NAIROBI – Neonatal sepsis is one of the leading causes of newborn deaths globally, and increasing pathogen resistance to available first-line treatments is a prime example of rising antimicrobial resistance.

That is why the Global Antibiotic Research and Development Partnership (GARDP) – a non-profit research organisation that develops new or improved antibiotic treatments – is seeking alternatives. GARDP’s first clinical trial of one such candidate, Fosfomycin, is taking place right now in the coastal region of Kenya to determine safety and appropriate dosing for infants.

GARDP’s research was one feature of a three-day conference that took place in Nairobi this week (23-25 July) on tackling antimicrobial resistance in Africa. The ReAct Africa and South Centre Conference, “Achieving Universal Healthcare While Addressing Antimicrobial Resistance,” drew together experts from 24 African countries to the event, co-sponsored by the United Kingdom-based Fleming Fund, along with the South Centre, Wellcome Trust, Swedish International Development Agency Sida, and others.

Antimicrobial resistance (AMR) is fast becoming a major public health problem worldwide. Estimates from a recent UN report suggest that up to 10 million people could lose their lives annually by 2050 if nothing is done to address the AMR threat, which can render anti-viral and anti-fungal medications, as well as antibiotics, ineffective. Along with overuse of medications in some countries, the lack of access to safe, affordable medicines in low- and middle-income countries can drive AMR, conference participants stressed.

“If we don’t address the problem of the inappropriate use and misuse of antibiotics then this is leading us to more untreatable infections, as well as infections that are more costly and difficult to treat,” said Viviana Muñoz Tellez – Coordinator, Health, Intellectual Property and Development Programme South Centre during the conference.

Lack of Data on AMR a Major Barrier

Addressing this problem means formulating appropriate policy, which ultimately is informed by data. However, availability of AMR data, especially in developing countries has been, and continues to be, a challenge. So generating better data is one key area in which players in the antimicrobial debate are increasingly focused. This is particularly true of the Wellcome Trust, a research charity organisation based in the UK, which has made surveillance and monitoring of AMR one of the pillars guiding it’s 5-year AMR programme.

“We are trying to build an evidence-base and improve data that is available for all sorts of decision-making – at the clinical level, at the doctor-patient level and policy-making levels,” said Jeremy Knox, Policy and Advocacy Lead on AMR at Wellcome Trust. Welcome Trust is working with WHO as well as research and civil society institutions around the world to explore how it can make better use of alternative and conventional sources of data. This includes data from the private and pharmaceutical sectors, as well.

Wellcome has also been supporting efforts to develop country by country evidence of what is the health burden of AMR today. And it is working with the Innovative Medicines Initiative (IMI) to improve rapid diagnostics, which can help ensure the right treatment and avoid unnecessary use of antibiotics.

Presenting political leaders with the data and the evidence showing why AMR is such a significant problem will help them prioritise actions to address the issue, Knox said, adding: “We are interested in behaviour change… We are trying to understand how we can turn awareness into lasting behaviour change, how we we can bring behavioural science to bear in AMR, be that public behaviour or even veterinarian behaviour.”

Jeremy Knox, Policy Advocacy Lead on AMR at Wellcome Trust

Counterfeit & Substandard Medicines Another Major Driver 

While overuse or misuse of antibiotics play a major role in the evolution of microbes, the same is true of the use of counterfeit and substandard medicines. This is a major contributing factor in exacerbating resistance, said Philip Nguyen, Director of the Quality Institute, US Pharmacopeial Convention (USP).

“There is a common saying in the US that what doesn’t kill you, makes you stronger. This is true of microbes [which go] through an incomplete course of antimicrobial treatment,” said Nguyen, who is also Advisor to MedsWeCanTrust Campaign (MWCT), a platform promoting the right to safe and quality medicines.

Counterfeits and substandard medicines may not have sufficient active ingredients to kill the pathogen in question. In other instances, they may not even contain any active parts or ingredients in the first place. Or, they may have the wrong type of active ingredients, in which case, they could be the wrong drug used to treat the problem.

“Either way, you are creating a system or environment to encourage resistance for microbes, which may lead to overuse of drugs” he explained. According to Nguyen, the need to prevent, detect and respond to pathogen resistance cannot be overstated. But the need to understand the complex interactions between counterfeit drugs and the human body is equally important.

“That is why there is active research happening all around the world, which USP is a part of, that tries to find out what happens when the body interacts with substandard or broken down components of medicine,” said Nguyen. He called for better market surveillance of drugs, especially the substandard versions, which is the job of regulators and regulatory systems.

Philip Nguyen, Director of the Quality Institute, US Pharmacopeial Convention

How Universal Health Coverage Can Combat AMR

Universal health coverage can therefore lead to better AMR control – by assuring people’s access to a reputable supply of medicines – and to advice from medical practitioners about how they should be used. Ghana is one example of this principle in action. It has provided health insurance coverage for the majority of its population – 18 million people out of a population of 28 million.

As a result, pregnant women and infants are now able to access healthcare at zero cost, courtesy of the universal health insurance programme, initiated in 2006. Since the programme also provides for key drug products free of charge, through hospital suppliers, patients do not have to buy products themselves from the pharmacy.

“All you need to do is simply present the health insurance card when seeking treatment and the medicine is provided free of charge,” said Boi Kikimoto, Head of Public Health and Food Safety, AMR Focal Point of Ghana. According to Kikimoto, provision of health insurance will go a long way towards addressing the issue of self-medication, which can in turn lead to over-use or misuse of drugs, resulting in antimicrobial resistance. Funding for this insurance programme comes from a small value-added tax imposed on goods and services sold in the country.

Repurposing Medicines to Combat AMR-Resistant Bacteria

As for the GARDP study of Fosfomycin, it is an example of the kind of research that needs to be done to find alternative treatments in cases where pathogen resistance has already developed. This is already the case for neonatal sepsis, a bacterial infection of the blood – where the WHO recommended treatment regime has not been updated in more than 50 years, and pathogen resistance to the first line of treatment, Ampicillin and Gentamicin, has already become significant in East Africa and South-East Asia.

