Digital health holds the potential to transform health systems so that they become more proactive and responsive to patients, advocates said at Wednesday’s launch of a two-day international conference that brought together members of the global healthcare and artificial intelligence (AI) communities in Switzerland’s pharmaceutical industry hub, Basel.

But using AI doesn’t inherently empower women or other vulnerable groups, some speakers and participants also pointed out. Policies have to be shaped to ensure that such technologies advance equity and access to health care.

The two-day Intelligent Health 2019 conference, organized by Novartis Foundation, brings together experts from some 67 countries, as well as representatives of the World Health Organisation, and other international agencies, along with tech giants such as Google and Microsoft.

“Digital tech can transform our health and care systems from being reactive to becoming proactive and even predictive. That’s the challenge the Novartis Foundation is now fully focused on,” said Dr. Ann Aerts, Head of the Novartis Foundation, speaking about the conference aims in a blog.

“Some of the biggest medical and health problems in the world today can be solved by harnessing the power of AI, big data and digital solutions. We have the potential to unite multi disciplinary groups ….from governments, corporates, healthcare providers and global clinician communities to radically transform the quality of lives globally” said Sarah Porter, CEO & Founder of Inspired Minds, a conference co-organizer.

However, like all innovations and technologies, AI is neutral, and humans have to ensure that it is used for everyone’s benefit, others emphasized.

“In order for AI tools to actually impact health outcomes positively, the algorithms need to be diverse and inclusive,” Stephanie Kukku, of UCL Hospital, London, was quoted as saying in a presentation.

Using AI doesn’t necessarily lead to the empowerment of patients, one participant pointed out in a tweet:  “We need to acknowledge the real barriers patients are facing to accessing quality care.”

 

 

Image Credits: A Health Blog.

Reducing pesticide self-poisonings is one of the most effective ways to reduce suicide deaths –the second leading cause of death among young people aged 15-29 years, after road injury, according to a new WHO report.

Release of the WHO report, Preventing suicide, a resource for pesticide registrars and regulators, coincided with World Suicide Prevention Day on Tuesday.

Photo: WHO

The report reflects the growing body of evidence that regulations to prohibit the use of highly hazardous pesticides can lead to reductions in national suicide rates. In Sri Lanka, a series of bans led to a 70% fall in suicides and an estimated 93 000 lives saved between 1995 and 2015. In the Republic of Korea – where the herbicide paraquat accounted for the majority of pesticide suicide deaths in the 2000s – a ban on paraquat in 2011-2012 was followed by a halving of suicide deaths from pesticide poisoning between 2011 and 2013.

Globally, there is one suicide death every 40 seconds. While 79% of the world’s suicides occurred in low- and middle-income countries, high-income countries have the highest rate, at 11.5 per 100 000, according to a WHO press release.

Globally, there are an estimated 10.5 deaths by suicide per 100 000 people a year. Rates varied widely, however, between countries, from 5 suicide deaths per 100 000, to more than 30 per 100 000. Nearly three times as many men as women die by suicide in high-income countries, in contrast to low- and middle-income countries, where the rate is more equal.

Image Credits: WHO.

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.

 

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.

[UNAIDS]

GENEVA, 14 August 2019—UNAIDS warmly welcomes the appointment of Winnie Byanyima as its new Executive Director. Ms Byanyima has more than 30 years of experience in political leadership, diplomacy and humanitarian engagement.

“I am honoured to be joining UNAIDS as the Executive Director at such a critical time in the response to HIV,” said Ms Byanyima. “The end of AIDS as a public health threat by 2030 is a goal that is within the world’s reach, but I do not underestimate the scale of the challenge ahead. Working with all its partners, UNAIDS must continue to speak up for the people left behind and champion human rights as the only way to end the epidemic.”

The United Nations Secretary-General, António Guterres, appointed Ms Byanyima as the UNAIDS Executive Director and United Nations Under-Secretary-General following a comprehensive selection process that involved a search committee constituted by members of the UNAIDS Programme Coordinating Board. The UNAIDS Committee of Cosponsoring Organizations made the final recommendation on the appointment to the Secretary-General.

Ms Byanyima brings a wealth of experience and commitment in harnessing the power of governments, multilateral agencies, the private sector and civil society to end the AIDS epidemic around the world. Ms Byanyima has been the Executive Director of Oxfam International since 2013. Prior to that, she served for seven years as the Director of Gender and Development at the United Nations Development Programme.

Ms Byanyima began her career as a champion of marginalized communities and women 30 years ago as a member of parliament in the National Assembly of Uganda. In 2004, she became the Director of Women and Development at the African Union Commission, working on the Protocol on the Rights of Women in Africa, an international human rights instrument that became an important tool for reducing the disproportionate effect of HIV on the lives of women in Africa.

