PRELIMINARY DRAFT 14/09/2010

THE BURDEN OF CELIAC DISEASE IN THE MEDITERRANEAN AREA

Luigi Greco , Laura Timpone , Carmela Arcidiaco

European Laboratory for Food Induced Diseases, University of Naples, Federico II.

MEDICEL : The Mediterranean Network for Coeliac Disease

Luigi Greco (coordinator), European Laboratory for Food Induced Diseases (ELFID) , Naples, ITALY
Abkari Abdelhak, Hopital des Enfant Ibn Rochd de Casablanca, Casablanca, MOROCCO
Abu-Zekry Mona, Children’s Hospital, G.I. Unit, CairoUniversity, Cairo, EGYPT
Attard Thomas,Univ of Malta, Med School, Guardamangia, Msida MSD 2080 MALTA
Barada Kassem Division of Gastr, , American University of Beirut Medical Center, Beirut , LEBANON
Bilbao Josè Ramon, Immunogenetics Laboratory, Hospital de Cruces, Bilbao, SPAIN
Boudraa Ghazalia, Clinique Amilcar Cabral, Oran , ALGERIA
Bouguerrà Faouzi, Hopital des Enfants de Tunis, Tunis, TUNISIA
Cullufi Paskal, Gastrohepatology of University Hospital Center "Mother Tereza" Tirana, ALBANIA
Dusanka Micetic-Turk. University Medical Centre Paediatric Dpt Ljubljanska, Maribor, SLOVENIA
Hugot Jean Pierre, Hopital Robert Debré, Gastroenterology, Paris, FRANCE
Kuloglu Zarife, Dpt of Pediatric Gastroenterology, AnkaraUniversity, Ankara,TURKEY
Roma Eleftheria, Aghia Sophia Children’s Hospital, Athens, GREECE
Shamir Raanan, Schneider Children's Medical Center of Israel, Tel Aviv, ISRAEL
Ter Terzic Selma, University Clinical Center Tuzla, , University of Tuzla, Sarajevo, BOSNIA ERZEGOVINA
Zrinjka Mišak, Children's Hospital Zagreb, CROATIA

INTRODUCTION

Recent epidemiological studies show that the prevalence of Celiac disease (CD) had been underestimated, affecting not only Europeans, but also populations of the Mediterranean countries, such as Middle East(1-4) andNorth Africa(5-7), where its prevalence is similar to that of Western countries.

In the Northern Africa Region and in the Middle East very high incidence of CD has recently been reported both in the general population and in at risk-group. These high frequencies are due to the wide consumption of wheat and barley and to the high frequency of the DR3-DQ2 CD predisposing haplotypes in these population(13,14). Prevalence of CD among low risk populations varies from 0,14% to 1,17% (15-17): 1%-1,3% in Turkey(18,19), 0,6%-0,96% in Iran(20-21), 0,5% in Egypt(22), 0,6% in Tunisia and Israel(23-24), <0,5% in Jordan, Lebanon, and Kuwait(1,10,16,25). Among high risk groups (patients with positive family history, insulin dependent diabetes mellitus, thyroiditis, etc) the prevalence of CD ranges from 2,4% to 44% assessed by serological markers and biopsy (26-27).

The use of wheat and other gluten-containing cereals is spreading all over the world, the consumption of wheat based pasta is increasing in Europe but also across Mediteranneum, where many countries are big producers also.The Italian nutritional style associated with the healthy features of the Mediterranean Diet was the cultural background supporting the widespread diffusion of the pasta. Unfortunately the side effect of this positive move has been the enormous increase of gluten intolerance. Now CD appears to be a widespread public health problem, involving also the population of developing countries as well as of China (8,9,14).

Robust estimates of a prevalence of 1:100 individuals result in more than 5 millions individuals from the Euro-Mediterranean Countries affected by permanent gluten intolerance (Celiac Disease).

We also are aware that less than 1 every 7 adult individual and less than 1: 5 children affected are correctly diagnosed and treated(1,10-12). In the next 10 years we have to face about 5 millions cases in the Mediterranean area. This is the largest global epidemic of food-induced permanent disease in the area.

The health toll of this ‘epidemic’ unfortunately includes growth failure, infant malnutrition, gastrointestinal diseases, anemia and more than 20 associated symptoms and conditions. The risk of cancer in undiagnosed adults is significantly increased and the mortality is doubled in the total cohort of affected(28-33). The financial burden of this specific food related problem has to be estimated to more than 5 Billions Euro/year.

