A literature review on the available evidence among the population of North Africa and the Middle East
Kiki Fockens, 2164531. Supervisor: Manon Geldof
INTRODUCTION: based on Goal 2 of the Sustainable Development Goals from the World Health Organisation celiac disease is becoming a worldwide health problem. The thought this disease only appears in developed countries has to end. There should be more attention for this disease, since the additional risks on not following a strictly gluten-free diet are big. The aim of this review is to compare the prevalence of celiac disease in the developing countries with each other and this review is based on the following research question: what is the prevalence of celiac disease among the population in the developing countries?
METHODS: For this literature review, PubMed and Google Scholar were searched. The search terms that were used were ‘celiac disease’, ‘coeliac disease’, ‘North Africa’, ‘Middle East’ and ‘developing countries’. Studies about diagnosing celiac disease on HLA DQ2 of DQ8 were excluded, just like articles specific about prevalence of celiac disease in patients with diabetes mellitus type 1.
RESULTS: In the studies that were performed in North Africa (Egypt, Libya, Tunisia and Sudan), the prevalence was between 0.64% and 1.13%. The studies performed in the Middle East (both in Iran) showed a prevalence of 0.96% in the northern parts, and a lower prevalence in the southern parts of Iran.
CONCLUSION: The conclusion of this review is that the prevalence in the developing countries, specified for North Africa and the Middle East, is similar to the prevalence known in the developed countries.
Keywords: celiac disease, North Africa, Middle East, prevalence, developing countries
In the year 2000 the World Health Organisation came up with the Millennium Development Goals to reduce extreme poverty worldwide. They set a deadline on 2015 for eight different targets, all focused on basic human rights, the rights of every human to health, education, shelter and security (World Health Organisation, 2000). Since we reached the year of 2015, the World Health Organisation set new goals to sustain the development all over the world: the Sustainable Development Goals. This review is based on one of the Sustainable Development Goals, ‘Goal 2: End hunger, achieve food security and improved nutrition, and promote sustainable agriculture’ (World Health Organisation, 2015). One of the problems with nutrition in developing countries is the unknown existence of food intolerances or food allergies.
A food intolerance that is thought to have a really low prevalence to no prevalence at all in developing countries is celiac disease. The World Gastroenterology Organisation (2012) defines celiac disease as follows: ‘Celiac disease is a chronic, immunologically determined form of enteropathy affecting the small intestine in genetically predisposed children and adults. It is precipitated by the ingestion of gluten-containing foods’
A multicenter study on the prevalence of celiac disease in the United States performed by Fasano et al. (2003) among at-risk groups and not-at-risk groups showed the following incidence:
– At risk, first-degree relatives: 1:10 (10%)
– At risk, second-degree relatives: 1:39 (2,6%)
– At risk, symptomatic patients: 1:56 (1,8%)
– Groups not at risk: 1:100 (1%)
These incidences are based on the available data of known cases of celiac disease, but worldwide there are more patients undiagnosed than diagnosed with celiac disease, this phenomenon is called the ‘Celiac Iceberg’ (World Gastroenterology Organisation, 2012). Cataldo and Montalto found in 2007 the main reason for the large number undiagnosed patients with celiac disease, is because of the mild complaints or because the patients have a silent, subclinical form of celiac disease. Other reasons that are named more specific for the developing countries are the minimal knowledge about the disease among the local medicals and the little availability of ways on diagnosing celiac disease (Kang et al., 2013).
For diagnosing celiac disease, the World Gastroenterology Organisation made a step-by-step action plan. The Gold Standard is by small intestine biopsy and celiac disease specific antibodies, like anti-transglutaminase antibodies, anti-gliadin antibodies and anti-endomysial antibodies. The biopsy is being judged by a pathologist on the intensity of damage to the mucosa. Marsh set up a classification for the implication of the damage in 1992 (WGO, 2012), see Table 1. Table 1 Marsh Stages
Unless the fact that celiac disease is in many cases still undiagnosed, celiac disease is becoming a public health problem in all the countries that use gluten as main ingredient for their meals. It is becoming a public health problem, since there are major risks on not following a gluten-free diet, like cancer (risk increase 1.35), malignant lymphomas, small-bowel neoplasia and osteoporosis (WGO, 2012). Even in the developing countries, the availability of gluten-containing food is rising. Cataldo and Montalto (2007) named two reasons for this change in food consumption: (1) the cultural and nutritional patterns in the developing countries are getting a much more ‘western’ pattern and (2) the developed countries are sending humanitarian aid (food, clothes etc.) to the developing countries and this food contains gluten, like wheat flour, cereals etc. Since the food industry is developing worldwide and really quick, the probability of a rising frequency of celiac disease all over the world is really likely (Cataldo and Montalto, 2007).
