Language:
Search
 
Laboratory Response to Influenza Pandemic Alert
National Institute of Health, Department of Medical Sciences
Thailand

The Problem

In Thailand, the responsibilities to detect and contain disease outbreaks rest under the Ministry of Public Health (MOPH). Usually, an index case of an outbreak is detected in a private or public clinical setting and then reported by an officer working in the area (e.g. district or provincial or regional offices) to disease control authority. Such investigation is usually supported by public health laboratory located in the region or at the central level. The Disease Control Department (DDC) of the MOPH is the national disease control authority and the Department of Medical Sciences (DMSc) of the MOPH is the national public health laboratory.

The DMSc is represented centrally by the National Institute of Health (Thai NIH) and regionally by the 14 Regional Medical Sciences Centers (RMSC) located across the country. The Thai NIH serves as the national reference laboratory for all communicable diseases and is fully equipped with diagnostic facilities including biosafety level [BSL]-3 laboratories and BSL-3 animal facilities. The RMSCs have less sophisticated facilities for virological investigations, e.g. none of them have BSL-3 laboratories nor the capacity to isolate virus. Only some RMSCs have been providing molecular diagnosis of infectious diseases as a routine service.

The report of the first human case of H5N1 in lower northern Thailand in 2004, after episodes of unexplained deaths of backyard chicken, alarmed the whole country, as it reminds us of influenza pandemic. As the standard measure, all chickens in affected areas were culled. This resulted in losses of income of farmers. In addition, human contacts of dying chickens were at risk of H5N1 disease. Health care workers were also concerned because they never had experiences in dealing with H5N1. The public paniced and, as a response, avoided consumption of chicken, albeit adequately cooked. Politicians were pressured by the public to get involved and take actions, although they were not technically prepared. The situation was further aggravated as more cases were suspected, e.g. 3,097 suspects during January, 2004 and March,2004). There were 12 confirmed human cases of H5N1 in this first episode, all of which were laboratory-confirmed at the Thai NIH using WHO-recommended methods, e.g. viral isolation and immunofluorescence assay (IFA). However, these conventional methods took a long time to complete, i.e. about 20 days.

With the growing public concern, the number of specimens sent to the Thai NIH rose from a usual average of 10 specimens per day, before the first human H5 case, to a maximum of 300 specimens within a week after the first case detection. On the average, 60 specimens per day were received and handled by three staff members of the Respiratory Virus Laboratory (which is Thailand’s WHO-designated National Influenza Center [NIC] since 1972) of Thai NIH which, taking turns, worked around the clock to get the laboratory results as soon as possible, despite the time-consuming procedures.

Various social groups were affected by the emergence of H5 disease in humans, e.g. farmers, cullers, health care workers, politicians, and the general public.

Solution and Key Benefits

 What is the initiative about? (the solution)
The main objective of this initiative was to have better laboratory response to the H5N1 outbreak in Thailand and to the influenza pandemic alert. This initiative included upgrading laboratory facilities at RMSCs, introducing new laboratory techniques, establishing standard operating procedures (SOPs), providing training and educational activities, establishing new means of results reporting, and adding mobile laboratories to the system.

In summary, this initiative provides a national network of strengthened public health laboratories for influenza viruses including H5N1. In the network, there are also companion laboratories at universities because laboratory labeling of H5N1 in a human case has significant negative consequences.

The initiative has resulted in following tangible benefits:
- thirteen laboratories at the RMSCs were upgraded and could handle molecular diagnosis of H5N1
- seven SOPs were developed at the Thai NIH and RMSCs on laboratory diagnosis of H5N1
- more than 7,000 physicians, nurses and health care workers were trained and provided with necessary information on collection, handling and transporting of specimens for H5N1 laboratory diagnosis and on interpretation of laboratory results
- thirty laboratory scientists at the RMSCs were trained on molecular diagnosis of H5N1
- total turnaround time from when the specimens reached the Thai NIH or the RMSCs to the time when unofficial results were posted on the website were reduced to 39 hours (as compared to 23 days before the initiative), i.e. a 93% reduction
- laboratory analysis time (the time from specimens received at the laboratory to the time results sent out from the laboratory) was reduced from 20 days (before the initiative) to 24 hours (with RT-PCR as the initiative), i.e. a 95% reduction in time for laboratory analysis; and then to 8 hours (with realtime RT-PCR as the additional initiative)
- two mobile laboratories were added to the system
- five locations were served by the two mobile laboratories where 2,900 specimens were tested with the same turnaround time as the permanent laboratories at the Thai NIH and the RMSCs
- Thai NIH established the Coordinating Center for Testing and Laboratory Surveillance (CCTLS) to serve as the one-stop service for all specimens coming to the institute (www.cctls.org)
- web-based reporting system through a secured and dedicated website was established at the CCTLS; other means of reporting, e.g. verified telefacsimile, was also used
- a 24-hour call center was established at the Thai NIH to provide communication means with customers
- a survey at the CCLTS on customers satisfaction showed that 93% of the customers satisfied or very satisfied with the services.

