Proceedings of a Workshop—in Brief

Building Regional Capacity Among South and Southeast Asian Countries to Address Emerging Infections and Global Health and Security

Proceedings of a Workshop—in Brief

NOTE: This is the summary of a workshop that was held in 2016. No summary was produced at the time, but the National Academies of Sciences, Engineering, and Medicine decided that it is important to document the meeting, particularly in light of the COVID-19 pandemic and the need for international cooperation to address infectious diseases.

Infectious diseases are a leading cause of death in many developing countries. South and Southeast Asia have large populations and many communities in need of improved living conditions, which increases their susceptibility to infectious disease outbreaks and the emergence of new pathogens, particularly viruses. The natural environment, animal- and crop-based agriculture, and the interactions between and among domesticated animals, wild animals, and humans in the region amplifies the vulnerability of populations to zoonotic infectious diseases. The impact of these diseases can be minimized through well-prepared and strong public health systems, at both local and global levels. Improving global health requires strengthening capacity related to diagnostics, laboratories, and early response systems, as well as coordination of human and animal disease surveillance.

Addressing the needs of the broader South and Southeast Asian region for more robust laboratory capacity is critical to this effort. India’s existing and planned laboratory capacity, capabilities in global health research (e.g., basic and applied research in epidemiology, pathogens, entomology, vector and host factors, and veterinary science), and expanding international partnerships, position it well to serve as a regional leader in global health.

The workshop Building Regional Capacity Among South and Southeast Asian Countries to Address Emerging Infections and Global Health and Security was designed to encourage scientists to examine global issues related to emerging infections and health safety, share experiences and approaches, and identify opportunities for regional cooperation to improve practices and research. More than 50 participants from 12 countries attended the workshop, held in Victoria, Seychelles, from May 8-11, 2016. Participants addressed both human and animal health, because zoonotic infections, such as avian flu and anthrax, have demonstrated that the boundaries between animal and human health are never fixed and increasingly cross. Plant health, which is relevant to human and animal health, was also addressed.

OPENING REMARKS

Rajendra Prasad, Fellow of the Indian National Science Academy (INSA), welcomed participants and discussed the history and mission of the organization. INSA supports and promotes research of national and international importance through professorial chairs. INSA supports fellows as senior scientists, honorary scientists, and INSA emeritus scientists, as well as through INSA’s own publications. The organization conducts international outreach efforts and supports bilateral exchanges with, and collaboration of, scientists at foreign academies of science.

Dianne Griffin, Vice President of the U.S. National Academy of Sciences (NAS), said that the organization serves as a nongovernmental, honorific organization that provides independent advice to the United States, both the government and the people. NAS also cooperates with other academies of sciences and scientific organizations on subjects of international importance.

Daniel Garcia, Senior Laboratory Advisor for the U.S. Centers for Disease Control and Prevention (CDC) Division of Global Health Protection in India, provides technical assistance to strengthen the government’s laboratory sector in line with the International Health Regulations (IHRs) and the Global Health Security Agenda (GHSA). He said that global health risks have increased through the emergence of new organisms, drug resistance, and intentional events, causing rapid and significant disease spread and causing considerable economic hardship. Garcia noted that these lines of effort and activities are overlapping and inter-related. The U.S. CDC is working with local government agencies and NGO partners across India to reach India’s goals. The two countries are working together to enhance laboratory detection of antimicrobial resistant (AMR) pathogens and to strengthen capabilities for surveillance, outbreaks, and epidemic investigations of a high-risk group of viral pathogens causing viral hemorrhagic fevers.

Garcia underscored the opportunity for India to serve the region and the world by providing training across countries and leveraging its own country expertise. Sharing data and synergizing across networks (i.e., influenza or AMR networks), will make India stronger and more prepared for emerging pathogens. Over time, it is important that the Indian domestic and regional public health platform expand to more seamlessly connect with animal health professionals and organizations to address the increasing prevalence of zoonoses and AMR.

OVERVIEW OF REGIONAL LABORATORY CAPACITY

Speakers discussed pressing challenges related to infectious disease research, prevention, and response in their countries as well as other needs related to laboratory and personnel capacity.

A representative from the Disease Surveillance National Coordinator office of Afghanistan, provided a detailed overview of the country’s efforts to further develop and strengthen laboratories across the Islamic Republic of Afghanistan. Afghanistan has completed a national strategic plan for a laboratory project and established a working group on policies related to public health and laboratories. The representative said that a national strategic plan, policies, and regulations are needed for the country’s laboratories, and a defined and responsive organizational structure will be necessary for implementation. A lack of experienced advisors and a proliferation of licensed and regulated private laboratories that do not follow quality control standards present a significant challenge. On a national level, there is no capacity to ensure regular interaction with peripheral laboratories, no structure to foster and facilitate international networks, and no mechanism to sustain or provide supervision of the overall laboratory structure.

Afghan experts enjoy positive collaborations with NIH Pakistan, NIV India, laboratories in Iran, and the Naval Medical Research Unit in Egypt (NAMRU -3). However, the poor condition of Afghan laboratories as well as poor coordination among Afghan stakeholders, donors, and government agencies managing collaborative projects hamper their effectiveness.

The representative concluded by affirming that the government of Afghanistan is committed to opening up laboratories for research to more fully utilize lab capacity and improve laboratories and laboratory networks across the country.

Syed Sayeem Uddin Ahmed, Programme on Emerging Infection in the Infectious Diseases Division, described current laboratory capacity in Bangladesh, noting that there are about 5,000 public and private sector laboratories, two of which are BSL-3 laboratories, and two others are in development. As of the time of the workshop, Bangladesh did not have a national focal point for laboratories, nor standard operating procedures, external quality assurance systems, or effective internal audit systems. The Biosafety Office of Bangladesh has developed multiple biosafety and biosecurity manuals and training programs.

