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Diagnostic testing is often considered by governments to be a non-essential cost to the healthcare system. A Lancet Commission on Diagnostics concluded that over 50% of the world’s population has no access to diagnostic services.¹ At the same time, a publication by Gavi, the Vaccine Alliance, showed that gaps in country testing capacity have important consequences for immunization programmes and that “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.”^2,3 In addition, new technologies such as machine learning, integrated with diagnostic testing, have the potential to increase the power of diagnosis, as has been shown in the diagnosis of tuberculosis. ^4,5

Since the pandemic, PCR and rapid tests have become part of the public lexicon. Yet the role of diagnostics to target the treatment of infections and help slow the emergence of antimicrobial resistance (AMR) remains obscure.

The value of diagnostics was most clearly demonstrated to political leaders and the public during the COVID-19 pandemic when polymerase chain reaction (PCR) testing accompanied by contact tracing contained initial outbreaks in Asia.⁶ The eventual use of rapid antigen tests permitted widespread community-based and self-testing, with self-isolation when positive, thus preventing onward transmission.⁷ Since the pandemic, PCR and rapid tests have become part of the public lexicon. Yet the role of diagnostics to target the treatment of infections and help slow the emergence of antimicrobial resistance (AMR) remains obscure.

The role of diagnostics in fighting AMR

Diagnostic testing, whether performed in laboratories or at the point of need, serves three functions in the fight against AMR: (1) surveillance to better understand the epidemiology of AMR, especially to enable more accurate presumptive patient management and strengthen empiric treatment guidelines where laboratory testing is not available, and for more effective infection prevention and control (IPC); (2) confirmation of aetiology in clinical diagnosis of infection to guide patient management; and (3) research, including new antimicrobial drug development and vaccine trials.

Diagnostics for AMR surveillance to make presumptive treatment more precise and health facilities safer

Diagnostic testing with assessment of AMR in IPC programmes, community surveys, and routine environmental monitoring in health facilities provides surveillance data needed to establish epidemiological patterns of AMR and identify and mitigate risks associated with IPC. Surveillance allows for evidence-based guidelines for accurate presumptive management of infections in regions of the world where laboratory testing has not yet been established, to improve and update empiric treatment guidelines, and to assess the effectiveness of the IPC strategy and the impact of special interventions to keep healthcare facilities safe.

A simple, rapid test that can distinguish bacterial from viral respiratory infections at the primary care level or home use would be a game-changer in reducing the unnecessary use of antibiotics.

Confirmation of diagnosis to guide patient management

Though clinical diagnosis of infection can be confirmed by diagnostic testing with antimicrobial susceptibility patterns to guide treatment, the reality is that diagnostic tests are either unavailable or under-utilised. A recent Fleming Fund-supported survey conducted by the Mapping Antimicrobial Resistance and Antimicrobial Use Partnership (MAAP) showed that of the over 50,000 medical facilities forming the laboratory networks of the 14 participating African countries, only 1% of laboratories conduct bacteriology testing and AMR analysis.⁸ Even at laboratories that offer traditional culture and susceptibility testing, results are only available after 48 hours. Thus, most clinicians prefer to use a syndromic approach and treat presumptively with broad-spectrum antibiotics, contributing further to the risk of AMR development. Studies in Nepal, Malawi and Uganda showed that up to 27, 30 and 59 antibiotic prescriptions, respectively, were given to children between birth and five years of age with no diagnostic testing.⁹

Molecular testing for detecting genes encoding resistance, or by-products such as enzymes or other proteins, is available in or outside laboratory settings with minimal training, and results are available after 1-3 hours. But, these tests are neither affordable nor accessible for most lower-income countries (LICs). Simple, rapid tests to detect host biomarkers that help distinguish between bacterial and viral infections, such as C-reactive protein (CRP) or procalcitonin, have shown promising results.^10,11,12 A simple, rapid test that can distinguish bacterial from viral respiratory infections at the primary care level or home use would be a game-changer in reducing the unnecessary use of antibiotics. This is now at the top of the World Health Organization (WHO) AMR research agenda for diagnostics and there is active research in this area. ^13,14