Very few countries from the Euro-Mediterranean Region are able to face this expanding problem : in many countries few cases are recognized, because of the low awareness and know-how to deal with the problem.

AIM

The aim of this work is to estimate the global burden related to undiagnosed Celiac Disease in the Mediterranean Area, as computed by morbidity, mortality and crude health cost .

METHODS , ASSUMPTIONS :

  1. Prevalence = 1%
  2. Incidence : new Cases/year estimated on 1% of the live births
  3. Symptomatic ADULTS : 1 every 7 cases , CHILDREN 1:5 cases
  4. Mortality on the total CD cohort : Standardized Mortality Rate 1,8 compared to age and sex matched population
  5. Delay between symptoms and diagnosis : adults 6 years, children 2 years
  6. Associated Conditions : 10% of total cohort (KB 30% : Turkey 2% Iran 33% , IDDM 10% (6.7-18.5%)
  7. Complications 16% of symptomatic
  8. Non GI Symptoms (only symptomatic) : Short Stature 25% Anemia 40% (20-80%) Osteopenia 30% (30-50%), Abnormal Liver Function 10% (Turkey 38% , Iran 25%)

MEDICAL COST

Annual Medical Cost in the year preceding the diagnosis of CD, excluding diagnostic costs, was estimated to $5023/patient, $1764 more than the cost of the same patients in the year following the diagnosis (34).

In the four years preceding the diagnosis of CD the direct medical cost was estimated to $11037/patient. A symptoms and age matched control individual cost $7073 in 4 years, with a difference of $3964 : about $1000/year/patient. This was due to increased In-patients admissions, Out-patient cost, Lab test, Radiology and Office visits (34). The diagnosis of CD brought a 30% reduction in direct medical expenditure. A similar 30% reduction in direct medical cost after diagnosis of CD was also reported by Green (35, 36) : the mean medical expenditure decreased from $8502 per capita to $7133 for the 2 years after the diagnosis of CD.

ESTIMATED EXCESS COST

We assume that the cohort of CD with no symptoms does not increase the average medical cost, compared to non CD individuals (but this should also be revised, since a significant number of patients identified by screening report a posteriori significant clinical symptoms) .

So medical cost are estimated only for 1:7adult and 1: 5 children CD, those symptomatic.

For each adult individual we assigned, on the basis of vast amount of reports, a minimal period of 6 years of delay between onset of symptoms and appearance of disease (5). 2 years of delay were assigned to children cases.

During these delay period the individual required , in excess of age and sex matched controls , at least:

EXCESS NEED OF MEDICAL RESOURCES COMPARED TO AGE AND SEX MATCHED CONTROLS / ADULTS / CHILDREN
In-patient admission / 2 / 1
Out-patient admission / 1 / 1
Medical consultations : primary care 2/year / 3 / 3
Specialized Consultations : / 2 / 1
Lab Test / 4 / 2

ESTIMATED THE MEDICAL COST (Euros, Italian NHS 2007 costs)

Consultations / Lab test / Hospital Admission / Out patient / TOTAL Euros
n / 5 / 4 / 2 / 1
COST ADULT € / 250 / 446 / 9.818 / 879 / 11.393
n / 4 / 2 / 1 / 1
COST CHILD € / 200 / 297 / 2.254 / 586 / 3.337

The cost of health services has been estimated by the standard Italian National Health System Costs of 2007.We summed the total cost of the medical services required for each child or adult patient to get a standardized cost/per patients before the diagnosis of CD was obtained. In this way we have an estimate of the financial load, only for medical expenses, of the symptomatic patients. No excess cost was attributed to asymptomatic ones.

The estimated cost according to the Italian NHS where then standardized for each country according to its Purchasing Power Parity (PPP) index. The concept is founded on the law of one price; in absence of transaction costs, identical goods will have the same price in different markets.

the purchasing power of different currencies is equalized for a given basket of goods.

The total load of medical expenses for each country was obtained by multiplying the individual cost by the number of symptomatic patients estimated (adults and children)

ESTIMATING THE BURDEN OF DISEASE

Classical G.I. Symptoms : 85% of symptomatic patients are likely to suffer from G.I symptoms, which include diarrhea, abdominal pain, vomiting, irritable bowel, gastritis.

