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Biomedical subjects

R D Semba

Publications and source records attributed to R D Semba.

At least 55 records · Page 3Linked to original sources

Effect of vitamin A supplementation on morbidity due to Plasmodium falciparum in young children in Papua New Guinea: a randomised trial.

BACKGROUND: Many individuals at risk of malaria also have micronutrient deficiencies that may hamper protective immunity. Vitamin A is central to normal immune function, and supplementation has been shown to lower the morbidity of some infectious diseases. We investigated the effect of vitamin A supplementation on malaria morbidity. METHODS: This randomised double-blind placebo-controlled trial of vitamin A supplementation took place in a P. falciparum endemic area of Papua New Guinea. Of 520 potentially eligible children aged 6-60 months, 480 were randomly assigned high-dose vitamin A (n=239) or placebo (n=241), every 3 months for 13 months. Malaria morbidity was assessed through weekly community-based case detection and surveillance of patients who self-reported to the health centre. Cross-sectional surveys were also done at the beginning, middle, and end of the study to assess malariometric indicators. Analyses were by intention to treat. FINDINGS: The number of P. falciparum febrile episodes (temperature > or = 37.5 degrees C with a parasite count of at least 8000/microL) was 30% lower in the vitamin A group than in the placebo group (178 vs 249 episodes; relative risk 0.70 [95% CI 0.57-0.87], p=0.0013). At the end of the study P. falciparum geometric mean density was lower in the vitamin A than the placebo group (1300 [907-1863] vs 2039 [1408-2951]) as was the proportion with spleen enlargement (125/196 [64%] vs 148/207 [71%]); neither difference was significant (p=0.093 and p=0.075). Children aged 12-36 months benefited most, having 35% fewer febrile episodes (89 vs 141; relative risk 0.65 [14-50], p=0.0023), 26% fewer enlarged spleens (46/79 [58%] vs 67/90 [74%], p=0.0045), and a 68% lower parasite density (1160 [95% CI 665-2022] vs 3569 [2080-6124], p=0.0054). Vitamin A had no consistent effect on cross-sectional indices of proportion infected or with anaemia. INTERPRETATION: Vitamin A supplementation may be an effective low-cost strategy to lower morbidity due to P. falciparum in young children. The findings suggest that clinical episodes, spleen enlargement, and parasite density are influenced by different immunological mechanisms from infection and anaemia.

Child, Preschool↗

Micronutrients and the pathogenesis of human immunodeficiency virus infection.

Micronutrient deficiencies may be common during human immunodeficiency virus (HIV) infection. Insufficient dietary intake, malabsorption, diarrhoea, and impaired storage and altered metabolism of micronutrients can contribute to the development of micronutrient deficiencies. Low plasma or serum levels of vitamins A, E, B6, B12 and C, carotenoids, Se, and Zn are common in many HIV-infected populations. Micronutrient deficiencies may contribute to the pathogenesis of HIV infection through increased oxidative stress and compromised immunity. Low levels or intakes of micronutrients such as vitamins A, E, B6 and B12, Zn and Se have been associated with adverse clinical outcomes during HIV infection, and new studies are emerging which suggest that micronutrient supplementation may help reduce morbidity and mortality during HIV infection.

Avitaminosis↗

Vitamin A and immunity to viral, bacterial and protozoan infections.

Studies in animal models and cell lines show that vitamin A and related retinoids play a major role in immunity, including expression of mucins and keratins, lymphopoiesis, apoptosis, cytokine expression, production of antibody, and the function of neutrophils, natural killer cells, monocytes or macrophages, T lymphocytes and B lymphocytes. Recent clinical trials suggest that vitamin A supplementation reduces morbidity and mortality in different infectious diseases, such as measles, diarrhoeal disease, measles-related pneumonia, human immunodeficiency virus infection and malaria. Immune responses vary considerably during different infections, and the available data suggest that the modulation of immune function by vitamin A may also vary widely, depending on the type of infection and immune responses involved.

Bacterial Infections↗

Human immunodeficiency virus load in breast milk, mastitis, and mother-to-child transmission of human immunodeficiency virus type 1.

Human immunodeficiency virus (HIV) type 1 load in breast milk and mastitis were examined as risk factors for vertical transmission of HIV-1. Six weeks after delivery, HIV-1 load and sodium (an indicator of mastitis) were measured in breast milk from 334 HIV-1-infected women in Malawi. Median breast milk HIV-1 load was 700 copies/mL among women with HIV-1-infected infants versus undetectable (<200 copies/mL) among those with uninfected infants, respectively (P<. 0001). Elevated breast milk sodium levels consistent with mastitis occurred in 16.4% of HIV-1-infected women and were associated with increased vertical transmission of HIV-1 (P<.0001). Median breast milk HIV-1 load was 920 copies/mL among women with versus undetectable among those without elevated breast milk sodium levels, respectively (P<.0001). Mastitis and breast milk HIV-1 load may increase the risk of vertical transmission of HIV-1 through breast-feeding.

