Africa Calls for Urgent New Public Health Order

The first international Conference on Public Health in Africa (CPHIA 2021), hosted by the African Union (AU) and Africa Centres for Disease Control and Prevention (Africa CDC) in December concluded its main programme following three days of sessions focused on the need to address long-standing health challenges on the continent, including vaccine inequity and weak health systems.

Over 140 African policymakers, scientists, public health experts, data experts, and civil society representatives presented the latest learnings and research from the COVID-19 pandemic, as well as the actions needed to better guard against current and future health crises.

During the opening ceremony, speakers reflected on the impact of COVID-19 in Africa over the past two years and lessons learnt.
“The inaugural Conference on Public Health in Africa is happening at an important time in history,” said Chairperson of the AU Commission H.E. Moussa Faki Mahamat. “The African continent has not been spared the devastating effects of COVID-19, pushing our health systems to the limits. But we have great hopes for the future, and a historic opportunity to build a New Public Health Order that can effectively guard against future health crises. This conference is the first step in making this a reality.

”The AU’s New Public Health Order calls for continental collaboration to bolster African manufacturing capacity for vaccines, diagnostics and therapeutics; strengthen public health institutions for people-centred care; expand the public health workforce; establish respectful, action-oriented partnerships; and engage with the private sector. These pillars are part of the continent’s approach to meeting the aspirations of the Agenda 2063 – the Africa We Want.

Photo credit: United Nations

“There is a need for renewed commitments by governments and national parliaments to increase domestic financing for health in Africa. This has been a priority of the African Union for several years, but progress has not been fast enough. We cannot continue to rely on external funding for something so important to our future,” said H.E. Paul Kagame, President of Rwanda and AU Champion for Domestic Health Financing. “We need to invest much more in national health systems. The ability to implement critical health programmes, including regular mass vaccination campaigns depends on the quality of national health services and the trust the public have in them.”

“Maybe the Ebola outbreak of 2014 to 2016 was a call to action that something bigger was to come. And maybe COVID-19 is the signal that something even bigger will come. So, we must be prepared and take our health security destiny into our own hands,” said Dr. John Nkengasong, Director of the Africa CDC. “It
means we have to fight the next pandemic in a way that is unparalleled to the way we are fighting this pandemic, and I am very convinced that we will do that given the mobilization, commitment and investments that are currently going on.”

 Prof. Salim Abdool Karim, Director of the Center for the AIDS Program of Research in South Africa (CAPRISA), who is among those leading research into the Omicron variant. Explaining the variant’s trajectory in South Africa, emphasized the need to continue trusting and implementing strong public health interventions.

“There is no need to panic. We’ve dealt with variants before, including those with immune escape. Closing borders has almost no benefit. Public health systems work, public interventions like masks and social distancing work. Let’s use them,” said Prof. Karim.

The Democratic Republic of Congo declares over the thirteenth Ebola Virus Disease Outbreak

The Democratic Republic of Congo (DRC) has reported zero case of Ebola since the country declared the end of the 13th Ebola virus disease (EVD) outbreak on the 16th December 2021.

This is the second EVD outbreak reported this year from the DRC. Results from genomic sequencing show that this outbreak is linked to the 2018 EVD outbreak reported from the same province.

The outbreak was declared on 08 October 2021 in Beni Health Zone in North Kivu Province. In this outbreak, a total of 11 cases (8 confirmed, 3 probable), nine deaths (6, 3) and two recoveries of EVD were reported. These cases were distributed across three health areas: Butsili (9 cases, 7 deaths, 2 recoveries), Bundji (1, 1, 0) and Kanzulinzuli (1, 1, 0). The cumulative case fatality ratio is 82%. The last confirmed case was reported on 30 October 2021. The outbreak was successfully contained within the Beni Health Zone and no further cases were reported in other provinces.

“This is another example from the DRC showing a good example of applying the knowledge and expertise gained from previous recurrent outbreaks to quickly fight and bring the 13th outbreak to an end,” said Dr John Nkengasong, Director of Africa Centres for Disease Control and Prevention (Africa CDC).

The African Union Commission, through the Africa CDC, had deployed frontline workers and experts from the headquarter to support response to the 13th outbreak and donated medical and non-medical supplies including infection prevention and control kits, and laboratory consumables. The Africa CDC will continue to work with the Government of DRC and other partners to better coordinate our efforts in strengthening health systems in the country and across Africa

FDA Approves Long-Acting Injectable Drug for HIV Prevention

Approval Marks Pivotal Expansion of HIV Prevention Options in the United States

The U.S. Food and Drug Administration has announced its first approval of a long-acting HIV prevention medication, marking a pivotal expansion of HIV prevention options in the United States.

