A legacy of progress in clinical pharmacology and social justice; remembering Peter Ian Folb

There are few effective and safe therapeutics for diseases that disproportionally affect impoverished populations, such as malaria and other neglected tropical diseases. But even these few therapeutics would not have been available without a critical mass in clinical pharmacology skills and a strong regulatory environment in the countries where these diseases are most prevalent.
The late Emeritus Professor Peter Ian Folb (1938–2022) was a visionary and a leading authority on the scientific basis of drug development, both as an academic and within medicines regulation. In 1996, he enabled the University of Cape Town Department of Pharmacology to become a World Health Organization (WHO) Collaborating Centre for Drug Policy and Research into Drug Development and Drug Safety, in conjunction with its sister department at the University of the Western Cape. This centre was the first WHO centre of its kind on the African continent and among low- and middle-income countries.
For 18 years, Folb was Chair of the South African Medicines Control Council. He advised on improvements to drug regulation and drug policy in 42 African and three European countries. He investigated and unravelled the apartheid government’s chemical and biological warfare programme for the South African Truth and Reconciliation Commission. Despite considerable political pressure, he led the Medicines Control Council’s principled stand of halting human trials on Virodene, a controversial drug based on a toxic industrial solvent that was claimed to be a treatment for human immunodeficiency virus, but that lacked sufficient evidence of efficacy or safety. He was awarded an honorary Doctor of Science degree by the University of Cape Town in 2016.

Folb was professor and head of the University of Cape Town Department of Clinical Pharmacology and chief specialist in internal medicine at Groote Schuur Hospital, Cape Town (1976–2003). Many of those who were influenced and guided by his vision continue to demonstrate the vital role that clinical pharmacology can play in the development and rational use of essential medicines to improve public health.
Folb played a leading role in developing the national drug regulatory framework and essential drugs programme, which underpins the rational use of quality-assured medicines. He published several books on drug safety, and for many years was co-editor of Meyler’s side effects of drugs – the international encyclopaedia of adverse drug events.
From 1993 onwards, Folb served on several international scientific committees. He was a member of the Drugs for Malaria committee, where he contributed to the scientific and strategic development of new treatments for malaria. He was also Chair of the WHO Special Programme for Research and Training in Tropical Diseases Special Task Force for Research into Severe Malaria. He held meetings with African regulatory authorities and directed the development of rectal artesunate as a pre-referral treatment of life-threatening severe malaria in infants and children in remote malaria-endemic settings where injectable treatment was not promptly available.

From 1997 until his retirement, Folb was director of the South African Medical Research Council Traditional Medicines Research Programme. He led the development of integrated primary health-care guidelines for both traditional and allopathic health-care professionals and received two innovation awards from the Department of Science and Technology for the development of novel medicines from medicinal plants in southern Africa. His boundary-breaking work researching traditional medicines using rigorous scientific standards recognized and rewarded the intellectual property of the communities that identified medicinal plants.
In addition to his 1997–1999 work for the South African Truth and Reconciliation Commission, Folb made other important contributions to promote a more equitable society and redress past injustices. For example, he challenged the South African Medical and Dental Council about the death in police detention of anti-apartheid activist, Steve Biko.

Folb balanced art and science, the personal and the professional. He wrote Haiku poetry, painted and created woodcuts, was a marathon runner, and an inveterate walker and a swimmer. He often said that when one walks fast for over 40 minutes, the brain switches to right-sided dominance. That is the time for solving problems and thinking strategically.
Throughout his life, he exemplified the best that a committed clinician scientist with unwavering integrity can contribute to advancing knowledge, health, and challenging social injustice. 

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Top Scholars in South Africa Honoured

Twenty-nine of the country’s leading scholars and scientists were inaugurated as Members of the Academy of Science of South Africa (ASSAf) at the annual Awards Ceremony on the 19th October 2022 and Karen Barnes, Professor in Clinical Pharmacology at the University of Cape Town has made the list.

As the official Academy of South Africa, ASSAf has a core function to honour the country’s most outstanding scholars by electing them to Membership of the Academy. ASSAf Members are drawn from the full spectrum of disciplines.

New Members are elected each year by the full existing Membership. Membership of the Academy is a great honour and is in recognition of scholarly achievement. Members are the core asset of the Academy and give of their time and expertise voluntarily in the service of society.

African Union releases embargoed 2021 Malaria Progress Report

On the eve of the 35th Assembly of the African Union, the African Leaders Malaria Alliance (ALMA), the African Union Commission and the RBM Partnership to End Malaria are excited to share with you the embargoed 2021 African Union Malaria Progress Report.

