. Staphylococcus aureus was the bacterial agent most frequently isolated from the blood of patients with LRI.

Transplantation of in vitro-cultured epidermis bearing melanocytes for repigmenting vitiligo.

A new method for repigmenting vitiligo by transplantation of in vitro-cultured epidermis bearing melanocytes is described. The artificially grown epidermis was implanted after vitiliginous skin was denuded with liquid nitrogen. Satisfactory repigmentation was attained. This technique offers a new approach for treating refractory vitiligo.

[In vitro culture of melanocyte-bearing epidermis and its application in the treatment of vitiligo and the stable leukodermas]. / Cultivo in vitro de epidermis portadora de melanocitos y su aplicación en el tratamiento del vitíligo y las leucodermias estables.

Skin specimens were cultured in vitro in a attempt to reproduce epidermal sheets bearing melanocytes. After exploring different parameters and culture conditions, 16 out of 45 samples yielded pigmented epidermal membranes with melanocytes. This epidermis bearing melanocytes was transplanted to a patient with segmental vitiligo and a satisfactory repigmentation was achieved. The factors contributing to the development of this pigmented in vitro cultured epidermis, and the potential of this technology for treating refractory but stable forms of vitiligo, are discussed.

Tropical spastic paraparesis in Colombia.

A high-incidence focus of tropical spastic paraparesis (TSP) occurs on the South Pacific coast of Colombia. Of 55 patients studied, 52 (94.5%) had IgG antibodies to the human T-cell lymphotropic virus type I (HTLV-I) in serum and/or cerebrospinal fluid. Control groups did not show similar high positivity. Our results suggest that HTLV-I or other antigenically related retroviruses may be the cause of TSP in Colombia. Similar clinical, laboratory, and epidemiological findings have been reported in widely remote geographical regions of the world, with very similar clinical pictures of TSP in all high-incidence regions. The demonstration of IgG antibodies in serum and cerebrospinal fluid of patients with TSP in the Caribbean and Seychelles Islands, southern Japan, and the Ivory Coast indicate that the HTLV-I retrovirus could be the cause of this "tropical" myeloneuropathy.

Epidemiology of tropical spastic paraparesis in Columbia and associated HTLV-I infection.

The clinical syndrome earlier designated as paraparesia espástica del Pacífico is an isolated form of tropical spastic paraparesis (TSP) that was reported in 1981 in the southern Pacific lowlands of Columbia in and near Tumaco. The clinical features are similar to those of TSP reported in Jamaica, Martinique, the Seychelles, and the Ivory Coast of Africa and resemble also those clinical features of the human T-lymphotropic virus type I (HTLV-I)-associated myelopathy described in southern Japan. Since HTLV-I infection is closely associated with TSP, we conducted a case-control study to evaluate the role of HTLV-I-associated risk factors among patients from the endemic focus in Tumaco, Colombia, and the seroprevalence rates of this virus in other geographical areas of the Pacific Colombian lowlands with and without TSP. From our seroprevalence study of antibodies to HTLV-I among TSP index patients, matched controls, household contacts (first- and second-degree relatives), and healthy controls from these areas, we found a strong association between HTLV-I and TSP. Also, there is a high seroprevalence of HTLV-I among sexual partners of patients and to a lesser extent among their offspring and other relatives some of whom had an early mean acquisition of antibodies to HTLV-I. Heterosexual promiscuity and other close interpersonal contact may play an important role in the transmission of TSP in the Pacific lowlands of Colombia.