Health equity in Europe has stagnated over the past decade, and in some case there are indications of a decline, a first-ever WHO report finds. However, advancing Universal Health Coverage (UHC) along with more inclusive policies for social welfare protection and political participation could put things back on track again.

A family prepares coffee following a power outage in FYR Macedonia. Living conditions are associated with health inequities. Photo: Tomislav Georgiev / World Bank

The Health Equity Status Report (HESR) report cites “financial hardship” as a major driver of health inequity in the WHO European Region, and pointing to “the critical importance of providing universal access to affordable health services.”

Released less than two weeks ahead of the planned UN High-Level Meeting on UHC, 23 September), the report places renewed focus on the third stated objective: of the planned UHC declaration – ensuring that “the cost of using services does not put people at risk of financial harm.”

The wide-ranging study of 53 countries in WHO’s European Region, analyzed data on life expectancy, infant mortality and other health indicators, in relation to socio-economic factors such as education, gender and income.

It found wide variations in equity indicators within and between European countries. For instance, while average infant mortality has decreased across Europe, the infant mortality rate in Azerbaijan (47.8 deaths per 1000 live births) is 25 times higher than the rate in Finland (1.9 deaths per 1000 live births).

Differences in life-expectancy and overall health based on gender, levels of education and income were also identified. The report also highlights inequities that are faced by so-called “new disadvantaged groups” such as adolescents who drop out of school early and people with chronic illnesses.

The retreat by many countries from public housing and social welfare programmes has impacted negatively on key equity indicators, the report notes. For example, 53% of countries in the Region reduced their spending on subsidies for housing and community assistance programs in the past 15 years, despite that among the health equity factors assessed, one-third are driven by poor living conditions.

In order to improve equity trends, the report recommends that countries enact health-promoting policies in 5 thematic areas:

Variations in life expectancy in Europe. Credit: WHO, European Regional Office
  • Invest in quality and affordable housing and safe neighborhoods;
  • Reducing out-of-pocket (OOP) health payments;
  • Reduce unemployment and implement job-promoting labour market policies (LMPs);
  • Equalize opportunities in education across the life course – including investing in adult education;
  • Strengthen social and political representation among marginalized groups.

“The Health Equity Status Report provides governments with the data and tools they need to tackle health inequities and produce visible results in a relatively short period of time, even within the lifetime of a national government of 4 years,” says Dr Zsuzsanna Jakab, regional director for WHO Europe, in a press release.

In a Lancet op-ed, HESR Initiative advisor, Dr Johanna Hanefeld, of the London School of Hygiene and Tropical Medicine, said that governments must, however, focus on deeper and more systemic changes as well.  These include, altering “the governance structures of policy processes to ensure the communities affected… have a meaningful voice that influences outcomes in these processes.”

 

Image Credits: Tomislav Georgiev / World Bank.

Solar panels supply energy for hot water at Bertha Gxowa Hospital in Johannesburg. Photo: Health Care Without Harm

Some 4.4% of the world’s climate emissions are from health care activities – meaning that if health care was a country, it would rank as the world’s fifth largest emitter in absolute terms – after the United States, China, India and Russia, but ahead of Japan and Brazil.

This is the key finding from a first-ever global report on climate emissions from health care, launched Tuesday by Health Care Without Harm (HCWH), an international NGO devoted to “greening” the health sector for the benefit of patients, health workers  – and the environment.

The report, Health care’s climate footprint: How the health sector contributes to the global climate crisis and opportunities for action, also found that the US health care sector is by far, the largest aggregate and per capita emitter – with a whopping 27% percent of the world’s total healthcare-related emissions, or 1.2 tons of CO2 equivalent per capita (tCO2e). That is 57 times more emissions per person than India, which has the lowest per capita emissions of the 43 developed and emerging economies, where detailed data was available for the report.

In absolute terms, China takes second place with 17% of emissions, and the European Union third place, with 12% of the world’s healthcare footprint. That is followed by Japan (5%), Russia (4%) and then Brazil, India, South Korea and Australia (2% each). Emissions from the rest of the world amount to no more than a quarter of the global total. The total climate footprint of the healthcare sector is estimated at 2 gigatons of CO2 equivalent emissions a year.

In terms of per capita emissions, the US is followed by Australia, Canada and Switzerland; most other European Union and developed countries; followed by a range of lower middle income countries. For other lower income countries, per-capita emissions couldn’t be reliably estimated.

The report’s launch comes just two weeks ahead of the planned UN Secretary General’s Climate Summit in New York City (23 September), and the study clearly takes aim at the much-discussed target for limiting global temperature rise to 1.5°C, saying that healthcare needs to do more of its share.

“Hospitals and health care systems paradoxically make a major contribution to the climate crisis,” said Josh Karliner, a lead author of the report as well as HCWH’s International Director of Programs and Strategy. “Healthcare has to step up and do its part to avoid catastrophic climate change, which would be devastating to human health worldwide.”

‘Decarbonizing’ the Health Care Sector

In line with that message, the also report outlines recommendations for areas where the health care sector could rapidly “decarbonize” including:

  • Net zero emissions building design and construction;
  • Investment in renewable energy and energy efficiency and climate-smart cooling technologies;
  • Sustainable waste, water, and transport management;
  • Better management of anaesthetic gases with high global warming potential;
  • Tele-medicine and digital health technologies that reduce patient travel and related infrastructure requirements.
  • Low-carbon procurement chains – for items ranging from pharmaceuticals to medical devices, as well as food and clothing, to improve efficiencies and reduce waste.
  • And at the other end of the spectrum – better waste management systems.

The report stresses that the health care sector remains dependent on energy supplies from national grids. “With 10% of health care facilities’ climate footprint coming from purchased energy, and with a large amount of the supply chain also consuming grid energy, decarbonization of national energy systems is essential to move health care to net zero emissions. “

However, low-carbon approaches to health care can be a win-win, fostering more equitable access to health care, and addressing health and safety risks that affect patients, health workers and the communities. For instance, some health-care facilities in low-income countries have developed their own renewable energy resources, which can provide power for health services more reliably, avoiding life-threatening interruptions in electricity supply.

“In energy-poor settings, powering health care with low-carbon solutions can enhance access to care, contributing to the advancement of universal health care for the poor and most vulnerable,” the report concludes.

The Climate Footprint of Different Health Care Activities

The study took a “cradle to grave” approach to the assessment, estimating emissions associated with everything from the procurement of chemicals and pharmaceuticals as well as rubber, cotton and plastic healthcare products to building design and energy management, transport, and waste. Key findings were:

  • More than one-half of the health sector’s footprint is due to generation and distribution of electricity or gas, heating/cooling, and related operational activities (53%).
  • Manufacturing and agricultural inputs (including food supplies and materials such as cotton for bandages), are the third (13%) and fourth (11%) largest source of emissions.
  • Transport represents about 7% of health sector emissions, while pharmaceutical products represent about 5%, followed by waste treatment (3%).

