Biomedical subjects

R D Semba

Publications and source records attributed to R D Semba.

At least 91 records · Page 5Linked to original sources

PubMed1995

Infant mortality and maternal vitamin A deficiency during human immunodeficiency virus infection.

The maternal factors that contribute to high mortality rates among infants born to women with human immunodeficiency virus (HIV) are unclear. We followed 474 HIV-infected mothers and their infants in Malawi from pregnancy through the infants' 12th month of life. Of the 474 HIV-infected pregnant women, 300 (63.3%) were deficient in vitamin A (serum level of vitamin A, <1.05 micromol/L). Mean serum vitamin A levels among mothers whose infants died were 0.78 +/- 0.03 micromol/L compared with 1.02 +/- 0.02 micromol/L among mothers whose infants had survived for the first 12 months of life (P <.0001). The overall infant mortality rate was 28.7%. We divided HIV-positive mothers into six groups according to serum vitamin A levels (micromol/L) as follows: group 1, <0.35; group 2, between 0.35 and 0.70; group 3, between 0.70 and 1.05; group 4, between 1.05 and 1.40; group 5, between 1.40 and 1.75; and group 6, >1.75. Infant mortality rates for each group were 93.3%, 41.6%, 23.4%, 18.5%, 17.7%, and 14.2%, respectively (P < .0001). Maternal vitamin A deficiency during HIV infection may contribute to increased infant mortality.

Adult↗

PubMed1995

Vitamin A deficiency and wasting as predictors of mortality in human immunodeficiency virus-infected injection drug users.

A nested case-control study of vitamin A deficiency and wasting as risk factors for mortality from AIDS and infections was done within a large prospective cohort of human immunodeficiency virus (HIV)-infected injection drug users (IDUs). Fifty adult subjects who died from AIDS and infections were matched with 235 controls who survived. Plasma vitamin A, weight, and body mass index were measured. Mean length of follow-up was 2.4 +/- 1.1 years. Vitamin A deficiency occurred in 50% and wasting occurred in 38% of patients in the last visit before death. CD4 cells count < 200/microL, wasting, and vitamin A deficiency were associated with mortality. There was a higher risk of death in HIV-infected subjects with vitamin A deficiency (odds ratio [OR], 4.6; 95% confidence interval [CI], 1.8-11.3) and wasting (OR, 8.8; 95% CI, 2.7-28.2). Vitamin A deficiency and wasting are common during HIV infection and are independent predictors of mortality in HIV-infected IDUs.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Maternal vitamin A deficiency and mother-to-child transmission of HIV-1.

Studies show that around 10-40% HIV-positive women will give birth to children who are also infected. However, the risk factors for transmission from mother to child are not well understood and the effects of maternal nutritional status are unknown. We conducted a study of vitamin A status in pregnant women as a risk factor for mother-to-child transmission of HIV in Malawi. Serum vitamin A, height, weight, CD4 T-cell counts, and duration of breastfeeding were measured in 338 HIV-positive mothers whose infant's HIV serostatus was known. Mother-to-child transmission of HIV was 21.9% among mothers whose infants survived to 12 months of age. Mean vitamin A concentration in 74 mothers who transmitted HIV to their infants was lower than that in 264 mothers who did not transmit HIV to their infants (0.86 [0.03] vs 1.07 [0.02], p < 0.0001). We divided HIV positive mothers to 4 groups, those with vitamin A concentrations of less than 0.70, between 0.70 and 1.05, between 1.05 and 1.40, and greater than or equal to 1.40 mumol/L. The mother-to-child transmission rates for each group were 32.4%, 26.2%, 16.0%, and 7.2%, respectively (p < 0.0001). Maternal CD4 cell counts, CD4%, and CD4/CD8 ratio were also associated with increased mother-to-child transmission of HIV. Maternal age, body-mass index, and breastfeeding practices were not significantly associated with higher mother-to-child transmission. Our study suggests that maternal vitamin A deficiency contributes to mother-to-child transmission of HIV.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Vitamin A, immunity, and infection.