The report, which will be presented to Heads of State and Government during the AU Summit this weekend, provides an update on the status of malaria on the African continent. It highlights activities undertaken, challenges faced, best practices learned by AU Member States and their partners to sustain malaria services and accelerate progress towards the goal of eliminating malaria in Africa by 2030. This report also provides updates on requests and calls to action made by the African Union Assembly.

Frank Kagoro and Professor Karen Barnes from CCOAT have published a new study with international colleagues highlighting the need for more rapid dissemination of molecular marker data to monitor artemisinin resistance

Study calls for rapid sharing of data to monitor artemisinin resistance.

A new study has highlighted the need for more rapid dissemination of molecular marker data to monitor artemisinin resistance. The paper, Mapping genetic markers of artemisinin resistance in Plasmodium falciparum malaria in Asia: a systematic review and spatiotemporal analysis, was published in the Lancet Microbe.

The study, conducted in Asia, aimed to develop up-to-date spatial distribution visualisations of the Kelch-13 (K13) markers of artemisinin resistance for policymakers to guide policy decisions. Researchers collated data from 72 studies published between 1 January 2010 and 31 March 2021, comprising K13 markers from 16,613 blood samples collected from 1991 to 2020 from 18 countries. Findings showed a steady increase in the prevalence of 'WHO-validated' K13 markers, reaching 62∙9 per cent in 2018. Overall, the prevalence of C580Y mutation increased from 48∙9 per cent in 2002 to 84∙9 per cent in 2018. Data showed that from 2002 to 2018, there has been a steady increase in geographic locations and the proportion of infected people with 'validated' artemisinin resistance markers.

Pictured above: Dr Frank Kagoro

Using mathematical modelling to fight malaria

Researchers have created a mathematical model to predict genetic resistance to antimalarial drugs in Africa to manage one of the biggest threats to global malarial control.

Malaria is a life-threatening disease caused by parasites and spread to humans through infected mosquitos. It is preventable and curable, yet resistance to current antimalarial drugs is causing avoidable loss of life. The World Health Organisation estimated there were 241 million cases of malaria worldwide in 2020, with more than 600,000 deaths.

In research published today in PLOS Computational Biology, an international research team used data from the WorldWide Antimalarial Resistance Network (WWARN), a global, scientifically independent collaboration, to map the prevalence of genetic markers that indicate resistance to Plasmodium falciparum – the parasite that causes malaria.

Lead author Associate Professor Jennifer Flegg from the University of Melbourne said malaria has devastating impacts on lower-income countries and effective treatment is key to elimination.

“The antimalarial drug sulfadoxine-pyrimethamine (SP) is commonly used in various preventative malaria treatment programs in Africa, particularly for infants, young children and during pregnancy. But we know its efficacy as a treatment is threatened in areas where resistance to SP is high,” Associate Professor Flegg said.

“The statistical mapping tool we have developed is critical for health organisations to understand the spread of antimalarial resistance. The model takes in the data that is available and fills in the gaps by making continuous predictions in space and time.

“Health agencies can use this tool to understand when and where SP is appropriate to use as part preventive malaria treatments and where other antimalarial methods may need to be explored.”

Professor Karen Barnes, Head of WWARN Pharmacology and Elimination, said there is a rapidly increasing need for malaria chemoprevention (drugs that prevent malaria infections), but there are limited treatment options available.

“This timely evidence of the extent of SP resistance across Africa will help to inform where SP preventive treatment, alone or in combination with other antimalarials, would be most likely to have the greatest impact,” Professor Barnes said.

Professor Feiko ter Kuile, Head of WWARN’s Malaria in Pregnancy Scientific Group, said the updated model of SP resistance in Africa was long overdue.

“A lot of the resistance mapping has understandably focused on the emerging resistance to the artemisinin-based antimalarials used for treating malaria. Increasing resistance of the malaria parasite to sulfadoxine-pyrimethamine in Africa has been a concern for several decades. However, easily accessible resistance data was lacking,” Professor ter Kuile said.

“This study combines all the available SP resistance data from the last two decades in a single model. It allows national malaria control programmes and researchers to get much-needed data on the degree of resistance in a given area in a given year. This allows us to understand better the impact of sulfadoxine-pyrimethamine resistance on the effectiveness of these preventive interventions and determine if and when to consider alternative drugs for chemoprevention.” - This is an extraction from the original Scimex article dated 12th August 2022. 

Reaching the unreachable with malaria treatment.

A special permit now allows specially trained malaria programme staff to treat malaria cases, advancing malaria elimination efforts by reaching more of those infected and treating them earlier.

South Africa has set the ambitious target of eliminating the local transmission of malaria by 2023. Currently local malaria transmission occurs along the north-eastern border regions of Limpopo, Mpumalanga and KwaZulu Natal provinces. A key step towards reducing the burden of malaria and advancing its elimination is the decision to permit Malaria Programme Environmental Health Practitioners (EHPs) to treat malaria cases. Up until now this has been the sole preserve of doctors and nurses.