Along with other chemicals, anaesthetic gases, including nitrous oxide and the fluorinated gases sevoflurane, isoflurane, and desflurane, are an unexplored source of health-care emissions, the report notes. Their Global Warming Potentials range between 130 kgCO2e/kg (sevoflurane) and 2540 kgCO2e/kg (desflurane), the report notes. At present, the majority of these gases enter the atmosphere.

The report is built upon earlier studies of health sector emissions at national level; a 2017 study by HCWH and the World Bank, which provided a rough estimate of 5% of global emissions due to health care activities in 2011; and a 2018 study of Organisation for Economic Cooperation and Development (OECD) countries, plus India and China. That study estimated that health care activities in the 36 countries sampled was responsible for 1.6 GtCO2e emissions or 4.4% of the total emissions from these nations in 2014.

However, this report claims to establish the first detailed estimate – going further in terms of the number of countries covered, as well as estimates of emissions from various activities. It also draws from the global World Input-Output Database (WIOD) database, to come up with initial estimates for emissions for low- and lower-middle income countries where data remains scarce.

The report also breaks down global emissions according to the framework established by the Greenhouse Gas Protocol, the world’s most widely used greenhouse gas accounting standard. It thus aligns the emissions analysis of health care activities with the Protocol’s generic categories: Scope 1 (direct emissions from health care facilities), Scope 2 (indirect emissions from purchased energy), and Scope 3 (all indirect emissions, not included in scope 2, that occur in the value chain, including both upstream and downstream emissions).

Health Care Climate Challenge  

“Health care must respond to the growing climate emergency not only by treating those made ill, injured, or dying from the climate crisis, but also by practicing primary prevention and radically reducing its own emissions,” said Karliner, of the report’s aim.

As part of that response, Health Care Without Harm has launched a Health Care Climate Challenge which some 200 institutions, representing the interests of over 18,000 health facilities in 31 countries, have joined. Collectively, they have made commitments to reduce their carbon emissions by more than 34.2 million metric tons of CO2e. To date, Karliner says, the network has collectively reduced over 6.8 million metric tons of CO2e. The corresponding energy efficiency upgrades and renewable energy generation improvements have saved the partner institutions over US$394 million.

“The good news is that there are hospitals and health systems all around the world leading by example and implementing climate-smart health care strategies.”

 

Image Credits: Health Care Without Harm, Health Care Without Harm.

A new Lancet Commission report calls for health policy leaders to agree upon an ambitious global plan to eradicate of malaria by 2050  – contrasting with a World Health Organization report released in August that concluded it was too early to set a target date for eradication.

The report Malaria eradication within a generation: ambitious, achievable, and necessary  sets out a detailed roadmap for achieving eradication in the next three decades. Authored by a group of 41 leading malariologists, economists, health policy experts, and biomedical scientists, the report concludes that eradication is possible with the right tools, political commitments – and another $2 billion annually in funding.

“For too long, malaria eradication has been a distant dream, but now we have evidence that malaria can and should be eradicated by 2050,” said Sir Richard Feachem, co-chair of The Lancet Commission on Malaria Eradication and director of the Global Health Group at the University of California, San Francisco (UCSF).

However, in an op-ed that appeared alongside the Commission’s massive report, WHO’s Director General, Dr Tedros Adhanom Gheyebresus, cautioned that malaria could “not be eradicated within this timeframe” with the currently available tools and strategies.

A yoA young girl reading under a malaria bednet. Photo: UNDP
A young girl reading under a malaria bednet. Photo: UNDP
WHO & Lancet Commission Differ on Feasibility of Eradication by 2050

In August, WHO’s Strategic Advisory Group on Malaria Eradication (SAGEme) issued a much more sobering assessment of trends. The WHO experts cautioned that the world was not even “on track to meet global targets for 2020.” And progress made in reducing malaria cases and malaria deaths has stagnated in recent years, with no change in malaria incidence or case-fatality since 2015.

SAGEme concluded that under even with the most optimistic scenarios, in 2050 there would still be 11 million malaria cases annually in malaria’s epicenter, Africa. The WHO report also comes against the history of a failed 14-year global WHO campaign to eradicate malaria in the 1950’s, which observers say has made the agency reluctant to set such an ambitious goal again, unless it is really attainable.

“A malaria-free world, which has been WHO’s vision since at least 1955, remains the ultimate goal of the global health community,” Dr. Pedro Alonso, director of WHO’s Global Malaria Programme told Health Policy Watch. “We have a global strategy, endorsed by the World Health Assembly in 2015, that gets the world 90% of the way to eradication.”

“No one yet knows what it will take to get the final 10% of malaria, or when we will be able to finish the job, but we know what needs to be done today,” Alonso said. But to make the “ultimate push” for eradication, he underlined that the world first needs to get “back on track” to meet the 2020 global goals for malaria. Countries need to embrace Universal Health Coverage, “to deliver malaria interventions to everyone who needs them,” he added.  And new R&D tools as well as more resources for health systems will also be critical.

“The global malaria community has clearly united around the vision of a world free of malaria and now we need to move forward to make it happen,” he concluded at the close of the Geneva Forum.

Meanwhile, David Reddy, Chief Executive Officer of the Geneva-based Medicines for Malaria Venture (MMV), applauded the focus that the recent reports by WHO as well as the Lancet Commission report had brought to the malaria issue – which could also help reinvigorate global commitments.

“With more than 400,000 people dying each year from this preventable and curable disease, these analyses will help to refocus and strengthen our efforts toward eradication,” said Reddy. “It is appropriate that these two comprehensive analyses support the view that malaria eradication is achievable and identify concrete measures to regain momentum toward a malaria-free world.”

He added that MMV was supporting research to develop tools that will support “the ultimate eradication of malaria” while also expanding its focus on access and product management to address key unmet needs, noting that “unless the important new tools we have co-developed can be readily available wherever and whenever they are needed, we will have fallen short on fulfilling the promise of our mission”.

 

Malaria Incidence per 1000 population.
Same Data, Two Conclusions

While malaria elimination refers to the interruption of transmission in a particular country or region, eradication typically means that there is complete interruption of malaria transmission globally, with zero cases across the globe.

Both the WHO SAGEme and Lancet Commission looked at the same social, environmental, and economic trends to assess the feasibility of malaria eradication, but came to different conclusions.

While committed to the idea of malaria eradication since 1948, WHO has been cautious about setting a target date. WHO claims that “optimal tools” have not yet been developed and the current burden of malaria cases is still too high to target eradication.  Successes in smallpox and polio eradication hinged on the low number of annual cases, and the availability of highly efficacious vaccines, points out a WHO Q&A.

Dr. Tedros, in his Op-Ed arguing that the “imperfect application of imperfect tools” has reduced the malaria burden, but has not been enough to push forward to malaria eradication.

As a result, the WHO SAGEme report concludes that setting a target with too many uncertainties “may actually be counterproductive.” It urges a more cautious approach that will assess the progress against malaria in five-year intervals, until a “tipping point” is reached where a time-limited malaria eradication campaign is fully feasible.