This initiative clearly benefited all concerned parties. The patients were provided with better and timely care and suspected cases were not put in isolation rooms unnecessarily. Physicians and nurses could allocate limited resources (e.g. antivirals, isolation rooms at hospitals) to H5N1 cases that really need them. Disease control authority had necessary laboratory information for containment activities. Laboratory scientists were under less pressure because a higher number of specimens could be accommodated with shorter turnaround time.

Actors and Stakeholders

 Who proposed the solution, who implemented it and who were the stakeholders?
The initiative was part of the overall efforts of the Ministry of Public Health to rapidly respond to the outbreaks of H5N1 as a means for pandemic influenza preparedness. At the Ministry level, a committee was established to streamline specimen collection, handling, transporting as well as reporting and interpreting of laboratory results. The committee was established by the Ministry Decree on April 1, 2004 and composed of 21 members (7 hospital-affiliated health care workers, 5 laboratory scientists, 4 epidemiologists, 3 physicians, and 2 laboratory technicians). The committee was chaired by one of the deputy director generals of the DMSc and met at least weekly, most of the time daily or every other day, over the six-week interval. The committee identified five core components to strengthen laboratory response to influenza pandemic alert, i.e. 1) the need for single national reference laboratory for H5N1 confirmation; 2) well-trained and well-dedicated laboratory personnel; 3) strengthened H5N1 and other potential pandemic influenza virus laboratory surveillance with appropriate clinical specimens and accurate and reliable methods, such as PCR; 4) well-defined laboratory reporting algorithms; and 5) a dedicated channel, such as secured website, to provide education to the health care workers and the general public and to report preliminary unofficial results to the attending physicians and the disease control officers.

The DMSc, by the Thai NIH, took the mandates as assigned by the committee and implemented the initiative. This was done in consultation the Strategic Advisory Group (SAG) for Emerging and Re-emerging Infections of the MOPH, and experts from
- academia (e.g. Mahidol University)
- disease control authority (e.g. Bureau of Epidemiology, Office of Influenza, and Bureau of General Communicable Diseases, of the Thai DDC)
- international organizations (e.g. WHO Country Office for Thailand)
- non-governmental organizations (e.g. Influenza Foundation of Thailand).
Needs and inputs from the RMSCs and the hospitals from which specimens were sent were also included in the operation of the mandate.

(a) Strategies

 Describe how and when the initiative was implemented by answering these questions
 a.      What were the strategies used to implement the initiative? In no more than 500 words, provide a summary of the main objectives and strategies of the initiative, how they were established and by whom.
The ultimate objective of this initiative is to provide a better system of laboratory response to influenza pandemic alert. The system takes H5N1 in humans as the test case of the initiative, which is based on the following strategies.

Customer orientation
The primary impetus for this initiative is the demand of the customers (e.g. health care workers, patients, and disease control authority) for faster, yet accurate, laboratory results to confirm or refute H5N1 infection in humans. Although the viral isolation technique is the gold standard and highly accurate, it is time-consuming and less sensitive than molecular technique. Therefore, newer and more sensitive analytic approaches were proposed and used in the initiative.

Full participation of all stakeholders
The design of the initiative, as well as choice of specific laboratory techniques, was done with full consultation with experts and stakeholders. The needs and the limitations of the RMSCs were taken into full account as it is not useful to devise an excellent laboratory technique that cannot be performed at the RMSCs and/or hospitals, where about half of the total specimens were tested.

Knowledge-based development
Design of a new laboratory method based on molecular technique needs in-depth knowledge of the circulating viruses as well as optimal condition for the test method. Since the viruses are ever-evolving and many clades of viruses are present and can be introduced independently into Thailand, the laboratory technique needs to be updated and the primers and the probes for use in the molecular techniques need periodic review and, possibly, redesign.

Continuous quality improvement (or total quality management)
It is fully realized that devise of a new laboratory technique is not the whole answer for better laboratory response to influenza pandemic alert. The initiative was therefore designed with multiple objectives, i.e. to shorten the time from specimen collection to reporting of test results, to improve quality of specimens collected, to enhance access to areas where it is usually hard to transport specimens out, and to increase satisfaction of customers at all levels. This is done through the continuous quality improvement (CQI) process which involves 4 continuous steps of Plan, Do, Check and Act (PDCA loop), until the desirable results are achieved.

