Innovations for Tackling Tuberculosis in the Time of COVID-19 Proceedings of a Workshop (2022) / Chapter Skim
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3 Detection
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The session began with progress updates on efforts to build a TB-free world by Jennifer Adams, acting assistant administrator, Bureau for Global Health at the U.S. Agency for International Development (USAID)
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Monique Mansoura, executive director for Global Health and Biotechnology at the MITRE Corporation, explored innovative strategies to synergize investments in health care systems with a focus on whether cancer and TB care can protect against pandemics. Edward Nardell, professor of medicine at Harvard Medical School and the Harvard T.H.
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Simultaneously, TB personnel and services were repurposed and deployed in the response to COVID-19. Their experience in case detection, contact tracing, and airborne infection control were essential for the new and unprecedented pandemic, said Adams.
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The scale-up of all-oral treatment regimens has been critical in continuing multidrug-resistant (MDR) TB treatment for patients throughout the restrictions and lockdowns brought on by the pandemic, Adams remarked.
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Certain diseases such as HIV and TB have received unique funding, but expansion of the entire health care delivery platform to the population would strengthen efforts focused on specific diseases, Goosby stated. Ministers of health can be their countries' strongest advocates for budgetary prioritization, but effective advocacy requires analyzing and understanding the situation and translating it into a narrative that attracts funding.
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Goosby warned against creating parallel systems of surveillance, which has happened in the past with HIV. Goosby added that the Biden administration has discussed strategies to increase pandemic preparedness by building upon established platforms, such as those for TB and HIV.
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Questions persist as to where that capability will reside and which entities will be responsible for different components, he added, noting that dialogue around national security versus global health programming remains in equilibrium. Discussion Referencing a divide between the national security and global health communities, Mansoura asked how these communities can be brought together in recognizing the security elements and economic effects of TB.
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Instead, systems and services that clearly designate the countries in which they are implemented as responsible for maintenance and continued performance should be created, Goosby remarked. The demands of the COVID-19 pandemic present an opportunity to reevaluate the global health development portfolio and expand platforms implemented in partnership with leaders responsible for the target population.
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REALITIES OF MULTIDRUG-RESISTANT TUBERCULOSIS Presented by Matteo Zignol, World Health Organization Zignol focused on the global burden and trends in MDR TB, the associated challenges that it poses to TB control, and progress in the treatment of MDR TB. Burden and Trends in Multidrug-Resistant Tuberculosis Zignol opened by presenting data about the global burden of TB and its epidemiological trends drawn from WHO's 2020 Global Tuberculosis Report (WHO, 2020)
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Zignol discussed findings from a 2017 study that modeled projected trends in the proportions of MDR TB and extensively drug-resistant (XDR) TB in India, the Philippines, Russia, and South Africa (Sharma et al., 2017)
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The global status of TB control has worsened because of the COVID-19 pandemic, and it will continue to worsen as the pandemic continues. He emphasized that DR TB is a major global health threat, but limited data are available to develop accurate projections of global DR TB trends.
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before -- yet new regimen uptake is slow in many countries, meaning that significant progress must be made quickly in order to reach the 2018–2022 global TB treatment targets. Discussion Noting that the uptake by countries of new WHO recommendations on TB control is often slow, Ditiu asked about the slow pace of diagnostic development and the slow uptake of treatment regimens.
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allocated an unprecedented $1.5 billion to expand and optimize the performance of COVID-19 testing technologies, $500 million of which was channeled to RADx via the National Institute of Biomedical Imaging and Bioengineering. RADx was built and layered upon the Pointof-Care Technologies Research Network (POCTRN)
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These projects included a wide range of diagnostic innovations, including POC and home-use diagnostic products, laboratory diagnostic tools, and laboratory products. A primary aim of the project was to accelerate the validation of emerging technologies, including next-generation technologies such as CRISPR and nanoparticle applications, noted McMahon.
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DETECTION 43 ing its rapid advancement from technological validation to emergency use authorization and commercial availability especially noteworthy. Impact Effect of Rapid Acceleration of Diagnostics Technology Projects McMahon described the impact of RADx projects as of July 2021.4 Cumulatively, RADx projects brought 667 million COVID-19 tests to market between September 2020 and July 2021, creating a COVID-19 diagnostic capacity equivalent to approximately 5 million tests per day.