Developed by ViiV Healthcare, the medicine is long-acting cabotegravir injected once every two months. FDA has approved the medicine for use by adults and adolescents weighing at least 35 kilograms who are at risk of sexually acquiring HIV. This milestone marks a vital expansion of biomedical HIV prevention options available to people in the United States. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, thanks and congratulates everyone who led, conducted and participated in the research that led to this important development.

An estimated 34,800 people in the United States acquired HIV in 2019, the most recent year for which data are available. Men who have sex with men, transgender women who have sex with men, and Black cisgender women are among those disproportionately affected by HIV in this country.

Until today, the only FDA-licensed medications for HIV pre-exposure prophylaxis (PrEP) were daily oral pills containing the HIV drugs tenofovir and emtricitabine. These medications are highly effective at preventing HIV when taken daily as prescribed. However, taking a pill daily while feeling healthy can be challenging. Long-acting injectable cabotegravir PrEP is a less frequent, more discreet HIV prevention option that may be more desirable for some people. 

The FDA approval is based on data primarily from two NIH-supported clinical trials, HPTN 083 and HPTN 084. Both trials compared the safety and effectiveness of a PrEP regimen containing long-acting injectable cabotegravir with a regimen of daily oral PrEP. HPTN 083 enrolled more than 4,500 cisgender men who have sex with men and transgender women who have sex with men in Argentina, Brazil, Peru, South Africa, Thailand, the United States and Vietnam. HPTN 084 enrolled more than 3,200 cisgender women in Botswana, Eswatini, Kenya, Malawi, South Africa, Uganda and Zimbabwe. The two trials found that both HIV prevention methods were safe and highly effective, but injectable cabotegravir was more effective than daily oral PrEP at preventing HIV acquisition. 

The HPTN 083 and HPTN 084 trials were sponsored by NIAID and conducted by the NIH-funded HIV Prevention Trials Network (HPTN). NIAID and ViiV Healthcare co-funded both trials; the Bill & Melinda Gates Foundation also supported HPTN 084. HPTN is co-funded by NIAID, the National Institute of Mental Health, the National Institute on Drug Abuse, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, all part of NIH.

Newly identified hormone may be a critical driver of type 1 and type 2 diabetes

A newly discovered hormone named fabkin helps regulate metabolism and may play an important role in the development of both type 1 and type 2 diabetes, according to research led by the Sabri Ülker Center for Metabolic Research at Harvard T.H. Chan School of Public Health.

The study showed blood levels of fabkin were abnormally high in mice and human patients with either type 1 or type 2 diabetes. The researchers found that blocking the activity of fabkin prevented the development of both forms of diabetes in the animals. Fabkin likely plays a similar role in humans and the hormone complex could be a promising therapeutic target, according to the researchers.

“For many decades, we have been searching for the signal that communicates the status of energy reserves in adipocytes to generate appropriate endocrine responses, such as the insulin production from pancreatic beta cells,” said senior author Gökhan S. Hotamisligil, director of the Sabri Ülker Center. “We now have identified fabkin as a novel hormone that controls this critical function through a very unusual molecular mechanism.”

The findings were published online in Nature on December 8, 2021.

Many hormones are involved in the regulation of metabolism, such as insulin and leptin. Fabkin is different from traditional hormones in that it is not a single molecule with a single defined receptor. Instead, fabkin is composed of a functional protein complex consisting of multiple proteins, including fatty acid binding protein 4 (FABP4), adenosine kinase (ADK) and nucleoside diphosphate kinase (NDPK). Through a series of experiments, the researchers determined that fabkin regulates energy signals outside of cells. These signals then act through a family of receptors to control target cell function. In the case of diabetes, fabkin controls the function of beta cells in the pancreas that are responsible for insulin production.

More than a decade ago, Hotamisligil and colleagues discovered that a protein known as FABP4 is secreted from fat cells during lipolysis, the process in which lipids stored within fat cells are broken down, typically in response to starvation. Numerous studies have since shown correlations between circulating FABP4 and metabolic diseases including obesity, diabetes, cardiovascular disease, and cancer. However, the mechanism of action was unknown.

In the new study, the researchers showed that when FABP4 is secreted from fat cells and enters the blood stream, it binds with the enzymes NDPK and ADK to form the protein complex now identified as fabkin. In this protein complex, FABP4 modifies the activity of NDPK and ADK to regulate levels of molecules known as ATP and ADP, which are the essential units of energy in biology. The researchers discovered that surface receptors on nearby cells sense the changing ratio of ATP to ADP, triggering the cells to respond to the changing energy status. As such, fabkin is able to regulate the function of these target cells.

