React Africa 2019: Universal Health Coverage Can Help Combat Antimicrobial Resistance

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 CentreWellcome 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.

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