Vitamin A Programme in India – Why the Controversy?

An excerpt from Sight & Life Newsletter. March 2002:Special Issue:55.
by Vinodini Reddy. Nutrition Consultant, Hyderabad, India

A Vitamin A supplementation programme has been in operation in India since 1970. Under this programme, which is sponsored by the Ministry of Health and Family Welfare (GOI), children between nine months to three years are given six monthly doses of vitamin A. The administration of the first two doses is linked with routine immunisation. Although the supplementation programme was started as a short-term measure to prevent blindness in children, it has been going on for the last three decades and its continuation has become a subject of national debate. The recent reports of child deaths after the administration of vitamin A during a mass campaign in Assam triggered a fresh controversy over the programme (1-3). The controversy is not confined to the campaign-type approach to vitamin A distribution. Also in question is the very existence of vitamin A deficiency (VAD) as a public health problem in India and the need for supplementation (4). Such debates often confuse the policymakers and cause setbacks to the ongoing programme, the implementation of which is already behind schedule. This paper is an attempt to review the available data and answer some of the questions raised by the critics.

Is VAD a public health problem in India?

Clinical deficiency:
Severe deficiency of vitamin A is known to produce corneal xeropthalmia/keratomalacia and blindness in children. Such cases are rarely seen in a community survey and require a large sample size for accurate estimates of prevalence. Hospital records show a significant decline in keratomalacia cases in the last two decades (5) and clinicians vouch for its rarity (6). However, clinical signs of mild xeropthalmia like Bitot’s spots and night blindness are still seen among children in poorer communities. The first repeat survey of the National Nutrition Monitoring Bureau (NNMB), conducted during 1988-90 in the same villages that were surveyed earlier during 1975-79 showed that the prevalence of Bitot’s spots has declined from 1.8 percent to 0.7 percent (7). However, the second repeat survey conducted in 1996-97 showed no further improvement (8) and the prevalence is still above 0.5 percent, which is the WHO cut off level for a public health problem. The national averages do not give a full picture because the prevalence rates vary widely, not only between the states but also within a state. Nevertheless, they provide useful information on time trends.

The India Nutrition Profile (1999) is often quoted to show low prevalence of clinical deficiency in the population, but the prevalence rates of Bitot’s spots published in this report cannot be used since they are based on pooled data of all age groups (9). In a few states like Haryana, Assam and Orissa, for which the data on preschool children are given separately, the prevalence is relatively higher. A survey in five northeastern states (Assam, Bihar, Orissa, West Bengal and Tripura) showed the prevalence of Bitot’s spots to be 0.7-2.2 percent and of night blindness to be 1.2-4.0 percent, indicating a public health problem in all five states (10). The survey also showed high prevalence of night blindness among pregnant women (3.2-16 percent). The district-wise data collected in the state of Uttar Pradesh showed Bitot’s spots in 5.6 percent of children (11). There was a wide variation in the prevalence between the districts, and even within a district from cluster to cluster, ranging from 0.2 percent to 13.7 percent.

A recent survey of the Indian Council of Medical Research (ICMR 1998) covering sixteen districts, mostly in northern and eastern regions, showed that the prevalence of Bitot’s spots ranged from 0-4.7 percent and of night blindness from 0.4-4.8 percent (12). The low prevalence of Bitot’s spots observed in a number of districts surveyed is used as an argument that VAD is no longer a public health problem. Yet, the prevalence of night blindness, though a subjective sign, cannot be ignored. If both indicators are used, VAD is a significant problem in seven districts. If the prevalence of corneal scars (>0.05 percent) is also considered, eleven out of sixteen districts have a significant problem. All available clinical and biochemical indicators are subject to limitations; therefore, WHO has recommended that at least two indicators be used for assessing the vitamin A status of a population (13).

Sub-clinical deficiency:
Xeropthalmia is well-recognised as an advanced state of deficiency. In communities where clinical signs of VAD are seen, sub-clinical deficiency can be expected to be more common. Large-scale data on serum retinol levels are not available to assess the extent of biochemical deficiency, but the community studies carried out in Andhra Pradesh (14), Tamilnadu (15) and Uttar Pradesh (11) indicate that 30-50 percent of children have retinol levels below 20mg/dl, which is the WHO threshold and which indicates there is a public health problem. These observations are corroborated by dietary data. Green leafy vegetables, milk and milk products are the major sources of vitamin A in Indian diets. Surveys carried out in different parts of the country show low consumption of these foods (16). The average intake of vitamin A is around 300 mg in women and 120 mg in children, and more than 80 percent have intakes less than 50 percent of the recommended dietary allowance (RDA).

