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Climate Change and Health Initiative to Expand Research, Build Resiliency

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A woman and child in a small boat paddling through flood waters
Credit: Athawit Ketsak/Shutterstock

Climate change is a global process that affects human health in a variety of complex ways. Wildfires, heat waves, hurricanes, floods, and other climate-related weather events can result in illness, injury, and death. Indirect health threats are cause for concern, too. For example, changes in temperature and rainfall can affect the lifecycle of mosquitoes that transmit diseases such as malaria and dengue fever, thereby paving the way for new outbreaks.

Environmental disruptions worsened by climate change can reduce air quality, diminish water resources, and increase exposure to higher temperatures and pathogens. As a result, we see greater health risks in susceptible individuals such as children, the elderly, the poor, and people with underlying conditions, both in America and around the world.

For decades, the National Institute of Environmental Health Sciences and other NIH institutes and centers (ICs) have advanced important research into how climate change affects health. But expanding knowledge in this area and addressing other key challenges will require much more collaboration. The time is now for an all-hands-on-deck scientific effort—across NIH and the wider biomedical research community—that spans many interconnected disciplines and fields of inquiry.

That is why I am excited to join forces with several other IC directors to launch the NIH Climate Change and Health Initiative. By working together, NIH institutes and centers can harness their technologies, innovative research approaches, and talent to advance the science of climate change and health. Through this timely effort, we will promote resilience in vulnerable communities because our research will help them to understand, prepare for, and recover from climate-related health challenges.

Our Strategic Framework outlines why it is important to go beyond studying the health effects of climate change. We must involve impacted communities in solutions-focused research that empowers them, health care practitioners, and health and social services agencies to reduce climate-related health risks. By generating scientific evidence for public health action, we can use a health equity approach to boost climate resiliency among at-risk groups, whether in the U.S. or low- and middle-income countries.

At the heart of the initiative is a push for transdisciplinary, team-based science that boosts training, research capacity, and community engagement. Our immediate goals are to use existing grant programs to strengthen research infrastructure and enhance communication, internally and externally.

Also, with dedicated support from several ICs and the Office of the Director (OD), NIH is funding a research coordinating center and a community engagement program. The coordinating center will help NIH scientists collaborate and manage data. And the community engagement program will empower underserved populations by encouraging two-way dialogue in which both scientists and community members learn from each other. That inclusive approach will improve research and mitigation efforts and reduce health disparities.

In addition, several Notices of Special Interest are now open for applications. The NIH invites scientists to submit research proposals outlining how they plan either to study the health effects of climate change or develop new technologies to mitigate those effects. Also, with OD support, a Climate and Health Scholars Program will launch later this year. Scientists working on important research will share their expertise and methodologies with the NIH community, spurring opportunities for further collaboration.

Going forward, any additional support from the White House, Congress, and the public will allow NIH to further expand the initiative. For example, we urgently need to test novel interventions for reducing heat stress among agricultural workers and to scale up early-warning systems for climate-related weather events. There is also opportunity to use laboratory-based and clinical methodologies to expand knowledge of how climate factors, such as heat and humidity, affect key cellular systems, including mitochondrial function.

To fill those and other research gaps, we must draw on an array of skill sets and fields of inquiry. Therefore, our Strategic Framework outlines the importance of supporting adaptation research, basic and mechanistic studies, behavioral and social sciences research, data integration, disaster research response, dissemination and implementation science, epidemiology and predictive modeling, exposure and risk assessment, and systems science. Tapping into those areas will help us tackle climate-related health challenges and develop effective solutions.

In recent years, in-depth reports and assessments have provided conclusive evidence that climate change is significantly altering our environment and impacting human health. Although the science of climate change and health has progressed, much work remains. We hope that the Climate Change and Health Initiative expands scientific partnerships and capacity throughout NIH and across the global biomedical and environmental health sciences communities. Greater collaboration will spur new knowledge, interventions, and technologies that help humanity manage the health effects of climate change and strengthen health equity.

(Note: The Initiative’s Executive Committee includes the following IC directors: Richard Woychik, National Institute of Environmental Health Sciences [chair]; Diana Bianchi, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Gary Gibbons, National Heart, Lung, and Blood Institute; Roger Glass, Fogarty International Center; Joshua Gordon, National Institute of Mental Health; Eliseo Pérez-Stable, National Institute on Minority Health and Health Disparities; and Shannon Zenk, National Institute of Nursing Research.)

