A cohort study of health effects of human T-cell lymphotropic virus type I infection in Jamaican children.

OBJECTIVE: Human T-cell lymphotropic virus type I (HTLV-I) infection in childhood is believed to play an important role in risk for adult T-cell leukemia/lymphoma. Although HTLV-I is known to be associated with infective dermatitis in childhood, other HTLV-I-associated morbidity in children has not been well studied. We sought to determine the HTLV-I-associated health effects in Jamaican children. METHODS: We compared incidence rates of several health outcomes in 28 HTLV-I-infected and 280 uninfected children clinically followed from age 6 weeks to a maximum of 10 years. Cox proportional hazards regression analysis was used to analyze these prospectively collected data, adjusting for confounding effects of other variables as necessary. RESULTS: HTLV-I-infected children had significantly higher incidence rates of seborrheic dermatitis (rate ratio [RR] = 4.8, 95% confidence interval [CI] = 1.9-12.5), eczema (RR = 3.1, CI = 1.2-7.9) and persistent hyperreflexia (RR = 3.7, CI = 1.6-8.2). Additionally, HTLV-I infected children had increased rates of severe anemia (RR = 2.5, CI = 0.8-7.9) and abnormal lymphocytes (RR = 2.4, CI = 0.8-7.6) that were of borderline statistical significance. CONCLUSIONS: Our study suggests that HTLV-I-associated skin diseases of childhood may include seborrheic dermatitis and eczema. Additionally, these data suggest that persistent hyperreflexia of the lower limbs may be an early sign of HTLV-I-associated neurologic involvement in children. Expansion and continued clinical observation of this cohort would be valuable.

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)

Mother-to-child transmission of human T-cell lymphotropic virus type I associated with prolonged breast-feeding

OBJECTIVES: We assessed the risk of transmitting human T-cell lymphotropic virus type I (HTLV-I) through breastfeeding. STUDY DESIGN/METHODS: To assess the risk of mother-to-child transmission of HTLV-I, 212 HTLV-I-seropositive women and 145 HTLV-I-seronegative women were enrolled in a prospective cohort study conducted in Kingston, Jamaica. Their offspring were examined at regular intervals, and HTLV-I serostatus was determined at each visit. RESULTS: Twenty-eight of the 181 children with at least one postnatal visit born to HTLV-I-seropositive women and (none of the children born to HTLV-I-seronegative women) were persistently seropositive, compared with only 8 (9 percent) of 86 children breast-fed for less than 12 months (relative risk, 3.4; 95 percent CI, 1.7 - 6.9). Compared with children weaned at younger ages, transmission of HTLV-I was associated with continued breast-feeding of children who were 12 to 18 months of age (relative hazard, 6.4; 95 percent CI. 2.1 - 180.2) and older than 18 months (relative hazard, 18.1; 95 percent, 1.4 - 29.5). Transmission was also associated with higher maternal antibody titer (a possible marker of virus load), prolonged duration of ruptured membranes during childbirth, and lower maternal income. CONCLUSIONS: These results suggest that limiting the duration of breast-feeding to less than 12 months for children born to HTLV-I-seropositive mothers may significantly reduce mother-to-child transmission of HTLV-I.(Au)

HLA DRBI *DQB1* haplotype in HTLV-I-associated familial infective dermatitis may predict development of HTLV-I-associated myelopathy/tropical spastic paraparesis

A possible causal association between infective dematitis and HTLV-I infection was reported familial infective dematitis (ID) occurring in a 26-year-old mother and her 9-year-old son. The mother was first diagnosed with ID in 1969 at the age of 2 years in the Dermatology Unit at the University Hospital of the West indies (U.H.W.I.) in Jamaica. The elder of her 2 sons was diagnosed with ID at the age of 3 years, also at U.H.W.I. Both mother and son are HTLV-I-seropositive. A second, younger son, currently age 2 years, is also HTLV-I-seropositive, but without clinical evidence of ID. Major hitocompatibility complex (MHC), class II, human leucocyte antigen (HLA) genotyping documented a shared class II haplotype, DRB*DQBI* (1101-0301), in the mother and her 2 sons. This same haplotype has been described among Japanese patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and has been associated with a possible pathologically heightened immune repsonse to HTLV-I infection. The presence of this haplotype in these familial ID cases with clinical signs of HAM/TSP may have contributed to their risk for development of HAM/TSP. The unaffected, HTLV-I seropositive younger son requires close clinical follow-up. (AU)

Frequency and time course of seroconversion in maternal and infant transmission of HTLV-1 (abstract)