The available data show that although the severe forms of blinding malnutrition have declined in the last two decades, milder grades of VAD still exist in many parts of India. National surveys provide only state level information and the limited data available from district surveys show a wide variation between districts. The magnitude of the public health problem varies depending upon the areas surveyed and the indicators used.

Is mild VAD a public health concern?

Apart from causing ocular signs, VAD is known to produce systemic changes, of which the most significant are alterations in epithelial integrity and immune status. Evidence for an association between VAD and infection was documented by Scrimshaw, et al some thirty years ago (17). Since then, supporting data from animal experiments and observational studies in humans have been published (18). Positive association between mild xeropthalmia and the risk of respiratory infection was reported in Indian children (19), while Indonesian children showed an association with both diarrhoea and respiratory infection (20). Children with clinical signs of VAD were found to be at greater risk of death than those without (21). A subsequent intervention trial in Indonesia showed a 34 percent reduction in mortality among children receiving six monthly doses of 200,000 IU vitamin A (22). This effect was seen even in children without clinical signs, highlighting the importance of sub-clinical deficiency. Controlled trials in other countries also resulted in a significant reduction in mortality: 19 percent in Ghana (23) and 30 percent in Nepal (24). The reduction was attributed to a fall in diarrhoea- and measles-related deaths. However, studies in India (25) and Sudan (26) using the same dose showed no effect. Trials of weekly supplements in India (15) and food fortification in Indonesia (27) showed higher reduction in mortality, indicating that the beneficial effect was due to improvement in vitamin A status by whatever means. A meta-analysis of data from eight intervention trials in pre-school children showed an average of 23 percent reduction in total mortality (28). However, this conclusion has been challenged because the results are not consistent (29). Subsequent studies in infants younger than six months have also shown variable results. The administration of a single dose of 50,000 IU vitamin A to neonates in Indonesia resulted in a significant reduction in mortality risk (30), while a similar trial in Nepal showed no effect (31). In a WHO multi-centric trial in Peru, Ghana and India, vitamin A supplements (25,000 IU) given along with DPT immunisation at six, ten and fourteen weeks did not affect morbidity or mortality (32).

There are a number of potential explanations for the variability in results across trials, including the age of the children and the dosage schedule. Smaller and more frequent doses seem to be more protective than large, periodic doses. A high prevalence of infections resulting in vitamin losses and depletion of stores can shorten the protective period of supplements. Vitamin A is likely to have a greater effect in areas where VAD is highly prevalent. Such other factors as concomitant nutritional deficiencies and access to health care can also modify the mortality effect. Thus, the impact of vitamin A may vary depending on the environmental conditions. An average 23 percent reduction in mortality may not be applicable to all ecological settings, but the positive impact of vitamin A in some situations cannot be denied.

After reviewing the studies on vitamin A and mortality, a National Consultation on the Benefits and Safety of Vitamin A administration, held in New Delhi in September 2000, concluded that the data are ‘not robust’ enough to recommend vitamin A supplementation for the purpose of mortality reduction in children (33). In India, infant deaths comprise up to 80 percent of under-five mortality in some states. Therefore, it is argued that an intervention with possible effect only beyond infancy will not be of much value for reducing child mortality (34).

It is true that vitamin A is not a panacea for all the illnesses that affect children in developing countries. However, the need for improving vitamin A status cannot be denied. The fact that a majority of the population subsists on inadequate diets, with vitamin A intakes less than half the recommended level and a significant proportion of children having clinical and sub-clinical deficiency is a matter of public health concern. The aim of the National Nutrition Policy is not only to prevent blindness in children, but also to eliminate VAD as a public health problem. In order to achieve the goal, intervention efforts should be accelerated.

What are the appropriate strategies for VAD control?

Multiple approaches, including vitamin A supplementation, food fortification, dietary diversification, and public health measures, have been suggested for prevention and control of VAD. Although pilot projects have demonstrated their efficacy and feasibility, large-scale implementation of these programs has met with limited success. This has led to considerable debate as to which of the interventions is most cost effective and sustainable. The choice is not simple; each one has its strengths and limitations. For maximum impact and efficacy, each strategy should be considered in the context of a country’s needs and priorities and its capacity to implement and sustain an intervention.

Vitamin A supplementation is the quickest way to improve the vitamin A status of a population and is the favoured strategy in areas where the problem is widely prevalent. Improving the diet, even if it is difficult to achieve in the short term, is of paramount importance since it contributes to improvement in overall nutritional status. Food fortification with vitamin A has proved to be an effective strategy for reducing VAD in some countries. A right mix of interventions tailored to the local circumstances is more likely to succeed in achieving the objective.

