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Vitamin A and Disease: Results of Trials in Northern Ghana

Results of two studies aimed at helping to clarify the effects of vitamin A supplementation on childhood mortality and morbidity respectively have been published in The Lancet. The studies were carried out on adjacent populations in northern Ghana by the Vitamin A Supplementation Trials (VAST) team - a collaboration between researchers from the London School of Hygiene and Tropical Medicine and the School of Medical Sciences of the University of Science and Technology, Kumasi, Ghana.

Both the “Survival Study” (mortality) and the “Health Study” (morbidity) involved the random double-blind administering of doses of vitamin A or placebo to children in the study populations over six months of age at four monthly intervals for the duration of the trials.

The Survival Study included 21,906 children aged 6-90 months who were followed up for up to 26 months (between September 1989 and December 1991). Either vitamin A or placebo doses were assigned randomly to each of the 185 geographical clusters into which the study area had been divided - 92 clusters were assigned vitamin A and 93 placebo treatment. Children aged 6-11 months received 100,000 IU retinol equivalents or placebo and those aged 12 months or older received 200,000 IU retinol equivalents or placebo during visits by trained fieldworkers in seven survey rounds over 2 years. At each visit the child was recorded as being present, temporarily absent, moved away, or dead. Parents of children found to be suffering from any illness at a fieldworker’s visit were advised to take them to the nearest health facility for diagnosis and treatment. Dosing compliance was similar in the two groups - an average of 89.5% of eligible children were successfully treated in each round. Children were screened for signs of xerophthalmia every four months.

The Health Study included 1455 children aged 6-59 months who were followed up for just over one year (June 1990-August 1991). In this trial vitamin A or placebo treatment was assigned randomly on an individual basis - the dose according to age was identical to the Survival Study. An average of 94.7% of eligible children received the supplement or placebo in each round. Morbidity surveillance was based on weekly home visits by field workers who carried out a detailed interview with parents recording the occurrence on each day of the week of 21 listed symptoms, signs and conditions. At weekly visits, fieldworkers were instructed to refer ill children to mobile clinics, according to specified criteria. Children were examined for signs of xerophthalmia every four months by a physician.

In both studies, children with confirmed active xerophthalmia or its sequelae (corneal scars) were withdrawn immediately from the study and given vitamin A. The prevalence of xerophthalmia at baseline was 0.7% in the survival study children and 1.5% in the health study children - rates which are very close to the threshold used by WHO to define a population as having a problem of public health significance. In each study rates in vitamin A and placebo groups were similar. Proportions of children with low baseline serum retinol concentrations were substantial in both trial populations.

In the survival study there were 892 deaths. The mortality rate - expressed as a proportion of “child-years of follow-up” was 27.1 per 1,000 child-years. 397 of the deaths were in vitamin A clusters (24.4 per 1,000 child-years) and 495 in placebo clusters (29.9 per 1,000 child-years). The ratio of mortality rates was thus 0.81 (or 19% less mortality in the vitamin A group).

A probable cause of death was established for 697 (78.1%) of the 892 deaths - the mortality rate due to gastroenteritis was significantly lower in the vitamin A clusters than in the placebo clusters.

In the health study there were only two significant differences between the vitamin A and placebo groups in the mean daily prevalence of the symptoms/conditions investigated in the weekly visits - prevalence of vomiting and refusal of food or breastmilk.

However, clinic attendance rates were significantly lower in the vitamin A group than in the placebo. Hospital admission rates were also significantly lower in the vitamin A group than in the placebo group. There were 26 deaths among trial children in the Health Study, 6 in the vitamin A supplemented group and 20 in the placebo group.

In discussing the results of these trials, the VAST study team highlight the “strong influence” found on the “occurrence of episodes of illness severe enough to lead the mother to take the child to a clinic, and those that subsequently resulted in the child being admitted to hospital - as well as an effect on mortality.” It appeared that vitamin A supplementation reduced the frequency of severe and lethal illness without decreasing the frequency of less severe illnesses.

The all-cause mortality results (19% less mortality in vitamin A clusters) of the survival study showed that improving vitamin A intake of at least some populations of young African children can substantially reduce their mortality. Moreover, this result occurred in an area where vitamin A deficiency was a problem of only marginal public health importance.

The authors of the study conclude that “the results of this study have important health policy implications. They show that improving the vitamin A intake of young children in areas where xerophthalmia exists, even at low prevalence, should be a high priority for both health and agricultural services. If routine interventions can be devised that effectively improve vitamin A status - the burden of xerophthalmia, other severe illnesses and mortality in children will be substantially reduced. As well as these direct benefits to population, there will be substantial indirect benefits owing to substantial reductions in clinic attendances and hospital admissions. Health services appropriate a significant proportion of national budgets, and economic and social costs incurred by the family of an ill child are also large.”

