Coverage of the vitamin A supplementation programme for child survival in Nepal: success and challenges.

BACKGROUND: Nepal's national vitamin A programme, which began in 1993 and continues twice yearly, targets pre-school-aged children in all districts of the country in an effort to reduce morbidity, mortality and nutritional blindness. OBJECTIVE: To characterize the coverage of the Nepal National Vitamin A Programme (NVAP) for pre-school-aged children in Nepal and to identify risk factors for failure to receive vitamin A supplementation. METHODS: The relationship between receipt of a vitamin A capsule and demographic and health indicators was examined in a cross-sectional study of 4013 children aged 12-59 months and their families who participated in the 2011 Nepal Demographic and Health Survey (NDHS), a nationally representative survey. Coverage of the vitamin A programme was compared with coverage estimates from surveys in 2001 and 2006. RESULTS: Coverage estimates of the national vitamin A programme for children aged 12-59 months as assessed by the 2001, 2006 and 2011 NDHS were 84.3%, 96.6% and 92.1%, respectively. Children who missed a vitamin A capsule were more likely to be younger and anaemic, have less educated parents, live in rural areas, and have higher child and infant mortality in the family. CONCLUSIONS: The national vitamin A supplementation programme in Nepal has relatively high coverage of children aged 12-59 months but still misses children in families with high child mortality. Further measures might be needed to sustain a high level of programme coverage.

Low serum carotenoids are associated with a decline in walking speed in older women.

BACKGROUND AND OBJECTIVES: Walking speed is an important measure of physical performance that is predictive of disability and mortality. The relationship of dietary factors to changes in physical performance has not been well characterized in older adults. The aim was to determine whether total serum carotenoid concentrations, a marker for fruit and vegetable intake, and serum selenium are related to changes in walking speed in older women. SUBJECTS AND METHODS: The relationship between total serum carotenoids and selenium measured at baseline, 12, and 24 months follow-up and walking speed assessed at baseline and every six months for 36 months was examined in 687 moderately to severely disabled women, 65 years or older, living in the community. RESULTS: Mean total serum carotenoids were associated with mean walking speed over three years of follow-up (P = 0.0003) and rate of change of walking speed (P = 0.007) in multivariate linear regression models adjusting for age, body mass index, and chronic diseases. Mean serum selenium was associated with mean walking speed over three years of follow-up (P = 0.0003) but not with the rate of change of walking speed (P = 0.26). CONCLUSIONS: These findings suggest that a higher fruit and vegetable intake, as indicated by higher total serum carotenoid concentrations, may be protective against a decline in walking speed in older women.

Low serum selenium is associated with anemia among older adults in the United States.

OBJECTIVE: We hypothesized that low serum selenium was associated with anemia in humans. SUBJECTS: A total of 2092 adults aged 65 and older, in the third National Nutrition Examination Survey, Phase 2 (1991-1994) (NHANES III). METHODS: Examination of the relationship between serum selenium and hematological indices in NHANES III. RESULTS: Anemia, defined by World Health Organization criteria, was present in 12.9%. Mean serum selenium among non-anemic and anemic adults was 1.60 and 1.51 micromol l(-1) (P=0.0003). The prevalence of anemia among adults in the lowest to highest quartiles of serum selenium was 18.3, 9.5, 9.7 and 6.9%, respectively (P=0.0005). The proportion of adults in the lowest quartile of selenium among those who were non-anemic or who had anemia due to nutritional causes, chronic inflammation, renal disease or unexplained anemia was 9.9, 27.5, 17.5, 24.0 and 15.4%, respectively. An increase in log(e) selenium was associated with a reduced risk of anemia (odds ratio per one standard deviation increase 0.75, 95% confidence interval 0.58-0.97, P=0.03), adjusting for age, race, education, body mass index and chronic diseases. CONCLUSION: Low serum selenium is independently associated with anemia among older men and women in the United States.

Malnutrition and morbidity among children not reached by the national vitamin A capsule programme in urban slum areas of Indonesia.

