Deaths trigger fresh controversy over vitamin A programme in India
BMJ 2001; 323 doi: https://doi.org/10.1136/bmj.323.7323.1206 (Published 24 November 2001) Cite this as: BMJ 2001;323:1206All rapid responses
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Vitamin A controversy leading to death of 14 children and other
symptoms of oberdose of Vitamin were found in 750 children. There is
confusion from various responses in BMJ and New Scientist. I searched
through Google.com and found that even the recommended dose may be cause
of death in children. We have decided to publish a special issue of
Chemistry Education, Vol.12, No.1,2002 on various aspects of lipids,
carotenoids and Vitamin and would like to include your views published in
23 November issue with the responses provided the editor permits to
include the materials published. In areas where pulse vitamin A was
administered there was no prior health check up of the children. There was
no data available on chilren's health.Probably it is better to involve
NGO's withaccountability in UNICEF's programme on children than the Govt.
agencies.
Competing interests: No competing interests
Did vitamin A distribution in Assam, India cause an epidemic
of illness or hysteria? The science and reported events
that have emerged from the recent vitamin A campaign clearly
point to the latter, despite myriad newspaper reports and
now letters to the editor, that are based on such media
reports, to the contrary.
First, did vitamin A kill a child the next day and up to 13
more children the following week as reported? Almost
certainly not. Even twice the intended, prophylactic dose
of 200,000 IU, if such were delivered, and it is not clear
that this happened, is not lethal but rather is the
treatment for even mild xerophthalmia recommended by the
World Health Organization (1). In blaming deaths on vitamin
A, critics have chosen to ignore the current 1-4 year old
mortality rate in India of ~7 deaths per 1000 children per
year (2). Thus, among an estimated 2.5 million children
participating in the vitamin A campaign, 17,500 would be
expected to die over the coming year, without getting
vitamin A, including 48 deaths the very next day (dividing
17,500 by 365). Over 325 deaths would be expected to occur
within a given week - far fewer than the 14 deaths that the
media turned up during the first post-campaign week. Any
inference to be drawn from these simple calculations and
observations supports previous, well founded evidence (3)
that vitamin A saves children's lives, not takes them.
Did vitamin A cause an unexpected epidemic of childhood
illness? High potency vitamin A has been known, since it
started being distributed in India three decades ago (4,5),
and from periodic reviews (6) and controlled trials (7), to
cause transient side effects, that include nausea, vomiting
and headache in about 3-9% of 1-4 year old children. The
ailments resolve spontaneously within 48 hours, as
reportedly occurred in Assam. In very young infants, about
the same percentage may develop an isolated, psuedomotor
cerebri (bulging fontanelle) that also subsides within 24-72
hours of vitamin A receipt (8-12). These consequences pose
the "risk" side of the benefit:risk ratio associated with
this program. At, say, an incidence of 5%, 125,000 children
would have been expected to develop side effects among the
2.5 million dosed children; again, many times more than the
15,000 cases reported by the media. Still, even 15,000
vomiting and nauseous children, presenting to health clinics
on one day, in one state, from a highly organized and
motivated, but politically charged, vitamin A program will
end up concentrating both the risk and public sensitivity.
This can result in high case load visibility, exaggerated
press coverage and flagrant accusations, as happened in
India this past week. Perhaps the fault was merely that
program operants, mothers and the press were not adequately
informed of risks of transient side effects that can, and do
occur, with high-potency vitamin A distribution.
Abandoning a highly effective, semi-annual campaign approach
(13), as presently under consideration by the Government of
India in response to the Assam incident, will not lower risk
of side effects, only dissipate cases over time. Educating
mothers and other constituencies to expect these ailments to
occur in some children would go far in preventing a similar
outburst in the future.
The "tragedy" being faced is not that some children
experienced side effects after taking vitamin A, but that
supplementation may be derailed as a result of this
incident, in a country such as India where such campaigns
are needed to reduce risks of xerophthalmia, infection and
death among its estimated 35 million vitamin A-deficient,
and 1.8 million xerophthalmic youngsters (West KP Jr,
submitted, 2001). A nutritious diet is undeniably preferred
to maintain adequate vitamin A status and health in
children. But until such a goal is achieved and sustained,
periodic vitamin A delivery can prevent blindness and
premature death in children today (3); this is the
evidence-based "benefit" side of the equation, which appears
to have been ignored in the current hysteria surrounding the
Assam program.
Keith P. West, Jr., Dr.P.H.
Professor
Alfred Sommer, M.D., M.P.H.
