Distribution of Pathogen Resources by the National Culture Collection for Pathogens in South Korea from 2015 to 2019

Introduction

In 2014, the Nagoya Protocol intended to recognize the bio-sovereignty of each country worldwide, and fair and equitable sharing of benefits arising out of the accessibility and utilization of genetic resources became effective. Therefore, each country established its own biological resource management system and prepared for disputes over the use of resources. In South Korea, the act on the promotion of collection, management, and exploitation of pathogen resources (hereafter referred to as the “Pathogen Resource Act”) became effective in 2017, and that on accessibility and utilization of genetic resources, and benefit sharing (hereafter referred to as the “Genetic Resources Act”) became effective in 2018. These helped in creating a management system for securing domestic biological resources, trading domestic and international resources, and utilizing them.

The National Culture Collection for Pathogens (NCCP) is designated as a national organization and plays a role in legislative, administrative, and policy measures on access and benefit sharing in accordance with the Pathogen Resource Act with regard to Article 13 (National Focal Points and Competent National Authorities) and Article 14 (Access and Benefit-Sharing Clearing-House and Information-Sharing) of the Nagoya Protocol. In addition, it is responsible for reporting access to genetic resources (pathogens) and plays a role in accordance with Article 16 (Approval for Outbound Transfer), Article 17 (Revocation of Approval for Outbound Transfer and Other Relevant Matters), and has also played various roles for Article 18 (Acquisition of Pathogen Resources by Foreigners and Other Relevant Matters) of the Pathogen Resource Act regarding Article 6 (Access to Genetic Resources) and Article 7 (Access to Traditional Knowledge Associated with Genetic Resources) of the Nagoya Protocol.

The NCCP in the National Institute of Health (NIH), Korea Disease Control and Prevention Agency (KDCA), in compliance with the Pathogen Resource Act, serves as a national organization responsible for the deposition, registration, preservation, quality control, commercialization, and distribution of pathogen resources. These resources are utilized in developing therapeutics, vaccines, diagnostic technologies, products, and quality control at the infectious disease research and academic institutions and public health, food, and biopharmaceutical industries.

The NCCP as a national biobank responsible for pathogen resource based on the Pathogen Resources Act collects, performs quality control, and stores pathogenic microorganisms and derivatives derived from domestically isolated pathogenic microorganisms that cause infectious diseases in humans, according to the definition of pathogen resources in Article 1 of the Pathogen Resources Act. To date, ∼27,000 strains have been stored, of which 7100 strains have been quality checked and registered on the NCCP list. Among them, ∼3000 Korean isolates and 38 kinds of bacterial resources from DSMZ in Germany secured through resource exchanges in 2017 and 2019, after signing a MOU in 2011, have been distributed.

The registered pathogen resources are mainly distributed to track the route of infection for infectious diseases caused by new and mutated strains and multidrug-resistant nosocomial infections, to understand the characteristics of causative pathogens, study pathogenic mechanisms, achieve positive control during development of treatments and vaccine candidates, and develop diagnostic test methods. They are used in cross-sectional analyses for determining the sensitivity and specificity rates of diagnostic methods during efficacy evaluation.

For high-value addition and high-quality control of the pathogen resources, the NCCP operates a quality management system (ISO 9001) annually to perform standardized and systematic preservation and management of pathogen resources. It also verifies the quality certificates from institutions requesting the pathogen resources that are available for distribution.

Herein, we present in detail the recent status of pathogen resource distribution over the past 5 years, including information regarding the resource types, purpose of distribution, research areas, and activity of the resource bank, such as the current national status of isolated strains, thereby promoting pathogen distribution toward infectious disease research and public health.

Materials and Methods

Results

Discussion

The NCCP began operating in 2004 with the goal of securing and utilizing national pathogenic resources. NCCP plays a pivotal role in managing microorganism (pathogen) bioresources. ¹ In 2012, a newly formed NCCP Task Force began systematic management of the resource bank. In addition, the NCCP facilitates exchange and cooperation among domestic and international pathogen resource-related institutions to expand the collection of useful pathogen resources. Through the development of high value-added useful resources, the NCCP has tried to contribute to developing the health care industry and achieve its vision of becoming a resource powerhouse. In addition, the NCCP diseminates information on the distribution methods and available resources using various methods, such as participation in promotional booths at relevant conferences at least seven times a year, and publication of annual reports and guidebooks in Korean and English to promote utilization of domestic pathogen isolates.

