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Journal of the American College of Nutrition, Vol. 26, No. 6, 630-638 (2007)
Published by the American College of Nutrition

Mapping Xerophthalmia in Mali: Results of a National Survey on Regional Distribution and Related Risk Factors

Jean-Francois Schémann, MD, PhD, Denis Malvy, MD, PhD, Germain Zefack, MD, Lamine Traoré, MD, Doulaye Sacko, MD, Bamani Sanoussi, MD, Albert A. Banou, MD, Omar Boré, MD, Sidi Coulibaly, MD and Mohamed el Moutchaidine, MD

IRD (Institute Research for Development), Dakar, SENEGAL (J.-F.S.), EA 3677
René-Labusquière Institute (Tropical Medicine and Hygiene Branch), University Victor-Segalen Bordeaux, Bordeaux, FRANCE (D.M.)
IOTA (African Institute of Tropical Ophthalmology) (G.Z., L.T.)
National Blindness Control Programme (D.S., B.S., A.A.B., O.B., S.C., M.e.M.), Bamako, MALI

Address reprint requests to: Dr. JF. Schémann, 9 rue de Calais, 75009 Paris, France. E-mail jfschemann{at}wanadoo.fr


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 POPULATIONS AND METHODS
 RESULTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Background: Vitamin A deficiency is recognized to be a severe public health problem in most of the sahelian countries. In Mali, several surveys had been performed at the district or regional level. Unfortunately, they did not cover the entire territory. In the aim of getting a general picture, we collected information on the frequency and presentation of xerophthalmia among the children under 10 years old population recruited in the setting of a national survey planned in 1996 and 1997 to evaluate the prevalence and determinants of trachoma in Mali.

Methods: In each of the seven regions (with the exception of Bamako district), a random sample of thirty villages was taken from the general population. In a subsample of those villages, children under 10 years of age were examined by an ophthalmologist and their related mothers interviewed. Diagnosis of night blindness and Bitot spot occurrence was used for data gathering. Information was collected on village's infrastructures and familial socioeconomic condition. Multiple logistic regression analyses were performed to purpose the best model to describe the relationship between each outcome variable and the various risk factors assessed.

Results: The prevalence of night blindness was estimated to be 1.95% (95% Confidence Interval [CI]: 1.58–2.39) and Bitot spots frequency to be 1.10% (95% CI: 0.83–1.45) among children between 2 and 6 years of age. Xerophthalmia prevalence was 2.51% (95% CI: 2.09–3.00) and nearly similar according to gender (2.68% among boys and 2.32% among girls). By region of the country and for the same age group, the prevalence ranged from 0.26% in the Kayes region to 7.02% in the Timbuktu region. In Mali, in four regions out of seven, the WHO thresholds defining a serious public health problem have been exceeded. The higher prevalence rates were found in Timbuktu, Mopti and Segou. After adjustment to season, the main risk factors were latitude, village size and poor sanitary coverage. The main protective determinants were education and rice culture.

Conclusions: This presentation illustrates a public health problem concerning vitamin A deficiency among young children in the general population and allows considering the effectiveness of substitutive intervention with vitamin A capsule distribution along with the improvement of vitamin A rich food production and consumption.

Key words: xerophthalmia, night blindness, Mali


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 POPULATIONS AND METHODS
 RESULTS
 ACKNOWLEDGMENTS
 REFERENCES
 
The term xerophthalmia covers all eye signs caused by vitamin A deficiency. Vitamin A acts in producing photosensitive pigments in the cells of the retina and in the differentiation of mucous-secreting epithelial cells. The lack of this essential nutrient leads to a decrease in night vision or night blindness, xerosis, keratinisation of the conjunctiva and of the cornea. The ultimate consequence is corneal necrosis and perforation of the eyeball. Vitamin A deficiency occurs widely among children in the developing countries. Many cases of children blindness are due to the irreversible corneal lesions caused by fragility of the corneal epithelium: every year, between 5 and 10 million new cases of xerophthalmia are noted among children, of whom between 250 000 and 500 000 will experience blindness [1]. Furthermore, numerous studies have shown a very clear increase in mortality rates among children with vitamin A deficiency [2,3].

