Diagnostics to make immunisation programmes more efficient, equitable, and effective
Authors: Lee M Hampton, Hope L Johnson, Seth F Berkley
Journal: The Lancet Microbe (2022)

Gaps in disease surveillance and diagnostic testing capacity are well documented,1Fleming KA Horton S Wilson ML et al.The Lancet Commission on diagnostics: transforming access to diagnostics.Lancet. 2021; 398: 1997-2050Google Scholar, 2Morgan OW Aguilera X Ammon A et al.Disease surveillance for the COVID-19 era: time for bold changes.Lancet. 2021; 397: 2317-2319Google Scholar and these gaps have important consequences for immunisation programmes. Timely, reliable diagnostic testing is essential for confirming where vaccine preventable diseases are occurring so that the right vaccines can be used in the right places, at the right times, and targeted at the right people. Although some vaccines are recommended by WHO for continual, regular use in routine immunisation systems in all countries, without the need for additional surge vaccination in response to outbreaks, many vaccines can be used more flexibly to reflect the variability of the diseases they prevent across different areas or different time periods (panel).3WHOWHO vaccine position papers.https://www.who.int/teams/immunization-vaccines-and-biologicals/policies/position-papersDate accessed: February 7, 2022Google Scholar, 4WHOSurveillance standards for vaccine-preventable diseases. World Health Organization, Geneva2018Google Scholar For diseases that threaten populations in some areas but not others, vaccines can be targeted for use in the at-risk areas without increasing morbidity and mortality in unvaccinated areas. For example, the symptoms of cholera resemble those of other causes of acute watery diarrhoea,4WHOSurveillance standards for vaccine-preventable diseases. World Health Organization, Geneva2018Google Scholar so diagnostic confirmation is needed to avoid targeting cholera-free areas with preventive or outbreak response vaccination campaigns.5Peak CM Reilly AL Azman AS Buckee CO Prolonging herd immunity to cholera via vaccination: accounting for human mobility and waning vaccine effects.PLoS Negl Trop Dis. 2018; 12e0006257Google Scholar For diseases that can cause epidemics, outbreak response vaccination campaigns can help mitigate and control surges in disease. As shown by past yellow fever, meningococcal, and Ebola outbreaks,4WHOSurveillance standards for vaccine-preventable diseases. World Health Organization, Geneva2018Google Scholar, 6Zhao S Stone L Gao D He D Modelling the large-scale yellow fever outbreak in Luanda, Angola, and the impact of vaccination.PLoS Negl Trop Dis. 2018; 12e0006158Google Scholar timely diagnostic confirmation is particularly important for outbreak response campaigns, which can be more effective if launched more quickly. Diagnostic testing as part of disease surveillance can also help make vaccination programmes more effective by identifying populations at risk for diseases despite previous vaccination efforts, allowing programmes to focus on reaching these populations, as has been done with measles vaccination.4WHOSurveillance standards for vaccine-preventable diseases. World Health Organization, Geneva2018Google Scholar Across these considerations, the greater the burden of morbidity and mortality or the vaccination costs that can be prevented through better targeting of vaccination, the greater the value of improvements in that targeting and of the diagnostic testing and disease surveillance systems that make it possible.PanelVaccine preventable diseases with WHO recommendations on use *COVID-19 has been omitted because WHO recommendations on routine vaccination are not yet available. WHO does recommend equitable use of COVID-19 vaccine in all areas. *COVID-19 has been omitted because WHO recommendations on routine vaccination are not yet available. WHO does recommend equitable use of COVID-19 vaccine in all areas.Diseases with vaccines recommended for routine use in all areas but not for use in outbreak response vaccination campaigns•Hepatitis B•Haemophilus influenzae type b•Human papillomavirus•Pertussis•Pneumococcus•Rotavirus•TetanusDiseases with vaccines recommended for targeted use through routine vaccination in some but not all areas, outbreak response vaccination campaigns, or both•Cholera•Dengue•Diphtheria•Ebola•Hepatitis A•Hepatitis E•Influenza•Japanese encephalitis•Malaria•Measles•Meningococcal•Mumps•Poliomyelitis•Rabies•Rubella•Tick-borne encephalitis•Tuberculosis•Typhoid•Varicella•Yellow fever Diseases with vaccines recommended for routine use in all areas but not for use in outbreak response vaccination campaigns •Hepatitis B•Haemophilus influenzae type b•Human papillomavirus•Pertussis•Pneumococcus•Rotavirus•Tetanus Diseases with vaccines