Objectives: To characterize the frequency and timecourse of seroconversion in infants acquiring HTLV-I infection from their mothers. Methods: 220 children born to HTLV-I seropositive women in Kingston, Jamaica were followed regularly for up to 36 months following birth. At each visit, mothers were interviewed and children were examined and blood samples taken. Results: A total of 30 children have seroconverted, including 17/86 (20 percent) of those completing >/= 24 months of follow-up. Analysis of serial Western blots (WB) on 7 seroconverters revealed maternal antibodies persisting for 7.3 months ([mean], [range 7.0 - 7.4]), followed by an absence of any antibody response lasting 8.3 months ([mean], [range 2.8 - 14.2]), followed by seroconversion (gag+env), occuring at 14.1 months ([mean], [range 9.8 - 21.5]). Six of these children were breast-feeding at the time of seroconversion and one had stopped breast feeding 8 months prior to seroconversion. Two mothers lacking gag antibody p24 on WB transmitted virus to their offspring. Conclusion: HTLV-I seroconversion in infants seems to occur only after the disappearance of maternal antibody, suggesting that this antibody may be protective, and raising the possibility that an HTLV-I vaccine could prevent transmission of virus. Current WB criteria that require presence of p24 antibody do not identify all individuals capable of transmitting HTLV-I

Mother-to-child transmission of human T-cell lymphotropic virus type I (HTLV-1) in Jamaica: association with antibodies to envelope glycoprotein (gp46) epitopes

To study mother-to-child transmission of HTLV-I in Jamaica, we screen antenatal patients in Kingston, Jamaica, from 1983 to 1985. Of 2,329 women, 81 (3.5 percent) were HTLV-I seropositive. Two to three years later, 36 seropositive mothers were recontacted, and blood was drawn from them and their children. All sera were tested for HTLV-I antibodies, and mother's sera were additionally tested for HTLV-I whole-virus antibody titer, syncytium-inhibition neutralizing antibody liter, and titers to six synthetic peptides from the HTLV-I envelope glycoprotein gp46. Seventeen of 74 (23 percent) [95 percent confidence interval (CI) 15-34 percent] children were seropositive. HTLV-I transmission was associated with breast-feeding duration > 6 months [relative risk (RR) 3.2; CI 0.4-22.1], maternal age > 30 years (RR 2.8; CI 1.0 - 7.8), and higher maternal whole-virus antibody titer (RR 3.3; CI 1.3 - 8.5). After controlling for higher whole-virus antibody titer, transmission remained associated with higher titer of neutralizing antibody and higher titer of antibody to the peptide sp4al, corresponding to amino acids 196 - 209 of the gp46 envelope glycoprotein. We conclude that mother-to-child transmission of HTLV-I in Jamaica is associated with longer duration of breast-feeding, older age, and higher HTLV-I antibody titer, in particular to a certain immunogenic portion of the gp46 envelope glycoprotein.(AU)

Perinatal transfusion transmission of HTLV-I: risk to mother and child - abstract

As part of a prospective study of transfusion-transmission of HTLV-I antibody (Ab) positive blood in the perinatal period. Pretransfusion seronegative recipients of HTLV-I-positive blood components were retrospectively identified and subsequently followed up monthly for six months and then semi-annually thereafter. At each visit, a questionnaire was administered, physical examination was done and blood was drawn to assess haematological and immunological status of recipients. Mothers who were transfused during pregnancy had their pregnancy outcome noted and where possible were followed up as mother/infant pairs. The outcome of subsequent pregnancies was noted. Thirty-nine subjects in our cohort of 66 were women and 21 of them were transfused during pregnancy or in the puerperium . Nineteen of these women received cellular HTLV-I Ab-positive blood products and two received acellular products. Nine of our 21 mothers who received HTLV-I-positive blood products seroconverted, yielding a seroconversion rate of 42 percent which is consistent with the overall cohort. Fourteen of the 21 pregnancies ended in viable children but two mother/infant pairs wre lost to follow-up. Of the 12 remaining mothers, 4 received transfusion antepartum (1 day to 15 weeks prior to delivery), while 8 were transfused either interpartum or up to three weeks post partum. All of the 12 mothers breastfed their babies for periods ranging from one week to four years (median duration of six months). Six of the 12 mothers were sreoconverters and 2 of the six children of these mothers have also seroconverted between one and two years following birth. This yields a mother/infant transmission rate of 33 percent which is more than the reported 20 percent rate in previous mother/infant studies. The difference, however, is not statistically significant. One seropositive child has developed Infective Dermatitis (ID), a recently described HTLV-I associated disorder. We conclude that, HTLV-1 transmission via blood transfusion to pregnant women poses a risk to mother and child. We propose that, where widespread screening for HTLV-antibodies is not feasible, screening of blood for transfusion in to pregnant mothers should be given priority as at least two individuals are at risk of infection and disease (AU)