Although a role for vitamin A in immunity to infectious diseases has long been suggested, only in the last decade have epidemiological, immunologic, and molecular studies yielded substantial evidence for a central role. The recent discovery of retinoic acid and retinoid X receptors has provided a molecular basis for the action of vitamin A and its metabolites at the level of gene activation. At least a dozen clinical trials have now demonstrated that vitamin A supplementation reduces severe morbidity and mortality from infectious diseases among children who have acute measles or who are from areas in which vitamin A deficiency is endemic. Vitamin A deficiency is an immunodeficiency disorder characterized by widespread alterations in immunity, including pathological alterations in mucosal surfaces, impaired antibody responses to challenge with protein antigens, changes in lymphocyte subpopulations, and altered T- and B-cell function. Vitamin A and its metabolites are immune enhancers that have been shown to potentiate antibody responses to T cell-dependent antigens, increase lymphocyte proliferation responses to antigens and mitogens, inhibit apoptosis, and restore the integrity and function of mucosal surfaces. Vitamin A and related retinoids may have potential applications in therapy for some infectious diseases.

Adult↗

PubMed1994

Effect of vitamin A supplementation on immunoglobulin G subclass responses to tetanus toxoid in children.

Previously, we demonstrated that administering vitamin A supplements to children resulted in a significant increase in the immunoglobulin G (IgG) response generated against a vaccine dose of tetanus toxoid (TT) (R. D. Semba et al., J. Nutr. 122:101-107, 1991). However, from these analyses we could not determine whether there was an increase in levels of IgG of the subclass presumed to be important for protection against challenge by the toxin or whether there was simply a general increase in the levels of all the IgG subclasses expressing anti-TT activity. The goal of this study was to determine the profile of the anti-TT IgG subclasses in children receiving vitamin A supplementation or a placebo in order to assess the potential utility of the enhanced anti-TT response. In a randomized, double-masked, placebo-controlled clinical trial, the levels of the different anti-TT IgG subclasses were measured in 139 Indonesian preschool children (3 to 6 years of age) 2 weeks before and 3 weeks after immunization. Baseline anti-TT levels and immunization histories were used to separate those children who were responding to TT for the first time from those who responded in a secondary fashion because of previous exposure to TT. Children who were given vitamin A prior to immunization had significant increases in IgG1 levels regardless of whether they were undergoing primary or memory reactions. In the group of individuals who underwent a secondary response to TT, vitamin A supplementation was also associated with a modest but significant change in the levels of anti-TT IgG3. There were only minor changes in the levels of anti-TT IgG2 and IgG4. Since IgG1 is the subclass associated with a protective response to TT immunization, these results suggest that vitamin A supplementation may be a safe and effective intervention to enhance the relevant humoral response to TT and other vaccine antigens.

Adjuvants, Immunologic↗

PubMed1993

Increased mortality associated with vitamin A deficiency during human immunodeficiency virus type 1 infection.

OBJECTIVE: To determine whether plasma vitamin A levels are associated with immunologic status and clinical outcome during human immunodeficiency virus type 1 (HIV-1) infection. PATIENTS AND METHODS: Analysis of vitamin A levels, CD4 T cells, complete blood cell count, and serologic markers for liver disease in a random subsample of 179 subjects from a cohort of more than 2000 intravenous drug users with longitudinal follow-up to determine survival. RESULTS: Mean (+/- SE) follow-up time was 22.8 +/- 1.1 months, and 15 subjects died during follow-up. More than 15% of the HIV-1-seropositive individuals had plasma vitamin A levels less than 1.05 mumol/L, a level consistent with vitamin A deficiency. The HIV-1-seropositive individuals had lower mean plasma vitamin A levels than HIV-1-seronegative individuals (P < .001). Vitamin A deficiency was associated with lower CD4 levels among both seronegative individuals (P < .05) and seropositive individuals (P < .05). In the HIV-seropositive participants, vitamin A deficiency was associated with increased mortality (relative risk = 6.3; 95% confidence interval, 2.1 to 18.6). CONCLUSION: Vitamin A deficiency may be common during HIV-1 infection, and vitamin A deficiency is associated with decreased circulating CD4 T cells and increased mortality. Vitamin A is an essential micronutrient for normal immune function, and vitamin A deficiency seems to be an important risk factor for disease progression during HIV-1 infection.

Adult↗

PubMed1993

Abnormal T-cell subset proportions in vitamin-A-deficient children.