On the other hand, the Lancet Commission argues that the target date should be set for 2050, believing that the goal is “a bold but attainable, and necessary one.”

While acknowledging that there are outstanding challenges to malaria eradication, the Commission’s report also is more optimistic about the R&D pipeline, calling it “robust” and noting that new tools are expected to be rolled out in the next decade.

Additionally, the report points to a ripe political climate for setting a target for eradication, noting many high-burden countries have increased malaria financing in the past decade.

Finally, the Commission’s report notes that in the absence of full-fledged of eradication, massive efforts would in fact be needed to sustain malaria elimination. For instance, malaria has already been eliminated in a number of countries, such as the United States. However, states must continue surveillance and control efforts to prevent malaria from being imported from other endemic countries.

Currently, global WHO targets sidestep the issue of eradication, and encourage regions to target malaria elimination “where it is feasible to do so,” meaning in countries with low burden of malaria.

Eradication: Ambitious but Possible

The Lancet Commission report, launched at a WHO-hosted Geneva Forum on Rising to the Challenge of Malaria Eradication this week, sounds a much bolder note, claiming that global eradication is possible by 2050 – providing there was sufficient political and research community leadership, finance, and country commitment.

The Commission also underlines that it is critical now to accelerate efforts for malaria eradication, to end “the never-ending struggle” against increasing drug and insecticide resistance, which could even lead to malaria resurgence, associated with more human, social and economic costs.

While malaria eradication by 2050 is feasible, this hinges on aggressive action in three major areas, described by the Commission as:

  • Strengthening existing malaria control programs by improving management and use of available tools;
  • Stimulating the research and development pipeline for new malaria medicines, vaccines, and mosquito control tools;
  • Mobilizing new financing from malaria-endemic countries and donors.

Human trials for the first malaria vaccine are underway in Malawi, and studies are being conducted to evaluate mass drug administration (MDA) as a new strategy for malaria elimination.

While noting the impressive scale-up in malaria funding over the previous two decades, the Commission calls for funders to mobilize an additional USD$2 billion annually in order to reach eradication, calling for domestic governments to take on 75% of the additional costs. Currently, global expenditure for malaria stands at about USD$4.3 billion annually.

The benefits, the Commission argues, outweigh the costs of investing in malaria eradication. Reducing the malaria burden by 90% by 2030 in the highest burden countries alone is estimated to yield over USD$280 billion in economic gains.

Once malaria is eradicated, it will no longer cripple economies, allow resources to be diverted to other health priorities, and contribute to individuals’ improved quality of life. More precise WHO estimates of the economic benefits of malaria control will also be published as part of a SAGEme report later this year.

History of Malaria Eradication Efforts Extend Back to 1950s

The WHO launched the first Global Malaria Eradication Programme (GMEP) in 1955.

The first GMEP made huge strides against malaria, contributing successful elimination in the United States and some South American countries.

The first GMEP also excluded Africa, the continent with the highest malaria burden in the world. After a 14-year battle, experts at the WHO agreed to post-pone the target date for malaria eradication until “conditions were more favorable.”

High-level commitment for malaria control decreased following the announcement. However, increased resistance to DDT, the primary insecticide used for malaria control, led to resurgence of malaria in many countries that relaxed control efforts in the 1980’s. In 2000, global momentum for malaria control increased again. Since then, malaria transmission has been interrupted in a number of countries.

However, over 400,000 people still die from malaria annually. In high-burden countries such as Ethiopia, malaria remains a leading cause of maternal mortality and death in young children.

Malaria is a biologically feasible target for eradication because humans are largely the only mammalian host.

Image Credits: UNDP, The Lancet .

New data revealing that survivors of Guinea’s 2013-16 Ebola outbreak were five times more likely to die within the first year after recovery, as compared to the general population, suggests a need to revisit WHO guidance on Ebola survivors’ monitoring and care, a top WHO official said on Friday.

The findings were part of a study published in Lancet Infectious Diseases earlier this week. The WHO-led study also found that people hospitalized with the Ebola virus for a longer period had higher overall mortality rates than those with shorter stays. Beyond a year, however, the study of some 1130 survivors found that mortality rates of survivors and the general population evened out. The study also pointed to kidney failure as the most common cause of death.

The findings have many implications for monitoring and treating survivors of the current outbreak in the Democratic Republic of the Congo, said Professor Judith Glynn, a senior author of the study from the London School of Hygiene & Tropical Medicine.

Siah Tamba puts on a light personal protective equipment (PPE). She is an Ebola survivor who now works at the Ebola treatment unit (ETU) in Sinje, Grand Cape Mount, Liberia, after losing her mother, sister, and daughter. The facility is operated by the International Organization for Migration (IOM) in partnership with Liberia's Ministry of Health and Social Welfare (MOHSW) and supported by USAID's Office of U.S Foreign Disaster Assistance. It opened with a capacity of 10 beds, but can rapidly scale to provide care to up to 50 people. The ETU is staffed with 23 medical professionals from Kenya, South Africa, Tanzania, Uganda and Ukraine, as well as 114 Liberians from Grand Cape Mount county, who were recruited and trained to offer clinical and non-clinical care within the facility. The staff received training from the World Health Organisation (WHO) and the MOHSW, and experienced hands-on training at the IOM-managed ETU in Tubmanburg, Bomi County, Liberia.
Ebola survivor dons protective gear to meet and support a patient currently undergoing treatment.

“Our results could help to guide current and future survivors’ programmes and the prioritisation of funds in resource-constrained settings. For example, those hospitalised with Ebola for longer may be at greater risk, and could be specifically targeted,” Glynn said in a statement.

“As the evidence increases on Ebola survivors it might be good to revisit the Ebola CRF,” tweeted Sylvie Briand, director of epidemic and pandemic diseases at WHO, referring to the protocols that guide monitoring, care and treatment.  Currently, interim WHO guidelines on caring for Ebola survivors do not call out kidney failure as a high risk.

While a range of chronic symptoms have been previously reported in Ebola survivors, this was the first study to systematically track and document mortality rates among Ebola patients after they successfully underwent treatment and were discharged.

The study followed up on survivors in Guinea, the first country hit by the 2013-2016 West African Ebola outbreak, for a year and nine months after they were discharged from treatment centers. In the first year (2015), some 55 people died, five times more than the 11 people who might have been expected to die based on mortality rates in the general population. But in the subsequent nine months of 2016, when the study continued, mortality did not differ between Ebola survivors and others.

Because few detailed medical records exist, researchers relied on interviews with family members as the main source of information. Based on reported symptoms, kidney failure was the suspected cause of death in 37 out of 55 cases. Researchers stressed that the lack of documentation available to rule out other causes was a limiting factor in their findings.

“The research suggests that we need to continue supporting those recovering from Ebola and provide health care to them long after they have recovered from Ebola virus disease,” Josie Golding a senior officer at Wellcome Trust told Health Policy Watch.

“And I think that we need to consider other variables that can impact patients recovering from Ebola. As observed in DRC, people affected by Ebola are often stigmatised. We must better understand how this can impact on the health of those survivors in terms of access to healthcare.”