Adult↗

Integration of vitamin A supplementation with the expanded program on immunization does not affect seroconversion to oral poliovirus vaccine in infants.

Childhood immunization programs may provide infrastructure for delivering vitamin A supplements to infants in developing countries. The effect of giving vitamin A, an immune enhancer, on antibody responses to trivalent oral poliovirus vaccine (TOPV) is unknown. A randomized, double-blind, placebo-controlled clinical trial was conducted to determine the effect of giving vitamin A simultaneously with TOPV on antibody responses to poliovirus. Infants (n = 467) received oral vitamin A, 15 mg retinol equivalent (RE), 7.5 mg RE or placebo with TOPV at 6, 10 and 14 wk of age. Antibody responses to poliovirus types 1, 2 and 3 were measured by a microvirus neutralization assay at enrollment and at 9 mo of age. Seroconversion rates to poliovirus types 1, 2 and 3 ranged from 98 to 100% in the three treatment groups, and there were no differences in mean antibody titers to poliovirus types 1, 2 and 3 among treatment groups. This study demonstrates that oral vitamin A does not affect antibody responses to poliovirus vaccine when integrated with the Expanded Program on Immunization.

Adult↗

Vitamin A as "anti-infective" therapy, 1920-1940.

In the last fifteen years, a large series of controlled clinical trials showed that vitamin A supplementation reduces morbidity and mortality of children in developing countries. It is less well known that vitamin A underwent two decades of intense clinical investigation prior to World War II. In the 1920s, a theory emerged that vitamin A could be used in "anti-infective" therapy. This idea, largely championed by Edward Mellanby, led to a series of at least 30 trials to determine whether vitamin A--usually supplied in the form of cod-liver oil--could reduce the morbidity and mortality of respiratory disease, measles, puerperal sepsis, and other infections. The early studies generally lacked such innovations known to the modern controlled clinical trial such as randomization, masking, sample size and power calculations, and placebo controls. Results of the early trials were mixed, but the pharmaceutical industry emphasized the positive results in their advertising to the public. With the advent of the sulfa antibiotics for treatment of infections, scientific interest in vitamin A as "anti-infective" therapy waned. Recent controlled clinical trials of vitamin A from the last 15 y follow a tradition of investigation that began largely in the 1920s.

Child↗

Breast-feeding, mastitis, and HIV transmission: nutritional implications.

In many developing countries, transmission of the human immunodeficiency virus (HIV) from mother to infant occurs through breast-feeding. Mastitis, an inflammatory process in the breast, may be common in lactating women in Africa and is associated with both higher HIV load in breast milk and mother-to-child transmission of HIV. Antioxidant micronutrient deficiencies may increase the risk of mastitis. Whether prevention, early diagnosis, and prompt treatment of mastitis will help reduce mother-to-child transmission of HIV in breast-feeding women needs further study.

Animals↗

Mastitis and immunological factors in breast milk of lactating women in Malawi.

Although an elevated sodium concentration in human milk is suggested to be an indicator of mastitis, it is unclear whether elevated sodium concentrations are associated with immunological and inflammatory mediators in human milk. We conducted a cross-sectional study to evaluate the relationships between elevated breast milk sodium concentrations and levels of lactoferrin, lysozyme, secretory leukocyte protease inhibitor (SLPI), interleukin-8 (IL-8), and RANTES (regulated on activation normal T cell expressed and secreted) in human milk at 6 weeks postpartum in 96 lactating women in Blantyre, Malawi. Mastitis, as indicated by an elevated breast milk sodium concentration, was present in 15.6% of the women. Women with and without mastitis had respective median levels of other factors as follows: lactoferrin, 1,230 versus 565 mg/liter (P < 0. 0007); lysozyme, 266 versus 274 mg/liter (P = 0.55); SLPI, 76 versus 15 microg/liter, (P < 0.0002); IL-8, 339 versus 25 ng/liter (P < 0. 0001); and RANTES, 82 versus 3 ng/liter (P < 0.0001). Elevated sodium concentrations in breast milk are associated with an increase in levels of some immunological and inflammatory factors in breast milk.

Adolescent↗

Mastitis and immunological factors in breast milk of human immunodeficiency virus-infected women.