OBJECTIVE: To determine whether vitamin A capsule programmes fail to reach children who are at higher risk of malnutrition and morbidity. Although it has been suggested that there are health disparities between children who are reached or not reached by these programmes, little quantitative work has been undertaken to characterize this relationship. STUDY DESIGN: As part of a national surveillance system, nutritional status and other factors were compared in 138,956 children, aged 12-59 months, who had and had not received vitamin A supplementation in urban slum areas in Indonesia. RESULTS: In total, 63.1% of children had received a vitamin A capsule within the previous 6 months. Among children who had and had not received vitamin A supplementation, respectively, the proportion with weight-for-age and height-for-age Z scores <-3 were 7.8% vs 8.6% (P<0.0001) and 9.4% vs 10.7% (P<0.0001), and with a history of diarrhoea in the previous week was 8.1% vs 10.7% (P<0.0001). In families where a child had or had not received vitamin A supplementation, the proportion with a history of infant death <12 months was 5.2% vs 7.2% (P<0.0001) and child death <5 years was 6.7% vs 9.2%, respectively (P<0.0001). Children who had not received vitamin A supplementation were also significantly more likely to be anaemic and have diarrhoea or fever on the survey day compared with children who had received supplementation. CONCLUSIONS: In the urban slums of Indonesia, children who do not receive vitamin A supplementation tend to be slightly more malnourished and ill, and are more likely to come from families with higher child mortality than children who receive vitamin A. Higher rates of child mortality in non-participating households suggest that reaching preschoolers could yield a disproportionate survival benefit. Importantly, children who are not reached by the vitamin A programme are also unlikely to be reached by vaccination and other services, emphasizing the need to identify and extend efforts to reach non-participants.

Micronutrient supplements and mortality of HIV-infected adults with pulmonary TB: a controlled clinical trial.

SETTING: Zomba and Blantyre, Malawi, Africa. OBJECTIVES: To determine whether daily micronutrient supplementation reduces the mortality of human immunodeficiency virus (HIV) infected adults with pulmonary tuberculosis (TB). DESIGN: A randomised, controlled clinical trial of micronutrient supplementation for HIV-positive and HIV-negative adults with pulmonary TB. Participants were enrolled at the commencement of chemotherapy for sputum smear-positive pulmonary TB and followed up for 24 months. RESULTS: A total of 829 HIV-positive and 573 HIV-negative adults were enrolled. During follow-up, 328 HIV-positive and 17 HIV-negative participants died. The proportion of HIV-positive participants who died in the micronutrient and placebo groups was 38.7% and 40.4%, respectively (P = 0.49). Micronutrient supplementation did not reduce mortality (hazard ratio [HR] 0.93, 95%CI 0.75-1.15) among HIV-positive adults. CONCLUSIONS: Micronutrient supplementation at the doses used in this study does not reduce mortality in HIV-positive adults with pulmonary TB in Malawi.

Serum antioxidants, inflammation, and total mortality in older women.

The inflammatory cytokine interleukin-6 (IL-6) has been linked to poor health outcomes in older adults. Oxidative stress triggers the production of IL-6, and antioxidant micronutrients play a critical role in decreasing this inflammatory response. The authors sought to identify the relations between serum levels of antioxidant nutrients and IL-6 and mortality in older women. Levels of alpha- and beta-carotene, lycopene, lutein/zeaxanthin, alpha-cryptoxanthin, total carotenoids, retinol, alpha-tocopherol, zinc, and selenium were measured at baseline in 619 participants in Women's Health and Aging Study I (Baltimore, Maryland, 1992-1998). IL-6 was measured at baseline and at follow-up 1 and 2 years later, and all-cause mortality was determined over a 5-year period. Participants with the highest serum levels of alpha-carotene, total carotenoids, and selenium were significantly less likely to be in the highest tertile of serum IL-6 at baseline (p < 0.0001). Those with the lowest levels of alpha- and beta-carotene, lutein/zeaxanthin, and total carotenoids were significantly more likely to have increasing IL-6 levels over a period of 2 years. Those with the lowest selenium levels had a significantly higher risk of total mortality over a period of 5 years (hazard ratio = 1.54, 95% confidence interval: 1.03, 2.32). These findings suggest that specific antioxidant nutrients may play an important role in suppressing IL-6 levels in disabled older women.

Low plasma selenium concentrations, high plasma human immunodeficiency virus load and high interleukin-6 concentrations are risk factors associated with anemia in adults presenting with pulmonary tuberculosis in Zomba district, Malawi.