Diagnostics to support the clinical development of new antimicrobials and their utility

The efficiency of clinical trials for novel antibiotics is undermined by delays in identifying and recruiting patients with the right target profile. Either patients are enrolled and subsequently found to be ineligible after laboratory testing, or recruited patients are put on another treatment regimen while awaiting laboratory tests to confirm their eligibility. Accurate, rapid diagnostics used at the point of care (POC) would permit faster, more targeted recruitment, increasing trial efficiency and reducing costs. The Innovative Medicines Initiative (IMI), established in 2008 by the European Commission to accelerate drug development, funded 15 rapid diagnostic development projects, of which 10 are still ongoing.¹⁵ Other initiatives are also contributing to the development of rapid diagnostic tests, including FIND, the US National Institutes of Health (NIH) and the Combatting Resistant Bacteria partnership (CARB-X). The co-development of rapid POC diagnostics and drugs for treating resistant bacteria should continue to be a priority. The introduction of any novel antibiotic would also benefit from a POC test to ensure its appropriate use, thus prolonging its useful life.

Vaccines can prevent infections, but accurate, reliable diagnostics are needed to make immunization programmes more efficient, equitable, and effective.

Moving forward

The United States National Academies for Science, Engineering and Medicine recently held a workshop to identify incentives and disincentives for the development of new antibiotics and complementary diagnostics and concluded that organizations and the public need to be engaged on the issue of diagnosis and appropriate treatment and take action.¹⁶ To meet this challenge, we have developed a series of free, online, self-guided courses on the FutureLearn and Global Health Continuing Professional Development learning platforms as part of a public-private partnership for AMR, focussing on the role of diagnostics for AMR, healthcare-associated infections, and building capacity for AMR surveillance.^17,18 Course materials are freely downloadable for teaching. To date, more than 15,000 learners from 134 countries have accessed these courses. We partnered with country/regional partners, academic institutions, and professional organizations to provide continuing professional development to enable countries to build capacity for antimicrobial susceptibility/resistance testing.

Conclusion

Diagnostics are needed for AMR surveillance, reducing inappropriate use of antibiotics in clinical medicine, more efficient and cost-effective drug trials, and ensuring the proper utility of novel antibiotics. Vaccines can prevent infections, but accurate, reliable diagnostics are needed to make immunization programmes more efficient, equitable, and effective. A three-pronged strategy that focuses on coordinated development and deployment of diagnostics, drugs and vaccines for AMR, underpinned by robust AMR surveillance to monitor impact and improve treatment guidelines, constitutes a comprehensive approach to tackling AMR head-on.

References

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4. Wang H, Jia C, Li H, Yin R, Chen J et al. (2022) Paving the way for precise diagnostics of antimicrobial resistant bacteria. Front Mol Biosci. 12;9:976705.
5. Orjuela-Cañón AD, Jutinico AL, Awad C, Vergara E, Palencia A (2022) Machine learning in the loop for tuberculosis diagnosis support. Front Public Health. 10:876949.
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10. Zhang K, Xie K, Zhang C, Liang Y, Chen Z et al. (2022) C-reactive protein testing to reduce antibiotic prescribing for acute respiratory infections in adults: a systematic review and meta-analysis. Journal of Thoracic Disease. 14(1):123-134.
11. Lubell Y, Blacksell SD, Dunachie S, Tanganuchitcharnchai A, Althaus T et al. (2015) Performance of C-reactive protein and procalcitonin to distinguish viral from bacterial and malarial causes of fever in Southeast Asia. BMC Infectious Diseases. 15:511.
12. Dewez JE, Nijman RG, Fitchett EJA, Lynch R, de Groot R et al. (2023) Adoption of C-reactive protein point-of-care tests for the management of acute childhood infections in primary care in the Netherlands and England: a comparative health systems analysis. BMC Health Serv Res. 23(1):191.
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15. Innovative Medicines Initiative (2024) Project Factsheets.[Accessed 22/01/2024]
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18. London School of Hygiene and Tropical Medicine (2020) The microbiology laboratory to address AMR [Accessed 22/01/2024]