5

Financing, Ambition, and Preparedness

The third session of the second part of the workshop explored strategies for eliminating tuberculosis (TB) in a global context dramatically changed by the COVID-19 pandemic. The session featured remarks by Tharman Shanmugaratnam, senior minister and coordinating minister for Social Policies of Singapore and co-chair of the G20 High-Level Independent Panel (HLIP) on Financing the Global Commons for Pandemic Preparedness and Response (PPR), in which he discussed the synergy involved in developing prevention and response efforts for TB and COVID-19 and summarized the HLIP’s strategies for such efforts. A panel followed, moderated by Peter Sands, executive director of the Global Fund to Fight AIDS, Tuberculosis and Malaria (the Global Fund), that explored how efforts to combat TB can be incorporated into the global health security and pandemic preparedness agenda. Panelists included John Bell, Regius Professor of Medicine at Oxford University; Bruce Gellin, chief of Global Public Health Strategy for the Rockefeller Foundation’s Pandemic Prevention Institute; Rebecca Katz, professor and director of the Center for Global Health Science and Security at Georgetown University; and Michael Callahan, clinical associate physician at Massachusetts General Hospital and president of the Division of Cellular Therapeutics at United Therapeutics. Margaret Hamburg, interim vice president of global biological policy and programs for the Nuclear Threat Initiative, moderated the second panel, which considered the economic rationale for financing the elimination of TB. The panelists were Mike Reid, assistant professor in the Department of Medicine at the University of California, San Francisco (UCSF), associate director of the UCSF Center for Global Health Delivery, Diplomacy, and Economics, and chief medical officer for the UCSF

Pandemic Initiative for Equity and Action; Bjørn Lomborg, president of the Copenhagen Consensus Center and visiting fellow at the Hoover Institution at Stanford University; Mark Dybul, chief executive officer of Enochian Biosciences, professor of medicine at Georgetown University, and former executive director of the Global Fund; and Amanda Glassman, executive vice president and senior fellow at the Center for Global Development and chief executive officer of the center’s branch in Europe.

In his opening remarks, Sands described the Global Fund as the largest provider of external financing for TB interventions, contributing approximately 75 percent of the world’s external TB financing. The organization’s 2020 report outlines that for the first time in the 20-year history of the Global Fund’s programmatic results, backslides occurred across all three diseases of HIV, TB, and malaria (Global Fund, 2021). The COVID-19 pandemic created massive disruptions in service provision and diverted human and financial resources, including laboratory capacity, from other diseases. Sands noted that of the three diseases of focus, TB efforts have been most undermined by COVID-19. From 2018 to 2020, the number of people treated for TB decreased by 1 million, representing an 18 percent decline in the number of cases being treated. Sands noted that this assuredly translates into hundreds of thousands of deaths. Thus, the COVID-19 pandemic has been a catastrophe on multiple fronts.

Disruption continued into 2021, said Sands. India’s TB program was disrupted when the pandemic began in 2020, but began regaining momentum at the end of 2020 and the beginning of 2021, as evidenced by a sharp increase in TB case notification rates. However, the COVID-19 surge brought on by the Delta variant in the late spring and summer of 2021 once again disrupted TB interventions, despite efforts made by national television programs and civil society to mitigate the damage. Sands pointed out that pandemics affect TB, but TB can also affect preparedness against pandemics. The laboratory capacity, molecular testing instruments, and contact tracing systems developed for TB have been used to address COVID-19. Indeed, the established TB testing capacity served as the backbone of COVID-19 molecular testing activity in many countries. Furthermore, many leaders within the TB community have been called on to serve as leaders of national COVID-19 responses because of their expertise in respiratory diseases. Sands remarked that while TB may have the most to lose from COVID-19, it also has the most to contribute. The interconnection between fighting TB and making the world safer from future pathogen threats—particularly respiratory pathogens—should be explored.

Victor Dzau, president of the National Academy of Medicine, remarked on the devastating consequences of TB experienced by his grandparents, parents, and other relatives during his childhood in Asia. The Global Fund and the President’s Emergency Plan for AIDS Relief (PEPFAR) have created resources for low-income countries so they can address chronic endemic and

pandemic diseases. Although it was necessary to pivot these resources to COVID-19, this came at a cost in setting back TB elimination efforts, including testing and treatment. Dzau suggested that the pandemic preparedness effort should avoid investing in silos and instead invest in programs that strengthen countries’ capacity to fight HIV, TB, and malaria. Building resilient health systems will provide better services for both TB and COVID-19 patients, he added.

A PLACE FOR TUBERCULOSIS IN THE PANDEMIC PREPAREDNESS AGENDA

Remarks by Tharman Shanmugaratnam, Co-chair, G20 High-Level Independent Panel

Tharman explored how to situate TB within the pandemic preparedness agenda. He noted that we are at an important juncture that has focused the world’s attention on infectious disease threats. We have to fortify our own defenses in a way that addresses not just one disease or prospective new disease at a time but recognizes that we have a plethora of both existing diseases that are unchecked and potential new ones. The effort can no longer be easily compartmentalized into global regions either. For instance, evidence suggests that human incursions into the natural environment, the deterioration of biodiversity, and climate change are increasing the likelihood of zoonotic spillovers and a broader spread of vector-borne diseases. Infectious disease threats and climate change are the central challenges of our times for national and global governments, he added.

Intersection of Pandemic and Endemic Diseases

A major pandemic interacts with endemic diseases, resulting in cost to human life from the pandemic disease as well as from the significant diversion of resources away from the treatment of endemic diseases. In the case of the COVID-19 pandemic, TB has been the most prominent casualty, said Tharman. Around the world, a startling reduction in health care system access has occurred, with manpower and facility occupancy diverted toward COVID-19. The pandemic has also affected human behavior, with fear of contracting the disease increasing people’s aversion to accessing medical treatment. Case notifications for TB significantly decreased throughout Asia in 2020 (WHO, 2021c), setting the stage for increases in TB cases and fatalities in the years to come. Thus, pandemic prevention and preparation is critical for limiting both the direct effects of the outbreak and the indirect effects resulting in neglect of treatment for other diseases. Additionally, the capacity to address endemic diseases—including surveillance systems for early detec-

tion, trained health workers in communities, and health care capabilities at the primary and tertiary levels—should be strengthened, recognizing the high degree of synergy between capabilities developed for endemic diseases and those required to treat a new pandemic.

Structural bias within the research and development (R&D) of treatments results in a commercial incentive to treat diseases prevalent in high-income countries versus diseases prevalent in low-income countries, observed Tharman. Once TB was no longer a major threat to high-income countries, the pharmaceutical industry and other groups that were engaged in R&D investment for vaccines and drugs had little commercial incentive to direct resources to TB. The bifurcated and inequitable nature of funding disease prevention and treatment is likely to decrease trust globally, he noted. The COVID-19 pandemic had seen a lack of access to lifesaving medical supplies in a large part of the developing world, putting this dynamic into sharp focus. He remarked that when combined with the continued inattention to endemic diseases, this lack of trust now risks becoming entrenched and more difficult to overcome. Thus, increased access to vaccines and other critical medical supplies required to address COVID-19 is an urgent need, as is acknowledging and treating endemic diseases in all regions of the world as important issues, said Tharman.

Elaborating on the lack of boundaries for infectious disease threats, he warned that the longer the pandemic spreads unchecked, the greater the risk that new COVID-19 variants will emerge. Likewise, the persistence of TB around the world coupled with improper use of drug treatments and inadequate testing is giving rise to drug-resistant TB, including multidrug-resistant TB (MDR TB). Continued neglect of TB control and improper treatment use could lead to an emergent pandemic of drug-resistant TB from which no part of the world is protected. Thus, he underscored the need for urgency in tackling COVID-19, preparing for future pandemics, and addressing endemic diseases—TB being foremost among them.