BACKGROUND: Although anemia is common among adults with pulmonary tuberculosis and human immunodeficiency virus (HIV) infection in sub-Saharan Africa, the factors contributing to its pathogenesis have not been well characterized. OBJECTIVE: To characterize the antioxidant micronutrient status, interleukin-6 (IL-6) concentrations, and HIV load in relationship with anemia in adults with pulmonary tuberculosis. SETTING: Zomba district, Malawi. METHODS: Erythropoietin, IL-6, plasma HIV load, and markers of micronutrient status (hemoglobin (Hb), plasma concentrations of retinol, alpha-tocopherol, carotenoids, ferritin, zinc, and selenium) were measured in 500 adults who presented with pulmonary tuberculosis in Zomba Central Hospital, Malawi. RESULTS: Among 370 HIV-positive and 130 HIV-negative adults, the prevalence of anemia was 88 and 77%, respectively (P = 0.002), and moderate to severe anemia (Hb < 80 g/l) occurred in 30 and 15%, respectively (P = 0.001). Geometric mean IL-6 concentration was 21.1 pg/ml, with no difference between HIV-positive and -negative adults. The erythropoietin response to anemia was not different between adults with elevated IL-6 and those with lower IL-6 concentrations. In a multivariate logistic regression model, HIV load, and lower plasma selenium concentrations were associated with moderate to severe anemia. In a final multivariate linear regression model, IL-6, plasma HIV load, and plasma selenium concentrations were associated with Hb concentrations. CONCLUSION: This study suggests that low selenium concentrations, high HIV load, and high IL-6 concentrations are associated with anemia in adults with pulmonary tuberculosis in sub-Saharan Africa.

Are lutein and zeaxanthin conditionally essential nutrients for eye health?

The carotenoids lutein and zeaxanthin are found in the macula in high concentrations and may play a role in the pathogenesis of age-related macular degeneration (ARMD). Lutein and zeaxanthin may protect the macula and photoreceptor outer segments throughout the retina from oxidative stress and play a role in an antioxidant cascade that safely disarms the energy of reactive oxygen species. Although lutein and zeaxanthin are not essential nutrients, studies are beginning to suggest that they fit the criteria for conditionally essential nutrients. Low plasma lutein and zeaxanthin concentrations or dietary intake are associated with low macular pigment density and increased risk of ARMD. Dietary deprivation of lutein and zeaxanthin in primates causes pathological changes in the macula. Should controlled clinical trials show lutein and/or zeaxanthin supplementation protects against the development or progression of ARMD and other eye diseases, then lutein and zeaxanthin could be considered as conditionally essential nutrients for humans.

Integration of vitamin A supplementation with the Expanded Programme on Immunization: lack of impact on morbidity or infant growth.

UNLABELLED: Vitamin A deficiency is associated with increased morbidity and mortality from diarrheal disease, measles, and malaria. It has been proposed that vitamin A supplementation could be linked with childhood immunization programs to improve child health. We conducted a randomized, double-blind, placebo-controlled clinical trial to evaluate the impact of linking vitamin A supplementation with the Expanded Programme on Immunization on morbidity and child growth. In West Java, Indonesia, 467 six-week-old infants were randomized to receive 7.5 mg retinol equivalent (RE), 15 mg RE, or placebo with childhood immunization contacts at 6, 10, and 14 wks and 9 mo of age. Child growth was assessed through anthropometry, and morbidity histories were obtained. Vitamin A supplementation had no apparent impact upon linear or ponderal growth or infectious disease morbidity in the first 15 mo of age when integrated with the Expanded Programme on Immunization. CONCLUSION: Although improving vitamin A nutriture is of general importance in reducing diarrheal and measles morbidity and mortality in developing countries, this clinical trial showed no apparent benefit of vitamin A capsules for infant health when given through childhood immunization programs.

Iron supplementation during human immunodeficiency virus infection: a double-edged sword?

Although iron supplementation is considered beneficial for groups at risk for anemia, concern has been raised that it could be harmful during human immunodeficiency virus (HIV) infection. Studies suggest: (1) faster HIV disease progression in thalassemia major patients receiving inadequate doses of iron-chelating drug; (2) higher mortality among patients receiving iron supplementation with dapsone compared with aerosolized pentamidine for prophylaxis against Pneumocytis carinii pneumonia; (3) higher iron stores and mortality among patients with haptoglobin Hp 2-2 phenotype; and (4) shorter survival among patients with high bone marrow iron deposition. These studies largely involved men in developed countries. Among HIV-infected pregnant women in Africa with a high prevalence of iron deficiency, no relationship was found between indicators of iron status and HIV disease severity. The available data do not contraindicate the current practice of iron supplementation in developing countries where there is a high prevalence of both HIV infection and iron deficiency.