Fosfomycin is approved in Europe and the US, but only for the treatment of uncomplicated urinary tract infection or cystitis. It has also been shown to be efficacious against neonatal sepsis. However, there is no information on neonatal safety and dosing for sepsis.

The Kenyan study of the safety and pharmacokinetics (the movement of a drug in and out of the body) of Fosfomycin will establish this information. This will also serve to generate data on drug resistance and effectiveness or lack thereof of the new treatment.

“GARDP is re-purposing an existing drug (Fosfomycin) for use in a combination regimen for the treatment of clinically diagnosed neonatal sepsis,” explained Dr. Monique Wasunna, Director of the Africa Regional Office of Drugs for Neglected Diseases initiative (DNDi).

GARDP was founded in 2016 by DNDi in partnership with the World Health Organization (WHO). It was hosted within DNDi before becoming a legal entity in 2019. GARDP is also conducting a global observation study in 19 sites in 11 countries to collect clinical information on confirmed sepsis in up to 3,000 newborns.

“So, we are trying to perform clinical trials to find out if a combination of Fosfomycin and another drug might be a better alternative to Ampicilin/Gentamicin that is currently being used,” reiterated Wasunna. The pharmacokinetics study is over – enrollment having been completed in February this year.

Once the safety issues of treatment are resolved and the pharmacokinetics results are satisfactory, a bigger clinical trial of the combination therapy will follow in a number of countries. In addition to Kenya, the study will be conducted in Uganda and Thailand – countries that have Ampicilin/Gentamicin as the first line treatment against neonatal sepsis.

“So, we are just doing the safety analysis and hopefully we will have the results by the end of August,” explained Wasunna. The new, bigger study involving several countries will potentially take place in 2020. It will take another two to three years before the effectiveness of a combination therapy involving Fosfomycin is known.

The first, smaller study in Kenya involved 120 patients, half of whom were put on Fosfomycin medication. The other half were on the current Ampicilin/Gentamicin regimen. However, the Phase III clinical trials will involve a minimum of 100 participants in each country taking part.

Lucy Andrews, Head of The Fleming Fund addresses the 2019 ReAct Africa and South Centre Conference by video, while Mirfin Mpundu, Conference Head, looks on from podium

Image Credits: GARDP, Geoffrey Kamadi.

[Wellcome Press Release]

A world-first research project will unravel how human embryos develop in the first weeks and months after fertilisation, improving our understanding of fertility, birth defects and regenerative medicine.

The £10 million Wellcome-funded Human Developmental Biology Initiative (HDBI) will build a ‘family tree’ of how cells divide and specialise following fertilisation*, to understand how tissues and organs develop and reveal new insights into how this process can go wrong.

Coloured scanning electron micrograph of a human embryo at the eight-cell stage. Photo: Science Photo Library

Around 3% of babies are born with developmental defects – problems that often start very early in pregnancy such as heart defects, spina bifida and cleft palate. But we know very little about why and how they happen.

The Initiative will create ‘family histories’ of cells from four particular time-points in development or organ systems – the early human embryo, the brain and spinal cord, the blood and immune system, and the heart and lungs.

For many years, developmental studies have relied on cellular and animal models. While this has provided important information, it’s also become clear that our understanding of early human development remains extremely limited.

To address this, the HDBI will tackle some of the biggest challenges that are holding the field back. Very few labs have access to human embryo tissue samples meaning that key pieces of research that will underpin the field have yet to be carried out. And when available, this tissue is incredibly diverse, reflecting the genetic and environmental origins, making insights hard to define.

By bringing the research community together, along with recent advances in embryo and organoid models, more sophisticated imaging techniques and genome editing mean that researchers can now gain an unprecedented insight into human development.

Professor Rick Livesey, based at UCL and one of the researchers leading the HDBI, said: “We know surprisingly very little about how humans develop. By understanding what is ‘normal’ in development we will be able to see how things can go wrong, offering new avenues for research. In addition, the insights from this work could help regenerative medicine reach its full potential.”

The project will involve donated human embryos and human foetal tissue. The UK has a strong regulatory and legal framework and the HDBI will work within and respect these regulations. The Initiative will actively work to consider the ethical issues raised by this growing area of research and includes a specific ethics programme and public engagement programme.

Andrew Chisholm, head of cellular and developmental science at Wellcome, said: “This new initiative brings together a diverse group of biologists from across the country to share their expertise and work together to build a ‘family tree’ of how different cells and tissues come together to form organs. This will create a treasure trove of data and technologies that will be made available to the community.

“Thanks to new techniques and technologies to study human development the HDBI will provide insights that could help our understanding of developmental disorders

The Human Development Biology Initiative is a five-year programme which involves researchers from UCL, the Francis Crick Institute, the Babraham Institute, University of Oxford, the University of Cambridge, the University of Dundee and the University of Newcastle. In addition, it will partner closely with the MRC-Wellcome Human Developmental Biology Resource.

Image Credits: Science Photo Library.

WHO’s declaration of the Ebola outbreak in the Democratic Republic of the Congo (DRC) a Public Health Emergency of International Concern has been shadowed by growing questions over vaccine strategy in a crisis that has dragged on for over a year, and now threatens to spread across borders. Until now, a ring vaccination strategy focusing on health workers and direct contacts of Ebola victims has been used, but questions are growing over whether that can really snuff out the epidemic, and whether a second vaccine should also be deployed alongside the first-line Merck vaccine that has proven so highly effective. Two senior Médecins Sans Frontières (MSF/Doctors Without Borders) officials – Dr Isabelle Defourny, MSF Director of Operations, and Dr Anne-Marie Pegg, Clinical Lead for Epidemic Response and Vaccination, who is currently in DRC – unwrap these issues here.