She holds an advanced degree in mechanical engineering (in energy conservation and the environment) from the Cranfield Institute of Technology and an undergraduate degree in aeronautical engineering from the University of Manchester.

The Secretary-General wishes to extend his appreciation and gratitude to the UNAIDS Deputy Executive Director, Management and Governance, Gunilla Carlsson, for her service as the Executive Director, a.i.

Fifa Rahman, Unitaid NGO Delegation board member and PhD Candidate at the University of Leeds, moderated a panel at the recent IAS Conference on HIV Science in Mexico entitled “How To Fix Our Medical R&D Model: A Spotlight On TB Treatment.” The panel featured speakers from Médecins Sans Frontières’ (MSF/Doctors Without Borders) Access Campaign, Drugs for Neglected Diseases initiative, Treatment Action Campaign, Treatment Action Group, The International Union Against Tuberculosis and Lung Disease (The Union), and the Mexican National Institute of Health Sciences and Nutrition (National Institute Salvador Zubirán). Here, Rahman shares highlights from the panel on why the medical research and development (R&D) model needs to be ‘fixed’, as well as ways to go about fixing it, including greater transparency, new incentives for investment in R&D that are alternatives to intellectual property, and increased NGO and community participation throughout the research and development process.

Health Policy Watch: At the IAS Conference on HIV Science in July, you moderated a panel on how to fix the medical R&D model, with a focus on tuberculosis (TB). Can you describe some of the key themes discussed during the panel regarding what needs to be ‘fixed’ about the medical R&D model? What were some of the specific strategies or solutions presented to go about doing this?

​Fifa Rahman: The profit-driven medical R&D model means that so-called ‘poor nation’ diseases like tuberculosis are underfunded. And while there are 7 antibiotics for TB in the R&D pipeline, this is insufficient to address the sheer burden of the disease that we have today. In discussion of this broken R&D model, several themes emerged – notably the need for details on public funding into research of drugs to be made public and transparent; that other forms of delinkage to separate R&D costs from product prices, such as prizes for developing new antibiotics, be funded; and that companies license their drugs, including to the Medicines Patent Pool (MPP).

Paula Fujiwara from The Union spoke about the Life Prize, which is aimed towards delivering an affordable, short-course treatment regimen that is effective against all forms of tuberculosis. How this would work is that donors would put their monies into a prize fund, and this prize funding (pegged at US$ 30 million) would be given to companies producing drugs that enter clinical trials to develop a pan-TB regimen, and that also fulfil all predefined criteria, such as addressing stewardship concerns and licensing to ensure access. This plan is guided by principles of access and affordability, and removes the drug development process out of the faulty profit-driven system. It’s a brilliant idea – but needs political commitment from donor countries.

Sharonann Lynch from MSF Access was supportive of the Life Prize idea, and additionally spoke about the need to regulate the margin of income over the cost of manufacturing, and that countries needed to commit to transparency of the cost of R&D to make this work.

HPW: The need for public health-driven R&D has been a major theme this year, with intense debate over how best to achieve this in multiple United Nations fora, including the World Health Organization, the Human Rights Council and more recently the General Assembly in negotiating the political declaration on universal health coverage (UHC). Do you see progress taking place nationally and internationally in advancing public health-driven R&D, and if so how? If not, why not?

FR: It’s hard to say. On one hand you’ve got developed and developing nations, including Italy, Malaysia, Spain, Brazil, an entire African bloc of nations, and the United States, endorsing a World Health Assembly (WHA) resolution on drug pricing and research and development transparency, which is clearly a major milestone. We’ve also got increased visibility on drug pricing debates. High drug prices are no longer a developing country issue, with buyers clubs being established on the cystic fibrosis drug Orkambi in the UK, and people dying due to substitution of originator insulin in the United States. We also have some of Switzerland’s top university hospitals teaming up to tackle high CAR-T cancer therapy prices and offer them at a third of the cost.

On the other hand you’ve got the United Kingdom intensely resisting drug pricing transparency at the WHA, and uncertainty around Democratic Presidential Candidates in the United States, and how the election will go in 2020. Despite the diminishing global dominance of the U.S. for some time now due to the rise of emerging market nations, and of course China, the impact of United States’ regime-making capacity will be greatly dependent on who wins in 2020. For example, a Joe Biden presidency would be vastly different to an Elizabeth Warren presidency in terms of how the U.S. would advance public health-driven R&D internationally.

HPW: Intellectual property (IP) and patents are widely seen to be core drivers that incentivise R&D of new health products, and in this light are viewed by a range of actors as essential for innovation in public health, even while they can lead to monopolies that restrict affordable access to health products. What is your perspective on the role of intellectual property and patents in public health-driven R&D, and can you describe some of the challenges they pose, particularly when negotiated as just one aspect of much more comprehensive trade agreements?