Finally, Golding said, researchers need to explore the long-term impacts of vaccination and treatments that have been become available since the Guinea outbreak. “We need to understand how long people are protected from Ebola, or what the impact vaccination can have in pregnant women.”

Notably Guinea’s Ebola victims did not receive the new WHO-prequalified Ebola treatments that are now being used in the DRC.

Infections Now Top 3000 Since August 2018

As of 4 September another milestone in the DRC epidemic had been passed as WHO reported 3054 Ebola cases  (2945 confirmed and 109 probable) since the outbreak began in August 2018, with 2052 deaths and 914 survivors, for a survival rate of about 30%.

In the latest report posted by WHO Friday evening, 57 new cases had been reported over the past week, slightly less than the average of 77 new cases in the weeks of August. However, while transmission in hotspots such as the Beni Health Zone in the province of North Kivu show signs of easing, “new hotspots are emerging elsewhere,” warned the WHO report. The epicenter of the outbreak has extended across the provinces of North Kivu and Ituri. The areas stretch along DRC’s long and porous border with the neighboring countries of Rwanda, Uganda, Burundi and South Sudan, which have been on high alert for the past few months, with several cases of transmission spilling over into neighboring Uganda.

Funding Shortfalls, Insecurity Continue to Plague Response

Funding shortages continue to plague the response. WHO has asked for an infusion of US$287 million to fund the core public health response to the epidemic between July and December 2019, but so far only about 45 million of those funds have been received and pledges will only fund response until the end of September, said WHO, which has appealed to donors to urgently provide more support.  On Thursday, USAID pledged some US$21 million more to the Ebola effort, bringing the total USAID funding for the DRC outbreak to US$158 million.

In a visit earlier this week to DRC, UN Secretary General Antonio Guterres also appealed to donors to follow through on their commitments urgently; “Ebola cannot wait, if the response is interrupted by one week, we might lose the battle,” he said in an interview broadcast over Twitter.

Guterres also said that more needed to be done to contain the violence that has plagued disease control efforts, due to the activities of armed militias operating in the areas of North Kivu, one of the epicenters of the epidemic.

“Combating Ebola requires freedom of movement, access, security,” the UN leader also observed, during a visit to an Ebola Treatment Center in Mangina, a rural municipality in Beni territory, North-Kivu province, where the first cases of Ebola was been detected over a year ago.

He said that increase cooperation between UN peacekeepers and DRC armed forces was necessary to overcome threats of “terrorist acts”. But efforts should also be intensified to demobilize local armed groups and reintegrate them into the civilian population.

Elaine Ruth Fletcher contributed reporting to this story.

Image Credits: UNMEER/Martine Perret 2015.

Facebook has begun rolling out a new algorithm that directs users searching for vaccine information to the United States Centers for Disease Control (CDC) website, in the case of US-based searches, and for users elsewhere, the World Health Organization website, as a top search pick.

The move was welcomed by WHO, officials at CDC, and other health experts as an important step in combating a wave of misinformation about immunization from vaccine opponents, so-called “anti-vaxxers,” that has swept over social media. The media fog, has in turn, been blamed for alarming parents, and contributing to the recent upsurge in measles cases in the US as well as vaccine resistance elsewhere.

“We welcome Facebook’s efforts to mitigate the spread of misinformation about vaccines and connect people to sources of accurate information … social media response is an important dimension of our broader efforts to build trust and confidence in immunisation,” Dr Heidi Larson, who runs the Vaccine Confidence Project at the London School of Hygiene and Tropical Medicine, told The Guardian, which had reported in February on the fact that Facebook users were being steered through popularity algorithms to anti-vaccine sites.

Facebook announced the new policy yesterday in a company newsroom post that said, “We are working to tackle vaccine misinformation on Facebook.” The company said it would “reduce rankings” for groups and pages that spread misinformation, and it would explore ways to promote sites that “provide people more accurate information from expert organizations about vaccines at the top of results for related searches.”

WHO Director General Dr. Tedros Adhanom Ghebreyesus, said in a statement: “The World Health Organization and Facebook have been in discussions for several months to ensure people can access authoritative information on vaccines and reduce the spread of inaccuracies. Facebook will direct millions of its users to WHO’s accurate and reliable vaccine information in several languages, to ensure that vital health messages reach people who need them most.”

“Vaccine misinformation is a major threat to global health that could reverse decades of progress made in tackling preventable diseases”, the statement added, noting that many “debilitating and deadly” diseases such as diphtheria, hepatitis, polio and measles can be effectively prevented through vaccination.

Some users were quick to note the challenges inherent in the Facebook move, including for WHO, which needs to ensure that users around the world can easily get to the relevant content on the vaccine issue in different languages. “Facebook is doing the right thing and the ball is now in the court of @WHO headquarters,” tweeted one commentator complaining, “The WHO page that @Facebook redirects to is only in English and has a readability of grade 4. Has the text been pretested with vaccine-hesitant parents?”

This reporter, signing onto Facebook from Europe Thursday evening, and searching under the word “vaccine”, got to the detailed US CDC vaccine information site as a first pick and as a second pick, to the general WHO Facebook page, promoting a Walk the Talk-Health For All walk/run event planned in New York City later this month ahead of the upcoming United Nations General Assembly. A reporter testing the new Facebook algorithm from New York City also landed on the general WHO facebook page when searching for “vaccines.”

A WHO spokeswoman said she had no further details about the nature of the WHO arrangement with Facebook or how it had been reached.  However, the Facebook action followed moves earlier this year by YouTube to reduce the frequency with which users would click into anti-vaccine propaganda, as well as an announcement last week by the social media platform Pinterest that it would curb misinformation on its website.  A WHO statement last week lauded “Pinterest’s leadership in protecting public health” and called upon other social media platforms to follow its example.

 

Search results for “vaccines” on Facebook.

 

A new WHO nutrition report highlights how healthier diets can combat obesity and leading noncommunicable diseases (NCDs) – suggesting that less consumption of free sugars, salt and saturated fat, particularly animal fat, will help reduce global trends of rising obesity, hypertension and cardiovascular disease.

But the report Essential Nutrition Actions – Mainstreaming Nutrition through the Life Course, steers clear of delivering recommendations on controversial policies that some nutrition advocates have said are needed to actually shift global diets to healthier foods – such as taxation of sugary drinks or graphic front-of-package labeling about unhealthy processed foods.

Graphic of a group of people eating food at a table
Photo: WHO

The report provides a broad compendium of guidance on nutrition and healthier diets at various stages of life, as well as in health emergencies. It brings together pre-existing WHO recommendations for combating obesity, hypertension and other NCDs, including advice to:

  • Reduce free sugars intake to less than 5% of total energy intake;
  • Limit salt intake to less than 5 grams a day;
  • Reduce fat intake to no more than 30% of total energy intake, saturated fats to less than 10% of total energy and transfatty acids to less than 1%;
  • Increase sodium intake to at least 3.5 grams a day;
  • Consume five portions of fruit and vegetables a day.

