3. Hussey 1990 confirmed that treatment with vitamin A reduced measles morbidity and mortality. The Pediatric Infectious Disease Journal: April 2005 - Volume 24 - Issue 4 - p 389. doi: 10.1097/01.inf.0000157349.86003.7d. Development of pneumonia, diarrhea, croup and otitis media. Four studies (Barclay 1987; Coutsoudis 1991; Hussey 1990; Ogaro 1993) reported on postmeasles croup. These two studies individually did not show any statistical reduction in the incidence of pneumonia. et al. Huff DL, The cost of a dose of vitamin A is around USD 0.02 (WHO 1998). Joanne Katz, Sc.D. Kumar R, However, data were collected and no side effects were reported in any of the studies. Peterson DE, The World Health Organization (WHO) and the United Nations International Children's Emergency Fund (UNICEF) issued a joint statement recommending that vitamin A be administered to all children diagnosed with measles in communities where vitamin A deficiency (serum vitamin A <10 g/dL) is a recognized problem and where mortality related to measle. However, vitamin A megadoses (200,000 international units (IUs) on each day for two days) lowered the number of deaths from measles in hospitalized children under the age of two years. Daulaire NM, Giving vitamin A to children with measles reduces their risk of death. Church MS, Although the waterbased product may be associated with greater mortality reductions the advantage may be offset by its lower stability, higher cost and nonavailability. It can also lead to complications with your skin, heart, lungs, tissues and immune system. An official website of the United States government. In a 100% susceptible population, a single case of measles results in 12 to 18 secondary cases, on average. The study, led by the University of Tampere in Finland, is part of the long-term . Research suggests that supplementation might reduce death due to measles. There was an 83% reduction in risk of mortality (RR 0.21; 95% CI 0.07 to 0.66) in the vitamin Asupplemented group in children under two years of age, in studies that used two doses of 200,000 IU of vitamin A (Barclay 1987; Coutsoudis 1991; Hussey 1990). Duggan M. Severe ulcerative herpes of mouth and eye following measles, Transactions of the Royal Society of Tropical Medicine and Hygiene, Expanded programme on immunization: programme for the prevention of blindness, Joint WHO/UNICEF statement on vitamin A for measles, A guide to the treatment and prevention of vitamin A deficiency and xerophthalmia, Using national immunization days to deliver vitamin A, Tissue changes following deprivation of fatsoluble A vitamin, World Development Report 1993: Investing in Health, Vitamin A for treating measles in children, A modified test for small study effects in metaanalyses of controlled trials with binary endpoints, The Cochrane Database of Systematic Reviews, The mean duration of pneumonia ranged across control groups from, The mean duration of pneumonia in the intervention groups was, The mean duration of diarrhea in days ranged across control groups from, The mean duration of diarrhea in days in the intervention groups was, The mean days stay in hospital ranged across control groups from, The mean stay in hospital in the intervention groups was, The mean duration of fever ranged across control groups from, The mean duration of fever in the intervention groups was. 'randomized controlled trial'/exp OR 'single blind procedure'/exp OR 'double blind procedure'/exp OR 'crossover procedure'/exp AND [embase]/lim 237,648 28 Feb 2011 Vitamin A status appeared to be satisfactory and at least 30% of Ogaro's participants had vitamin A levels greater than 20 ug/dl. This evaluates the value of measurement on experimental intervention (E) minus measurement on control intervention (C) separately for each participant. Minder C. Bias in metaanalysis detected by a simple, graphical test. The dose is given orally once a day for 2 days and . Randomized controlled trials (RCTs) in children with measles given vitamin A or placebo, along with standard treatment. HY and Chao Min Wan (CW) were responsible for data extraction and rewriting the updated review. Djunaedi E, Six of the studies (Barclay 1987; Coutsoudis 1991; Dollimore 1997; Hussey 1990; Ogaro 1993; Rosales 1996) were conducted in Africa, one in Japan (Kawasaki 1999) and one in England (Ellison 1932). Bhaskaram P, Infants (618) were randomly allocated to receive 30 mg vitamin A or a placebo with the measles immunization. One explanation is through depletion of hepatic stores. government site. As vitamin A supplementation has shown to lead to a reduction in morbidity and mortality in children under 5 years of age, the World Health Organization recommends intramuscular vitamin A