Lymph node pathology in infants of HTLV-I seropositive mothers - abstract

In a cohort of seronegative mother-infant pairs being studied for perinatal transmission of the human T-lymphotropic virus type (HTLV-I), it was noticed that some infants developed persistent lymphadenopathy for which no specific cause was apparent. In order to determine whether this lymphadenopathy reflected a specific lymphoreticular abnormality, the lymph node pathology was studied, using morphological and immunohistochemical methods. Of 17 infants with lymphadenopathy, 16 were from seropositive mothers. Twenty-four infants (7.0 percent) in the cohort group seroconverted. Only 4 of these were infants with lymphadenopathy. Seroconversion in these tended to occur later than in infants without lymphadenopathy (mean 12 months; range 10 - 18 months). The lymph node histology showed non-specific reactive hyperplasia with a predominance (14/15) of mixed and paracortical hyperplasia. On immunohistochemistry, CD25 staining, characteristic of neoplastic transformation by HTLV-I, was positive in 6/11 cases but without correlation with seropositivity in these infants. This pattern of hyperplasia is unusual in infancy. As in HIV-induced lymphodenopathy, although the changes are not specific, they are sufficiently distinctive, particularly in HTLV-I endemic areas, to warrant serological testing of infants and mothers. The immune reponse without seroconversion appears aberrant. (AU)

Beta-2-microglobin levels in HTLV-I infection - abstract

The human T-lymphotropic virus (HTLV-I) is endemic to the Caribbean and its importance as a possible cause of disease is increasing. Initial reports were of the association of HTLV-1 infection with adult T-cell lymphoma/leukaemia (ATL). Since then, tropical spastic paraparesis (TSP), infective dermatitis, polymyositis and more recently, crusted scabies have been reported to occur in individuals sero-positive for the virus. á2-microglobulin is a small peptide which forms the light chain of the HLA antigen that is present on the surface of nucleated cells. It has been shown to be an index to tumour burden in patients with lymphoma and to provide valuable information on the prognosis and response to therapy in patients infected with HIV. Here we reported on the serum á2-microglobulin levels in patients with lymphoma, TSP, infective dermatitis, children of HTLV-1-positive mothers and the relationship between HTLV-1 infection and á2-microglobulin levels. (AU)

Maternal infant transmission of HTLV-I in Jamaica - abstract

HTLV-I has been aetiologically linked with adult T-cell leukaemia and tropical spastic paraparesis. Studies from Japan have shown that transmission from mother to child is the principal mode of early-life infection; breast milk has been implicated as the route of this transmission. To study the frequency of, and risk factors for, maternal-infant transmission in Jamaica, we screened women attending a Kingston antenatal clinic for the presence of HTLV-I antibodies. Of 2,329 women screened, 81 (3.5 percent) were seropositive. Two to three years following screening, 35 seropositive mothers were successfully recontacted, a questionnaire was administered, and blood was collected from the mothers and the child of the original pregnancy (index child) as well as any other children. Five of 34 (15 percent) index children and 8 of 31 (26 percent) siblings were seropositive. Having a seropositive child was significantly associated with older maternal age (p<0.05) and a higher level of maternal antibody titre (p<0.05). Seropositive index children tended to breast feed for longer than seronegative index children (11 months vs 1 month; p=0.18). We conclude that HTLV-I transmission occurs in Jamaica at rates similar to those seen in Japan. Older age and measures of higher "viral load" such as elevated antibody titre are associated with transmission. Although the evidence is suggestive that transmission occurs through breast-milk, a larger study is currently underway to this tissue (AU)

The contribution of the labour ward midwife in the prevention of low Apgar scores - abstract