While recommending limited saturated fat intake, the report avoids reference to evidence about cancer risks from red meat and processed meat consumption, as reported in 2015 by WHO’s own International Agency for Research on Cancer (IARC). IARC described processed meat as “carcinogenic to humans” and red meat as “probably carcinogenic“.

Extensive guidance is, however, provided for well-tread health and nutrition strategies to address malnutrition and undernutrition, such as: vitamin and mineral supplementation of food staples; exclusive breastfeeding in the first six months of life; and safe drinking-water and sanitation to reduce diarrhoeal disease that can exacerbate  malnutrition; and breastfeeding in the first six months of life.

“Health services must integrate a stronger focus on ensuring optimum nutrition at each stage of a person’s life,” said a WHO press release, noting recent World Bank estimates that smarter investments in nutrition could save 3.7 million lives by 2025.

Diets Through the Life Course

In an interview on WHO’s Twitter channel, WHO’s Nutrition Director, Francesco Branca, director of WHO’s Nutrition Department, stressed the importance of fresh foods and plant-heavy diets at early childhood, adolescence and for older people.

“Good nutrition starts very early in life,” said Branca. In early childhood diets should be “mainly made of complex carbohydrates, not too much fat, particularly not the fat that comes from animal sources, and not too much  free sugars, the ones that you find in sugar sweetened beverages,” Branca added. Diets should also include “enough fruits and vegetables, five portions; as for animal foods, a little bit because we also have to be concerned about the impact that the diets we consume have on the environment,” he said.

An report last month by the Intergovernmental Panel on Climate Change (IPCC) put it more bluntly. The UN’s top body of climate scientists said shifting global diets away from red meat consumption and towards healthier plant-based alternatives is critical for combating climate change as well as halting land degradation so as to ensure long-term food system sustainability and food security.

Adolescents should reduce consumption sugar sweetened beverages and processed foods, Branca added. Adolescent girls, in particular, can benefit from folic acid and iron supplementation, which may also reduce health risks to their children, should they give birth.

Older people, in particular, should have “diets low in sodium, to protect from hypertension, and very rich in plant food, with adequate preparation. Sometime elderly do not have the opportunity to go out and do their shopping. We see a lot of elderly people who are malnourished,” he said.

For women, dietary consumption of phytoestrogens, from sources such as soy or flaxseed, may be helpful to combat menopausal symptoms as well as other NCDs. “People living in SE Asia consuming large sources of phytoestrogens through their lives seem to have an easier menopause,” Branca said. “Consumption of soy, flaxseed, may be important for prevention of cardiovascular disease and certain cancers.”  He noted that evidence of health benefits from food supplements, is not as robust.

Consumption of plant-based oils rich in unsaturated fats should be preferred throughout all life stages, Branca  noted, “because they have the least impact on our arteries” while consumption of industrially-processed trans-fats should be avoided altogether.

Fresh fruits and vegetables in Maldives market. Photo: WHO/V. Gupta-Smith

“You find some of these in prepackaged foods, we are trying as WHO to ask Industry to remove these toxic products from our foods, he said. In May, WHO Director General Dr Tedros Adhanom Ghebreyesus said that he had secured a commitment from leading food and beverage producers to phase out trans-fats by 2023. WHO estimates that consumption of industrial trans fat, commonly included in processed foods, leads to more than 500,000 deaths every year due to cardiovascular disease.

As for policy implications of the report, Branca said that it was important for governments to display leadership in “what the right diet is, informing consumers, creating and shaping the food environment.”  He noted that “some countries have established a tax on sugary sweetened beverages or clear packaging information,” although the report itself avoids mention of such  examples.

In its press release, WHO cited progress made over the past three decades in combating undernutrition, as reflected in a global decline in stunting (low height-for-age ratio) among children under 5 years old from 252.5 million children in 1990 to 149.0 million children in 2018. However, globally, the world now faces a “double burden” of malnutrition from inadequate food intake, as well as over consumption of unhealthy foods.

As a result, obesity is on the rise. Proportions of children considered overweight rose from 4.8% to 5.9% between 1990 and 2018, an increase of over 9 million children. Adult overweight and obesity are also rising in nearly every region and country of the world.  In 2016, some 1.3 billion people were considered overweight, of which 650 million (13% of the world’s population) were obese.

Obesity is a major risk factor for diabetes, says WHO, as well as for heart disease and stroke); musculoskeletal disorders such as osteoarthritis – a degenerative disease of the joints; and some cancers (including endometrial, breast, ovarian, prostate, liver, gallbladder, kidney, and colon).

Image Credits: WHO, WHO/V. Gupta-Smith.

Amid stalled global progress on reducing malaria cases and deaths since 2015, the World Health Organization has called for renewed and accelerated research and development (R&D) of new tools for malaria prevention and treatment, improved use of data, and strengthened international, regional, and sub-national cooperation.

WHO’s Strategic Advisory Group on Malaria Eradication (SAGme) said in the executive summary of their 23 August report that while much progress was made between 2000 and 2015, “the world is not on track to meet the 2020 milestones,” which could undermine the goal of reducing malaria cases and deaths by 90 percent by 2030.

“To achieve a malaria-free world we must reinvigorate the drive to find the transformative strategies and tools that can be tailored to the local situation. Business as usual is not only slowing progress, but it is sending us backwards,” said Dr Marcel Tanner, Chair of SAGme, according to a WHO press release.

“Freeing the world of malaria would be one of the greatest achievements in public health,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General, in the release. “With new tools and approaches we can make this vision a reality.”

Photo: WHO/Griff Tapper

Research and development of new tools for prevention and treatment are among the top priorities outlined by the SAGme report. Current insecticide-treated mosquito nets and indoor residual spraying are referred to as “old and imperfect,” protecting populations at home but leaving them vulnerable outdoors. Expanded vaccine research and development will also be critical, it says.

Today, however, “less than 1% of funding for health R&D investment goes to developing tools to tackle malaria,” the release states.

“We need the commitment of political leaders to provide adequate funding from international and domestic sources to ensure access to affordable health care,” said Dr. Pedro Alonso, Director of the Global Malaria Programme at WHO, in a 22 August press briefing.

“The economic and societal benefits of malaria eradication would be massive,” he said.

WHO estimates the cost of scaling up malaria interventions through 2030 at US $34 billion, which would be comprised of a combination of international and domestic funding from affected countries. Such a scale-up, it says, would prevent an additional 2 billion malaria cases and 4 million deaths by 2030.

Through this investment of US $34 billion, the Strategic Advisory Group forecasts the economic gain for the highest burden countries to be estimated at US$ 283 billion in total GDP through 2030.

Challenges to Eradication

Outlined by the WHO in its 2018 World Malaria Report and reiterated by Friday’s SAGme report, the fight against malaria has stalled after fifteen years of progress between 2000 and 2015. With progress towards meeting the 2020 Global Technical Strategy for Malaria 2016–2030 (GTS) milestones “off track,” the WHO and the Strategic Advisory Group on Malaria Eradication call for action to remove barriers that may pose a risk to achieving a 90 percent malaria case and mortality reduction by 2030.

