With support from Germany, virologists in Uzbekistan have designed their own reference panel for influenza. Not only will this help to strengthen surveillance for seasonal and pandemic influenza, but it will also ensure quality PCR diagnostics at regional laboratories across the country.

Last month, the virology laboratory at the Sanitary and Epidemiological Welfare and Public Health Committee (Sanepidcom) at the Ministry of Health in Tashkent, Uzbekistan was more crowded than usual. Fourteen cryogenic shipping cases – specially designed to maintain their contents at a constant temperature of minus 40 degrees Celsius – were lined up in a row, waiting to be packed with precious cargo. Once ready, they would be sent out to regional laboratories across the country and a controlled exercise to assess the quality of laboratory diagnostics in Uzbekistan would begin.

An Uzbek-German collaboration breaks new ground

The boxes contained identical reference panels with influenza samples prepared by virologists at Sanepidcom in cooperation with experts from the Robert Koch Institute, a German government agency responsible for disease control and prevention. Reference panels, also known as interlaboratory comparison panels, are tools which can be used by national laboratories, such as Sanepidcom, to check the reliability of diagnostic results being generated at the labs which they oversee.

This particular reference panel was significant, because it marked the first time that virologists in Uzbekistan had created their own influenza panel from scratch, rather than using one prepared by another institution, such as the World Health Organization, or purchased from an outside supplier. The collaboration with the Robert Koch Institute which made this possible was supported by the German Federal Ministry for Economic Cooperation and Development (BMZ), and coordinated by the Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ) which implements a project on the management of advanced medical technology in Uzbekistan on behalf of BMZ.

External quality assurance and professional testing are key responsibilities of reference laboratories

The idea to create a customised reference panel for influenza came from Sanepidcom, which wanted to evaluate the quality of the PCR (polymerase chain reaction) diagnostics being carried out by regional laboratories. ‘Up until now there has been no external quality assurance for the regional laboratories which do PCR tests for influenza,’ says Dr Iskander Zaitov, a virologist at Sanepidcom. ‘The panel will help us to do a comparative analysis across the different labs and warn us of any systematic errors associated with test systems or with the performance of testing.’ Although the panel is designed specifically for influenza, it will help to detect issues related to PCR testing in general, he explains.

 It is a core responsibility of reference laboratories to evaluate the performance of lower-level laboratories, which play a critical role in disease surveillance, and to ensure the reliability of results. Reference panels offer a standardised way of doing this. Each laboratory simultaneously runs a pre-defined set of tests on an identical set of samples and submits the results to the reference laboratory – in this case, Sanepidcom – where they are analysed and compared. For any discrepancies identified, the experts at the reference laboratory work with the staff at the regional laboratory to understand where the mistake is and what its cause might be. If necessary, additional training or support can be provided. In Uzbekistan, undergoing external quality assurance is a prerequisite for regional laboratories to receive accreditation.

A panel tailored to the epidemiological context of the country

The collaboration between Sanepidcom and the Robert Koch Institute dates back to 2021, when experts from the Institute travelled to Uzbekistan under the auspices of the German Epidemic Preparedness Team (SEEG) to strengthen capacities for SARS-CoV-2 diagnostics and improve internal quality assurance. SEEG is a multi-sectoral, multi-disciplinary rapid response team supported by BMZ, the German Federal Ministry of Health (BMG) and the German Federal Ministry of Agriculture (BMEL).  

‘We have long wanted to create a panel for PCR testing of respiratory infections and influenza,’ says Dr Zaitov, ‘but we did not have any experience preparing a panel ourselves and could not find sufficient information on the Internet to guide us.’ Following the successful collaboration with the SEEG experts, Sanepidcom turned to German development cooperation with a request to facilitate further technical assistance.

Dr Cristina Domingo, a microbiologist at the Robert Koch Institute, was part of the original SEEG mission to Uzbekistan and worked closely with Dr Zaitov and his colleagues over the course of many months last year to design the reference panel. ‘The aim was to create a panel which demonstrates that a laboratory has diagnostic capacity that is “fit for purpose,”’ she explains. This means that the panel should be neither too easy, nor too challenging.

The panel they designed together uses international reference controls for influenza, which she provided from Germany, as well as samples collected from Uzbekistan’s own regional labs. ‘What they have done is completely tailored to the epidemiological context of the country,’ Dr Domingo explains. ‘This is really very advanced.’

Overcoming logistical challenges to build a system for the future

While the design and creation of the panels was time consuming and technically demanding, it did not throw up any fundamental challenges. The same cannot be said for the logistics of the exercise. Uzbekistan is a sprawling country. From Tashkent it takes a full day by train to reach the furthest of the regional laboratories. Each of the 14 panels needs to reach its destination in exactly the same condition in which it was evaluated at the reference laboratory. Dry ice – the standard solution in Western Europe for maintaining molecular samples at low temperature during transit – is very expensive in Uzbekistan.

After exhausting all local options, the solution was to import cryogenic boxes for transporting the panels; special labels, suitable for extremely low temperatures, to identify each vial; and temperature logs which would digitally record the temperature inside the case from the moment it left Sanepidcom until the moment it was opened at its destination. All of this took considerable time and effort to organise, but now there is a panel distribution system in place which can be used for future exercises, as well.

‘The partners in Uzbekistan are really committed and they take the initiative,’ says Dr Domingo. ‘They know the country situation and they find approaches which work. I find this really valuable, because I learn, too. Dry ice was not possible, so we had to adapt. These are learnings that can be applied in other countries and situations.’

Quality assurance builds confidence in laboratory systems

While the focus of this exercise has been influenza, reference panels can be designed to evaluate the quality of diagnostics for other types of diseases. Dr Zaitov and his colleagues at Sanepidcom hope to build upon this experience and set up external quality assurance panels for other respiratory viruses which, like influenza and SARS-CoV-2, are diagnosed on the basis of samples from the nose or throat. Eventually they would like to adopt it, using a different methodology, for other diseases such as polio or measles. ‘Not every lab is able to do what this team has done,’ says Dr Domingo. ‘I expect that they will use what they have learned with this panel and widen the scope even further.’

This investment in external quality assurance will yield important public health benefits. ‘Good quality laboratory performance is really important for the entire surveillance system,’ says Elena Mun, the technical advisor with GIZ who is responsible for coordinating this collaboration between Sanepidcom and the Robert Koch Institute. It also builds popular trust: ‘If our labs in Uzbekistan can pass external quality assurance, patients can be confident in the diagnostic results they receive.’

Karen Birdsall
March 2024