Female students (number) 0 800,000 1,600,000 2,400,000 2000 2002 2004 2006 2008 2010 2012 2014 Social sciences Medical sciences Engineering Basic sciences fields Art sciences Agriculture All subjects A B Historical timeline of contemporary Sanctions are intensified Anglo- Beginning Sanctions Constitutional revolution Soviet of Iran- are lifted and foundation of the first Occupation War Iranian parliament of Iran Sanctions End of Iran- Anglo- (WW II) are Iraq War American enforced Coup

1785 1850 1910 1925 1941 1951 1953 1979 1980 1988 2010 2016

Foundation of Pahlavi Islamic Amir Kabir Reforms Dynasty Nationalization Revolution of Iranian Oil 52 wks Industry Reign of Qajar Dynasty

45 wks First Pahlavi Era

23.8 wks Second Pahlavi Era Phase III

Islamic Republic Period

Fertility rate, total (births per woman)

1970 0 2 4 6 1975 1980 1985 1990 1995 2000 2005 2010 2015 World Africa Middle EastandNorth Iran Figure 1- Development of modern system in Iran

Dar al-Fonun is founded Foundation of the Faculty of is More than 50 public Department of Medicine is University of Tehran established at the University of medical schools are established at Dar al-Fonun Tehran founded in Iran operates independently

1851 1860 1918 1923 1928 1934 1950 1956 1966 1970 2012 2016

Department of Pharmacy Foundation of is established at Dar al- Shiraz, Tabriz, and Fonun Mashhad Medical Seven medical schools are The first Iranian tutors were Schools founded in different cities of employed at Dar al-Fonun A bill was passed to send Iran student abroad for education

Faculty of Dentistry is founded at the University of Tehran Infection control timeline A leprosy rehabilitation center is founded in Khorasan Parliament National approves a Pasteur National malaria National smallpox free institute is A leprosarium is eradication institute of vaccination vaccination founded established in Tabriz program is public health is campaign program launched established

1850 1910 1921 1926 1933 1934 1939 1942 1947 1950 1952 1961 1965 1978

A vaccination Smallpox is official bill is passed Vaccination Institute of A plague eradicated by the department of Malariology A TB research in Iran parliament the Pasteur is founded sanitarium center is Institute is at the is founded formed by Institute of formed Pasteur in Tehran Institute the Pasteur parasitology Institute and Malariology is founded at Pasteur Institute Under−5 Mortality Rate (per 1,000) Population (number in thousands) 0 50 100 150 200 0 10,000 20,000 30,000 40,000 1970 1970 C A 1975 1975 1980 1980 1985 1985 1990 1990 1995 1995 2000 2000 2005 2005 2010 2010 2015 2015 genders Both Male Female

Adult Mortality Rate (per 1,000) Life expectancy (at birth) 0 150 300 450 600 0 20 40 60 80 1970 1970 D B 1975 1975 1980 1980 1985 1985 1990 1990 1995 1995 2000 2000 2005 2005 2010 2010 2015 2015 Male Female Male Female Figure Legends

Figure 1. Prime Minister Mohammed Mosaddegh.

(image may be subject to copyright)

Figure 2. Tertiary education attainment rate in Iranian female university students

(data from the online database of Statistical Center of Iran at https://www.amar.org.ir/english/Databases-Systems/Time-Series)

Figure 3. Artificial eye back to 2800-2900 B.C. (A) and trepanned skull surgery for hydrocephalus from 4800 years ago (B) in Shahr-I Sokhta,

(the permission to use these images is granted)

Figure 4. Avicenna

(image may be subject to copyright)

Figure 5. Timeline of major sociopolitical events in Iranian history, 1785 – 2016

Figure 6. Total fertility rate in Iran, the Middle East and North Africa, and the world

(data from the online database of the world bank available at https://data.worldbank.org/indicator/)

Figure 7. Timeline of major events in medical , 1951 – 2016

Figure 8. Timeline of major events in Iran to address public health challenges and infectious diseases,

1850 - 1978

Figure 9. Trends in population size (A), life-expectancy at birth (B), under-5 mortality (C), and adult mortality (D) in Iran, 1970 to 2015

(data from the Global Burden of Diseases 2015 study available at http://www.healthdata.org/gbd/data -A and B-, from the the National and Sub-National Burden of Diseases, Injuries, and Risk Factors, published in Measuring Iran's success in achieving

Millennium Development Goal 4: a systematic analysis of under-5 mortalities at national and

subnational levels from 1990 to 2015 Mohammadi, Younes et al. The Lancet Global Health, Volume

5, Issue 5, e537 - e544 -C-, and from the online database of the world bank available at https://data.worldbank.org/indicator/) Side panels

Panel 1: The approach we followed in the development of this paper (methods)

In the preparation of this manuscript, the following steps were designed and followed. We initially developed a preliminary conceptual framework based on the existing historical and well- documented facts about Iranian history of medicine, followed by a systematic review of Persian and English literature to identify sentinel events or breakthroughs for inclusion in this paper. We then identified relevant English and Persian material through searching available databases, including PubMed, Google Scholar, and Scientific Information Database (SID, a Persian database), without any time-period limitation and using different combinations of the relevant words, such as ‘Health’, ‘Medicine’, ‘Sciences’, ‘Research’, and ‘Education’, restricted to Iran. Subsequently, we expanded our search to the references of the manuscripts we found. We did not confine our search to any specific type of manuscript and included all relevant papers, books, and historical reports, both in English and Persian. Then we sorted the extracted milestones and breakthroughs to depict a timeline showing different time periods. We also developed a process to acquire feedbacks from renowned Iranian scholars, who are considered to be experts in the field of Iranian

History of Medicine. Moreover, the progressing version of the manuscript was sent to the aforementioned scholars at different stages, and the contents were revised based on their comments and guidance. Furthermore, it was presented in several sessions and the comments of the invited experts were applied to the subsequent revisions of the manuscript. After drafting the main conceptual framework of the paper, using peer discussion interactive method, several rounds of expert peer review were followed to integrate the scientific evidence based on their opinions, to complete all of the pre-defined sections of the manuscript. Panel 2: Medical research and scientific productions

From ancient times to the present day, Iran has witnessed formal and non-formal research structures carrying out medical research. However, it was only in recent years that research and scientific productions reached their climax in the country, [1-3] and the invention and production

of high-tech products significantly increased. [4] During recent decades, Iranian researchers have

been particularly productive in several fields, such as pharmacology, toxicology, chemistry,

physics, computer sciences, engineering, and clinical medicine. [5, 6] This upsurge coincides with

the introduction of one of the main national conventions in Iran; the ‘Health Innovation and

Science Development Plan’, which has been developed based on the ‘2025 Vision of Iran’

document. Indeed, the ‘Comprehensive Scientific Map of Iran’ (which includes the ‘Health

Innovation and Science Development Plan’) outlines a coordinated and dynamic collection of

goals, policies, strategies, and requisites, which will direct the country toward being recognized as

one of the leading nations in science in the region.