Professor and Dean
Bloomberg School of Public Heatlh
Johns Hopkins University
Baltimore, MD USA
References
1. Sommer A. Vitamin A Deficiency and its Consequences: A
Field Guide to Detection and Control. 3rd ed. Geneva: World
Health Organization, 1996.
2. UNICEF. The State of the World?s Children 2001 - Early
Childhood. New York City: UNICEF, December 2000.
3. Sommer A, West KP Jr. Vitamin A Deficiency: Health,
Survival and Vision. Oxford: Oxford University Press, 1996.
4. Nair VN. Report on vitamin A prophylaxis programme in
Kerala State. SEA/NUT/Xeroph Meet/5, Regional Office for
South-east Asia. Dehli: World Health Organization, 1972.
5. Gafar MA. Report on vitamin A prophylaxis programme in
Mysore State. SEA/NUT/Xeroph Meet/4, Regional Office for
South-east Asia. Dehli: World Health Organization, 1972.
6. Bauernfeind JC. The safe use of vitamin A. A report of
the International Vitamin A Consultative Group (IVACG).
Washington DC: The Nutrition Foundation, September 1980.
7. Florentino R, Tanchoco CC, Ramos AC, Mendoza TS,
Natividad EP, Tangco JB, Sommer A. Tolerance of
preschoolers to two dosage strengths of vitamin A
preparation. Am J Clin Nutr 1990;52:694-700.
8. West KP Jr, Khatry SK, LeClerq SC, Adhikari R, See L,
Katz J, Shrestha SR, Pradhan EK, Pokhrel RP, Sommer A.
Tolerance of young infants to a single, large dose of
vitamin A: a randomized community trial in Nepal. BWHO
1992;70:733-39.
9. Agoestina T, Humphrey JH,m Taylor GA, Usman A, Subardja
D, Hidayat S, Nurachim M, Wu L, Friedman DS, West JP Jr.
BWHO 1994;72:859-68.
10. Rahman MM, Mahalanabis D, Wahed MA, Aminul M, Habte D.
Administration of 25,000 IU vitamin A doses at routine
immunization in young infants. European J Clin Nutr
1995;49:439-45.
11. Baqui AH, de Francisco A, Arifeen SE, Siddique AK, Sack
RB. Bulging fontanelle after supplementation with 25,000 IU
of vitamin A in infancy using immunization contacts. Acta
Paedeiatr 1995;84:863-66.
12. Iliff PJ, Humphrey JH, Mahomva AI, Zvandasara PZ,
Bonduelle M, Malaba L, Natho KJ. Tolerance of large doses
of vitamin A given to mothers and their babies shortly after
delivery. Nutr Res 1999;19:1437-46.
13.Helen Keller International, Bangladesh. The nutritional
surveillance project in Bangladesh in 1999. Towards the
goals of the 1990 World Summit for Children. Dhaka: Helen
Keller International, 2000.
Competing interests: No competing interests
It is most unfortunate that many such public health interventions
are being promoted which lacks conclusive evidence in terms of public
health benefits.There are no sound RCTs to show that vit A supplemenation
is linked to reduction in infant/child mortality.Also prevalence of VIt A
deficiency has gone down over past decade in many parts of the country for
many reasons.
What is really worrying that entire PH system delivers "best" in
campaign mode.Be it pulse Polio or "pulse IUD" or pulse TT for women or
Family Health Awareness Campaigns conducted by the National AIDS control
organisation to treat RTIS/STIs in campaigns. Such campaigns diverts the
attention from routine primary health care( extra money for training/
IEC/POL etc ) and many stakholders including donor agencies feel happy
that their own agendas are covered.
It is high time that Indian Health authorities strenthen health care
delivery infrastructure and address glaring infrastructure gaps. Shaort
term measures might be needed for managemnt of outbreaks etc but there is
no substitute for quality Primary Health care, which still remains adream
for millions of people in India.
Competing interests: No competing interests
Dear Sir
The recent deaths in Assam state ,India after the administration of
massive doses of VA has cautioned all the public health specialist in
world about the Safety issues related to use and mode of
administration of vitamin A in large doses particularly in campaign mode
as anintervention for reduction in under five mortality
According Government of India, VA administration should be done as
a part of routine Primary Health Care and Vertical Approach for single
nutrient should be discouraged.. (1)The recent surveys conducted by
Indian Council of Medical Research in 1999 in Dibrugarh and Nagaon
districts of Assam state ,in which more than 11,000 children per district
were covered utilising the thirty cluster approach, revealed that only
0.3% of children were suffering from Bitot’s Spot, a maker of VA
deficiency. (2). This data proved scientifically that VAD was not a Public
Health Problem. When there was no evidence of VA deficiency in Assam,
why should the administration of VA through campaign mode be adopted?.
