The spread of SARS-CoV-2 has put laboratories in Kyrgyzstan to the test. Since 2020, Germany has been part of a multi-partner effort to broaden and deepen testing capacity in the country, including the introduction of genetic sequencing.
Timely, accurate laboratory diagnostics needed now, more than ever
Since the start of the COVID-19 pandemic, health authorities around the world have been grappling with a pressing challenge: how to rapidly scale up laboratory testing capacity to keep pace with a fast-moving and shape-shifting virus.
Widespread access to testing is essential for preventing and controlling the spread of SARS-CoV-2. In many countries, however, the capacity to perform molecular diagnostics has been concentrated in a handful of laboratories, leading to huge testing backlogs and long turnaround times. As the pandemic has deepened, the emergence of virus variants has complicated the picture even further. Governments urgently need information about the variants in circulation to adopt appropriate public health measures, but often there is no local capacity to undertake genetic sequencing of SARS-CoV-2.
As the demands on laboratory systems continue to grow in the face of global health crises, regional and international laboratory partnerships, sequencing networks and other forms of technical collaboration are more important than ever. In Kyrgyzstan, where the pandemic has pushed the laboratory system to its limits, a remarkable multi-stakeholder collaboration has helped to broaden and deepen laboratory diagnostic capacity in line with the country’s COVID response plan.
An exemplary collaboration
Anchored by the German Epidemic Preparedness Team (SEEG), the Promotion of Primary Healthcare (PPH) project and the World Health Organization (WHO), a group of partners has combined expertise to provide tailored training in genetic sequencing techniques to laboratory personnel working in central laboratories in Bishkek and training in molecular diagnostics to staff at the sub-regional laboratory in Osh.
‘German development cooperation supports measures aimed at strengthening the performance of Kyrgyzstan’s health system as a whole, and laboratories are a key part of this,’ explains Valerie Broch Alvarez, the head of the PPH project, which is implemented by the Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ) GmbH on behalf of the German Federal Ministry for Economic Cooperation and Development (BMZ). ‘The pandemic has shown the need to work at multiple levels, from ensuring basic capacities at peripheral laboratories right up to the introduction of cutting-edge sequencing techniques at the national level.’
As part of Germany’s immediate support for Kyrgyzstan’s COVID response in 2020, GIZ, working on behalf of BMZ, entered into a financial agreement with WHO aimed at strengthening the Kyrgyz laboratory system. ‘Since the beginning of the COVID-19 pandemic, WHO has been providing technical assistance to train national laboratory specialists on biosafety and the safe collection, transportation, processing and preparation of samples for further testing,’ explains Dr Nazira Artykova, the WHO Representative in Kyrgyzstan. ‘This not only aids the response to the current pandemic, but also strengthens the health system to respond effectively in the case of future health emergencies.’ The additional resources from Germany allowed WHO to intensify its efforts in the areas of infection prevention and control, the training of laboratory technicians, and the provision of infrastructure support. As the pandemic progressed, this cooperation deepened in the context of two specific laboratory strengthening interventions, which are described below.
Established by German Federal Ministry for Economic Cooperation and Development (BMZ) and the German Federal Ministry of Health (BMG) in late 2015, the German Epidemic Preparedness Team (SEEG) draws upon the expertise of some of Germany’s leading public health and research institutions: the Bernhard Nocht Institut for Tropical Medicine, Charité Universitätsmedizin, and the Robert Koch Institute. The German Federal Ministry of Food and Agriculture (BMEL) joined the collaboration in 2021, with the Friedrich-Loeffler-Institut contributing expertise on animal health and supporting the implementation of the One Health strategy. Responding to requests from partners, SEEG assembles multi-disciplinary teams of experts – including microbiologists, virologists and epidemiologists – who work directly with their peers in partner countries to strengthen systems for detecting and containing infectious disease outbreaks.
Genetic sequencing: A groundbreaking request to the German Epidemic Preparedness Team
In November 2020, during an initial visit by SEEG experts to Kyrgyzstan, the Ministry of Health requested technical support from Germany in the area of genetic sequencing. Variants of SARS-CoV-2 had begun emerging in countries around the world, but laboratories in Kyrgyzstan were not able to determine whether any of them were circulating locally. Samples had to be sent abroad to international WHO reference laboratories for sequencing, which made it impossible to understand changes to the epidemiological situation in real time.
Since the start of the pandemic, SEEG had provided rapid support to laboratories in 20 countries, but this marked the first time that it would train partners on sequencing techniques. The SEEG experts knew that the choice of laboratory was crucial. While in Bishkek, the team members assessed several laboratories and concluded that the National TB Reference Laboratory, whose establishment had been supported in part by Germany via KfW Development Bank, offered a suitable setting for training experts from several leading Kyrgyz institutions. These included the Center for State Sanitary and Epidemiological Surveillance and the Republican Center for Quarantine and Particularly Dangerous Infections, both of which were closely involved in the development of the training concept.
‘Sequencing work is more technically challenging than other types of diagnostics,’ says Dr Norman Nausch, a GIZ technical advisor who led the second SEEG mission to Kyrgyzstan. ‘One needs an established molecular laboratory which operates according to certain standards, as well as highly-trained staff with specific technical expertise. It cannot be done in just any laboratory.’
Because the cost and the work involved in sequencing are significantly greater than in standard diagnostics, there should also be a long-term perspective for sustaining the investment, explains Dr Nausch. This includes systems for procuring reagents and a partner who provide ongoing technical support. In the case of the National TB Reference Laboratory, that partner was the Research Center Borstel, a leading lung research center in Germany which has been working closely with staff at the laboratory for many years, including in the area of genetic sequencing for tuberculosis.