Human milk contains important immunological factors that protect the breast from infection and are thought to protect infants from infection, including human immunodeficiency virus (HIV) infection. Human milk immunological factors have not been well characterized in HIV-infected lactating women. Lysozyme, secretory leukocyte protease inhibitor (SLPI), sodium (an indicator of mastitis), and HIV were measured in breast milk of 334 HIV-infected women at 6 weeks postpartum. Women with mastitis, as indicated by elevated breast milk sodium concentrations, had higher median levels lysozyme (290 vs 221 mg/L, p < 0.04), SLPI (38 vs 19 mg/L, p < 0.0001) and HIV (920 copies/mL vs undetectable, p < 0.0001) compared with women without mastitis. Lower total plasma carotenoid levels (p < 0.02) and higher maternal HIV load (p < 0.006) by quartile were risk factors for mastitis. Mastitis, as indicated by elevated breast milk sodium levels, is associated with high concentrations of immunological factors and higher HIV load in breast milk.

Adult↗

Oral iodine supplementation does not reduce neutralizing antibody responses to oral poliovirus vaccine.

Iodine deficiency is a major cause of impaired mental development, goitre, and cretinism in many parts of the world. Because existing immunization programmes can be used to deliver oral iodized oil (OIO) to infants at risk, it was important to know whether OIO could adversely affect the antibody response to vaccines, such as trivalent oral poliovirus vaccine (OPV). A randomized, double-blind, placebo-controlled clinical trial was conducted in Subang, West Java, Indonesia, in which 617 eight-week-old infants received either OIO or a placebo (poppy-seed oil) during a routine visit for their first dose of OPV as part of the Expanded Programme on Immunization (EPI). The infants received two boosters of OPV at 4-week intervals after the first dose, and were followed up when 6 months old. Neutralizing antibody titres to poliovirus serotypes 1, 2, and 3 were compared in serum samples that were taken from 478 of these infants just before the first dose of OPV and at 6 months. It was found that oral iodized oil did not reduce the antibody responses to any of the three serotypes of OPV. These results indicate that oral iodine may safely be delivered to infants at the same time as oral poliovirus vaccine according to current EPI immunization schedules.

Analysis of Variance↗

Carotenoid status of pregnant women with and without HIV infection in Malawi.

OBJECTIVE: To characterise the major plasma carotenoids in pregnant women with and without HIV infection attending antenatal clinic in Blantyre, Malawi. DESIGN: A cross sectional study. SETTING: Antenatal clinic of Queen Elizabeth Central Hospital, Blantyre, Malawi. SUBJECTS: Nine hundred women (697 HIV-positive and 203 HIV-negative women) in their second trimester of pregnancy. MAIN OUTCOME MEASURES: Plasma carotenoid levels as related to HIV status and level of disease progression. RESULTS: There were no significant differences in plasma carotenoid levels between HIV-positive and HIV-negative women. Median (25th, 75th percentiles) plasma levels of carotenoids for all women in the study were alpha-carotene, 0.040 (0.23, 0.071) mumol/L; beta-carotene, 0.350 (0.192, 0.595) mumol/L; beta-cryptoxanthin, 0.050 (0.029, 0.091) mumol/L; lutein/zeaxanthin 0.646 (0.426, 0.976) mumol/L; lycopene, 0.088 (0.055, 0.138) mumol/L, and total carotenoids 1.321 (0.884, 1.874) mumol/L. Mothers had higher mean plasma concentrations of alpha-carotene (p < 0.04), beta-carotene (p < 0.0001), lutein/zeaxanthin (p < 0.0001), and total carotenoids (p < 0.0001) in the wet season than the dry season. No seasonality was observed for beta-cryptoxanthin, lycopene, or retinol. CONCLUSION: This study suggests that pregnant women with and without HIV infection in Blantyre, Malawi have relatively low plasma carotenoid levels and poor dietary intake of provitamin A carotenoids.

Carotenoids↗

Catheter complications in AIDS patients treated for cytomegalovirus retinitis.

PURPOSE: To describe the complications of central venous catheter use for intravenous therapy of cytomegalovirus (CMV) retinitis in patients with AIDS. METHODS: Retrospective review of 388 patients with AIDS and CMV retinitis treated with intravenous medications through an indwelling catheter. RESULTS: The catheter complication rate was 1.2 complications per person-year (0.33 complications per 100 catheter-days). Current injecting drug use increased the risk of infectious complications [hazard ratio (HR), 1.73; P=0.04] whereas former use did not (HR, 0.96; P=0.88). Subdermal port catheters increased the risk of bacteremia (HR, 1.78; P=0.05). Mortality for the first complication was 5.8%. Forty percent of patients required catheter removal, and 86.8% of these patients required reinsertion of another catheter. CONCLUSIONS: Catheter complications are a substantial problem in patients with CMV retinitis treated with daily intravenous therapy.