Nurse preparing the Merck Ebola vaccine in Bikoro, DRC, in 2018. Photo: MSF/Louise Annaud

Health Policy Watch: What’s happening with the response to the Ebola epidemic in DRC?

Dr Isabelle Defourny

Dr Isabelle Defourny: The Ebola epidemic in east Democratic Republic of Congo is still not contained. More than 1,600 deaths from the Ebola virus have been reported since the outbreak was first declared on August 1, 2018, and, during the first seven months of the epidemic (August 2018 to March 2019), over 1,000 confirmed and probable cases were declared. Between March and June 2019, this number doubled, with 1,000 new cases in what’s a short period of time. The end of April was the peak, with more than 120 cases a week. There’s still a huge amount of new cases, between 75 and 100 every week. In a context like this, it’s extremely difficult to accurately track the epidemic’s chains of transmission.

During the outbreak in 2014, all that could be done was to isolate patients and administer them largely ineffective drugs. With the vaccines and experimental drugs available to us in 2019, we’re now able to offer people the chance to protect themselves individually as well as access to promising treatments.

According to the information provided after the epidemic broke out, most confirmed cases’ personal contacts were vaccinated and then monitored by the Ministry of Health’s teams. Very probably, this helped contain the epidemic for a while. It’s the first time vaccination has been implemented on such a large scale, which is an extremely positive development.

HPW: Is this approach still possible today?

ID: Let’s say it needs to be adapted and enhanced. Right now, “ring” vaccination is being used. This entails vaccinating anyone who’s been in contact with someone infected with Ebola as well as all of their contacts. The reasoning behind the method isn’t bad per se. But, implementing it is time-consuming and challenging (problems with identifying each and every person’s individual contacts) and it’s not adapted to the insecurity affecting North Kivu. In addition, the number of people vaccinated is too small to contain the spread of the epidemic. The teams also have issues transporting from Kinshasa vaccines that must be stored at a constant temperature of -60°C.

HPW: A change of strategy is therefore necessary to contain the epidemic?

ID: Absolutely. In fact, in May, the SAGE group’s experts recommended modifying the vaccination strategy in DRC so that more people can be vaccinated. Until now, the main obstacle to implementing extended vaccination has been the small stock of Merck vaccine — the only one shown to be effective in an epidemic. According to the WHO’s latest information, 600,000 Merck vaccine doses are now available.* If this is the case, there’s no longer any good reason for not immediately stepping up vaccination.

People in DRC understand the usefulness of vaccination and, in fact, are asking to be immunised. However, with just around 50 contacts of one confirmed case vaccinated, it’s likely that only one-quarter to one-third of those at risk are protected. DRC’s stock of vaccines is extremely low, usually less than 1,000 doses. With its supply only sporadic, and issues with contact tracing, we’re not yet able to say this is an emergency response strategy.

Whereas some anticipate a rapid end to the epidemic, we see no signs to back up such predictions. Quite the contrary as there’ve been alerts only recently in Uganda and near the border with south Sudan.

Other vaccines exist. They should be tested in an epidemic zone to be prepared should this one spread and to be able to dispose of a wider range of vaccines in the event of future outbreaks.

HPW: Regarding the Johnson & Johnson vaccine – I understand it hasn’t been field tested as rigorously as the Merck version, and it takes longer to confer immunity, but once it does so, it actually protects against multiple strains of Ebola and is available in 1.5 million doses. Can you just clarify then the opportunities as well as communications barriers to deploying this now that a PHEIC has been declared; and if used in a periphery zone, periphery in DRC, or border zones of neighboring countries?

Dr Anne-Marie Pegg

Dr Anne-Marie Pegg: Obviously, with over 170,000 doses now administered, there is more data available with regards to vaccine tolerance, as well as “real-world” conditions for vaccination activity. It is true that studies of a similar scale and intent have not been conducted with the Johnson & Johnson vaccine, but immunobridging data (which refers to an evaluation of human immunogenicity against a model that describes immunogenicity and survival in non-human primates) supports clinical benefit. Additionally safety studies in well over 2,000 participants support the safety of the vaccine.

As mentioned, once the full 2-dose regimen is received, it protects not only against Ebola Zaire (the strain of virus responsible for this epidemic) but also other strains of Ebola virus, as well as Marburg (another hemorrhagic-fever-causing virus).

The optimal strategy for the deployment of this vaccine remains under discussion and review. If the vaccine were to be deployed in the “periphery” of the epidemic, this could mean zones that are neighbouring those currently experiencing high transmission (particularly those where population movements are known to be frequent). It could also be used in a preventative manner for front line health workers and others who may be at high risk in neighbouring countries (where the Merck vaccine has been deployed) in order to maintain the Merck stock for reactive efforts.

HPW: Regarding the Merck vaccine – what is hindering Merck production of more doses? Is it a financial barrier or something else? Particularly since this vaccine was developed with Canadian public funds and then merely purchased by Merck, it would seem there is a public obligation to speed things up. Finally in terms of counting remaining doses, of the original 300,000 vaccine doses made available some 170,000 were already administered. Then even if the dose was halved, it would seem that only about 430,000 doses (available now) remain at that?*

AP: That would need to be clarified with Merck directly. Recently there has been a renewed scale-up of production, with additional doses said to available in the early part of 2020. However the supply chain as to how many will be available and with what delivery schedule (all at once? several thousand per month?) remains unclear.

HPW: Anything else you care to note about the complexity of the community outreach mission on the ground. Please include any other messages that you believe are important.

AP: MSF supports expanding access to vaccination, regardless of the vaccine deployed in these efforts. Effective vaccine is one real innovation that has come out of research done in previous outbreaks, and it has the potential to significantly alter the course of the epidemic. Vaccination demand is high – but the current strategy is not well adapted to the actual epidemic situation. This is not a criticism of the efforts deployed by surveillance teams – it is the reality of trying to track a huge volume of people in a complex, often insecure context with high population density and significant population movement. A strategy more adapted to this context – such as geographic targeting of hotspots – needs to be deployed quickly and efficiently to rapidly scale up the numbers of at-risk people who are able to be vaccinated.

