Could yaws be the second disease to be eradicated?

Until a few years ago, yaws was such a neglected tropical disease that even infectious disease graduates from the most prestigious global health institutions had never heard of it. This was the case for Dr. Oriol Mitja, a Spanish doctor with a postgraduate diploma from the London School of Hygiene and Tropical Medicine (LSHTM). Soon after arriving on the island of Lihir in Papua New Guinea to fill a temporary job offer, Dr. Mitja encountered his first cases of the disease.

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Yaws is an infectious disease of the skin caused by the spiral bacterium Treponema pallidum, and belongs to a group of chronic bacterial infections generally known as treponematoses. The disease is transmitted through skin-to-skin contact and causes disfiguring ulcers, which when untreated, can penetrate cartilage and bone, resulting in long-term disability. 

Interestingly, yaws was one of the first diseases targeted for eradication by the World Health Organization (WHO) soon after its inauguration in 1948. The WHO led a successful campaign between 1952 and 1964 and saw the prevalence of the disease diminish by over 95% worldwide, from about 50 to 100 million cases down to 2.5 million. During this campaign, the disease was treated using a single dose of intramuscular (IM) benzylpenicillin. Unfortunately, as the disease was cleared from most high-income countries, funding and resources became scarcer, and the campaign was deemed ‘successful’ and abandoned. The remaining 5% of places with the disease were primarily remote areas, making delivery of treatment more challenging. Yaws became known as the disease “that begins where the roads end”.

“Yaws became known as the disease “that begins where the roads end””

After Dr. Mitja learnt about the disease from local health workers he started looking into the causative organism, investigating a close relative of Treponema pallidum, the subspecies that causes syphilis. He realised that oral azithromycin (a different antibiotic) had been proven to be effective in the treatment for syphilis and decided to assess its efficacy in treating patients with yaws. The use of azithromycin was particularly well-suited to administration in remote areas: the drug can be easily administered as an oral tablet, making it a more affordable and efficient alternative to IM benzylpenicillin. Treating yaws patients with azithromycin was an innovative and exciting idea, and marked a new hope in the efforts to eradicate the disease. 

In 2012, Dr Mitja and his team published a paper in The Lancet proving the efficacy of single-dose azithromycin to treat yaws compared to IM benzylpenicillin. Their paper was pivotal in the campaign for yaws eradication. In that same year, the WHO held a consultation to recommend mass treatment of yaws using single-dose oral azithromycin and set an ambitious aim to eradicate the disease by 2020. This new campaign has resulted in a significant decrease in prevalence of yaws in many endemic regions. A notable success of the renewed campaign is India achieving eradication of yaws in May 2016. 

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However, such a project, like anything involving antimicrobials, was a race against the clock: the sooner eradication could be achieved, the lower the risk of resistant strains developing against the newfound treatment. Unfortunately, when targeting neglected tropical diseases, one of the greatest hurdles remains funding. Despite the new findings, the project still required an estimated $1 billion to make yaws eradication achievable. Consequently, it took several years until the Brazilian pharmaceutical company EMS Pharma agreed to take on the project, pledging a donation of azithromycin to help in the efforts to tackle yaws. 

Five years later, yaws remains endemic in 11 countries, with Papua New Guinea, Ghana, the Solomon Islands, and Ivory Coast reporting most of the cases. It is difficult to estimate the impact the current COVID-19 pandemic has had on neglected tropical disease control activities; momentum and global interest in the subject have faded, and most projects have been put on hold. However, this episode also reminds us that, when countries come together and rally behind a common objective, unimaginable feats can be achieved. The COVID-19 pandemic is an important reminder of the need for a global approach to public health.  

“When countries come together and rally behind a common objective, unimaginable feats can be achieved”

A ‘One Health’ approach is also increasingly recognised as integral to disease eradication. In the case of yaws, a remaining obstacle to eradication is the potential for there to be an animal reservoir. For a disease to be eradicable, it needs to be localised and for there to be an effective and affordable treatment available—criteria met by yaws. But the disease must also have no animal reservoir: if the disease is carried by animals and proved to be transmissible from animals to humans, it makes eradication practically impossible. Initially, it was assumed that yaws had no animal reservoirs, but recent studies in which Treponema pallidum has been isolated from primates in Africa suggest otherwise. More studies are required to confirm whether primates could transmit the infection to humans, but from what we are learning about disease eradication more broadly, it is essential we use a One Health approach to yaws eradication, recognising the interconnectedness of the environment, animals, and people. Taking a One Health approach to yaws eradication would involve bringing together an interdisciplinary team of medical doctors and scientists, as well as veterinarians and environmental specialists to tackle the disease together.  

The road ahead to yaws eradication will be long and more challenges will arise, but with global input and an interdisciplinary approach, the future looks a little brighter. Since the renewed interest in yaws eradication, public awareness on the topic and media coverage are still limited. Thus, this article aims to contribute to the spread of awareness on the subject, hoping to shed some light on one of the most exciting targets in public health. To this date, only one disease has ever been eradicated: smallpox. Could yaws be the next?