The authors showed that the insulin-producing beta cells of the pancreas are a target of fabkin and that the hormone is a driving force behind the development of diabetes. When the researchers used an antibody to neutralize fabkin in mice, the animals did not develop diabetes. When the antibody was given to obese, diabetic mice, they reverted to a healthy state.

“The discovery of fabkin required us to take a step back and reconsider our fundamental understanding of how hormones work.” said lead author Kacey Prentice, research associate in the Sabri Ülker Center and Department of Molecular Metabolism. “I am extremely excited to find a new hormone, but even more so about seeing the long-term implications of this discovery.”

Decreased vehicle emissions linked with significant drop in deaths attributable to air pollution

Decreasing vehicle emissions since 2008 have reduced by thousands the number of deaths attributable to air pollution, yielding billions of dollars in benefits to society, according to a new study led by researchers at Harvard T.H. Chan School of Public Health.

The study also found that although the public health burden of large trucks has been greatly reduced, passenger light-duty vehicles, such as SUVs and pickup trucks, continue to contribute a significant amount of air pollution in major metropolitan areas.

The study was published online December 13, 2021 in the journal PNAS.

“Recent reductions in vehicle emissions have yielded major health benefits, even though only small progress has been made on reducing their climate impact,” said first author Ernani Choma, a research fellow in Harvard Chan School’s Department of Environmental Health. “Our results indicate that to achieve further public health and climate gains, even more stringent policies will be required.”

Although the health and climate burden of vehicle emissions in the U.S. has been widely studied, the benefits of recent reductions in vehicle emissions—spurred by federal air pollution regulations and technological innovations by car manufacturers—were not well known. The new study provides estimates that compare the actual health and climate impact of reduced vehicle emissions with what that impact would have been had emissions not been reduced. Researchers calculated the so-called “social benefits” attributable to decreasing emissions—in this case, the monetary value to society of the reduction in deaths attributable to air pollution and climate impacts avoided.

Using recent national emissions data, the researchers modeled four scenarios for emissions in 2017: actual emissions as well as three alternative scenarios in which county-level emissions were the same as they were in 2014, 2011, and 2008. Each of the scenarios factored in the types of vehicles being driven and how many miles they traveled, detailed data about air pollution levels across the U.S., mortality rates, and trends in demographics—including an aging population that is becoming more susceptible to air pollution over time.

The researchers estimated that reductions in emissions yielded $270 billion in social benefits in the U.S. in 2017—mostly due to the estimated value of reduced mortality risk from fine particulate matter (PM2.5) air pollution—and, to a lesser degree, to reduced “social costs” from greenhouse gas emissions, which are calculated from a range of factors such as human health impacts, changes in agricultural productivity, natural disasters, risk of conflict, and more.

The researchers also estimated that deaths attributable to air pollution due to vehicle emissions dropped from 27,700 in 2008 to 19,800 in 2017. The decrease in deaths was not as large as researchers expected, because many factors offset the progress in reducing emissions, such as a larger and aging population, larger vehicles replacing smaller ones, and more miles traveled per vehicle. On the other hand, the authors noted, if vehicles were still emitting at 2008 levels, those emissions would have caused 48,200 deaths attributable to air pollution in 2017—which would have represented a 74% increase between 2008 and 2017.

The study found significant recent progress in reducing emissions from heavy-duty trucks, but less progress with passenger light-duty vehicles, including cars, SUVs, and pickup trucks. Passenger light-duty vehicles accounted for two-thirds of the public health burden from transportation-related air pollution in 2017, the authors said. They noted that emissions from these vehicles in large metropolitan areas are so harmful that they are responsible for 30% more attributable deaths than all heavy-duty trucks across the nation.

“If the trends of increased population density with an aging population, and a shift to larger passenger vehicles continue, emissions, especially in urban areas, will continue to become more harmful and it will be harder to achieve further public health gains by small incremental improvements in new vehicles,” said John Spengler, Akira Yamaguchi Professor of Environmental Health and Human Habitation and senior author of the study. “Our study findings strengthen the case for policies at the municipal level that encourage electric vehicles while discouraging conventional gasoline vehicles and for making our cities more accessible for non-motorized transportation such as biking or walking.”

