Building Integrated Testing Programs for Infectious Diseases

Abstract

In 2005, the World Health Organization (WHO) established the International Health Regulations (IHR) in response to increased international travel, trade, and the emergence of diseases and health threats of potential global impact [1]. The eighth core capacity of IHR states that the laboratories play an important role in all phases of alert and response, including detection, investigation, and response, and that countries should ensure that mechanisms are in place for timely and reliable laboratory results for the identification of infectious agents [1]. Also, the 2008 WHO Maputo Declaration calls on national governments and donors to strengthen laboratory systems to address challenges associated with the scale-up of human immunodeficiency virus (HIV), tuberculosis (TB), and malaria diagnostics [2].

In response, investments by governments and partners have strengthened laboratory services and systems in many countries [3, 4]. However, these have often been vertical and disease-focused, both in the laboratory and at the point of care, linked to earmarked funding mainly intended to address influenza, HIV, TB, or malaria diagnostic needs [5, 6]. This has resulted in reduced ability of health systems to introduce new essential tests or respond to emerging diseases.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing has relied heavily on diagnostic capacity established previously for influenza, HIV, TB, malaria, and other tests [7]. Although this initially disrupted testing for these diseases [8–10, 11], testing programs recovered and SARS-CoV-2 is increasingly being integrated into routine testing services for other diseases. This highlights an opportunity to extend integration beyond SARS-CoV-2 to other diseases [10, 12]. This perspective provides 5 recommendations to enable this change.

Establish Multidisease Policies

In 2019, WHO recommended that countries develop integrated testing services and policies [13]. COVID-19 disrupted the development of these policies; however, opportunities now exist to design integrated national testing policies, plans, guidelines, and standard operating procedures covering multiple diseases and tests, rather than separate policies for each disease or test. In addition to integrated testing policies, multidisease treatment guidelines are needed to enable better-integrated follow-on care for patients.

Use Common Health Systems

Delivering a diagnostic test result requires not just a test itself, but a range of supportive health systems such as data, sample logistics, quality assurance, instrument maintenance, supply chain, and training. In these past, these ancillary health systems have often been developed in silos for specific tests, leading to duplication and inefficiency. COVID-19 drew on health systems established for other diseases and demonstrated that common systems are feasible. For example, the Africa Centres for Disease Control and Prevention and partners have used the Stepwise Process for Improving Quality checklist, developed originally for point-of-care HIV test quality assurance, for SARS-CoV-2 [14, 15].

Adjacent disease programs may need to redesign delivery of their services, including integration of patient pathways, funding streams, testing algorithms and supply chain, and treatment modalities. This will require test operators and clinicians to be cross-trained on the use and interpretation of multiple assays, and for clinicians to be able to routinely order tests and provide an integrated package of follow-on care and treatment where needed. For example, the integration of point-of-care HIV and sexually transmitted infection testing (eg, HIV/syphilis) requires close alignment of adjacent disease programs. Similarly, the integration of respiratory infection screening (eg, SARS-CoV-2/influenza testing or bidirectional COVID-19/TB testing) or diagnostics for triple elimination of HIV/syphilis/hepatitis B vertical transmission requires improved integration of policies and processes across the cascade of care from case finding, to testing and treatment for each disease.

Optimize Diagnostic Networks

Diagnostic network optimization is a valuable tool for integrated testing. Model-based geospatial analysis is used to map networks of testing sites and clinics to identify the optimal type, number, and location of testing centers and sample transport networks to improve test access and laboratory utilization and efficiency and reduce costs [16]. Optimization can be used for any testing service where testing sites need to service a larger footprint of health facilities. Optimization exercises will recommend where changes in capacity or logistics are needed and inform investment decisions [17].

For example, many laboratory nucleic acid testing instruments can detect multiple pathogens and hence can service testing needs for SARS-CoV-2, TB, HIV, malaria, influenza, viral hepatitis, human papillomavirus (HPV), sexually transmitted infections, and other infections. Studies have demonstrated that laboratories can run tests for multiple infections on the same instruments. The introduction of HIV testing on instruments used for TB diagnosis did not disrupt TB test services in Malawi and Zimbabwe [18, 19]. Several countries undertook optimization exercises during the coronavirus disease 2019 (COVID-19) pandemic to rapidly scale up SARS-CoV-2 nucleic acid testing while maintaining adequate HIV and TB nucleic acid testing services [20, 21].