In 1995, the World Health Organization (WHO) identified 39 countries in which vitamin A deficiency constituted a real public health problem [4]. In sub-Saharan African countries, a number of surveys on vitamin A deficiency have been carried out. In Mali, the African Institute of Tropical Ophthalmology (IOTA) conducted surveys in various regions through epidemiological evaluation of blindness or more specific studies during the 1980s [58]. Unfortunately, these surveys did not cover the entire territory and were often conducted using different designs. It was therefore not possible to map precisely xerophthalmia feature in Mali on the basis of these previous reports.

During a national survey planned in 1996 an 1997 to evaluate the prevalence and determinants of trachoma in Mali, we collected information on the frequency and presentation of xerophthalmia among the infant population [9].


    POPULATIONS AND METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 POPULATIONS AND METHODS
 RESULTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Outline of the Survey
This survey was conduced in 1996 and 1997. The survey was based on a two level, cross-sectional random cluster sample design, using procedures suggested by WHO prevention of blindness programme [10]. Mali was divided into seven administrative regions plus the district of Bamako, the capital. Stratification was carried out in these seven regions, excluding the Bamako district (Fig. 1). The sampling frame was the list of villages drawn up for the 1987 national census [11]. No urban and rural stratification was effected in these regions. Only the administrative districts of the capitals of the regions were excluded from the sampling frame. For each of the seven administrative regions, 30 villages, namely 30 clusters, were drawn at random in accordance with the principle of probability proportional to the population, using the cumulative total method. The design allowed covering 210 villages. In each of the selected villages, a sub-sample of households was drawn at random in order to provide the necessary number of children and women. Starting from an initial household chosen at random, the neighbouring houses were visited one by one. For the requirement of trachoma survey, 1890 children under 10 years old were examined in each regional stratum, i.e. 63 per cluster. In each village, sufficient locations were visited to recruit the required quota of individuals. All children under 10 years old from the sample were recorded on a register. The survey was conducted from May to June 1996 for the Mopti and Timbuctu regions, from January to February 1997 for Kayes and Gao regions and from May to July 1997 for the Sikasso, Segou and Koulikoro regions.


Figure 1
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Fig. 1. Mali Administrative Regions

 
The protocol was submitted to and approved by the IOTA ethical committee.

Clinical Examination
All children between 0 and 10 years were examined by an ophthalmologist with a x 2.5 magnifying glass and a flash lamp. The xerophthalmia outcome was diagnosed when a Bitot's spot, specific corneal lesions or night blindness occurred. Night blindness was documented for children aged over 24 months. The mothers were questioned for each of their children about the occurrence of night blindness. Three questions were asked in this purpose: does the child see well in the daytime? Does the child see well at night? Does the child suffer from night blindness (the vernacular term for night blindness was used)? A child was recognized experiencing night-blindness if a positive answer was occurring for the two last questions. Children recognized not seeing well during daytime were not included. Individuals owing reliable signs of xerophthalmia received a pill containing 200 000 units of vitamin A [12].

At the village level, demographic (population size, ethnic groups), structural (distance to the closest medical centre, the existence of a school in the village) and economic (primary agricultural products) information's were collected.

At the household level (defined as persons sharing a common doorway), the head of household was questioned about his/her educational attainment, profession and any history of having lived in a city or abroad. We asked questions on common ownership of goods or animals in the household (radios, bikes, motorbikes, carts, ploughs, traction bulls, monkeys, cattle and small ruminants). By adding the monetary values of all these goods and family possessions a proxy indicator of household wealth was derived and expressed in FCFA (1 FCFA is equivalent to 0.0018 US$). Each mother was also asked about her education level.

Data Processing and Analysis
Data were recorded on standardized forms, reviewed daily for accuracy and completeness. The administrative, environmental and economic data concerning the village were collected on a special form. There was also a form for collecting demographic and environmental information from the head of each household. A detailed protocol was drawn up for staff taking part in the survey. Several training sessions were organized so as to standardize data collection and examination procedures. Two teams worked in tandem in each region to collect the information and have achieved the process through two weeks. Two supervisors paid regular visits to the team members.