At several junctures, scientific production was affected by different conditions such as the Islamic

revolution, war and political instability. [6-8] Particularly, during the 1980s, as a result of war,

embargo, and emigration of many skilled scholars, science production in Iran showed a significant

decline. [1, 9] However, in the 1990s, different policies focused on supporting research activities

and production of knowledge were adopted. Based on a report in 2010, Iranian science

productions had the fastest growth rates in the world and expanded 11 times faster than the mean

of world science production growth, only followed by Turkey, with a scientific publication growth

rate five times faster than the global average. [3] Most of Iran’s scientific publications are done

without research collaboration with the outside world. [10] This could be a major challenge as it may keep the scientists and academics away from the benefits of collaboration and partnership.

The proportion of papers produced in collaboration with other countries decreased from 35% in

1996 to less than 20% in 2008. [1] Although this might mean that the country could continue to grow its products despite relative isolations and the difficulties the academics confronted in publishing articles and attending international conferences (due to costs and difficulties in obtaining visas), it calls for actions to reverse this trend. Moreover, limitations in research can be attributed to under-investment in Research and Development (R&D) systems in the country. [11]

That aside, only a small fraction (about 0.5%) of these outputs are categorized into the highly cited publication group, i.e. have a notable impact on the academic community. [11] There are also signs that within the last couple of years the growth has slowed down, and hence, more investment is needed if the country hopes to reach leading countries in terms of scientific impact in the future. Panel 3: The national Iranian thalassemia prevention program

Beta-thalassemia is one of the most common hereditary diseases in Iran, with 4.5% of the population carrying at least one of the genes (about 10% around the north and south). [12] The

Thalassemia Prevention Program was established in 1995-1997 and was designed as a first

example of controlling a genetic disease through the primary healthcare network with the main

strategy of screening couples intending to get married. [12] Two national networks of genetic

counseling centers and prenatal genetic diagnostic labs were developed and integrated into the

network. In the screening program, couples detected as carriers of beta-thalassemia are offered

genetic counseling. Those who test positive but choose to proceed with their marriage are offered

genetic testing for their children. Selective abortion is permitted based on the law and religious

decree. [13, 14]

The incidence of new cases of thalassemia major, estimated to be around 1 per thousand live

births in 1997, declined by more than 70% during the implementation of the program. [15-17] This

decline was mostly due to prenatal diagnosis, which was carried out by the members of the

national genetic diagnosis network. [18] Following this decline, scientists and policy makers are

focusing on controlling alpha-thalassemia HbH disease, [19-22] which is much less common. The

success of this program has been acknowledged by various national and international

organizations [15, 17, 23, 24] and has been proposed as a model for other countries [25] to develop

community-level genetic screening programs for disorders such as phenylketonuria, hemophilia

and inborn errors of metabolism. Panel 4: Controlling iodine deficiency in Iran

Iodine deficiency is the leading cause of preventable mental retardation worldwide. Two decades

ago Iran was among the countries severely affected by iodine deficiency. Various research projects

conducted in different provinces reported a high prevalence of goiter with low urinary iodine

excretion in many individuals. [26-28]

Since 1989, iodine deficiency disorder (IDD) has been identified as a priority health problem in

Iran. Thereafter, salt iodization began in 1990, and the production and distribution of iodized salt along with public education increased gradually. By 1993, however, only 70% of urban and 50% of rural households consumed iodized salt. A law for the mandatory production of iodized salt was passed in 1994 and the IDD elimination program, using universal salt iodization (USI), was

implemented in the same year, fulfilling 10 programmatic indicators set by WHO/UNICEF/ICCIDD.

The results of the second national survey in 1996, 7 years after the initiation of salt iodization and

2 years after USI, showed the effectiveness of the program with urinary iodine excretion levels exceeding 100 μg/L in 85% of participants, more than 90% of households’ consumption of iodized salt, and a marked reduction in goiter prevalence. [29, 30]

Iran was announced to be IDD free by WHO-EMRO in the year 2000. National monitoring surveys

on goiter, urinary iodine, and household consumption of iodized salt conducted every 5 years

indicated the sustainability of IDD elimination in Iran. [26, 27, 29, 30] Panel 5: Ethical and legal aspects of organ transplantation

Iran has a long history of organ transplantation and is one of the most successful countries in the Middle Eastern region in terms of the number of transplantations conducted per capita.

[31] Transplantation activity in Iran began in 1935, when the first corneal transplant was performed, followed by kidney (1968), bone marrow (1991), liver (1993), heart (1993), and lung transplantations (2000). [32-34]

However, ethical considerations and concerns have been frequently discussed among physicians, legal experts, and religious scholars. Many ethical concerns focus on Iran’s model of encouraging live kidney donations. [35-37] Opponents of the policy argue that it may have resulted in the exploitation of vulnerable people. [32] On the other hand, proponents believe the policy is a model for the world, as Iran has managed to have a short waiting list for kidney transplants, and that governmental support might reduce the likelihood of exploitation. [31]

Iran is also quite ahead of other Muslim countries in terms of the number of transplantations from cadavers and brain-dead cases. This happened as a result of a legislation in 2000 (Organ