*According to a subsequent statement by Merck to Health Policy Watch, there are currently 245 1.0mL doses available now for shipment to the DRC, yielding 490,000 vaccines at the .5 mL strength currently being used by emergency teams, while more production is planned over the coming 6-18 months.

Dr Isabelle Defourny is a specialist doctor in gynaecology-obstetric and has worked in emergency and medical projects of MSF for nearly a decade. Isabelle is Director of Operations for MSF in France, a role she held since 2015.

Dr Anne-Marie Pegg has worked with MSF for 11 years in different contexts, including armed conflicts and epidemics, as emergency coordinator and medical coordinator. She is now part of the medical department of MSF in Paris.

Image Credits: MSF/Louise Annaud.

The Global Innovation Index 2019 was released today with an overarching theme of “Creating Healthy Lives – The Future of Medical Innovation.”

In addition to ranking countries according to their innovation performance on 80 indicators, this year’s Index also analyses the medical innovation landscape, and how emerging innovations, such as artificial intelligence (AI), genomics, and mobile health applications, will impact delivery of healthcare in developed and developing countries.

The Global Innovation Index 2019 found that overall, “Switzerland is the world’s most-innovative country followed by Sweden, the United States of America (U.S.), the Netherlands and the United Kingdom (U.K.),” according to a World Intellectual Property Organization (WIPO) press release.

The Index also identifies India, South Africa, Chile, Israel and Singapore as regional leaders, and found China, Viet Nam and Rwanda topping their income groups.

In the overview section, which introduces this year’s theme of “The Future of Medical Innovation,” the Index poses key questions the edition aims to address:

  • “What is the potential impact of medical innovation on society and economic growth, and what obstacles must be overcome to reach that potential?
  • How is the global landscape for research and development (R&D) and medical innovation changing?
  • What health challenges do future innovations need to address and what types of breakthroughs are on the horizon?
  • What are the main opportunities and obstacles to future medical innovation and what role might new policies play?”

From its analysis, five key messages emerge:

  1. “High quality and affordable healthcare for all is important for sustainable economic growth and the overall quality of life of citizens. While significant progress has been achieved across many dimensions over the last decades, significant gaps in access to quality healthcare for large parts of the global population remain.
  2. Medical innovations are critical for closing the gaps in global healthcare provision. These innovations are happening across multiple dimensions, including core sciences, drug development, care delivery, and organizational and business models. In particular, medical technology related innovations are blossoming, with medical technology patents more numerous and growing at a faster path than pharmaceutical patents for the last decade. However, some challenges need to be overcome—notably, a decline in pharmaceutical R&D productivity and a prolonged process for deploying health innovations due to complex health ecosystems.
  3. The convergence of digital and biological technologies is disrupting healthcare and increasing the importance of data integration and management across the healthcare ecosystem. New digital health strategies need to focus on creating data infrastructure and processes for efficient and safe data collection, management, and sharing.
  4. Emerging markets have a unique opportunity to leverage medical innovations and invest in new healthcare delivery models to close the healthcare gap with more developed markets. Caution should be taken to ensure that new health innovations, and their related costs, do not exacerbate the health gap between the rich and poor.
  5. To maximize the potential for future health innovation, it is important to encourage collaboration across key actors, increase funding from public and private sources, establish and maintain a skilled health workforce, and carefully evaluate the costs and benefits of medical innovations.”

“Innovation in the field of health is now being increasingly driven by data (Internet of Things) and artificial intelligence, in both diagnosis and prognosis. Unprecedented challenges need urgent attention in ethical, social and economic dimensions,” said Bruno Lanvin, INSEAD Executive Director for Global Indices and co-editor of the Global Innovation Index 2019, quoted in the press release.

“As the power of medical decisions moves farther away from medical professions, regulators, governments, business and civil society need to establish limits to the ways in which the holders of big data and advanced algorithms can make or influence health decisions. In the absence of swift action, innovation in health and medicine may become a significant source of inequality,” he said.

A United States congressional committee met today to vote on whether or not to recommend Andrew Bremberg for confirmation as Ambassador to the United Nations in Geneva. Bremberg is a controversial pick due to his extreme stance against abortion and his pledge to vote against any UN resolution that includes the right to abortion where legal, even in cases of sexual violence.

In the lead-up to the vote by the US Senate Foreign Relations Committee today, 38 US and international organisations sent an open letter to Senate leaders opposing the nomination of Bremberg and calling on all Senators to vote against his confirmation.

“The U.S. Ambassador to the United Nations in Geneva is a position of critical importance. The person occupying this role will be responsible for representing the U.S. in efforts to address some of the world’s biggest challenges, including health, human rights, and humanitarian crises and the resulting refugee and migration trends. Mr. Bremberg’s confirmation hearing, written responses, and previous record in government indicate he will not only obstruct, but actively work against the interests of individuals and communities worldwide who face the greatest barriers to sexual and reproductive health, rights, and justice,” stated the letter.

Andrew Bremberg responding to questions at the 20 June hearing of the Senate Foreign Relations Committee

Andrew Bremberg, currently serving as Assistant to the President and the Director of the Domestic Policy Council, previously worked as Aide to Republican Senator and Senate Majority Leader Mitch McConnell.

Today’s closed hearing vote will also determine the recommendation of Kelly Craft as US Ambassador to the United Nations in New York. Craft, who’s family own a major coal company and is a major Republican donor, currently serves as US Ambassador to Canada.

In an exchange between Bremberg and Senator Robert Menendez at the 20 June hearing of the Senate Foreign Relations Committee, Menendez cited the recent US threat to veto a UN Security Council resolution on gender-based violence in conflict over a reference to survivor’s access to sexual and reproductive health, asking: “Should victims of sexual violence be able to terminate the pregnancy where legal?”

Bremberg replied: “Senator, I don’t believe that abortion is a moral solution to any problem.”