Adopt All-Inclusive Pricing and Combination Tests

Many diagnostic tests require multiple components that are purchased separately to deliver the test—for example, reagents, plastic consumables, controls, delivery costs, instruments, and maintenance. This often results in high costs or incomplete supplies. A shift toward purchasing of bundled supplies by countries and donors has helped to overcome this. For example, procurement of HIV viral load tests has moved progressively toward a volume-based cost-per-test inclusive of reagents, instruments, service, and distribution costs, commonly referred to as all-inclusive pricing [17, 22]. All-inclusive pricing ensures key services and supplies such as instrument maintenance or controls are not overlooked during procurement and favors more efficient use of instrument capacity. It also enables less cumbersome and more transparent procurement and lowers the risk of stockouts by distributing accountability across both buyer and supplier. Per-test cost drops at higher volumes; hence, all-inclusive, integrated nucleic acid testing for multiple infections will lower costs, expand test access, and improve efficiency. All-inclusive pricing is not restricted to nucleic testing; it is applicable to any reagent and instrument-based test (eg, chemistry or bacteriology testing), as well as instrument-free rapid tests.

Bundled procurement can also enable integration through combination assays or individual tests sold together, such as combination HIV/syphilis tests and antenatal screening panels (HIV, syphilis, hepatitis). Bundling these tests together provides opportunities to improve supply chain as well as test access.

Share Innovation Across Diseases

Integrated testing enables best practices, technology, and health system innovations developed for certain tests (eg, COVID-19) to be used to improve the test access and health outcomes for other diseases [23]. For example, before COVID-19, test turnaround times for referred nucleic acid testing were lengthy and variable—around 2 months on average for priority tests such as early infant HIV diagnosis [24]. However, turnaround times under a week were routine for SARS-CoV-2 through improvements in sample referral and results delivery systems and more efficient laboratory operations [25]. Results were delivered in fixed time periods, usually directly to patients.

SARS-CoV-2 test result data systems have significantly increased visibility of test results for clinical and surveillance use. Extending these enhanced systems to other tests such as HIV early infant diagnosis and viral load, TB, and HPV screening could yield health benefits. For example, the Senaite real-time data system used to deliver SARS-CoV-2 testing results in Zimbabwe has been extended to HIV viral load and infant diagnosis [26].

COVID-19 has also prompted increased efforts to establish local manufacturing of diagnostics, laboratory consumables, and personal protective equipment to improve supply security, addressing commodity supply gaps and expanding the supply pipeline. Several regional manufacturing initiatives are already under way [27]. For example, the Institut Pasteur of Dakar has established a regional manufacturing base in Senegal to address test supply needs for SARS-CoV-2 and other diseases of epidemic potential [28]. Morocco has manufactured a SARS-CoV-2 polymerase chain reaction detection kit to support local testing [29]. If successful for COVID-19, local manufacturing of other tests may benefit other disease areas.

DISCUSSION AND CONCLUSIONS

Covid-19 has illustrated that integrating SARS-CoV-2 diagnostics into existing testing programs for influenza, HIV, TB, malaria, and other diseases is feasible under emergency pandemic response conditions. However, a permanent shift to routine integrated testing faces significant barriers and requires alignment across different disease programs, donors, technical agencies, implementing partners, and suppliers. There is a need to integrate funding, health systems, testing venues, testing algorithms, and data reporting systems as well as supply chain, including forecasting, procurement, storage, and distribution systems. Updated guidelines and policies for testing, treatment, procurement, and other health systems will be needed.

Once operational, integrated testing will meet challenges. Surges in testing demand for some diseases can undermine testing for others; for example, prioritized testing during SARS-CoV-2 waves resulted in backlogs of HIV and TB tests. Testing bottlenecks due illness among test operators or breakdowns of equipment will place multiple disease programs at risk. Exceptions will exist, for example where funding or capacity limitations prevent integration. Siloed systems will still be needed in certain scenarios, such as targeted screening in high-disease-burden populations or the transport of samples with different storage or delivery time requirements.

Integration will need to become the core policy of laboratory networks, championed by leaders and supported by broad consensus among stakeholders, different disease programs, and donors to ensure appropriate resource allocation and prioritization. While this may take time to establish, progress is necessary because better integrated testing will strengthen both pandemic preparedness and clinical disease management, and ultimately enable countries to achieve universal healthcare and the requirements of the WHO IHR.

Notes

Disclaimer. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the funding agencies.

Financial support. This work was supported by the US President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention and Unitaid.

References

Author notes