Transplantation and Brain Death Act) based on Shia scholars’ Fatwa (decree), authorizing such practices. [38, 39] The act stipulates that brain death must be diagnosed and certified by a transplantation team, consisting of a neurologist, a neurosurgeon, an internist, and an anesthesiologist. Then, cadaveric organs and tissues are used for transplantation if the consent of the deceased (i.e. written will or signed donor card) or the next of kin is available. Cadaveric organ donation has increased in recent years due to increased public awareness and better medical equipment and laboratory facilities. [39, 40] There are several certified Brain Death

Identification Units and tissue banks nationwide. [41] So far, about 35,000 kidneys, 5,000 livers, 450 hearts, 100 lungs, 5,000 corneas, 5,000 bone marrows, 2,700 heart valves, 150 pancreases, and many bone and skin transplantations have been conducted in the country. [42] Panel 6: Iran’s pharmaceutical industry

Although the modern pharmaceutical system in Iran dates back to the first decade of the 20th century and the first pharmaceutical company was established in 1946, the pharmaceutical market has grown rapidly in the recent decade. Two fundamental reforms took place following the 1979 Revolution, the nationalization of the pharmaceutical industry, and the establishment of the generic scheme. Furthermore, the industry moved towards the private and the semi- governmental sector led by the government between 1988 and 1993. As of 2015, more than 120 companies were involved in drug manufacturing and 100 private companies and 40 designated emergency medicine centers were engaged in importing medicines. More than 40 companies are engaged in nationwide drug distribution, while four of them have 50% of the market share. The number of companies that produce Active Pharmaceutical Ingredients (API) is more than 30

(mostly owned by the private sector) and is growing; the policies of the Ministry of Health and

Medical Education promote the independency of API importation. The manufacture of finished products and the distribution of medicines are largely undertaken by governmental organizations.

In 2015, Iran’s total medicine market sales value was around $4 billion (compound annual growth rate (CAGR) greater than 20%), with domestic pharmaceutical production sales of more than $3 billion, and imported medicine market sales value of around $1 billion. In terms of volume, more than 95% of the market is covered by domestic manufacturers. More than 13,000 members of the

‘Iranian Association of Pharmacists’ are working in hospitals and community pharmacies; nearly

6% are working in the industry. [43] Although the economic situation in the country has influenced the market size, multiple factors are collectively influencing the growing demand for medicines in

Iran; population growth, increased coverage, improved income and per capita GDP, transition to non-communicable diseases, advances in pharmaceutical and

advanced therapies, and possibly lowered medicine prices at the international level. [44] The strengths of Iran’s pharmaceutical system are in its generic scheme; nationally-consistent pricing

schemes across the public and private sectors, governmental subsidization of , supported

coverage of the medicines used in primary healthcare (PHC) services -especially across rural areas,

governmental subsidization and distribution of specialized medicines (e.g. for cancer, or multiple

sclerosis), the maturity of the pharmaceutical industry and growth of knowledge-based biomedical

and innovation firms in this area, and affordable prices of most medicines. However, the main

challenges of the system are:

− The need for meeting high-level Good Manufacturing Practice (GMP) and international

standards required to increase the opportunities for export (given the large capacities for

extra production), especially to the Commonwealth of Independent States (CIS) and

Middle Eastern markets,

− Coverage of the least expensive products by the public and governmental insurance

schemes, which causes a lowering of quality of medicines in compensation for affordability,

− Irrational prescription and overuse of medicines by physicians (especially of antibiotics)

and the public, including self-,

− Financial and industrial sanctions and fluctuations in foreign exchange rates which affect

various parts of the industry,

− Prolonged delays in reimbursement by insurance organizations,

− Weak control over the importation of smuggled branded medicines,

− Frail medicine coding and tracking systems from production to consumption, − Fragile intellectual property rights in the Research and Development (R&D) sectors, which

discourage the private sector from investment,

− Illegal or uncontrolled marketing and advertisements for some medicines and health

products,

− Lack of national clinical practice guidelines for clinicians and healthcare providers,

− Improper and insufficient use of cost-effectiveness analyses on newly developed or newly

marketed products to decide on their inclusion within the national pharmacopeia, and

− A weak post-marketing surveillance system on adverse drug events within the community. Panel 7: Health services for refugees

The refugee crisis is a recently emerging health concern for the Middle East and European

countries due to the Syria, Libya, and Yemen crises. However, in Iran, the refugee issue has a

history of 30 years and its experiences regarding relevant achievements and challenges might

provide lessons for other recently involved countries. Based on the census report of 2016,

1,650,000 refugees live in Iran. Most of them are Afghan refugees (around 1,583,000 people) and

the other are from Iraq (around 34,500), (around 14,300), and Turkey (713). [45] There

are a considerable number of illegal Afghan refugees, who earn their low income from various

illegal jobs. Injuries (mostly occupational), and infectious diseases (including tuberculosis and

malaria) are common health problems among Afghan refugees. In Sistan and Baluchestan province, only about 10% of Afghan refugees use bed nets against mosquito bites at night, while

60% of Iranians use them. Lower rates of vaccination and impaired growth and development are main health concerns among refugee children recently entering Iran. [46] However, based on an

agreement between the UNHCR (The UN Refugee Agency), the UNICEF (The United Nations

Children's Fund), and the Ministry of Health and Medical Education, community health workers

(including a Behvarz, or a refugee who is trained in primary healthcare (PHC) delivery) provide PHC

services including vaccination, growth monitoring, oral rehydration therapy, modern methods of

family planning, maternal care, and a few for symptomatic treatment in refugee

camps. All refugees who attend a PHC delivery site, such as a health house or health post, will

receive all necessary PHC services. Based on the results of a study in Kerman, South-east Iran, the

coverage of BCG, polio, diphtheria, tetanus, and pertussis (DTP), Hepatitis B, as well as measles,

mumps, and rubella (MMR) vaccinations among Afghan refugees was greater than 95% from 2010 to 2012. This coverage was significantly higher than the vaccination coverage of children residing in . [47] Based on a contract with private companies and in coordination with the Ministry of Interior, the UNHCR provides health insurance to only those refugees who are registered by the Ministry of Interior. The insurance covers less than 50% of existing refugees in Iran, and a considerable number of unregistered refugees are not utilizing the healthcare they need. Even though there are success stories regarding the provision of health services especially in the PHC, there is no comprehensive approach for addressing the underutilization of healthcare among refugees. [48] Panel 8: Healthcare in informal settlements