administration for all children as soon as acute measles is diagnosed, followed by a second dose the next day, even in developed countries where measles is . Huff DL, Pokhrel RP, 1.5 Age more than two years (> 200,000 IU), 4.2 Recovery from diarrhea in < five days, 4.5 Compete clinical recovery in < eight days, 4.12 Recovery from pneumonia in < eight days, Randomized clinical trial using a random number table, 200,000 IU vitamin A orally for 2 days, or routine treatment without vitamin A, Random sequence generation (selection bias), Randomized clinical trial using a random numbers table, Blinding (performance bias and detection bias), Randomized, placebocontrolled, doubleblind trial, 60 children aged 4 to 24 months hospitalized with complicated measles, WHO recommended dose (54.5 mg < 12 months or 109 mg > 12 months) of retinyl palmitate drops or a placebo syrup, The patients were allocated to treatment or placebo groups according to a random numbers table, Vitamin A or placebo was administered by the same person, Blinding of participants and personnel (performance bias), Blinding of outcome assessment (detection bias), 946 children aged 6 to 90 months, in the community, 100,000 IU of vitamin A for children aged 6 to 11 months or 200,000 IU of vitamin A for older children every 4 months for 2 years, The study area was divided into 185 small geographic units, each comprising 30 to 77 compounds. In children under the age of two years formulation did not make any difference as the oilbased product was associated with a statistically significant reduction in the risk of mortality and the waterbased vitamin A effect almost reached statistical significance. A similar but apparently stronger reduction effect (66%) was seen in children hospitalized with measles, although this was not significantly different from the 30% seen in lowincome country community settings. Gunn RA. Barclay 1987 drew attention to the importance of vitamin A therapy in reducing measles mortality and led to the 1987 joint recommendation between the World Health Organization (WHO) and the United Nations International Children's Fund (UNICEF) for the administration of a single oral dose of vitamin A (200,000 international units (IUs), or 100,000 IUs in infants) at the time of initial measles diagnosis in nonxerophthalmic children who lived in areas where measles casefatality rates were greater than 1% (WHO 1988). None of the studies included in this review reported any adverse effects. In some clinical trials, vitamin A reduced the severity of illness and mortality in children with measles (Barclay 1987; Coutsoudis 1991; Hussey 1990) even in areas where eye signs of vitamin A deficiency were rare (VAST Study 1993). 64 If 85% efficacy is assumed for single dose measles vaccine, these serology results would . MEDLINE (OVID) McCabe G, Problems with the pancreas that occur with cystic fibrosis increase the risk of vitamin A deficiency . #9. Dossetor J, We support the WHO recommendation that two doses of vitamin A (200,000 IU) be given to all cases of measles, especially to children under the age of two with severe measles, in addition to the standard treatment. #11 AND #14 112 28 Feb 2011 Skip to content Care at Mayo Clinic Care at Mayo Clinic About Mayo Clinic Request Appointment Overview What is vitamin A deficiency? Whittle HC, Two studies used waterbased vitamin A formulations while the other three used an oilbased formulation. Where more than one trial included similar participants and interventions, without significant clinical or methodological diversity or statistical heterogeneity, we used a fixedeffect model. The association between use of vitamin A supplements and reduced risk of lung, prostate and other types of cancer is unclear. Eight trials met the inclusion criteria (2574 participants). However two doses reduced overall and pneumoniaspecific mortality in children aged less than two years. There was considerable variation in the outcomes measured and reported in the studies. The protective effect of vitamin A supplementation was seen only in hospitalized children. However, these symptoms are minor and transitory, with no known longterm effects and requiring no special treatment (WHO 1998). Vitamin A reduces the risk of death from measles by 87% for children younger than 2 years. 2 exp MEASLES VIRUS/ Kawasaki Y, Sension MG, Kawasaki (Kawasaki 1999) reported on this outcome and there was an increased risk in the vitamin A group of developing acute laryngitis but this was not statistically significant. Duration of hospitalization, fever, pneumonia and diarrhea. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue et al. Vitamin A in a single dose for treating measles in children was not associated with a reduced risk of mortality. Three significant studies (Barclay 1987; Coutsoudis 1991; Hussey 1990) present most frequently in all the five subgroup analyses: dose, formulation, hospitalization, age and casefatality in the study area. Fawzi WW, We carried out subgroup analyses for dose, formulation, age, hospitalization and pneumoniaspecific mortality. Diarrhea Skin problems While vitamin A is essential for good health, it can be toxic in high doses. The data is updated regularly with the most recent official country reporting collected through the WHO/UNICEF joint reporting process. We used the new 'Risk of bias' domains and judgements from the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011), a specific tool for assessing risk of bias in each included study. The effect estimate was included in a metaanalysis using the generic inversevariance method in RevMan 2011. West KP Jr, Coutsoudis A, Raghuramulu N, #2. measles:ab,ti AND [embase]/lim 11,518 28 Feb 2011 Yang Huiming, Wan Chaomin and Mao Meng took over this review from D'Souza RM and D'Souza R and updated it. Seven trials reported an adequate method of ensuring allocation concealment. RT @NHSEnglandLDN: Has your child missed an MMR (measles, mumps and rubella) vaccination? They looked at ambulatory participants who were followed up closely for one month with daily and weekly visits to urban health centres. Vitamin A supplementation in northern Ghana: effects on clinic attendances, hospital admissions, and child mortality. Comparison 1 Vitamin A versus placebo, Outcome 2 Morbidity (dichotomous data). As there were many outcomes reported by single studies there is the possibility that some effects would appear to be significant by chance alone. Therefore, the presence of correlated characteristics between these factors cannot be ruled out as firstly the data cannot be stratified because the raw data were not available and, secondly, there were too few studies to stratify across the five subgroups. There is the possibility that more severe clinical cases of measles are more likely to benefit from vitamin A treatment. It is clear that the studies were heterogeneous in several ways. The World Bank 1993 study declared vitamin A supplementation to be one of the most costeffective of all health interventions. The community studies did not include children who were very sick as they were referred for hospitalization. Hussey (Hussey 1990) and Coutsoudis (Coutsoudis 1991) reported on herpes stomatitis. Hussey (Hussey 1990) showed a statistically significant reduction in hospital stay by almost five days in the vitamin Atreated group (MD 4.72; 95% CI 7.22 to 2.22) while Kawasaki (Kawasaki 1999) showed a reduction by almost half a day but this was not statistically significant (MD 0.40; 95% CI 1.08 to 0.28). Children with low levels of vitamin A are more likely to have a more severe case of measles. Underwood BA, Three of the four hospitalbased studies (Barclay 1987; Coutsoudis 1991; Hussey 1990) which used the twodose regimen demonstrated a protective effect on mortality. Karyadi D. Vitamin Afortified monosodium glutamate and health, growth, and survival of children: a controlled field trial. WHO Guideline1 Vitamin A supplementation in infants and children 6-59 months of age Summary Vitamin A deficiency affects about 19 million pregnant women and 190 million preschool-age children, mostly from the World Health Organization (WHO) regions of Africa and South-East Asia. Hence, authors of earlier reviews were not able to compare dosages in subgroup analyses. Overall, the quality of evidence for the use of vitamin A for measles in children can be considered as moderate. The summary estimate of these studies shows a statistically significant reduction in duration of diarrhea by almost two days in the vitamin Atreated group (MD 1.92; 95% CI 3.40 to 0.44). In four studies that reported large reductions in mortality, measles mortality fell but acute respiratory infection (ARI) mortality did not change (Daulaire 1992; Rahmathullah 1990; VAST Study 1993; West 1991). In settings where vitamin A deficiency is a public health problem, the World Health Organization (WHO) recommends a high-dose vitamin A supplement every six months for children 6-59 months to reduce child morbidity and mortality. The evidence partly supports the WHO recommendation of two 200,000 IU doses. In this third update, no new trials were included or excluded. Broughton M, and as a result attenuates the therapeutic effect estimates for vitamin A treatment of measles. the contents by NLM or the National Institutes of Health. 