Planned Parenthood Global responded in a Tweet saying: “The Trump admin continues to nominate anti-rights players to critical diplomatic positions, jeopardizing women’s and human rights protections. E.g. Andrew Bremberg, nom for US Ambassador to UN in Geneva, who opposes abortion even in cases of rape.”

Bremberg, a top pick of US President Donald Trump, is also chief architect of Trump’s expanded version of the “global gag rule,” an international policy that prohibits any foreign NGO that receives US funding from providing abortion services, counseling or referrals.

It requires these organisations to certify that they do not engage in abortion-related activities, and forces them “to choose between providing a comprehensive spectrum of reproductive health care and receiving critical US funding,” according to a report by the International Women’s Health Coalition, one of the signatories to the open letter.

Despite US attempts to restrict abortion services through the gag rule, evidence shows that the rule actually increased rates of abortion by 40 percent between 2001-2008 in areas where the policy was in effect, according to a recent study published in The Lancet Global Health. The study explains that this rate is associated with the rise of pregnancies in these areas, which are related to the policy’s impact on limiting family planning services including modern contraception.

After being rescinded by President Barack Obama in 2009, the gag rule was reinstated by President Trump in 2017 and renamed as “Protecting Life in Global Health Assistance.” Under this policy, the rule was expanded beyond just international family planning assistance to include all US funding for “global health assistance,” amounting to some US$ 9 billion.

According to the expanded policy, global health assistance “includes funding for international health programs, such as those for HIV/AIDS; maternal and child health; nutrition; infectious diseases, including malaria and tuberculosis; global health security; and voluntary family planning and reproductive health.”

A staunch advocate of the global gag rule, Bremberg, in his opening statement at the 20 June hearing, said: “If confirmed, I will advocate for reforms at UN organizations to protect US sovereignty and the broader world order we have fought so hard to create. We contribute more to the United Nations than any other country. It is our duty to ensure these funds are spent effectively, efficiently, and in a manner consistent with American values and interests.”

If recommended by the Committee in today’s vote, Bremberg’s confirmation will still be subject to a vote by the full Senate.

There is no shortage of Merck’s life-saving Ebola vaccine on the ground in the Democratic Republic of Congo, and more doses will be produced, sufficient to immunise 1.3 million people over the next 6-18 months, a spokesman for Gavi, the Vaccine Alliance, told Health Policy Watch on Tuesday. Meanwhile, Merck, producer of the V920 investigational vaccine, confirmed that it is ramping up production in both US and German production sites to make more vaccines available as soon as possible.

But those upbeat statements, contrast sharply with reports by Médecins Sans Frontières (MSF) from ground zero of the outbreak in the Democratic Republic of Congo, where vaccine stocks are reported to be “extremely low”, supply is “sporadic”, and a ring vaccine strategy focused on immunising contacts of Ebola victims is no longer sufficient to contain the disease outbreak, extending across some 500 square kilometres, and to the borders of Rwanda and Uganda.

Health worker administers Merck vaccine in Ugandan community of Kirombe, near DRC border.

Merck Says Vaccine Available Right Now for Shipment

“We have informed our collaborators that there are 245,000 1.0 mL doses currently in Merck control and available for shipment,” said Pam Eisele, a spokesperson for Merck, in an emailed response to a query by Health Policy Watch. Based on the current dosing strategy of .5mL, that would be enough vaccine to immunise nearly 500,000 more people.

“Beyond the doses already donated and shipped to the WHO, Merck is now forecasting a cumulative targeted investigational supply of ~900,000 1.0 mL doses over the next 6 to 18 months,” Eisele added. “These new doses will be produced by both leveraging efforts at our manufacturing facility in Germany as part of ongoing registration activities, and temporarily, leveraging a clinical manufacturing facility the company has in the United States.”

The Merck supply can cover “an additional 1,300,000 people” over the next 6-18 months, said a Gavi spokesman, noting the fact that the recommended vaccine dose has been halved from 1.0 mL to .5mL.

“We have not experienced any shortage of vaccine so far during this outbreak and there is enough vaccine on the ground to meet the current needs based on the current vaccination strategy,” said the spokesman, who asked not to be referred to by name. However, he cautioned that “whether or not the increased doses are sufficient to fulfill the demands depends on the evolution of the outbreak, access to the communities on the ground and evolution in vaccination response strategy.”

MSF Sees a Different Picture on the Ground

However, the Gavi and Merck statements contrast sharply with the picture painted by MSF field workers. In comments relayed from the DRC, Isabelle Defourny, MSF Director of Operations, said “DRC’s stock of vaccines is extremely low, usually less than 1,000 doses.”

“With its supply only sporadic, and issues with contact tracing, we’re not yet able to say this is an emergency response strategy,” she added, referring to last week’s World Health Organization declaration of the outbreak as Public Health Emergency of International Concern.

“People in DRC understand the usefulness of vaccination and, in fact, are asking to be immunised. However, with just around 50 contacts of one confirmed case vaccinated, it’s likely that only one-quarter to one-third of those at risk are protected,” she observed.

Defourny said that a broader vaccination strategy should be adopted, in line with recommendations already made by WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) in May, involving faster use of the Merck vaccine as well as “testing” of other alternative vaccines – a clear reference to a second formulation in-the-waiting, produced by Johnson & Johnson.

“The number of people vaccinated is too small to contain the spread of the epidemic,” Defourny said in her remarks, noting that contact identification must be carried out in communities in a contact zone, beset by high levels of mistrust.

“Until now, the main obstacle to implementing extended vaccination has been the small stock of Merck vaccine — the only one shown to be effective in an epidemic,’’ she said. “In May, the [WHO] SAGE group’s experts recommended modifying the vaccination strategy in DRC so that more people can be vaccinated. If, indeed, more doses are available, then “there is no longer any good reason for not immediately stepping up vaccination,” she stressed.

Issues of vaccine strategy and supply have dogged the Ebola crisis for the past 10 days.