Since 1970, administration of vitamin A is a 100% centrally sponsored
scheme. Under this scheme 100 ml of vitamin A bottle and a spoon with a
marking of 2 ml is being provided to the functionaries for administration
of Vitamin A . The functionaries are familiar with use of this spoon.
In Assam, a 5 ml cup for administration of VA was provided by an
International agency , instead of spoon. As per the press reports ,the
functionaries were possibly not properly trained in use of cup and over
dose of vitamin A solution was administered leading to side effects and
related deaths . (3)
Indian scientists have been advocating that the campaign approach
should be avoided as disturbs the routine health care activities of the
worker. Also the emphasis is to achieve the targets of campaign and no
efforts is made to provide health education to the mothers of the
beneficiaries, which is the major intervention for the sustainable
elimination of the VAD from the area. (4,5,)
There are agencies/organisations who have been advocating the key
role of vitamin A administration in bringing reduction in early child
hood mortality. The studies with positive or no effect have been
published in equal number and the results are still inconclusive to
recommned vitamin A to be used as a intervention to reduce early
childhood mortality. It is a known fact that the studies which have only
demonstrated positive impact of VA are getting wide publicity by
organizations who are supporting the cause of universal distribution of
vitamin A. International and Bilateral Voluntary agencies working in
India are actively promoting the universal distribution of VA , although
the problem of VA deficiency exists in only selected geographical pockets.
These agencies instead of targeting specific VA deficient areas, are
promoting the distribution of VA to entire country . Is it cost
effective use of limited of resources in a poor country.
The deaths related to Vitamin A administration would lead to
erosion of faith of people on government health care system and cause
serious set back to pulse polio campaign in the state which is at the
verge of elimination of the polio.
( Dr. Umesh Kapil)
Additional Professor Public Health Nutrition
Department of Human Nutrition,
All India Institute of Medical Sciences,
New Delhi 110 029, INDIA
email: kapilumesh@hotmail.com
References:
1.National consultation on benefits and safety of administration of
Vitamin A to
preschool children and Pregnant and Lactating mothers. Indian
Pediatrics 2001,38 ,
37-42
2.Micronutrient deficiency disorders in 16 districts of India, Indian
Council of
edical Research, New Delhi, 2001
3. Probe ordered in to vitamin A deaths , The Times of India, New
Delhi,14.11.2001
4.Srikantia S.G. The National Nutrition Monitoring Bureau. In:
Towards better nutrition : Problems and policies. Eds. Gopalan C and
Harvinder Kaur, 1993. Nutrition Foundation of India, pp-359-372.
5.World Health Organization ; New Delhi, Gopalan C. Nutrition
Research in South East Asia: Emerging Agenda for Future, Regional
Publication , SEARO, No. 23 1994; pp 56-57.
Competeing interests NIL
Competing interests: No competing interests
The eminent Indian nutritionist C. Gopalan who first advised the
administration of Vitamin A for under-fives meant it to be an interim
measure only. He recommended that concomitant changes in dietary
consumption of Vitamin A in poor communities should quickly replace the
need for high dose orally administered Vitamin A. Sadly, the scientific
community is powerless against the pharmaceutical industry. And once
again, children from developing countries bear the cost.
Competing interests: No competing interests
Dear Editor,
The deaths during the Vitamin A programme in India have caused anxiety and concern among health care providers. It is important to know what went wrong (if anything at all) so that we can learn from the experience. One of the possible explanations put forward is the over dose of the vitamin due to changes in the spoons/cups that were used for administering vitamin A in the programme. If this is true then hypercalcemia induced by vitamin A (1) should be considered among other things for this unfortunate happening.
According to van Darn (2)increasing incidence of vitamin A toxicity is related to vitamin A supplementation for unfounded reasons. The author describes the common
symptomatology of vitamin A toxicity, including hypercalcemia, hepatomegaly, and dermatological and neurological effects. Vitamin A in large doses (long term use of greater than 50,000 units per day) causes hypercalcemia as a result of a direct effect on bone (3)and Hypercalcemia crisis or severe hypercalcemia represents a life-threatening emergency (4) and occasionally can cause arrthymias. There has been an earlier report of acute toxicity due to vitamin A over dosage during measles immunisation campaign in India (5)
It is needless to say we need to restore the confidence of the people in public health programmes and this can only be done through impartial and through enquiry in to these incidents. It is heartening to note than the Central Bureau of Investigation (CBI), the Indian federal government agency will be investigating this episode and we hope that the CBI will be able to determine exactly what happened to these unfortunate children during the programme.