This study analyzed the pathogen resources distributed by the NCCP from 2015 to 2019, categorized by the year, purpose of distribution, type of pathogen, and type of institutions. Through this analysis, we wanted to determine the status of how resources are being utilized in vaccine and therapeutics development; quality control and evaluation of pharmaceutical, medical, and food testing facilities; as reference for research on diagnostic agents and kits; and as substances for cross-tabulation analysis.

Over the past 5 years, the major distribution occurred in 2016. This peak occurred mostly after the Nagoya Protocol became effective (October 12, 2014) when the need for a bioresource management system emerged in every country to share profits equitably or prepare for international disputes. Consequently, the establishment of the Pathogen Resource Act and the national management of pathogen resources led to reporting and advertisement of related materials, which may have increased the distribution. The major distribution observed in 2016 is believed to be owing to the active advertisement of developed reference microorganisms (35 genera, 39 species) for use in public health centers and medical science education by the NCCP.

Furthermore, in 2019, it is believed that several factors helped increase pathogen resource requests. These include the increased awareness of domestic pathogenic microorganism isolates by implementing the Genetic Resources Act in August 2018, which eased the accessibility of applicants and reduced the time spent on administrative procedures by improving the application process, allowing people to request pathogen resource distribution online. The distribution was noticeably higher in February, March, September, and October than in other months. This is most likely owing to institutions preparing project plans, executing research tasks, and verifying results during these periods.

Out of the 7801 distributed cases, the number of distributions was similar between the national and public research institutions (2291) and universities and nonprofit organizations (2441), with the most distributions occurring toward private profit institutions or industries (3069). Furthermore, the majority of the distributions accounted for developing diagnostic agents and kits for infectious diseases (3188). More than 68.6% of the distributions to private industries were used for quality control and research on diagnostic technology. This may be owing to the recent outbreak of new infectious diseases, which increased investment and interest in biopharmaceutical industries, resulting in the development and commercialization of related products.

According to resource-specific analysis, dengue viruses and influenza viruses A and B were the most distributed. In 2018, 100 strains of dengue viruses were distributed to detect the causative pathogens of mosquito-mediated diseases and develop a diagnostic agent for a novel virus. The incidence of dengue fever has increased since 2012. A total of 149 patients were reported in 2012, 252 in 2013, 165 in 2014, 255 in 2015, 313 in 2016, and 171 in 2017^2–4 in South Korea. The sudden increase in the number of pathogens from 4 cases in 2015 to 63 in 2016 is related to a 54.5% increase in patient reports in 2015 compared with 2014 and believed to influence the enhancement of diagnostic technology development to confirm and diagnose pathogens.

Influenza virus is continuously distributed and is usually used for the identification of mutations in the development of molecular diagnostic agents and quantitative diagnostic sensors. Seasonal detection of influenza virus for surveillance of influenza patients was the highest in 2017–2018, with 2013 and 1101 cases of influenza types A and B, respectively. The average number of influenza type A cases was 1400 in 2015, 2016, and 2019. The average number of influenza type B cases was 675, which was similar between the seasons of 2015–2016 and 2018–2019. However, the number was the lowest (322) in the season of 2016–2017.^5,6 In 2018, 2304 cases were detected, wherein 799 cases were of type B, 660 of type A (H3N2), and 575 of type A (H1N1pdm09). The number was the highest in the season of 2017–2018, which could be the potential reason for the renewed increase in distribution of these pathogen resources in 2019.