There is no lack of ambition in current plans, such as in the World Health Organization’s (WHO’s) End TB Strategy, which includes targets, pillars, and a multisectoral accountability framework (WHO, 2015). Tharman noted that other global health organizations—including the Global Fund, the Stop TB Partnership, and others—have also made meaningful advances in partnerships with one another and with employer groups and global funds. For instance, in 2020 the World Economic Forum, the Confederation of Indian Industry, Johnson & Johnson, Royal Philips, Fullerton Health, the Global Fund, and the Stop TB Partnership were involved in an initiative to address TB in the workplace.¹ However, a fundamental problem is lack of

___________________

¹ This initiative is called Ending Workplace TB. See https://www.ewtb.org (accessed January 1, 2022).

investment and financing for the TB eradication effort and for infectious disease threats more broadly, he added.²

Tharman remarked that we need a basic reset of the system to address the current gaps. This reset need not attempt a grand reconstruction of multilateralism, nor can it simply be about incremental changes in existing institutions, because the system is fragmented, dependent on bilateral contributions, reactive, and wholly inadequate. He envisions reforms to involve creative ways of strengthening multilateralism, improving existing bilateral initiatives, and simultaneously strengthening ways to address endemic threats and new health care security threats. The first step in this complex work is incentivizing national governments to increase activity in identifying and addressing infectious disease threats, said Tharman. This work has not been adequately prioritized in the budgets of a broad range of countries for a variety of reasons. Because infectious disease threats can cross borders, containing these threats is of national, regional, and global benefit, and is therefore a global public good. Therefore, financing systems should extend beyond domestic resource mobilization guidance to low-income countries; they should provide international support to incentivize investment in the capacities in these countries that carry international benefit. Tackling infectious disease threats should also not be limited to bilateral aid strategies. Instead, the issue should be framed as a matter of collective investment in global public goods that will benefit nations of all income levels, he added.

Strategy for Collective Investment in Global Public Goods

The G20 HLIP on Financing the Global Commons for PPR created a strategy for this collective investment that features key strategic moves (G20 HLIP, 2021). First, global health organizations require more reliable funding from both bilateral and multilateral sources in order to fulfill their missions, said Tharman. Stronger multilateral funding provided on a reliable basis is needed to address WHO’s insecure financial footing. Global health organizations—including the Global Fund, the Global Alliance for Vaccines and Immunisation (Gavi), the Coalition for Epidemic Preparedness Innovations (CEPI), One Health Partners, and others—all require reliable funding to fully address their mandates.

The second strategy is to strengthen the role of international financial institutions (IFIs) in tackling infectious diseases. These institutions include the World Bank, the International Monetary Fund (IMF), various regional

___________________

² For more information on global targets for mitigating TB, see the following resources from the UN High-Level Meeting on the Fight Against TB (UNHLM TB): https://www.stoptb.org/advocacy-and-communications/unhlm-tb-key-targets-and-commitments.

development banks, and bilateral commercially oriented development banks that play useful roles in various regions. The IFIs have largely focused on country programs for country benefit. The context in which IFIs were founded led them to design programs at the national level addressing health care, education, infrastructure, and other areas. For instance, the World Bank and IMF were founded after World War II in response to issues surrounding economic reconstruction and balance of payments, which were countries’ own internal problems. Tharman stated that the time has come to repurpose IFIs to address threats to the global commons, because tackling these threats—in addition to poverty eradication and ensuring inclusive growth—is the central challenge countries face. Addressing threats to the global commons requires investment in global public goods on a national and regional level and, to some extent, in global facilities and networks. This will require the World Bank and IMF to work with other multilateral development banks. Additionally, an increase in grant resources is needed to incentivize investment in capacity building. Commercial loans are inadequate, given that the rest of the world will derive benefit from these investments in low-income countries. Strengthening the role of IFIs in tackling infectious disease threats and, more generally, threats to the global commons will multiply capital for these endeavors, he remarked, by using resources of shareholders through the capital markets, as well as by incentivizing governments to do their part. Thus, repurposing IFIs for the current era is important in meeting the central challenge facing individual countries, that of threats to the global commons, he remarked.

The third strategic move is the creation of a new global financing mechanism that provides an overlay on the financing of individual organizations. The current system is gravely underfunded and unpredictably funded; it will not be repaired by increasing bilateral funding for existing institutions alone, said Tharman. A multilateral layer of financing is needed to work synergistically with the individual organizations that play critical roles in global health security. A challenge in creating such an overlay is avoiding further fragmentation or the introduction of new inefficiencies into the system. This can be accomplished with the creation of a global health threats fund. Rather than serve as an operational entity, this global health security fund would bring forth additional resources for existing organizations. For example, such a global health threats fund could provide additional resources to the International Development Association, the Global Fund, Gavi, or any other organization working to garner support for programs that deal with both emerging and existing threats, on the condition that the organization also used funds from bilateral or philanthropic sources. In other words, the multilateral fund would not divert resources that otherwise would have gone to existing organizations, but instead seek to supplement such funds.

Integrating Pandemic Preparedness and Endemic Disease Control

Efforts to prevent and prepare for future pandemics should be integrated with efforts to address endemic diseases to the fullest extent possible, Tharman stated. Preventing and preparing ourselves well for pandemics is critical not only in its own right but because of the much broader cost pandemics impose on society, not the least being the neglect of other pressing public health needs, he emphasized. The nature of the facilities and human resources required to address pandemics and endemics is the same. Efforts to contend with TB and other infectious diseases involve building the capability to detect, diagnose, and treat disease quickly. In addition, capacities such as global surveillance networks, data sharing, and genomic sequencing are in need of massive scaling up, he remarked.³

Currently, international, national, and regional facilities are underprepared. Resolving issues of supply capacity should aim to radically shorten the time required to roll out vaccines, therapeutics, personal protective equipment, and other critical supplies on a global scale. This increased capacity could be used in interpandemic years to meet the needs caused by endemic diseases and other public health requirements. Even excess capacity maintained for a future pandemic would be a worthwhile investment, as the funds spent on manufacturing capacity will be recouped many times over through the rapid delivery of critical supplies thus reducing the costs of a pandemic, he added. The most efficient preparation for future pandemics relies on and reinforces the work involved in tackling endemic diseases.

A new multilateral funding mechanism has the potential to strengthen multilateralism, achieve better synergy with bilateral efforts, and improve relationships between institutions to network more effectively and attack problems more seamlessly. The G20 HLIP estimated that a global health threats fund would require a minimum of $10 billion per year. Tharman remarked that although this figure sounds high, it is a small sum relative to the potential gains and to a country’s ability to afford it. Spread out over countries, this figure comes to approximately 0.02 percent of gross domestic product (GDP), reflecting a small sum if distributed across countries on a fair and equitable basis. Thus, politics, not finance, is the constraint in moving this initiative forward.

Political will is needed to invest collectively in collective security. Investing in collective security is not only a global good, it is also for the good of each individual nation. Finance is not the constraint, but rather it is myopia in governance and politics that is causing the holdup in many parts of the

___________________

³ The WHO supranational reference lab system works to expand and link TB genomic sequencing. See Gilpin and Mirzayev, 2019.

world; that is, the lack of recognition that one’s own country’s interests are best served through collective investment in collective health care security, and what is now needed is leadership to push this through. The $10 billion figure—a conservative estimate that does not take into account all the investments necessary—illustrates the gross underfunding of the system. Tharman noted that one of the few benefits of COVID-19 is that it has forced perspective shifts to an extent that past epidemics and pandemics did not. The current climate can be capitalized upon to make bold changes in international cooperation to preserve health security.

Discussion

Sands began by remarking that in the context of the global financial crisis of 2007–2008, governments were prepared to invest significant sums of money into preventing future financial crises. He posited that the investments made after the global financial crisis back then helped prevent an immediate financial crisis at the onset of the COVID-19 pandemic. Turning to the need for pandemic preparedness, Sands noted that it will require the level of funding being discussed by the G20 HLIP, but pointed out that the current global external funding for TB is only around $1 billion per year. This underinvestment in TB juxtaposed with the proposed amount of new funding for pandemic preparedness appears inequitable, with large sums of money designated to meet new and future threats that might kill people alongside hesitancy to spend much smaller amounts of money on diseases that are currently killing people. Even within high-TB-burden countries, funding is often not allocated equitably because the disease is primarily contracted by people outside of the elite class. Sands asked,

Tharman said in response that today’s international financing of global health security—essentially composed of efforts to prevent and combat infectious disease threats—totals approximately $15 billion in governmental and philanthropic investments. At a minimum, an additional $15 billion is needed, one-third of which would be channeled through existing routes for specific missions, thereby significantly increasing funding for organizations. The remaining two-thirds could create a predictable, multilateral layer of funding to support the system by connecting silos. He stated that a central challenge is establishing governance of global health security that ensures attention is appropriately placed on areas of need and that financing is raised, rather than rediverted, for these areas. Tharman emphasized that the total funding needed pales in comparison to the costs of a major outbreak,

thus the social return on these investments is high. Much synergy exists between addressing endemic diseases and preventing the next pandemic; therefore funding the former will strengthen the latter.

Amanda Glassman, executive vice president and senior fellow at the Center for Global Development and chief executive officer of the center’s branch in Europe, asked about the finance implications and incentive opportunities regarding the TB burden in middle-income countries. She suggested that one reason only $1 billion in international financing has been directed at TB is because middle-income countries theoretically have the ability to independently finance these basic public health services. Tharman held that international financing support and incentives will be needed for investments in certain global public goods even for middle-income countries. Although low-income countries will require grant money, other forms of international financing can be effective for middle-income countries. He added that extending IFI support to middle-income countries for this defined purpose is in the world’s interest.

