Estimating the time of HTLV-I infection following mother-to-child transmission in a breast-feeding population in Jamaica

Mother-to-child transmission of human T-cell lymphotrophic virus type 1 (HTLV-I) is primarily due to prolonged breast-feeding (>6 months) in the post-natal period. Most infant infections are not identifiable until 12-18 months of age by available whole virus Western blot serologic tests because of their inability to distinguish passively transferred maternal antibody from infant antibody. We investigated two methods to assess more accurately the time of infant infection. In prospectively collected serial biospecimens, HTLV-I-specific immunoglobulin (Ig) isotypes of IgM and IgA were determined by Western blot and HTLV-I proviral DNA was detected by polymerase chain reaction (PCR). IgA and IgG reactivity was assessed in periodic serum samples from 16 HTLV-I-seropositive children while IgM reactivity was observed in 100 percent of children at 24 months of age and 73 percent of children at 6-12 months of age; however, this could represent maternal and not infant antibody. Both IgA and IgM reactivity were insensitive indicators of infection, with only 50 percent of children showing reactivity at 24 months of age. PCR testing was performed in biospecimens obtained from 11 of these children. An estimated median time of infection of 11.9 months was determined by PCR, which was similar to the median time to infection determined by whole virus Western blot (12.4 months; P=0.72). PCR Tests support a median time to infection that is similar to that estimated by whole virus Western blot. (AU)

Adeno-associated virus and development of cervical neoplasia

Evidence from several sources has suggested that adeno-associated virus (AAV) infection might protect against cervical cancer, in part, by interfering with human papillomavirus (HPV)-induced tumorigenesis. Detection of AAV type 2 (AAV-2) DNA in cervical tissues has been reported. However, there have been few in vivo studies of women with cervical HPV infection or neoplasia, and these have reported inconsistent results. Therefore, we used polymerase chain reaction (PCR) assays targeted to the AAV-2 rep and cap genes to test tissue specimens from women in an epidemiological study of cervical neoplasia in Jamaica. We tested 105 women with low-grade cervical intraepithelial neoplasia (CIN-1), 92 women with CIN-3/carcinoma in situ or invasive cancer (CIN-3/CA), and 94 normal subjects. PCR amplification of human beta-globin DNA was found in almost all cervical specimens, indicating that these materials were adequate for PCR testing. The prevalence of HPV DNA, determined by HPV L1 consensus primer PCR was, as expected, strongly associated with presence and grade of neoplasia. Each of the AAV PCR assays detected as few as 10 copies of the virus genome. However, none of the 291 cervical specimens from Jamaican subjects tested positive for AAV DNA. Negative AAV PCR results were also obtained in tests of cervical samples from 79 university students in the United States. Exposure to AAV was assessed further by serology. Using a whole virus AAV-2 sandwich enzyme-linked immunosorbent assay, we found no relationship between AAV antibodies and presence or grade of neoplasia in either the Jamaican study subjects or women enrolled in a U.S. cervical cancer case (n = 74) - control (n = 77) study. Overall, the data provide no evidence that AAV infection plays a role in cervical tumorigenesis or that AAV commonly infects cervical epithelial cells.(Au)

Type-specific prevalence of human papillomavirus DNA among Jamaican colposcopy patients

Human papillomavirus (HPV) types differ in their associations with cervical cancer. Therefore, the types of HPV in precancerous lesions are important. In many regions with high cancer incidence, the HPV types in precancerous lesions have not been well studied. In Jamaica, a country that has high cervical cancer incidence, 174 colposcopy patients were tested for HPV DNA using polymerase chain reaction. HPV DNA detection was strongly related to presence and grade of cervical neoplasia (P<.001). Furthermore, severe neoplastic change was most highly associated with HPV DNA types also considered high-risk for severe neoplassia in other populations. HPV-45 DNA, a high-risk type uncommon in most previously tested countries, was detected in 12 percent of patients who had neoplasia. Thus, cervical neoplasia in Jamaica, as elsewhere, is linked to HPV. The high prevalence of HPV-45 DNA was notable, and its relation to high cervical cancer incidence in Jamaica must be assessed. (AU)

Glomerulonephritis after human parvovirus infection in homozygous sickle-cell disease

Glomerulonephritis with proteinuria of sufficient degree to manifest the nephrotic syndrome followed aplastic crises induced by human parvovirus (B19) in seven patients with homozygous sickle-cell disease, within 7 days in five patients and 6-7 weeks in two. Segmental proliferative glomerulonephritis was found in all four patients who underwent acute renal biopsies and focal segmental glomerulosclerosis was found in the fifth patient who had a biopsy 4 months later. One patient recovered completely, one died in chronic renal failure after 3 months, and the others had impaired creatinine clearance, four with continuing proteinuria (AU)

Identification of human T-cell leukemia/lymphoma virus type I antibodies, DNA, and protein in patients with polymyositis

