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Genetics and genomic medicine in Tunisia

2018; Wiley; Volume: 6; Issue: 2 Linguagem: Inglês

10.1002/mgg3.392

2324-9269

Houda Elloumi‐Zghal, Habiba Chaabouni Bouhamed,

Genetics and Neurodevelopmental Disorders

Genetics and genomic medicine in Tunisia. A Carthagian beauty who is still, from the Andalusia time, carries in her voice, a flowing hymn. O Tunisia, the dreams, you are the guard of arts, melodies, and scents. Farooq Juwaida Tunisia is situated on the northern coast of Africa, bordered by Algeria to the west, Libya to the southeast and the Mediterranean Sea along its northern and eastern sides (Figure 1). It is the smallest country in North Africa and covers 163,610.0 sq. km; slightly larger than Georgia (World bank #92), with 1,148 km of coastline. Tunisia is divided into 24 governorates; the capital Tunis is the smallest and the most populated. As of 1 July 2015, the number of inhabitants was 11,154,370 (5,557,966 males and 5,596,404 females), 2.94 times higher since independence (3.78 millions in 1956). About 45% of the population is represented by individuals between the ages of 25 and 54, with a median age of 32.4 years. The growth rate is estimated at 0.86%. The majority of the population occupies the northern and coastal region of the country, with 66.8% living in urban areas. Because of its strategic location at the crossroads of Europe, Africa and the Middle East, Tunisia witnessed the succession of many civilizations throughout its history. Its population is ethnically heterogeneous, with the presence of the indigenous Berbers together with people from the invading civilizations (Phoenicians, romans, Arabs, and others) as well as from migration. Formal Arabic is the official language, however, natives speak a dialect of Tunisian Arabic and Shilha is still used by Berbers. French is the language used in most of the institutions; it plays an important role in education and the press. English is currently considered the second foreign language and it is now introduced at the elementary school level. The overwhelming majority of Tunisians (98%) are Muslim, the rest are Christians, Jews, and others. The Tunisian family size average is 4.1; it is getting smaller in big cities (General population census 2014, National Institute of Statistics). There is prevalence of consanguineous marriages and geographic endogamy, mainly in the more rural areas. Consanguinity rate ranges from 20.1% to 39.33% (Ben Arab, Masmoudi, Beltaief, Hachicha, & Ayadi, 2004; Riou, el Younsi, & Chaabouni, 1989). Based on the 2014 statistics, Tunisia is classified in the high development category with a human development index (HDI) value of 0.721 compared to 0.486 in 1980, an increase of 48.4%. Furthermore, the gross national income per capita increased by 101.8%. However, this development is unevenly distributed and is much higher in the eastern coastal regions. Regional inequities are considered the main barrier to socioeconomic development, with more developed coastal regions and an impoverished interior. As per 2010 data, 15.5% of the population is living below the poverty line. Such gaps between the different regions became more evident after the 2011 revolution (Hermassi, 2013). A few years after the revolution, Tunisia's economy remains weak, with a high unemployment rate (17.6%); particularly among young people and university graduates where it reaches 37.6%. This situation led to labor emigration mainly to European countries. Bilateral labors agreements were signed with a number of these countries with the expectation that these young workers will later return home. Unfortunately, the lack of job creation in Tunisia together with skill mismatches and the imposed restriction of immigration by European countries created a massive illegal migration flow (mainly to Europe). Furthermore, this situation worsened following the Civil war in Libya as around 1.8 million Libyans have fled to Tunisia. Just after the independence, our first president, Habib Bourguiba, enacted a law that allows all inhabitants to have access to free schools regardless of their religion, sex or race. Later, in 1991, the first 9 years of schooling became compulsory and education was established as a national priority. However, the government does not mandate preschool, and most of the facilities are private. In 2008, the World Bank reported that 96.79% of people between the ages of 15 and 24 were literate, which provides a strong foundation of hope for the future of literacy in Tunisia. The rate of illiteracy among women was somewhat higher than that among men. The 2014 data showed that 32.8% of adult Tunisian women have reached at least a secondary level of education compared to 46.1% of their male counterparts. The report showed that 31.3% of parliamentary seats are hold by women, compared to only 14% in Arab states. However, female participation in the labor force is much lower compared to men (25.1 versus 70.9%). The education