Metropolitan cities in Iran have been facing rapid growth of heavily populated urban areas during the past decades, with important challenges, such as substandard housing and development of slums, i.e. informal settlements. Informal settlements have largely come to notice since 1961 following changes in oil prices and societal reforms, and contain mostly immigrants from rural areas, foreign immigrants, and poor urban inhabitants. Exact official statistics on the demographics of informal settlements are limited. However, Iran’s Ministry of Health and Medical Education has estimated a population of around 10,300,000 people live in these settlements. Slums commonly face issues such as poverty, undersupplied social, educational and healthcare services, stigma, and fewer official career opportunities, making them prone to social harm and exclusion. Although there is no national study on the social and health status of informal settlements, provincial studies have shown these facts about their inhabitants:

− Students’ height in primary schools of slums in Zahedan city, Sistan and Baluchestan

province, South-East Iran, is 3-5 cm shorter and their weight is nearly 6 kg lower than their

peers in non-slum populations,

− Slum populations in Koohdasht city, Lorestan province, west Iran, are primarily facing the

following issues, in descending order of importance, lack of a water sewage system;

limited support from municipalities, low income, social deviance, substance abuse, high

unemployment rates, lack of social support, low level of sanitation and hygiene, and

limited welfare and recreational facilities,

− Overall, between 56.6% and 93.2% of vaccines were overdue in 24-47 month-old children

living in the suburbs of five metropolises, [49] − The coverage rate of family planning programs for safe methods was 51.4% and 34% of

pregnant women had not received standard healthcare due to a lack of access to health

centers in the Iranian metropolis of Shiraz, South Iran, [50]

− Smear-positive tuberculosis had an incidence of 65 in 100,000 in Sanandaj, west Iran, in

comparison to the national estimates of 20-25 in 100,000, [51] and

− From a criminological perspective, 56.0% of thieves, 53.3% of substance abusers, and

64.0% of street fighters in Kurdistan province have come from slum populations.

The Ministry of Health and Medical Education has financed and started a program in 2013-2014 entitled the Health Transformation Plan in which there is a planned package of services for informal settlements. In this package, there is a health house for every 12,500 persons at the first level and a community healthcare center for every 25,000-50,000 persons at the second level.

These newly established efforts have been active for a relatively short period and they have not been evaluated critically and comprehensively. However, decreasing the rate of rural-urban migration, increasing employment opportunities, and inter-sectoral collaboration along with enhancing community participation are long-term strategies by the government to improve the social and health status of informal settlements. Panel 9: The Health Transformation Plan -aimed at achieving Universal Health Coverage

After two decades of establishment of the Primary Healthcare (PHC) System in Iran, the necessity

to reform healthcare in Iran was obvious. The first programs planned for these reforms which led to financial resource allocation (for its research phases) date back to 2002, wherein resources were taken into account for this purpose with a joint project between Iran and the World Health

Organization. Then, since 2004, this project was followed by a joint project with the World Bank and its end-result was an in-depth analysis of the situation in Iran, as well as planning for the implementation of reforms in the . [52] The results of these programs were included in the third to fifth development plans of the country as articles. [53] However, except for the

establishment of rural insurance and a network of family physicians in rural areas, other important

parts of it were not really implemented. There are several reasons for the lack of implementation

of reforms in the health system; the lack of political support and the lack of resource allocation

were the most important ones, among others. In 2014, the General Health Policies were

announced by the Supreme Leader of the Islamic Republic of Iran, drawing the framework of health propagation for future years. The newly functioning government supported the Health

Transformation Plan as a significant social reform plan and devoted the required resources to it.

Interventions related to this plan consisted of four sections, including:

− The provision of medicines and equipment (which till 2013 were too problematic due to

the sanctions and failure in their management),

− Treatment: Eight intervention packages were designed in the first step, which have

targeted mainly public hospitals and for protecting people against the financial risks of

expenditures and improving infrastructures of public service delivery and accordingly the quality of services and people's satisfaction. However, almost eight months after the

beginning of the first phase of this section, the change in relative valuation of services was

also applied, which can be considered as a fundamental change in services,

− The increase in the coverage of basic insurance through which, within an interval of more

than one year, a population of almost 10 million persons had benefited from, and

− The Primary Care Transformation Plan, the most important sections of which include the

coverage of services in city suburbs and the reconstruction of the PHC system in terms of

facilities and equipment in rural areas and towns as well as the provision of active services

in urban areas. The initial assessments after the first year indicate a reduction in out-of-

pocket costs and the proportion of households facing catastrophic health expenditure as

well as an increase in recipients’ satisfaction with the services received. [54] Although

primary indicators have indicated improvements in the short-term, to better evaluate this

plan we should wait for changes in impact indicators, which generally appear in the long

term. Panel 10: Religion’s role in the success of family planning policies

Iran has been praised for the record low reduction in fertility rate as a result of implementing

a successful family planning program. Different phases of the population policies have been

influenced by political and religious considerations. [55-57] Unlike several Muslim countries, in which religious scholars have selected an overtly negative view toward family planning, [58]

religious leaders in Iran in the late 80s and 90s adopted such policies, that allowed the Ministry

of Health and Medical Education to use its vast network of primary health centers and health

houses to implement the population policy in the country. Such an approach has since

influenced other Muslim countries. [59]

As a health and social policy, family planning started in 1966, before the Islamic Revolution.