The night blindness prevalence rate in children was calculated for children aged from 2 to 10 for each region. Bitot spot rate was concurrently calculated in children aged from 0 to 10 years. A "xerophthalmia" variable, corresponding to a diagnosis of night blindness and/or Bitot's spot, was established. Results are presented for the three age groups 0–2 years, 2–6 years and 6–10 years.

The seven regions were combined in a single file for an overall analysis of the situation at the country level. Since the sample size of each stratum was not proportional to the population of the region under examination, allowing presenting data able to be directly extrapolated to the country as a whole, it was necessary to weight data for regions according to their population size. In the concern of adjustment for the cluster random sampling design, a sampling design effect of 1.5 was incorporated in the calculation of confidence limits.

Categorical outcomes, such as prevalence rates were initially compared by the chi square test or Fisher's exact test. Continuous data across groups were compared by analysis of variance (ANOVA) if normally distributed. The Wilcoxon rank-sum test was used for non-normal data. Odds ratio (OR), 95% confident interval (CI) limits, and p-values were calculated to compare status between groups.

Risk factors analysis was conducted among the 2 to 10 years individuals. A univariate analysis was performed and the association between the xerophthalmia and each potentially explanatory determinant was estimated separately.

A series of logistic regression analysis was initially performed and associations between each outcome variable and each explicative individual risk factor were examined separately. Then, to determine whether or not there was evidence of interaction in the data, the role of the various risk factors on each outcome variable was investigated. Finally, multiple logistic regression analyses were performed to find the best fitting and the best parsimonious model to describe the relationship between each outcome variable and the various risk factors assessed. Each determinant was tested and kept in the multivariate model if it was significantly contributive, considered as a confounding variable when it was associated with both the outcome variable and a different risk factor, or as an effect modifier variable when it interacted with another risk factor. In each model and for each contributive factor, results were expressed as odds ratios (or adjusted odds ratios) associated with their 95% confidence interval estimate.

The multivariate analysis was conducted with consideration of two different survey seasons (May-July and January-February) and three different latitude levels (10.39° to 13°, 13° to 15° and 15° to 20.12°).

The statistical analyses were performed using EPI-INFO 6.03 (Center of Disease Control and Prevention, Atlanta, GA, USA) and STATA (Stata Corporation 702 University Drive East College Station, TX 77840 USA).


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 POPULATIONS AND METHODS
 RESULTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Sample Description
In all, 13 490 children aged under 10 were enrolled in the seven regions of Mali as a whole, Due to recruitment constraints and sampling limits, Koulikoro and Segou contributed to less than the expected number of participants, 1568 and 1366 respectively (Table 1). The distribution of children by age showed that children aged between two and four were slightly over represented as compared with the age distribution among the 1996 Malian general population. Contrarily, children between the ages of eight and ten appeared to be under-represented. Comparing the sample distribution by gender with that of the general population, we noted a slight over-representation of girls.


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Table 1. Regional Distribution of Children Aged under 10 among the Studied Sample and among the General Population

 
Xerophthalmia Prevalence per Region
The prevalence rate of night blindness among children between 2 and 6 ranged from 0.17% in Kayes to 6.13% in Timbuktu (Fig. 1 and Table 2). This sign affected 1.91% (95% confidence interval [95% CI]: 1.58–2.39) of Malian children of this class age. The prevalence of Bitot's spots ranged from 0.26% in Kayes to 1.81% in Segou and was estimated at 1.10% (95% CI: 0.83–1.45) for the whole Mali.


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Table 2. Prevalence Rate (95% CI) of Xerophthalmia Signs by Age Groups and Regions

 
Xerophthalmia, defined as the presence of one and/or the other of these signs affected 2.51% (95% CI: 2.09–3.00) of all children aged from 2 to 6 in Mali. Its prevalence ranged from 0.26% in the Kayes region to 7.02% in Timbuktu.

