William N Gibbs

Sexual Transmission of Human T-Lymphotropic Virus Type I (HTLV-I)

STUDY OBJECTIVE To study the seroprevalence of human T-lymphotropic virus type I (HTLV-I) in a sexually active population and to determine sexual behavior risk factors for infection. DESIGN Cross-sectional seroprevalence study using enzyme-linked immunosorbent assay (ELISA) and Western blot. Risk-factor data were gathered by administered questionnaire and chart review. SETTING Two urban, primary care clinics for persons with sexually transmitted diseases run by the Jamaican Ministry of Health. PATIENTS Of the 2050 consecutive patients presenting with new episodes of sexually transmitted disease, 1977 patients were eligible for analysis. MEASUREMENTS AND RESULTS Overall HTLV-I seroprevalence was 5.7%; prevalence increased with age from 1.6% (age, 14 to 19 years) to 5.1% (age, 30 years and older) in men and from 5.3% (age, 14 to 19 years) to 14.1% (age, 30 years and older) in women. Compared with a reference cohort of food service employees, age-adjusted HTLV-I seroprevalence was increased in female patients with sexually transmitted disease (odds ratio = 1.83; CI, 1.41 to 2.83) but not in male patients with sexually transmitted disease. Independent risk factors for HTLV-I infection in women included having had more than ten lifetime sexual partners (odds ratio = 3.52, CI, 1.28 to 9.69) and a current diagnosis of syphilis (odds ratio = 2.12; CI, 1.12 to 3.99). In men, a history of penile sores or ulcers (odds ratio = 2.13; CI, 1.05 to 4.33) and a current diagnosis of syphilis (odds ratio = 3.56; CI, 1.24 to 10.22) were independent risk factors for HTLV-I infection. Of 1977 patients, 5 (0.3%) had antibodies to human immunodeficiency virus type 1 (HIV-1), including 2 with HTLV-I and HIV-1 coinfection. CONCLUSIONS We conclude that HTLV-I is transmitted from infected men to women during sexual intercourse. Our data are consistent with the lower efficiency of female-to-male sexual transmission of HTLV-I, but penile ulcers or concurrent syphilis may increase a mans risk of infection.

Erythrocyte Hb-S Concentration AN IMPORTANT FACTOR IN THE LOW OXYGEN AFFINITY OF BLOOD IN SICKLE CELL ANEMIA

The blood in sickle cell anemia has a very low oxygen affinity and, although 2,3-diphosphoglycerate (2,3-DPG) is increased, there is doubt as to whether this is the only factor responsible. In this study of 15 patients with sickle cell anemia (Hb SS) no correlation was found between oxygen affinity (P(50) at pH 7.13) and 2,3-DPG in fresh venous blood. Whole populations of Hb SS erythrocytes were therefore separated, by an ultracentrifuge technique, into fractions of varying density. The packed red cell column was divided into three fractions; a bottom fraction rich in deformed cells or irreversibly sickled cells (ISC), with a very high mean corpuscular hemoglobin concentration (MCHC); a middle fraction containing cells with the highest content of fetal hemoglobin; and a top fraction containing reticulocytes and discoid cells but free of deformed cells. Oxygen affinity was shifted to the right in all layers (mean P(50) (pH 7.13)+/-1SD: top 46.3+/-2.9 mm Hg: middle 49.8+/-4.9 mm Hg; bottom 61.0+/-5.8 mm Hg) compared with normal blood (top 32.1+/-0.7 mm Hg: bottom 30.1+/-0.5 mm Hg). 2.3-DPG was increased in the top fraction, but was low or normal in the bottom fraction (top 21.8+/-3.4 mumol/g Hb: middle 17.7+/-2.2 mumol/g Hb; bottom 13.8+/-3.1 mumol/g Hb; normal whole blood 14.3+/-1.2 mumol/g Hb). The level of 2,3-DPG in top fractions could not account for the degree of right shift of P(50), and in the middle and bottom fractions the even greater right shifts were associated with lower levels of 2,3-DPG. Top fraction cells depleted of 2,3-DPG had a higher, but still abnormally low, oxygen affinity. A strong relationship was found between oxygen affinity and MCHC. The fractions with the greatest right shift in P(50) had the highest MCHC (top 32.4+/-2.0; middle 36.2+/-3.1; bottom 44.6+/-3.2 g/100 ml, respectively) and the plot of P(50) vs. MCHC showed a positive correlation (r = 0.90, P < 0.001). The red cell population in sickle cell anemia is not homogeneous but contains cells of widely varying Hb F content, 2,3-DPG, and hemoglobin concentration. Paradoxically, the cells with the lowest O(2) affinity have the lowest 2,3-DPG, but they also have the highest concentration of Hb S. The dense, deformed cell called the ISC is but the end stage in a process of membrane loss and consequent increase in hemoglobin concentration. The P(50) of Hb SS blood is, to a large extent, determined by the presence of these cells (r = 0.85, P < 0.001). Increased concentration of Hb S in the cell favors deoxygenation and crystallization even at relatively high P(o2). Lowered affinity for oxygen appears to be closely associated with Hb S concentration and not with 2,3-DPG content.