Following the revolution, the country renounced the program for several years. [55] Religious

leaders announced that contraceptive use was inconsistent with Islamic tenets, and

emphasized that marriage and family formation (including child rearing) were basic Islamic

virtues. The government also adopted a policy of encouraging married couples to opt for more

children. As a result, Iran’s population rose from 34 million in 1976 to nearly 50 million in

1986, with an average growth rate of 3.9% per year. [55, 58]

It was in 1989, after the end of the war with Iraq that concerns about economic and social

implications of population growth convinced the government to reverse its policies. [60] The High

Judicial Council declared that “There is no Islamic barrier to family planning”, [61] followed by

approval of the family planning Act by the Parliament in 1994. [62] It has been argued that without

the approval of the Supreme Leader’s Fatwa (decree) and the implicit or explicit support of

religious leaders this would not have been possible, although the role of other socioeconomic factors in the success of the program cannot be ignored. [55, 58, 63-65] Population growth reduced dramatically to 1.6% in 2004, [57] and to around 1.2% in 2015. [66] Panel 11: Reduction of maternal mortality as one of the Millennium Development Goals (MDGs) in Iran

The maternal mortality ratio (MMR) was estimated at 123 per 100,000 live births in 1990, and reached 25 in 2015. [67] In addition to the major attempts made by the primary healthcare (PHC) system to improve the health of children and mothers in Iran, the maternal mortality surveillance system was formed during the last fifteen years. In this system, following the death of the mother, a complete review is conducted in the form of a verbal autopsy. Then, data of the cause(s) of death are gathered and sent to the committee at district level and in turn at provincial level to investigate the cause of death. The importance of this system is not merely to report the numbers of deaths, but also to design important interventions for the health system to cope with maternal mortality.

This program is conducted directly under the supervision of the main health authorities in each province. [68] According to the 2015 United Nations report, with 80% reduction in MMR, Iran has been one of the nine leading countries that could achieve the MDGs target. [67] However, it is worth mentioning that there is a remarkable geographical inequity in maternal mortality in Iran; the disadvantaged province of Sistan and Baluchestan is the most affected province. According to the national maternal mortality surveillance in 2007, the MMR was 24.7 in 100,000 at national level, while the estimate for this province was as high as 61.3. At the same time, the female- illiteracy-rate and Human Development Index were 21.8 and 0.70 at the national level, respectively, whereas these figures were estimated at 32.7 and 0.56 for Sistan and Baluchestan, i.e. the lowest in the country. Panel 12: Road injuries as a major national problem

Road injuries have been among the top 5 causes of mortality in Iran in the last 3 decades. [69]

Concordant with the rapid motorization of the country, road injuries began to significantly rise

from the year 2000. [70] Such rapid increases in number of road injuries made Iran appear among

countries with the highest burden of road injuries in only half a decade. Using multiple sources of

available country-level data, the road injury deaths were estimated at 44 per 100,000 in 2005, a

50% increase compared to the year 2000. Car occupants and pedestrians constituted 36% and

29% of all road injury deaths, respectively. Interestingly, with 51% of total nonfatal injuries,

motorcycle riders were the victims with the highest road injury morbidity estimate, whereas 2,979

road injury deaths (9.7% of total road injury deaths) occurred in the under 15-year-old age group.

Compared to the same age group estimates from countries with similar sociodemographic

features as Iran (e.g. Turkey and Egypt), road injury mortality stands out as an exceptional problem

among children and adolescents in Iran. [71] More recent studies providing road injury statistics

indicate a steady decline in both fatal and nonfatal road injuries in Iran starting from the year 2007.

[72]

The contributing factors are generally categorized into three groups, human, environmental, and

vehicle-related factors. Previous studies indicate that the human factor may be the main

determinant of high road traffic casualties in Iran. [73, 74] These include driving behaviors, driver’s mental and physical abilities, errors and violations; among these, risky driving behaviors are the main factors. Some studies show that Iranian drivers have more aggressive violations compared to drivers in similar countries. [75-77] Among environmental factors, poor road quality is a major

determinant: e.g. lack of special roads for low-speed cars, inadequate road lighting and road signs and large numbers of blind spots. [76, 78] Qualitative studies show that the low quality of the fleet

management system and over-production of low quality vehicles, and in recent years, increasing high-speed cars are the main challenges observed in vehicle related factors. [75]

While it is difficult to attribute the decline in road traffic casualties to any specific policy change, it

is suspected that better police patrolling along with formulation and implementation of new

regulations have made a major contribution towards bending the uprising curve of road injury

events. The government has invested substantial resources to reverse the rising trend of road

injury burden. A large number of preventive interventions have been implemented to improve

various factors involved in fatal road crashes. The Ministry of Health and Medical Education and

the Red Crescent Organization are negotiating on a national plan for a new post-crash system,

which substantially increases timely access to ambulance care. Seatbelt use laws are now being

effectively enforced. Speed cameras have been installed along most highways. Police have taken

increasingly serious measures to penalize high-risk behaviors. Transport authorities have taken

measures to build new roads and highways compatible with safety standards and make corrective

changes to make existing roads safer, and car manufactures have been obliged to build safer cars.

Airbags are becoming more available in domestically manufactured cars. Despite all these

measures, there is still room for improvement to ensure a continuous decline in the road injury

toll. For instance, road safety policies for children are missing, a road safety or injury data

surveillance system is also urgently needed; and motorcycle or bicycle helmet laws are not

effectively enforced. The government needs a systematic view toward managing risk in the

transport system. In Iran and other developing countries, this view can be adopted from the World

Bank guidelines for developing road safety capacity. [79] Panel 13: Iran’s opium use challenge

A nationally representative survey of 7,841 Iranians in 2011 estimated that the 12-month

prevalence of illicit drug use disorder was 2.4%, corresponding to over 1 million Iranians. [80] The

use of , particularly opium itself, was responsible for nearly 90% of such disorders. Cannabis

and amphetamine-type stimulants were used much less commonly, and the use of cocaine,

inhalants, and hallucinogens was rare. Men, divorced, and poorer and lower educated individuals

were more likely to have such disorders. [80] These data, while staggering, may indeed underestimate the true prevalence; self-reports during household surveys and exclusion of

homeless, incarcerated, or institutionalized individuals leads to underestimation of illicit drug use.

