Who are most vulnerable to fungal diseases?

When it comes to combating disease risk, a good place to start is by asking: who’s most vulnerable, and where do they live? Because, in this modern world, where there are about a million and a half people airborne around the planet at any moment in time and with no major city more than about 24h from any other, infections can move fast and in significant numbers. They go where people go. And we’re seeing a very significant and increasing flux of people from poorer parts of the world towards richer economies as those latter countries seek to tap into sources of cheaper labour and skills. But it’s in those poorer places, where people are migrating from, and where underlying diseases that drive the emergence of novel fungal infections are common - that human conflict with nature is intensifying and with it the risk of fungal disease emergence. These are also often the same places where climate change is likely to intensify the problem. This is very much within the purview of Nelesh Govender, epidemiologist at Wits University in Johannesburg…

Nelesh - Low and middle-income countries are particularly vulnerable to fungal diseases. I work in South Africa, and we have a large population at risk of infections that are both life-threatening and disabling. We've got the largest population living with HIV worldwide, and these people are at risk of deadly fungal infections such as cryptococcal meningitis or pneumocystis pneumonia. People are also at risk of superadded fungal infections such as aspergillosis. In hospitals in low and middle-income countries, these hospitals often have higher-than-expected bed occupancy, so they're overcrowded. They've also got limited resources for infection prevention, and this can set the scene for large disease outbreaks, especially among very vulnerable populations—for example, sick, small newborns who have to stay in hospital for weeks to months.

Chris - From all of those risk factors you've outlined, it sounds like this is a problem that's a clinical iceberg. It's probably much bigger than we already document, and it's likely to get worse because all of the pressures you've just summarised are intensifying.

Nelesh - I think that's absolutely true. Low and middle-income countries just don't have the capacity to respond to fungal disease epidemics. We have a lack of diagnostic tests, which affects our ability to identify cases of fungal disease. This really delays life-saving treatments, and many people will then die unnecessarily. It also reduces our ability to track or monitor fungal infection outbreaks. We also have a lack of access to antifungal medicines, which means that even when we do recognise fungal diseases, they're not treated and people suffer or die as a consequence. And even when antifungal medicines are available, we often see weak stewardship. These medicines are used inappropriately—for the wrong indication, at the wrong dose, for the wrong duration.

Chris - Some people often say that because many of these problems are not a first-world problem, rich countries are less affected. They don't tend to be very high up the priority pecking order for funding and research in those places. But they nevertheless should be reminded that what starts in poorer places often makes its way to richer places. And I suppose we've seen that with diseases like COVID and with HIV. So is this one of the same? Is it that we can't afford to take our eye off fungal infections because, as the problem intensifies, it could well spill over and become a priority everywhere?

Nelesh - We currently see hundreds of thousands of cases of cryptococcal meningitis, mostly among people living with HIV. It's caused by a fungus called Cryptococcus. It's listed as a critical pathogen by the World Health Organization. We've got evidence that this fungus may have actually emerged in Africa to become a pathogen, principally through its ability to grow at human body temperature. But we believe there's an extraordinary variety of non-pathogenic cryptococcal fungi in the African environment, associated with soil, beetles, and small mammals. Potentially, as the climate changes in Africa, we're concerned that some of these non-pathogenic fungi could also gain virulence traits to cause human infections. And these human infections may affect people across the world, not just in low and middle-income countries. I think there's a shared global threat from fungi, and so we really do need to take this threat very seriously.

Chris - Do you know what's really surprising to me? It's that no one's talking about this. I know you and I are, and we're trying to raise awareness in this programme, but most people are unfamiliar with what is happening. Is the fungal threat creeping up on us in the same way that antibiotic resistance has? And to a certain extent, like other pandemics—such as obesity—we've sort of sleepwalked into this situation.

Nelesh - Well, we've tried really hard for that not to happen. In 2022, I was involved in an expert group with the World Health Organization. We developed a fungal priority pathogen list, which flagged 19 fungi that affect human health. We're currently working on a blueprint for action to address fungal diseases globally. One of the key action items, of course, is awareness and education. This podcast, I think, will go a long way towards raising the profile of fungal diseases.
But of course, we also need to think more broadly. We need to build capacity to facilitate the diagnosis of fungal diseases. We need better surveillance to understand the burden of fungal diseases. We need to track fungal antimicrobial resistance. We need to monitor outbreaks and emerging threats. We need antifungal stewardship. We've got a really limited antifungal armamentarium—there really are very few antifungals available. So we also need research and development for new medicines, new diagnostics, and new technologies.