There have been done some single studies about the prevalence of celiac disease in different developing countries, but how does the prevalence of celiac disease in these countries relate to each other? Do we find the same prevalence of celiac disease in all these countries or do they differ from each other? The aim of this review is to compare these prevalences with each other and this review is based on the following research question: what is the prevalence of celiac disease among the population in the developing countries?
For this review two databases were searched, named PubMed and Google Scholar. The searches were done in those two databases between June 1st 2015 and June 10th 2015.
First PubMed was searched for articles about the prevalence of celiac disease. Since celiac disease is also spelled as coeliac disease, all the search terms included [‘celiac disease’ OR ‘coeliac disease’]. First the database was searched on celiac disease and ‘developing countries’. This showed 51 results. Because of the fact that all the articles that were shown were about countries in the Middle East or North Africa, the following search terms were specified for ‘Middle East’ and ‘North Africa’. This only showed a lot of reviews and the same articles that were found earlier with the previous search term. So no new articles were included with these search terms.
The search in Google Scholar showed no additional articles to use in this review. Searching with the same search terms as were used in PubMed came up with the same articles that were already included from the search in PubMed.
The results of the searches (51 hits) were screened on titles. Out of the articles which titles seemed to relate to this specific research question, the abstracts of 36 studies were read. If the abstract answered the research question, this was the case in 11 studies, the whole article about the study was read. If the article still related to this research question, the article was included for the literature review.
With the search terms used in for this literature review, there were also found a lot of reviews about the prevalence of celiac disease. The articles that were used in those reviews were also screened. In an attempt to use the ‘snowball searching’ method, those reviews were screened as well. Since most of the reviews were from the year 2000 or even older, most of the articles, used in those reviews, were also too old to use for this literature review. Although some of them led to other articles that were useful for this review.
Like already named before, all the searches showed a lot of reviews. The searches showed a lot of specific articles on the prevalence of celiac disease among diabetes mellitus type 1 patients as well. Those articles were excluded for the results, since the researcher was not only looking for the prevalence of celiac disease among at-risk groups, but for the prevalence of the whole population. The articles written in other languages than English were excluded as well, since the reviewer is not familiar with languages other than English.
Studies on the prevalence of celiac disease only based on whether the patients were positive for HLA DQ2 or HLA DQ8 genes, genes that increase the risk on getting celiac disease, and not diagnosed by a duodenal biopsy were also excluded from this review. The European Society of Pediatric Gastroenterology and Nutrition (ESPGAN) published guidelines in 1970 about the diagnosis of celiac disease: ‘required a sequence of three small intestinal biopsies, including abnormal mucosa when taking a diet containing gluten, clear improvement when taking a gluten-free diet and deterioration with rechallenge’. In 2012 the ESPGAN published new guidelines, which ‘indicates that symptomatic children with tTG levels at least ten times above normal and positive EMA and DQ2/8 do not need duodenal biopsies to make the diagnosis of CD’.
Per article that was included for this review, the following parts were systematically written down: (1) the method of diagnosing celiac disease used in this study, (2) the age of patients in research groups, (3) the number of celiac disease patients found in this study, and (4) if there were any particularities per study.
Table 2 shows the results per article of the articles that were used in this literature review.
In the articles included for this review, there was a difference between studies that included suspected patients, studies that tested random-selected participants and there was one study that did both.
The studies that were performed with random-selected participants showed an overall percentage of 0.64-1.13%. All those studies diagnosed celiac disease with the same methods, first they performed a serological screening. Once the participants showed positive sera for anti-tTG or anti-gliadin antibodies, they underwent a small intestine biopsy to confirm or exclude celiac disease.
One study (Catassi et al. 1999) showed an exceptional high prevalence of celiac disease: 5.6% among random selected schoolchildren in Saharawi. In the article the writers searched for a statement why this disease was so high in this area, but they only were guessing for primary malnutrition and intestinal infections. They did not found an explanatory reason.
The study performed by Ageep (2012) contained 172 patients suspected for celiac disease, because of chronic diarrhea, weight loss or stunted growth. Out of those 172 patients, 128 were diagnosed with celiac disease. This leads to a percentage of 74.4%, divided over five main tribes that live in this area. The method of diagnosing celiac disease was by serological screening on anti-tTG and anti-gliadin antibodies and questionnaires, so they did not undergo a small intestine biopsy to confirm the disease.