With a shared aim, GIZ and WHO coordinate efforts
WHO laboratory experts from the Euro regional office, as well as experts based in Bishkek, were also exploring ways to support the development of sequencing capacity in Kyrgyzstan and had reached a similar conclusion about the National TB Reference Laboratory as an institutional home for these new techniques. They had entered into contact with the Research Center Borstel to develop online trainings for staff at the laboratory on sequencing techniques for SARS-CoV-2, with a face-to-face training and mentoring support to follow.
Recognising the potential synergies between the WHO and SEEG initiatives, Valerie Broch Alvarez put the different actors into contact and encouraged them to build upon one another’s contributions. She coordinated closely with Mustafa Aboualy, a Technical Officer at WHO who leads the laboratory strengthening work in Central Asia. ‘There was quite a lot of overlap between the planned GIZ and WHO activities,’ Aboualy recalls. ‘Thanks to flawless coordination between the different players, we were able to join everything together into a proper approach.’
The first locally generated sequencing results
In February and March 2021, staff at the National TB Reference Laboratory took part in three online training modules on SARS-CoV-2 genetic sequencing which were prepared by Research Center Borstel and supported by WHO. In mid-May, a seven-member SEEG delegation arrived in Bishkek to pick up where the theoretical trainings left off. ‘This was a perfect synergy,’ recalls the WHO’s Aboualy. ‘SEEG built directly on the first phase of the work and brought in the practical, hands-on part of the training.’
The SEEG team comprised experts from GIZ and the Institute of Virology at Charité-Universitätsmedizin in Berlin, as well as the Martsinovsky Institute for Medical Parasitology and Tropical Medicine, at Sechenov University in Moscow, which has worked with experts from Charité on similar missions in the past. The involvement of Russian-speaking specialists contributed significantly to the achievement of objectives, as it allowed more technical content to be covered in a shorter time.
Over the course of five days, the SEEG team trained 11 laboratory staff from the National TB Reference Laboratory, the Center for State Sanitary and Epidemiological Surveillance, and the Republican Center for Quarantine and Particularly Dangerous Infections in high-throughput sequencing techniques for SARS-CoV-2. This was followed by training in bioinformatics, so that participants could begin developing skills to analyse and interpret the sequencing results. The content for the training program was aligned with the theoretical introduction provided by WHO and Borstel, thereby ensuring a coherent and streamlined experience for the participants.
By the end of the week, the participants had successfully sequenced a selection of 96 previously collected samples which had been frozen and kept in storage. This marked the first time that SARS-COV-2 had been sequenced in the country. Although the results were not representative, they did provide the Ministry of Health and other decision-makers with an indication of the type of data that could be generated in the country if a systematic sequencing strategy was put in place.
For Gulmira Kalmambetova, the director of the National TB Reference Laboratory, this was a major achievement: ‘I find it amazing that this high technology can now be implemented in this part of the world,’ she says. ‘It provides a huge opportunity to see how the pandemic is unfolding here, and to be prepared for possible outbreaks of variants that are already spreading in other countries.’
Strengthening molecular diagnostics and quality management in Osh
In addition to support for genetic sequencing, the Ministry of Health also asked SEEG to support main public health laboratory in Osh, Kyrgyzstan’s second-largest city.
While the medium-sized laboratory had the basic equipment needed to carry out molecular diagnostics for SARS-CoV-2, many of the staff were unfamiliar with PCR diagnostic techniques and some lacked biosafety training. Moreover, the lab’s work processes were not optimised to enable high-volume testing. This had become clear during the first wave of the pandemic, which started and was concentrated in and around Osh, as the great majority of samples had to be transferred across the country, to Bishkek, for testing.
Once again, SEEG, PPH and WHO coordinated their activities to develop a comprehensive training programme. The team from SEEG carried out a four-day training on biosafety and basic PCR testing for 11 staff at the laboratory. Immediately thereafter, a team of WHO experts conducted an advanced training on the use of single-nucleotide polymorphism (SNP) assays, which can screen for the presence of major variants. This method allows laboratories to rapidly identify samples with specific mutations that can be redirected for sequencing.
During the time in Osh, with the involvement of advisors from PPH, the SEEG and WHO teams assessed the laboratory infrastructure, workflows and procedures, and developed recommendations for easy-to-implement measures which could improve the quality of the laboratory’s work. WHO is in discussion with the Ministry of Health about further support to the laboratory in Osh to enable it to play a leadership role among laboratories in the region. The PPH project, which works closely with partners in Osh, is also exploring ways to support the laboratory, with a particular focus on infection prevention and biosafety.
New technologies can be introduced, but the capacities must be sustained
The COVID pandemic has created an opportunity to introduce new diagnostic technologies to laboratories in Kyrgyzstan, but ensuring that these new capacities are sustained – and that they contribute to system-wide improvements in laboratory services – will require continued support.
The Ministry of Health has a key role to play in ensuring that genetic sequencing is embedded in the national approach to SARS-CoV-2 surveillance, including the development of a strategy on the selection of samples to be sequenced and channels for reporting and analysis of results. The success of such an approach will depend not only on the specialist laboratories with the capability to carry out state-of-the-art diagnostics, but on the performance of the laboratory system as a whole.
‘We have seen that the quality of the samples coming into PCR laboratories depends on the people who work in the sample collection unit and in the peripheral laboratories,’ explains Gulmira Kalmambetova. ‘If we have good quality samples, we will have good results. Biosafety and the implementation of quality management systems are key components that should be supported by partners.’
The smooth working relationships established between the various technical partners over the past year provide a strong basis for continued collaboration in these areas – in Kyrgyzstan and beyond. SEEG and the Primary Healthcare in Kyrgyzstan project are planning a meeting next year where partners from across the region will be exchange scientific and operational experiences with COVID diagnostics, including genetic sequencing.
Karen Birdsall
October 2021