Consistent with these findings, the United Nations Office of Drug and Crimes (UNODC) reports that

Iran has the highest rate of opium use in the world, with 452 tons per year. [81]

Iran’s proximity to Afghanistan, where 92% of the world’s opium is produced, certainly plays a role

in the high consumption rates. Another important contributing factor is the long history of opium

use in Iran for medicinal (e.g., analgesic) and recreational purposes. Iranians substantially

increased their cultivation and export of opium between 1850 and 1880 to reduce their foreign

trade deficits. Cultivation of opium was allowed in Iran until the increased oil revenue in the 1950s

made it unnecessary. [82]

Opium use has negative societal, economic, and medical consequences. It results in lethargy,

chronic fatigue, drowsiness, memory impairment, and consequently lower productivity and

income. [83] It also causes chronic constipation, chronic obstructive pulmonary disease, and death

due to overdose. [83] Furthermore, recent epidemiologic and laboratory studies have shown that

opium use increases the risk of several malignancies, including cancers of the esophagus, stomach, larynx, lung, and bladder. [84] Opium has also been associated with higher risk of cardiovascular

diseases, [85] and a doubling of overall mortality rate. [86]

Reduction of opium use needs a combination of societal and individual interventions. Creating

jobs, law enforcement, and securing the borders are clearly important. Iran seizes the largest

amount of opium in the world, but unfortunately that is only a small fraction of opium trafficked

through the country. Providing proper information to the general population about health hazards

of opium use, such as its carcinogenic potential, [84] may be part of the solution. Treatments in

specialized clinics, and providing the right replacement can have major effects, too. Despite the

availability of 6,000 drug treatment centers in Iran, in 2011, only an estimated 23.5% of those with

drug use disorders received some form of service at healthcare facilities. [80] Low service uptake may be partly related to the high cost. In 2011, the average out-of-pocket cost for those with drug use disorder was $2,120, [87] which depleted 24% of the average family income. Perhaps because

of cost considerations, the most commonly used services were self-help groups, followed by

obtaining medication directly from pharmacies, without prescription. [80] However, over half of all those with drug use disorders received no service from healthcare clinics, self-help groups,

pharmacies, or other potential sources, indicating a major unmet need.

The large number of opium users, substantial unmet treatment needs, and the recent findings

that opium use can increase the risk of cardiovascular diseases and cancer pose a major challenge

to the health of Iran’s population, requiring urgent action. References

1. Habibzadeh F. Geopolitical changes and trends in Middle Eastern countries' contributions

to world science over the past three decades. Arch Iran Med 2011; 14: 310-311.

2. Kheirandish E, Bier C, Yousefi Najm a-D. Sciences, Crafts, and the Production of Knowledge:

Iran and Eastern Islamic Lands (ca. 184–1153 AH/800–1740 CE). Iranian Studies 2008; 41: 433-

436.

3. MacKenzie D. Iran showing fastest scientific growth of any country. New Scientist (Science

in Society) 2010.

4. Hassanzadeh M, Nourmohammadi G, Noroozichakoli A. Organization of Science in Iran: A

holistic review. COLLNET Journal of Scientometrics and Information Management 2009; 3: 53-59.

5. Abdollahi M. Perspectives of science in iran. Iran J Pharm Res 2010; 9: 207-208.

6. Kharabaf S, Abdollahi M. Science growth in Iran over the past 35 years. J Res Med Sci 2012;

17: 275-279.

7. Constitution of the Islamic Republic of Iran. Tehran, Iran1979.

8. Malekzadeh R, Mokri A, Azarmina P. Medical science and research in Iran. Arch Iran Med

2001; 4: 27-39.

9. Wilsdon J. Knowledge, networks and nations, Global scientific collaboration in the 21st century, The Royal Society 2011.

10. Adams J, King C, Pendlebury D. Global Research Report: Middle East - Exploring the

Changing Landscape of Arabian, Persian and Turkish Research Global Research Report2011.

11. Ismail SA, McDonald A, Dubois E, Aljohani FG, Coutts AP, Majeed A, et al. Assessing the

state of health research in the Eastern Mediterranean Region. J R Soc Med 2013; 106: 224-233. 12. Samavat A, Modell B. Iranian national thalassaemia screening programme. Bmj 2004; 329:

1134-1137.

13. Fallah MS, Samavat A, Zeinali S. Iranian national program for the prevention of thalassemia and prenatal diagnosis : mandatory premarital screening and legal medical abortion. Prenat Diagn

2009; 29: 1285-1286.

14. Samavat A. Iranian Ministry of Health Ministry, Health Deputy, Genetics Office, Personal communication. 2014.

15. Haddow JE. Couple screening to avoid thalassemia: successful in Iran and instructive for us. J Med Screen 2005; 12: 55-56.

16. Hadipour Dehshal M, Tabrizi Namini M, Ahmadvand A, Manshadi M, Sadeghian

Varnosfaderani F, Abolghasemi H. Evaluation of the national prevention program in iran, 2007-

2009: the accomplishments and challenges with reflections on the path ahead. Hemoglobin 2014;

38: 179-187.

17. Christianson A, Streetly A, Darr A. Lessons from thalassaemia screening in Iran. Bmj 2004;

329: 1115-1117.

18. Management feature of major beta-thalassaemia incidence in Iran. Iranian Ministry of

Health Ministry, Health Deputy, Genetics Office 2008.

19. Hafezi-Nejad N, Khosravi M, Bayat N, Kariminejad A, Hadavi V, Oberkanins C, et al.

Characterizing a cohort of alpha-thalassemia couples collected during screening for

hemoglobinopathies: 14 years of an Iranian experience. Hemoglobin 2014; 38: 153-157.

20. Najmabadi H, Ghamari A, Sahebjam F, Kariminejad R, Hadavi V, Khatibi T, et al. Fourteen-

year experience of prenatal diagnosis of thalassemia in Iran. Community Genet 2006; 9: 93-97. 21. Ebrahimkhani S, Azarkeivan A, Bayat N, Houry-Parvin M, Jalil-Nejad S, Zand S, et al.

Genotype-phenotype correlation in Iranian patients with Hb H disease. Hemoglobin 2011; 35: 40-

46.

22. Zeinali S, Fallah MS, Bagherian H. Heterogeneity of hemoglobin h disease in childhood. N

Engl J Med 2011; 364: 2070-2071; author reply 2071.

23. Elton P. Learning from low income countries: thalassaemia screening in Iran provides evidence for programme in Lancashire. Bmj 2005; 330: 478; discussion 479.

24. Arnold Christianson, Christopher P. Howson, Modell B. The March of Dimes Global Report on Birth Defects: The Hidden Toll of Dying and Disabled Children. White Plains, New York: March of Dimes Birth Defects Foundat ion 2006.

25. Strauss BS. Genetic counseling for thalassemia in the Islamic Republic of Iran. Perspect Biol

Med 2009; 52: 364-376.