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Because many diagnostic tools can be linked to public health systems in valuable ways, the RADx deployment core assists every RADx project in optimizing its use of the digital health infrastructure. Lessons for Tuberculosis Control McMahon highlighted several factors that have contributed to the success of the program and could be applied to TB control efforts: (1)
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and various Department of Defense programs provided funding and support for rapid manufacturing scale-up of newly developed diagnostic tools. McMahon also emphasized the importance of RADx's narrow focus on ensuring commercial viability and bringing diagnostic tools to market as fast as possible.
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. Discussion Gail Cassell, senior lecturer on global health and social medicine at Harvard Medical School, asked whether TB might be well suited for addition into a multiplex test or whether standalone tests would be preferable for detecting TB.
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However, the growing install base and integrated COVID-19 response from clinics and laboratories has come at the expense of certain TB control efforts.7 Moving forward, he suggested focusing on building back and expanding TB control capacity by building upon advances brought forth by the COVID-19 response, such as the expansion of digital health infrastructures and innovations in self-sampling and home-use tests. For TB control efforts to adapt to the new disease control landscape, TB control programs will need to break out of their silos, he said.
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Innovations for Tackling Tuberculosis in the Time of COVID-19 Presented by Zvi Marom and Eran Zahavy, BATM Marom and Zahavy discussed BATM Advanced Communications' innovative approach to tackling TB amid the COVID-19 pandemic. Its approach is to focus on substantially reducing the cost of diagnostic testing and to initiate TB treatment rapidly after an accurate diagnosis, including the diagnosis of antibiotic resistance in the same test.
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If adapted for TB diagnosis, this technology could use a single sputum sample to diagnose TB, detect specific mutations to identify antibiotic resistance, and optimize patient treatment. Additionally, NATlab diagnostic devices harness Internet connectivity and AI to predict disease trends using diagnostic data; for example, NATlab diagnostic tools were used to predict and map the movement of the COVID-19 pandemic.
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Although AI interpretation has the potential to decrease cost and increase operational effectiveness, the technology will need further calibration to address confounders that can undermine its accuracy, such as history of TB, age, and the radiography equipment used. Implementation Challenges with New Tuberculosis Diagnostics Presented by Kaiser Shen, United States Agency for International Development Shen shared insights from his work at USAID on POC TB diagnostics, TB diagnostic networks, and implementation challenges.
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IMPROVING ADHERENCE, INFECTION CONTROL CAPACITIES, AND COST-EFFECTIVENESS Integrated Community Response to the COVID-19 Pandemic in Karachi, Pakistan Presented by Aamir Khan, IRD Khan discussed the comprehensive approach to COVID-19 and TB testing implemented in Pakistan that adapted the Interactive Research and Development (IRD) model of integrated community response to TB control.
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Provision of Oxygen Therapy, COVID-19 Screening, and Phone-Based Contact Tracing Khan provided an overview of efforts to provide oxygen therapy, conduct COVID-19 screening, and use phone-based contact tracing for COVID
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Lessons Learned from Adapting Integrated Community Response to COVID-19 in Karachi Khan highlighted lessons learned from Karachi's COVID-19 experience and IRD's adaptation of existing TB systems to manage the pandemic surge. A COVID-19 surge can quickly overwhelm any active TB screening system.
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Moreover, Karachi's initial pandemic response was bolstered by the existing TB contact-tracing systems, mental health support systems, private-sector provider networks, and data-collecting and -reporting systems. Telehealth and Digital Adherence Technologies Presented by Bruce Thomas, The Arcady Group Thomas discussed how DATs can facilitate differentiated and virtual care for persons affected by TB.
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(Global Fund, 2021) Differentiated Care Through Integrated Digital Adherence Technologies Thomas discussed the challenges in TB treatment adherence and the potential benefits of DATs, which have particular value in the context of the COVID-19 pandemic.
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. He also presented an example of a patient adherence timeline, which detailed a patient's treatment adherence over time, including treatment registration, medication receipt, automated patient reminders and adherence, instances of patient non-adherence, health staff interventions, and overall adherence at the time of treatment completion.