Impact of vitamin A supplementation on anaemia and plasma erythropoietin concentrations in pregnant women: a controlled clinical trial.

INTRODUCTION: Although studies suggest that vitamin A or its metabolites influence the synthesis of erythropoietin in vitro and in animal models, it is unclear whether vitamin A supplementation increases plasma erythropoietin concentrations in humans. OBJECTIVE: To determine whether daily vitamin A supplementation increases plasma erythropoietin concentrations in pregnant women with a high prevalence of anaemia. METHODS: A randomized, double-blind, controlled clinical trial was conducted to examine the effect of daily vitamin A (3000 microg retinol equivalent), iron (30 mg), and folate (400 microg) versus iron (30 mg) and folate (400 microg) (control) on haemoglobin and plasma erythropoietin concentrations in 203 pregnant women in Malawi, Africa. RESULTS: Mean gestational age at enrollment was 23 wk, at which time 50% of the women were anaemic (haemoglobin <110 g/L). Mean (+/-SEM) change in haemoglobin from enrollment to 38 wk was 4.7+/-1.6 g/L (p=0.003) and 7.3+/-2.3 g/L (p=0.003) in the vitamin A and control groups, respectively. Mean change in plasma erythropoietin concentrations from enrollment to 38 wk was 2.39+/-5.00 (p=0.63) and -2.87+/-3.92 IU/L (p=0.46) in the vitamin A and controls groups, respectively. There were no significant differences between vitamin A and control groups in the slope of the regression line between log10 erythropoietin and haemoglobin at enrollment or 38 wk, and between enrollment and follow-up within either group. CONCLUSIONS: Vitamin A supplementation does not appear to increase haemoglobin and plasma erythropoietin concentrations among pregnant women with a high prevalence of anaemia in Malawi.

Iodine in human milk: perspectives for infant health.

Iodine is essential for normal growth, mental development, and survival of infants. The main source of iodine for breastfeeding infants is the iodine found in human milk. Despite the importance of iodine for infant health, there have been limited studies addressing human milk iodine concentrations. The newly recommended Adequate Intake of iodine for infants is 110 microg/day for infants 0-6 months and 130 microg/day for infants 7-12 months. Further studies of human milk iodine are needed to ensure that iodine prophylaxis is providing sufficient iodine for mothers and infants worldwide.

Improved antioxidant status among HIV-infected injecting drug users on potent antiretroviral therapy.

Low serum antioxidant levels in HIV-infected people have been attributed to altered metabolism associated with excess oxidative stress. We conducted a study to examine serum antioxidant levels in 175 HIV-positive and 210 HIV-negative injecting drug users (IDUs) in Baltimore, Maryland. At the time of data collection, 30 of the HIV-positive IDUs were receiving antiretroviral therapies (ART) including a protease inhibitor (PI), 43 ART without a PI, 22 monotherapies, and 80 not on any ART. Serum antioxidants examined included retinol, alpha-tocopherol and gamma-tocopherol, alpha-carotene and beta-carotene, lycopene, lutein/zeaxanthin, and beta-cryptoxanthin. Mean serum levels of lycopene and lutein/zeaxanthin were significantly lower in HIV-positive IDUs than HIV-negative IDUs. Contrary to the findings in other studies, however, levels of the remaining antioxidants in HIV-positive study subjects were not lower than in HIV-negative study subjects. In fact, serum alpha-tocopherol levels were significantly higher in HIV-positive IDUs than HIV-negative IDUs (medians = 744 microg/dl and 718 microg/dl, respectively; p = .04). Among HIV-positive study subjects, there were significant differences in antioxidant levels by ART regimen. In multivariate models adjusting for injecting drug use, dietary intake, supplement intake, gender, and alcohol intake, significant overall differences by ART regimen were observed for alpha-tocopherol, beta-carotene, and beta-cryptoxanthin. Serum levels of these three antioxidants were significantly higher in the PI group than in the other three ART groups combined (p = .0008, 0.02, and 0.02, respectively). These data provide indirect evidence of the effectiveness of PIs in lowering oxidative stress levels in HIV-positive IDUs.