Although vitamin A deficiency in children seems to increase susceptibility to infection and community trials have shown that vitamin A supplementation can reduce childhood mortality from infectious diseases, the underlying biological mechanisms are largely unknown. We conducted a randomised, double-masked, placebo-controlled clinical trial among children in West Java, Indonesia, to determine whether vitamin A deficiency is associated with abnormalities in T-cell subsets and whether vitamin A supplementation affects T-cell subsets. We studied 55 children aged 3-6 years--30 with xerophthalmia and 25 without. Acutely malnourished children (< 80% of reference weight-for-height) were excluded. CD4/CD8 ratios and the proportions of circulating CD4 naive, CD4 memory, CD8, CD45RA, and CD8, CD45RO T-cell subsets were measured. Children with xerophthalmia had lower CD4/CD8 ratios (p < 0.08), lower proportions of CD4 naive T cells (p < 0.03), and higher proportions of CD8, CD45RO T cells (p < 0.04) than those without xerophthalmia. 26 children were given vitamin A supplementation (60 mg retinol equivalent) and 29 received placebo. 5 weeks later the vitamin A group had higher CD4/CD8 ratios (p < 0.001), higher proportions of CD4 naive T cells (p < 0.01), and lower proportions of CD8, CD45RO T cells (p < 0.05) than the placebo group. Vitamin-A-deficient children have underlying immune abnormalities in T-cell subsets and these abnormalities are reversible with vitamin A supplementation.

Analysis of Variance↗

PubMed1992

Depressed immune response to tetanus in children with vitamin A deficiency.

A randomized, double-masked, placebo-controlled clinical trial was conducted with 236 preschool children, age 3-6 y, in Indonesia to assess immune status in mild vitamin A deficiency. The immune response to tetanus immunization was used as a measure of immune competence. Clinically normal children (n = 118) and children with mild xerophthalmia (n = 118) were randomly assigned to receive oral vitamin A (60,000 micrograms retinol equivalent) or placebo treatment for a total of four study groups. Two weeks after treatment, children were immunized with diphtheria-pertussis-tetanus vaccine. The immunoglobulin G (IgG) responses to tetanus at baseline and 3 wk following immunization were measured by ELISA. After adjusting for previous tetanus immunization, clinically normal and xerophthalmic children receiving vitamin A had a significantly greater IgG response to tetanus than clinically normal and xerophthalmic children receiving placebo (P less than 0.05). These results suggest that children with mild vitamin A deficiency have a relative immune depression compared with children who have been supplemented to normal vitamin A levels.

Antibody Formation↗

PubMed1991

Experimental ocular onchocerciasis in cynomolgus monkeys. IV. Chorioretinitis elicited by Onchocerca volvulus microfilariae.

Onchocerciasis is a major cause of blindness worldwide, and much of the blindness is caused by onchocercal chorioretinitis. In an experimental animal model for ocular onchocerciasis, intravitreal injections of 10,000 live Onchocerca volvulus microfilariae isolated from infected humans into the eyes of cynomolgus monkeys (Macaca fascicularis) resulted in patchy, progressive loss of retinal pigment with pigment clumping. Areas of pigment loss were less extensive in animals that had been sensitized with microfilariae. Intravitreal injections of dead O. volvulus microfilariae resulted in mild vitritis with relatively less clinical change noted in the retina and choroid. Histopathologic examination revealed thinning and loss of outer retinal layers with pigment migration into the retina, and inflammation was more pronounced in eyes that received live microfilariae. Clinical changes appeared in eyes receiving live microfilariae before the development of significant antibody or cell-mediated immune responses. O. volvulus microfilariae appear to be more suitable than O. lienalis microfilariae in producing lesions which resemble human onchocerciasis in the primate model.

Animals↗

PubMed1990

Response of Bitot's spots in preschool children to vitamin A treatment.

In a double-masked, placebo-controlled, clinical trial in Indonesia, 88 preschool children between the ages of 36 and 72 months with Bitot's spots were randomly assigned to 200,000 IU of oral vitamin A or placebo and followed up for five weeks. Baseline and follow-up serum vitamin A levels were obtained. Of the 45 children receiving vitamin A, 33 (73.3%) showed complete cure and disappearance of Bitot's spots, six (13.3%) had disappearance of some but not all Bitot's spots, and six (13.3%) were unresponsive to treatment. The nonresponsive children were older, all male, and had higher initial mean serum vitamin A levels, 23.0 micrograms/dl, compared to 15.9 micrograms/dl in the cured group (P = .017). These data suggest that normal vitamin A status may be found in approximately 13% of children with Bitot's spots before vitamin A intervention and that one fourth of those who had Bitot's spots originally will not be cured of all Bitot's spots after intervention. These are important factors to consider when using Bitot's spots in prevalence surveys as a clinical sign of vitamin A deficiency.