8 Vitamin A.mp. Except for the community studies by Rosales and Dollimore, the studies were conducted in hospitalized participants. In the 2007 update, no new trials were included or excluded. #8 OR #9 29,143 28 Feb 2011 Publication bias cannot reasonably be assessed in this review. 7 pneumon*.tw. Schrijver J, Infected people are usually contagious from 4 days before until 4 days after rash onset. Dolllimore N, The evidence from these studies can only be generalized in relation to lowincome countries. If your child has missed a dose, we will contact you. Milton RC, Randomized controlled trials (RCTs) in children with measles given vitamin A or placebo along with standard treatment. Two doses of vitamin A reduced the incidence of croup (RR 0.53; 95% CI 0.29 to 0.89) but not pneumonia morbidity (RR 0.92; 95% CI 0.69 to 1.22), nor diarrhea morbidity (RR 0.80; 95% CI 0.27 to 2.34). Two doses of vitamin A (200,000 international units (IUs) on consecutive days) reduced the mortality in children aged less than two years and pneumoniaspecific mortality. This suggests that basic health care then was not dissimilar to that available in Africa in the 1980s and 1990s. The dose is given orally once a day for 2 days and . This comprises a description and a judgement for each entry in a 'Risk of bias' table, where each entry addresses a specific feature of the study (Higgins 2011). Kogbe OI, sharing sensitive information, make sure youre on a federal Accessibility When these studies were stratified by dose, the reduction in the incidence of croup was greater for the three studies (Barclay 1987; Coutsoudis 1991; Hussey 1990) that used two doses of vitamin A (200,000 IU). Comparison 1 Vitamin A versus placebo, Outcome 3 Morbidity (continuous data). If, however, there was evidence of heterogeneity of the treatment effect between trials then we either pooled only homogeneous results or we used a randomeffects model (in which case the CIs would be broader than those of a fixedeffect model). The Dollimore study is a subanalysis of the Ghana Vitamin A Supplementation Trials [VAST] that administered vitamin A to children prior to onset of measles; which should have excluded the study from the review since the objective was to determine whether vitamin A therapy, commenced after measles has been diagnosed, is beneficial in preventing mortality. #13. random*:ab,ti OR placebo*:ab,ti OR factorial*:ab,ti OR crossover*:ab,ti OR 'cross over':ab,ti OR 'crossover':ab,ti OR assign*:ab,ti OR allocat*:ab,ti OR volunteer*:ab,ti OR ((singl* OR doubl*) NEAR/1 blind*):ab,ti AND [embase]/lim 801,952 28 Feb 2011 Egger M, Mosteller F. Vitamin A supplementation and child mortality. She remarked that this could be attributed to the absence of emergency and malnourished cases. Coutsoudis (Coutsoudis 1991) found that the vitamin A group had a 1.5 times better chance of complete clinical recovery than the placebo group, which was statistically significant. The only study carried out in a highincome country (Japan) used onefourth of the recommended dose (100,000 IU), showed a reduced morbidity and did not report any toxicity. Effect of vitamin A on diarrhoeal and respiratory complications of measles, Efficacy of a single oral dose of 200,000 IU of oilsoluble Vitamin A in measlesassociated morbidity. 2. Chinese Cochrane Center, Chinese Center of EvidenceBased Medicine, West China Hospital of Sichuan University, China. Smith JS, Impact of vitamin A supplementation on childhood mortality. Measles Tools and Resources For additional information and resources about measles, visit www.nfid.org/measles and view the following resources: Measles is a major cause of death in children in low-income countries and is particularly dangerous in children with vitamin A deficiency. 9 exp Vitamin A/ Secondly, not all settings, even in Africa, have high measles casefatality rates and the usefulness of vitamin A supplementation where mortality and severe complications are much less frequent, has had limited study" (Ogaro 1993). Reply. Cystic fibrosis. Five studies are reported to be doubleblinded (Coutsoudis 1991; Dollimore 1997; Hussey 1990; Ogaro 1993; Rosales 1996). Vitamin A deficiency is a recognized risk factor in severe measles (Frieden 1992). Comparison 1 Vitamin A versus placebo, Outcome 1 Mortality. Finally, we registered a permanent search with Current Contents to notify the authors by email of any new trials published in journals indexed by Current Contents. Ross AC, In 1997, the WHO and UNICEF recommended that 200,000 IUs of vitamin A be given twice to children with measles who were over the age of one year and lived in areas where vitamin A deficiency may be prevalent (WHO 1997). In Barclay's study (Barclay 1987) the staff and participants were blinded but not the treating physician who also assessed the outcomes. Most of the deaths were due to pneumonia. At this cost "to achieve significant reductions in hospitalizations and costs in terms of mortality and longterm morbidity, vitamin A therapy for the management of measles is highly costeffective" (Cervinskas 1996). 