recommended for targeted use through routine vaccination in some but not all areas, outbreak response vaccination campaigns, or both •Cholera•Dengue•Diphtheria•Ebola•Hepatitis A•Hepatitis E•Influenza•Japanese encephalitis•Malaria•Measles•Meningococcal•Mumps•Poliomyelitis•Rabies•Rubella•Tick-borne encephalitis•Tuberculosis•Typhoid•Varicella•Yellow fever National public health institutes, ministries of health, and academic and civil society organisations are important for generating and applying the data needed to target vaccination. Gaps in the availability of fit-for-purpose commercial diagnostic tests can seriously hinder these institutions' ability to detect changes quickly and accurately in disease incidence and distribution, particularly tests without sizable markets in high-income countries. Enabled by diagnostic technologies such as nucleic acid amplification and immunochromatographic testing, international efforts can help address these gaps through multiple measures. Such measures include pooling procurement across countries and supporting the rigorous evaluation of the performance and quality of test kits to identify which tests warrant widespread use. This approach has been successfully used with diseases that generate large numbers of samples to be tested annually in low-income and middle-income countries, such as HIV, malaria, tuberculosis, and COVID-19. Efforts by Gavi, the Vaccine Alliance over the past 3 years to improve yellow fever diagnostic capacity in African countries at high risk for yellow fever outbreaks indicate that these methods can also help address diagnostic market failures for diseases with low or erratic testing volumes.7Johnson BW Demanou M Fall G et al.Laboratory capacity assessments in 25 African countries at high risk of yellow fever, August–December 2018.Pan Afr Med J. 2021; 38: 402Google Scholar, 8Hampton LM Improving yellow fever diagnostic testing for more efficient, effective, and equitable vaccination.https://www.gavi.org/vaccineswork/improving-yellow-fever-diagnostic-testing-more-efficient-effective-and-equitableDate: Sept 7, 2021Date accessed: February 7, 2022Google Scholar Only about 20 000–30 000 samples a year are currently sent for yellow fever testing worldwide, due in part to the effectiveness of the yellow fever vaccine, but Gavi has worked with manufacturers to identify, procure, and distribute proven diagnostic test kits and with countries to train staff on the use of these test kits. This in turn has helped countries improve their ability to confirm yellow fever cases, determine if yellow fever vaccination efforts are needed, and access global support for outbreak response vaccination in a timely manner. In light of this experience, Gavi has now decided to allocate a small portion of its resources to improve the availability and use of fit-for-purpose diagnostic tests for cholera, typhoid, meningococcus, measles, and rubella, in addition to yellow fever.9Gavi, the Vaccine AllianceGavi Board approves malaria vaccine programme funding, COVAX 2022 strategic approach and measures to maintain, restore and strengthen routine immunisation.https://www.gavi.org/news/media-room/gavi-board-approves-malaria-vaccine-programme-funding-covax-2022-strategic-approachDate: Dec 3, 2021Date accessed: February 7, 2022Google Scholar Gavi support for targeted vaccination against these diseases is forecast to prevent more than 2·3 million deaths and cost approximately US$1·7 billion during 2021–25,10Gavi, the Vaccine AlliancePrevent, protect, prosper: 2021–2025 investment opportunity. Gavi, the Vaccine Alliance, Geneva2019Google Scholar so even small improvements in targeting use of these vaccines will have a great effect. As the number of diseases that can be prevented through vaccination increases, including important regional or local diseases, suitable diagnostic testing to guide efforts to prevent those diseases will be essential. In an era with both more attention to infectious diseases of epidemic potential and opportunities to reduce the harm caused by endemic diseases through vaccination, high quality diagnostics will be crucial to improving both responses to epidemics and routine preventive vaccination. Global and national stakeholders should work together to ensure that diseases with targeted vaccines are included in efforts to develop broad, sustainable disease surveillance and diagnostic testing systems. We declare no competing interests. All authors have been involved with the conceptualisation and implementation of Gavi, the Vaccine Alliance's support for medical diagnostic and disease surveillance capacity strengthening. LMH is a Senior Specialist for Disease Surveillance and Vaccine Safety; HLJ is Director for Monitoring, Evaluation, and Learning; and SFB is Chief Executive Officer of Gavi.