OBJECTIVE: To investigate a possible association between human T cell leukemia/lymphoma virus type I (HTLV-I) and polymyositis (PM). METHODS: Sera and muscle biopsy samples from 9 Jamaican PM patients were compared with specimens from American HTLV-I positive PM patients and normal controls. Sera were evaluated for HTLV antibodies by enzyme-linked immunosorbent assay and Western blot. The biopsy samples were analyzed for HTLV-I/II DNA by polymerase chain reaction and were also immunohistochemically stained for HTLV gp46 envelope protein. RESULTS: Seven of the 8 Jamaican PM patients from whom sera were available were HTLV-I seropositive. The muscle biopsies of all 9 Jamaican patients demonstrated severe lymphocytic infiltration, cellular degeneration, myofiber atrophy, and fibrosis. Each muscle biopsy specimen contained HTLV-I DNA. Two of 6 samples demonstrated intense staining for HTLV-I gp46 in many of the invading mononuclear cells and weak staining for HTLV-I gp46 in many of the other specimens were weakly positive for gp46 in rare mononuclear cells. All controls specimens were negative for the presence of HTLV-I DNA and protein. CONClUSION: HTLV-I is associated with an inflammatory muscle disease characterized by direct invasion of the affected muscle by HTLV-I-infected mononuclear cells.(AU)

Human T-lymphotropic virus type I DNA in spinal cord of tropical spastic paraparesis with concomitant human T-lymphotropic virus type I negative Hodgkin's disease

We studied a 58 year old black women from Barbados who simultaneously developed myelopathy and lymphoma with human T-lymphotropic virus type I (HTLV-I) antibodies in serum and cerebrospinal fluid and died 3 years after onset. Neuropathological examination showed typical tropical spastic paraparesis (TSP). The polymerase chain reaction (PCR) demonstrated defective proviral genome retaining the HTLV-I pX and env regions in thoracic spinal cord, the level most severely affected. Defective HTLV-I in the nervous system retaining the pX region may be relevant to pathogenesis because circulating CD8+ cytotoxic lymphocytes specific for HTLV-I pX occur in HTLV-I myelopathy. This patient's lymph node biopsy specimen was consistent with Hodgkin's disease (HD), nodular sclerosis subtype, of B-cell origin. The PCR in the paraffin-embedded lymph node involved by HD failed to amplify HTLV-I proviral sequences. Complete HTLV-I proviral amplification was obtained in paraffin-embedded lymph node form positive controls (adults T-cells leukemia). To our knowledge the association of TSP and HD has not been reported previously. Despite claims the HD may be associated with HTLV-I, we demonstrated absence of HTLV-I infected T-cell in the lymphoid infiltrate of HD in this case, positive HTLV-I serology notwithstanding.(AU)

Sequence variation in the capsid protein genes of human papillomavirus type 16

We have cloned and sequenced the L1 and L2 genes from human papillomavirus type 16 (HPV16) DNA-containing cervical cytology samples collected from the U.K. and Trinidad. Samples containing high copy numbers of HPV16 DNA were selected as being likely to contain fully functional virus DNA molecules in an episomal state, rather than in an integrated and possibly altered state. In comparison with the perviously published sequence of HPV16 isolated from an invasive cancer a variety of differences were detected in both L1 and L2. The pattern of changes appears to be different in samples from the two geographic regions. One of the differences (resulting in D at position 202 of the L1 protein) reported recently to be functionally important for virus particle assembly was found to occur in all the samples examined. Variations in L1 found within known immunoreactive regions or hydrophobic domains should be taken into account in design of prophylactic vaccines for HPV16 based on virus-like particles. All variations within L2 protein were found in hydrophilic domains in the carboxy-terminal half of L2. These positions were highly variable among other types of papillomavirus and are located outside the known L2 immunoreactive region. (AU)

Detection of oncogenic HPV DNA by a consensus polymerase chain reaction method in genital carcinomas in twenty women in Barbados

Paraffinized tissue from Barbadian women with histologically proven gential carcinoma was subjected to a consensus polymerase chain reaction method. Nineteen patients had cervical and one, vaginal carcinoma. The histological types were 17 squamous cell carcinoma, 2 adenocarcinoma and 1 adenosquamous carcinoma. HPVDNA was detected in 18/20 (90 percent). HPVDNA type 16 in 13 (65 percent), type 33 and type 45 in 1 (5 percent) each and 3 (15 percent) could not be typed. HPVDNA, type 16, was detected in one (50 percent) of the two cases of adenocarcinoma and 12/17 (71 percent) cases of squamous cell carcinoma. DNAHPV, type 33, and type 45 were each detected in 1/17 (6 percent) cases of squamous cell carcinoma. No HPVDNA, type 18, was detected (AU)

Screening for prolonged incubation of HTLV-I infection in British and Jamaican relatives of British patients with tropical spastic paraparesis [see comments]