Efforts to develop national and regional networking include, for example, working with the U.S. CDC to upgrade labs to deal with pathogens. Because the existing laboratory network in Bangladesh is granular and insufficient in terms of coverage, and because there is a desire to transition from reliance on to cooperation with foreign labs, greater regional collaboration is essential. These are critical needs, as Bangladesh is a hotspot for emerging infectious diseases, including Nipah Influenza A Virus (IAV), Zika, and MERS-CoV.

Monipheap Uch, Cambodian National Medical Microbiology Laboratory Network, discussed current diseases under surveillance in Cambodia: acute diarrhea, severe respiratory infections, acute hemorrhagic syndrome, flaccid paralysis, diphtheria, rabies, and neonatal tetanus. Surveillance systems are in place related to communicable diseases. Research on health equity, quality of care, nutrition, and traffic-related incidents is being conducted at the National Institute of Public Health, but no research on communicable diseases was in process at the time of the workshop. Challenges related to infectious disease and response include personnel, funding, technical issues, and resources, including training, supplies, and equipment. To address some of these issues, the country has developed a web-based database system and a computer-based laboratory surveillance system, which are providing timely and accessible data on communicable diseases and pathogens.

Rakesh Bhatnagar, along with Jaishree Garhyan, Jawaharlal Nehru University School of Biotechnology in New Delhi, India, shared the school’s experience with creating a functional and affordable BSL-3 laboratory at the university. The lab is well equipped for all routine molecular biology work and has facilities like RT-PCR, FACS, a Fermentor, and a tissue culture facility. Challenges have arisen in maintaining and sustaining the facility. Initial funding included only construction, set up, and maintenance for two years, but operation of a BSL-3 facility requires consumables on a continuous basis (e.g. personal protective equipment and replacement filters). Extensive research has been conducted in the BSL-3 lab, including on anthrax and tuberculosis.

Herawati Sudoyo, Eijkman Institute for Molecular Biology in Jakarta, Indonesia, presented on the country’s laboratory capacity to support early detection of emerging infections. Indonesia has been identified as a high-risk area for emerging diseases (including Zika), but at the time of the workshop diagnostic capacity for most pathogens was limited. Other challenges include shortage of qualified and trained personnel, insufficient diagnostic capacity to contribute to regional networks on emerging disease, and inadequate biosafety measures. Strong political commitment is needed around policy and resources as well as expanded training and laboratory capacity building. One of Indonesia’s strengths is infrastructure, which includes a BSL-3 facility, a BSL-2 lab, and other research laboratories and animal facilities. Indonesian researchers have multiple international collaborations, and there is a desire to expand and deepen these partnerships.

Darouny Phoneko, Institut Pasteur du Laos, presented on infectious disease and successful laboratory research as well as laboratory challenges in Laos. Between 2007 and 2011, influenza lab surveillance for influenza-like illnesses (ILI) and severe acute respiratory infections (SARI) took place in 10 locations across the country in collaboration with the Lao-Oxford-Mahosot Hospital and the Wellcome Trust Research Unit; similarly, multiple sites in Indonesia were studied for non-malarial fever. Key challenges facing the country’s labs include a lack of human and financial resources and coordination among agencies involved in laboratory management. However, a strength of the system includes coordinated efforts through the National Committee on Communicable Diseases and Control as well as strong political support.

Yoke-Fun Chan, University of Malaysia, presented on regional laboratory capacity in her country, where the top five notifiable diseases are dengue fever, tuberculosis, food poisoning, hand, foot, and mouth disease, and HIV/AIDS. Malaysia has a dedicated high-containment laboratory for infectious disease research and has developed emergency responses to address global health emergencies. Legislation related to infectious disease research is in place in Malaysia, including in research governance and responsible science. Ongoing needs include additional investment in active and predictive surveillance; a high-containment facility budget for maintenance; highly trained research personnel; stronger public-private partnerships; and improved research governance.

Munazza Nazir, Quaid-i-Azam University, discussed infectious disease challenges in Pakistan and associated challenges to addressing them through the country’s public health and research laboratories. He stated that approximately 26 percent of deaths are attributable to infectious diseases, a situation made worse by unsafe drinking water, and advocated for dedicated funding to fight infectious diseases.

Although Pakistan’s indicators suggest improved disease control, the country needs to strengthen its laboratories and other disease diagnostic systems; educate and train healthcare workers; identify hazards and minimize risks; reexamine routine practices essential to infection control; and strengthen practices and procedures around clinical waste management. Finally, applied research focusing on impact and involving surveillance, screening, treatment, and large-scale awareness of infectious diseases of concern should be increased.

Edith Sangalang Tria, Philippine Biosafety and Biosecurity Association (PhBBA), discussed regional laboratory capacity in the Philippines. The National Program of Laboratory Safety and Biosecurity seeks to ensure a safe and secure environment by adhering to international standards in the handling, use, storage, and transport of pathogens. The Philippine Integrated Disease Surveillance and Response (PIDSR) was developed as a strategy to organize and integrate the different aspects of the nation’s disease surveillance system at the local and national levels. Among other areas, the PIDSR assists with priority setting, policy making, planning, implementation, resource allocation as well as anticipating possible outbreaks as a part of overall prevention measures.

Tzer Pin Raymond Lin, National Public Health Laboratory in Singapore, discussed laboratory capacity to address infectious disease in the country, where public health agencies coordinate with public hospitals, and research institutions, on response efforts. Research funding in Singapore is traditionally allocated for basic science and new knowledge discovery. In addition, there are specialized grants to support translational clinical research, communicable disease-public health research, and large grants to encourage collaboration and support policy and practice.

Questions remain about how to focus these research efforts—on pathogens or clinical syndromes, or on laboratory engineering.