Earlier this year the Director General approved a Section 22(A)15 application which permits malaria programme health workers on the ground (Environmental Health Practitioners, EHPs) to treat malaria cases and thus not only expand the number of professionals able to treat malaria, but also reach more of those infected and treat them earlier. Until now, malaria cases detected in the field were asked to go to the nearest health facility for treatment. However, many would go untreated as they were unable or unwilling to visit these health facilities. Travel costs were prohibitive, people did not appreciate the need for treatment as they were asymptomatic or, as undocumented migrants, they feared attending a public facility. COVID19-related concerns have further contributed to reluctance to seek malaria treatment promptly.

Delays in malaria treatment of even a few days can result in progression from uncomplicated to life-threatening severe malaria and increase malaria transmission in their community. This highlights the public health value of malaria treatment being provided in the field by EHPs, who are best placed to reach unreachable infections.

This intervention has been led by Professor Karen I Barnes, from the Division of Clinical Pharmacology and Founding Director of the UCT MRC Collaborating Centre for Optimising Antimalarial Therapy (CCOAT). She is co-chairs the South African Malaria Elimination Committee. The National Department of Health Directorate of Malaria, Vector- Borne and Zoonotic Diseases and the SAMEC Case Management sub-committee has been key in developing the application and progressing it through to signature by the Director-General. The Limpopo MEC for Health, Dr Phophi Ramathuba was the first to award her province’s malaria EHPs with training certificates, when she led the malaria team on door-to-door community rapid testing & treatment together with launch of indoor residual spraying season.

Most malaria programme EHPs have now been trained how to treat malaria, including the assessment of malaria disease severity, identifying those at higher risk of severe malaria and the appropriate use of first line treatment. UCT-accredited CPD certificates are being issued to those who have successfully completed this training. Pharmacists at selected hospitals who will be responsible for the weekly supply of patient-ready packs of artemether-lumefantrine to trained EHPs have also been trained. Thus, the malaria programmes are now poised to roll out EHP treatment of malaria cases detected during routine field surveys. 

This achievement, together with community health workers now being trained to perform malaria rapid diagnostic tests, will enable the malaria programme to reach most malaria infected individuals and significantly decrease the malaria parasite reservoir. These are key components for reducing the burden of malaria and advancing its elimination in South Africa.


Above: Prof KI Barnes with Mr QE Mabunda, Director of the Limpopo Malaria Elimination Programme at EHP training event. 

AboveEHPs receiving training certificates from the Limpopo MEC for Health, Dr Phophi Ramathuba

CCOAT and IDDO/WWARN TDR post-doctoral fellow led malaria workshop

CCOAT and IDDO/WWARN TDR post-doctoral fellow Dr Daniel Yilma presented his latest malaria research at a recent workshop in Ethiopia. CCOAT’s Professor Karen Barnes presented on ‘Single low dose Primaquine for transmission blocking – to advance elimination’ and Professor Ric Price and Dr Kamala Ley-Thriemer, Menzies School of Health Research, discussed their work on ‘The Challenges in Plasmodium vivax malaria elimination’

Dr Daniel Yilma, pictured above, lead organizer of the workshop from Jimma Univeristy with National Malaria Program of Ministry of Health jointly organized a workshop that was supported by WHO/TDR on 15th November 2021 at Capital Hotel, Addis Ababa, Ethipoia on "Safe and Effective Use of Antimalarial Treatment for Transmission Blockage and Radical Cure towards Malaria Elimination in Ethiopia: Evidences for Policy

The main aim of the workshop is for evidence dissemination to strengthen the policy and guideline on safe and effective radical cure and transmission blocking antimalarial treatment implementation in Ethiopia. The workshop was also designed to create a platform for collaboration, scientific dialogue and linking malaria researchers with policy makers and implementers.

The scientific presentation started with two presentations on the impact of radical cure and transmission blocking treatment for malaria elimination at global and regional level and moderated by Dr. Samuel Girma, USAID/PMI. The Challenges in Plasmodium vivax malaria elimination was presented by Dr. Kamala Ley-Thriemer and Prof. Ric Price, Menzies school of health research and Single low dose Primaquine for transmission blocking – to advance elimination was presented by Prof. Karen Barnes,  University of Cape Town. Read full article for more information.

The World Health Organization has recommended the widespread use of the RTS,S/AS01 (RTS,S) malaria vaccine among children in sub-Saharan Africa and in other regions with moderate to high malaria transmission.

Watch the video where Prof Karen Barnes Professor in the Department of Medicine: University of Cape Town and Co-Chair at the South Africa Malaria Elimination Committee and Prof Shabir Madhi, Professor of Vaccinology at Wits University discuss further.