Central corneal lesions were rarely encountered and reported in only seven cases among a sample of more than 13 000 children.

Age and Gender
The distribution of signs of xerophthalmia was studied according to the age of the children enrolled. The highest prevalence rates of night blindness were observed in the two to six-years age group, where 1.95% of children were affected. The highest Bitot's spot prevalence rates up to 1.26% were found in children aged between six and ten.

Distribution of these clinical signs according to gender showed that xerophthalmia was more frequent in boys than in girls. Between the ages of 2 and 6, 2.26% of boys experimented night blindness and only 1.75% of females. Bitot's spots were identified among 1.11% of male children and among 0.98% of females.

Season and Latitude
Compared with May-June periods, prevalence of xerophthalmia was lower in January-February (Table 3). Considering latitude, children living in the northern dry areas of Mali were more likely to present xerophthalmia (Table 3). These two modifying factors need to be considered simultaneously and to be entered in the model studying xerophthalmia risk factors.


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Table 3. Univariate Analysis of Xerophthalmia Risk Factors

 
Wealth
Children living in proper houses or ones with a corrugated iron roof had a lower risk of xerophthalmia (Table 3). Some consumer goods such mopeds or TV were associated with a lower prevalence. Ownership of at least one cow per family was also linked with a lower prevalence, whereas that of sheep or goats did not appear to have any impact.

The proxy indicator of household's wealth was inferior for children with xerophtahlmia signs (732,022 FCFA as opposed to 810 000 FCFA if no xerophthalmia sign), although not significantly (p = 0.17).

Multivariate Analysis of Risk Factors
The size of the village seemed to be an important explanatory factor. Children from villages with 1000 to 5000 inhabitants or more than 5000 inhabitants were at higher risk of xerophthalmia than those living in a village of fewer than 1000 inhabitants (OR = 2.36 [95% CI:1.66–3.35] and 4.07 [95% CI:2.58–6.40], respectively) (Table 4).


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Table 4. Multivariate Analysis of Xeropthtalmia Risk Factors

 
Distance to the nearest medical centre was also a contributing factor with an increased prevalence of xerophthalmia as the distance between the village and the medical center increased.

Schooling appeared to be a protective factor, as suggested the low prevalence level of xerophthalmia when there is a school in the village (OR = 0.59 [95% CI: 0.43–0.88]) or when the child's mother received previous schooling (OR = 0.57 [95% CI: 0.31–1.07]). As far as the children were concerned, attendance at a nondenominational school appeared to be protective in the univariate analysis. Nevertheless, this result was not contributive in the multivariate analysis.

The production of millet was associated with high prevalence rates of xerophthalmia (OR = 1.75 [95% CI: 1.13–2.72]). On the other hand, children living in villages with rice production were less likely to have xerophthalmia signs (OR = 0.69 [95% CI: 0.50–0.94]). The availability of market gardens was not significantly associated with a reduced risk of xerophthalmia.

The largest ethnic group was the Bambara people, predominant in 20.3% of villages, followed by the Peuhl, the Sarakole and the Dogon. Using the Bambara as reference, there were no statistical differences for villages belonging to Peulh, Moor or Malinke groups. However, the risk was significantly lower among the Sarakole (OR = 0.46 [95% CI: 0.27–0.82]), the Bozo (OR = 0.08 [95% CI: 0.01–0.58]), the Senoufo (OR = 0.58 [95% CI: 0.25–1.36]) or the Songhaï ethnic groups (OR = 0.40 [95% CI: 0.21–0.75]) (Table 4).


    DISCUSSION
 
Vitamin A Deficiency as a Public Health Problem in Mali
The survey was conducted on a long period of time between May 1996 and July 1997 at different seasons and with two different harvests. This has to be considered when comparing regions. Subsequently the aggregation of regional results in a national one should only be considered as a proxy indicator of the severity of the problem in the whole country.

WHO considers that there is a serious public health problem if, in a population of preschool age children, the prevalence of night blindness or of Bitot's spots exceed 1% and 0.5% respectively [13].