26. Delshad H, Mehran L, Azizi F. Appropriate iodine nutrition in Iran: 20 years of success. Acta

Medica Iranica 2010; 48: 361.

27. Delshad H, Amouzegar A, Mirmiran P, Mehran L, Azizi F. Eighteen years of continuously sustained elimination of iodine deficiency in the Islamic Republic of Iran: the vitality of periodic monitoring. Thyroid 2012; 22: 415-421.

28. Azizi F, Kimiagar M, Nafarabadi M, Yassai M. Current status of iodine deficiency disorders in the Islamic Republic of Iran. Eastern Mediterranean Region health services journal 1990: 23-27.

29. Azizi F, Sheikholeslam R, Hedayati M, Mirmiran P, Malekafzali H, Kimiagar M, et al.

Sustainable control of iodine deficiency in Iran: beneficial results of the implementation of the mandatory law on salt iodization. Journal of endocrinological investigation 2002; 25: 409-413. 30. Azizi F, Mehran L, Sheikholeslam R, Ordookhani A, Naghavi M, Hedayati M, et al.

Sustainability of a well-monitored salt iodization program in Iran: marked reduction in goiter prevalence and eventual normalization of urinary iodine concentrations without alteration in iodine content of salt. Journal of endocrinological investigation 2008; 31: 422-431.

31. Larijani B, Zahedi F, Taheri E. Ethical and legal aspects of organ transplantation in Iran.

Transplant Proc 2004; 36: 1241-1244.

32. Broumand B. Transplantation activities in Iran. Exp Clin Transplant 2005; 3: 333-337.

33. Forouzannia K, Hosseini H, Rafie M, Sadr- Bafghi M, Motafacker M, Noori- Majelan N. First

Case of Heart Transplantation in Afshar Hospital , Yazd with 1 Year Follow-Up. The Journal of

Shahid Sadoughi University of Medical Sciences 2004; 12: 70-75.

34. Malek Hosseini SA, Lahsaee M, Zare S, Salahi H, Dehbashi N, Firoozi MS, et al. Report of the

first liver transplants in Iran. Transplant Proc 1995; 27: 2618.

35. Bagheri A. Compensated kidney donation: an ethical review of the Iranian model. Kennedy

Inst Ethics J 2006; 16: 269-282.

36. Ghods AJ, Savaj S. Iranian model of paid and regulated living-unrelated kidney donation.

Clin J Am Soc Nephrol 2006; 1: 1136-1145.

37. Oliver M, Woywodt A, Ahmed A, Saif I. Organ donation, transplantation and religion.

Nephrol Dial Transplant 2011; 26: 437-444.

38. Larijani B, Zahedi F, Malek-Afzali H. Medical ethics in the Islamic Republic of Iran. East

Mediterr Health J 2005; 11: 1061-1072.

39. Larijani B, Zahedi F, Taheri E. Deceased and living organ donation in Iran. Am J Transplant

2006; 6: 1493. 40. Akrami SM, Osati Z, Zahedi F, Raza M. Brain death: recent ethical and religious considerations in Iran. Transplant Proc 2004; 36: 2883-2887.

41. Mahdavi-Mazdeh M, Heidary-Rouchi A, Aghighi M, Rajolani H. Organ and tissue transplantation in Iran. Saudi Journal of Kidney Diseases and Transplantation 2008; 19: 127-131.

42. Transplantation ISoO. Organ transplantation statistics in Iran. Tehran: Iranian Society of

Organ Transplantation 2012:11.

43. Kebriaeezadeh A, Koopaei NN, Abdollahiasl A, Nikfar S, Mohamadi N. Trend analysis of the pharmaceutical market in Iran; 1997–2010; policy implications for developing countries. DARU journal of pharmaceutical Sciences 2013; 21: 52.

44. Davari M, Walley T, Haycox A. Pharmaceutical policy and market in Iran: past experiences and future challenges. Journal of Pharmaceutical Health Services Research 2011; 2: 47-52.

45. Population and Housing Censuses. vol. 2017. Statistical Centre of Iran.

46. Basseri HR, Raeisi A, Holakouie K, Shanadeh K. Malaria prevention among Afghani refugees in a malarious area, southeastern Iran. Bull Soc Pathol Exot 2010; 103: 340-345.

47. Dehghan A, Khanjani N, Zahmatkesh R. The Immunization Coverage of Afghan Children at the Health Centers Supported by the United Nation Higher Commission in Kerman, Iran. Journal of Community Health Research 2013; 2: 117-123.

48. Smith M. for refugees. Asia Pacific Family Medicine 2003; 2: 71-73.

49. Rejali M, Mohammadbeigi A, Mokhtari M, Zahraei SM, Eshrati B. Timing and delay in children vaccination; evaluation of expanded program of immunization in outskirt of Iranian cities.

Journal of research in health sciences 2015; 15: 54-58. 50. Joulaei H, Bhuiyan AR, Sayadi M, Morady F, Kazerooni PA. Slums’ access to and coverage of primary health care services: a cross-sectional study in Shiraz, a Metropolis in Southern Iran.

Iranian journal of medical sciences 2014; 39: 184.

51. Rashidian. M, Taherpour. A, S S, M. R. The Prevalence of Tuberculosis in Slums of Sanandaj

[in Persian]. Kurdestan Medical Sciences University Journal 2001; 6: 19-23.

52. Gressani D, Larbi H, Fetini H. Islamic Republic of Iran health sector review, volume II: background sections. Human Development Sector, Middle East and North Africa. Washington, DC:

The World Bank Group2008.

53. Rostamigooran N, Esmailzadeh H, Rajabi F, Majdzadeh R, Larijani B, Dastgerdi MV. Health system vision of Iran in 2025. Iranian journal of public health 2013; 42: 18.

54. Framework for health information systems and core indicators for monitoring health situation and health system performance – 2015. vol. 2017. WHO Eastern Mediterranean

Region2015.

55. Abbasi MJ, Mehryar A, Jones G, McDonald P. Revolution, war and modernization:

Population policy and fertility change in Iran. Journal of Population Research 2002; 19: 25-46.

56. Donohue JJ, Esposito JL. Islam in transition: Muslim perspectives, Oxford University Press

New York 2007.