Sunee Sirivichayakul, Chulalongkorn University, discussed emerging infectious disease laboratory research in Thailand, including challenges, such as differentiating serious emerging infectious disease from conventional upper respiratory infections. The country has a BSL-2 and BSL-3 facility, both of which are frequently used in the initial identification of the causative agent from the suspected case. Operational and maintenance costs are high, particularly for the BLS-3 laboratory. Resource limitations, she underscored, should not compromise strict adherence to laboratory safety regulations, overseen by external safety committees.

A lack of education and awareness of how diseases are transmitted in the early phases of epidemics make disease containment at the clinical and laboratory challenging, which creates fear among laboratory workers. Education and laboratory safety training for laboratory assistants and personnel is needed. Finally, overall research capacity building and funding are needed to attract and retain scientists from developing countries to the fields of microbiology, pathogenesis, and the development of test kits, drugs, and vaccines.

Nguyen Tran Hien, National Institute of Hygiene and Epidemiology, noted that laboratory diagnostic capacity is at the heart of surveillance and response to emerging diseases in Vietnam. The country has two laboratory systems: once responsible for infectious disease surveillance and response, the other responsible for public health, preventative medicine, and therapeutics. At the time of the workshop, the Public Health Laboratory (PHL) network’s national laboratories included 200 laboratories in 63 provinces and over 674 PHLs at the district level. The country has taken steps to develop and update national guidelines on sample collection, transportation, and testing for emerging infectious diseases. Vietnam has also provided guidance to ensure biosafety in labs, strengthened the public health system through policy and strategic planning, infrastructure, supply and maintenance of equipment, and upgraded specimen referral systems and quality management. A strong laboratory system requires strong governmental support, sufficient funding, material, and infrastructure as well as intersectoral collaboration between preventive and care and treatment, and between the health and veterinary sectors.

RECOGNIZING AND IDENTIFYING EMERGING AND RE-EMERGING DISEASE

Syed Faisal Mahmood, Aga Khan University (Pakistan), and Tran Hien Nguyen, National Institute of Hygience and Epidemiology (Vietnam), facilitated a discussion about actions to counter recent outbreaks, including the emergence and geographic spread of various diseases.

Emerging Zoonotic Infections: The Need for Containment Laboratories

D.T. Mourya, National Institute of Virology (NIV) in Pune, India, discussed biorisk concerns associated with zoonotic infections. Newly emerging, re-emerging, and “deliberately emerging” diseases are affecting countries across the globe. The NIV has developed proactive surveillance activities and studies around these diseases, including avian influenzas H9N2 and H11N1. The NIV and the U.S. Centers for Disease Control and Prevention (CDC) initiated a network for enhancing laboratory capabilities across the country, including one laboratory network focusing on Middle East Respiratory Syndrome Coronavirus (MERS-CoV).

Global Influenza Surveillance

Daniel Jernigan, CDC, discussed global influenza surveillance efforts. Because of the influenza virus’ gene assortment, there is a persistent risk of emergence of a pandemic virus. The 1918 pandemic caused an estimated 50M deaths. In 2008, the World Bank estimated that a severe pandemic would cost $3 trillion.¹ In fact, the emerging novel influenza A viruses are a global health security threat, with a 13-fold increase in human cases from the 1990s to 2015.² He noted the need to implement a comprehensive strategy on these issues, along with flexible risk assessment tools, and a focus on laboratory infrastructure at the outset.

Through the Global Health Security Agenda (GHSA), the CDC, in partnership with other agencies and nations, and public and private stakeholders, seeks to accelerate progress toward a world safe and secure from infectious disease threats, Jernigan said. He noted that the U.S. government identified $1.7 billion to support activities in 31 of the GHSA countries [in 2015]. System-wide solutions can improve coordination of detection and response and can address various safety risks at critical points in the system. Laboratory infrastructure, with safety elements incorporated, is critical for emerging infectious disease detection and response.

Emerging Fungal Infections and Drug Resistance

Rajandra Prasad, Amity University, Gurgaon, discussed fungal infections and multidrug resistance (MDR), including MDR in fungi. Worldwide reporting of trends in fungal emerging infectious diseases show a rise, particularly in animal-infecting fungi since 2000. In both animals and plants, an unprecedented number of fungal diseases have recently caused some of the

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most severe die-offs and extinctions ever witnessed in wild species, jeopardizing food security.³ Human activity is also intensifying fungal disease dispersal by modifying natural environments. Fungi also pose an increasing threat to plant and animal biodiversity. Risk factors predisposing humans to fungal infections include malnutrition, radiation therapy, cytotoxic chemotherapy, neutropenia, HIV/AIDS, surgical devices, malignancy, age, and alteration of microbial flora. Prasad underscored that trends in fungal infectious disease and antifungal drug resistance are increasing, and the threats that the fungi pose to plant and animal biodiversity are on the rise, with wider implications for human and ecosystem health.

Emerging Pathogens: Research Challenges Imposed by the Regulatory Framework in India

Sumathy Kandaswamy, Bharat Biotech Intl. Ltd., India, discussed emerging pathogens in the country, focusing on research opportunities and challenges, including the need for simplification and harmonization of regulatory structures. Emerging infections in India include typhoid, hepatitis, rota, schistosomiasis, e. coli, cholera, other vector-borne diseases such as JE, dengue, chikungunya, malaria, trypanosome, leishmania, and filarial. Political and scientific commitment are needed, but there has been a lack of clarity on disease burden, focuses of public health, and policies.

She also introduced Bharat Biotech, a vaccine manufacturing company in Hyderabad, India. The company has been involved in the development of a chikungunya vaccine and a Zika vaccine. Kandaswamy noted, partnerships were essential. For example, in work on a Zika vaccine, Bharat Biotech cooperated with and/or received support from Indian contract research organizations, the European Medicines Agency, and the University of Texas Medical Branch, among others.