The relationship between the workload of the labour ward midwife and neonatal outcome was retrospectively studied over a 3-year period. The Apgar scores were used as an index of neonatal outcome. The ratio of monthly deliveries to the number of midwives assigned to the labour ward for that month was used as an index of workload. There was a total of 8,066 live-births, with an average monthly delivery rate of 227.6. The average number of midwives assigned to the labour ward per month was 13.6. There were 15 midwives/month in the first year of the study as compared with 12 in the third year. As a result, the workload for each midwife increased from 15 deliveries per month in the first year to 18 in the third year. There were, on average, 14 deliveries per midwife each month between January and June and 20 between July and December. Within any particular month, workloads (X) were positively correlated with the proportion of deliveries with Apgar scores of less than 7 at 1 minute (Y = 0.9003 X 10.2034, p < 0.001), and of less than 4 at 5 minutes (Y = 0.1636 X - 0.9683, p < 0.01). Decreasing numbers of midwives (X) were correlated with increasing percentages of deliveries with an Apgar score of less than 7 at 1 minute (Y = 18.0483 - 0.4773 X p < 0.05). Decreasing numbers of midwives (X) were also correlated with increasing percentages of low birth weight infants with an Apgar score of less than 7 at 5 minutes (Y = 27.4813 - 1.1823 X, p < 0.05). It is suggested (1) that more midwives should be assigned to the labour ward during the July - December period, (2) that the work efficacy of midwives should be improved, and (3) that more midwives should be recruited (AU)

HTLV-I in Jamaica - abstract

Human T-cell lymphotropic virus (HTLV-I) is a retrovirus that has a world-wide distribution. It is endemic in Jamaica and Southern Japan but there are clusters in the South Eastern U.S.A. and other parts of the Caribbean. The virus is associated with acute T-cell leukaemia/lymphoma (ATL), a particularly aggressive form of post-thymic lymphoid malignancy and tropical spastic paraparesis (TSP), known to us as Jamaican neuropathy. In 1983, a joint project between the National Cancer Institute and the National institutes of Health (NCI/NIH) in Bethesda, Maryland and the Pathology Department, UWI, Jamaica was started. Among the various research tasks were: studies on non-Hodgkin's lymphoma (NHL) with respect to the relationships of ATL to HTLV-I, epidemiological studies to define prevalence rates, risk factors and possible modes of transmission (sexually, maternal/child, transfusion), and a neurological study to further evaluate the association of TSP with HTLV-I. Each of these studies has so far yielded valuable information. ATL in Jamaica is associated with 47 per cent HTLV-I seropositivity. It shows a broad range of clinical expression: leukaemia, hypercalcaemia, lytic bone manifestations such as skin involvement, leukaemia and hypercalcaemia are strongly related to seropositivity. The lymphomas may be of various histological subtypes. Of 136 lymphomas classified to date, 14 were medium-sized cell, 65 were large cell, 26 were mixed cell and 31 were pleomorphic. The disease has a median life expectancy of 18 weeks but there is an indolent group with a median life expectancy of 81 weeks. Hypercalcaemia is the most important prognostic determinant. HTLV-I prevalence is strongly age - and sex-dependent. Although the overall prevalence rate is 5.4 percent. In men, prevalence rises from 1.6 percent in those less than age 20 years to 5.1 percent in those 30 years or older. In women, prevalence increases from 5.3 percent in those less than 20 years to 14.1 percent in those aged 30 years or older. These figures suggest relatively ineffectual maternal-child transmission (probably by breast feeding) followed in later life by sexual transmission, with male to female transmission being more efficient than female to male. HTLV-I can also be transmitted by transfusion of cellular blood products. The definition of possible intermediate outcome of virus infection, the pathobiology of ATL and TSP, and factors predicating the development of disease provide the basis of our current research (AU)

Neonatal deaths in the University Hospital of the West Indies - abstract

A retrospective study over the 3-year period 1/10/83 - 30/9/86 showed that the neonatal mortality rate at the University Hospital had risen from 15.8 per 1,000 livebirths, 20 years ago, to 16.6 per 1,000 livebirths at the present time. The birth weight specific neonatal mortality rate for 1,000 - 1,499 gm neonates had risen from 30.1 percent, ten years ago, to 46.6 percent at the present time. The male:female ratio was 1.36:1, with a statistically significant predominance of male neonatal deaths in the 1,500 - 1,999 gm birth weight group. Fifty-nine point seven per cent of the neonatal deaths occurred in the first 24 hours of life. The 5 major causes of death were: respiratory failure 37 percent, neonatal asphyxia (25 percent), congenital anomalies (17 percent), prematurity (15 percent), and neonatal sepsis (7 percent). Over the past 10 - 20 years, deaths from respiratory failure and neonatal asphyxia have gained in importance; while neonatal deaths 20 years ago, to 45 percent at the present time. It is suggested that the prevention of neonatal asphyxia and the provision of an adequate number of experienced neonatology-trained nurses are the basic requirements for any system which attempts to reduce the neonatal mortality rate. It is further suggested that an increase in availability of ventilatory support and other intensive care facilities would help to further reduce the neonatal mortality rate (AU)