The national research and reference laboratory for arboviruses and viral hemorrhagic fevers was established in November 2000 in response to a public health requirement,  specifically the outbreak of Crimean-Congo viral hemorrhagic fever at the Pasteur Institute of Iran. This laboratory is a national reference center in the field of research and diagnosis of arboviral diseases and viral hemorrhagic fevers, with a particular focus on Crimean-Congo hemorrhagic fever (CCHF). It provides its services not only to Iran but also to other countries in the region. The samples of arboviral diseases from all over the country are sent to this laboratory for diagnosis and research.

 

Due to the successful performance and prompt laboratory diagnosis provided by this laboratory, which has played an effective role in improving the national healthcare system for arboviral diseases over the past 23 years, the mortality rate from Crimean-Congo fever has decreased from around 40% during the early years of the disease epidemic in the country to 10% currently. This demonstrates that Iran is one of the successful countries in the region and the world in managing this disease. In this context, we interviewed Dr. Mohammad Hassan Pouriayevali, Head of the Department of Arboviruses and Viral Hemorrhagic Fevers at the Pasteur Institute of Iran.

Dr. Mohammad Hassan Pouriayevali was born in Isfahan in 1981 and holds a specialized doctorate in virology from Tarbiat Modares University. He has been working at the Pasteur Institute of Iran since 2009.

Identification and research in the field of arboviruses and viral hemorrhagic fevers

In 2000, following an infectious epidemic in Chaharmahal and Bakhtiari province, later found to be caused by Crimean-Congo hemorrhagic fever, the country's health system decided to establish a specialized laboratory in this field in the country. The laboratory was initially set up with the cooperation of the Pasteur Institute of Senegal and the research center in South Africa, and then with the efforts of the head of the laboratory at the time, Dr. Sadegh Chinikar, the Arbovirus Laboratory and Viral Hemorrhagic Fevers were launched at Pasteur Institute of Iran. This laboratory aimed  to identify arboviral diseases in the country and conduct research in this field. In 2008, due to the establishment of quality management systems in the laboratory, it received national reference approval from the Ministry of Health's reference laboratory and  operated  as the national reference laboratory for arboviruses and viral hemorrhagic fevers.

Ticks and mosquitoes are the main vectors of arboviruses in Iran

Arboviruses are a group of viruses that are transmitted through arthropods. The most common arboviruses found in Iran are the Crimean-Congo hemorrhagic fever virus and the West Nile fever virus.

The main hosts of the Crimean-Congo hemorrhagic fever virus are domestic animals such as cattle, sheep, and goats. This virus is usually transmitted to other animals and humans through the bites of hard ticks of the Hyalomma species. Additionally, the virus can be transmitted through contact with the blood and secretions of infected humans or animals, or contact with the meat or carcasses of infected animals.

Among other arboviruses endemic in  Iran is the West Nile fever virus transmitted by the Culex mosquito. Other arboviruses, such as dengue and chikungunya, are not native to Iran and are transmitted through Aedes mosquitoes. Recent reports have identified mosquitoes carrying these diseases in the country, indicating a potential threat of transmission shortly.

Crimean-Congo hemorrhagic fever disease report from all provinces of the country

The symptoms of Crimean-Congo hemorrhagic fever can appear one to two days after the virus enters the body, with initial symptoms such as fever, muscle pain, and lethargy. Afterwards, hemorrhagic symptoms may appear in the individual. If proper treatment is administered and the disease is controlled promptly, the person can survive; otherwise,  a percentage of people may die due to severe complications of the disease.

In Iran, an average of 100 positive cases of Crimean-Congo hemorrhagic fever are detected each year, and the current mortality rate due to the disease is around 10%. Previously, most positive cases were reported in southern and southeastern provinces of the country, such as Sistan and Baluchistan as well as  Kerman. One possible reason for this was the importation of infected livestock from neighbouring countries to the east. However, in recent years, cases of the disease have been reported from almost all provinces of the country, with Kerman and Mazandaran reporting more cases than other provinces.

West Nile fever is a disease with mild symptoms

West Nile fever is another important arbovirus endemic to Iran, with the highest number of infections reported in southwestern provinces, particularly Khuzestan province. Like Crimean-Congo hemorrhagic fever, cases of this disease have been reported in all provinces of the country. This disease mainly presents with mild symptoms in humans, and most cases have been identified through serological testing.

Detection methods for most arboviruses

Equipping the reference laboratory with state-of-the-art diagnostic facilities for most of the world's arboviruses has been a longstanding policy at Pasteur Institute of Iran. In this context, the laboratory is capable of detecting non-indigenous arboviruses that may pose a threat to the country's health system, including Zika, yellow fever, Alkhurma, Ebola, and Marburg viruses.