Case Study of Texas Ebola Patient

James LeDuc, Galveston National Laboratory, described the impact on biocontainment laboratories, the critical management of acute cases, and lessons learned related to a patient with Ebola. Based on his experiences with the arrival of an Ebola-infected patient in his home state of Texas in 2014, LeDuc offered his observations related to four important topics: communications, technical assistance prior to an identified case, critical management of acute cases, and waste management. The Dallas County Health and Human Services Department was responsible for immediate containment efforts, along with a team of CDC staff to identify potentially exposed contacts, initiating monitoring of contacts, reviewing plans for triage patient testing as well as infection control practices. On October 26, 2014, the Texas Task Force on Infectious Disease, Preparedness, and Response issued a document outlining key issues related to the case.⁴

THE BIOTECH REVOLUTION: OPPORTUNITIES AND CHALLENGES

Rani Faryal Faheem Tahir, Quaid-i-Azam University, Pakistan, and Chiek Sivhour, Battambang Referral Hospital Laboratory, Cambodia, led a session addressing challenges and opportunities for addressing infectious diseases through advances in biotechnology.

Genome Editing: An Overview of National Academies-Related Efforts

Diane Griffin, U.S. National Academies, summarized a National Academies meeting on technological advances that make it possible to edit genomes. CRISPR/Cas9 is a gene editing technology derived from the adaptive anti-phage immune system of bacteria. The power of the technology was initially recognized in early 2014 and spread rapidly throughout laboratories across the globe. Although scientists called for a moratorium on human embryo gene editing, soon after that a Chinese laboratory reported on their work editing genes in nonviable human embryos. This ignited further discussion and immediacy around the technology.

The National Academies convened an international summit on human genome editing on December 1–3, 2015.⁵ While the summit resulted in no final recommendations, concluding statements were made about the need for basic and preclinical research to understand the technologies, identify risks, and understand embryonic biology.

Biotechnology in Pakistan

Zabta Khan Shinwari, Pakistan Academy of Sciences, discussed challenges and opportunities related to infectious disease research in Pakistan. The country has developed a well-coordinated livestock disease control network, however there is a need to strengthen capacity building of veterinary institutions, establishing animal disease surveillance and monitoring systems, and promote the One Health concept. Shinwari also discussed plant diseases facing the country, including biotechnology being developed to address these challenges.

Pakistan offers significant opportunities to engage on biotechnology development due to many advantages, including a large, English-speaking talent pool; capabilities in chemistry, pharmacology, information technology, and statistics; relatively low research costs; and a significant number of scientists in pharma/biotech research and development. However, it deals with

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challenges in developing a strategy for the knowledge economy that would include biotechnology, such as resource limitations, a lack of awareness, and poverty, among others. With the growing fear of pandemics and epidemic infectious disease, scientists are using biotechnology to develop new tools for the rapid and sensitive detection of pathogens. Additionally, a promising area of “reverse vaccinology” is being developed, based on computational analysis of the entire genetic sequence of microbial pathogens.

Pathogen Discovery and Prediction of Infectious Disease Outbreaks

B. Ravindran, Institute of Life Sciences, Bhubaneswar, discussed developments in genomics that can contribute to pathogen discovery. Advances include genome sequencing to identify emerging viruses, global communication networks, rapid diagnostics, and new approaches to vaccine development and therapeutic design. Ravindran underscored that research via high throughput sequencing and computational strategy on species like bats led to discovery of 58 novel viruses; extrapolation of this suggests that 320,000 novel virus are waiting to be discovered. This will help us predict future pandemic outbreaks. Also, genomic and computational analysis are being conducted at high containment laboratories throughout the country.

Recombinant and Spore Vaccines for Anthrax

Yogendra Singh, University of Delhi, discussed the challenge of tuberculosis, which kills about 1.2 million people each year, and anthrax, which can also be lethal. A recombinant anthrax vaccine is yet not available; however, research is underway. Anthrax in India exists but is not a widespread problem. Cutaneous infection is common in forest areas and villages that have been in contact with infected animals. A spore vaccine could help in reducing animal cases.

The Pace and Proliferation of Emerging Biological Technologies

Pawan Dhar, Jawaharlal Nehru University, discussed synthetic biology as an engineering approach to build biological molecules and systems. Synthetic biology in the Indian context has included laboratory work⁶ to make artificial genes and proteins, including a database of potential genes. Through this work, the country has also presented a new drug discovery pipeline to address malaria, breast cancer, infectious microbes, and Alzheimer’s disease. Yet, these technological advances have a potential for misuse. Protocols and guidelines are necessary to address this issue, and in the case of whole genome cloning, guidelines specific to the technology have not yet been developed.

Genetic Polymorphism and Susceptibility to Infectious Diseases

Ravindran discussed research on the relationship between genetic polymorphisms, DNA sequences that are uncommon variations from the norm in a population, and susceptibility to infectious diseases. In particular, not all infected patients display disease severity uniformly and a disease spectrum is observed. In studying genetic polymorphism relation to susceptibility to infectious diseases in human populations, researchers examine single nucleotide polymorphism in a variety of genes or deletion/insertion in the coding or non-coding regions of specific genes, using methods such as high-throughput single-nucleotide polymorphism (SNP) arrays or genome-wide association studies.

DEVELOPING AND SUSTAINING REGIONAL COLLABORATION

Workshop participants discussed the importance of developing and sustaining regional collaboration and partnerships to address emerging infections, including building laboratory capacity.

Emerging Infections and Technologies and Building Regional Networks

Mark Smolinski, Skoll Global Threats Fund, Skoll Foundation, discussed the work of the Foundation “to safeguard humanity from global threats,” including pandemics. The foundation focuses its resources where it can have the greatest impact in harnessing technologies that are revolutionizing other sectors but that have not made their way to public health, such as early detection, verification, real-time reporting, diagnostics, rapid response, and new models of governance. In ending pandemics, three areas are highlighted: applying technology to find, report, and verify outbreaks faster; building local capacity to create and adapt new tools; and working across borders (national and sectoral) to stop epidemics.