(Source: Ghana VAST Study Team (1993). Vitamin A Supplementation in Northern Ghana: Effects on Clinic Attendances, Hospital Admissions, and Child Mortality. The Lancet, 342, 7-12)

Eliminating IDD in the Americas: 31 Countries Sign Declaration on Universal Salt Iodization

The Regional Meeting on Universal Salt Iodization Towards the Elimination of Iodine Deficiency Disorders in the Americas took place in Quito, Ecuador on April 9-11 1994, and resulted in the signing of a Declaration on Universal Salt Iodization by 31 countries including 23 from the Americas region, reinforcing commitment in the Americas towards the World Summit for Children Goal of eliminating iodine deficiency disorders by the year 2000, and the intermediate mid-decade goal to iodize all salt in all countries where iodine deficiency disorders (IDD) are a public health problem by the end of 1995.

The meeting, which was cosponsored by UNICEF, PAHO, the Ecuador Ministry of Health, ICCIDD, CIDA, the MI-IDRC and the AGCD, was attended by Mr Sixto Duran-Ballen, President of Ecuador, Mr James P Grant, Executive Director of UNICEF, Mr Patrick) Abad-Herrera, Minister of Health for Ecuador, Dr Helena E Restrepo, personal representative of the Director of PAHO/WHO, national and international health professionals, state ministers, public health specialists and executives of private salt producers.

The host country for the meeting, Ecuador, is one amongst 13 countries in the Americas that have achieved 90% or more of edible salt fortification with iodine, and where iodine deficiency is close to being eliminated. Speaking at the opening session of the meeting, Mr James Grant, Executive Director of UNICEF, thanked the Ecuadorian government for “the worldwide leadership Ecuador is providing in the effort to eliminate iodine deficiency disorders - the leading cause of mental retardation among children which affects some 650 million people and puts 1.5 billion people at risk.” Dr Patricio Abad-Herrera, Minister of Public Health of Ecuador, spoke of the severity of the problem of iodine deficiency: “this deficiency is at the origin of endemic goiter, cretinism, learning problems, low labour productivity and even abortions. It has already been proven that the intelligence quotient of populations with iodine deficiencies is 15% lower than the rest.”

However, that the means are available to provide adequate iodine to all through the iodization of salt was recognized in the Declaration, and also by Dr Helena E Restrepo, Director of the Health Promotion and Protection Division of PAHO/WHO who pointed out “it has been shown historically, and Ecuador among other countries is proving it today, that irrespective of the level of development it is possible to ensure that the population consumes the necessary amount of iodine.”

At the meeting, Mr James Grant himself was awarded the “Medal of the National Order of Merit with the Rank of High Official” by the President of the Republic of Ecuador, Sixto Duran Ballen, on behalf of the National Government “for his extraordinary efforts and dedication towards improving the living conditions for all children of the world.”

(Source: Report on the Regional Meeting for Universal Salt Iodization Towards the Elimination of Iodine Deficiency Disorders in the Americas, April 1994)

Diet and Cancer Prevention

Antioxidant vitamin supplements such as vitamins A, C, D & E are taken widely in the USA for their reported neutralizing effect on “free radicals” - molecules thought to be responsible for, amongst other things, playing a part in causing cancer in humans. Considerable epidemiological evidence does indicate that these nutrients are linked with decreased risk of contracting certain types of cancer and heart disease. However, most studies have looked at the effects of diets that are rich in particular vitamins - but which contain other nutrients as well - thus people with high vitamin intakes may share other characteristics that protect them from disease.

In the United States, the Food & Drug Administration (FDA) accepts that foods rich in vitamin E and beta carotene can help prevent cancer, but will not authorize health claims for supplements until controlled studies establish that these alone bring the same benefits.

That is not to say that supplements cannot provide benefits, some studies, such as that in the Linxian province of China (see SCN News No. 9 p.45) suggest they do, but, evidence is emerging that other substances found in fruits and vegetables may also play an important part in cancer prevention.

Compounds called “phytochemicals” are plentiful in fruits and vegetables (it is estimated that tomatoes contain around 10,000 of them) - where they serve the function of protecting the plants from sunlight - and they may also be beneficial to humans. Devra Lee Davis, senior science adviser at the US Public Health Service is reported to have said “There is growing evidence that these natural products can take tumours and defuse them... they can turn off the proliferative process of cancer.”

In Praise of Magic Bullets

contributed by J. Peter Greaves, former Senior Adviser (Micronutrients), UNICEF, now retired.

Nutrition is notorious for its fashions, and at the moment it is distinctly fashionable to deride the concept of “magic bullets”, deny that they may exist, accuse people of promoting the concept to the exclusion of all else (I don’t know who such people can be), and then abuse them roundly. I think this attitude is unthinking, unfair and unwise.

