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Query: UMLS:C0024530 (malaria)
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Dr. Nils Daulaire, senior health adviser to the US Agency for International Development (USAID), announced their plan to supplement basic food products with vitamin A which will save millions of children in Third World countries from death and diseases. Vitamin A testing conducted in Nepal and Indonesia resulted to significant reductions in the rate of childhood death. Aside from reducing the death rates from illnesses such as pneumonia, diarrhea, and malaria, vitamin A also decreases the severity of the symptoms. In recognition of these benefits, USAID and other major food and drug companies will soon begin their first vitamin A fortification and distribution projects in India, Nicaragua, and Bangladesh. The plan will also be initiated in Zambia on May 13 with a program to fortify sugar. The US government will allocate $25 million for child survival programs.
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PMID:Vitamin A: lifesaver for the Third World. AID, private sector to bring it. 1232 6

Retinol (vitamin A alcohol) may have a beneficial role in the host response to malaria in humans and previously published data have suggested that it has a direct inhibitory effect on the growth of Plasmodium falciparum in vitro. To further investigate the role of retinoids as potential antimalarial agents, we assessed the effect of all-trans-retinoic acid (RA), 9-cis-RA and 13-cis-RA, as well as retinol itself and its ester, retinyl palmitate, on 3H-hypoxanthine uptake by the laboratory-adapted strains of P. falciparum 3D7 and K1. In addition, we examined the influence of three specific RA receptor antagonists, ER 27191, Ro 415253 and AGN 194301, on retinoid-induced growth inhibition of 3D7. All-trans-RA, 9-cis-RA and 13-cis-RA in concentrations ranging from 1 x 10(-4) to 5 x 10(-10) M each had antimalarial activity, but at IC50 values (5.9 x 10(-5) to 7.9 x 10(-5) M) that were less than those of retinol (2.5 x 10(-5) to 3.2 x 10(-5) M). Retinyl palmitate had minimal effect on 3H-hypoxanthine uptake. Each of the three specific antagonists inhibited growth of 3D7 (IC50 range 1.2 x 10(-5) to 3.0 x 10(-5) M) but, in isobolographic analysis, were antagonistic to retinol (dose factor potentiation, DFP 0.46-0.79) and, in the case of Ro 415253, to all-trans-RA (DFP=0.39). Although we did not attempt to quantify losses of retinoids from the system, these data suggest that retinol has greater antimalarial activity than its RA metabolites and especially retinyl palmitate. The specific RA receptor antagonists showed paradoxical antimalarial activity but consistently antagonised the effect of retinol and all-trans-RA in isobolographic experiments. We conclude that RA metabolites may be less suitable than retinol per se as antimalarial agents and that P. falciparum might possess or acquire a RA receptor-like moiety.
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PMID:In vitro antimalarial activity of retinoids and the influence of selective retinoic acid receptor antagonists. 1287 28

In order to evaluate the association between serum vitamin A levels and ocular lesions attributable to non-complicated malaria, 200 patients seen consecutively at the Malaria Outpatient Clinic of FUNASA, Manaus, Amazonas, Brazil were included in this study. Ophthalmologic examination consisted of indirect binocular ophthalmoscopy under medicamentous mydriasis, biomicroscopy with a portable slit lamp and measurement of central visual acuity. Vitamin A serum concentration was determined by HPLC, and deficiency was defined as serum values equal to or lower than 0.35 micromol/l. Serum vitamin A values between 0.36 and 0.70 micromol/l were considered as marginal levels. Hypovitaminosis A (</=0.70 micromol/l serum levels) was observed in 33% (66/200) of the patients. Ocular lesions were associated with serum levels </=0.35 micromol/l (P < 0.001). Vitamin A deficiency was more frequent in patients with high parasitaemia (P = 0.029) and their first episode of malaria (P = 0.016). None of the patients showed clinical or ophthalmologic signs attributable to hypovitaminosis A.
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PMID:Serum vitamin A levels in patients with ocular lesions attributable to non-complicated malaria in the Brazilian Amazon region. 1518 37

A preliminary study from our laboratory found retinol (vitamin A alcohol) to have in vitro activity against Plasmodium falciparum at concentrations close to those in normal human serum (1-3 microM). To characterize the antimalarial potential of retinol in more detail, the 3D7 and K1 laboratory strains of P. falciparum were maintained in continuous culture and [3H]hypoxanthine incorporation and microscopy were used to assess the effect of retinol against asexual stages of the parasite life-cycle. Losses of retinol and retinol-associated hemolysis were also quantified in the in vitro culture system. There were retinol losses of >50% but no hemolysis was observed with added retinol concentrations up to 100 microM. All stages of parasite development showed comparable sensitivity to retinol including merozoite invasion (range of mean IC50 values 10.1-21.4 microM after adjustment for losses). Retinol pre-treatment of uninfected RBC did not inhibit merozoite invasion. Retinol treatment was associated with increased vacuolization within the parasite food vacuole and evidence of parasite membrane rupture. These appearances were similar to those seen with quinoline and artemisinin compounds. Although these data do not support a role for acute retinol supplementation in the treatment of falciparum malaria, they add to knowledge regarding potential antimalarial therapies and justify assessment of more potent synthetic retinoids and their metabolites.
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PMID:Characterization of the effect of retinol on Plasmodium falciparum in vitro. 1536 39