Mekong Delta Disease Surveillance Program

Moe Ko Oo, Mekong Basin Disease Surveillance (MBDS) Foundation, noted that the MBDS encompasses Thailand, Cambodia, Vietnam, Laos, Myanmar, and China, and serves as region policy-making body that tackles strategies including cross-border cooperation, labs, risk communication, community-based surveillance, and animal-human interface. In addition to implementing international health regulations in 2007, the MBDS is also involved with development and implementation of the Asia Pacific Strategy for Emerging Infectious Diseases Plans which supports regional preparedness, alert, and response and related monitoring and evaluation. MBDS is mainly focused on cross-border and subnational information sharing. MBDS is also conducting a cross-border baseline assessment of the time-to-disease detection, to assess the lag time of disease report among different disease reporting systems, i.e., national surveillance systems. Ko Oo underscored the priority of MBDS to “train, retrain, and retain” personnel (see Figure 1).

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Achievements of MBDS include building trust, developing cooperation, and sharing benefit and group values among member countries, among other activities. Other advantages of MBDS include an established network that can support early detection and prompt response, ongoing engine for information exchange, mechanism and tool development, capacity building, regional platform, multisectoral teams, communication sharing and exchange.

Expanded Programme on Immunization, HIV, and Avian Influenza National Programs

Tran Hien Nguyen, National Institute of Hygiene and Epidemiology, discussed the Expanded Programme on Immunization (EPI), HIV/AIDS, and avian influenza public health programs in Vietnam. The EPI structure includes staff at the regional, provincial, district, and community levels, who are focusing on immunization. The program has supported, for example, a widespread immunization campaign against rubella and measles for 20 million children. Nguyen noted the importance of political commitment at the highest levels, ensuring fairness in health care and vaccine equity, especially in remote and ethnic areas, and the need for effective support of international agencies and foreign governments.

Nguyen also discussed the country’s efforts to address avian influenza, with the objective to reduce the risk to humans and animals from the virus along with other emerging infectious diseases.

ZOONOTICS AND ONE HEALTH

Sukanta Chowdhury, Avian Influenza Working Group, Bangladesh; H.K. Prasad, Mizoram University, India; WikuBakti Rawono Adisasmito, Indonesia One Health University Network; Supaporn Wacharaplusesadee, Chunalongkorn University, Thailand; and Mohammad Hafiz Rasooly, Ministry of Public Health, Afghanistan, participated in a panel highlighting examples from the region of specific research projects involving zoonotic infections.

Afghanistan

Rasooly began by noting that despite progress, Afghanistan has the worst health indicators in the region, and communicable and vaccine-preventable disease still kill thousands of Afghanis annually. Diseases include pneumonia, measles, Crimean-Congo hemorrhagic fever (CCHF), cholera, malaria, TB, rabies, brucellosis, and diarrhea. In 2006, the Ministry of Public Health established surveillance systems to address communicable diseases. About 500 sentinel sites cover 15 diseases and there is one reference laboratory for humans, a BSL-2, as well as one for animals. Rasooly expressed a hope for more collaboration with the other participating countries to address the lack of disease surveillance in the animal sector along with poor capacity of research in both animal and public health sector labs. There is a need to focus on capacity building for biotechnology along with more sharing of data and expertise.

Bangladesh

Chowdhury presented an overview of zoonotics and One Health in Bangladesh, noting that Southeast Asia is considered a hotspot for emerging infections. Threats include zoonotic pathogens from wildlife and from non-wildlife, drug-resistant pathogens, and vector-borne pathogens. With support from NIH, CDC, and others, ongoing disease surveillance is taking place including on avian influenza surveillance in poultry, and for human infections with avian influenza among live-bird market workers, among others. Outbreak investigations take place using the One Health Approach, with collaboration among physicians, laboratory scientists, veterinarians, anthropologists, and epidemiologists. Epidemiological research at the animal-human interface is necessary to identify cause, transmission, and risk factors and these projects rely on external funding. Strengthening the regional network for sharing epidemiological and laboratory data is necessary.

India

Prasad discussed his research on susceptibility and resistance to tuberculosis in India. He and colleagues have examined several immunological parameters, including the quality of immunocompetent cells and circulation of T cells in patients with tuberculosis among family contacts. Other work includes examining mycobacterial pathogens in human samples and in cattle samples. A key challenge is that M. tuberculosis

can crisscross the species barrier though aerosol and oral transmission.

With funding from the Department of Biotechnology, a multiinstitutional collaborative study of candidate vaccines was being conducted at the time of the workshop. He emphasized that the fight against TB must also consider the zoonotic aspect of the disease.

Indonesia

Adisasmito discussed efforts to improve global health safety through strengthening the national university laboratories in Indonesia, noting that the country is a hotspot for zoonotic diseases and a future hotspot for antimicrobial resistance. It is important to have the capability to identify and predict and prevent infections related to avian influenza, rabies, Zika, and leptospirosis, among others.

Establishing and strengthening the laboratory network is urgent, noted Adisamito. There are three essential laboratory functions, including rapid determination of outbreak causes, characterization of the pathogen, and suggestions for appropriate therapy and control measures. At the time of the workshop Indonesia had more than 11,000 health laboratories, but no central coordination or command center. There were also nine BSL-3 and seven BSL-2 certified laboratories in the country at the time.

Additionally, the Southeast Asia One Health University Network (SEAOHUN) was established in 2011 supported by USAID, consisting of Indonesia, Thailand, Vietnam, and Malaysia.⁷ The One Heath Laboratory Network linked nine regional laboratories, targeting zoonotic diseases to enhance rapid detection.