The types of bacterial resources distributed in 2015–2019 included B. cereus, Campylobacter jejuni, Clostridium perfringens, E. coli, Haemophilus influenzae, Listeria monocytogenes, Salmonella enterica serotypes (Typhimurium, Enteritidis) S. aureus, Streptococcus pneumoniae, and Vibrio parahaemolyticus. These bacteria are usually related to infectious diseases of biosafety levels 2 and 4 and are causative pathogens for intestinal infectious diseases. In addition, Salmonella enterica serotype Typhi and Paratyphi A/B, the causative pathogens of typhoid and paratyphoid, grade 2 infectious diseases, were steadily distributed. In addition, the genus Shigella, the causative pathogen of bacterial dysentery and cholera, and Vibrio cholerae species were distributed widely. These pathogenic microorganisms are known to cause waterborne and foodborne infectious diseases and have been distributed for utilization in the quality control of food testing facilities' periodic assessment and infectious disease test training at public health agencies.

Based on the annual surveillance report of the KDCA, the number of patients with pneumonia caused by S. pneumoniae has steadily increased since 2015 (36 people in 2014, 228 people in 2015, 441 in 2016, 523 in 2017, 670 in 2018, and 526 in 2019). ³ Furthermore, except in 2018, the number of pathogen distribution steadily increased until 2019. The distribution was usually for vaccine and therapeutics research, development of diagnostic technology, and quality control.

Scarlet fever, a standardized example of bacterial respiratory disease, had an increased patient incidence from 2013 to 2017 owing to the inclusion of pathogen isolation culture for patient screening but decreased in 2018 and 2019. ³ The pathogen resource distribution of Streptococcus pyogenes, the causative pathogen of scarlet fever, has also been reported to decrease since 2017. Furthermore, since the mass outbreaks in North Gyeongsang Province in 2015, the incidence of whooping cough has continuously increased. The reported cases were 5809 in 2014, 7002 in 2015, 11,911 in 2016, 22,838 in 2017, 15,777 in 2018, and 7562 in 2019. The number of pathogen resource distribution for Bordetella pertussis, the causative pathogen of whooping cough, was ≤4 cases annually, which confirms that the increased incidence of bacterial infection does not necessarily correlate with the number of pathogen resource distribution.

In 2020, the government set a goal for reducing the use of antibiotics by 20%. The government came up with a plan to manage national antibiotic resistance in August 2016 and to conduct a survey targeted at medical institutions after conducting a national survey on medical-related infections in February 2018, followed by a comprehensive plan for their prevention management in 2018–2022. ⁷ As part of the government's policy to expand and enhance the surveillance system and the operation of a reporting system for various multidrug-resistant infections, many of the relevant pathogens were distributed to examine the causative pathogens and develop treatments.

K. pneumoniae, a carbapenem-resistant Enterobacteriaceae; Acinetobacter baumannii, a multidrug-resistant A. baumannii; and P. aeruginosa, a multidrug-resistant P. aeruginosa, were distributed more in 2019 than in other years, with 62, 72, and 54 cases, respectively. ¹ This increase could be owing to the expansion and enhancement of surveillance systems and a comprehensive plan for nosocomial infections.

For derivatives, there was nothing specific other than the nucleic acid resources of viruses being largely distributed in 2018, and those of bacteria in 2019. Requests for these derivatives were usually from middle- and small-sized industries and small research institutes without the appropriate biosafety research facilities to handle viruses based on their risk level. Recently, the NCCP has planned to expand the management of derivative resources to promote research and product development by these small- and medium-sized organizations such that all available resources can be distributed. ⁸

At present, the profits and values of bioresources are emphasized in all countries globally. Moreover, the competition to secure resources and economic burdens continues to increase since the Convention on Biological Diversity and Nagoya Protocol proclamation. Therefore, this article was written to enhance the recognition of pathogen resources and promote pathogen resource distribution by presenting the current status of utilization of domestically distributed pathogens for various purposes, thereby publicly announcing the activities of the NCCP.

In the future, the NCCP, in compliance with the Pathogen Resource Act, will strengthen the cooperation among related ministries of living genetic resource. In addition, through reinforcement and scientific management of the characteristic, including biological information of additional resources, we will endeavor to further the utilization of high value-added pathogen resources in the field of public health and related industries.