OBJECTIVE -- To compare the prevalence of antibody to and proviral DNA of the retrovirus HTLV-I in relatives of 11 British patients with tropical spastic paraparesis who migrated from Jamaica before they developed symptoms, and to examine factors possibly related to transmission of HTLV-I. DESIGN -- Migrant family study. Antibody state was determined by several methods and confirmed by western blotting; the polymerase chain reaction was used to detect proviral DNA. SETTING -- Britain and Jamaica. SUBJECTS -- All available first degree relatives: those born and still resident in Jamaica (group 1); those born in Jamaica who migrated to Britian (group 2); and index patients' children who were born and resident in Britian (group 3). All had been breast fed and none had had blood transfusions. RESULTS -- Of the 66 living relatives, 60 were traced. Seroprevalence among those born in Jamaica (irrespective of current residence) was 22 percent (10/46; 95 percent confidence limits 9 to 34 percent) compared with zero among British born offspring (0/14) and was higher in group 2 at 33 percent (7/21; 12 to 55 percent) than in group 1 at greatest mean age.) Proviral DNA was not detected in any subject negative for HTLV-I antibody, making prolonged viral incubation in those negative for the antibody unlikely. CONCLUSION -- In this sample factors related to place of birth and early residence were more important in transmission of HTLV-I than naternal or age effects. In areas with a low to moderate prevalence policies of preventing mothers who are carriers of the virus from breast feeding would be premature (AU)

High human T-cell lymphotropic virus type I proviral DNA load with polyclonal integration in peripheral blood mononuclear cells of French West Indian, Guianese, and African patients with tropical spastic paraparesis

Human T-cell lymphotropic virus type I (HTLV-I) proviral integration status was examined by Southern blot analysis in peripheral blood mononuclear cell (PBMC) DNA from patients presenting a tropical spastic paraparesis (TSP) and serological evidence of HTLV-I infection. Surface phenotype and morphological aspects of PBMC were also studied. A polyclonal HTLV-I proviral integration was found in the PBMC of the 10 patients studied irrespective of their geographical origin (French West Indies, French Guiana, and Africa), the duration of their clincal illness, or the HTLV-I antibody titer. Furthermore, by dilution experiments and hypothesizing that only one copy of HTLV-I proviral DNA is present in one call, we estimated that this HTLV-I integration is present in 3 percent to 15 percent of their PBMC. All 10 TSP/HTLV-I patients studied had an average of 10 percent of thier lymphocytes abnormal, presening either a misshapen nucleus or an adult T-cell leukemia/lymphoma(ATL)-like feature. Moreover, an elevated CD4/CD8 ratio associated with the presence of activated T cells with a high level of DR expression was observed in most patients. The significant frequency of viral-positive PBMC and the important load of HTLV-I proviral DNA that we observed in TSP/HTLV-I patients might play an important role in the pathogenesis of this recently identified clinico-virological entity. (AU)

Comparison of a human T-cell lymphotropic virus type I strain from cerebrospinal fluid of a Jamaican patient with tropical spastic paraparesis with a prototype human T-cell lymphotropic virus type I

The isolation and characterization of a human T-cell lymphotrophic virus type I (HTLV-I) from cerebrospinal fluid of a Jamaican patient with tropical spastic paraparesis is described. The virus isolate is a typical type C retrovirus as seen by electron microscopy and is related to prototype HTLV-I isolated from patients with adult T-cell leukemia but is not identical to this prototype HTLV-I as seen by restriction enzyme mapping.(AU)

Molecular epidemiology of HTLV-I-associated non-Hodgkin's lymphomas in Jamaica

As part of epidemiologic studies of human T-lymphotropic virus (HTLV)-I-associated malignancies in Jamaica, the authors evaluated 26 patients with non-Hodgkin's lymphoma for the presence of integrated HTLV-I provirus in their malignant cells. Fifteen of 26 patients had integrated provirus. All 15 also were HTLV-I antibody positive. Eleven patients did not have integrated provirus, and all 11 were antibody negative. All of the antibody-positive cases had onset of their disease in adulthood (age range, 21-57 years) as opposed to the broad age range of negative cases (4-66 years). Clinical features which were more common in provirus positive than negative patients included leukemic phase, skin involvement, and hypercalcemia, which are all features frequently seen in HTLV-I-associated adult T-cell leukemia/lymphoma (ATLL). The presence of skin involvement, circulating malignant cells, abnormal liver function tests, or the presence of two or more of these four features were statistically significantly different between virus-positive and virus-negative cases. Although the survival of positive cases (6 months) was shorter than that of negative cases (9 months), this was not statistically significant. The only significant determinant of survival was hypercalcemia, with those who developed hypercalcemia at some point in their disease course, independent of their HTLV-I status, surviving a mean of 5 months as compared to a mean of 17.5 months in those who never became hypercalcemic. The six HTLV-I-positive lymphomas that underwent cell typing were all primarily OKT4 positive, whereas two HTLV-I antibody-negative cases that were typed were B-cell lymphomas. (AU)