At a high level meeting convened by the UN’s Office for the Coordination of Humanitarian Affairs on 15 July, Wellcome Trust’s Josie Golding suggested that the second trial vaccine, produced by Johnson and Johnson, and currently warehoused in Europe, should be deployed as a second-line response to combat the widening circle of infection, reserving the more limited quantities of the Merck formulation for front-line response.

However, DRC’s government, which must agree, has so far resisted introducing a second formulation, which some fear could fuel miscommunication after a hard-won battle to gain acceptance for the Merck vaccine, which has proven to be highly effective as well as fast-acting. The J&J formula, while apparently effective against more diverse strains of Ebola, takes much longer to provoke immunity and while it has been tested in healthy volunteers, it has not ever been deployed in actual field conditions.

On Monday, outgoing DRC Health Minister Oly Ilunga, blew open any semblance of unity between government and aid workers. In his parting remarks before resigning, Ilunga blasted what he described as pressures by unnamed actors to introduce the second vaccine, saying that it didn’t have the field record of the Merck formulation, and therefore would mean an “experiment” with people in the DRC.

Meanwhile, over 1700 people have died from the DRC Ebola epidemic since the outbreak began, including new cases daily over the past week, in the city of Beni and other areas in the North Kivu and Ituri regions where the outbreak has been centered. Some 729 people have recovered, according to the most recent DRC Health Ministry reports.

Image Credits: WHO/AFRO.

The 2019 ReAct Africa Conference on Antimicrobial Resistance (AMR), which opened Tuesday in Nairobi, Kenya, will focus on ways to advance universal health coverage while combating antimicrobial resistance (AMR) on the continent. Some 24 African countries are taking place in the three day event co-sponsored by the United Kingdom-based Fleming Fund dedicated to supporting low- and middle- income countries to tackle AMR, along with the South Centre, Wellcome Trust, Swedish International Development Agency Sida, and others.

The conference is tackling a wide range of policy issues that affect AMR response: from preventing and managing infections with effective water and sanitation strategies, to medicines quality and regulation; and AMR in the animal and environmental sectors. The conference will also showcase models of country success as well as gaps in National Action Plans when it comes to AMR responses needed to meet the threat of bacteria, viruses and other pathogens that are increasingly resistant to medications.

“AMR is increasingly becoming one of the key global challenges and at the same time the people in the developing countries will suffer the most,” said Viviana Muñoz Tellez, Coordinator, Health, for the South Centre’s Intellectual Property Development Programme, addressing participants during the plenary session. For more about the conference, see here:

(L to R) Olga Perovic, AMR Lead, National Institute for Communicable Diseases South Africa; Laetitia Gahimbare – World Health Organization, Africa Region; Andreas Sandgren, Deputy Head of Office, Policy Advisor, ReAct Europe and Marlon Banda, Pharmaceutical Services Churches Health Association of Zambia & Board Chairman field questions during the plenary session of the ReAct Africa and South Centre Conference 2019.

Image Credits: Geoffrey Kamadi .

The Democratic Republic of the Congo’s Health Minister, Oly Iluga, resigned Monday, following his removal Saturday as the head of the country’s Ebola response – after the country’s President Felix Tshisekedi placed management of the crisis under direct presidential supervision.

DRC Health Minister Oly Ilunga Kalenga speaking at the World Health Assembly in May 2019.

“As a result of your decision to place the response to the Ebola outbreak under your direct supervision… I hereby submit my resignation as health minister,” Oly Ilunga wrote to President Felix Tshisekedi, in a letter in French, posted on Ilunga’s Twitter page. “As in any war, because that is what this is, the lines of authority must be clearly identified and defined. There cannot be several centres of decision-making for risk of creating confusion…”

Iluga also voiced his concerns over the possible introduction of a second experimental vaccine into the battle against the deadly virus, calling it an “experiment.”

Proponents of introducing the second vaccine, produced by Johnson & Johnson, have pushed to deploy the 1.5 million available doses of the vaccine in peripheral zones where Ebola could potentially spread, reserving use of the field-tested Merck vaccine for front-line response.

Only 300,000 doses of the Merck vaccine have been produced, and more than 164,000 people have already been vaccinated; although since the original vaccine dose has since been reduced by almost half, estimates vary as to how many doses are left.

But Iluga said that it would be “illusory” to think that the new J&J vaccine, which requires two doses over the course of several weeks to provoke immunity, could play a decisive role in the course of the Ebola epidemic.

Iluga’s resignation followed on the heels of WHO’s announcement last Wednesday (17 July) of a Public Health Emergency of International Concern (PHEIC) during a week of heightened concern over possible spread of Ebola beyond the borders of DRC and into neighboring Uganda and Rwanda, as well as Burundi and South Sudan.

While no fresh Ebola cases have yet been reported outside of DRC, Uganda went on high alert after an infected fish-monger visited a Ugandan market in a border community on 11 July, repeatedly vomiting in the public market, before returning to DRC where she died on 15 July.

WHO officials said at last week’s press conference announcing the Ebola emergency that discussions were underway with the DRC government about deployment of the second vaccine. Previous Ministry of Health reservations had centred around concerns that introduction of a second vaccine might stimulate community misunderstandings, after a hard-fought campaign to win support for the use of the Merck vaccine in Ebola-affected communities. The Merck vaccine has been deployed in a “ring vaccine” strategy, immunizing health workers and community members suspected of having come into contact with other Ebola victims.

However, judging from the 32 new Ebola cases that were reported by the DRC Ministry of Health over just the past two days, Friday and Saturday, that strategy has not yet managed to break the chain of continued infection, particularly in the North Kivu city of Beni, where 16 of those new cases were reported. Some 1737 people have died so far from Ebola since the outbreak began on 1 August, while 729 have recovered, according to the most recent DRC Health Ministry report.

DRC Health Minister Oly Ilunga Kalenga’s letter of resignation, posted today on his Twitter account @OlyIlunga.

Image Credits: WHO/Cipriani.