In India, the National Vitamin A prophylaxis programme was started with the primary aim of reducing blindness in children, which was a significant problem at that time. Under this programme, sponsored by the Ministry of Health and Family Welfare, children between 1-5 years were given oral doses of 200,000 IU vitamin A every six months. Evaluation studies in the late 1970s revealed poor implementation of the programme and inadequate coverage in most of the states (35). The programme has been reviewed several times since then and efforts were made to correct the existing deficiencies. Currently, vitamin A is given only to children less than three years old who are at greatest risk; and the administration of the first two doses is linked with routine immunisation to improve the coverage. A dose of 100,000 IU is given along with measles vaccine at nine months of age and 200,000 IU with DPT booster at fifteen months (36).

In recent years, there has been considerable debate on the continuation of the vitamin A supplementation programme. Since keratomalacia and resulting blindness is no longer a significant problem, opponents argue that there is no need for supplementation and that milder forms of deficiency can be addressed through alternate strategies aimed at dietary improvement (29). It is true that dietary intervention is the most logical approach. Right from the beginning, supplementation was conceived as an interim measure to be discontinued once effective dietary improvement is achieved. Unfortunately, the dietary situation has not changed in the last three decades. Vitamin A intakes of children are less than half the RDA even today, with a significant proportion of them having clinical evidence of deficiency. Under these circumstances, it is not wise or ethical to withdraw the benefits of supplementation.

There is also a controversy about the universal approach currently adopted, because VAD is not uniform throughout the country (29, 34). The cost of vitamin A supplements is estimated to be Rs. 3.20 per child per year, which is a negligible proportion of the total health expenditure (37). A selective approach, covering only the districts where VAD is a public health problem, would be a more cost-effective strategy. It requires district mapping for VAD signs all over the country. This is possible if the states take responsibility for conducting surveys and monitoring the program. When such data are not available, priority should be given to backward areas that are identified using ecological indicators.

The mode of delivery of the vitamin has also been a subject of intense discussion. Under the national programme, children are given vitamin A along with routine immunisation (measles, polio & DPT). While international agencies have been vigorously promoting supplementation linked with routine, as well as campaign-based immunisation, it is not considered a short-term measure but a low-cost, sustainable strategy to combat VAD in developing countries (38). Efforts have also been made to expand the programme to cover pregnant and lactating women and infants younger than six months, although the studies failed to demonstrate clear benefits in these groups (39). These efforts have met great resistance in the Indian context. In recent years, Pulse Polio Immunisation (PPI) has been implemented as a national campaign, offering an opportunity to deliver vitamin A. However, the Indian Academy of Paediatrics disapproved the linking of vitamin A delivery with PPI, primarily due to the lack of sufficient evidence for the benefit of supplements in infancy, the chances of destabilisation of routine services, and the fact that PPI is a temporary programme (40). Of the two states that included vitamin A in the PPI campaigns during 1990-2000, improved coverage was achieved in Orissa but not in Uttar Pradesh due to poor logistic support (11). Considering the inconsistent results and the fact that PPI itself is coming to an end, the National Consultation on Vitamin A also recommended that vitamin A should not be linked with PPI; instead, the ongoing programme of supplementation linked with routine immunisation should be strengthened to achieve high coverage (>90 percent) for at least the first two doses (33). There is also a need to strengthen the education component of the programme to improve diet as a long-term goal.

Dietary improvement is, undoubtedly, the most logical and sustainable strategy to prevent VAD. There is general consensus at both the national and international levels that its contribution to the improvement of overall nutrition justifies the continued efforts in this direction. However, past efforts concentrated on supplementation, and not much attention was paid to the planning and implementation of food-based programmes. Green leafy vegetables (GLV) and fruits are plentiful in season and are well within the economic reach of even the poor (29). Availability alone, however, does not ensure programmatic success. A change in dietary habits and increased access to vitamin A-rich foods are required. In recent years, efforts have been made to achieve these objectives through educational and horticultural interventions. These projects have been mostly small-scale and are yet to be incorporated into national programmes. Even these small projects have failed to demonstrate a significant impact on vitamin A status because they focussed on GLV as the main source of vitamin A (41). Bioavailability of B-carotene is lower from GLV than from other vegetables and fruits. Young children cannot consume leafy vegetables in sufficient quantities to meet the vitamin requirements. Based on feeding trials with selected vegetables, a factor of 26 (instead of 6) has been suggested for conversion of B-carotene to vitamin A (42). However, even this is debated because bioavailability of carotene varies widely, not only with the food source but also with the way it is prepared and the level of such other dietary components as fibre and fat. A detailed discussion on this issue is beyond the scope of this paper, but it is unlikely that promotion of GLV alone will eliminate VAD. Dietary diversification programmes must include a variety of vegetables and fruits as well as animal foods such as milk and eggs. We should not settle for something ‘cheap’, but make all possible efforts to improve the quality of diets. 