AIDS-Related Opportunistic Infections↗

Association between measures of vitamin A and the ocular fundus findings in cerebral malaria.

OBJECTIVE: To investigate the relationship between serum vitamin A levels and conjunctival impression cytology and retinal whitening present in Malawian children with cerebral malaria. METHODS: Standard retinal examination and conjunctival impression cytology were performed at hospital admission on 101 consecutively admitted children with cerebral malaria. Blood samples were drawn from 56 children at 24 hours, frozen at -20 degrees C, and transported for assessment of vitamin A levels by high-performance liquid chromatography. Associations among fundus findings and vitamin A measurements were sought. RESULTS: The whitening of the retina that we have previously described in children with cerebral malaria was found to be associated with a mean+/-SD serum vitamin A level of 0.29+/-0.1 micromol/L, compared with a mean vitamin A level of 0.41+/-0.2 micromol/L in children without retinal whitening. Children with retinal whitening were 2.77 (95% CI, 1.06-7.3) times more likely to have abnormal conjunctival impression cytology results than those without whitening. No child had any clinical or ophthalmologic evidence of chronic vitamin A deficiency. CONCLUSIONS: The retinal whitening described in children with cerebral malaria is associated with low serum vitamin A levels and with abnormal conjunctival impression cytology results and may be due to acute vitamin A deficiency at the tissue level.

Child↗

Vitamin A supplementation and human immunodeficiency virus load in injection drug users.

The use of vitamin A therapy during human immunodeficiency virus (HIV) infection is under clinical investigation, and vitamin A could potentially modulate HIV replication because the virus genome contains a retinoic acid response element. A randomized, double-masked, placebo-controlled clinical trial was conducted to determine the impact of single high-dose vitamin A supplementation, 60-mg retinol equivalent (200,000 IU), on HIV load and CD4 lymphocyte count. HIV-infected injection drug users (120) were randomly allocated to receive vitamin A or placebo. Plasma vitamin A level, CD4 lymphocyte count, and HIV load were measured at baseline and 2 and 4 weeks after treatment. Vitamin A supplementation had no significant impact on HIV load or CD4 lymphocyte count at 2 and 4 weeks after treatment. This study suggests that high-dose vitamin A supplementation does not influence HIV load.

Adult↗

Maternal vitamin A deficiency and infant mortality in Malawi.

The relationship between maternal vitamin A deficiency during pregnancy and infant mortality is unclear. We conducted a prospective cohort study of 377 HIV-negative women and their infants in Blantyre, Malawi. Serum vitamin A levels were measured during the second or third trimester of pregnancy and infants were followed during the first year of life. From delivery until 12 months of age, 18 infants died (47.7 per 1000). Mothers of infants who died had lower serum vitamin A levels during pregnancy (0.74 +/- 0.13 mumol/l) compared with mothers of infants who did not die (1.02 +/- 0.03 mumol/l) (p = 0.055). Infants born to women whose vitamin A levels were in the lowest quartile (< 0.32 mumol/l) had three-fold higher likelihood of mortality than infants born to women whose vitamin A levels were in the higher quartiles (p < 0.03). These results suggest that maternal vitamin A deficiency during pregnancy may contribute to higher infant mortality rates.

Adult↗

Expression of adhesion molecules and CD28 on T lymphocytes during human immunodeficiency virus infection.

Adhesion molecules, which play a major role in lymphocyte circulation, have not been well characterized in human immunodeficiency virus (HIV) infection. T-lymphocyte populations, including CD3, CD4, CD28, and adhesion molecules (L selectin, LFA-1, VLA-4, and ICAM-1) were measured by flow cytometry in a cross-sectional study of 100 HIV-infected and 49 HIV-seronegative adults. HIV-infected adults had lower numbers of CD3+ lymphocytes expressing L selectin (P < 0.0001) and VLA-4 (P < 0.01) and higher numbers of CD3+ lymphocytes expressing LFA-1bright (P < 0.002) than did HIV-negative adults. By CD4+-lymphocyte count category (>500, 200 to 500, or <200 cells/microl), HIV-infected adults with more advanced disease had lower percentages of CD3+ lymphocytes expressing L selectin and VLA-4 and higher percentages of CD3+ lymphocytes expressing LFA-1. The percentages of CD3+ CD28+ lymphocytes and of CD3+ L selectin+ lymphocytes were positively correlated (Spearman coefficient = 0.86; P < 0.0001), and the percentage of CD3+ CD28+ lymphocytes and the CD3+ LFA-1bright lymphocyte/CD3+ LFA-1dim lymphocyte ratio were negatively correlated (Spearman coefficient = -0.92; P < 0.00001). The results of this study suggest that HIV infection is associated with altered expression of adhesion molecules.

Adult↗