Gail Cassell, senior lecturer on global health and social medicine at Harvard Medical School, asked how increased accountability and demonstrated, documented data can be used to show a return on investment (ROI). She also asked what body or governance structure might be best suited to reviewing accountability and ROI. Tharman suggested strengthening financial governance to raise substantially greater amounts of funds on a sustained basis. This need not require a cumbersome process involving a large number of country representatives. Instead, principles need to be clearly set along with rigor in their application. The G20 HLIP proposed achieving this through the formation of an expanded G20 grouping that also includes major developing regions, global health organizations, and major multilateral organizations. This group would be responsible for identifying gaps in the system, continuously assessing risks, and prioritizing funding needs. He added that the group would have a permanent secretariat. The actual deployment of funds would feature the commercial discipline involved in ensuring ROI—which, in this case, is a quantification of social returns on investment, rather than private returns. Collaboration between institutions would be encouraged to increase coordination on the ground. Tharman commented that sustaining high levels of funding from donors and the broader group of countries in the world will require good governance and demonstration that funds are being well used and achieving desired effects over time.

Cassell asked whether the G20 HLIP will continue to lead this effort. Tharman responded that HLIP has made a set of proposals that are currently being actively considered. Discussion continued during the United Nations (UN) General Assembly in September 2021 and in the G20 summit in October 2021. He hoped that concrete actions would be taken at the G20 summit to launch and strengthen these mechanisms over the next year. Sands

called for capitalizing on the current opportunity to transform the approach to current and future health threats.

ACHIEVING SYNERGY IN GLOBAL HEALTH SECURITY PREPAREDNESS AGAINST RESPIRATORY PATHOGENS

Sands opened the panel discussion on achieving synergy in global health security preparedness against respiratory pathogens by suggesting that TB can either become a part of the pandemic preparedness agenda in making the world safer from future pathogens or it can be sidelined as a long-standing disease that primarily affects poor people, resulting in its deprioritization in the face of new threats. Sands asked for pragmatic next steps after the COVID-19 pandemic to prepare for future pandemics and to eliminate TB.

Large-Scale Vaccination Infrastructure

Presented by John Bell, Oxford University

Bell remarked that the COVID-19 pandemic has been a challenging time for global public health, in part because of the various silos rampant within the field. Infrastructure is needed that supports the capacity to address a wider range of pathogens, including both chronic pandemic pathogens (e.g., TB, malaria) and acute pandemic pathogens such as COVID-19. The current moment offers an opportunity to pivot from structures of the past to build a systematic program to prepare global public health for pathogen threats, both chronic and acute. The revolution in vaccines that has occurred during the COVID-19 pandemic began 15 years ago in an R&D agenda that was accelerated by the pandemic and has resulted in powerful, programmable platforms in the form of RNA and adenovirus. Additional candidate vaccines also show promise, including an adenovirus malaria vaccine for which data show nearly 80 percent efficacy (Yusuf et al., 2019) and the highly anticipated data on the M72 candidate vaccine for TB, Bell noted. Opportunities for multiplex coronavirus and influenza vaccines may become a cornerstone of future developments. The world’s capacity to implement large-scale vaccination programs has been strengthened by expansion in vaccine manufacturing capacity (including RNA, adenovirus, and protein subunits) and the necessary supply chain of adjuvants. Such campaigns will not only address COVID-19 but also a host of other pathogens that could include TB. Maintaining the operability of facilities in interpandemic periods is important for pandemic preparedness, and the rollout of a set of potential adult vaccines would be an excellent method of facility maintenance, said Bell.

The capacity for low-income countries to implement large-scale vaccination programs remains limited, and absorption capacity will need to be substantially expanded to achieve near-universal COVID-19 vaccination coverage, Bell remarked. Information technology systems, logistics, and clinics are required to build a global public health system for adult vaccines. A strategy that expands capacity to administer vaccines for influenza, TB, malaria, and COVID-19 boosters would strengthen PPR efforts. Furthermore, additional injectables could be considered, such as long-acting, annual injectables for a variety of health needs (e.g., small interfering RNA for cardiometabolic disease protection, long-acting HIV drugs, or contraception). A system that prevents multiple diseases at once could generate massive efficiencies of scale, he added.

Another structure that could result from the COVID-19 pandemic is better genomic surveillance and sequencing associated with a global cloud infrastructure for managing data and providing immediate analysis, said Bell. Such a system could affect multiple major pathogens. Although it may be tempting to focus new systems on COVID-19, he cautioned against continuing to operate within silos. Instead, common infrastructure and systematic approaches can be created that address a range of different diseases while improving cost-effectiveness and ROI.

Identifying Alignments in Surveillance Efforts

Presented by Bruce Gellin, Rockefeller Foundation

Gellin echoed Bell’s comments that using expanded vaccination capacity for vaccines beyond COVID-19 will aid in justifying the investments. For vaccines to be effective, they must turn into vaccinations. He suggested that the TB community can contribute its extensive experience in contact tracing, community-based surveillance, and community delivery. Seasonal and pandemic influenza, TB, and COVID-19 are all respiratory pathogens, thus maintaining silos for each pathogen is not the most effective approach to addressing these diseases.⁴

Bolstering early warning surveillance systems during interpandemic periods can improve detection capability and provide baseline data, said Gellin. Epidemiology, surveillance, and data sharing are currently being used to address COVID-19 variants. Although the process begins with genomic surveillance, the compilation of a range of data informs researchers of cur-

___________________

⁴ Gellin added that when he worked on antimicrobial resistance, TB was in its own silo in spite of widespread awareness of MDR TB. He suggested that perhaps shifting language, for example, referring to extensively drug-resistant TB (XDR TB) as variants would garner more attention.

rent disease activity, areas where pathogens are emerging, and the degree to which outbreaks can be predicted. Gellin noted that the long history of TB can provide data for the surveillance system. The surveillance systems that have been created during the COVID-19 pandemic (e.g., the Rockefeller Foundation’s Pandemic Prevention Institute, WHO’s Hub for Pandemic and Epidemic Intelligence, the UK’s Global Pandemic Radar) could productively collaborate like gears within an engine. Investments in early surveillance could enable targets to be established. Alignments between efforts would capitalize on the developments that stem from each pathogen, creating a common system for prevention, identification, surveillance, and treatment.

Applying Tuberculosis Research to the COVID-19 Pandemic

Presented by Rebecca Katz, Georgetown University

Katz described significant variation in TB mitigation approaches implemented across the United States and how this variation intersects with health security. In 2014, she conducted a study examining U.S. local-level capacity and policy around the use of isolation and quarantine as containment measures (Katz and Vaught, 2017). Interviews conducted with TB control officers around the United States informed case studies of TB outbreaks in the decade prior. The study’s goal was to better understand the approaches used by local health departments to identify and contain outbreaks and to determine isolation protocols used. Katz described remarkable variation around the country in terms of (1) social distancing interventions, (2) handling of noncompliant patients by local public health entities, (3) the degree of judicial and community support, (4) financial resources, and (5) incentives and enablers used to maintain isolation of infectious TB patients. For instance, some jurisdictions placed infectious patients in negative pressure jail cells, while others enabled isolation by paying heating bills, delivering groceries, and providing electronic tablets and Wi-Fi to facilitate family communication. Identifying evidentiary standards, risk assessment, political will, and community support can inform how these factors affect the ability to institute social distancing policies. Katz noted that this study was informative of how jurisdictions later managed early COVID-19 cases. The purpose of the study was to use TB as a mechanism for understanding the capacity of health departments to implement physical distancing measures in a pandemic, and its findings demonstrate how capacity building for TB and PPR affect one another.

Katz and colleagues have mapped budgetary data for the Global Fund onto the joint external evaluation indicators of the International Health Regulations (Boyce et al., 2021). Although the Global Fund invested in TB—and not in pandemics—much of the TB work was pivoted to COVID-19.

Even prior to the pandemic, strengthened TB response and capacity building demonstrated direct links with health security capacity building. Examples of crossover capabilities include contact tracing and the ability to address antimicrobial resistance (AMR), which includes laboratory analysis and sequencing. Prior to the COVID-19 pandemic, the few examples of robust contact tracing efforts included sexually transmitted infections and TB tracing conducted in schools, airports, and among vulnerable populations, noted Katz. The Global Fund has used GeneXpert as a platform for both TB and COVID-19 in assessing overall laboratory capacity-building efforts and incentives, enablers, and enforcement of physical distancing measures for isolation and quarantine. Such overlaps indicate an opportunity for pragmatism in investments and strategies that consider how different programs affect one another, she added.