I should like to defend magic bullets. In fact, I should like to extol them. After all, what is a bullet? A small object that can be targeted to an individual in order to kill. So what is a magic bullet, if not a small object that can be targeted to an individual in order to save its life? Is there not something magical about the very idea? How wonderful if it were true! And of course we know that it can be true. A single capsule of vitamin A, delivered every 4 to 6 months, can save the life of a child. Or can save the remaining eye if given promptly to a child who has already lost the other through severe xerophthalmia. A single shot of iodized oil, or one oral capsule, given to a woman before or during pregnancy, can prevent a still-birth, or the birth of a cretin - permanently stunted in body and mind. To me these effects are magical, and I hope I never lose my wonder at their effect, or my gratitude that we do have these tools in our armoury. Of course we have other tools too, more sustainable in the long term, more affordable, but until these alternatives are deployed and functioning well, not to use supplementation as a strategy, if it can be managed effectively, is to me unethical, if not immoral. No-one who has studied the Montreal “Ending Hidden Hunger” reports, if nothing else, can accuse any of the major actors there of advocating supplementation as the major policy. To anyone who argues otherwise one is tempted to respond in the words of the Duke of Wellington, who when accosted in the street by someone who said, “Mr Smith, I believe,” is reported to have replied: “Sir, if you believe that, you will believe anything.”

To be fair, many of the “magic bullet mockers” are recalling the fashion of some three decades ago, when deficiency of protein was held to be the major nutrition problem - but protein is hardly a bullet. And anyway the concept was shown to be thought by some at that time to be the factor limiting protein utilisation and consequent growth. But the massive supplementation trial in Tunisia showed that to be without practical significance. We can all agree that there are no shortcuts to the abolition of poverty and underdevelopment, or to the underlying factors responsible for protein-energy malnutrition. But we can be grateful that there are some actions that can be taken to control micronutrient malnutrition with immediate effect.

(Adapted from an address at the opening of the first PAMM training programme in Atlanta in September 1992)


Dr Paul Talalay, of Johns Hopkins Medical Institutions has led a team investigating the effects of a phytochemical found in broccoli, cauliflower, brussels sprouts, turnips and kale, called sulforaphane. The results have been published in the Proceedings of the National Academy of Sciences (April 1994). Results showed that of 25 rats injected with a carcinogen known as DMBA, 68% got mammary tumours. Of 39 animals that were also injected with low or high doses of sulforaphane, only 35% and 26% respectively did.

In addition, it is reported that Dr Talalay has added sulforaphane to human cells growing in a lab dish showing that it may boost the synthesis of anticancer enzymes.

Research is continuing into the effects that other phytochemicals, isolated from a wide range of fruit and vegetables, can have at different stages in the multi-step process leading to cancer, lessening the risk of contracting the disease.

(Source: “Beyond Vitamins” by Sharon Begley, Newsweek, April 25, 1994)

New Method for Treating Dental Caries

A method of treating dental caries, requiring neither drills, nor water, nor electricity was presented at the headquarters of the World Health Organization (WHO), Geneva, on World Health Day (7 April 1994), which this year focused on oral health.

“Atraumatic restorative treatment” as the technique is called, consists of manually cleaning dental cavities caused by caries, and filling them with a material called “glassionomer”, which adheres effectively to the tooth and also releases fluorides that offer protection against any future caries.

Dental caries often goes untreated in the most underprivileged communities in the most remote areas of the world, and results in large, painful cavities in the teeth. Often, when treatment is finally provided, all that can be done is to extract the decayed tooth.

The new method offers hope. Only a few instruments, which can be carried easily in a satchel, are required for treatment. This, and the fact that no electricity or water is needed means that treatment can be carried out in even the remotest areas.

The procedure has been developed by a team led by Professor Taco Pilot of the University of Groningen in the Netherlands - a WHO Collaborating Centre for Research in Oral Health Services. It is now being tested in the field - in rural areas of Thailand, in collaboration with Khan Kaen University, and in Zimbabwe, in collaboration with the Dental Department of the Ministry of Health.

(Source: WHO Press Release, 7 April 1994)

Progress in the Elimination of Neonatal Tetanus

In 1989, the World Health Assembly committed WHO to achieving the elimination of neonatal tetanus by 1995, which in many countries accounted for up to 25% of all infant deaths in the early 1980s (elimination is defined as less than one case of tetanus for every 1000 births occurring in each administrative district throughout the world.)

What progress has there been towards this goal? According to a report prepared for the WHO Executive Board which met in Geneva in January of this year “the number of infants dying each year from tetanus in the first three weeks of life has been cut in half since 1980 and is now estimated at 500,000 worldwide. In addition, over 30,000 deaths of women from the same cause are being prevented each year.”