Night blindness is not specific of xerophthalmia and other factors can create night blindness. Because of budget constraints, it was not possible during this survey to confirm vitamin A deficiency by serum testing. Nevertheless we have proven in other studies conducted in several regions of Mali that night blindness was strongly associated with very high prevalences of vitamin A deficiency. In the Bandiagara region [14], night blindness was discovered in 4.3% of children aged 6 months to six years and serum retinol was lower than 0.35 µg/L in 43.8% of the sampled children. The biochemical deficiency attested by the Modified Relative Dose Response test was still more frequent (77%).

In Mali, these thresholds have been exceeded in four regions out of seven. In the region of Gao-Kidal, the prevalence of Bitot's spots was close to the threshold value. The problem was very important in Timbuktu, Mopti and Segou. The least affected regions were Kayes and Sikasso, in the south-western part of Mali.

The survey was carried out before National Immunization Days (NIDs) were implemented in 1998. Mass distribution of vitamin A supplements unlikely interfered with the study results. However, some non-governmental organizational programs could have potentially distributed doses of vitamin A as part of the primary health care system. Nonetheless this situation was surely very limited as attested by the 1996 Demographic and Health Study that reported a 9.7% percent of children less than 3 years of age having received vitamin A dose during the preceding year [15].

Age
Young children are particularly prone to xerophthalmia. Their needs are greatest and the basic intake often inadequate. Concurrent vitamin loss as a result of infection and malabsorption from diarrhoea episodes are quite common. Indeed xerophthalmia was more frequent in children under the age of 6.

Gender
Boys more frequently presented signs of xerophthalmia, either night blindness or Bitot's spots. This finding recurs frequently in vitamin A surveys and may be explained in various ways: boys are more susceptible to diarrhoea, have less resistance to the stress of malnutrition and are therefore more likely to present vitamin deficiency than girls [4]. Girls also remain closer to their mothers during the work of preparing meals and have access to more diversified intakes including dark green leaves vegetables and fruits.

Risk Factors
Seasonal Variations.
Bias linked to seasonal variations need to be discussed in the search of social and environmental determinants. The prevalence estimates of xerophthalmia were not similar in the regions of Gao and Timbuktu, with Gao being the least affected region. Climatic conditions are broadly similar, although the population and way of life are different (the Tamachek predominate in Timbuktu and the Songhaï in Gao). The two surveys did not take place at the same time: Timbuktu was surveyed in June 1996, at the end of the dry season, when nutritional conditions are at their worst; Gao was visited in February 1997, a season with still full granaries.

The factors contributing to vitamin A deficiency are common to all the members of a family or a village community as a whole, which explains the distribution differences between areas, as well as a clustering effect that has to be taken into account in analysis proceeding [16]. One isolated clinical case is usually evidence of a biochemical vitamin A deficiency in the other members of the community. It is considered that children suffering from biochemical vitamin A deficiency are 10 times as numerous as those with xerophthalmia [14]. For these children, supplementation with high dose vitamin A capsules (100,000 IU/200,000 IU) can reduce mortality by 23–30%[23].

Vitamin A balance essentially depends on the micronutrient content in food. This content is constituted by the consumption of retinol present in animal products and by that of a precursor in the form of provitamin A carotenoids, predominantly found in fruits and vegetables. In most of the populations exposed to xerophthalmia, vegetables are the main source of vitamin A, and even without seasonality, it is very difficult to meet all needs for vitamin A with vegetables and fruits. It is unfortunately linked to seasonal variations in the produce availability. This explains why the content has to exceed daily needs so as to constitute sufficient hepatic reserves of vitamin A in order to live through periods of shortage. The effectiveness of carotene rich foods in improving vitamin A status is still not fully understood and warrants further investigations [1719].

A certain number of factors, such as diarrhoea events or intestinal parasitic diseases, are recognized to hinder the absorption of vitamin A. Other events, such as measles or respiratory infections, increase metabolic requirements. Mild malnutrition is also an obstacle to the absorption, hepatic storage and transportation of the vitamin. All these factors are common among children in Mali [20].