Innovation in Technology and Finance

Presented by Michael Callahan, Massachusetts General Hospital and United Therapeutics

Noting the destabilizing effects of TB upon public health infrastructures and all-cause failures, Callahan suggested that TB would be an appropriate addition to the global health security agenda. Operational public health intervention programs for TB have been decimated by a focus on COVID-19, whereas COVID-19 implementation strategies have benefited from therapy, surveillance, and other programs developed for TB. He likened this to the way in which PEPFAR work benefited the infrastructure, therapeutics delivery, and movement of samples in the response to the 2012–2013 Ebola outbreak in West Africa. Callahan suggested examining the destabilizing influences of a pandemic on the treatment of other diseases and assessing the ability to use preexisting infrastructure during a pandemic.

To justify the inclusion of TB in the global health security agenda from an evidentiary standpoint, Callahan highlighted data comparing the effects of TB and COVID-19. He shared that each year, 900,000 people die directly from TB disease, a figure that does not include secondary effects of long-term sequelae of highly toxic antimicrobials and infections from peripherally inserted central catheters for aminoglycoside treatment. While 4.7 million people died from COVID-19 within a 19-month period,⁵ this rate will likely drop with continued distribution of quality vaccines, converting COVID-19 from a pandemic to an endemic. In contrast, he noted, TB has not reached endemicity thresholds despite the many years that humans have coexisted with

___________________

⁵ Data as of September 16, 2021 from https://coronavirus.jhu.edu/data/mortality (accessed January 2, 2022).

the disease. Comparing the adjusted cost ratios of TB and COVID-19—without adjusting for age, gender, or comorbidities—underscores the high cost of treating TB. In his experience working in austere medical settings, treating MDR TB and XDR TB patients eliminates available capacity to treat other acute illnesses, including malaria and respiratory and diarrheal diseases. Callahan shared that the cost index accepted by WHO for MDR TB management in affluent nations is $152,000 and includes first-line therapy failures with isoniazid. In comparison, Kaiser Permanente calculated that the adjusted cost of hospital care for a COVID-19 patient in the United States and Canada—for cases not requiring extracorporeal membrane oxygenation or extended ventilation—ranges from $51,000 to $78,000 (Hackett, 2020).

Callahan highlighted innovations that could be used to address TB. New medical countermeasures include gene-encoded therapies and host modulating therapies. He underscored the challenges in acquiring funding for messenger RNA (mRNA) vaccines, noting that prior to the success of mRNA vaccines against COVID-19, 11 years elapsed before Moderna and BioNTech were funded by a second federal agency. He added that influenza vaccines are more technically challenging to develop, and these limits to the technology can only be expanded by rigorous competitive investment in multiple categories. To address TB, Callahan commented that from a strategic standpoint, the process of addressing Mycobacterium tuberculosis should focus on avoiding selection for resistance that will decimate antimicrobial classes used for other lifesaving therapeutic purposes, notably for respiratory infections. He mentioned the potential for host modulating therapies such as DNA therapies that can temporarily disrupt large encoded biologics and enzyme systems necessary for infection or target the bacteria itself. For example, there are phase 2 studies that have generated enthusiasm around the ability of host modulating therapies to deny a host enzyme system that is necessary to a pathogen for a short period of time, without exerting a selective pressure to lead to escape use. This area of inquiry is largely focused on retroviruses and drug-resistant hepatitis C viruses and is expanding into bacterial pathogens, including mycobacteria, he added.

Financial management is another area of innovation. The U.S. Agency for International Development’s PREDICT program and the Defense Advanced Research Projects Agency (DARPA) have used financial management strategies that highlight diseases with low profit margins to capture the interest of foreign investors. Callahan remarked that a “twinning” strategy of coupling diseases with low profit margins to diseases with high net worth has been extraordinarily successful. For example, two hepatitis C drugs that generate $6 billion in annual revenue were yoked to drugs for dengue. This brought the dengue portfolio into phase 2 trials, but profit-seeking business interests abandoned it during licensing. Had DARPA held those drugs, better small-molecule inhibitors for dengue and other flaviviruses likely would have

entered phase 3 studies and possibly even licensure to address a disease that infects over 400 million people each year.

This strategy may be useful for mycobacteria because several of the drug targets are conserved across other Gram-negative bacteria. Another strategy is using the target product profile for low- and middle-income countries (LMICs). Callahan commented that technologies to address HIV that did not work in cities such as Boston and London proved to be effective in directly inserted antiretroviral therapy programs in African countries. These less expensive, more effective therapies designed for LMIC settings were justified by their clinical usefulness and cost-effectiveness. The demonstrated value of these treatments then propelled their readoption by the high-income countries that made them and are now considered the standard of care. Moving forward, target product profiles should include the clinical treatment environment and the need for longitudinal patient monitoring, said Callahan. He added that treatment and release is now being used for a number of influenza therapies.

AMR and the selection of resistance should be reconciled with the clinical pragmatism of large-scale public health delivery systems, Callahan remarked. Antimicrobial stewardship programs in LMICs can be ineffective in the situation of an imminent, acute clinical decision to save a patient. He noted that devastating events have occurred when AMR was considered without understanding the rational use of antimicrobials for strategic reasons. For instance, if rifampicin is used as the empiric presumptive therapy for meningococcal disease to routinely treat thousands of children in sub-Saharan Africa, subsequent cases of TB in the region will be rifampicin-resistant in the following months to years, said Callahan. Thus, understanding the bystander public health casualties is important when addressing AMR.

Discussion

Surveillance Systems

A participant asked about the features a system would need to boost national capacity for pandemic preparedness surveillance while simultaneously benefiting people with TB symptoms presenting at primary health care clinics. Gellin emphasized that surveillance is more than remote data aggregation and must include local capacity for identification and analysis. The COVID-19 pandemic has developed the recognition that localities and central focus points alike need to understand both the big picture and the specific on-the-ground implications. Data sharing also plays a role: the sourcing, sharing, and use of data at all levels contribute to an effective system. However, data sharing is built upon trust. Katz remarked that strengthening the health care system overall affects surveillance. Improved access to

care worldwide increases the likelihood a person will be seen by a medical professional, have their symptoms diagnosed, and obtain lab results. Thus, building a strong health care system can simultaneously strengthen pandemic preparedness and address population health concerns. The entire public health and health care system—rather than a specific disease—should be considered in determining the systems to build.

Tracking Progress in Prevention

Sands remarked that among the attractions of disease-specific silos are the advantages of easily defined outcomes and highly focused targets. For example, desired outcomes of a TB-specific program include decreases in infections and deaths. Measuring performance becomes more difficult for a system focused on multiple pathogens, sustainable capability, and integration. He noted that results of health systems investments that were not directly linked to disease-specific outcomes have been mixed, and asked how a system can be highly focused without using silos and managing performance while achieving integration. Katz replied that the activities that are measured become the activities that are performed. However, the health security and pandemic preparedness space has never been measured well. Before the COVID-19 pandemic, it was difficult to raise sufficient funds to build PPR capacity owing to the lack of a compelling metric (e.g., a measure for how much safer the population would be). In contrast, TB and malaria programs are able to generate figures on the numbers of lives saved. Katz suggested developing a new approach to formulating ROI to determine what types of PPR investments are needed and how these are tracked.

Bell recounted that approximately 20 years ago he met someone at a workshop who had obtained a large amount of funding for global TB control. When he asked how this had been managed, the person replied that he was ruthless in communicating the terrible aspects of TB while dismissing all other diseases. Bell suggested this reflected a culture in which researchers interested in broad, systems-based interventions cannot obtain funding, but this culture appears to have changed in the modern day. A potential strategy is to develop a system that focuses on surveillance and vaccination for a single pathogen, then expand it to additional pathogens once the system is established. Bell emphasized the importance of developing measurable outcomes and the effect of efficiencies of scale on ROIs.

Diagnostics Technology

Kenneth Castro, professor of global health and epidemiology at Emory University, stated that in some countries with low TB incidence—including the Netherlands and the United States—universal genotyping is used to better understand transmission dynamics and to identify locations warranting additional attention. He remarked that investment in laboratory services

infrastructure and rapid feedback capacity should include TB and other infectious pathogens. Gellin echoed the importance of establishing broader surveillance. Creating a surveillance system begins with collecting and examining samples, and genomic surveillance could become the standard moving forward. The opportunity to develop simpler at-home diagnostics could also play a role by empowering people to better understand their risks when going out in public. Offering incentives is a potential strategy for developing such technologies for TB and a range of respiratory pathogens, he added.