Thailand

Wacharapluesadee began by discussing the rationale for the One Health approach, to reducing pandemic risk and promoting public health. At the time of the workshop, the PREDICT Project (Reducing Pandemic Risk Promoting Global Health) encompassed 31 countries and was an effort to work across multiple sectors and understanding and address the emergence of zoonotic disease.⁸

In Thailand, PREDICT includes two phases. A key focus of phase I, or PREDICT 1 (2009-2014), was local capacity-building to improve wildlife surveillance in hotspot regions where emergence of pathogens of wildlife origin is mostly likely to occur. PREDICT enhanced capacity for early detection of disease threats in wildlife and assisted with operationalizing One Health at a government and on-the-ground implementation level. This effort supported the development of the government’s first coordinated wildlife disease surveillance project to characterize the viral pathogen diversity in macaque populations. In PREDICT 2 (2015-2019), the One Health approach will be applied to document virus sharing among diverse species and characterization pathways for disease emergence.

CULTURES OF RESPONSIBILITY

Cultures of responsibility involve regulation, training, leadership, and communities of trust. S.R. Rao, India, and T.S. Saraswathy Subramaniam, Malaysia, moderated discussions around the role of culture, including how communities of trust can be fostered and supported for safety, security, and the productivity of research.

Preparing the Next Generation

Shinwari began by discussing the important role of youth in the productivity of research. At the time of the workshop, there were about 1.8 billion under-25-year-olds in the world, one billion of whom are in the 15–24 age group. This significant increase has resulted in a global crisis of youth unemployment and underemployment. Universities and other institutions should play a role in addressing this crisis, Shinwari said. As the world’s population is getting younger, careers in science, technology, engineering, and math will empower and enable the next generation to excel in the global marketplace.

Shinwari noted that the number of higher education institutions has grown in Pakistan since 2000. To increase educational opportunities in the sciences for youth in Pakistan, Shinwani discussed several projects underway, including awareness-raising seminars at local universities to introduce students to different aspects of biosafety and biosecurity.

Finding the Balance: Regulation, Safety, Security, and Productivity

Franz began by noting that it was only after the terrorist attacks on the United States in September 2001, that the USA Patriot Act of 2001 and the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 created significant rules and regulations, including around the registration of persons who work in laboratories.

Franz added that while biotech laboratory risks are a serious concern, the number of related deaths has been minimal compared to the more than 700,000 hospital acquired infections in the U.S. each year—or 250,000 deaths each year related to medical illnesses. Over-regulation of the life science enterprise can impede the ability to provide healthcare, food and agriculture, and energy; as well as impede economies, the ability to recruit young scientists into the infectious disease field, and the ability

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to compete globally. For safe and secure infectious disease research, Franz noted that regulations are necessary but not sufficient for labs. Regulations cannot substitute for leadership, and layering unnecessary bureaucracy on top of regulations is counterproductive.

Vaccine Development in India: Capacity Building, Prospects, and Challenges

S.R. Rao, former advisor in the Department of Biotechnology (DBT) in India, discussed the role that vaccines play in public health, including the vaccine market in India, which is making affordable vaccines in developing countries. For example, the DBT’s Vaccine Research and Development Programme began in 1987 and focused on the development of new and improved vaccines and the production of some of the WHO Expanded Programme on Immunization vaccines (e.g., polio, measles). The Indo–U.S. Vaccine Action Programme also has trained 250 young scientists in U.S. laboratories, which helped the program to move vaccination research forward.

Collaborative vaccine development is a powerful tool: vaccine development, clinical trial, and commercialization are complex and require many steps with involvement of multiple partners. Additionally, public-private partnership programs have been effective in promoting innovation. Also, the National Immunization Programme of the Government of India is a strong example of policy makers regulating the prices directly, so that the vaccines reach the masses at an affordable cost.

Major hurdles faced by the vaccine industry include lack of technological capacity, the high cost of R&D, long and complex clinical trials that result in longer time to licensure, among other issues. While rapid response to emerging pathogens is difficult, systems vaccinology and research is critical to advancing this area and supporting public health.

REGIONAL BIOSECURITY AND BIOSAFETY

A discussion addressed regional biosafety and biosecurity, particularly how Cambodia, India, Malaysia, Philippines, Singapore, and Vietnam are developing national approaches around the operation of high-containment laboratories. The session also addressed issues related to maintaining safe and secure biocontainment laboratories, as discussed by representatives from India, Indonesia, Laos, and Malaysia.

Regional Biosafety/Biosecurity: Panel Discussion

Joseph Kanabrocki, University of Chicago, and Iram Iqrar, Quaidi-Azam University, Pakistan, moderated a discussion around national approaches of operating high-containment laboratories to inform lessons learned and opportunities. Kanabrocki began the session by noting the high costs in maintaining facilities, which he said is a common issue across all countries.

Cambodia

Sokunna Sau, Ministry of Health, discussed biosafety initiatives in Cambodia, noting that there are 91 public health laboratories, of which only 6 have microbiology laboratories capable of bacterial culture, identification, and antibiotic testing. There are also 27 BSL-2, 3 BLS-2+, and 1 BSL-3 facilities. A key initiative is increasing training opportunities around biosafety. There is also an opportunity to collaborate with international and national partners to improve biosafety.

Cambodia’s national plan for 2016–2020 includes related priority activities and training needs, including developing a national health laboratory policy with the scope suitable to the country context and dissemination of national biosafety guidelines to guide work at all public health labs. The plan also outlines how to establish laboratory biosafety regulations and biosafety curriculum training to provide to trained safety officers, among other areas.

India

Gopal Pande, formerly with the Centre for Cellular and Molecular Biology and now an independent consultant, spoke about the role of regulatory guidelines and personnel training in mitigating risks caused by emerging infectious organisms. Currently in India, there is no national certification and validation authority/systems and a lack of training mechanisms and curricular training. The country is working to address these issues by establishing context-, location-, and risk-specific guidelines for handling storage and disposal of hazardous microorganisms; creating a statutory body for validation/certification of biosafety facilities and for certifying biosafety professionals; and developing improved and more contemporary training and educational tools.

