13.3.1. Testing algorithms – these should be country specific and in place before an outbreak happens
Countries should develop testing algorithms for routine testing for measles and rubella based on existing surveillance and laboratory capacity and that are consistent with the epidemiological setting and Measles: Vaccine Preventable Diseases Surveillance Standards and Rubella: Vaccine Preventable Diseases Surveillance Standards. The algorithm should include use of IgM testing and RT-PCR, if available, for case confirmation including routine or reflex testing of measles negative specimens for rubella. Special testing for ruling out cases with false positive IgM results or classifying breakthrough infections should be included if capacity is available. If local testing capacity is limited, algorithms should include contingency plans for referral of specimens to reference laboratories for specialized testing. Testing algorithms should include a plan for collecting representative specimens for virus detection and genotyping from all chains of transmission and from sporadic cases. Laboratories performing genotyping should have the ability to submit sequence information to MeaNS/RubeNS. GMRLN laboratories should be accredited for serology, virus detection and genotyping based on regional requirements.
The country specific outbreak response plans should describe how the routine testing algorithm could be modified during an outbreak response when the number of specimens increases substantially. The outbreak response plan should describe a threshold for switching from case-based investigation to epidemiological linkage and outbreak monitoring. This switch has major implications for measles surveillance and is the responsibility of the national MR program. Outbreak scenarios in which this will be required, such as scale and geographic range should be reviewed in advance, triggers identified and agreed with surveillance system including the national laboratory calls for use of laboratory testing and epidemiologic linkage for case confirmation together in a sustainable way that allows maximization of laboratory resources. In this context, laboratory testing for every suspected case is no longer necessary and a limited number of specimens should be collected during the early stages of an outbreak. The number of specimens should be adequate to confirm the outbreak as measles or rubella. A clear plan for prioritizing testing to support public health initiatives while not overwhelming the laboratory should be developed and should rely on epidemiologic linkage to minimize unnecessary testing.
Some points to consider for testing during outbreaks:
- Intensified passive and active surveillance should be established in the affected districts and neighbouring areas still not affected by the outbreak with a focus on areas with known immunization gaps.
- Case investigations should include the required minimum number of data elements (unique identifier, name, residence, age, sex, clinical symptoms, date of rash onset, date of specimen collection if done, vaccination status, travel history) but can move from individual case investigation forms to a line-listing of cases. Line lists should be available to both laboratory and epidemiologic staff in real time.
- The program should define a level of measles or rubella activity that would trigger the transition from case-based surveillance to line listing of cases. There should be clear trigger points for transition to outbreak response mode.
- Specimens for case confirmation should be collected during the initial phase of the outbreak to confirm the etiology of the outbreak. For measles and rubella outbreaks, specimens should be collected at least every two months, and more frequently depending on need to monitor transmission to previously unaffected areas (districts, schools, institutions etc.) as determined by program and laboratory staff.
- Epidemiologic linkage should be used to confirm cases and reduce the need for laboratory confirmation.
- The outbreak response plan could consider establishing time limits on the minimum and maximum numbers of specimens submitted from defined areas. For example, for the next month each “district’ should submit at least X but no more than Y specimens/week. Changes in specimen numbers can be made after consultation with MR program and laboratory staff. (See checklist below)
- Outbreak response vaccination may increase the frequency of vaccine reactions. In outbreaks settings where there is a possibility of exposure, rapid laboratory confirmation of vaccine reactions will help limit unnecessary response activities. Laboratories should consider available option for confirming vaccine reactions by genotyping or with a validated vaccine specific real time RT-PCR assay.
- The laboratory should be prepared to provide protocols for specimen collection, shipment, and storage.
- If specimens for virus detection are not routinely collected from suspected cases, representative specimens (preferably respiratory specimens) should continue to be collected for genotyping which reflect the scale and distribution of the outbreak, Sequence information can provide valuable information on the transmission patterns of infection and help identify new sources of virus. Systematic real time genotyping may be a lower priority and program, and laboratory staff should discuss the appropriate timing and scale of genotyping including referring specimens for genotyping to a reference laboratory, aiming at genotyping 80% of chains of transmission and sporadic cases as required for the verification process. In case there is no local capacity for genotyping, collected specimens should be stored at -70°C until shipping to the RRL. While it is critical to collect specimens for genotyping in a timely manner, collaboration between epidemiologists and laboratory is recommended to determined which specimens are a priority for genotyping based on the epidemiological situation. Therefore, to conserve resources, some of the collected specimens will not need to be genotyped if genetic information is already available for that chain of transmission.
- Establish a formal protocol between laboratory teams and epidemiologists to determine which specimens should be selected for genotyping to cover all chains of transmission. Prioritize samples from new or unexplained transmission chains or underrepresented geographic or demographic groups. Use subnational epidemiologic maps or tables with DSID data routinely for clear guidance and systematic tracking.
13.3.2. Rubella and mixed outbreaks
Laboratory plans should consider the possibility cases of rubella and other febrile rash illnesses may be present and ensure that laboratory testing capacity, either in country or through a reference laboratory, is available for reflex testing. Parallel testing for measles and rubella may already be in place. In this situation, in the context of measles outbreak, parallel testing for rubella should be switched to sequential testing of measles negative specimens only.