Effective communication
This initiative is multi-dimensional and national in scale and scope. It involves activities before, during, and after specimens arrives at the laboratories. The whole initiative introduces several new components, e.g. new laboratory methods, mobile laboratories, and web-based reporting system, as well as strengthens existing components, e.g. laboratory safety, knowledge and skills of laboratory personnel. Therefore, effective communication is needed to ensure smooth implementation of the initiative and make sure that the new system is functioning well as planned and can be sustained in the longer term. Communication is made through several channels at different levels, e.g. MOPH-convened committee, Thai NIH-appointed task group, and internal meetings.

(b) Implementation

 b.      What were the key development and implementation steps and the chronology? No more than 500 words
The initiative was divided into three phases, e.g. pre-implementation, implementation, and post-implementation.

In the pre-implementation phase, the following steps were taken:
January, 2004: Existing laboratory systems at the Thai NIH and the RMSCs were reviewed
January, 2004: A task group was established at the Thai NIH to devise a new laboratory system. The task group was chaired by one of the deputy directors of the Thai NIH and composed of representatives from all units concerned of the Thai NIH.
January, 2004: A committee was set up by the MOPH to streamline laboratory testing and reporting processes for suspect H5N1 infection in humans.
January, 2004: RT-PCR method for diagnosis of H5N1 was established at the Thai NIH and later at the RMSCs.
August, 2004: Necessary SOPs were developed and adopted at the Thai NIH and the RMSCs.
September, 2005: A prototype mobile laboratory was built to provide molecular testing services for H5N1. The other mobile laboratory was later added.
January, 2005: Laboratory scientists at the RMSCs were trained on RT-PCR.
From April, 2004-present: Health personnel including disease control authority were trained on specimen collection, handling, and transport, as well as interpretation of laboratory results.
December, 2005: Realtime RT-PCR method was introduced at the Thai NIH as an additional routine method for H5N1 detection.

During implementation, the steps taken were:
January, 2004: Molecular diagnosis services (conventional RT-PCR) were provided to detect and confirm H5N1 in suspect cases.
May 2004: CCTLS was established at the Thai NIH as the one-stop services for all laboratory testing needs including detection and confirmation of H5N1 in humans.
May 2004: Call center was established at the Thai NIH as the main channel of communication between the DMSc and customers.
August 2004: Web-based reporting system was developed.
January 2005: Realtime RT-PCR method was introduced as a routine method for H5N1 detection at the Thai NIH.
October, 2005: Mobile laboratories were dispatched to hard-to-access areas to provide on-site services for laboratory confirmation of H5N1.
February 2007: Thai NIH and RMSCs entered into an inter-laboratory comparison scheme with the WHO Collaborating Centres for Reference and Research on Influenza as external quality assurance.


Post-implementation steps and activities included:
After implementation:
- Customers’ satisfaction was periodically assessed and weaknesses and unmet needs of the customers were identified for further improvements.
- In April, July and October 2006, three international workshops were organized at the Thai NIH to provide training to scientists and technicians from influenza laboratories from 9 countries (Thailand, Myanmar, Cambodia, Laos PDR, Vietnam, Nepal, The Philippines, India, Indonesia)
March 2006: A plan was developed to organize a proficiency testing program at the Thai NIH for RMSCs laboratories (starting in March 2006) and laboratories of neighboring countries (starting in 2008).

(c) Overcoming Obstacles

 c.      What were the main obstacles encountered? How were they overcome? No more than 500 words
This initiative received strong supports from policymakers of the MOPH, the DMSc, and the Thai NIH with adequate financial resources. The major obstacle was the shear extent of the H5N1 problem. Although the number of human cases of H5N1 in Thailand was relatively small, as compared to some countries in the region, the impacts are enormous. Not only that lives of the H5N1 victims were lost, but also significant economic losses and social consequences of the outbreaks were witnessed at all levels. Panic among the general public and the health care workers partially explained the increased number of specimens sent for testing, which, in turn, demanded a comprehensive initiative to deal with the problem systematically.

During the first episode of the H5N1 in humans in Thailand in early 2004, a significant number of specimens were collected and sent to Thai NIH and the RMSCs. A guideline for testing algorithm was quickly developed to screen the specimens. Skills of scientists and technicians from various laboratory sections within the DMSc were pooled and additional laboratory space and facilities were shared by other laboratories at the Thai NIH to cope with the increased workload of H5N1 testing.

Due to the high stake of positive laboratory results for H5N1, several borderline or equivocal or suspicious results were repeated, mostly unnecessarily. Therefore, in consultation with the SAG and experts, a revised guideline for testing algorithm was developed, which helped reduce the need for unnecessary repeating of the testing.

The reliability of laboratory testing for H5N1 in human specimens is significantly increased if the testing is informed by laboratory results for H5N1 detection in animal specimens from the same epidemiologically-linked areas. At the beginning, it was difficult to obtain the necessary data from the animal side. However, with continued efforts to forge closer communications at both policy and operational levels, synchronization of data and information became better over time.