Malaysia

T.S. Saraswathy, Institute for Medical Research, noted that Malaysia is a hotspot for emerging disease, including EV71, SARS, Nipah, influenza, and MERS CoV. For each outbreak, lessons learned included that a public health response must be comprehensive and cannot focus solely on laboratory capacity. Capacity must also be strengthened in such areas as surveillance, simulation, crisis preparedness, and risk communications. Malaysia has developed a coordinated laboratory response, including a network of laboratories as well as a research oversight and review process (see Figure 2). However, more training is needed for researchers on pathogens.

The government is taking effective administrative steps for mitigation of biological risks, including developing a national

goal for research and diagnosis around safe laboratory practices. Adequate resources are needed to improve basic biosafety infrastructure, facilities, and equipment, along with a biorisk policy and culture of responsibility/code of conduct. Biosafety associations also have an important role to play as champions for biosafety and biosecurity, by complementing and supplementing government efforts and acting as a resource for training and research, Saraswathy said.

Philippines

Edith Sangalang Tria, San Lazaro Hospital, Philippines, discussed efforts around risk assessment for biohazards, biosafety program management, laboratory containment facilities design, certification and re-certification, operational biosafety practices, among other issues. Important activities organized in the country to address the need for increased biosafety practices, included various trainings, including the Commodity Identification Training, part of the Biological Weapons Development and Export Control Act. The training was aimed at equipping staff in knowledge on identifiable commodities that can be used as materials or sources of WMDs, including biological agents and toxins, among other areas.

Singapore

Viji Vijayan, Duke-NUS Graduate Medical School, noted that her institution has an annual enrollment of more than 60 medical students and a strong Ph.D. program. There are four wet bench lab-based programs. The Medical School is focusing on new and more effective methods for the early identification, treatment, prevention, and control of new and emerging pathogens. As a world-class regional infectious disease center for reference and research in the Asia-Pacific region, it has one high-containment facility, at animal BSL-3.

Vietnam

Thi Cam Van Ha, Ministry of Health General Department of Preventive Medicine, Vietnam, discussed biosafety regulations, challenges, and priorities in the country. Vietnam has regulations in place that define the conditions for facilities, equipment, and personnel at each biosafety level. Nationwide there are more than 5,000 BSL-1 and -2 labs, but only 600 of them are certified. Institutes in four regions are authorized by the Ministry of Health to perform the technical training and certification biosafety training for their region. In addition, authorized training centers develop standard training materials appropriate to biosafety levels.

Strengths include a set of relatively completed regulations on biosafety, with biosafety as a high government priority. However, this is still a new concept in the country and regulations need to be revised in accordance with the national and regional situations particularly given that most facilities do not yet meet the biosafety conditions, especially at the provincial level. Staff training and resources for laboratories are still a concern.

Needs and Opportunities at Biocontainment Laboratories: A Regional Panel Discussion

Sibgha Tayyab, Quaid-i-Azam University in Pakistan, and Gopal Pande, retired from the Centre for Cellular and Molecular Biology in India, moderated a panel discussion around needs and opportunities at biocontainment laboratories.

India

D.T. Mourya, National Institute of Virology in Pune, discussed the challenge to develop infrastructure with biosafety controls and trained staff. While India has significant laboratory capacity, including BSL-3 and BSL-4 laboratories, a key challenge is that many infectious diseases are not in national focus because accurate information of the disease profile and disease burden are not known. Awareness about biorisk management at primary health centers, district hospital laboratories, and many national laboratories is inadequate and a strong laboratory infrastructure and trained staff on biosafety issues is needed. Another challenge relates to biocontainment laboratories. Several biocontainment laboratories are being launched, but they are still not sufficient. Steps are needed to ensure biorisk management without hampering research, including increasing the awareness of biosafety among administrators, scientific leaders, scientists, and technical staff; the development of national guidelines and training programs; and establishment of procedures to monitor biosafety in scientific activities.

Indonesia

Herawati Sudoyo, Eijkman Institute for Molecular Biology, Indonesia, said that it is critical to raise public awareness and build capacity within the region through national and regional biorisk/biosafety associations and other relevant stakeholders. Indonesia and other countries are involved in regional and international activities around biorisk management. The country’s National Strategy and Initiative to Mitigate Biorisk addresses the development of BSL-3 facilities, human-capacity development in biorisk management, and development of a code of conduct on biosecurity. Sudoyo discussed the need for continuous funding as well as long-term commitment to strengthening and improving laboratory biosafety practices and biosecurity. All countries need to work together to achieve One Health, said Sudoyo.

Laos

Darouny Phonekeo, Institut Pasteur du Laos (IPL), noted that a laboratory assessment was conducted by the National Center for Laboratory and Epidemiology (NCLE) in 2011 in all provinces using the WHO Laboratory Assessment Tool, including the biosafety program. The results indicated that all laboratories had less than optimal capacity, and thus, targeted training was offered. This also occurred at IPL, where biosafety training and exercises have taken place, including for military and civilian facilities. IPL has a BSL-2+ facilities (not BSL-3 because of air handling equipment such as exhaust systems), with BSL-3 practices.

Malaysia

Sazaly Abu Bakar, University of Malaysia, noted that the country has issued a laboratory biosafety and biosecurity policy and guidelines. The county is also developing a biorisk standard operating procedure and conducting a biorisk/assessment and inspection. Additionally, Malaysia’s Laboratory Biosafety and Biosecurity Policy and Guidelines state all institutions with personnel performing activities involving the handling, manipulating, working, using, storing, and disposing of infectious and potentially infectious agents/materials and microbial toxins must institute an organizational-level Institutional Biosafety and Biosecurity Committee. It must provide proper facilities commensurable with the biosafety risk levels of the infectious and potentially infectious agents/materials and microbial toxins handled.