Non-Hodgkin Lymphoma in Jamaica and its Relation to Adult T-Cell Leukemia-Lymphoma

Of 95 patients consecutively diagnosed with non-Hodgkin lymphoma, 52 (55%) had antibodies to human T-cell leukemia-lymphoma virus, type I. Antibody positivity was strongly associated with skin involvement, leukemia, and hypercalcemia (p less than 0.02). Two patients had systemic opportunistic infections. Neither meningeal nor lung infiltration was detected, and lymph node infiltration was diffuse in all patients. Of 36 patients who received immunophenotypic classifications, 30 had diseases that affected the T-cell system, and the cells of all tested patients with these diseases showed the helper/inducer (T4) phenotype. Twenty-seven of these thirty-six patients were found to have adult T-cell leukemia-lymphoma, and of the 27, 24 had antibodies to HTLV-I. The median duration of survival in patients with adult T-cell leukemia-lymphoma was 17 weeks, but a subgroup of 9 patients had indolent courses and a median survival of 81 weeks, which suggests that the disease has differing expression with courses that range from smoldering and indolent to acute and rapidly fatal. Hypercalcemia was the most important prognostic determinant of adult T-cell leukemia-lymphoma.

Hyperinfection Syndrome with Strongyloides Stercoralis in Malignant Lymphoma

Hyperinfection with Strongyloides stercoralis occurred in three patients with malignant lymphoma. The probable cause in each case was alteration of the immune responses either as a result of the malignant lymphoma or by the treatment given. Though thiabendazole (Mintezol) has produced reasonable results in the treatment of the hyperinfection syndrome, preliminary data suggest that the new broad-spectrum anthelmintic levamisole (Ketrax) is more effective. All patients who live or have lived in an area where strongyloidiasis is endemic should be investigated to detect the presence of the nematode before and during treatment with drugs with immunosuppressive properties. In view of the high mortality with S. stercoralis hyperinfection, vigorous therapy should be instituted before the use of immunosuppressive drugs.

Glucose 6 phosphate dehydrogenase deficiency and neonatal jaundice in Jamaica

Summary. Glucose‐6‐phosphate dehydrogenase (G6PD) deficiency was detected in 16 (69.6%) of a group of 23 neonates who had unexplained moderate or severe jaundice. This proportion is significantly more than the 9.4% observed or the 22.2% expected in Jamaican neonates who are not moderately or severely jaundiced (P<0.003), and significantly more than the 12.6% observed or the 21.0% expected in older Jamaican children and adults (P<0.003). Phenobarbitone therapy and phototherapy reduced the need for exchange transfusion but this was necessary in eight patients. Two babies developed kernicterus and one died. On the other hand, only two of 21 neonates who were identified as G6PD deficient at birth subsequently became moderately or severely jaundiced, and this could be attributed to other causes in both cases. These findings indicate that apparently spontaneous neonatal juandice is important in infants who have the G6PD A— enzyme. However, the jaundice is probably precipitated by unknown factors to which the G6PD deficient neonate is more susceptible than the infant who is not G6PD deficient. There is also a slightly increased incidence of G6PD deficiency in neonates who develop jaundice because of ABO or Rh(D) iso‐immune disease, infection or prematurity.

Molecular and immunologic analysis of a chronic lymphocytic leukemia case with antibodies against human T-cell leukemia virus

The human T‐cell leukemia virus type‐I (HTLV‐I) is a unique, exogenous, horizontally transmitted retrovirus which is T‐cell tropic, and has been associated with a specific type of aggressive leukemia/lymphoma of mature T‐cell origin. In a survey of lymphoid malignancies in Jamaica, antibodies to HTLV‐I were also found in 6 of 17 patients with chronic lymphocytic leukemia (CLL), raising the possibility of an etiologic relationship. Further studies were undertaken on one of these patients to clarify the nature of the disease and possible virus relationship. Cell surface marker analysis of her peripheral blood cells documented that the majority of circulating lymphocytes were B‐cells. DNA‐cloned probe analysis with a complete HTLV‐I proviral genome of these peripheral malignant B‐cells, was negative for integrated virus. A T‐cell line was established in culture from her peripheral blood. The presence of HTLV‐I in the cultured T‐cell line was established by the detection of expressed viral specific gag protein p‐19 and proviral DNA. Thus, a B‐cell lymphoid malignancy can occur in the presence of HTLV‐I infected T‐cells, suggesting the possibility of an indirect leukemogenic mechanism.

Spinal cord compression in thalassaemia.

Two cases of spinal cord compression resulting from extramedullary haemopoiesis in patients with thalassaemia of intermediate clinical severity are reported. The association between mild thalassaemia with long survival and the risk of spinal cord compression from extramedullary haemopoietic deposits is emphasised.

Glucose‐6‐Phosphate Dehydrogenase Deficiency and Homozygous Sickle Cell Disease in Jamaica

Summary. The relationship between D‐glucose‐6‐phosphate: NADP oxido‐reduc‐tase (E.C.I.1.1.49; glucose‐6‐phosphate dehydrogenase; G6PD) deficiency and homozygous sickle cell (SS) disease was examined in 120 patients. The proportion of hemizygotes (22‐6%) was slightly more than that observed, and the combined proportions of heterozygotes and homozygotes (28‐3%) were slightly less than would be expected, in the general population, but the differences were not significant. However, the proportion of patients of abnormal G6PD status in the 10‐19 years age group was 41‐7%, significantly more than that found in the 20‐29 years age group (0‐02

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‐Hodgkins 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.

Splenic Histiocytosis Associated with Thrombocytopenia

Two young Jamaican women of Chinese idiopathic thrombocytopenic purpura were found to have lipid-laden histiocytes in their spleens; their condition has improved following splenectomy. The electron mi