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During the subsequent transition to scale phase, funded by Unitaid, DATs were scaled up to more than 70,000 patients. In 2020, the Global Fund began providing multiyear support for DATs in approximately 13 countries, and continued phases of innovation since 2020 have been led by Global Health Labs and the Bill & Melinda Gates Medical Research Institute.
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Through sustained commitments from leadership, governments, and investors, these synergies can improve care and preparedness. Mansoura maintained that TB and cancer care are naturally aligned in the effort to build a stronger critical infrastructure to support pandemic preparedness.
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Such an approach is key for leveraging synergies and achieving benefits, cost-effectiveness, and building capacity. A primary challenge in global health security is persistence in building capacity and the maintenance of sustained commitments.
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. The control of both infectious diseases and noncommunicable diseases requires early detection and rapid response, and thus building capacity and capability in those areas will have multiple benefits.
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Both disease groups require similar health care capacity for physical examination, laboratory and molecular diagnostics, diagnostic imaging, treatment and recurrence prevention, and modulation to address immune response and inflammation. An integrated health care system could offer flex competence in areas applicable across infectious diseases, noncommunicable diseases, pandemics, and disasters: • Prevention of infectious diseases and immunization; • Population surveillance; • Prevention of noncommunicable diseases (e.g., screening, healthy lifestyle promotion, diet)
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Mansoura emphasized the need for readiness assessments to meet standards as a key for global flex competence. In 2019, the Global Health Security Index was published, measuring the health preparedness of each country.12 However, the COVID-19 pandemic revealed that this index was not highly effective at predicting countries' pandemic preparedness, and it remains unclear how this can best be measured (Crosby et al., 2020)
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Resources that are redirected in a crisis response can create major deficits in other health care areas and damage existing structures of care; these consequences can be avoided by preparation and integration efforts across the infectious disease, noncommunicable disease, and preparedness communities. Environmental Transmission Control Lessons from COVID-19 and Tuberculosis Presented by Edward Nardell, Harvard Medical School and the T.H.
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In contrast, SARS-CoV-2 can spread asymptomatically for a short infectious period of roughly 48 hours, making it unusual among infectious diseases. The outbreak of COVID-19 at the Skagit Valley Chorale rehearsal in March 2020 was instrumental in confirming that SARS-CoV-2 is primarily airborne, rather than spread through droplets, said Nardell (Miller et al., 2021)
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These devices are not limited by air flow; instead, they treat large volumes of air instantaneously, making them highly economical. GUV air disinfection is also safe for room occupants and effective against various infectious disease agents, including MTB, SARS-CoV-2, influenza viruses, and the measles virus.
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Because windows are closed when air conditioners are in use and ductless air conditioning units do not use ventilation, ductless air conditioners create unventilated spaces. In addition to cooling spaces, it is also necessary to replace the ventilation lost to ductless air conditioners.
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Although progress has been made toward achieving the UN High-Level Meeting targets for 2022 for scaling up the provision of TPT to people of all ages and people living with HIV, efforts to scale up TPT for household contacts have been insufficient to meet the 2022 goals. Notably, less than 1 percent of the targeted 20 million household contacts age 5 years or older have received TPT (WHO, 2020)
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Improving screening and testing for TB infection: 1. Reevaluate the cost, feasibility, yield, and cost-effectiveness of testing for TB infection among household contacts age 5 years or older.
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. The DOLPHIN TOO trial is amending the original protocol to describe the rate of decline of plasma HIV-1 viral load among antiretroviral naïve participants starting isoniazid preventive therapy or 3HP regimens with a dolutegravir antiretroviral regimen.15 TPT guidelines for children younger than 5 are complex, Churchyard explained.
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Churchyard also discussed the use of TPT for household contacts of TB patients by presenting results from the Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients (PHOENIx MDR-TB) trial conducted in eight high-burden countries.20 The PHOENIx MDR-TB feasibility trial demonstrated that 77 percent of household contacts of MDR TB patients were in a high-risk group for developing TB (Gupta et al., 2020)
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. Future Tuberculosis Preventive Treatment Regimens Churchyard emphasized the importance of managing the global burden of TB infection to meet End TB targets.
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72 INNOVATIONS FOR TACKLING TUBERCULOSIS ther innovation, said Churchyard. To that end, additional ultra-short-course regimens are currently being evaluated.
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