What went wrong with the vitamin A campaign in Assam?

The reported deaths of over a dozen children and the illnesses of a large number following vitamin A administration during a mass campaign in the north-eastern state of Assam has caused considerable anxiety and concern among health professionals (1-3). The campaign was stopped immediately and the Government set up an inquiry. Some doctors blamed the stock of vitamin A supplied. However, testing of vitamin A samples from batches used in the campaign showed nothing wrong with the vitamin supplied (43). They conformed to the standards of quality specifications, so the reported adverse reactions were not attributable to quality of the product supplied.

Some nutritionists have questioned the campaign approach adopted by the state, when the national guidelines recommend vitamin A administration along with routine immunisation (44). Unfortunately, the rate of national immunisation coverage is also low (49percent). According to NFHS-2, the rate of national coverage for at least one dose of vitamin A (linked with immunisation) is only 30 percent, and in Assam, it is even lower at 15.4 percent (45). Recently, some of the states in India, including Assam, have initiated a vitamin A campaign, with UNICEF support, to improve the coverage. This is the third round of vitamin A distribution in Assam. The first two rounds in this state as well as in the other states of Andhra Pradesh, Karnataka and Orissa were uneventful. During this round, UNICEF replaced the traditional 2ml spoons with 5ml cups for administering vitamin A. It is possible that the newer method and inadequate training of health workers might have led to overdosing in some cases. Though the cup had 2ml markings, health workers cannot be expected to measure the dose accurately, especially in a mass campaign where hundreds of children are covered in a day.

The administration of large doses of vitamin A is known to produce such side effects as headache, vomiting and bulging fontanel in 1-2 percent of children, but these symptoms are mild and disappear within 48 hours (46). According to newspaper reports, up to 15,000 children out of the 3 million who received vitamin A during the campaign became ill (47). This is much less than what is expected (up to 60,000) with vitamin A dosing.

The Assam episode started with the death, after consuming vitamin A, of a two-year-old child from the Tea-garden community. This triggered panic among the parents. Thousands of people rushed with their children to the nearest Health Centre, some of them complaining of fever, vomiting and diarrhoea. Normally, these symptoms do not attract mass attention, but the media has sensationalised the event in Assam leading to a wave of mass concern. All deaths and illnesses that occurred in children during the following week were attributed to vitamin A. There is no evidence that vitamin A causes death, even if a child had received twice the recommended amount (400,000 IU). This is the dose recommended by the WHO for treatment of xeropthalmia (48). The vitamin A program has been in operation for the past several years in India and in sixty other countries. So far, not a single case of death attributable to vitamin A dosing was reported. The lethal dose of vitamin A is not known, but a review of the case reports of children getting 300,000 – 900,000 IU do not suggest severe toxic effects that could be fatal (49). It is not surprising that the investigation conducted by the State Department of Health and UNICEF revealed that, in most of the cases, deaths were due to causes unrelated to vitamin A (50). The causes included cardiac failure, severe anaemia, high fever, foreign body aspiration, etc. Considering the current mortality rate of 28/1000 in 1-4 year old children (45), 15 deaths reported in the week following vitamin A administration are far fewer than the expected number.

Inadequate training of health workers, lack of supervision and negligence toward children who developed symptoms might have contributed to the confusion. There are important lessons to be learned from this episode. The community may lose faith in Government-sponsored, public health programmes if adequate precautions are not observed. The major precautions for vitamin A administration include avoiding massive doses in young infants by ensuring that the dose limit is not exceeded, and having the administration carried out by trained health workers under strict supervision. Adequate steps should be taken to educate the community about the benefits of vitamin A supplementation and the possibility of transient side effects. Extra precautions are needed for treating sick children. WHO has recommended that sick children who are at greater risk, particularly those with measles and severe protein-energy malnutrition (PEM), should be given an additional dose of vitamin A (48). However, this approach can create problems if adequate precautions are not taken. If a child who is seriously ill dies after receiving the dose, vitamin A may be blamed as the cause of death (as happened in Assam). Such cases should be referred to the nearest health centre for full treatment. Efficient management is crucial for success of any public health programme.

Conclusion

VAD still exists as a public health problem in many parts of India and there is a need for continued efforts to improve the vitamin A status of the population. It is unfortunate that the Assam episode led to so much controversy, putting an end to the vitamin A campaign there and also in other states. However, this should not be viewed as a setback, but as an opportunity to strengthen the ongoing programme of supplementation linked with routine immunisation and to accord higher priority to dietary approaches as a long-term sustainable solution.

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Posted November 2003