There are several key objectives for maintaining a unified network of laboratories to support measles and rubella programme goals:
- to develop and improve standardized protocols for the laboratory confirmation of measles and rubella;
- to establish standards for quality assurance and quality control;
- to administer and implement standardized global proficiency testing;
- to monitor the performance of network laboratories through annual accreditation;
- to provide training resources and facilities for staff of network laboratories;
- to facilitate inter-laboratory cooperation for expanding national and regional capacity;
- to maximize the efficient use of limited reagents and validated reference materials;
- to share expertise and data to track transmission of measles and rubella viruses;
- to provide support including WHO funding to enhance and maintain laboratories in limited resource settings.
The laboratories in the GMRLN are organized into four levels: global, regional, national and sub-national laboratories. The global and regional laboratories have been established as centers of excellence and act as reference facilities for national and sub-national labs. National and sub-national laboratories are nominated by the Ministry of Health of each Member State. The sub-national laboratories may be organized according to governing administrative levels and/or geographic areas (e.g., province/state, district/prefecture) [1].
Some of the laboratories may have more than one designation. For example, those RRLs that are responsible for first-line testing of samples by IgM and/or RNA detection fulfill the responsibility of a national laboratory. A description of general areas of responsibilities for the four levels of network laboratories is given below:
• Global Specialized Laboratory (GSL): The responsibilities of the GSL extend to measles and rubella laboratories in all regions and countries.
Technical support/Training: Provides technical advice, consultation and specialized training to regional and national laboratories. Assists in preparation of global reports and summaries of network activities. Develops periodic proficiency testing for regional laboratories.
Research: Contributes to the development and validation of novel methods and the standardization of procedures and protocols. Evaluates diagnostic kits and develops and improves methods.
Quality Assurance: Prepares standards, proficiency panels (IgM/serum and virus strains) and training materials.
Virologic surveillance: Develops and maintains standard protocols and databases for molecular epidemiology.
• Regional Reference Laboratory (RRL): Laboratories designated as an RRL have demonstrated the capacity to undertake international responsibilities and collaborate closely with the GSLs. Each WHO region may have up to four RRLs.
Reference Testing: Samples referred by National and Sub-National Laboratories are tested to provide case classification using standard and specialized methods. The RRL provides support for genetic characterization for samples referred for virologic surveillance.
Quality Assurance: Performs validation of their own and national laboratory results using a validated assay and internal controls. Coordinates proficiency testing, provides confirmatory testing for National Laboratories.
Technical support/Training: Provides training and consultation to national laboratory staff in collaboration with WHO.
Research: Collaborates with GSLs in the development and evaluation of new or improved methods.
Reports to: Country programme manager, National Laboratories and WHO.
• National Laboratory (NL): The NLs communicate directly with immunization programme managers.
Testing: Provides case classification for clinically suspected measles and rubella using IgM detection by EIA. Performs virus isolation or direct RT-PCR or both with samples collected for virologic surveillance. If facilities and capacity do not support molecular testing, the NL forwards clinical samples, virus isolates, or RT-PCR positive samples to the designated RRL. Performs epidemiologically essential serological surveys.
Quality assurance: Participates in annual proficiency programme. A proportion of specimens are sent to the RRL for confirmatory testing. Monitors the quality of Sub-National Laboratories under its responsibility.
Reports to: Country programme manager, sub-national laboratories and WHO.
• Sub-National Laboratory (SNL): In many countries, the responsibility of first-line testing of specimens for case classification is shared by laboratories at the sub-national level. This may be necessary because of population size and/or logistical challenges.
Testing: Provides case classification for clinically suspected measles and rubella using IgM detection by EIA. Samples collected for virologic surveillance are processed and packaged for shipment to the National or Regional Reference Laboratory for molecular testing and genetic characterization.
Quality assurance: Participates in annual proficiency programme. A proportion of specimens are sent to the NL for confirmatory testing.
Reports to: Country programme manager, National Laboratories.
In May 2018, there were 713 laboratories in the GMRLN conducting measles and rubella surveillance for 191 countries. These laboratories were based in 165 countries and included 506 sub-national, 180 national, 14 regional reference and three global specialized laboratories [2].