Blindness↗

PubMed1990

Assessment of vitamin A status by a disk applicator for conjunctival impression cytology.

Conjunctival impression cytology was performed on 236 Indonesian preschool children, half of whom had mild xerophthalmia and half of whom were age-matched controls. We devised an applicator that applies a paper disk of fixed area to the conjunctiva with even pressure. The disk applicator was used to collect impression cytology specimens from the temporal bulbar conjunctiva of one eye while the original strip technique was used on the other eye. Mean (+/- SD) serum retinol values for children with normal and abnormal discs were 22.0 +/- 8.6 micrograms/dL and 18.0 +/- 7.2 micrograms/dL P less than .0001). Mean serum values for normal and abnormal strips were 21.7 +/- 8.6 micrograms/dL and 19.0 +/- 7.7 micrograms/dL (P less than .03). Specimens obtained with the new disk applicator corresponded more closely with serum vitamin A levels and therefore vitamin A status than those obtained with the traditional strip technique.

Child↗

PubMed1990

Longitudinal study of lesions of the posterior segment in onchocerciasis.

Onchocerciasis is a major cause of blindness, and much of the blindness due to onchocerciasis is caused by chorioretinitis. Little is known about the progression of lesions in the posterior segment in either untreated or treated disease. The authors studied the progression of onchocercal chorioretinitis in 57 patients from 1 to 3 years. Changes were documented from detailed ocular examinations, fundus photographs, and fluorescein angiograms, and included live intraretinal microfilariae, intraretinal hemorrhages, cotton-wool opacities, intraretinal pigment, white and shiny intraretinal deposits, retinal pigment epithelial window defects, and atrophy. Depigmentation at the edge of chorioretinal scarring progressed at a rate of up to 200 microns per year. Ivermectin or mebendazole treatment did not appear to alter the progress of depigmentation at the edge of chorioretinal scars. These observations suggest that onchocercal chorioretinitis is associated with early changes in the retina and retinal pigment epithelium, and that disease in the posterior segment may progress rapidly.

Animals↗

PubMed1989

Ivermectin treatment of patients with severe ocular onchocerciasis.

The treatment of onchocerciasis with diethylcarbamazine and suramin is associated with an exacerbation of ocular disease. This occurs more frequently in patients with severe onchocercal ocular disease. We assessed ocular changes following ivermectin treatment in 39 patients with severe ocular onchocerciasis. Patients were treated with 100, 150, or 200 micrograms/kg of ivermectin at either 1 or 2 year intervals and followed for 3 years. There was no evidence for an acute exacerbation of either anterior or posterior segment eye disease, and there was a marked improvement in ocular status in the group as a whole. There was a significant decrease in onchocercal involvement which was maintained for at least 3 years. Annual treatment with ivermectin can be used safely in patients with severe ocular disease and is beneficial over a prolonged period of time.

Adolescent↗

PubMed1988

Experimental ocular onchocerciasis in cynomolgus monkeys. III. Roles of IgG and IgE antibody and autoantibody and cell-mediated immunity in the chorioretinitis elicited by intravitreal Onchocerca lienalis microfilariae.

Intravitreal injection of small numbers (10-500) of microfilariae (Mf) of Onchocerca lienalis in eyes of cynomolgus monkeys induces posterior segment lesions which resemble those occurring in human onchocerciasis in some respects. In order to determine the potential roles of antibody and cell-mediated immune responses in the formation of these lesions, anti-Onchocerca and anti-retinal IgG and IgE antibody and peripheral lymphocyte blastogenic responses were followed in eight monkeys, for one week to five months after intravitreal injection of Mf. Significant ocular inflammation occurred well before any antibody or peripheral lymphocyte blastogenic responses could be detected. It may be that direct effects of Mf, e.g., by activation of complement via the alternative pathway fulfill important roles in the pathogenesis of the posterior segment lesions.

Animals↗

PubMed1988

Experimental ocular onchocerciasis in cynomolgus monkeys. II. Chorioretinitis elicited by intravitreal Onchocerca lienalis microfilariae.