Availability of affordable, quality health services is recognised as a major challenge to malaria eradication. “To eliminate malaria and prevent the re-establishment of transmission, a country will require strong political commitment and investment in universal health coverage, with a well-functioning primary health care system at its base,” stated the executive summary.

“Health system quality is strongly correlated with malaria progress across the spectrum of malaria endemicity,” it said, and a strong governance framework will be needed “to bring together health systems infrastructure, service delivery, civil society and communities.”

A second key challenge is regarding data analysis and surveillance and response. “We need to further improve the quality and the use of data to detect changes in malaria transmission and adequately respond,” said Dr Alonso during Thursday’s press briefing.

Improved data will serve as “an active tool that helps the decision makers [on] how to proceed” SAGme Chair Dr Marcel Tanner said in the briefing. In addition to addressing current needs, improving data and surveillance will allow for rapid and effective action in the event of changes in malaria transmission resulting from global trends such as urbanization, climate change and population growth.

“Today, we can say it is feasible to reach eradication but we cannot lay an exact date [for it],” Dr Tanner said in the briefing. However, the report notes that there still remains the possibility of reaching a 90 percent malaria reduction rate by 2030, provided new tools and approaches are implemented.

Image Credits: WHO/Griff Tapper.

The World Health Organization concluded that the current risk to human health of microplastics in drinking-water is low, according to a report released today. However, it says that further research is needed to more accurately assess the effects of exposure to microplastics.

“We urgently need to know more about the health impact of microplastics because they are everywhere – including in our drinking-water,” said Dr Maria Neira, Director of the Department of Public Health, Environment and Social Determinants of Health at WHO, quoted in a press release. “Based on the limited information we have, microplastics in drinking-water don’t appear to pose a health risk at current levels. But we need to find out more. We also need to stop the rise in plastic pollution worldwide.”

The main message of the report is “to reassure drinking-water consumers around the world that based on this assessment, the risk [to human health] is low,” said Dr Bruce Gordon, Coordinator of the Department of Water and Sanitation at WHO, in a press conference on the release of the analysis.

Photo: WHO/European Pressphoto Agency (EPA)

“This report focused on drinking-water, and there’s [also] a need to consider the other environmental pathways,” noted Jennifer de France, Technical Expert at WHO’s Department of Water and Sanitation and co-author of the report, in the press conference.

The WHO is now calling for more data collection in three priority areas: the occurrence of microplastics in the water cycle, the physical impacts of smaller microplastic particles, and the risk from total exposure to microplastics.

In the meantime, WHO recommends that global stakeholders focus on the known health risks of microplastics in drinking-water and pre-emptively reduce plastic pollution to limit human exposure and protect the environment.

This report was produced in response to an analysis released in 2018 that detected the presence of microplastics in tap water and bottled water, leading to concerns about the potential health risks.

Review of existing research has found that microplastics above 150 micrometers are not readily absorbed by the human body; concentrations of chemical additives found in microplastics in drinking-water are currently too low to cause adverse effects; and harmful bacteria are not likely to colonize the small particles.

WHO has therefore concluded that microplastics in drinking-water currently do not represent a significant hazard to human health, and does not recommend routine monitoring of microplastics in drinking-water at this time.

Stimulating Research on Microplastics

However, WHO says that additional investigative research is warranted based on the poor quality of existing studies and the proliferation of plastics in the environment.

Although research published in the last two years showed improved scientific rigor, most of the studies reviewed for the report lacked sufficient quality controls. Thus, WHO recommends that results from existing studies should be interpreted with caution.

Additionally, the report is limited to examining microplastic exposure only in the context of drinking-water.

Microplastics have also been found in air and food. In response, WHO has initiated a review on the potential health effects from microplastics due to total environmental exposure.

The research pipeline for microplastics in drinking-water is growing. According to Gordon, there has been an exponential increase in the number of studies published in the past year.

Keeping the Focus on Known Risks

In addition to motivating new research, WHO is pushing to reduce plastic pollution and prioritise increasing access to existing water treatment technologies to protect against known hazardous chemicals and water-borne diseases.

“We know from WHO data and UNICEF data that over 2 billion people drink water that is faecally contaminated, and that causes almost 1 million deaths per year. That has got to be the focus of regulators around the world,” said Gordon.

Unsafe drinking and tap water is a leading cause of diarrheal diseases such as cholera. Taken together, diarrheal diseases are the second leading cause of death in children under 5, and kill more children annually than AIDS, malaria, and measles combined.

Safe water treatment systems also reduce exposure to microplastics. Proper wastewater treatment can remove more than 90 percent of microplastic particles. Drinking-water systems are optimised to remove particles of even smaller size, filtering out microplastics smaller than one micrometer.

Ensuring the quality of water treatment systems and using existing guidelines and knowledge on water safety will also improve the removal of microplastics from drinking-water as a by-product.

The WHO report on microplastics in drinking-water was released on the heels of a World Bank Report that called attention to the economic effects of worsening water quality in many developing nations.

According to the World Bank analysis, poor water quality limits economic growth in some countries by one-third.

Both reports recommend increasing efforts to reduce plastic pollution and invest in improving water treatment systems.

“We strongly are pushing or promoting around the world to reduce plastic pollution. And that is out of great concern for this occurrence we’re seeing; it’s everywhere. And that is irrespective of any human health assessment,” said Gordon.

Plastics in the Environment

Global plastic production has increased exponentially since the 1950’s.

In 2017, approximately 407 million tons of plastic were produced, with intentional microplastics estimated to represent less than 0.1% of total plastics production. Unintentional, or secondary microplastics, break off of larger plastic pieces with regular wear and tear, and represent a larger share of microplastics found in the environment.

Researchers estimate that by 2050, over 12 billion tons of plastic could end up in landfills or the environment.

Image Credits: WHO/European Pressphoto Agency (EPA).

The US Food and Drug Administration (FDA) last week approved a tuberculosis (TB) treatment regimen containing a new drug, pretomanid, offering a shorter, more effective course of treatment for highly drug-resistant strains of TB, the world’s leading cause of death by infectious disease.

Pretomanid is only the third TB drug to be approved in over 50 years, and amidst the excitement from achieving this milestone, activists are calling for the developer and newly licensed producer of pretomanid to ensure that those most in need of the treatment will be able to access it.

“This newly approved regimen containing pretomanid could be a lifesaver for people with XDR-TB [extensively drug-resistant TB], but it’s not time to celebrate yet,” said Sharonann Lynch, HIV & TB Policy Advisor for Médecins Sans Frontières’ (MSF/Doctors Without Borders) Access Campaign. “The approval of this new regimen by the US FDA is just the first step. We now need pretomanid to be registered and available at an affordable price in all countries, prioritising those with the highest TB burden.”

José Luis Castro, Executive Director of the International Union Against Tuberculosis and Lung Disease (The Union), commented: “The Union welcomes a new shorter all-oral regimen for XDR-TB… and we emphasise the need that it will be affordable and made available to National TB Programmes to adopt and scale up to offer effective treatment options to people with this severe form of TB.”