These results have mainly been achieved by the immunization of women with tetanus toxoid vaccine before or during their pregnancy. This measure serves two functions: it provides long-term protection against tetanus for the mother; and, importantly, protects her newborn child during the early weeks of life when tetanus spores, implanted in the infant’s umbilical cord as a result of unhygienic birth practices, can lead to the disease. Improving hygiene during and after delivery is also part of the strategy to eliminate the disease. Public health workers working on immunization programmes also take the opportunity to educate mothers and birth attendants on how to conduct hygienic births.

Fourteen countries are at present responsible for 80% of the estimated global neonatal tetanus cases, namely Bangladesh, China, Ethiopia, India, Indonesia, Kenya, Nepal, Nigeria, Pakistan, Somalia, Sudan, Uganda, Viet Nam, and Zaire, and it is to these countries that the WHO Executive Board has urged that priority support be given.

Neonatal tetanus tends to affect the poorest people in countries in greatest need. As Dr Henderson, Assistant Director General at the World Health Organization has stated: “Tetanus is but one among many problems associated with childbirth which threaten the lives of mothers & their newborns... eliminating this one problem will not solve them all. But tetanus is a warning beacon. Wherever it occurs, it demonstrates abject failure of the health system. So eliminating this disease automatically requires health workers to recognize and respond to the problems which have generated it, ensuring that all mothers have access to the basics of good maternal care.”

For further information please contact: Dr Francois Gause, Medical Officer, Expanded Programme on Immunization, WHO, Geneva. Tel: (41 22) 791 4414 Fax: (41 22) 791 0746.

(Source: WHO Press Release, 25 January 1994)

Making the Code Work: World Breastfeeding Week, 1-7 August, 1994

World Breastfeeding Week this year focussed on the International Code of Marketing of Breastmilk Substitutes. In preparation for the Week, the World Alliance for Breastfeeding Action (WABA) Secretariat and the WABA Code Compliance Task Force prepared a six page Action Folder explaining clearly the issues surrounding the code, the events since 1939 which led to the adoption of the Code in 1981, and developments since then, together with ideas for ways to act to raise awareness about the Code at Local, National and International Level. The following information is taken from the English version of the folder.

The International Code of Marketing of Breastmilk Substitutes was adopted at the World Health Assembly in 1981. It provides guidelines for the regulation of marketing practices used to sell products for artificial feeding, thus providing a tool for the encouragement and protection of breastfeeding.

According to the Action Folder “The Code applies to: artificial milks for babies; other products used to feed babies, especially when they are marketed for use in a feeding bottle or to babies under six months of age. The Code also applies to feeding bottles and teats... The Code includes these 10 important provisions:

· No advertising of any of these products to the public

· No free samples to mothers

· No promotion of products in health care facilities, including the distribution of free or low-cost supplies.

· No company sales representatives to advise mothers

· No gifts or personal samples to health workers

· No words or pictures idealizing artificial feeding, or pictures of infants on labels of infant milk containers

· Information to health workers should be scientific and factual

· All information on artificial infant feeding, including that on labels, should explain the benefits of breastfeeding, and the costs and hazards associated with artificial feeding

· Unsuitable products, such as sweetened condensed milk, should not be promoted for babies

· Manufacturers and distributors should comply with the Code’s provisions even if countries have not adopted laws or other measures”

“Every day as many as 4,000 infants and young children die because they are not breastfed...over many years, companies have invented clever slogans, striking images, free samples, or supplies, and all kinds of appealing gifts to persuade mothers and health workers that while “breast is best”, bottle feeding is almost as good as breastfeeding.”

To be effective, the code must be enforced in every country. Several countries - Brazil, Burkina Faso, Guatemala, India, Kenya, Mexico, Nepal, Nigeria, Peru and the Philippines - have introduced the whole code as national legislation. Many of these countries have also taken other steps to discourage bottle-feeding, as have Bangladesh, Guinea-Bissau, Honduras, New Zealand, Norway, Papua New Guinea, Paraguay, Swaziland, Sweden, Trinidad & Tobago, & the United Kingdom.

(Source: as given at end of article)

As stated in the action folder, it is hoped that this year’s World Breastfeeding Week theme will achieve the following aims:

“Raise awareness about the International Code, its purpose and its potential;

“Remind Governments of the Innocenti target date.” (The Innocenti Declaration was adopted by participants at the WHO/UNICEF policymakers meeting on “Breastfeeding in the 1990s: A Global Initiative,” co-sponsored by USAID and SIDA, and held in Florence, Italy, 30 July - 1 August 1990. Included was a resolution for all governments to implement the International Code and other related resolutions of the World Health Assembly by 1995); and

“Stimulate public interest groups, professional organizations, and the general public to monitor enforcement of the Code.”

For further information please contact: WABA, PO Box 1200, 10850 Penang, Malaysia. Tel: 60 4 6584816 Fax; 60 4 6572655.

(Source: World Breastfeeding Week 1994 Action Folder, April 1994)


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