FR: It’s no secret that there is a lot of patent abuse, over-patenting, and evergreening, and as a result patients are deprived of access to medicines which should now be off-patent. The system also encourages price gouging of which we’ve seen numerous examples, but which is particularly visible with stories like that of Tobeka Daki who died of breast cancer not having access to Herceptin.

Trade-related IP binds IP to enforceable regimes, and requires countries to increase intellectual property protection which enables price gouging and evergreening as described. But there are signs of hope. You see, trade-related IP responds to pharmaceutical markets, and as we move towards more biologic medicines and personalised medicines, the IP regime will respond accordingly. Over the past few years as we saw blockbuster drug lists increasingly dominated by biologic drugs, we saw the United States demanding specific intellectual property provisions for biologic drugs in the Trans-Pacific Partnership (TPP) and the United States-Mexico-Canada Agreement (USMCA). In the former, and as will be shown in upcoming research in my PhD, despite economic interdependence on the United States, countries including Australia, Malaysia and Chile formed strong coalitions based on common ideation rejecting intellectual property maximisation on biologics. So while trade-related IP responds to trends in the market, whether or not countries accept them is dependent on other political economy factors – including their economic interdependence on other large powers, the visibility and emphasis of drug pricing debates in developed nations, and the ability of developing nations to effectively utilise tools that can increase their bargaining power in trade negotiations.

HPW: You’re currently serving as a board member of Unitaid on behalf of the NGO delegation. Can you explain why Unitaid, a major global funder of public health-driven R&D, includes an NGO representative as well as a Community representative in its Executive Board? Do you think the medical R&D system can do better at including NGOs and affected communities in its R&D process, and if so how? Do you think this may also help to fix the medical R&D model?

FR: The Unitaid NGO Delegation represents NGO entities and experts within those entities, and the Communities Delegation represents communities living with the diseases. Both of these delegations play a very important role within the decision-making body of Unitaid because they bring unique perspectives to grant approval and governance processes.

As the Board Member for the NGO Delegation I can speak on its behalf but not the Communities, and I can say that the NGO Delegation draws upon expert opinion from over 200 NGOs across the world, including input on whether there are already suitable generics for a proposed investment; whether there is proper waste disposal for plastic canisters from malaria indoor spraying; whether the underinvestment in TB is best served by projects on digital adherence technologies; or whether we would be better placed investing in something like the Life Prize or investing in fixing broken paediatric pharmaceutical procurement systems. We also frequently engage with Unitaid grantees – which I think increases the robustness of our feedback to the Board and Secretariat. Alongside the role of the Communities and NGO Board Members, we always hope and expect that the other Board Members, and especially the Secretariat, also find ways to consult directly with NGOs and affected communities to sharpen their approach to ensuring affordable medicines and diagnostics.

We as a Delegation think that NGOs should be consulted more upstream in the R&D process, precisely because of our insight into access, affordability, and equitability issues, as well as to ensure that new medicines and diagnostics are designed in a manner that is best suited to use in particular settings, or to ensure that such products are acceptable to the people who must ultimately use them.

As to the question on ‘how?’ – there are a few approaches. One promising avenue is to ensure prominent NGO and community participation at the WHO as it continues to update and expand the Health Product Profile Directory, which was launched by TDR, WHO’s Special Programme for Research and Training in Tropical Diseases, earlier this year. It is also important that major public funders of R&D, whether in the U.S., Europe or elsewhere, find ways to consult and work directly with NGOs and communities – especially since so many of the crucial inventions that are ultimately brought to the market are brought forward by intramural or extramural research hosted by these institutions. Finally, major philanthropic funders such as the Wellcome Trust and the Gates Foundation, and many of their key recipients, and in particular product development partnerships, can play a crucial role in ensuring the participation of communities and NGOs both upstream and also as products enter the market, where their contributions are equally needed.

Such interventions can help to ensure that medical R&D, as far as initial investments made in the public sector and philanthropies, are more attuned to the needs of communities at the outset. Yet the breakdown of the R&D model requires much deeper changes to how R&D is conducted, including a need to search for incentives outside of intellectual property; the importance of public health funders demanding a public return on public investment; a need to promote transparency across the R&D process; and much more substantial political will of governments to both balance the power of pharmaceutical companies and to bring down prices of new medicines and vaccines when these other interventions fail to ensure affordability of new medicines.

Fifa Rahman is the Board Member for NGOs at Unitaid, working on good governance, timeliness of investments, and procurement transparency, among other things. She was formerly the head of policy at the Malaysian AIDS Council, and worked on a HCV compulsory licence. She is now based in the United Kingdom working on a PhD on trade negotiator tactics in intellectual property negotiations at the University of Leeds.