system in Tunisia is recognized as one of the most modernized in the region. Several laws were instated to help with the integration of special needs students. However, not enough specialized centers to help patients with developmental and cognitive delays are offered and the increase in the number of integrative schools was paralleled by an increase in enrolled students. Furthermore, there is a lack for trained professionals that can meet the needs of these patients. UNICEF data showed that 90% of teachers in integrative schools are not prepared to teach special education and did not receive any formal and specific training (Shaub, 2016). Evidence of Paleolithic settlement was found in different archeological sites in Tunisia, one of the oldest being Sidi Zin in the Northwest of the country (Gragueb, 1980). Excavated by Gobert in 1950, the site of Sidi Zin is located 11 km south of the city of Kef, and is particularly known for its Acheulian levels. Artifacts from the Mousterian level, characteristic of the middle Paleolithic, were also found and included small bifaces, sidescrapers, and thick points (Aouadi-Abdeljaouad & Belhouchet, 2012). During recent excavations by Tunisian and British researchers near Tozeur, in the southwest of the country, flint tools—among other artifacts—were discovered and reported to be the oldest evidence of human activity in Tunisia (92,000-years old). Bones indicating the presence of savannah animals and therefore fresh water were unearthed. The excavation of the Aïn El-Guettar Mousterian site, located approximately 15 km southeast of Gafsa, yielded a faunal assemblage dominated by bovids and equids. The site was associated with a lithic industry with Levallois technology (Aouadi-Abdeljaouad & Belhouchet, 2008; Gruet, 1954). The same site also showed the presence of the Aterian, another Middle Stone age culture. The Aterian industry is based mostly of flakes, Levallois techniques, scrapers and racloir tools. The earliest Aterian sites are believed to be well over 40,000-year old (Frigi, Cherni, Fadhlaoui-Zid, & Benammar-Elgaaied, 2010). Furthermore, stone tools were found in the northern and central coastal areas of Tunisia going back to the Aterian civilization. Small flint tools of around 20,000 BC were attributed to a new culture that became the precursor to North Africa's Iberomaurusian civilization (18,000 to 8,000 BC). Small retouched blades, backed bladelets, simple endscrapers, geometrical pieces, among other artifacts were found in the site of Ouchtata, northwest of Tunisia. The Iberomaurusian people belonged to the Mechtoid anthropological type, also known as Mechta el-Arbi or Mechta-Afalou that inhabited the region during the late Paleolithic and Mesolithic. The Iberomaurusian culture was thought to have emerged either as a result of the migration of Cromagnoids from the Iberian Peninsula, or from the local Aterian culture (Ferembach, 1985). During the Holocene, the Capsian civilization covered the period between 10,000 and 7,500 BP. This culture was discovered during the excavation of the site of El-Mekta, located by Boudy in 1906 on the eponymous hill, 10 km north of Gafsa in southwest Tunisia (Morales et al., 2015) (Figure 2). Archeologists were able to find stone and bone tools, shell beads and decorated bones, ostrich shell containers, as well as stylized women's heads carved from limestone. The Capsians left shell heaps near their dwellings, indicating that snails were an important part of their diet. Evidence for hunting, fishing, food processing and cooking was also abundant. Remains of Aleppo pine as well as Acorns were the commonly detected in the plant assemblage recovered from site El-Mekta (Morales et al., 2015). Capsians might be the immediate ancestors of Berbers (Rahmani, 2004). The later Neolithic people possibly introduced the Afro-Asiatic languages (Arredi et al., 2004; Sanchez-Mazas, 2000). The indigenous Berbers of Tunisia are called "Amazigh" which means "free people". During the historical period, the first important invasion was that of the Phoenicians, ancestors of present-day Lebanese, who used their maritime expertise to establish trading posts in many cities across the Mediterranean (Zalloua et al., 2008). In the eigth century B.C (around 814 BCE), after she fled from her brother Pygmalion, king of Tyre (what is today Lebanon), Elissa, also known as "Dido", and her followers established the colony of "Kart-Hadasht" (latin Carthago) known as "Carthage" and meaning "New City". Carthage later became the greatest naval power of the Mediterranean. The temple of Eshmun, the Punic god of healing, was at that time built on the peak of Byrsa Hill, the highest point in the city of Carthage. During the Roman Empire, a cathedral (known now as Saint Louis Cathedral) was built atop of its ruins. All we know about the Phoenicians is through Greek and Roman sources, since all evidence was destroyed and the Carthaginian literature was lost. Recently, a Punic burial crypt was accidentally discovered