Links:

Environmental Health Topic: Climate Change (National Institute of Environmental Health Sciences /NIH)

NIH Climate Change and Health Initiative (NIH)

NIH Climate Change and Health Initiative Strategic Framework (NIH)

Research Coordinating Center to Support Climate Change and Health Community of Practice (NIH)

Research Opportunity Announcement: Alliance for Community Engagement—Climate Change and Health (National Heart, Lung, and Blood Institute / NIH)

Notice of Special Interest: Climate Change and Health (NIH)

Notice of Special Interest: Innovative Technologies for Research on Climate Change and Human Health Small Business Technology Transfer (R41/R42 Clinical Trial Option) (NIH)

Notice of Special Interest: Innovative Technologies for Research on Climate Change and Human Health, R43/R44 Small Business Innovation Research (R43/R44 Clinical Trial Optional) (NIH)

Note: Dr. Lawrence Tabak, who performs the duties of the NIH Director, has asked the heads of NIH’s Institutes and Centers (ICs) to contribute occasional guest posts to the blog to highlight some of the interesting science that they support and conduct. This is the 14th in the series of NIH IC guest posts that will run until a new permanent NIH director is in place.


Tuberculosis: An Ancient Disease in Need of Modern Scientific Tools

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Two men, one holds an award
Caption: Here I am with Paul Farmer, who was a strong voice for improving TB prevention and treatments in resource-scarce settings, when he came to NIH in 2007 to deliver my institute’s James C. Hill Memorial Lecture. Credit: NIH

Although COVID-19 has dominated our attention for the past two years, tuberculosis (TB), an ancient scourge, remains a dominating infectious disease globally, with an estimated 10 million new cases and more than 1.3 million deaths in 2020. TB disproportionately afflicts the poor and has long been the leading cause of death in people living with HIV.

Unfortunately, during the global COVID-19 pandemic, recent gains in TB control have been stalled or reversed. We’ve seen a massive drop in new TB diagnoses, reflecting poor access to care and an uptick in deaths in 2020 [1].

We are fighting TB with an armory of old weapons inferior to those we have for COVID-19. The Bacillus Calmette–Guérin (BCG) vaccine, the world’s only licensed TB vaccine, has been in use for more than 100 years. While BCG is somewhat effective at preventing TB meningitis in children, it provides more limited durable protection against pulmonary TB in children and adults. More effective vaccination strategies to prevent infection and disease, decrease relapse rates, and shorten durations of treatment are desperately needed to reduce the terrible global burden of TB.

In this regard, over the past five years, several exciting research advances have generated new optimism in the field of TB vaccinology. Non-human primate studies conducted at my National Institute of Allergy and Infectious Diseases’ (NIAID) Vaccine Research Center and other NIAID-funded laboratories have demonstrated that effective immunity against infection is achievable and that administering BCG intravenously, rather than under the skin as it currently is given, is highly protective [2].

Results from a phase 2 trial testing BCG revaccination in adolescents at high risk of TB infection suggested this approach could help prevent TB [3]. In addition, a phase 2 trial of an experimental TB vaccine based on the recombinant protein M72 and an immune-priming adjuvant, AS01, also showed promise in preventing active TB disease in latently infected adults [4].

Both candidates are now moving on to phase 3 efficacy trials. The encouraging results of these trials, combined with nine other candidates currently in phase 2 or 3 studies [5], offer new hope that improved vaccines may be on the horizon. The NIAID is working with a team of other funders and investigators to analyze the correlates of protection from these studies to inform future TB vaccine development.

Even with these exciting developments, it is critical to accelerate our efforts to enhance and diversify the TB vaccine pipeline by addressing persistent basic and translational research gaps. To this end, NIAID has several new programs. The Immune Protection Against Mtb Centers are taking a multidisciplinary approach to integrate animal and human data to gain a comprehensive understanding of the immune responses required to prevent TB infection and disease.

This spring, NIAID will fund awards under the Innovation for TB Vaccine Discovery program that will focus on the discovery and early evaluation of novel TB vaccine candidates with the goal of diversifying the TB vaccine pipeline. Later this year, the Advancing Vaccine Adjuvant Research for TB program will systematically assess combinations of TB immunogens and adjuvants. Finally, NIAID’s well-established clinical trials networks are planning two new clinical trials of TB vaccine candidates.