Socio-Economic Level of Families.
It is generally agreed that vitamin A deficiency affects the children of poor families. We postulated that the level of wealth in the families of the affected children could be low. When we constructed an indicator of wealth by adding up the commercial value of the families’ various possessions, no significant correlation with the frequency of occurrence of xerophthalmia was found; therefore this estimator was not kept in the model. Interestingly, the same indicator was used in the trachoma survey and a very strong association was then found between trachoma status and poverty [21]. Relation between poverty and xerophthalmia appears not so strong than with trachoma.

Village Environment.
It is also paradoxical that the disease frequency was inversely related with the size of the village. It may be postulated that children are fed in a more systematic, more consistent way in a traditional, remote, closed village society. The degree of health cover, as defined by the presence of a medical centre within 5 or 15 km seems to have an impact, and to be associated with a lower prevalence of vitamin deficiency. However, it is difficult to interpret this finding. For example, the proximity of medical centre might make it easier to distribute vitamin A capsules for childbirth or during childhood diseases.

Level of Education.
Schooling appears to have a marked impact on the frequency of vitamin deficiency. The presence of a school, or the fact that the mother has attended school, was very significantly associated with a lower prevalence of xerophthalmia. On the other hand, the role played by the schooling received by the children of the family did not stand out in a multivariate analysis. The educational system is poorly developed in Mali (less than 30% of children in rural areas attend school), but it might be hoped that it would promote a change in children feeding habits. The fact that the head of the family has spent a period of time abroad might increase the diversity of the family's diet and food habit.

Agricultural Production.
In the Sahelan countries, the basic food is a cereal (millet, sorghum or rice) and a sauce made from cooking leaves, fresh or dried fish or meat depending on socio-economic level [21].

It is surprising and unexpected that villages producing millet have a higher prevalence. Rice, which is taking on increasing importance in the Malian diet, seems to have a protective effect even when this variable is standardized on latitude. It has been introduced more recently than the traditional cereals such as millet and may point to a search for increased diversity of food which encourages beta-carotene rich vegetables in the diet. The sauces accompanying this cereal are often different, for example peanut sauce or bean-leaf sauce.

Ethnic Group.
Despite a different way of living we did not detect any difference between Bambara villages and Peuhl or Moor ones. Indeed, if Bambara are traditional farmers, Peuhls are more specialized in cattle breeding and then subsequently more likely to get more milk products for their children, and Moors live on the Mauritanian border, in dry regions which do not lend themselves to cultivation. Possible explanations to the lower risk of Sarakole, Bozo, Songhai or Senoufo people need to be very careful. Some cultural factors could interfere concurrently to richness, mobility or education.

A National Policy
In 1990, the heads of state and government made a commitment to allocate resources for controlling vitamin A deficiency before the end of the decade. Activities were conducted in many countries but very little in Africa as yet. Real progress has been made in certain zones, particularly South America and Asia. The problem is still very acute in Sub-Saharan Africa and will remain so while dietary intake remains limited. The urgency of the situation makes it legitimate to use palliative strategies by distributing high doses of vitamin A, for example during national vaccination campaigns. These findings together with the results of more specific surveys in limited areas have been strong arguments for advocating vitamin A supplementation during Malian NID's. The measure is successfully applied every year to the entire country since December 1998. This intervention must firmly be completed by the promotion of an active and effective food policy to control this clearly identified micronutrient deficiency [22].


    ACKNOWLEDGMENTS
 TOP
 ABSTRACT
 INTRODUCTION
 POPULATIONS AND METHODS
 RESULTS
 ACKNOWLEDGMENTS
 REFERENCES
 
The survey conducted by IOTA and the Malian blindness prevention program was funded by a grant of the European Community. We will thank the Malian Ministry of Health for its strong implication through all regional health structures.

Received July 19, 2006. Accepted June 3, 2006.


    REFERENCES
 TOP
 ABSTRACT
 INTRODUCTION
 POPULATIONS AND METHODS
 RESULTS
 ACKNOWLEDGMENTS
 REFERENCES
 


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