by gardeners while planting a tree at the front of the National Museum of Carthage, situated on Byrsa Hill, at the site of the Phoenician acropolis (http://www.inp.rnrt.tn/index.php?option=com_content&view=article&id=75:jeune-homme-de-byrsa&catid=3: activites&Itemid=7&lang=en). The skeletal remains of a young man along with funerary goods were found, all dated to the late sixth century BC (Morel, 2011). DNA extracted from a small bone sample was used for the first complete ancient Phoenician mitochondrial genome study. An international team of researchers showed that the mitochondrial genome of this "young man of Byrsa" belongs to the haplogroup U5b2c1, a European derived haplotype absent in North Africa and in Lebanese (Matisoo-Smith et al., 2016). Data from other remain throughout the Mediterranean will help us understand the origin of Phoenicians and trace their migrations. Following the third Punic war (149–146 BCE) between the Romans and Phoenicians, the Roman Empire became the most powerful force in the Mediterranean region and the region was completely Latinized and Christianized. The Vandals, a Germanic tribe, later succeeded Romans; they reigned for almost a century before falling to the armies of Byzantines in 533 AD (Brett & Fentress, 1997). By the end of the seventh century A.D, the Islamic invasion of North Africa was carried by armies from the Arabian Peninsula (Lapidus, 2002). They founded the city of Kairouan, about 90 miles south of Carthage, and they spread Islam as well as the Arabic language in the region. Fatimids' invasion then followed in the 11th century AD. The Ottomans then ruled Tunisia for over 400 years. During the 16th and 17th centuries, epidemic waves, cricket invasions, and starvations led to the death of thousands of individuals. Tunis was then affected by the plague for 19 years; nearly 1,000 individuals died because of epidemics of plague, cholera and typhus in 1918. As the Ottoman Empire declined, the Berlin Congress of 1878 convened to discuss the future of the North African provinces. As a result, Britain acquiesced to France's control of Tunisia and in exchange took over Cyprus. In 1881, the French sent their troops to invade Tunisia and imposed the treaty of Bardo. In 1883, the Bey of Tunis signed an agreement that made Tunisia a French protectorate. It is not until 1956 that Tunisia got her independence from France and became a republic under the leader Habib Bourguiba. On 25 July, 1957, a republic was declared and Bourguiba became the first president of Tunisia. In November 1987, his appointed first prime minister "Ben Ali" removed him from power after a bloodless coup. The latter stayed in power for 23 years until the Tunisian revolution and the collapse of the regime on 14 January 2011. On 27 January 2014, the new president signed the latest approved constitution replacing the one instated in 1959 and amended in 1988 and 2002. The country is still recovering after this political unrest and the violence threatening economic progress. Although Berbers are the autochthonous inhabitants of the country, the major historical settlements had a crucial impact on the genetic structure and diversity of the current population. As a result, the latter derives its origins from Phoenicians, Romans, Vandals, Byzantines, Africans, Arabs, Turks, Europeans as well as immigrants. Despite all these historical admixtures, some genetic isolates still exist. The best example is the inhabitants of Jerba, an island in the South-East of Tunisia (Loueslati et al., 2006). To determine the degree of heterogeneity of this population, analysis of 16 Alu and 3 Alu/STR compound systems was carried on 268 healthy unrelated individuals originating from the north-center and the south regions. Similar levels of gene diversity were found in both groups. Interestingly, the northern sample showed higher frequencies of Berber and sub-Saharan African-specific combinations than the southern sample (El Moncer et al., 2010). An indication of sub-Saharan gene flow was also shown by a previous mtDNA haplotype data (Turchi et al., 2009). Trans-Saharan trade is believed to be the main source of the African flow to the region, although few came from the Arab invasions and from Europe during the colonization of the Maghreb (Northwest Africa). South Tunisia constituted the gateway for Arab tribes invading North African cities. Archeological and historic records suggest that such migration is ancient and could be traced back to 9000 years BP, characterized by an ethnic contribution from present-day Sudan (El Moncer et al., 2010). According to the official census in 2014, the population living in the south of the country comprises Berbers, Black people, Jews, and Arabs. Most of the studies agreed that the southern Tunisians are native Berbers that were later Arabized during the Arab invasions in the 11th century (Hajjej et al., 2006; Hajjej, Sellami, et al., 2011). In an effort to trace the origin of the southern population, a recent "anthropological" study