-Associated Conditions : the minimal estimate is Short Stature (20% children) , Anemia (40%), Osteopenia (30%), Abnormal Liver Function (10%).

-Mortality has been reported in excess of 1.8 compared to age and sex matched controls (33)

RESULTS

TABLE I : Population statistics in the Mediterranean region

TABLE II : Estimated Prevalence of Celiac Disease

TABLE III : Excess Cost of undiagnosed symptomatic Celiac Patients

TABLE IV : Symptoms and diseases associated to symptomatic Celiac Patients

TABLE V : Excess mortality in the undiagnosed cohort of patients

DISCUSSIONwill follow the conclusion of the 15-16 September 2010 meeting

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THE BURDEN OF CELIAC DISEASE IN THE MEDITERRANEAN AREA

TABLE I POPULATION NOW AND IN THE NEXT 10 YEARS

Population / Children 0-14 / Median age / Population growth rate (%) / Children0-14 in 10 years / Total population in 10y
ALBANIA / 3.639.453 / 714.250 / 29,9 / 0,546 / 829.795 / 3.838.167
ALGERIA / 34.178.188 / 8.696.320 / 26,6 / 1,196 / 8.664.171 / 38.265.899
BOSNIA / 3.842.566 / 668.063 / 39,8 / 0,339 / 510.101 / 3.972.829
CYPRUS / 1.084.748 / 10.847 / 35,5 / 1,69 / 184.190 / 1.268.070
CROATIA / 4.489.409 / 698.458 / 41 / -0,05 / 649.169 / 4.466.064
EGYPT / 78.866.635 / 26.020.307 / 24,8 / 2,033 / 30.083.678 / 94.900.222
FRANCE / 64.057.792 / 11.968.654 / 39,4 / 0,549 / 12.078.097 / 67.574.565
GREECE / 10.737.428 / 1.530.992 / 41,8 / 0,127 / 1.522.030 / 10.873.793
ISRAEL / 7.233.701 / 2.015.859 / 29,1 / 1,671 / 2.145.154 / 8.442.452
ITALY / 58.126.212 / 7.870.226 / 43,3 / -0,04 / 7.132.086 / 57.853.019
LEBANON / 4.017.095 / 1.034.885 / 29,3 / 1,107 / 1.030.385 / 4.461.787
LIBYA / 6.324.357 / 63.244 / 23,9 / 2,172 / 2.383.966 / 7.698.007
MALTA / 403.532 / 65.306 / 39,5 / 0,4 / 62.709 / 419.673
MAROCCO / 31.285.174 / 8.967.576 / 25 / 1,099 / 9.254.154 / 34.723.415
SYRIA / 21.762.978 / 217.630 / 21,7 / 2,006 / 8.161.117 / 26.128.631
SLOVENIA / 2.046.976 / 287.275 / 41,5 / 0,007 / 328.540 / 2.078.249
SPAIN / 40.525.002 / 5.864.419 / 41,1 / 0,072 / 5.908.545 / 40.816.782
TUNISIA / 10.486.339 / 2.377.034 / 29,2 / 0,98 / 2.425.490 / 11.514.000
TURKEY / 72.561.312 / 18.859.334 / 27,7 / 1,3 / 20.353.448 / 80.252.000
MEDITER / 455.668.897 / 97.930.679 / 33,1 / 0,905 / 104.022.014 / 499.547.626

TABLE II : PREVALENCE OF CELIAC DISEASE FOR NEXT 10 YEARS

Population Prevalence estimated at minimum rate of 1% / Estimated Celiacs today at 1% / Estimated celiac children today at 1% / Projected prevalence of CD in next 10 yrs / Projected celiac children in 10 years
ALBANIA / 36.395 / 7.143 / 38.382 / 8.298
ALGERIA / 341.782 / 86.963 / 382.659 / 86.642
BOSNIA / 38.426 / 6.681 / 39.728 / 5.101
CYPRUS / 10.847 / 1.840 / 12.681 / 1.842
CROATIA / 44.894 / 6.985 / 44.661 / 6.492
EGYPT / 788.666 / 260.203 / 949.002 / 300.837
FRANCE / 640.578 / 119.687 / 675.746 / 120.781
GREECE / 107.374 / 15.310 / 108.738 / 15.220
ISRAEL / 72.337 / 20.159 / 84.425 / 21.452
ITALY / 581.262 / 78.702 / 578.530 / 71.321
LEBANON / 40.171 / 10.349 / 44.618 / 10.304
LIBYA / 63.244 / 632 / 76.980 / 23.840
MALTA / 4.035 / 653 / 4.197 / 627
MAROCCO / 312.852 / 89.676 / 347.234 / 92.542
SYRIA / 217.630 / 79.275 / 261.286 / 81.611
SLOVENIA / 20.470 / 2.873 / 20.782 / 3.285
SPAIN / 405.250 / 58.644 / 408.168 / 59.085
TUNISIA / 104.863 / 23.770 / 115.140 / 24.255
TURKEY / 725.613 / 188.593 / 802.520 / 203.534
MEDITER / 4.264.968 / 976.389 / 4.644.529 / 1.040.220