13.3.3. Staffing and laboratory workflows
The increase in testing capacity required to respond to outbreaks needs to be planned. Pressures on laboratories for specimen transport, data entry, booking in and timely reporting of results are often overlooked and should be part of advance planning. The scale of testing and sustainability required needs forward planning including staffing and laboratory consumables. Prepositioning of laboratory kits should be considered. Laboratories may consider use of measles-specific rapid diagnostic tests (RDTs) if available. Laboratories should carefully evaluate their current workflows and anticipate needs to establish surge capacity. Analysis of workflows should include all aspects of testing from receipt of specimen to reporting of results. It is important to consider components of the workflow that may be rate limiting such as availability of BSCs, access to facilities for RT-PCR, and key equipment. Laboratories should consider needs for supplies, test kits and reagents and have a plan for acquisition of material in a surge situation (see section on IRR below).
Laboratories should also consider availability of trained staff and develop a surge testing plan. For example, it may be beneficial to cross train laboratory staff in other areas to perform measles and rubella testing in an emergency. Consideration should be made to lengthening current test turnaround times to increase batch sizes, to reduce hands-on time and to optimise available assay consumption.
Laboratories should develop estimates of testing capacity for routine surveillance and outbreaks situations. For example, the maximum capacity for routine testing is X samples per week that can be accessioned, tested and reporting. This number can increase to Y with during outbreaks with surge staffing and laboratory space.
Laboratories can use the checklist provided in the Annex to develop plans for surge capacity (Annex A08).
13.3.4 Procurement of laboratory reagents and supplies
- Domestic procurement. All countries in particular middle-income countries (MICs) and High-Income countries (HICs) are strongly encouraged to devise an outbreak procurement component included in their national laboratory testing policy, including increased access to domestic funding or other sources (see above 3. Contingency finance) and potential waivers on routine tendering processes.
- International Reagent Resource (IRR). The IRR has made a major impact in ensuring consistent and timely supply of measles and rubella, IgM EIA kits, and key molecular reagents. This has helped to prevent national and local stockouts and the system is now in place for most eligible countries. Some countries require funding to release IRR reagents out of national customs, which should be factored into this planning process. It takes time to arrange shipments, and so countries are encouraged to confer with their surveillance and laboratory colleagues to plan for continuity of supplies during outbreaks and not to wait until outbreaks are established. Laboratories should work with the Regional Laboratory Coordinator and IRR Team at CDC to discuss contingency plans for outbreaks. Laboratories should make sure that there is at least one registered IRR user and one back up available for emergency orders. IRR is primarily intended for low-income countries (LICs) and eligibility for middle income countries (MICs) during outbreaks should be decided based on available funding and stocks.
- WHO HQ kit stockpile. Measles IgM EIA kits can be made available through WHO HQ on a case-by-case basis. These are held to support emergency situations.
13.3.5 Laboratory Role in Outbreak Response
Once an outbreak is confirmed through GRMLN-supported testing, the laboratory’s role shifts to sustaining response efforts; laboratory teams play a critical role in informing and sustaining the public health response. This includes:
- Communicating results from case confirmation rapidly to outbreak coordination bodies.
- Maintaining testing throughput to monitor the evolution of the outbreak.
- Coordinating with national and partner laboratories to provide sequencing and genotyping where relevant.
GRMLN’s role in rapid laboratory confirmation is critical to triggering outbreak response immunisation campaigns. To ensure timely response, lab workflows should aim to provide confirmation within 72 hours of receiving adequate specimens. In settings where routine surveillance is weak, lab data may serve as the first objective signal of outbreak onset. GRMLN can also support EPI teams by sharing epidemiologic and virologic data to inform vaccination targeting (e.g. genotype-linked transmission chains, risk of importation).
GRMLN labs should support case management by rapidly confirming measles in high-risk patients or clusters. Timely confirmation can enable prioritisation of isolation measures, targeted resource allocation, and reduction of nosocomial transmission.
GRMLN confirmation is a key eligibility criterion for accessing the Measles Outbreak Response Fund (ORF). Therefore, ensuring rapid, accurate, and well-documented lab confirmation of at least two unrelated measles cases within a defined time (typically 60 days) is essential. Reporting, especially in Gavi-eligible countries, to avoid delays in ORF application. In humanitarian contexts, alternative specimen transport pathways or simplified referral forms may be required to expedite confirmation and response.
13.3.6 Adaptations for Humanitarian and Fragile Settings
In humanitarian settings, these functions may require adapted procedures to maintain sample flow and result delivery under access constraints.
- GRMLN coordination should be integrated with Health Cluster structures or equivalent humanitarian response mechanisms to support lab surge capacity, facilitate sample transport, and enable response despite logistical barriers. GRMLN focal points should be included in national or interagency outbreak coordination mechanisms, and work in tandem with EPI and surveillance units to ensure laboratory elements (confirmation, sequencing, reporting) are synchronised with broader response strategies.
- In those settings, lab support for outbreak response may require non-traditional approaches. Where central laboratories are inaccessible, GRMLN should facilitate alternative confirmation pathways, such as designated decentralised labs, collaboration with NGO-run clinics, or even mobile labs. Syndromic surveillance backed by RDTs or batch testing may be used in low-access areas, with GRMLN assisting in quality assurance and training. Wherever possible, simplified lab reporting tools and remote result communication (e.g. SMS, email alerts) should be in place to avoid delays. The role of GRMLN also includes supporting cross-border surveillance and sequencing, which is critical where displaced populations move between epidemiologic zones.