of 250 unrelated Southern Tunisians was conducted using HLA typing, commonly used to track human migrations (Fernandez Vina et al., 2012). Data were compared to those of other Tunisians, Middle Eastern Arab-speaking individuals along with Mediterranean and sub-Sahara African populations. DRB1*07:01–DQB1*02:02 was found to be the most frequent haplotype in Southern Tunisians (18.02%). This haplotype was also present in Tunisian Berbers (16.03%) (Hajjej, Almawi, Hattab, El-Gaaied, & Hmida, 2016). In fact, the HLA class II allele DRB1*07:01 was present at 22.06% in the southern population, and was detected at high frequencies in Tunisian Berbers (17.6%) and in Ghannouchians (28.7%) occupying a village situated at the eastern south of Tunisia and characterized by high endogamy, behaving like an isolate (Hajjej, Hajjej, et al., 2011). Following the Arab invasion of Tunisia, Berbers migrated to the south and populated the mountainous regions to escape persecution. This resulted in a low admixture between them and the Arab tribes. This fact was further confirmed by the HLA typing data that demonstrated the low contribution of Arabs to the southern genetic pool (Hajjej et al., 2016). A Y-chromosome lineage analysis was carried on 94 individuals from three Northern and southern Berber-speaking isolates. Two of the isolates exclusively carried the haplogroup E1b1b1b, also found in other Berber-speaking groups in North Africa. These two groups lived in the mountains, and historically escaped persecution by the Arab tribes "Banu Hilal and Banu Soulaym" around 1048 AD. Haplogroup J (subtype J1e), previously associated with the Islamic expansion, was found in 31.4% of the third Berber group, living in the plains, indicative of genetic admixture and gene flow from the Near East. However, and in contrast to the mtDNA studies findings, the Y-chromosome data did not show any evidence of sub-Saharan African paternal lineages (Fadhlaoui-Zid et al., 2004, 2011). Another study investigating the profile of HLA class I and class II genes was carried on a total of randomly selected 376 unrelated Tunisians originating from the North, South and center of the country. A*02:01(16.76%) and DRB1*07:01 (19.02%) alleles, both present at high frequency in Berbers, were found to be the most frequent alleles. Common haplotypes found in Tunisians were also seen in Western Mediterranean populations. There was no evidence of an effect of the Arab invasions (7th and 11th centuries AD) on the genetic makeup of the Tunisians including the autochthonous Berbers. This suggests that no or minimum admixtures occurred between Berbers and Arab tribes. One possible explanation can be the modest number of Arab invaders during the 7th century. Moreover, establishment of settlements did not follow this invasion. Haplotype studies showed that the current inhabitants of the country are closely related to Iberians (Basques and Spaniards) as well as to North Africans but not to Eastern Arabs (Hajjej, Almawi, Hattab, El-Gaaied, & Hmida, 2015). Following the Bizerte crisis with France and the 6-day War of 1967, thousands of Jews fled the country. Nowadays, Tunisian Jews constitute less than 0.1% of the total population (1,500); they are mainly clustered in the island of Jerba. Although they constitute a distinct branch, North African Jews showed a significant relatedness to European and Middle Eastern Jews. The Jews from Jerba and the rest of Tunisia were highly endogamous, with very low level of admixture with Arab and Berber inhabitants as shown by Y-chromosome studies (Campbell et al., 2012). It is believed that the first evidence for Jews in North Africa goes back to 312 BCE when King Ptolemy of Egypt settled Jews in the cities of Cyrenaica in current-day Libya. Historians also reported that in 70 CE, the Roman Emperor Titus destroyed the Great Temple of Jerusalem leading to the deportation of 30,000 Jews to Carthage in present-day Tunisia. Others traced the origins of Jews in Tunisia to Andalus and Levant (Lucette & Abraham, 1991). Following the Arab invasion, some Jewish communities remained in the country but were subject to civil and religious suppression resulting in the high degree of endogamy. The newly drafted constitution in 2014 placed national health care at a higher priority and "proclaimed health as a human right and required national healthcare coverage for the poorest of Tunisians" under Article 38. Since its independence in 1956, Tunisia made health care free for all through a government-funded system. Four years later, a social protection system with a health insurance scheme and a subsidized care was implemented. In 1996, the implementation of "large scale reform" was intended to improve coverage and accessibility to healthcare (Achour, 2011). Several insurance plans covering different professional groups were merged under the "social security Fund". The benefit package was also extended to include providers in the private sector. Furthermore, an optional complementary health