A new BMJ study by French researchers has reinforced the link between consumption of sugar-laced sodas & fruit juices and cancer incidence, in particular breast cancer. The study – the largest ever of its kind – is significant because while the link between sugar consumption and diabetes, obesity, and hypertension has been well documented, there have been fewer studies on sugary drinks as a cancer risk, the authors note.

The BMJ study, “Sugary drink consumption and risk of cancer: results from NutriNet-Santé prospective cohort,” involving 101,257 adults, including 79,724 women, found an increase in daily sugary drink consumption of 100 ml was associated with a sharp raise of overall cancer incidence as well as of breast cancer.

According to Eloi Chazelas, co-author, “We observed that a 100mL per day increase in the consumption of sugary drinks (which represents a small glass) was associated with approximately an 18% increased risk of overall cancer, and approximately 22% for breast cancer.”

In specific sub-analyses, both pure fruit juices and other sugary drinks also were associated with an increased overall risk of cancer, he told Health Policy Watch.

Participants came from the French NutriNet-Santé cohort of an even larger Franco-Belgium study examining the relationship between nutrition and health, in terms of not only cancer incidence, but also cardiovascular diseases, diabetes, and hypertension.

The study began in 2009 with participants added on a rolling basis until 2018; some participants were followed for as long as 9 years, with a median period of 5 years, with the average age of participants 42 years.

The study examined consumption of 97 sugary drink items and 12 artificially sweetened beverage items. The sugary drinks included fruit juices comprising 100 percent fruit juice, without added sugar.

Asked about the study’s findings, WHO Senior External Relations Officer Menno van Hilten told Health Policy Watch that WHO has not so far systematically reviewed potential associations of sugar consumption with cancer risks. WHO has not been looking at cancer as an outcome of free sugars consumption yet,” he said, adding that WHO also doesn’t comment on individual studies. Rather, WHO works on systematic reviews of evidence once evidence has accumulated.

However, overall, WHO has been pressing for stronger policy measures to cut sugar consumption, including guidelines recommending strict limitations in sugar consumption, including in sugary drinks, due to its already well-documented links to obesity, diabetes and tooth decay. It has also supported policies to raise awareness on the health hazards brought by sugary drinks as well as policy measures that make healthier food choices cheaper and more accessible.

Sugar in Drinks: Why Can It Increase Cancer Risk, Not Only Diabetes?

Sugary drinks and the sugar they contain are already known risk factors for obesity, weight gain, insulin resistance, and increased proinflammatory markers, all of which are risk factors for cancer. But a direct link between sugary drinks and cancer has been less explored, according to the authors, with very few prospective studies conducted on the association between sugary drinks and individual cancer sites.

Mechanisms underlying a link between sugary drinks and cancer might involve insulin resistance, according to the study, as foods with a comparatively higher glycaemic index, cause a rapid rise in blood sugar levels, or glycaemic load, and have been linked with breast cancer, hepatocellular cancer, and diabetes-related carcinomas.

Additionally, sugary drink consumption tends to increase weight gain, further adding to their cancer risks: “Excess weight is a strong risk factor for mouth, pharynx, larynx, oesophageal (adenocarcinoma), stomach (cardia), pancreatic, gallbladder, liver, colorectal, breast (postmenopause), ovarian, endometrial, prostate (advanced), and kidney cancers,” the study notes, building on previous results.

But beyond weight gain, sugary drinks might promote gains in visceral adiposity independently of body weight, according to the study. Visceral adiposity, which refers to fat accumulation around the visceral organs, is responsible for much higher chronic disease risk than fat on the thighs, NutriNet-Santé study coordinator Dr Mathilde Touvier told Health Policy Watch.

At this stage, it seems the authors cannot say whether different types of sugar and their different sources produce different effects in the body, and additional research is planned in the context of a new project of the NutriNet-Santé study.

The study found that the median sugar content for sugary drinks was 10.7g/100ml, while most public health agencies set the recommended level at zero. Only water is recommended, even if unsweetened coffee or tea can also participate to the daily liquid intake.

Can the same conclusions be drawn about sugary foods and cancer? According to Touvier, very few studies have been carried out so far and the topic will be investigated in NutriNet-Santé soon.

100 Percent Fruit Juices Also in Culprit Group; What About Whole Fruits?

For those who thought that unsweetened fruit juices were healthy, the conclusion of the study is brutal. Making up 45 percent of all sugary drinks that are consumed overall, 100 percent fruit juices also were positively associated with an overall increased rate of cancer.

If fruit juice is unhealthy, why does WHO recommend eating at least 400 g, or five portions, of fruit and vegetables per day (excluding starchy roots)?

According to Touvier and Chazelas, “entire fruits contain more dietary fibres,” and this means that the body absorbs the sugar contained much more slowly, leading to a lower overall glycaemic load than for fruit juice. Whole fruits also help satiate the appetite more rapidly than juice, as they said “eating an orange is more efficient in filling the stomach than drinking the juice of one orange.”

100% fruit juices generally contain high levels of simple sugar, sometimes higher than regular soda, and their glycaemic indexes are higher than that of whole fruits, the study found.

The recommendation on fruit juices in France is “less than one glass per day.”

Artificial Sweeteners Off the Hook, Not a Blank Check

While study results partly exonerate artificially sweetened drinks, Touvier told Health Policy Watch that those results should be taken cautiously, because the number of consumers of artificially sweetened beverages was limited, as well as the amounts consumed.

Touvier, who also heads the Equipe de Recherche en Epidémiologie Nutritionnelle (EREN) in Paris, warned about drawing hasty conclusions about artificial sweeteners not having an impact on cancer incidence. “The message from this paper should definitively not be to switch from sugary drinks to artificially sweetened beverages.” The adverse cardiometabolic health effects of artificial sweeteners have been reported and some experimental studies suggested potential adverse effects, she explained, adding that further investigation is needed.