Cassell remarked that new technology is being developed for COVID-19 that enables at-home diagnostic and screening stations to perform tests in the field instead of relying on laboratories—potentially reducing both expense and personnel required for testing as well—and emphasized how important a point-of-care diagnostic could be in addressing TB. She asked about other examples of progress and how these may affect technological advances for TB. Callahan replied that the international community has focused on lateral flow assays for muramyl dipeptide and other TB markers. Current challenges relate to technical complications in obtaining sputum samples and preparing them for the tests. Groups including Wellcome Trust, the Tropical Diseases Research Centre, and the Agency for Science, Technology and Research (A*STAR) Singapore have been working on sample preparation technology that could revolutionize TB diagnostics. For example, A*STAR is working to address TB risk in Singapore by controlling TB in other nations; it has invested in a program for the diagnosis of any lower respiratory tract infection that has expansive usefulness outside of TB. Gellin highlighted the need for diagnostic technology that can be moved distally, but he cautioned that when using at-home and in-field testing, efforts should be made to capture the data to avoid losing it for the public health surveillance system.

Factors Affecting the Perception of Urgency

Sands remarked on the sense of urgency around COVID-19 that is lacking with respect to TB, posing challenges to mobilizing political will and scientific interest in the disease. He presented a scenario in which a new disease emerges that kills 1 million people a year, has a latent infection rate of 25 percent of the world, and creates variants that evolve in ways that make it extremely difficult to treat, and carry high case fatality rates. In such a scenario, would a vaccine timeline of 4 to 5 years suffice, or would the 100-day target apply?⁶ Would the pace at which accurate point-of-care

___________________

⁶ The 100-day target has been discussed as a goal for PPR in a number of initiatives including the American Pandemic Preparedness Plan and the pandemic preparedness partnership of the G7 (see https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/992762/100_Days_Mission_to_respond_to_future_pandemic_threats__3_.pdf, accessed January 2, 2022).

diagnostics are being developed be considered satisfactory? Sands suggested that the length of time TB has existed has engendered a familiarity with the disease that undermines the sense of urgency that would arise if it were a novel disease with identical consequences.

Callahan believes that a new disease with the same morbidity, mortality, and economic effects as TB would generate a startled response, in contrast to the apparent fatigue around TB. New arguments for combating TB are economic and financial, and rebalancing within the global coalition from public health government to corporate and civic bodies is taking place, he noted. For example, an Islamic health coalition associated with the Red Crescent is focusing efforts on TB throughout Indonesia in response to the devastation TB has caused in mosques and rural communities, as well as the complexity of accessing care deemed “halal”—or permissible—by the Imam. Callahan suggested that capturing the attention of coalitions that are not traditional public health groups could energize the effort because these coalitions bring new targets for measurement and are able to see that TB causes business disruption, economic devastation, and bystander casualties involving other diseases.

Currently, governments and populations in all parts of the world are determining the “tolerable” rates of COVID-19 as calculations are made regarding policy decisions, reopening schools, investment levels, and measures that are recommended or required, said Katz. She remarked on the subjective nature of tolerance as it pertains to rates of infection, morbidity, and mortality. Personal calculations will not necessarily match those of political leaders, while the calculations of political leaders vary in different parts of the world. She suggested that the current awareness of COVID-19 morbidity and mortality presents an opportunity to recast conversations about diseases that the public has normalized. Sands added that normalization is a human coping mechanism that can lead to accepting things that should be deemed unacceptable. Gellin remarked that the conversations around learning to manage COVID-19 in the event it cannot be eradicated would be a challenge should the same thinking be applied to TB. Owing to the long-standing nature of TB and its lack of visibility among populations that are not contracting the disease, people may be complacent about addressing it. Should that prove to be the case, the TB community will need to improve efforts to raise awareness regarding the numbers of people affected by this disease, stated Gellin. Bell noted that although the public tolerates seasonal influenza that kills tens of thousands of people in the United States each year, alarm arises when there is a pandemic or epidemic, leading to greater attention to vaccines. The way in which people address these issues is not always logical, as reflected in the management of TB.

Sands noted that people tend to be more willing to tolerate diseases that are not killing people in their close circles, and less troubled about

a disease that causes deaths in other parts of the world or even in other parts of the city. This has been the case with TB and HIV, which disproportionally affect marginalized and poor populations. Unless PPR efforts address this tendency to normalize a level of risk to certain parts of society, it may translate to a high level of ongoing threat with high morbidity and mortality cost, he warned, predicting that the tendency to be complacent about high levels of mortality in poorer or marginalized populations will continue until it is disrupted. Bell added that the issues that directly affect people’s lives are the ones that spur them to take action. Gellin noted a similarity in complacency around climate change. Although the effects of climate change seem to be becoming more evident to the public, the lack of direct implications on people’s lives thus far has resulted in a lack of urgency. Katz commented that a benefit among the terrible aspects of the COVID-19 pandemic is an increase in global population awareness of disease communicability.

Using the energy and perspectives of communities that have traditionally been outside of the health system could bring in new ideas and increase levels of commitment to addressing TB, said Sands. He recounted a quote attributed to medical anthropologist Paul Farmer, “The idea that some lives matter less is the root of all that’s wrong with the world.” Sands suggested that a PPR agenda that marginalizes the TB response would not fulfill an inclusive vision of protecting everyone. Bell replied that this is even more the case with malaria, which tends to be less prevalent than TB in Western countries. This raises issues around how pandemics are defined and who defines them, said Sands. Common usage of the term pandemic seems to refer to the disease death rates in wealthy countries, and this perception should be addressed in PPR efforts.

Capitalizing on the COVID-19 Pandemic

Sands asked the panelists to offer final thoughts on the role of TB in the PPR agenda. Bell described a scenario that could take place over the course of the next 18–24 months, in which COVID-19 becomes broadly controlled in developed economies. At that point, interest in PPR declines, marking a return to the status quo without advancing efforts to fight TB. To avoid this scenario, he suggested capitalizing on the current sense of urgency by putting structures in place for PPR from which TB efforts would benefit. Bell added that it will likely be several decades before another such opportunity to create PPR systems appears. Gellin said that instead of focusing efforts on one disease and hoping these efforts will benefit other diseases, lessons learned from multiple diseases should be packaged together and can be addressed synergistically. Bell added that this approach creates a multiplier for results and thus a more persuasive argument for investments.

Katz was hopeful that the panic-to-neglect cycle will last longer than 2 years before returning to a phase of neglect, but how long the world’s attention on PPR will be sustained is uncertain. Should the strategy developed by the G20 HLIP prove successful in raising billions of dollars annually for PPR, this would capitalize on the current opportunity to make smart investments in a holistic, global system that better addresses all biological threats. Callahan commented that there is cause for optimism in the potentially transformative innovations occurring in new medical countermeasures, lateral flow assays, point-of-care diagnostics for TB, and sample prep technology. In the past, some promising technologies have been stymied and suppressed within the legacy disease environment, but the dated system for TB could be restructured to be innovative and capitalize on technological advances. Sands predicted that including TB in the PPR agenda would scale opportunity, but TB’s inclusion will require bringing to bear the efforts of leaders, policy makers, and the TB advocacy community. The history of TB demonstrates that fully addressing the disease will not happen by its own accord, he added.

MAKING THE CASE FOR FINANCING TUBERCULOSIS ELIMINATION

Margaret Hamburg, interim vice president of Global Biological Policy and Programs for the Nuclear Threat Initiative, moderated the panel on the financing of programs and implementation of policies directed at the ultimate goal of TB elimination. In terms of a panic-to-neglect cycle, current public awareness of the threat of communicable diseases and the magnitude of health tragedies—and social and economic dislocations—they can cause provides an opportunity for action. At the same time, an environment of fatigue from COVID-19 can present challenges to a public overwhelmed by living in a world of biological threats. Furthermore, as the world emerges from the current COVID-19 crisis, many priorities will compete for attention and funding. Investments in TB elimination simultaneously address health, humanitarian, and safety needs.

Economic Analysis of the Cost of Failing to Achieve the End TB Targets

Presented by Mike Reid, University of California, San Francisco

Reid outlined the full-income cost of failing to end the TB epidemic. The Lancet Commission TB strategy calls for a 90 percent reduction of the 2015 TB deaths by the year 2030 (Reid et al., 2019). He remarked that meeting this target seems highly improbable, and that the 2019 report highlighted that achieving this target by 2045 is also unlikely. In the context of the

COVID-19 pandemic, it is critical for high-TB-burden countries and their donor partners to understand why ending TB is essential.