Molecular Network of Crimean-Congo hemorrhagic fever

Since last year, a molecular network for the diagnosis and study of Crimean-Congo hemorrhagic fever has been established in Iran, with plans to expand it to other arboviruses, as well. This network involves ten  universities of medical sciences across the country, including Ardabil, Birjand, Jundishapur, Zahedan, Kurdistan, Kerman, Gilan, Mazandaran, Mashhad, and Hormozgan, who collaborate with the Arbovirus reference laboratory to diagnose the disease. Currently, samples are sent simultaneously from health centers to both the collaborating laboratories and  Pasteur Institute of Iran.

With comprehensive and ongoing evaluations at the ten selected universities and obtaining necessary approvals, it is hoped that the molecular diagnostic test for Crimean-Congo hemorrhagic fever will be performed independently at these centers. This will eliminate the need to send samples from all over the country to Tehran for diagnosis, making the diagnosis process faster and more efficient.

Expanding the laboratory network of arboviruses

Experiences gained during the COVID-19 pandemic have shown that relying solely on a laboratory for identifying infectious agents prone to outbreaks may not be effective in quickly detecting and controlling these agents. Therefore, a need exists to expand the detection network throughout the country. Given the identification of Aedes aegypti mosquitoes in Hormozgan province, as well as the previous history of identifying other Aedes mosquitoes in Sistan and Baluchistan province, the country may face outbreaks of diseases transmitted by Aedes mosquitoes, such as dengue fever and chikungunya, in the southern provinces. These epidemics could quickly spread throughout the country.

 

To address this, the molecular diagnosis network for Crimean-Congo hemorrhagic fever is being expanded to include the molecular diagnosis network for arboviruses. A series of centers where the probability of disease outbreaks is higher have been selected, and these centers have been equipped and evaluated to act as colleagues of the reference laboratory in the rapid diagnosis of leading epidemics. By exchanging technical information and diagnostic kits, these laboratories are now capable of diagnosing leading epidemics. Hormozgan University of Medical Sciences has obtained the necessary approvals for the diagnosis of dengue and chikungunya, and Zahedan University of Medical Sciences is currently in the evaluation process.

Aedes mosquitoes pose a risk for the emergence and spread of new arboviruses

Fortunately, there have not been any endemic cases of dengue or chikungunya fever in the country so far. All cases that have been confirmed molecularly or serologically have been imported, which means that the patient was infected in a neighbouring country and entered Iran either before or after the onset of symptoms. However, there is a possibility that Iran may face an outbreak of these diseases in the future since the mosquito that transmits these viruses is circulating in Hormozgan province.

Identification of the first case of COVID-19 in this department

After identifying the possibility of coronavirus entering the country in 2018, the Pasteur Institute of Iran formed a team in the form of a rapid response laboratory for infectious diseases. among other active laboratories at the Pasteur Institute of Iran, this team selected the arbovirus laboratory, to conduct preliminary tests to identify this disease.

As a result, the initial launch of the diagnosis of COVID-19 in the country and the definitive diagnosis of the first case of the disease from Qom province were performed  in the Arbovirus Reference Laboratory. About six months after the detection of the first case of the disease in the country, the National Reference Laboratory of COVID-19 was established at the Pasteur Institute of Iran. Since then, the National Reference Laboratory of Arboviruses and Viral Hemorrhagic Fevers of the Pasteur Institute of Iran has focused solely on its own field of activity.

The need to improve the biological safety level of the laboratory for more advanced research

This department currently has four faculty members and six experts working as a national reference laboratory. However, we are facing challenges in terms of human resources and physical space. To detect arboviral agents, we have upgraded our biosafety level to level 2, but to conduct more advanced studies on most arboviruses, a laboratory with biosafety level 3 or 4 is required. This is especially true for basic and pathogenic studies of arboviruses and more developed research studies, which require laboratories with higher safety levels.

We hope to expand research in this field by establishing a biosafety level 3 laboratory at the Pasteur Institute. This will enable us to conduct more advanced studies on arboviruses and improve our understanding of their biology, transmission, and pathogenesis.

International communication

Since 2014, the World Health Organization has been evaluating the reference laboratories of countries and accrediting them based on the results they provide. The Arbovirus Reference Laboratory has been under evaluation  since 2014 and has fortunately obtained good grades over  these years

Activities in the international field

Since the establishment of the reference laboratory, we have maintained a good relationship with the World Health Organization. We have also provided advice and support to neighbouring countries as much as possible. As a center specializing in arboviruses within the international Pasteur network, we have established strong relationships with the Pasteur Institute of Paris and the Pasteur Institute of Senegal.

In recent years, Afghanistan faced limitations in diagnosing Crimean-Congo hemorrhagic fever, and our experts travelled there to provide training. Similarly, diagnosing the disease in Iraq was initially challenging due to the situation in that country. However, after the 2019 outbreak of Crimean-Congo hemorrhagic fever in Iraq, we advised them to establish a diagnostic laboratory in the area and supplied them with kits produced in the national reference laboratory for arboviruses and viral hemorrhagic fevers of the Pasteur Institute of Iran to facilitate rapid diagnosis and control of the epidemic.