References:
1) Badrinath P. Promed mail posting. http://www.promedmail.org/pls/askus/f?p=2400:1001:4443::NO::F2400_P1001_... visited on 23rd November 2001.
2) van Dam MA. The recognition and treatment of hypervitaminosis A. Nurse Pract 1989;14:28, 30-1.
3) http://www.mod-med.com/1999/fevrier/hyperclcemia.htm visited on 23rd November 2001.
4) Edelson GW, Kleerekoper M. Hypercalcemic crisis.Med Clin North Am 1995;79:79-92.
5) Aggarwal A. Acute toxicity of vitamin A administered with measles immunization. Indian Pediatr. 1997;34:456-7.
Competing interests: None
Competing interests: No competing interests
Vitamin A supplementation and control of vitamin A derficiency
In the 24 November 2001 BMJ [1], Ganapati Mudur reported on the
illness and death occurring among children in the North East of Assam,
India, following supplementation with vitamin A. Pending results of a full
investigation of these reports, we would like to make some general
observations about the global burden of vitamin A deficiency.
Vitamin A deficiency remains a major global public health problem; it
is the world's greatest single cause of childhood blindness and a major
contributor to child mortality and morbidity. About 250 million preschool
children are currently vitamin A deficient [2]. To remedy this situation
WHO recommends a combination of vitamin A supplementation, food
fortification, dietary improvement and general public health measures, for
example breast feeding promotion and immunization. However, in most
countries concerned, neither dietary improvement nor fortification is
likely to be achieved in the near future. Vitamin A supplementation is a
safe, reliable programme strategy that can be rapidly implemented on a
national scale; it has been widely used for the last twenty years, and its
effectiveness in correcting vitamin A deficiency has been amply
demonstrated. For example, a meta-analysis of eight studies showed that
vitamin A supplementation lowers the risk of all-cause mortality by 23%
and the risk of mortality from measles by 50%, while it reduces the
severity of diarrhoea [3].
Vitamin A supplements, administered at the recommended dose, are safe
[4]. Transient side-effects (bulging fontanelle, nausea, headache,
diarrhoea) may occur in 0.5-9 % of cases but these symptoms disappear
within 24 hours [5]. Since 1998, WHO and UNICEF have advocated delivering
vitamin A supplements through immunization services in order to increase
the number of children adequately protected against a deficiency of this
vitamin [6]. In 2000, with 76 countries linking vitamin A distribution to
routine immunization services or national immunization days as part of the
Intensified Polio Immunization Campaign, over 200 million children
received at least one large dose of vitamin A with no report of severe
side-effects or even toxicity. In 2000, vitamin A supplements were
administered with oral polio vaccine to children between 12 and 42 months
of age during national immunization days in Orissa State, India. Transient
side-effects were observed in only 3% of children, a result which was not
significantly different from the prevalence observed in children who
received oral polio vaccine alone (2.8%) [7].
The consequences of vitamin A deficiency are extremely damaging for
both the health and survival of children. WHO and UNICEF estimate that
between 1998 and 2000, vitamin A supplementation prevented as many as
700,000 to one million child deaths [8]. There is no question of the
urgent need for measures to correct vitamin A deficiency. In situations
where food fortification or dietary improvement cannot be implemented
rapidly, supplementation at the recommended dose remains the most
appropriate approach for preventing and treating a deficiency of this key
vitamin.
Bruno de Benoist, MD, Msc
Focal point for Micronutrients
Department of Nutrition for Health and Development
World Health Organization
CH 1211 Geneva 27, Switzerland
Email: debenoistb@who.ch
Werner Schultink, PhD
Senior Adviser, Micronutrients
Nutrition section
UNICEF
3 United nations Plaza
New York, NY 10017, USA
wschultink@unicef.org
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5. JH Humphrey, RN Ichord. Safety of vitamin A supplementation of
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6. WHO, UNICEF. Integration of vitamin A supplementation with
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Geneva. 1998
7. Bhaskaram P, Gorstein J, Goodman T, Hossaini R, Khanum S, de Benoist B,
Krishnaswami K. Safety and feasibility of administering high-dose vitamin
A with OPV as part of immunisation campaign in Orissa. XII IVACG Meeting.
Hanoi, Vietnam. 12-15 February 2001.
8. P. Ching, M. Birmingham, T Goodman, R Sutter, B Loevinsohn. Childhood
mortality impact and costs of integrating vitamin A supplementation into
immunization campaign. Am. J. Public Health. 2000; 90: 1526-1529.
Competing interests: No competing interests