Emergency Structures for Public Health Responses in India

N.K. Ganguly, Indian Council of Medical Research, noted that several agencies addressing public health issues in India and as such, a unified structure and more coordination is needed. While creating pandemic preparedness plans, it is imperative that legal frameworks are fully integrated into the plans from the national level to the local levels to ensure a healthcare continuum prior to, during, and after a pandemic. Transparency of the public health crisis management systems, global cooperation, and capacity building are important.

Ganguly discussed Indo-U.S. partnerships, which can serve as catalysts to facilitate and promote bilateral collaboration in science, technology, and biomedical research in health sciences. There is also an interagency umbrella organization mechanism for bilateral discussion between the United States and India on health collaboration and program implementation with working groups organized on non-communicable disease, infectious diseases, strengthening health systems and service, and maternal and child health. There are vaccine-related collaborations underway, as well as a new program, the Indo-US partnership on Anti-Microbial Resistance. The Bloomberg Philanthropies has also partnered with the Government of India to encourage smarter urban development that improves people’s lives through the “Smart Cities Challenge.”

Ganguly noted that outbreaks will occur in regions where they have not been observed before, and the dynamics of these outbreaks may be different; thus, there is a need for vaccines and antiviral therapeutics, and they must be available in sufficient quantities prior to an outbreak.

NEXT STEPS: COLLABORATIONS AND PARTNERSHIPS

Workshop participants discussed next steps around collaborations and partnerships. As well as existing capabilities and related needs, such as access to biocontainment facilities. The discussion was summarized by James LeDuc and Indira Nath, INSA.

LeDuc noted the workshop discussion around the tremendous laboratory capacity that exists within the region, with most countries having functional BSL-2 and BSL-3 laboratories, and India and perhaps others with BSL-4. The rapidly evolving landscape in technology may require use of biocontainment laboratories to ensure safety and security, LeDuc said. Most countries have a robust program of biosafety and biosecurity in place in association with their biocontainment laboratories to include biosafety officers, institutional review boards, and national guidelines and standards, and thus a strong foundation is in place throughout the region. There are opportunities for harmonization and further development of best practices in biocontainment operations, maintenance, and scientific investigation.

LeDuc added that there is a dynamic and highly educated young workforce. Global demographic conditions will lead to excess capacity of highly skilled persons in some countries in the region, while other countries are facing an aging

population and will require inward migration to sustain and grow their technical workforce. Educational opportunities should focus on meeting global demand by ensuring that students are trained to internationally accepted standards and are exposed to international learning. The need for training was also frequently discussed. Sharing of best practices may also help in creating a culture of responsibility among all people working with infectious diseases.

Regarding surveillance, LeDuc noted that there is a need to further develop regional capacity to share information on infectious diseases of international importance, with the Mekong Basin as a model to replicate.⁹ The interface between human and animal health is key, and existing models of regional collaboration may serve as a foundation for further development. The One Health concept offers an opportunity for further regional cooperation and information sharing.

LeDuc said that participants discussed the opportunity to further the development of regional biosafety associations that would allow consistency in guidelines, procedures, and best practices. The role of the biosafety officer is evolving with advances in science, and there will be a continuing need for coordinated development of new practices and procedures to ensure safety. LeDuc noted that most countries have established national guidelines for biosafety. Building on this foundation, there is an opportunity for region-wide harmonization of biosafety guidelines as they are revised and updated.

Certification and validation were discussed, and Nath said this is an area for more harmonization. Another concern is how to protect those in the field and the physicians who first see patients. Standard operating procedures are needed for these groups, both to protect their health and to minimize the danger of them spreading an infection further.

Nath observed she heard more discussion about biosafety than biosecurity and suggested this as an issue for the future. She also asked how to use the meeting to bring the region closer. More frequent, smaller meetings with focused discussions could be one way, with white papers prepared to share with governments.

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DISCLAIMER: This Proceedings of a Workshop—in Brief was prepared by JENNIFER SAUNDERS as a factual summary of what occurred at the meeting. The statements made are those of the rapporteur(s) or individual meeting participants and do not necessarily represent the views of all meeting participants; the planning committee; or the National Academies of Sciences, Engineering, and Medicine.

COMMITTEE TO PLAN A SOUTH ASIA REGIONAL WORKSHOP ON BIOLOGICAL SAFETY AND BIOLOGICAL RISK MANAGEMENT: JAMES LEDUC, Galveston National Laboratory and The University of Texas Medical Branch at Galveston; DAVID R. FRANZ, SBD Global; DIANE E. GRIFFIN, Johns Hopkins Bloomberg School of Public Health; and JOSEPH KANABROCKI, University of Chicago

STAFF: MICAH LOWENTHAL, Director, RITA GUENTHER, Senior Program Officer, BENJAMIN RUSEK, Senior Program Officer, NICOLE CERVENKA, Associate Program Officer, HOPE HARE, Administrative Assistant

REVIEWERS: To ensure that it meets institutional standards for quality and objectivity, this Proceedings of a Workshop—in Brief was reviewed by JAISHREE GARHYAN, Stanford University; JOSEPH KANABROCKI, University of Chicago; and SARA SAWYER, University of Colorado Boulder. THOMAS ARRISON, National Academies of Sciences, Engineering, and Medicine, served as the review coordinator.

SPONSORS: This workshop was supported by the Kumar and Shela Patel Endowment and the United Sates Department of State, grant S-LMAQM-11-GR-0065.

Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2022. Building Regional Capacity Among South and Southeast Asian Countries to Address Emerging Infections and Global Health and Security: Proceedings of a Workshop—in Brief. Washington, DC: The National Academies Press. https://doi.org/10.17226/26584.

For additional information regarding the workshop, visit https://www.nationalacademies.org/pga/policy-and-global-affairs. Policy and Global Affairs Copyright 2022 by the National Academy of Sciences. All rights reserved.