insurance managed by mutual health insurance companies was also introduced. Following the 2004 reform, Tunisia's National Health Insurance Fund "CNAM" (Caisse nationale d'Assurance maladie) was created, aiming to provide universal health coverage for those affiliated with national insurances (CNSS and CNRPS). Coverage was extended to include inpatient and outpatient services provided by the private sector. In late 2007, CNAM introduced a reimbursement scheme also called the "two sector scheme", where beneficiaries can use either public or private providers but are required to first pay then request reimbursement from the CNAM (Makhloufi, Ventelou, & Abu-Zaineh, 2015). Such reform has raised the coverage from 54.6% in 1995 to 88% in 2008 (Abu-Zaineh, Romdhane, Ventelou, Moatti, & Chokri, 2013). The current health insurance coverage consists of two main insurance schemes, a formal mandatory health insurance (MHI), currently run by CNAM, and a state-subsidized medical assistance scheme (MAS). The MHI covers the public and the private sector employees as well as self-employed workers. Most of those ineligible for MHI scheme are entitled to MAS, publicly funded and managed by the Ministry of Social Affairs. Individuals living on the poverty line or earning the minimum wage rate are entitled to receive "Free medical cards" or a "reduced-fee plans" respectively, both accepted by public sector healthcare services. Data from the Tunisian HealthCare Utilization and Morbidity Survey showed that 66% of the population are covered by MHI, 22% benefit from MAS, while about 12% remains without access to health insurance coverage (National institute of public health 2008). In recent years, a few private insurance schemes were developed but only benefited a small portion of the population (Abu-Zaineh et al., 2013). Recent data showed that the Tunisian household spend a lot of money on healthcare, and the average out of pocket payments represented almost 45% of the total health expenditure in 2010 (Chahed & Arfa, 2014). Furthermore, although CNAM partially covers birth-related health expenses at private facilities, it does not cover costs related to premature births, which are much higher. Although the health insurance package allows the enrollees to use providers from private and public facilities, and despite the existence of two insurance schemes, the system has its flaws. The reimbursement mechanisms limit coverage for a predetermined list of chronic illnesses and surgical interventions, and reimbursement is subject to an annual expenditure capita per household. Moreover, the public facilities are underfunded; in particular, after 2011, many medications and lab tests are not available, and the number of specialist and doctors is insufficient outside big cities and coastal regions. In addition and because of the limited budget of these facilities and the inefficient management, most of the equipment is not serviced and never replaced. On the other hand, the private sector entails high copayments and extra fees making it impossible for a large number of inhabitants to afford it. Since 1982, the country implemented a large network of primary health care centers. Currently, health care services are provided by three different sectors: public, private, and parastatal. Based on the national Statistics Institute and the Ministry of Public Health (MoPH), there are currently 14 general hospitals, 22 Institutes, centers and specialized hospitals mainly located in the large urban cities, 36 regional hospitals providing secondary care, 110 public district hospitals (PDHs), and 2,123 basic health centers. The public health infrastructure is expanding; as such new projects are underway including a second University Hospital in Sfax and another four hospitals or centers planned. The private sector is the second provider of health care in the country. As of 2014, it operates 82 clinics, with 7,283 medical offices. The parastatal sector is managed by other public departments such as the social security fund (SSF), operates four hospitals, representing 2.5% of hospital beds, six polyclinics, and nine healthcare facilities offering in-house medical services. MoPH manages all of the public sector facilities, comprising 85% of total hospital beds and more than 55% of medical personnel (Abu-Zaineh et al., 2013). Public hospitals receive 55% of total outpatient and inpatient care in the country (Ministry of health. Annual Statistical book of hospital's indicators. Tunisia: Department of publics' Hospital; 2011). Despite the increase in the number of hospitals and clinics, about 69% of the total hospital capacity is concentrated in the eastern coastal region of the country. Because of these striking regional differences, many areas have no access to medical services. In 2012, hospital bed density reached 2.1 per 1,000 (Ministry of health, MoH). Overall, the average medical doctor's density is about 1.1 per 1,000, however, it is remarkably uneven, ranging from 3.3 to 3.5 doctors for every 