Unfortunately, the overall evidence on the economics of TB has been heterogeneous and has lacked a comprehensive assessment of TB epidemics’ effects on economic welfare, said Reid. Numerous studies have used a variety of tools to assess the economic effect of TB, including the macroeconomic implications of TB treatment and control activities. Commissioned by the Global TB Caucus in 2017, KPMG conducted an analysis on the effect of TB mortality on per capita domestic groups by projecting estimated economic losses attributable to TB-related mortality between 2015 and 2030 (Global TB Caucus, 2017). The analysis found that maintaining the TB status quo and failing to achieve the UN Sustainable Development Goals (SDGs) would result in 28 million TB deaths within that 15-year time, at a global economic cost of nearly $1 trillion. The greatest losses in GDP were projected for Southeast Asia. Reid added that such macroeconomic studies that measure the effect of health improvements on economic productivity do not necessarily capture the intrinsic value that people place on their improved health. For this reason, many economists have asserted the usefulness of a full-income approach to assessing the effect of investing in health.

A full-income approach accounts for the value of additional life years in assessing economic productivity (Jamison et al., 2013). Reid described how two countries may have identical GDP but have starkly different TB burdens. The population of the country with low TB burden, “country A,” lives longer and in better health than the population of “country B,” where more people die from TB. An approach using GDP as the only measure of health does not capture the monetary value of country A’s better performance. National income accounts do not reflect the reduced mortality risk in country A. In contrast, a full-income approach seeks to capture the value of life years gained by including the value of change in annual mortality rates in assessing changes in GDP. Reid remarked that estimating the growth of a country’s full income—rather than using GDP alone—provides a more accurate, complete picture of the value of investments.

Reid and colleagues evaluated the effect of investing in TB programs and the economic dividend that could be generated from reduced TB mortality (Silva et al., 2021). The analysis involved calculations of life expectancy gains from 2020 to 2050 under three scenarios in 120 countries. The first scenario featured the steady 2 percent decline in TB deaths that signifies business as usual. The second scenario envisioned meeting the SDG target of ending the TB epidemic by 2030; the third scenario involved meeting the target by 2045. Additionally, the researchers attempted to evaluate the excess deaths caused by disruptions in TB services related to the COVID-19 pandemic. Reid noted that this evaluation involved assumptions and outputs from a modeling paper commissioned by the Stop TB Partnership (Cilloni et al., 2020).

Researchers determined the current full-income loss associated with TB using 2018 data, in which approximately 1.4 million people died from all forms of TB. The full-income losses were estimated to be $580 billion, or approximately $407,000 per TB death. The highest losses were concentrated in sub-Saharan Africa, a region that accounted for $200 billion in accrued losses. In other words, had the 1.4 million TB deaths in 2018 been averted, $580 billion of full-income losses would also have been averted, Reid explained. Additionally, life expectancy at birth for individuals living in those 120 countries would increase by an average of 0.47 years.

The analysis estimated that should the current 2 percent rate of declining TB deaths continue annually until 2050, 32 million deaths will occur, said Reid. The economic losses caused by these deaths are estimated to be $17.5 trillion. Southeast Asia would experience the highest economic losses—totaling approximately $7 trillion—and countries in sub-Saharan Africa would see the greatest effect on life expectancy with a reduction of 0.84 years. In contrast, meeting the SDG target by 2030 would result in an estimated 8 million deaths over the next decade and an associated economic loss of $4 trillion dollars. Meeting the SDG target by 2045 would avert an estimated 13.7 million deaths and $7.3 trillion in economic losses. Therefore, the overall cost of inadequate action incurred by meeting the SDG target in 2045 rather than in 2030 is over $3.3 trillion and 5.7 million deaths, Reid noted.

Reid and his colleagues also assessed the effect of COVID-19 on TB-related economic losses by estimating the health care costs resulting from excess TB deaths in three countries (Reid et al., 2020). They found that TB cases were likely to increase as a result of COVID-19-related service disruptions in 2020. A 3-month suspension of programs during lockdown and a 10-month recovery period for programs to return to prepandemic activity were estimated to result in an excess of TB-related health costs totaling $1.95 billion in India, $96 million in Ukraine, and $29 million in Kenya. Applying the full-income approach to these modeling assumptions, researchers estimated that even in the best-case scenario of the SDG target being met in 2030, the COVID-19-related disruptions in TB services in 2020 could create $447 billion in full-income losses (Silva et al., 2021). Reid stated that even the relatively short-lived disruption of TB services caused by the COVID-19 pandemic is predicted to lead to substantial full-income losses in the next 15 years.

Outlining the limitations of the analysis, Reid noted that the full-income analysis did not capture the economic implications of nonfatal TB. Additionally, the estimates of TB mortality are crude and may be conservative, which affects the economic estimates based on these figures. However, the research indicates that substantial full-income losses will arise if efforts to respond to the TB epidemic are not increased. Moreover, the amounts of funding currently being invested in TB programs pale in comparison to the

huge potential economic losses. He added that these findings have important implications for ministries of finance and donor partners.

The research provides compelling reasons for investing in the scale-up of evidence-based, patient-centered programs, including increased focus on high-burden settings, in concert with a broader global health security agenda. It also provides evidence in support of greater prioritization of investment in health by high-burden countries, said Reid. Governments can be incentivized to increase efforts, especially given that the benefits of investment are estimated to exceed the cost by a factor of five (Reid et al., 2019). Furthermore, these investments strengthen global public goods from which all nations will benefit. Reid asserted that the current moment affords a propitious, unique opportunity to use the political will and investment in responding to COVID-19 and preventing future pandemics toward efforts to end TB. COVID-19 and TB serve as reminders of the value of prioritizing health, allocating financial and human resources for universal health coverage, and addressing the needs of vulnerable populations in particular.

Making a Compelling Case for Strengthening TB Control and the Consequences Thereof

Presented by Bjorn Lomborg, Copenhagen Consensus Center

Lomborg explained that his work involves examining a vast range of areas to determine where the application of resources may be most effective. Working with more than 300 of the world’s top economists, including Nobel laureates, the Copenhagen Consensus Center (CCC) explores issues such as climate, health, and HIV in countries including Haiti, Bangladesh, India, Ghana, Malawi, and Uganda. CCC has analyzed the SDGs in an effort to prioritize them. The SDGs include approximately 300 targets, many of which are not currently on track to be met by 2030. Lomborg noted that the CCC worked with over 100 economists to prepare publications on a large range of topics in order to evaluate the costs and benefits of the SDG areas, partnered with media outlets in 20 low-income countries to publicize the research; the CCC also published a large book with Cambridge University Press and a shorter book for increased accessibility that details the research findings (Lomborg, 2015, 2018). Lastly, CCC created a one-page synopsis that lists the cost and benefit analyses for 80 different activities within the SDG agenda.⁷

The analysis identified decreasing TB deaths as a good investment, with every dollar spent on TB prevention and treatment generating $43 worth of

___________________

⁷ The synopsis is available from https://www.copenhagenconsensus.com/sites/default/files/post2015brochure_m.pdf (accessed December 15, 2021).

social good, said Lomborg. The costs of addressing TB include $4.3 billion for latent TB screening to identify the estimated 2.7 million undiagnosed cases each year, $2.2 billion for treatment of 5.8 million people with drug-sensitive TB, and $1.6 billion for the 500,000 people with MDR TB. This totals $8.1 billion in annual spending—or $907 per person with TB—to address all TB cases worldwide. Savings in life years was used as the defining benefit of these interventions in this analysis, which is estimated at an average savings of 20 life years. Researchers used the disability-adjusted life year (DALY) metric to measure the overall disease burden of early TB-related death and used time discounting to account for loss of future healthy years of life. Calculations were conducted with different discount rates and DALY benefit amounts to account for a variety of backgrounds. The analysis used 3 and 5 percent discount rates and DALY benefit amounts of $1,000 and $5,000. The median benefit of this range of calculations is $38,594. Factoring in the cost of $907 per person with TB, the resulting benefit-to-cost ratio is 43. This signifies that $43 of social good will be generated from each dollar spent on eliminating TB, Lomborg explained.