57. Hoodfar H, Assadpour S. The politics of population policy in the Islamic Republic of Iran.

Stud Fam Plann 2000; 31: 19-34.

58. Roudi-Fahimi F. Iran's family planning program: responding to a nation's needs. vol. 19.

Washington. DC: Population Reference Bureau 2002. 59. Patterson RL. Improving family planning in Pakistan: Lessons learned from Iran. vol. Master

of Arts: DARTMOUTH COLLEGE 2013.

60. Moinifar HS. Religious Leaders and Family Planning in Iran. Iran & the Caucasus 2007; 11:

299-313.

61. Mehryar AH. Ideological basis of fertility changes in post-revolutionary Iran: Shiite

teachings vs. pragmatic considerations. Tehran: Institute for Research on Planning and

Development 2000; 18.

62. Abbasi-Shavazi MJ, McDonald P, Hosseini-Chavoshi M. The fertility transition in Iran,

Springer 2009.

63. Manenti A. Health situation in Iran. Medical Journal of The Islamic Republic of Iran 2011;

25: 1-7.

64. Mehryar AH, Ahmad-Nia S, Kazemipour S. Reproductive : pragmatic

achievements, unmet needs, and ethical challenges in a theocratic system. Stud Fam Plann 2007;

38: 352-361.

65. Simbar M. Achievements of the Iranian family planning programmes 1956-2006. East

Mediterr Health J 2012; 18: 279-286.

66. The World Bank. Population growth (annual %) | Data. vol. 2017.

67. Alkema L, Chou D, Hogan D, Zhang S, Moller A-B, Gemmill A, et al. Global, regional, and

national levels and trends in maternal mortality between 1990 and 2015, with scenario-based

projections to 2030: a systematic analysis by the UN Maternal Mortality Estimation Inter-Agency

Group. The Lancet 2016; 387: 462-474. 68. Yazdizadeh B, Mohammad K, Nedjat S, Changizi N, Azemikhah A, Jafari N, et al. Application

of Capture-Recapture for Fine-Tuning Uncertainties about National Maternal Mortality Estimates.

International journal of preventive medicine 2014; 5: 624.

69. Naghavi M, Shahraz S, Sepanlou SG, Dicker D, Naghavi P, Pourmalek F, et al. Health

transition in Iran toward chronic diseases based on results of Global Burden of Disease 2010. Arch

Iran Med 2014; 17: 321-335.

70. Naghavi M, Shahraz S, Bhalla K, Jafari N, Pourmalek F, Bartels D, et al. Adverse health

outcomes of road traffic injuries in Iran after rapid motorization. Arch Iran Med 2009; 12: 284-294.

71. Bhalla K, Naghavi M, Shahraz S, Bartels D, Murray CJ. Building national estimates of the

burden of road traffic injuries in developing countries from all available data sources: Iran. Inj Prev

2009; 15: 150-156.

72. Bahadorimonfared A, Soori H, Mehrabi Y, Delpisheh A, Esmaili A, Salehi M, et al. Trends of fatal road traffic injuries in Iran (2004-2011). PLoS One 2013; 8: e65198.

73. Mohammadi M, Imani M, Tajari F, Akbari F, Rashedi F, Ghasemi A, et al. Human and vehicle factors in motor vehicle crashes and severity of related injuries in South East Iran. J Health Scope

2012; 1: 61-65.

74. Motevalian SA, Asadi-Lari M, Rahimi H, Eftekhar M. Validation of a persian version of motorcycle rider behavior questionnaire. Ann Adv Automot Med 2011; 55: 91-98.

75. Khorasani-Zavareh D, Mohammadi R, Khankeh HR, Laflamme L, Bikmoradi A, Haglund BJ.

The requirements and challenges in preventing of road traffic injury in Iran. A qualitative study.

BMC Public Health 2009; 9: 486. 76. Shams M, Rahimi-Movaghar V. Risky driving behaviors in Tehran, Iran. Traffic Inj Prev 2009;

10: 91-94.

77. Morowatisharifabad MA. The Health Belief Model variables as predictors of risky driving

behaviors among commuters in Yazd, Iran. Traffic Inj Prev 2009; 10: 436-440.

78. Zamani-Alavijeh F, Niknami S, Bazargan M, Mohamadi E, Montazeri A, Ghofranipour F, et al. Risk-taking behaviors among motorcyclists in middle east countries: a case of islamic republic of Iran. Traffic Inj Prev 2010; 11: 25-34.

79. Bliss T, Breen J. Country guidelines for the conduct of road safety management capacity reviews and the specification of lead agency reforms, investment strategies and safe system projects, World Bank Global Road Safety Facility 2009.

80. Amin-Esmaeili M, Rahimi-Movaghar A, Sharifi V, Hajebi A, Radgoodarzi R, Mojtabai R, et al.

Epidemiology of illicit drug use disorders in Iran: prevalence, correlates, comorbidity and service utilization results from the Iranian Mental Health Survey. Addiction 2016; 111: 1836-1847.

81. United Nations Office on Drugs and Crime. World Drug Report 2010. United Nations

Publication, vol. 12.

82. Regavim RB. The most sovereign of masters: The history of opium in modern Iran, 1850–

1955, University of Pennsylvania 2012.

83. Kalant H. Opium revisited: a brief review of its nature, composition, non-medical use and relative risks. Addiction 1997; 92: 267-277.

84. Kamangar F, Shakeri R, Malekzadeh R, Islami F. Opium use: an emerging risk factor for cancer? Lancet Oncol 2014; 15: e69-77. 85. Masoudkabir F, Sarrafzadegan N, Eisenberg MJ. Effects of opium consumption on cardiometabolic diseases. Nat Rev Cardiol 2013; 10: 733-740.

86. Khademi H, Malekzadeh R, Pourshams A, Jafari E, Salahi R, Semnani S, et al. Opium use and mortality in Golestan Cohort Study: prospective cohort study of 50,000 adults in Iran. Bmj 2012;

344: e2502.

87. Amin-Esmaeili M, Hefazi M, Radgoodarzi R, Motevalian A, Sharifi V, Hajebi A, et al. Out-of- pocket cost of drug abuse consequences: results from Iranian National Mental Health Survey. East

Mediterr Health J 2017; 23: 150-160.