TABLE III : EXCESS COST OF UNDIAGNOSED SYMPTOMATIC CELIAC PATIENTS

Purchasing Power Parity / Symptomatic adults 1:7 next 10y / Sympomatic children 1:5 next 10y / Standirdized Cost for adult € / Standardized Cost for children € / Total Cost Adult next 10 y k€ / Total Cost Children next 10 yr k€ / TOTAL Cost Symptomatic next 10 yr k€
ALBANIA / 7,16 / 4.298 / 1.660 / 2.804 / 821 / 12.050 / 1.363 / 13.413
ALGERIA / 6,87 / 42.288 / 17.328 / 2.688 / 787 / 113.685 / 13.645 / 127.330
BOSNIA / 7,36 / 4.947 / 1.020 / 2.881 / 844 / 14.251 / 861 / 15.112
CYPRUS / 17,70 / 1.548 / 368 / 6.928 / 2.029 / 10.728 / 748 / 11.476
CROATIA / 28,54 / 5.453 / 1.298 / 11.171 / 3.272 / 60.914 / 4.248 / 65.163
EGYPT / 6,12 / 92.595 / 60.167 / 2.396 / 702 / 221.893 / 42.233 / 264.126
FRANCE / 33,68 / 79.281 / 24.156 / 13.181 / 3.861 / 1.045.005 / 93.265 / 1.138.269
GREECE / 29,88 / 13.360 / 3.044 / 11.695 / 3.426 / 156.242 / 10.428 / 166.669
ISRAEL / 28,39 / 8.996 / 4.290 / 11.112 / 3.255 / 99.968 / 13.965 / 113.932
ITALY / 29,11 / 72.458 / 14.264 / 11.393 / 3.337 / 825.483 / 47.600 / 873.083
LEBANON / 14,23 / 4.902 / 2.061 / 5.568 / 1.631 / 27.293 / 3.361 / 30.654
LIBYA / 14,33 / 7.591 / 4.768 / 5.608 / 1.643 / 42.570 / 7.831 / 50.402
MALTA / 23,58 / 510 / 125 / 9.230 / 2.704 / 4.707 / 339 / 5.046
MAROCCO / 4,60 / 36.385 / 18.508 / 1.802 / 528 / 65.561 / 9.769 / 75.330
SYRIA / 4,70 / 25.668 / 16.322 / 1.839 / 539 / 47.215 / 8.794 / 56.009
SLOVENIA / 29,69 / 2.500 / 657 / 11.619 / 3.403 / 29.043 / 2.236 / 31.279
SPAIN / 33,70 / 49.869 / 11.817 / 13.189 / 3.863 / 657.736 / 45.653 / 703.389
TUNISIA / 8,25 / 12.984 / 4.851 / 3.230 / 946 / 41.942 / 4.590 / 46.532
TURKEY / 12,48 / 85.569 / 40.707 / 4.883 / 1.430 / 417.816 / 58.220 / 476.036
MEDITER / 17,92 / 514.901 / 208.044 / 7.012 / 2.054 / 3.894.102 / 369.149 / 4.263.251