As we look to the future, we must apply the lessons learned in the development of the COVID-19 vaccines to longstanding public health challenges such as TB. COVID-19 vaccine development was hugely successful due to the use of novel vaccine platforms, structure-based vaccine design, community engagement for rapid clinical trial enrollment, real-time data sharing with key stakeholders, and innovative trial designs.

However, critical gaps remain in our armamentarium. These include the harnessing the immunology of the tissues that line the respiratory tract to design vaccines more adept at blocking initial infection and transmission, employing thermostable formulations and novel delivery systems for resource-limited settings, and crafting effective messaging around vaccines for different populations.

As we work to develop better ways to prevent, diagnose, and treat TB, we will do well to remember the great public health icon, Paul Farmer, who tragically passed away earlier this year at a much too young age. Paul witnessed firsthand the devastating consequences of TB and its drug resistant forms in Haiti, Peru, and other parts of the world.

In addition to leading efforts to improve how TB is treated, Paul provided direct patient care in underserved communities and demanded that the world do more to meet their needs. As we honor Paul’s legacy, let us accelerate our efforts to find better tools to fight TB and other diseases of global health importance that exact a disproportionate toll among the poor and underserved.

References:

[1] Global tuberculosis report 2021. WHO. October 14, 2021.

[2] Prevention of tuberculosis in macaques after intravenous BCG immunization. Darrah PA, Zeppa JJ, Maiello P, Hackney JA, Wadsworth MH,. Hughes TK, Pokkali S, Swanson PA, Grant NL, Rodgers MA, Kamath M, Causgrove CM, Laddy DJ, Bonavia A, Casimiro D, Lin PL, Klein E, White AG, Scanga CA, Shalek AK, Roederer M, Flynn JL, and Seder RA. Nature. 2020 Jan 1; 577: 95–102.

[3] Prevention of M. tuberculosis Infection with H4:IC31 vaccine or BCG revaccination. Nemes E, Geldenhuys H, Rozot V, Rutkowski KT, Ratangee F,Bilek N., Mabwe S, Makhethe L, Erasmus M, Toefy A, Mulenga H, Hanekom WA, et al. N Engl J Med 2018; 379:138-149.

[4] Final analysis of a trial of M72/AS01E vaccine to prevent tuberculosis. Tait DR, Hatherill M, Van Der Meeren O, Ginsberg AM, Van Brakel E, Salaun B, Scriba TJ, Akite EJ, Ayles HM, et al.

[5] Pipeline Report 2021: Tuberculosis Vaccines. TAG. October 2021.

Links:

Tuberculosis (National Institute of Allergy and Infectious Diseases/NIH)

NIAID Strategic Plan for Tuberculosis Research

Immune Mechanisms of Protection Against Mycobacterium tuberculosis Centers (IMPAc-TB) (NIAID)

Partners in Health (Boston, MA)

[Note: Acting NIH Director Lawrence Tabak has asked the heads of NIH’s Institutes and Centers (ICs) to contribute occasional guest posts to the blog to highlight some of the interesting science that they support and conduct. This is the seventh in the series of NIH IC guest posts that will run until a new permanent NIH director is in place.]


Zooming in on Global Health Research

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In past years, Roger Glass (top left), director of NIH’s Fogarty International Center (FIC), and I have taken an in-person group photo with the FIC fellows and scholars. This year, due to the international health and travel challenges posed by the global COVID-19 pandemic, a Zoom composite of some of the young researchers will have to do! I spoke to the group on the morning of July 13 as part of FIC’s week-long Global Health Program for Fellows and Scholars. The program provides collaborative, mentored global health research training in low- and middle-income countries. Individual students, postdoctoral fellows, or faculty from the U.S. and abroad apply for a 12-month placement at a participating global institution. The meeting has brought together 122 fellows and scholars (US and international), seven Fulbright Fogarty Fellows, 16 alumni, and many others to the event. As you can see in my photo, I had to be out of town this year, and I spoke to everyone buckled up while returning to the Washington, D.C. area. But I didn’t want to miss this opportunity to share my vision for global health research and point to some of the many opportunities available in global health for young academics from the U.S. and other nations.

Genome Data from Africa Reveal Millions of New Variants

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H2Africa logo
Credit: Human Heredity and Health in Africa Initiative

The first Homo sapiens emerged in Africa hundreds of thousands of years ago. We are all descended from that common pool of ancestors. Put another way, we are all Africans. While it’s not possible to study the DNA of these vanished original human populations, it is possible to study the genetic material of today’s African peoples to learn more about the human genome and its evolution over time. The degree of genetic diversity in Africa is greater than anywhere else in the world.