In the study of Cataldo et al. in 2002 the researchers searched for a difference in prevalence of celiac disease between diagnosed immigrant children in Italy and diagnosed Italian children. They found that the immigrant children can similarly be affected with celiac disease like the Italian children. The researchers explain this, by growing up in the exact same environment as the Italian children.
The study that included random selected participants and suspected patients (Abu-Zekry et al. 2008) showed a low prevalence in the random group (0.53%) and a high prevalence in the suspected patient group (4.7%). The writers concluded that their found prevalence is similar to the prevalence of celiac disease in the general population.
If you divide the studies in North Africa and the Middle East, the prevalences are almost similar (North Africa 0.64-1.12%, the Middle East 0.96%). This contributes to the thought that celiac disease has worldwide the same prevalence, with some exceptions of extreme high or extreme low prevalences.
A conclusion out of all the articles used for this review, is that one of the biggest reasons celiac disease is still undiagnosed in such a big part of the population, is because of the fact that a lot of people have no to limited symptoms, they have a silent or subclinical form. Cataldo and Montalto (2007) made a table in their review with the most frequent symptoms of celiac disease. In general, when a person has no symptoms, there is no reason to detect those cases. But next to the known increased risks of not following a gluten-free diet, Dicke showed in 1953 the importance of diagnosing celiac disease and being on a gluten-free diet when you are a celiac. He showed that the patients who were diagnosed with celiac disease showed a real improvement in health during the Second World War, because there was no gluten-containing food available. Once the war was over and the gluten-containing food came back in their diets, the patients worsened directly. This shows the importance of detecting as much patients as possible and is one of the reasons why there should be a lot more attention on celiac disease worldwide.
Another problem that comes forward in most of the articles is the lack in knowledge about the disease. The medicals in the developing countries still think celiac disease is a disease off the developed countries, with no appearance in the their countries. A thing that contributes to this thought is because the equipment is not available in the developing countries or they are too expensive. One of the articles used in this review (Alaradi et al., 2011) shows the prevalence based on a new improving test, the rapid anti-tTG test. The diagnosed patients with this new test were checked by small intestine biopsy and the group that didn’t have celiac disease, was randomly checked with biopsies as well. This test is really easy in use and friendly in price. With this new and upcoming test, it will be a lot easier to diagnose celiac disease patients.
A notable fact that was found during the literature searches, is that, when searching on the prevalence of celiac disease in the developing countries, only studies about countries in North Africa and the Middle East were found. As a suggestion for further research, a prevalence study on celiac disease in the sub-Saharan region is recommended, since there is no available data about.
Limitations and strength of this review
One of the limitations in this review is that not all the articles diagnosed celiac disease with the same method. Seven out of eight articles did a serological screening, when this screening showed positive sera, they continued with a small intestine biopsy. They confirmed celiac disease mainly on this biopsy, but sometimes patients were diagnosed without a biopsy, because they did not want to undergo a biopsy. One of articles only screened on sera and questionnaires and based their diagnosis on this. For a next review, it would be better to select the articles on the exact same method of diagnosing celiac disease.
A second limitation is the fact that there were some really old articles included (Cataldo et al., 2002 and Catassi et al. 1999). Those articles were included, despite the fact they were from more than ten years ago, because they contained a lot of information that was useful for this review. It was interesting to mention the high prevalence of celiac disease in the Sahara, since this prevalence is exceptional high compared with the rest of the world (Catassi et al., 1999). Also the article of Cataldo et al. (2002) about the prevalence of celiac disease among immigrant children in Italy was worth including in this review, because it helps a little more to learn about the risk factors of developing celiac disease. Those children grew up with the exact same environment as the Italian children. It seems that the prevalence in both groups is the same.
A limitation that is more general about a literature review than about this specific review is that meta-analyzes or systematic reviews are a lot more probative. A literature review is more depending on the articles you find in the short time of searching and with the limited search terms that were used for this review. With a systematic review or meta-analysis, all the articles that were found are read and these methods dig way deeper in to the subject than a literature review. For this literature review specific, the time to select, read and write about the articles was pretty short. If there was more time for this review, it would be more thoroughly on all levels.
The conclusion of all the articles included in this review is that the prevalence in the developing countries, specified for North Africa and the Middle East, is similar to the prevalence known in the developed countries, around 1%. An extra point to conclude is that celiac disease is worldwide underdiagnosed and there is a need to pay more attention on the symptoms, subclinical and silent forms.
A literature review on the available evidence among the population of North Africa and the Middle East