For example, there is a lack of human data on cocktails of artificial sweeteners and other food additives, and a large-scale project is being launched by NutriNet-Santé on that topic. In particular, chemical compounds in sugary drinks, such as 4-methylimidazole in drinks containing caramel colourings, could influence cancer incidence.

Policy Implications

Along with guidelines issued in 2015, WHO in 2017 issued guidance suggesting taxation of sugary drinks as a measure to help reduce overall sugar consumption and thus disease risks. Civil society groups also have been active in promoting food labelling and tax policies at the national level to reduce consumption of sugar and sugary drinks.

Last January, at the WHO Executive Board meeting, a large consensus formed in support of a recent WHO review of evidence on the effectiveness of taxes on sugar-sweetened beverages as a means to reduce sugar consumption. The review was part of a report following up on United Nations General Assembly’s high level meeting on the prevention and control of noncommunicable diseases (NCDs). The WHO drew on nine recent peer-reviewed studies of evidence of the impact of reducing sugar consumption through taxation of sugar-sweetened beverages at national and sub-national levels.

The WHO review examined the outcomes of taxes on included fruit juices and sweetened or flavoured milk-based drinks.

Only Italy and the United States pushed back against the findings, asking that the summary of evidence – on how taxes on sugar-sweetened drinks may help reduce unhealthy sugar consumption – be deleted from the progress report on tackling NCDs, and that public awareness-raising measures should rather be the focus of NCD prevention.

Vital Strategies, a large NGO working with governments, notes that there are currently 45 countries which have implemented taxes or levies on sugary drinks. In an interview with Health Policy Watch, Sandra Mullin, Senior Vice President of Vital Strategies for Policy, Advocacy and Communications explained different policy levers that can be used to curb sugary drinks consumption, and make healthier choices easier for consumers.

Besides taxes, other policy levers include restricting the marketing and availability of unhealthy products to children, clear warning labels, communication campaigns to create awareness, and other pricing and policies to make healthy food choice more accessible.

In a related development this month, the World Health Organization’s Regional Office for Europe raised alarm about the high level of sugar found in certain brands of baby foods, incorrectly marketed as suitable for infants under the age of six months.

Earlier this year, the BMJ published another study showing that tobacco industry giants built some of the leading sugary drink brands that have been marketed to children over the past 50 years, using marketing strategies developed by the tobacco industry.

Image Credits: PIXNIO.

[DNDi Press Release]

Geneva/New Delhi – 22 July 2019

The results of an innovative “infectivity” study conducted by the Drugs for Neglected Diseases initiative (DNDi) and the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) confirm that people successfully treated for visceral leishmaniasis in South Asia can still infect others if they develop a skin condition known as post-kala-azar dermal leishmaniasis (PKDL). The results were published in Clinical Infectious Diseases this week.

Patients can develop PKDL – skin lesions in the form of rashes and nodules – usually six months to one year after successfully completing treatment for visceral leishmaniasis, a deadly parasitic disease transmitted by sandflies also known as kala-azar, or black fever. PKDL lesions contain the same parasite that causes kala-azar. The objective of the study was to assess whether parasites in the skin of PKDL patients could be transmitted to the sandflies that transmit kala-azar.

“This is the largest study of its type to date. Until now, information on the role of PKDL was scarce and scattered across decades of different research initiatives,” said Dr Jorge Alvar, Senior Leishmaniasis Advisor at DNDi and co-principal investigator of the study. “The results unequivocally show that PKDL is of pivotal importance for maintaining transmission of the disease in-between epidemics.“

As part of the trial, PKDL patients allowed themselves to be bitten by laboratory-reared sandflies (which were free from infection) by plunging their hands into a cage for 15 minutes containing male and female sandflies. The sandflies were then analysed for the parasites that cause kala-azar.

The results showed that nearly 60% of the 47 PKDL patients in the study passed on the parasites to sandflies. This means the insects could then go on to infect someone else.

“Because PKDL is not fatal it has largely been ignored by public health efforts, and many scientific questions around its role have remained unaddressed,” said Dr Dinesh Mondal, Senior Scientist at the icddr,b and principal investigator of the study. “While these new findings don’t answer all our questions, they do show that early treatment of PKDL patients will be a critical element of any leishmaniasis public health and elimination strategy.“

People with PKDL sometimes remain untreated for a long time. Transmission of the disease could therefore be occurring even when kala-azar is controlled and small numbers are being reported.

“Great strides have been made in the control of kala-azar in South Asia, but this study shows that now we must engage in active PKDL case detection and provide prompt treatment as an integral part of kala-azar control and elimination,” said Dr Suman Rijal, Director of the DNDi Regional Office in India. “PKDL must be addressed in order to sustain elimination or we risk jeopardizing our earlier successes.“

Forty-seven PKDL and 15 kala-azar patients were tested by xenodiagnosis. The results showed that depending on the type of PKDL lesion, 35% (9/26) of the macular to 86% (18/21) of the nodular PKDL patients in the study passed on the parasites to sandflies (p 0,0009), while 67% of the 10/15 kala-azar control patients did. This means the insects biting the skin of a PKDL patient could then go on to infect someone else.

DNDi is now preparing a similar study in Sudan. DNDi is also running clinical trials to test two treatment regimens for patients with PKDL, in South Asia and East Africa, in a bid to make treatments simpler, safer, and more effective. Learn more

Read stories of people struggling with PKDL in Bihar state in India, one of the areas in the country most affected by kala-azar:

Story – The disease that strikes back

About DNDi

A not-for-profit research and development organization, DNDi works to deliver new treatments for neglected patients, those suffering with Chagas disease, sleeping sickness (human African trypanosomiasis), leishmaniasis, filarial infections, mycetoma, paediatric HIV, and hepatitis C. Since its inception in 2003, DNDi has delivered eight new treatments to date, including new drug combinations for kala-azar, two fixed-dose antimalarials, and DNDi’s first successfully developed new chemical entity, fexinidazole, approved in 2018 for the treatment of both stages of sleeping sickness.

Image Credits: DNDi.