A high benefit-to-cost ratio can influence decision makers in investment choices, and CCC has found that tackling TB is one of the fundamentally best investments that can be made for many countries, said Lomborg. As part of its work in India, the organization partnered with Tata Trusts to form Rajasthan Priorities.⁸ The group determined that TB—which kills about 40,000 people in Rajasthan each year—was the most effective use of investment dollars. Sixty percent of Rajasthani people with TB receive treatment in private care settings, but it is often substandard. Although some may argue that the solution is moving TB care to the public sphere, Lomborg noted that the most realistic solution is to improve private care. The national strategic plan supported by Prime Minister Modi focuses on engagement with private care providers by offering subsidies for people to receive high-quality diagnostic tests and TB treatment in both private and public provider settings. The plan also offers patients treatment adherence support through call centers and works with private care settings to improve TB notification practices. Lomborg noted that the average annual cost for the services included in the plan is $2 million, but the benefit is $373 million. In this case, the benefit-to-cost ratio is 171, meaning that if you spend one dollar, it can deliver up to 171 dollars of social benefit derived from the program. He emphasized how influential the benefit-to-cost ratio can be in establishing TB as one of the best investments a country can make.

___________________

⁸ This group engaged with stakeholders from the Rajasthani government, academic institutions, and the private sector. Bibek Debroy, chairman of the Economic Advisory Council to Prime Minister Modi, was an eminent Rajasthan Priorities panelist. See https://www.copenhagenconsensus.com/rajasthan-priorities.

CCC’s current project, Halftime for the SDGs, is assessing how much progress has been made on SDGs by 2022. Although the SDGs are approaching the halfway point on the timeline, the world is not on track to make most or possibly any of the promises made by 2030. Given that reality, the Halftime for the SDGs project is highlighting 15 goals determined to be the smartest investments for the global community to focus on, and TB is one of the best investments among the SDGs, said Lomborg. CCC will be working with other organizations, such as Stop TB, to advocate for the prioritization of TB and other top investments with decision makers.

Smart Investments in Ending TB

Presented by Mark Dybul, Georgetown University

Dybul highlighted the effect of COVID-19 on TB interventions, noting that India—a country that had been increasing TB investment, as Lomborg described—has substantially reduced investment in TB over the past 12–18 months because of the pandemic. He added that in the current environment, persuasive ROI arguments for individual interventions are making direct links to PPR. Despite being in the second year of the COVID-19 pandemic, a global response to the pandemic has yet to develop; this was the focus of the G20 summit in October 2021. Nationalism has impeded progress on a global plan to address a pandemic that affects everyone, including wealthy people and high-income nations, he added. This challenging atmosphere makes it more difficult to address a disease such as TB that affects marginalized people in lower-income countries.

Dybul said that for TB interventions to be effective in the current context, they should be linked to pandemics, both in terms of determining the steps that are needed now and in anticipating needs 5 to 10 years in the future. Moreover, this discussion of needs must translate into action; then, the systems created must also be sustained. He remarked that the best way to sustain PPR systems is to intentionally invest in current existing pandemics, such as TB, rather than focusing on interpandemics. Systems built for current pandemics can then be used for surge capacity when intervening pandemics, such as COVID-19, arise. Investing in systems for TB has revealed that a strong ground game is the most effective approach. This involves identifying cases in areas where people may be resistant to health care and health systems and conducting contact tracing. The process also requires diagnostics, particularly molecular diagnostics (e.g., GeneXpert platform pivoted from TB diagnostics to testing for COVID-19 in low-income countries). Once cases are identified, a system should be in place to provide treatment to people who may lack access to health care or be resistant to the health care system. Dybul emphasized that the components of such a system are

simultaneously high-return investments for TB and high-return investments for sustainable PPR capability.

Many people who contract TB are marginalized and do not generally access health systems, said Dybul. A number of current TB programs are successful in finding people with the disease, providing care services, and conducting contact tracing in low-income settings. Advances in diagnostics and molecular diagnostics present an opportunity to build TB systems that expand beyond response to include surveillance and preparedness. The Stop TB Partnership has focused on mobile diagnostics, and these could include TB as well as diabetes, hypertension, breast cancer, prostate cancer, and other diseases. Mobile units could have magnetic resonance imaging and X-ray machines. Not only is such a system necessary to address TB, it also provides primary health care, noted Dybul. Momentum is growing toward strengthening primary health care, which is itself a PPR system component. He remarked that the types of TB interventions Reid and Lomborg discussed are precisely the systems needed for primary health care and PPR. Placing TB in the context of building and sustaining preparedness and response systems before the next pandemic creates a persuasive argument for investment in the current environment.

Implications for Tuberculosis from the High-Level Independent Panel on Financing the Global Commons for Pandemic Preparedness and Response

Amanda Glassman, Center for Global Development

Glassman said that the G20 HLIP has examined the economic rationale for financing PPR and the role of subsidies at the international level, otherwise known as international financing. HLIP distinguished international financing from aid based on their purposes, and determined that international financing should be reserved for global public goods. A global public good is a good or activity that is nonexclusionary at the global or regional level, meaning that the benefits of its consumption accrue beyond an individual, a local government, or a nation. These goods are often not provided by the market, and they tend to lack a political constituency, because the benefits of prevention are intangible and not immediately visible.

Global public goods include the development of a vaccine that prevents transmission of an infectious disease, said Glassman. Considered a “best shot public good,” a single nation or even an individual can develop a vaccine that will benefit everyone if used. Another type of public good is known as a “weakest link public good.” For example, an individual country’s poor performance in controlling an infectious disease such as TB can drive adverse outcomes beyond its borders. Infectious disease control is therefore a “weakest link good” where the actions at the weakest link in the

chain affect the entire world’s outcomes. Glassman remarked that HLIP has argued that international financing—not aid—should create clear incentives for governments around the world to devote more resources to these uses. Some governments require international subsidies before they are able to devote resources to these goods, because the competing demands on scarce public spending are relatively so substantial that they often lead to underprioritization of public goods. For example, many low-income countries spend a larger percentage of their budgets on hospital care than on preventative primary health care.

HLIP acknowledged that investments in the broad set of actions needed to combat both existing and emerging infectious diseases are a contribution to global public goods, said Glassman. Initiatives addressing TB care, poverty, housing, and cash transfers could influence the trajectory of TB and of health systems overall. Controlling an infectious disease involves health care coverage, access to care, hospital availability, workforce, quality care, coverage of specific interventions, community engagement, health behaviors, and innovation and technology for medical countermeasures. HLIP has proposed three strategies to address an area of great need in which numerous existing organizations are already working:

1. Push complementary financing to existing entities already working in this space (e.g., WHO, CEPI, Gavi, the Global Fund) to enable scaling up of efforts.
2. Focus on high priority—but relatively underaddressed—global public goods that are currently inadequately funded or are funded in a piecemeal or irrational fashion (e.g., surveillance of respiratory pathogens, end-to-end financing of medical countermeasures from R&D to procurement).
3. Create financial incentives for countries to increase preparedness across the board.

Glassman outlined how these strategies apply to TB. Although the disease has existed for at least 9,000 years and economic development has helped to address it, MDR TB is a cross-border threat that signifies a “global public bad” that must be constrained. The core agenda for existing funding is expanding screening and first-line treatment using high-quality medicines, ensuring adherence, and enhancing progress on surveillance. Glassman noted that exploration of how to accelerate progress or make more effective use of funds does not discount the efforts of the numerous organizations working in this space. The first HLIP strategy could enable scaling up of these current efforts. Regarding surveillance, although the Global Fund invests in surveillance efforts, significant challenges to quality persist. These include difficulty in conducting continuous surveillance of drug resistance, limited

understanding of in-country geographic distribution of drug resistance, limited capacity to detect outbreaks or hotspots, and limited engagement of private providers. Glassman suggested that the pandemic preparedness effort focus on improving surveillance, potentially by combining surveillance of TB with that of other pathogens.

She noted that accepting government self-reports on their coverage of screening and treatment raises issues for the current TB response. Academic literature indicates a discrepancy between self-reports and researchers’ observations in terms of growth of MDR TB or stagnant or increasing TB case rates. A thorough understanding of the circumstances cannot be gleaned in the absence of an adequate surveillance system. Additional funding could help define a quality surveillance system to address respiratory pathogens overall, including TB, influenza, and COVID-19. This system could then be measured in terms of completeness, accuracy, and timeliness, and these data would ideally be in the public domain, said Glassman.

Significant TB burden exists within middle-income countries that have the capacity to fully fund excellent TB programs, Glassman stated. However, competing demands for care, which have been exacerbated by COVID-19, hinder the full funding of TB efforts. Furthermore, TB primarily affects low-income communities within these countries where people may wait to seek care until later in their disease trajectories. The political economy of prevention complicates screening; people who are very poor will tend not to use preventative care services because of the substantial opportunity cost involved. This issue is often not addressed when developing programs, she noted.