Chorioretinitis due to onchocerciasis is a major cause of blindness, and the pathogenesis is poorly understood. We have developed an experimental model for onchocercal chorioretinitis using cynomolgus monkeys (Macaca fascicularis). Two normal monkeys and two monkeys which had received prior sensitization with subcutaneous injections of live Onchocerca lienalis microfilariae were given intravitreal injections of either 0, 10, 50 or 500 live microfilariae. Posterior segment changes included disc edema, venous engorgement, retinal vasculitis, intraretinal hemorrhage, and progressive retinal pigment epithelial (RPE) disturbances. Histopathological findings included perivascular infiltrates with eosinophils, eosinophilic choroiditis, and RPE hypertrophy, hyperplasia and loss of pigment. Microfilariae in the retina had no surrounding inflammation but were found adjacent to areas of RPE alterations. Overall the inflammatory reaction in the two unsensitized monkeys was more severe than that seen in the sensitized monkeys. The retinal appearance of the monkeys resembled that found in human onchocerciasis, and this model appears to be a promising one for future investigations.

Animals↗

PubMed1985

Conjunctival nodules associated with onchocerciasis.

A 14-year-old native of Ethiopia with previously treated onchocerciasis moved to California where he was examined for evidence of persisting nematode infestation. Skin and conjunctival biopsy specimens initially disclosed no abnormalities. Subsequently, conjunctival nodules developed, and a biopsy specimen of one of these revealed microfilariae of Onchocerca volvulus lying adjacent to a necrotic eosinophilic granulomatous inflammatory nodule. To our knowledge, nodules of this type have not heretofore been reported to be a notable feature of ocular onchocerciasis. This type of inflammation has a relationship to degenerating microfilaria in onchocerciasis and in other nematode infestation.

Adolescent↗

PubMedDate not supplied

Relation of vitamin A and carotenoid status to growth failure and mortality among Ugandan infants with human immunodeficiency virus.

Although growth failure is common during pediatric infection with human immunodeficiency virus (HIV) and associated with increased mortality, the relation of specific nutrition factors with growth and mortality has not been well characterized. A longitudinal study was conducted with 194 HIV-infected infants in Kampala, Uganda. Plasma vitamin A, carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin), and vitamin E were measured at age 14 wk, and weight and height were followed up to age 12 mo. Vitamin A and low plasma carotenoid concentrations were predictive of decreased weight and height velocity. Between ages 14 wk and 12 mo, 32% of infants died. Underweight, stunting, and low concentrations of plasma carotenoids were associated with increased risk of death in univariate analyses. Plasma vitamin A concentrations were not associated with risk of death. In a final multivariate model adjusting for weight-for-age, plasma beta-carotene was significantly associated with increased mortality (odds ratio: 3.16, 95% confidence interval: 1.38 to 7.21, P < 0.006). These data suggest that low concentrations of plasma carotenoids are associated with increased risk of death during HIV infection among infants in Uganda.

Body Height↗

PubMedDate not supplied

Denture use, malnutrition, frailty, and mortality among older women living in the community.

BACKGROUND: The relationships between denture use, malnutrition, frailty, and mortality in older women have not been well characterized. OBJECTIVE: To determine whether women who use dentures and have difficulty chewing or swallowing are at higher risk of malnutrition, frailty, and mortality. DESIGN: Cross-sectional and longitudinal study of 826 women, aged 70-79, from the Women's Health and Aging Studies, two population-based longitudinal studies of community-dwelling women in Baltimore, Maryland. At enrollment, data on frailty and self-reported denture use and difficulty chewing or swallowing that limited the ability to eat was collected, and plasma vitamins A, D, E, B6, and B12, carotenoids, folate, and albumin were measured. RESULTS: 63.5% of women reported using dentures, of whom 11.6% reported difficulty chewing or swallowing food. Denture users with and without difficulty chewing or swallowing and those not using dentures had, respectively, geometric mean (95% Confidence Interval [C.I.]) total plasma carotenoid concentrations of 1.481 (1.302, 1.684), 1.616 (1.535, 1.700), and 1.840 (1.728, 1.958) micromol/L, respectively (P < 0.0001), and 25- hydroxyvitamin D of 50.90 (44.25, 58.55), 47.46 (45.15, 50.40), and 54.0 (50.9, 56.8) nmol/L (P < 0.0001). The proportion using dentures among non-frail, pre-frail, and frail women was 58%, 66%, and 73%, respectively (P = 0.018). Women who used dentures and reported difficulty chewing or swallowing had lower five-year survival (H.R. 1.43, 95% C.I. 1.05-1.97), after adjusting for potential confounders. CONCLUSIONS: Older women living in the community who use dentures and have difficulty chewing or swallowing have a higher risk of malnutrition, frailty, and mortality.

Aged↗