Drug-resistant tuberculosis patient in Mumbai, India. Photo: MSF/Atul Loke/Panos Pictures

Unlike the two other new drugs in the TB arsenal, bedaquiline and delamanid, pretomanid is the first FDA-approved TB drug to be developed and registered by a non-profit organisation, the TB Alliance.

In 2000, resistance to decades-old front-line TB drugs was becoming increasingly common, yet there were no new antibiotics in the TB development pipeline. In response to this global gap in research and development (R&D), the TB Alliance was formed as a product development partnership (PDP) dedicated to “the discovery, development, and delivery of better, faster-acting and affordable tuberculosis drugs that are available to those who need them.”

After almost 2 decades and 19 clinical trials in 14 countries, pretomanid is the first TB treatment the Alliance has successfully registered with the FDA.

Mylan, a US based pharmaceutical corporation, was granted the first license to produce, register, and supply pretomanid in April 2019. Mylan is expected to bring the drug to market by as early as January 2020, pending anticipated guidance from the World Health Organization on the new treatment regimen.

A Potentially Game-Changing New Treatment

Pretomanid is listed to be given in a 3-drug regimen known as BPaL (bedaquiline + pretomanid + high dose linezolid) based on results from the landmark Nix-TB trial in South Africa.

Although the trial only enrolled 109 participants, results showed unprecedented cure rates of 89 percent in patients with extensively drug resistant tuberculosis (XDR-TB), representing a significantly higher success rate than the historical 34 percent cure rate.

The newly approved regimen is also much shorter and easier to administer – the 6-month treatment course consists of only 5 daily pills, taken orally.

Dr. Madhukar Pai, a TB expert and advisor for TB Alliance, explained in a recent article that patients often struggle to complete their full courses of therapy for XDR-TB due to drug toxicity and the long length of treatment.

Existing treatment regimens for XDR-TB require 6-8 drugs, administered both orally and intravenously, taken for up to 2 years. The intravenous drugs can cause serious side effects such as vertigo, deafness, and visual or auditory hallucinations, and patients can be required to take up to 40 pills a day.

While there are still concerns about contraindications from the high doses of linezolid required in the new BPaL treatment course, this shorter, simpler regimen holds promise for significantly improving adherence to treatment, quality of life while on treatment, and chance of complete cure.

More studies to test whether BPaL’s treatment efficacy can be maintained at lower doses of linezolid are underway.

Questions Around Treatment Access Remain

A number of TB stakeholders are cautiously optimistic about BPaL’s approval, claiming that the drug regimen means little if it cannot be delivered to patients in need.

Historically, there have been challenges in bringing new TB tools to scale. One of the necessary drugs in the newly approved BPaL regimen, bedaquiline, was approved for use against MDR-TB in 2012, yet MSF estimates that only 20 percent of people who require the drug are able to access it.

Bedaquiline remains priced out of reach for many people in low- and middle-income countries, and a number of high-TB burden countries have not yet registered the drug to allow importation and distribution.

MSF has been advocating for Janssen Pharmaceuticals, the only producer of bedaquiline, to halve the price of the drug to US$ 1 a day. They have recommended that the price for a 6-month course of BPaL be no more than US$ 500 per person.

Mylan has yet to release its launch price for pretomanid in low- and middle-income countries, and they hold exclusive rights for producing the drug until November 2020.

However, Daniel Everitt, VP and senior medical officer at the TB Alliance, says: “In all of the lower-income countries, [TB Alliance] will be encouraging other manufacturers, generic manufacturers, to get into the market — to get competition to drive down the price as well.”

TB Alliance is also poised to receive a Priority Review Voucher (PRV) as a reward for developing pretomanid. PRVs can be sold to pharmaceutical companies for as much as US$ 350 million, and activists have urged TB Alliance to apply potential profits from sale of a PRV to efforts to increase access to pretomanid.

On the regulatory side, TB experts have been calling on the WHO and high-burden countries, such as India and Russia, to develop guidelines and policies to ensure access to BPaL once it is brought to market. India has expressed interest in starting its own pretomanid trials soon.

WHO is in the process of updating existing treatment guidelines for MDR-TB which is expected to incorporate evidence on the BPaL regimen.

WHO is currently inviting health professionals, TB patients, policy makers, and other TB stakeholders to submit comments to the MDR-TB Guideline Development Group between August 8 and August 20 2019. New treatment guidelines are set to be released in late 2019.

Current Status of XDR-TB

“By the end of 2016, XDR-TB had been reported by 123 WHO Member States. Information from countries with reliable data suggests that about 6.2% of MDR-TB cases worldwide have XDR-TB. In 2016, there were an estimated 490 000 new cases of MDR-TB worldwide,” the WHO reports.

XDR-TB is highly underreported, so the true burden of disease is likely higher than official figures indicate.

Image Credits: MSF/Atul Loke/Panos Pictures.

[TB Alliance]

NEW YORK (August 14, 2019)—Pretomanid, a novel compound developed by the non-profit organization TB Alliance, was approved by the U.S. Food & Drug Administration (FDA) today for treating some of the most drug-resistant forms of tuberculosis (TB).1 The new drug was approved under the Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD pathway) as part of a three-drug, six-month, all-oral regimen for the treatment of people with extensively drug-resistant TB (XDR-TB) or multidrug-resistant TB (MDR-TB) who are treatment-intolerant or non-responsive (collectively “highly drug-resistant TB”).1,2

The LPAD pathway was established by FDA as a tool to encourage further development of antibacterial and antifungal drugs to treat serious, life-threatening infections that affect a limited population of patients with unmet needs.

“FDA approval of this treatment represents a victory for the people suffering from these highly drug-resistant forms of the world’s deadliest infectious disease,” said Mel Spigelman, MD, president and CEO of TB Alliance. “The associated novel regimen will hopefully provide a shorter, more easily manageable and highly efficacious treatment for those in need.”

The three-drug regimen consisting of bedaquiline, pretomanid and linezolid – collectively referred to as the BPaL regimen – was studied in the pivotal Nix-TB trial across three sites in South Africa. The trial enrolled 109 people with XDR-TB as well as treatment-intolerant or non-responsive MDR-TB.2

Nix-TB data have demonstrated a successful outcome in 95 of the first 107 patients after six months of treatment with BPaL and six months of post-treatment follow-up.2 For two patients, treatment was extended to nine months. The new drug application contains data on 1,168 people who have received pretomanid in 19 clinical trials that have evaluated the drug’s safety and efficacy.2 Pretomanid has been clinically studied in 14 countries.