11 6 and 10, 1 exp MEASLES/ Madhusudan J, The review authors (HY, CW) independently extracted data and when disagreement arose on the suitability of a trial for inclusion in the review, or on its quality, we reached a consensus by discussion. Two studies (Coutsoudis 1991; Kawasaki 1999) reported on the duration of fever, in days. The degree of retinol depression is associated with the severity of illness (Butler 1993). In Hussey's study there was almost six days' reduction in duration of pneumonia in the vitamin Atreated group (MD 5.8; 95% CI 8.2 to 3.5) and two days reduction in the Coutsoudis study (MD 1.9; 95% CI 2.2 to 1.6). 5 pneumonia.mp. Day SE, Xerophthalmia is a severe drying of the eye surface caused by a malfunction of the tear glands. The fatality rate in hospitalized children often exceeds 10% (Morley 1969a) and casefatality ratios of up to 20% have been found in community studies in West Africa (Aaby 1984). Reddy V, Overall, the seroconversion rates did not differ between vitamin A (89.5%) and placebo (87.6%) groups. As all studies did not report on all possible morbidity outcomes the conclusions we were able to draw about the effect of vitamin A on measlesrelated morbidity are limited. In the first data collection round, information was obtained on whether each child had ever been hospitalized or had ever had measles. Coovadia HM. To determine whether vitamin A is beneficial in preventing mortality, pneumonia and other secondary infections in children with measles. The study showed a statistically significant reduction by two days in the vitamin Atreated group (MD 2.00; 95% CI 2.71 to 1.29). Other studies have reported no significant effect on morbidity or mortality even though they were sufficiently large to do so (Dollimore 1997; Vijayaraghavan 1990). Buy; The study, a part of the VIDI trial, observed the impact of the standard 10 g and a tripled 30 g dose of Vitamin D on children from the age of two Both studies were individually statistically significant. Measles is still a major cause of childhood morbidity and mortality in some lowincome countries. The World Health Organization (WHO) recommends administration of an oral dose of 200,000 IU (or 100,000 IU in infants) of vitamin A per day for two days to children with measles in areas where vitamin A deficiency may be present. Before But when measles does occur, vitamin A can be an effective treatment when appropriately administered by a healthcare professional. There were 1750 cases reported in the Netherlands in 1999 despite a 96% immunization rate in children over 14 months of age (Sheldon 2000). The summary estimate from these studies showed a slight reduction in diarrhea in the vitamin Atreated group but this was not statistically significant. Butler JC, 13 8 and 12, #15. Vitamin A can, therefore, be used for the treatment of measles and may be beneficial either by reducing the effects of measles infection (therapeutic effect) or preventing the subsequent development of secondary infection (protective effect), or both (Coutsoudis 1991). Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies. These factors, in addition to the fact that a single dose of vitamin A was used in both studies, are probably the major reasons for perceived lack of efficacy of vitamin A treatment. Measles vaccination resulted in a 73% drop in measles deaths between 2000 and 2018 worldwide We carried out subgroup analyses (determined a priori) (D'Souza 1999) for age, dosage, formulation (oil or waterbased), setting (hospital or community) and geographic area (varying measles casefatality rates). However, the mean duration of pneumonia, diarrhea and fever in the intervention groups were shorter, and the mean number of days in hospital in the intervention groups was less. This raises an issue about whether randomization balanced this important confounder. ITT analysis). This would also further accentuate the reduction of immunocompetence that is associated with measles infection (Whittle 1979). Dose 1 is to be administered at age 9 months and Dose 2 at age 15 months. We described for each included study the method used to conceal the allocation sequence in sufficient detail and determined whether intervention allocation could have been foreseen in advance of, or during recruitment, or changed after assignment. The summary estimate of the two studies shows no statistically significant reduction in the days in hospital (MD 2.39; 95% CI 6.60 to 1.83).
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