Vitamin A supplementation to preschool children is known to decrease the risks of mortality and morbidity from some forms of diarrhea, measles, human immunodeficiency virus (HIV) infection, and malaria. These effects are likely to be the result of the actions of vitamin A on immunity. Some of the immunomodulatory mechanisms of vitamin A have been described in clinical trials and can be correlated with clinical outcomes of supplementation. The effects on morbidity from measles are related to enhanced antibody production and lymphocyte proliferation. Benefits for severe diarrhea could be attributable to the functions of vitamin A in sustaining the integrity of mucosal epithelia in the gut, whereas positive effects among HIV-infected children could also be related to increased T-cell lymphopoiesis. There is no conclusive evidence for a direct effect of vitamin A supplementation on cytokine production or lymphocyte activation. Under certain circumstances, vitamin A supplementation to infants has the potential to improve the antibody response to some vaccines, including tetanus and diphtheria toxoids and measles. There is limited research on the effects of vitamin A supplementation to adults and the elderly on their immune function; currently available data provide no consistent evidence for beneficial effects. Additional studies with these age groups are needed.
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PMID:Effects of vitamin a supplementation on immune responses and correlation with clinical outcomes. 1602 Jun 84

Reduced plasma retinol concentrations occur in human malaria but the benefits of supplementation remain uncertain. We assessed the in vivo efficacy of retinol administration, and its effect on lipid peroxidation, in a Plasmodium berghei murine model. Animals received vehicle (n=17) or retinol (i) before P. berghei inoculation (four doses), (ii) at parasitaemia 10-15% (three to four doses) or (iii) before and after inoculation (six to seven doses; n=15 in each group), with euthanasia on day 8 post-inoculation or when the parasitaemia exceeded 50%. Multiple-dose pre-inoculation retinol reduced endpoint parasitaemia by 24% (P=0.001 versus controls). A reduction of 18% (P=0.042) was observed when retinol was given to parasitaemic animals. Retinol was ineffective when given both before and after infection (11% reduction; P=0.47). Although retinol supplementation did not change plasma retinol concentrations, liver retinol content increased and correlated inversely with endpoint parasitaemia (r=-0.45, P=0.001). Malaria infection augmented concentrations of the free radical lipid peroxidation end-product F(2)-isoprostanes in plasma, erythrocytes and liver by 1.8-, 2.8- and 4.9-fold, respectively, but retinol supplementation had no effect on these increases. Consistent with some human malaria studies, prophylactic retinol reduces P. berghei parasitaemia. This effect relates to augmentation of tissue retinol stores rather than to retinol-associated changes in oxidant status.
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PMID:Retinol supplementation in murine Plasmodium berghei malaria: effects on tissue levels, parasitaemia and lipid peroxidation. 1715 53

The study was undertaken to asses the impact of drought on childhood illnesses and nutrition in under five children of rural population using three stage sampling design. The study has been carried out in 24 villages belonging to 6 tehsils of Jodhpur district which was a drought affected desert district of Western Rajasthan in 2003. A total of 914 under five children (0-5 years) could be examined for their childhood illnesses, malnutrition, dietary intake and clinical signs of nutritional deficiency. Childhood illnesses observed at the time of drought were respiratory (7.5 %), gastroentrological (7.5%), and 5.6% fever (viral, malaria and jaundice), higher in males than females. Children suffered from recent and long term malnutrition were 39% and 26% respectively as per National Centre for Health Statistics (NCHS) standards. The extent of malnutrition was significantly higher in females than in males (p<0.01). Vitamin A & B complex deficiencies were 0.7% and 3/% respectively. The protein energy malnutrition (PEM) was observed in 44.4%. Overall mean calorie and protein intake deficit was observed to be very high (76.0 & 54.0 %). The comparison of present drought results with earlier studies in normal and drought conditions showed higher prevalence of PEM and deficiencies of calories & proteins in their diet. Respiratory, gastroentrological and fever were main childhood illnesses observed and were higher in males at the time of drought. PEM, vitamin A & B- complex deficiencies, anemia along with deficit in calories and proteins in their diet was observed higher in present study as compared to non desert areas, which may be due to the harsh environmental conditions in desert areas and paucity in the consumption of daily food intake. Due to inadequate consumption of daily food, the children were suffering from PEM resulting in several childhood illnesses. Effective measures making availability of adequate calories and proteins to all age groups especially to under five children through the ongoing nutrition programs needs to be ensured.
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PMID:Childhood illnesses and malnutrition in under five children in drought affected desert area of western Rajasthan, India. 1737 Jun 94