TB, in all forms, must be treated with a combination of drugs; the most drug-sensitive forms of TB require six months of treatment using four anti-TB drugs.3 Treatment of XDR-TB or treatment-intolerant/non-responsive MDR-TB has historically been lengthy and complex; most XDR-TB patients currently take a combination of as many as eight antibiotics, some involving daily injections, for 18 months or longer.3,4 Prior to recent introduction of new drugs for drug-resistant TB, the World Health Organization (WHO) has reported estimates for treatment success rates of XDR-TB therapy at approximately 34 percent and about 55 percent for MDR-TB therapy.4

“Until very recently, people infected with highly drug-resistant TB had poor treatment options and a poor prognosis,” said Dr. Francesca Conradie, principal investigator of the Nix-TB trial. “This new regimen provides hope with 9 out of 10 patients achieving culture negative status at 6 months post-treatment  with this short, all-oral regimen.”

Pretomanid is a new chemical entity and a member of a class of compounds known as nitroimidazooxazines. TB Alliance acquired the developmental rights to the compound in 2002. It has been developed as an oral tablet formulation for the treatment of TB in combination with bedaquiline and linezolid, two other anti-TB agents, and is now indicated for use in a limited and specific population of patients.1 Adverse reactions reported during the Nix-TB trial of the BPaL regimen include hepatotoxicity, myelosuppression, as well as peripheral and optic neuropathy.1 Please see additional safety information in the Important Safety Information below and in the accompanying pretomanid Full Prescribing Information.

Pretomanid is only the third new anti-TB drug approved for use by FDA in more than 40 years, as well as the first to be developed and registered by a not-for-profit organization.5,6 Pretomanid was granted Priority Review, Qualified Infectious Disease Product, and Orphan Drug status. As a product development partnership, TB Alliance has collaborated with and received significant support from numerous governments, academia, philanthropic institutions, the private sector, civil society organizations and other partners over the course of pretomanid’s development.

Pretomanid is expected to be available in the United States by the end of this year. In addition to the U.S. FDA, TB Alliance has submitted pretomanid as part of the BPaL regimen for review by the European Medicines Agency and has provided data to the World Health Organization for consideration of inclusion in treatment guidelines for highly drug-resistant TB.

INDICATION

Limited Population: Pretomanid Tablet is an antimycobacterial indicated, as part of a combination regimen with bedaquiline and linezolid for the treatment of adults with pulmonary extensively drug-resistant (XDR), treatment-intolerant or non-responsive multidrug‑resistant (MDR) tuberculosis (TB).  Approval of this indication is based on limited clinical safety and efficacy data.  This drug is indicated for use in a limited and specific population of patients.

Limitations of Use:

  • Pretomanid Tablets are not indicated for patients with:
    • Drug-sensitive (DS) tuberculosis
    • Latent infection due to Mycobacterium tuberculosis
    • Extra-pulmonary infection due to Mycobacterium tuberculosis
    • MDR-TB that is not treatment-intolerant or non-responsive to standard therapy
  • Safety and effectiveness of Pretomanid Tablets have not been established for its use in combination with drugs other than bedaquiline and linezolid as part of the recommended dosing regimen.

IMPORTANT SAFETY INFORMATION

Contraindications
Pretomanid Tablets used in combination with bedaquiline and linezolid are contraindicated in patients for whom bedaquiline and/or linezolid is contraindicated.

Warnings and Precautions 

  • Hepatic adverse reactions were reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid.  Monitor symptoms and signs and liver‑related laboratory tests.  Interrupt treatment with the entire regimen if evidence of liver injury occurs.
  • Myelosuppression was reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid.  Monitor complete blood counts.  Decrease or interrupt linezolid dosing if significant myelosuppression develops or worsens.
  • Peripheral and optic neuropathy were reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid.  Monitor visual function.  Obtain an ophthalmologic evaluation if there are symptoms of visual impairment.  Decrease or interrupt linezolid dosing if neuropathy develops or worsens.
  • QT prolongation was reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid.  Use with drugs that prolong the QT interval may cause additive QT prolongation.  Monitor ECGs.  Discontinue the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid if significant ventricular arrhythmia or if QTcF interval prolongation of greater than 500 ms develops.
  • Reproductive effects: Pretomanid caused testicular atrophy and impaired fertility in male rats. Advise patients of reproductive toxicities in animal studies and that the potential effects on human male fertility have not been adequately evaluated.
  • Lactic acidosis was reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid.  Consider interrupting linezolid or the entire combination regimen of Pretomanid Tablets, bedaquiline, and linezolid dosing if significant lactic acidosis develops.

Adverse Reactions
Most common adverse reactions (≥10%) are peripheral neuropathy, acne, anemia, nausea, vomiting, headache, increased transaminases, dyspepsia, decreased appetite, rash, pruritus, abdominal pain, pleuritic pain, increased gamma-glutamyltransferase, lower respiratory tract infection, hyperamylasemia, hemoptysis, back pain, cough, visual impairment, hypoglycemia, abnormal loss of weight, and diarrhea.

Please see Full Prescribing Information at www.tballiance.org/pretomanid

About Tuberculosis
Tuberculosis is a global disease, found in every country in the world. It is the leading infectious cause of death worldwide. In 2017, 10 million people fell ill from active TB and 1.6 million died. It is an airborne disease that can be spread by coughing or sneezing. There are more than half a million cases of MDR-TB annually, with about 6% of those cases being XDR-TB. Current WHO figures report that 127 countries have reported cases of XDR-TB. Drug-resistant forms of TB currently accounts for close to 1 in 3 deaths due to antimicrobial resistance annually.

About TB Alliance
TB Alliance (The Global Alliance for TB Drug Development, Inc.) is a not-for-profit organization dedicated to finding faster-acting and affordable drug regimens to fight TB. Through innovative science and with partners around the globe, we aim to ensure equitable access to faster, better TB cures that will advance global health and prosperity. TB Alliance operates with support from Australia’s Department of Foreign Affairs and Trade, Bill & Melinda Gates Foundation, Cystic Fibrosis Foundation, European & Developing Countries Clinical Trials Partnership, Germany’s Federal Ministry of Education and Research through KfW, Global Health Innovative Technology Fund, Indonesia Health Fund, Irish Aid, Medical Research Council (United Kingdom), National Institute of Allergy and Infectious Disease, Netherlands Ministry of Foreign Affairs, United Kingdom Department for International Development, and the United States Agency for International Development.

For more information on the pretomanid application and regulatory approval process, please visit:

1. Pretomanid and BPaL. Full Prescribing Information. August 2019.

2. TB Alliance. Pretomanid and BPaL Regimen for Treatment of Highly Resistant Tuberculosis. Oral presentation at: Antimicrobial Drugs Advisory Committee; June 6, 2019; Silver Spring, MD.

3. The Review on Antimicrobial Resistance. Tackling Drug- Resistant Infections Globally. May 2016.

4. World Health Organization (WHO). Global TB Report 2018.

5. Fox W. Studies on the treatment of tuberculosis undertaken by the British Medical Research Council Tuberculosis Units. Int J Tuberc Lung Dis. 1999;3(10):S231-S279.

6. U.S. Food and Drug Administration. Drug Approvals and Databases. Available at: https://www.fda.gov/drugs/development-approval-process-drugs/drug-approvals-and-databases

Image Credits: TB Alliance.