Progress continues to be made in this important area of genomic research. The latest step forward is a study just published in the journal Nature that analyzes more than 400 complete human genomes, including 50 distinct groups of people from 13 African countries. This work has uncovered about 3.4 million unique gene variants that had never before been described, greatly expanding our knowledge of human genetic variation and its implications for health and disease.

This work is the latest from the Human Heredity and Health in Africa (H3Africa) Initiative , which I helped establish a decade ago. This partnership between NIH, the Wellcome Trust, and the Alliance for Accelerating Excellence in Science in Africa (AESA) seeks to train a new generation of African scientists in genomic science and other disciplines, while conducting state-of-the-art health research on the African continent. The hope is to help these scientists use their new knowledge to improve human health in Africa and to help fill significant gaps in our knowledge of the diversity within human genomes.

The new study was led by Zané Lombard, the University of the Witwatersrand, South Africa; Neil Hanchard, Baylor College of Medicine, Houston; and Adebowale Adeyemo, NIH’s National Human Genome Research Institute, Bethesda, MD. It also included more than 50 other H3Africa data providers and data analysts from across Africa and around the world.

These researchers sequenced and analyzed the genomes of 426 individuals, almost all from studies and countries within the H3Africa Consortium, the network of NIH and Wellcome Trust-funded research sites in Africa. These individuals were carefully selected to provide broad coverage of the diverse landscape of African genomic variation. They also included many populations that hadn’t been studied at the genetic level before. The team focused its attention on single-letter differences, also known as single nucleotide variants (SNVs), located across the 3 billion DNA letters of the human genome.

All told, the researchers observed more than 31 million confirmed SNVs. Of the 3.4 million newly discovered SNVs, most turned up in the genomes of individuals from previously unstudied African ethnic groups with their own distinct languages. Even among SNVs that had been previously reported, several were found much more often than in other populations. That’s important because medical geneticists often include information about frequency in deciding whether a gene variant is a likely cause of rare disease. So, this more complete picture of normal genetic variation will be valuable for diagnosing such genetic conditions around the globe.

The researchers also found more than 100 regions of the genome where the pattern of genetic variation was suggestive of underlying variants that were evolutionarily favored at some time in the past. Sixty-two of those chromosomal locations weren’t previously known to be under such strong natural selection in human populations. Interestingly, those selected regions were found to contain genes associated with viral immunity, DNA repair, reproduction, and metabolism, or occurred close to variants that have been associated with conditions such as uterine fibroids and chronic kidney disease.

The findings suggest that viral infections, such as outbreaks of Ebola, yellow fever, and Lassa fever, may have played an important role over centuries in driving genetic differences on the African continent. The data also point to the possibility of human adaptation to differences across the African continent in local environments and diets, and these adaptations could be relevant to common diseases and traits we see now.

The researchers used the data to help gain insight into past migrations of human populations. The genetic data revealed complex patterns of ancestral mixing within and between groups. It also uncovered how distinct groups likely moved large distances across Africa in the past, going back hundreds to thousands of years. The findings also offered a more complete picture of the timing and extent of the migration of speakers of Africa’s most common language group (Bantu) as they moved from West Africa to the southern and eastern reaches of the continent—a defining event in the genetic history of Africa.

There’s still much more to learn about the diversity of human genomes, and a need for continued studies, including many more individuals representing more distinct groups in Africa. Indeed, H3Africa now consists of 51 projects all across the continent, focused on population-based genomic studies of many common health conditions, from heart disease to tuberculosis. As the cradle of all humanity, Africa has much to offer genomic research in the years ahead that will undoubtedly have far-reaching implications for people living in all parts of our planet.

Reference:

[1] High-depth African genomes inform human migration and health. Choudhury A et al. 2020 Oct;586(7831):741-748.

Links:

Human Heredity and Health in Africa (H3Africa) (NIH)

H3Africa (University of Cape Town, South Africa)

NIH Support: National Human Genome Research Institute; National Institute of Allergy and Infectious Diseases


Public Health Policies Have Prevented Hundreds of Millions of Coronavirus Infections

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Touchless carryout
Credit: Stock photo/Juanmonino

The alarming spread of coronavirus disease 2019 (COVID-19) last winter presented a profound threat to nations around the world. Many government leaders responded by shutting down all non-essential activities, implementing policies that public health officials were hopeful could slow the highly infectious SARS-CoV-2, the novel coronavirus that causes COVID-19.