Humans have evolved complex immune systems to protect against infection by pathogens. However, pathogens possess a remarkable genetic versatility that allows them to gain new vigour and so escape such population immunity. Conflicting pathogen-host objectives, therefore, lead to the evolutionary equivalent of an "arms race". Typically, in this struggle, pathogens attempt to deplete their host of specific nutrients that are essential for immune system function. After infection, the resulting deficiency of nutrient(s) may cause many of the disease symptoms and sequela. In malaria, Plasmodium falciparum, for example, depletes its host of Vitamin A, possibly resulting in blindness in some cases. However, 200,000 International Units of Vitamin A, given to children every three months can reduce significantly their susceptibility to malaria. This would seem to be a minimum child dosage for the treatment of the disease. In contrast, the Coxsackie B virus causes a selenium deficiency that may result in myocardial infarction or Keshan disease. However, table salt fortified with 15ppm anhydrous sodium selenite can cause dramatic drops in the incidence of Keshan disease, while selenium supplementation also reduces re-infarction rates. HIV-1 depletes its host of four nutrients: selenium, cysteine, glutamine and tryptophan, resulting in symptoms known as AIDS. Open and closed clinical trials in South Africa, Zambia and Uganda, involving daily adult doses of 600mcg l-selenomethione, and some 500mg l-glutamine, hydroxytryptophan and N-acetyl cysteine, however, have shown that such supplementation can reverse the symptoms of AIDS and prevent HIV-1 infected patients declining into this disease. It is obvious, therefore, that supplementation of diet with specific nutrients can reduce infection by particular pathogens. In addition, if infection still occurs, their use as a treatment may prevent many of the symptoms and sequela commonly associated with diseases such as malaria, myocardial infarction and AIDS.
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PMID:Host-pathogen evolution: Implications for the prevention and treatment of malaria, myocardial infarction and AIDS. 1759 May 22

Vitamin A and retinoic acid have previously been shown to confer some protection against a severe course of malaria by fostering the phagocytosis of parasitized erythrocytes. Phagocytosis of erythrocytes is stimulated by phosphatidylserine exposure at the cell surface. The present study has thus been performed to explore the effect of retinoic acid and the specific retinoic acid receptor (RAR) agonist 4-(E-2-[5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl]-1-propenyl) benzoic acid (TTNPB) on erythrocyte annexin V binding, which reflects phosphatidylserine exposure at the cell surface. A 24 hours exposure to either, retinoic acid (3 microM) or TTNPB (3 microM), indeed significantly increased annexin binding, an effect paralleled by decrease of forward scatter reflecting cell shrinkage. According to Fluo3 fluorescence, exposure to either, retinoic acid (10 microM, 24 hours) or TTNPB (10 microM, 6 hours), significantly increased cytosolic Ca(2+)-activity, a known trigger of phosphatidylserine exposure. Infection of erythrocytes with Plasmodium falciparum increased phosphatidylserine exposure, an effect increased in the presence of TTNPB. In conclusion, retinoid acid and TTNPB trigger phosphatididylserine exposure and cell shrinkage of erythrocytes, typical features of suicidal erythrocyte death or eryptosis. The eryptosis could participate in the accelerated clearance of parasitized erythrocytes from circulating blood following treatment with retinoids.
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PMID:Retinoic acid induced suicidal erythrocyte death. 1820 86

In recognising the success attained through community-directed treatment with Ivermectin, there has been a growing interest to use a similar approach for delivery of interventions against other communicable diseases. This study was conducted in 2007 to evaluate the impact of community directed intervention (CDI) on delivering five health interventions namely Vitamin A supplementation (VAS), community-directed treatment with Ivermectin (CDTi), distribution of insecticide-treated nets (ITN), directly observed treatment of tuberculosis (DOTS), and home-based management of malaria (HMM). The study was carried out in onchocerciasis endemic districts of Kilosa, Muheza, Lushoto, Korogwe and Ulanga districts in Tanzania. A total of 250 households were involved in the study for the period of two years. During the first year, one new intervention was added in each study district. A second new intervention was then added in the same manner during the second study year. In the control district all interventions, with the exception of Ivermectin distribution, continued to be delivered in the traditional manner throughout the study period. Results showed that Ivermectin treatment coverage in the CDI districts (88%) was significantly (P<0.005) higher than in the control district (77%). The coverage of VAS was 84 +/- 7%, showing very little difference between control and intervention districts (P>0.05). The DOTS treatment completion rate was observed only in Korogwe where 4 out 7 patients had completed their treatment. The proportions of pregnant women and <5 years children sleeping under ITN in the CDI districts (range: 83-100%) were significantly higher (P< 0.05) than those in the control district (40-43%). There was also a higher proportion of malaria cases referred in the intervention districts (42%) than in the control district (21%) (P<0.005). Likewise, the proportion of <5 years children who were presumptively diagnosed with malaria and received appropriated treatment within 24 hours in the intervention districts (17-29%) was higher than those in the control district (4%) (P<0.005). The costs incurred per integrated programme in the intervention districts were much lower than those in the control district. In conclusion, our results showed higher coverage of interventions in the CDI districts without necessarily increasing the cost.
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PMID:Community directed interventions for malaria, tuberculosis and vitamin A in onchocerciasis endemic districts of Tanzania. 1940 85


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