The other obstacle is the very nature of the influenza viruses that are highly variant. Antigenic shift and antigen drift are well-known phenomena of the influenza viruses resulting from genetic mutations or re-assortments. As a result, laboratory methods need to be periodically reviewed and modified to the changing viruses. New probes and primers are likely to be needed for PCR diagnosis in the near future. However, design and synthesis of the probes and primers are quite expensive and can pose significant financial burdens to influenza control program.

(d) Use of Resources

 d.      What resources were used for the initiative and what were its key benefits? In no more than 500 words, specify what were the financial, technical and human resources’ costs associated with this initiative. Describe how resources were mobilized
Although this initiative was built on existing public health systems and infrastructures of Thailand, it demanded significant financial, technical and human resources, which needed to be mobilized additionally. As the response to the threats by the emergence of H5N1 in poultry and humans, the Royal Thai Government allocated special funds for containment of the outbreaks. The special funds were used together with regular budgetary resources of the government agencies concerned. The special appropriations of the special funds of 30 million US dollars (exchange rate of 1 US dollar = 35 Thai baht) were made in 2005-2006 by the Parliament at the request of the Government.

The financial resources, both regular and special, used for preparing and mounting laboratory response for influenza pandemic alert include the following activities (exchange rate used in this calculation is 1 US dollar = 35 Thai baht):
- procurement of 6 thermocycler machines for PCR diagnosis of H5N1 (59,900 US dollars)
- procurement of two mobile laboratories for avian influenza and other emerging viral infections (857,000 US dollars)
- procurement of PCR probes and primers and other necessary reagents (100,000 US Dollars)
- design and maintenance of a dedicated secured website for laboratory coordination located at the Thai NIH (10,000 US dollars and 3,000 US dollars /year)

This initiative did not hire additional human resources. Rather, it mobilized manpower from other laboratory sections within each organization and subjected existing personnel to overtime works. The costs for the increased manpower needs are as follows:
- overtime payments for personnel (5,000 US dollars)
- training costs for laboratory personnel (25,000 US dollars)
This initiative received technical supports from many persons and organizations including SAG, academia, governmental and non-governmental organizations, as described above. The costs for these technical resources could not be enumerated monetarily.

Sustainability and Transferability

  Is the initiative sustainable and transferable?
The initiative is believed to be highly sustainable for a number of reasons.
1. From a financial point of view, this initiative capitalized on existing infrastructures and systems. Therefore, the overall costs were significantly less, as compared to an initiative, which sets up a whole new system.
2. For the social and economic perspectives, this initiative is economically and socially viable and acceptable. The economic and social threats of H5N1 and other potential pandemic influenza viruses are far greater than the investments needed in this initiative. It would be socially disruptive and politically incorrect if this kind of initiative were not launched.
3. This initiative does not create negative cultural and environmental impacts. Neither does it infringe on regulatory requirements of any agency or institution in Thailand or elsewhere.
4. Technology developed in the initiative, e.g. computer software, database, can be applied to accommodate other diseases or used by other institutes. The computer application is open-source and not patented, and can be made freely available, upon request, to an individual or organization that needs it.
5. Experiences in design and implementation of this initiative have been included as part of the training provided by the Thai NIH to the RMSCs as well as to the laboratories from other countries, e.g. Myanmar, Laos PDR, and Cambodia. These experiences will be used as the knowledge for other developments.

Lessons Learned

 What are the impact of your initiative and the lessons learned?
There are a number of key success factors for this initiative.
1. The initiative is designed with customer focus.
2. It is built on existing systems and infrastructures with mobilizations of additional resources only if and as needed.
3. It enlists full participation of stakeholders and partners in all processes of design, implementation and evaluation.
4. It is designed based on existing knowledge which includes scientific knowledge related to H5N1 as well as knowledge of existing systems and conditions of H5N1 outbreaks in Thailand and elsewhere in the world.
5. It has a built-in mechanism to ensure that quality is assured and will be continuously improved.
6. An emphasis is placed on effective communication for both within and outside the initiative to ensure broad awareness of the initiative of the outside public; and clear understanding of detailed implementation and up-to-date knowledge of the progress of this initiative of the insiders.

Contact Information

Institution Name:   National Institute of Health, Department of Medical Sciences
Institution Type:   Government Agency  
Contact Person:   Dr. Pathom Sawanpanyalert
Title:   Director  
Telephone/ Fax:   +(66)2 9510000 ext. 99354-5
Institution's / Project's Website:   +(66)2 5899865
E-mail:   pathoms@loxinfo.co.th  
Address:   88/7 Tivanon Road
Postal Code:   11000
City:   Muang
State/Province:   Nonthaburi
Country:   Thailand

          Go Back
Print friendly Page