But the shutdown has come at a heavy cost for the U.S. and global economies. It’s also taken a heavy personal toll on many of us, disrupting our daily routines—getting children off to school, commuting to the office or lab, getting together with friends and family, meeting face to face to plan projects, eating out, going to the gym—and causing lots of uncertainty and frustration.

As difficult as the shutdowns have been, new research shows that without these public health measures, things would have been much, much worse. According to a study published recently in Nature [1], the implementation of containment and mitigation strategies across the globe prevented or delayed about 530 million coronavirus infections across six countries—China, South Korea, Iran, Italy, France, and the United States. Take a moment to absorb that number—530 million. Right now, there are 8.8 million cases documented across the globe.

Estimates of the benefits of anti-contagion policies have drawn from epidemiological models that simulate the spread of COVID-19 in various ways, depending on assumptions built into each model. But models are sophisticated ways of guessing. Back when decisions about staying at home had to be made, no one knew for sure if, or how well, such approaches to limit physical contact would work. What’s more, the only real historical precedent was the 1918 Spanish flu pandemic in a very different, much-less interconnected world.

That made it essential to evaluate the pros and cons of these public health strategies within a society. As many people have rightfully asked: are the health benefits really worth the pain?

Recognizing a pressing need to answer this question, an international team of scientists dropped everything that they were doing to find out. Led by Solomon Hsiang, director of the University of California, Berkeley’s Global Policy Laboratory and Chancellor’s Professor at the Goldman School of Public Policy, a research group of 15 researchers from China, France, South Korea, New Zealand, Singapore, and the United States evaluated 1,717 policies implemented in all six countries between January 2020, when the virus began its global rise, and April 6, 2020.

The team relied on econometric methods that use statistics and math to uncover meaningful patterns hiding in mountains of data. As the name implies, these techniques are used routinely by economists to understand, in a before-and-after way, how certain events affect economic growth.

In this look-back study, scientists compare observations before and after an event they couldn’t control, such as a natural disaster or disease outbreak. In the case of COVID-19, these researchers compared public health datasets in multiple localities (e.g., states or cities) within each of the six countries before and several weeks after lockdowns. For each data sample from a given locality, the time period right before a policy deployment was the experimental “control” for the same locality several weeks after it received one or more shutdown policy “treatments.”

Hsiang and his colleagues measured the effects of all the different policies put into place at local, regional, and national levels. These included travel restrictions, business and school closures, shelter-in-place orders, and other actions that didn’t involve any type of medical treatment for COVID-19.

Because SARS-CoV-2 is a new virus, the researchers knew that early in the pandemic, everyone was susceptible, and the outbreak would grow exponentially. The scientists could then use a statistical method designed to estimate how the daily growth rate of infections changed over time within a location after different combinations of large-scale policies were put into place.

The result? Early in the pandemic, coronavirus infection rates grew 38 percent each day, on average, across the six countries: translating to a two-day doubling time. Applying all policies at once slowed the daily COVID-19 infection rate by 31 percentage points! Policies having the clearest benefit were business closures and lockdowns, whereas travel restrictions and bans on social gatherings had mixed results. Without more data, the analysis can’t specify why, but the way different countries enacted those policies might be one reason.

As we continue to try to understand and thwart this new virus and its damage to so many aspects of our personal and professional lives, these new findings add context, comfort, and guidance about the present circumstances. They tell us that individual sacrifices from staying home and canceled events contributed collectively to a huge, positive impact on the world.

Now, as various communities start cautiously to open up, we should continue to practice social distancing, mask wearing, and handwashing. This is not the time to say that the risk has passed. We are all tired of the virus and its consequences for our personal lives, but the virus doesn’t care. It’s still out there. Stay safe, everyone!

Reference:

[1] The effect of large-scale anti-contagion policies on the COVID-19 pandemic. Hsiang S, Allen D, Annan-Phan S, et al. Nature. 2020 June 8 [published online ahead of print].

Links:

Coronavirus (NIH)

Global Policy Lab: Effect of Anti-Contagion Policies (University of California, Berkeley)

Video: How much have policies to slow COVID-19 worked? (UC Berkeley)

Hsiang Lab (UC Berkeley)

Global Policy Lab Rallies for COVID-19 Research,” COVID-19 News, Goldman School of Public Policy, June 5, 2020.


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