Hyporetinolemia and acute phase proteins in children with and without xerophthalmia.

BACKGROUND: The relations among hyporetinolemia, acute phase proteins, and vitamin A status in children are unclear. OBJECTIVE: The objective was to examine the relations between acute phase proteins and plasma retinol concentrations in children with and without clinical vitamin A deficiency (Bitot spots and night blindness). DESIGN: The study was a nonconcurrent analysis of acute phase protein concentrations and other data from a previous clinical trial. Preschool children, 3-6 y of age, with (n = 118) and without (n = 118) xerophthalmia were assigned to receive oral vitamin A (60 mg retinol equivalent) or placebo and were seen at 5 wk. All children received oral vitamin A (60 mg retinol equivalent) at 5 wk. RESULTS: At baseline, alpha(1)-acid glycoprotein (AGP) was elevated in 42.9% and 23.5% (P < 0.003) and C-reactive protein (CRP) was elevated in 17.7% and 13.7% (NS) of children with and without xerophthalmia, respectively. Hyporetinolemia (retinol < 0.7 micromol/L) occurred in 61.0% and 47.4% (P < 0.04) of children with and without xerophthalmia, respectively. A history of fever, a history of cough, and nasal discharge noted on examination were each associated with elevated acute phase proteins. Vitamin A supplementation increased plasma retinol at 5 wk but had no significant effect on concentrations of acute phase proteins. CONCLUSIONS: Elevated acute phase protein concentrations and infectious disease morbidity are closely associated during vitamin A deficiency.

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.

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.

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.

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.

PIP: This is a randomized, placebo-controlled clinical trial on the effect of oral iodized oil (OIO) on the immune response to oral poliovirus vaccine (OPV). 617 8-week old infants were enrolled in the study conducted in Subang, West Java, Indonesia. Infants received either IOI--at which time they also received OPV and diphtheria-pertussis-tetanus vaccine--or a placebo (poppy seed oil) during their first Expanded Program on Immunization (EPI) contact for their first dose of OPV. After the first dose, 2 boosters of OPV were received by the infants at 4-week intervals, and there was a final follow-up evaluation when infants reached their 6th month. Serum samples were collected from each infant at enrolment and at follow-up. A total of 478 pairs of pre-immune and postimmune sera were collected for evaluation. Neutralizing antibody titers to poliovirus serotypes 1,2, and 3 were compared in serum samples. The range of measured neutralizing antibody activity was 0.01-14 IU for type 1, 0.05-49 IU for type 2, and 0.01-11 IU for type 3 poliovirus. After the immunization, 2 (0.4%), 1 (0.2%), and 16 (3.3%), respectively, of the infants had no detectable neutralizing antibodies to all 3 poliovirus serotypes. It was found that OIO did not reduce the antibody responses to any of the 3 serotypes of OPV but did improve infant survival in the same cohort. These findings indicate that oral iodine supplementation may be safely combined with the delivery of the first dose of OPV according to EPI schedules.

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.

PIP: A randomized double-blind placebo-controlled trial was conducted to assess the efficacy of vitamin A supplementation on morbidity due to Plasmodium falciparum among 520 children aged 6-60 months in a malaria-endemic area of Papua New Guinea. Malaria morbidity was assessed through weekly community-based case detection and surveillance of patients who self-reported to the health center. Cross-sectional surveys were also conducted at the beginning, middle, and end of the study to assess malariometric indicators. Laboratory tests were also analyzed for species-specific density. Findings showed that the number of episodes of falciparum malaria among young children in Papua New Guinea was 30% lower in those who received vitamin A than in the placebo recipients. The children, mostly aged 12-36 months, had fewer febrile episodes, fewer enlarged spleens and lower parasite density. No significant differences were observed for hemoglobin concentration or prevalence of anemia for any age group. The findings suggest that clinical episodes, spleen enlargement, and parasite density were influenced by immunological mechanisms that were different from infection and anemia. It also suggests that vitamin A is effective, inexpensive, and a programmatically practical tool in controlling P. falciparum malaria.

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.