1,000 people in the governorates of Tunis, Sfax and Medinine to 0.2 to 0.4 in the south of the country. In 2014, the total expenditure of Tunisian healthcare system was about 7% of GDP (gross domestic product). Although it is covering 80% of the population, the public sector receives only 20% of the total health expenditures, while the private facilities benefit from 60%. Just after the declaration of independence in 1956, the "Code of Personal Status" was instituted. These laws were one of the most revolutionary in the Arab and Islamic world. Tunisia was the first country in the region to abolish polygamy. The law also ensured the right to equal pay for men and women. Since 1959, Tunisian woman received the right to vote and to stand for election. The right to use contraceptives was protected under law since 1961. A family planning program was instituted in 1966, raising the legal age of marriage and providing free access to contraception and counseling for all women throughout the country. Contraceptive usage rate was estimated at 62.5% in 2012 (WHO). First in Africa, this plan also aimed to slow the population growth. The fertility rate is one of the lowest in the region, decreasing from seven children per woman in 1960 to only two currently (CIA world factbook: https://www.cia.gov/library/publications/the-world-factbook/geos/ts.html). The National Board for Family and Population was later created in 1973, and abortion was legalized for any woman within the first trimester regardless of husband's approval (Hajri, Raifman, Gerdts, Baum, & Foster, 2015). Reproductive health services are provided mainly by a network of 2,091 primary health care centers, 36 reproductive health centers, and 20 youth centers [Ministère de la Santé, Direction de la Santé et de la Planification, Carte sanitaire 2011 (Tunis: Ministère de la Santé, May 2013)]. However, they are unevenly distributed between the remote rural areas and more industrialized regions. For more detailed information, please refer to the following site: http://www.santetunisie.rns.tn/images/articles/csfinale2011.pdf Since 2001, primary health care services include prevention and treatment of sexually transmitted infections with free and confidential HIV tests; furthermore, antiretroviral drugs are freely provided. During the last 50 years, Tunisia made big progress in increasing life expectancy and decreasing infant mortality. The average life expectancy was 74.9-year old in 2014 (73.9 for men and 77.4 for women) with an increase by 12.8 years compared to 1980 (Human development report 2015: http://www.factfish.com/statistic-country/tunisia/human%20development%20index). A decline of infant mortality rate (before reaching 1 year of age) was achieved, decreasing from 178.7 per 1,000 in 1962 to 51.4 per 1,000 in 1985, and to an estimated 12.1 per 1,000 live births currently. Such rates are two times higher in the rural areas than in the urban ones. In 2015, WHO reported a neonatal mortality rate of 8.2 [5.8–11.4] compared to 16.1 [13.5–19.0] in 2002. Reproductive health is measured by maternal mortality and adolescent birth rates. For every 100,000 live births, 46 women die from pregnancy related causes, this marks a striking improvement compared to 131 per 100,000 in 1990. Deliveries attended by skilled personnel reached 97.6% in 2013, compared to only 76.3% in 1990. Adolescent birth rate is estimated at 4.6 births per 1,000. The current birth rate is 16.4 births per 1,000 while the death rate is 5.7 per 1,000 inhabitants, 2,411 stillbirths were reported (https://knoema.com/atlas/Tunisia/Infant-mortality). The incidence of tuberculosis is estimated at 35 per 100,000 people in 2014. This number includes new pulmonary, smear positive, and extrapulmonary tuberculosis cases (Knoema data). Unlike other North African countries, Tunisia has no malaria and only a few cases of HIV. Increased vaccinations among youth led to the almost complete eradication of polio, measles, and neonatal tetanus. In recent years, the life expectancy at birth has increased with 3% of deaths being due to communicable diseases while noncommunicable diseases accounted for 72% of deaths. (http://www.borgenmagazine.com/strengthening-tunisias-healthcare-system/). The population in Tunisia is now aging. With a change in the life style, the burden has shifted from infectious diseases to the emergence of noncommunicable and chronic diseases (hypertension and diabetes) as well as injuries. The top three causes of mortality are ischemic heart disease, cancers and respiratory tract diseases. An increased prevalence of obesity was recorded, with a rate of 27.1% in adults in 2014 (CIA factbook). Breast cancer and cervical cancer screening have also been introduced into basic health care services as part of the country's National Cancer Control Plans. [Ministère de la Santé, Direction de Santé, Plan pour la lutte contre le cancer 2015–2019 (Tunis: Ministère de la Santé, 2015).] Tunisia counts 12 officially registered transplant centers (http://