Additionally, governments tend to opt for purchasing low-quality medicine because of the decreased cost, despite the availability of higher-quality medicine through the Global Fund’s pooled procurement facilities. She suggested that new funding should act in cooperation with existing funding to include incentives for using high-quality medicine. Historically, small grants have been issued to civil society to provide service among key populations. However, population-based public health projects are insufficient to meet the need, said Glassman. Multilateral development banks could be used during this economic crisis to incentivize increases in budgeted spending for this purpose, surveillance performance, and the use of pooled procurement mechanisms. Financing mechanisms for R&D that engage middle-income country purchasers could also encourage innovation. For example, advanced market commitments could illustrate the savings that a country such as India could expect via investing in these innovations. Glassman remarked on the opportunity to find synergies with PPR that address both old and new pandemics.

Discussion

Engaging Political Leadership

Hamburg stated that despite the remarkable ROI of treating TB, the level of disease burden, and the numerous consequences of the disease, efforts to eliminate TB have been underfunded and underappreciated for many decades. This underscores the importance of engaging ministers of both finance and health in TB elimination efforts.⁹ Hamburg asked how information regarding the reality of TB can be used to engage critical decision makers, such as foreign ministers, in moving TB efforts forward. Lomborg pointed out that if there were a simple answer, TB would have been fully addressed by now. TB, along with many other underfunded items on the global agenda, does not tend to attract people’s attention. In the case of HIV, fear that the spread of disease could escalate out of control swayed many decision makers. In contrast, TB has existed for a long time and does not appear to be escalating: many people continue to die from it, yet it does not cause alarm. To address this tragic lack of urgency in the face of TB death rates, he suggested helping finance ministers understand that TB spending is a good investment that is not about getting things right but is about getting them less wrong.

Dybul echoed the importance of engaging finance members, noting that once India’s finance minister and prime minister became involved, the country’s TB efforts began to increase. This in turn garnered the attention of chief executive officers, such as those in Rajasthan. Movement on this issue requires engagement from political leadership, but gaining buy-in from finance ministers is challenging, because many people who die from TB are poor, marginalized, and do not tend to go to hospitals. Dybul noted that India and countries in Southeast Asia with high TB burdens are not low-income countries, but they have many competing priorities and treating TB in poor, marginalized populations will not boost the economy in the way that other investments might. However, COVID-19 has highlighted how quickly a pathogen can spread in urban centers. This heightened awareness offers an opportunity to engage with policy makers and emphasize that responding to existing pandemics will build and sustain systems needed for the next new pandemic.

Dybul noted that the diagnostic systems and approaches needed to address TB are relevant to other respiratory diseases and can be incorporated into the PPR system, thus the current moment also presents an opportunity to

___________________

⁹ She noted in the case of HIV, once finance and military leaders understood the ramifications of the disease in domains beyond health, HIV was addressed in a serious and sustained fashion.

highlight how investments made now in TB and PPR systems could result in tremendous future savings. Reid added that COVID-19 has highlighted the economic dividend of investing in health more generally, providing a context for investing in TB specifically. Additionally, the HIV response demonstrated that civil society can influence governments by voicing discontent with mortality rates. The TB community could do more to empower civil society voices in high-burden countries to apply pressure to governmental leaders, he added.

Targeted Versus Systemwide Interventions for Tuberculosis

Hamburg noted that the creation of silos within global health may have inadvertently decreased the broad value of investments and missed opportunities for synergy. She highlighted Lomborg’s argument that all SDGs cannot be met by 2030, and that therefore some of them should be prioritized. She asked Lomborg whether these ideas conflict with one another or if synergies and system strengthening can be pursued within the context of TB, given that advancing R&D, improving public health and disease control, and creating health systems that are better able to manage patients will also increase preparation for other respiratory diseases and threats. Lomborg replied that this is a methodological issue. Addressing one silo at a time is simpler than looking across a range of areas, because most data pertain to individual silos. Additionally, an argument made for a specific threat can be more effective than one for a broad range of needs. Furthermore, systems that cut across silos may include highly effective programs as well as noneffective pieces, in which case the overall effect of the effort may be diluted, said Lomborg.

Glassman suggested that the COVID-19 pandemic could serve as a powerful motivator to invest in surveillance that would benefit TB efforts. For instance, at the start of the COVID-19 pandemic, India received negative attention when it was unable to conduct accurate death counts, even in the country’s capital. Given the possibility of a future influenza pandemic, creating a system that can use the same equipment, techniques, and metrics to address multiple respiratory pathogens could prove helpful on a number of fronts. Additionally, existing disease burdens can be used to assess the accuracy of surveillance systems. For example, data from serosurveys can be compared to health services data to identify areas of improvement for health services data collection. Glassman remarked that TB efforts and cross-silo systems need not be juxtaposed, as both can benefit from joint investments and the current political climate in response to COVID-19.

Closing Reflections

Hamburg asked the panelists for final comments. Reid remarked on the need for a global health framework that prioritizes the integration of

universal health care and the health security agenda; TB provides a context for developing such a framework and should be prioritized. Lomborg commented that in an environment of competing priorities, TB should be repeatedly emphasized as an excellent investment to gain buy-in from heads of state and finance ministers. Dybul noted that in spite of the COVID-19 Delta variant, there is persistent nationalism around COVID-19 and a failure to understand that variants can develop and cross borders. He stated that the likelihood of a vaccine-resistant variant is high, and that it is not yet known whether the Mu or Lambda variants will resist vaccines. It is possible that COVID-19 will become endemic in lower-income countries, like TB and malaria, while other regions largely ignore the threat as soon as the crisis has passed in their areas. Now is the time to disrupt this long-standing pattern by building the capacities for protection through a global systemwide response.

Glassman emphasized the importance of checks and balances in designing systems to address pathogens. Many mechanisms solely fund governments—with a resultant lack of transparency—but complementary investment can fund universities, civil society, and research institutes in responding to TB, COVID-19, and other pathogens. She added that some governments will never prioritize response efforts, so the global health community should develop techniques to raise awareness and increase the political costs associated with failing to finance a response. Furthermore, communities working on existing diseases should view the health security agenda as an opportunity rather than as competition, she said. Advocacy should focus on replenishing global funding for Gavi and generating funds to forge connections and address the gaps highlighted by workshop participants. Hamburg remarked that a powerful case can be made to create needed systems, but advocates must make this case to the appropriate policy makers for those ideas to translate into sustained action backed by political will and commitment.

FINAL COMMENTS

In her final comments on the workshop, Cassell remarked that of all the innovations needed to address TB, diagnostics are prime. Better diagnostics are required both to identify infected patients and to generate data that illustrate the level of need regarding TB. A UN meeting was held in 2000 to determine efforts for the eight Millennium Development Goals (MDG). Noting that the sixth MDG was “to combat HIV/AIDS, malaria, and other diseases”—and that TB was one of the “other diseases”—Cassell suggested that this workshop has provided rationale for rephrasing the goal as combating “TB and other diseases.” Ministers of finance and health can be powerful advocates for investing in systems to address TB. Often the situation is framed as requiring a policy solution, when in actuality it is an action solution that is needed, said Cassell. She echoed Callahan’s comments regarding

the need to create actionable priorities and to advocate for these with heads of state, finance ministers, and health ministers.

Recounting National Academy of Medicine meetings organized with the Russian Medical Academy and with National Academies in China to address MDR TB (IOM, 2011, 2014), Cassell wondered about the potential role that the U.S. National Academy of Sciences might take in developing and advocating for actionable priorities. From her position on the steering committee of the InterAcademy Partnership for Science, Health, and Policy, Hamburg believes that the organization would welcome the chance to use its network of academies and regional associations of academies in identifying key priorities for action and in engaging their scientific, public health, and medical communities in this effort.¹⁰ Furthermore, Hamburg remarked that engaging the full range of stakeholders—including academies around the world—is important in this effort. She recalled that during her time as health commissioner in New York City in the 1990s, a resurgence of TB included unexpected and unwelcome drug resistance. This issue was successfully addressed because there was a plan that identified critical goals and objectives and involved stakeholders from different sectors, disciplines, and public and private organizations across the city. The Department of Health helped stakeholders understand the nature and scope of the problem, the strategies needed to address it, and their specific roles and responsibilities in the effort. All parties involved were held accountable for progress. Hamburg noted that this approach is challenging in a city the size of New York, much less on a global stage, even though the same issues apply.

Castro emphasized a well-known adage: Never let a crisis go to waste. He stated that the COVID-19 pandemic has provided such a crisis, noting that many speakers in this workshop have highlighted the need and ways to leverage and align the work in the TB field to bolster future PPR. He closed with optimism that the energy evident throughout the workshop would be channeled toward eliminating TB.

__________________

¹⁰ This is an umbrella organization that consists of academies of science and medicine around the world. See https://www.interacademies.org (accessed January 2, 2022).