Rare gene mutation in some Black Americans may allow earlier screening of heart failure

Researchers have linked a rare genetic mutation found mostly in Black Americans and other people of African descent to an earlier onset of heart failure and a higher risk of hospitalization. The findings suggest that earlier screening for the mutation could lead to faster treatment and improved outcomes for heart failure in this vulnerable group, the researchers said. The results of the study, which was largely supported by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, appear in the Journal of the American College of Cardiology: Heart Failure.

“This is the most comprehensive evaluation of the association between this mutation and measures of cardiac structure, heart function, and heart failure risk in an exclusively Black population,” said lead study author Ambarish Pandey, M.D., assistant professor of internal medicine in the Division of Cardiology at University of Texas Southwestern Medical Center in Dallas. “The results also highlight the importance of early genetic screening in patients at higher risk for carrying the mutation.”

Heart failure is a chronic, debilitating condition that develops when the heart can’t pump enough blood to meet the body’s needs. Despite the name, it does not mean that the heart has stopped beating. Common symptoms include shortness of breath during daily activities or trouble breathing when lying down. The condition affects about 6.5 million people in the United States alone. Black Americans are at higher risk for the condition than any other racial/ethnic group in the U.S., and they experience worse outcomes.

The genetic variant studied in the current research had long ago been linked to a higher risk of heart failure in people of African ancestry. Known as TTR V142I, the gene can cause a condition called transthyretin amyloid cardiomyopathy, which is potentially fatal because protein builds up inside the heart. However, little was known about the impact of the mutation on important clinical-related factors such as heart structure, heart function, hospitalization rates, and blood biomarkers. 

To learn more, the researchers studied TTR V142I in a group of middle-aged participants from the 20-year-long Jackson Heart Study, the largest and longest investigation of cardiovascular disease in Black Americans. Of the 2,960 participants selected from the study, about 119 (4%) had the genetic mutation, but none had heart failure at the start. The researchers followed the participants for about 12 years between 2005 and 2016.

During the study period, the researchers observed 258 heart failure events. They found that patients who carried the genetic mutation were at significantly higher risk of developing heart failure, compared to those without the mutation. These patients also developed heart failure nearly four years earlier and had a higher number of heart failure hospitalizations. Researchers said they found no significant difference in death rates between the two groups during this study period.

During follow-up studies, however, they observed significant increases in blood levels of troponin, a protein complex that is an important marker of heart damage, among carriers of the genetic mutation. They did not see any significant associations between the genetic mutation and changes in heart structure and function as evaluated by echocardiographic and cardiac MRI assessments.

“What that means is that the gene is causing heart damage slowly over time,” said Amanda C. Coniglio, M.D., the lead author of the study and a physician with Duke University School of Medicine in Durham, North Carolina. “The changes are subtle but significant.”

The researchers noted that more studies will be needed to continue assessing participants’ heart structure and function and to see, long-term, if increased hospitalization risk translates into higher risk of death.

“Identification of genetic susceptibility to amyloid cardiomyopathy is an important advance related to heart failure, especially given its disproportionate effect on older and multiethnic populations,” said Patrice Desvigne-Nickens, M.D., a medical officer in the Heart Failure and Arrhythmia Branch in NHLBI’s Division of Cardiovascular Sciences.

Adolfo Correa, M.D., Ph.D., study co-author and former director of the Jackson Heart Study, agreed. “About half of Black American men and women living in the United States today have some form of cardiovascular disease, but the root causes are poorly understood,” he said. “This study brings us a step closer to better understanding this particular form of gene-related heart failure, as well as the life-saving importance of early screening.”  
  

A high-fiber diet may improve the response of melanoma patients to immunotherapy

A diet rich in fiber may help some people being treated for melanoma respond to immunotherapy treatment by influencing the gut microbiome, according to a new study led by researchers at the Center for Cancer Research at the National Cancer Institute (NCI), part of the National Institutes of Health, and the University of Texas MD Anderson Cancer Center. Results from the study, which analyzed both people with melanoma and mouse models of the disease, appear in Science.

Among patients with advanced melanoma who underwent immunotherapy with immune checkpoint blockers, those who consumed at least 20 grams a day of dietary fiber survived the longest without their disease progressing. In contrast, use of probiotic supplements appeared to lessen somewhat the effectiveness of immune checkpoint blocker regimens. Probiotics are live microorganisms typically consumed as a supplement to improve gut health.

“The data suggest that one can target the composition of the gut microbiota and affect the ability of the patient to respond to immunotherapy,” said Giorgio Trinchieri, M.D., chief of the Laboratory of Integrative Cancer Immunology in NCI’s Center for Cancer Research, one of the study’s coleaders. “Consuming a diet rich in fiber, like fruits, vegetables, and legumes, could improve your ability to respond to immunotherapy.”