TABLE IV SYMPTOMS AND DISEASES ASSOCIATED TO SYMPTOMATIC CASES

Symptomatic adults 1:7 next 10y / Sympomatic children 1:5 next 10y / GI Symptoms / Anaemia / Osteopenia / Abnormal Liver / Shoirt Stature Children
ALBANIA / 4.298 / 1.660 / 5.064 / 2.383 / 1.787 / 596 / 332
ALGERIA / 42.288 / 17.328 / 50.674 / 23.847 / 17.885 / 5.962 / 3.466
BOSNIA / 4.947 / 1.020 / 5.072 / 2.387 / 1.790 / 597 / 204
CYPRUS / 1.548 / 368 / 1.629 / 767 / 575 / 192 / 74
CROATIA / 5.453 / 1.298 / 5.738 / 2.700 / 2.025 / 675 / 260
EGYPT / 92.595 / 60.167 / 129.848 / 61.105 / 45.829 / 15.276 / 12.033
FRANCE / 79.281 / 24.156 / 87.921 / 41.375 / 31.031 / 10.344 / 4.831
GREECE / 13.360 / 3.044 / 13.943 / 6.561 / 4.921 / 1.640 / 609
ISRAEL / 8.996 / 4.290 / 11.293 / 5.315 / 3.986 / 1.329 / 858
ITALY / 72.458 / 14.264 / 73.714 / 34.689 / 26.017 / 8.672 / 2.853
LEBANON / 4.902 / 2.061 / 5.918 / 2.785 / 2.089 / 696 / 412
LIBYA / 7.591 / 4.768 / 10.506 / 4.944 / 3.708 / 1.236 / 954
MALTA / 510 / 125 / 540 / 254 / 191 / 64 / 25
MAROCCO / 36.385 / 18.508 / 46.659 / 21.957 / 16.468 / 5.489 / 3.702
SYRIA / 25.668 / 16.322 / 35.692 / 16.796 / 12.597 / 4.199 / 3.264
SLOVENIA / 2.500 / 657 / 2.683 / 1.263 / 947 / 316 / 131
SPAIN / 49.869 / 11.817 / 52.433 / 24.674 / 18.506 / 6.169 / 2.363
TUNISIA / 12.984 / 4.851 / 15.159 / 7.134 / 5.350 / 1.783 / 970
TURKEY / 85.569 / 40.707 / 107.335 / 50.511 / 37.883 / 12.628 / 8.141
MEDIT / 514.901 / 208.044 / 661.823 / 311.446 / 233.584 / 77.861 / 45.483

TABLE V : EXCESS MORTALITY IN THE UNDIAGNOSED CASES

Undiagnosed Celiacs have 1,8 Standard Mortality Rate (Nat.Rev.Gastroenterol Hepatol. 2010 Mar;7(3):158-62) / projected prevalence of CD in next 10 yrs / Death rate deaths/ 1,000 population / Population Expected Deaths next 10 y / Celiacs Deaths Next 10 y / Excess Death in Celiacs next 10 yr
ALBANIA / 38.382 / 5,07 / 184.520 / 3.503 / 1.557
ALGERIA / 382.659 / 4,64 / 1.585.868 / 31.960 / 14.204
BOSNIA / 39.728 / 8,63 / 331.613 / 6.171 / 2.743
CYPRUS / 12.681 / 6,4 / 69.424 / 1.461 / 649
CROATIA / 44.661 / 11,75 / 527.506 / 9.446 / 4.198
EGYPT / 949.002 / 4,88 / 3.848.692 / 83.360 / 37.049
FRANCE / 675.746 / 8,56 / 5.483.347 / 104.119 / 46.275
GREECE / 108.738 / 10,51 / 1.128.504 / 20.571 / 9.143
ISRAEL / 84.425 / 5,43 / 392.790 / 8.252 / 3.667
ITALY / 578.530 / 10,72 / 6.231.130 / 111.633 / 49.615
LEBANON / 44.618 / 6,03 / 242.231 / 4.843 / 2.152
LIBYA / 76.980 / 3,41 / 215.661 / 4.725 / 2.100
MALTA / 4.197 / 8,38 / 33.816 / 633 / 281
MAROCCO / 347.234 / 4,74 / 1.482.917 / 29.626 / 13.167
SYRIA / 261.286 / 3,72 / 809.583 / 17.496 / 7.776
SLOVENIA / 20.782 / 9,2 / 188.322 / 3.441 / 1.530
SPAIN / 408.168 / 9,99 / 4.048.448 / 73.397 / 32.621
TUNISIA / 115.140 / 5,2 / 545.290 / 10.777 / 4.790
TURKEY / 802.520 / 6 / 4.353.679 / 86.672 / 38.521
MEDIT / 4.995.476 / 7,01 / 31.703.339 / 612.086 / 272.038

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