Immunotherapy with immune checkpoint blockers helps restore the immune system’s natural ability to recognize and kill tumor cells. These drugs have been transformative in melanoma, improving how long some people with advanced disease live, sometimes by years. However, for many patients, immune checkpoint blockers fail to stop their tumors from growing. Several studies have suggested that the composition of the bacteria in the gut may influence the response to immunotherapy.

“The question is, can we change the composition of the type of bacteria in the gut and improve the ability of the patient to respond?” Dr. Trinchieri said.

In a previous study, Dr. Trinchieri and a different group of collaborators showed that some people with melanoma who initially did not respond to treatment with an immune checkpoint blocker did respond after receiving a fecal transplant from a patient who had responded to the drug. The fecal transplant, they concluded, had introduced different gut bacteria that helped make it easier for immune cells to invade and kill their tumors.

“Dietary fiber intake and use of probiotic supplements have also been shown to affect the composition of gut bacteria. More cancer patients are taking probiotic supplements in an effort to improve their gut health, but little is known about how probiotics—which basically change the ecology of the gut bacteria—impact immunotherapy response,” he said.

The connection between fiber intake and immunotherapy response has also been unclear. However, a recent study led by Romina Goldszmid, Ph.D., also of NCI’s Center for Cancer Research, showed that mice fed a diet rich in pectin, which is a fiber abundant in apples, were able to stave off tumor growth by activating immune cells and reprogramming the tumor microenvironment.

In the new study, Dr. Trinchieri and study co-leads Carrie R. Daniel, Ph.D., M.P.H., and Jennifer A. Wargo, M.D., of the University of Texas MD Anderson Cancer Center, and their collaborators looked at the composition of fecal microorganisms (the gut microbiota), dietary habits, and probiotic supplement use among patients who were being treated for advanced melanoma with immune checkpoint blockers.

Among the 128 patients whose dietary fiber intake was known, those who reported consuming at least 20 grams of dietary fiber per day (an amount the researchers designated as “sufficient” for the purposes of this study) lived longer without their cancer progressing than those who consumed less dietary fiber. Every 5-gram increase in daily dietary fiber intake corresponded to a 30% lower risk of progression of the disease.

The researchers also looked at the impact of dietary fiber on the response to treatment with anti-PD-1 drugs, a category of immune checkpoint blockers, in mouse models of melanoma. To mimic the different diets in the melanoma patients, they fed mice either a fiber-rich or a low-fiber diet, injected the mice with melanoma cells, and then treated the mice with anti-PD-1 therapy. Mice given the fiber-rich diet had delayed tumor growth after anti-PD-1 treatment, compared with mice given the low-fiber diet.

The researchers then repeated the experiments in germ-free mice—that is, mice that have no bacteria in their guts.

“In germ-free mice, the diet made no difference in the immunotherapy response,” Dr. Trinchieri said. “That suggests that the diet is affecting the response to immune checkpoint therapy by changing the composition of the gut microbiota.”

Dr. Trinchieri noted that one possible mechanism through which dietary fiber exerts its beneficial effect is by increasing the types of bacteria in the gut, such as Ruminococcaceae, that produce high levels of certain short-chain fatty acids that have an antitumor effect.

“We did see an increase in one of these short-chain fatty acids, propionate, in mice that were fed a high-fiber diet,” Dr. Trinchieri said. “Moreover, patients whose cancer responded to immunotherapy had a greater abundance of Ruminococcaceae bacteria in their gut microbiota compared with those who did not respond to therapy.”

The researchers also looked at the impact of probiotics on gut bacteria in the mouse model of melanoma. Mice fed probiotics had a reduced response to treatment with anti-PD-L1 drugs and developed larger tumors than control mice. Further analysis showed that mice fed probiotics had lower levels of tumor-killing immune cells, suggesting a weakened immune response.

In the human study, nearly one-third of the patients reported they had taken a probiotic supplement within the past month. Although the researchers noted that the small sample size and variety of probiotics used by the patients made it difficult to draw definitive conclusions about the association between probiotic use and response to immune checkpoint blockers, they did observe that patients who consumed the highest levels of dietary fiber with no probiotic use survived the longest.

“The impact of dietary fiber and probiotics on the gut microbiota is only part of the bigger picture,” Dr. Trinchieri cautioned. “Many factors can affect the ability of a patient with melanoma to respond to immunotherapy. However, from these data, the microbiota seems to be one of the dominant factors. The data also suggest that it’s probably better for people with cancer receiving immunotherapy not to use commercially available probiotics.”