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The rise of the superbugs and what this means

Maneka Sanjay Gandhi

Candida auris, a dangerous fungal infection that emerged in 2009 in Japan, has now spread worldwide, especially in hospitals. It is a superbug: a germ that has evolved defences against all medicines. These include antifungals such as fluconazole (Diflucan), the antifungal drug of choice in many countries, and recently introduced antifungals known as echinocandins. It is responsible for the increasing, hospital-acquired, invasive infections worldwide and a threat to intensive care units, because it can survive normal decontaminants such as chlorhexidine and bleach. Some hospitals have had to rip out floor and ceiling tiles to get rid of it. If it gets into the bloodstream it can be life threatening especially for people with weakened immune systems.

The rise of C auris has been little publicised, partly because it is new. Outbreaks have been kept confidential by hospitals and governments, as publicising them would scare people into not going for other treatment. In America, the Centre for Disease Control is not allowed to make public the name of hospitals involved in outbreaks.

The symptoms of C auris — fever, aches, fatigue — are not unusual, making it hard to recognise the infection without testing. It is frequently misdiagnosed. One sign is that fever and chills don’t subside after antibiotics treatment. Coma, organ failure, and death may occur if appropriate treatment is delayed. Around 30-50 per cent of patients, who contract Candida auris, die. The fungus can live for a long time on patients’ skin, and in health care facilities, allowing it to spread to new patients.

Why is it spreading so rapidly across the globe?

One reason is the indiscriminate doling out of antibiotics and antifungals by the medical community. This allows microbes to adapt, evolve, and outsmart drugs. Without antimicrobials that work, common medical procedures, like hip operations, C-sections, or chemotherapy, have become more dangerous. Gonorrhoea, certain strains of tuberculosis to name a few, no longer respond to any medicine.

The more important reason though is that each country uses the same drugs on animals grown for food. In India, we use tonnes of antibiotics and antifungals in poultries, piggeries. Animals are forcibly grown in such terrible conditions that keeping them alive, till they are large enough to be killed, is impossible without them. Their antibiotic/antifungal laced faeces spreads in land and water. We eat contaminated food and drink contaminated water. Modern agricultural practices also depend on these drugs. C auris’s resistance is traceable to industrial agriculture’s mass application of fungicides on diverse crops like wheat, banana, barley, among others.

In a paper ‘Worldwide emergence of resistance to antifungal drugs challenges human health and food security’ by scientists Matthew C Fisher and colleagues published in Science 2018, six main classes of fungicides – azoles, morpholines, benzimidazoles, strobilurins, succinate dehydrogenase inhibitors, anilinopyrimidines – have been identified, which were hardly used in agriculture before 2007. It is not a coincidence that the fungi affecting us have all turned into superbugs in that period.

Azoles, used in both crop protection and medical settings, are broad-spectrum fungicides, annihilating a wide range of fungi rather than targeting a specific type. They are now 26 per cent of all fungicides used.

Candida auris is not the only deadly fungus which is showing multidrug resistance. Aspergillus fumigatus, has been killing two lakh people every year. This species colonises decaying vegetation in fields, forests, and compost heaps. It attacks immune compromised humans. Azole antifungals itraconazole, voriconazole, and posaconazole have long been used to treat pulmonary asperillogosis, the infection caused by A fumigatus, but in the last ten years it has developed a resistance to antifungal drugs. Studies, comparing long-term azole users and patients just beginning to take the drug, have shown that drug-resistant A fumigatus was prevalent in both groups, demonstrating that the resistance has come from the food they are exposed to, rather than the medicines they were taking. Studies done in Bogota, Columbia, found A fumigatus in agricultural fields using fungicides. Soils were sampled from an array of crop fields treated with itraconazole or voriconazole fungicides. A. fumigatus was grown in the lab on agar treated with the same antifungals. In more than 25 per cent of cases, A fumigatus persisted despite the fungicide treatment. This simply means that, due to agricultural practices, Aspergillus is entering hospitals already adapted to the antifungals designed to check its spread.

Drug resistant strains of Candida albicans, C glabrata and Cryptococcus neoformans, have also been recently reported. There is also a growing threat from pathogenic fungi such as Aspergillus terreus, Scedosporium spp, Fusarium spp, and members of the Mucorales.

Azole fungicides need to be banned in crop management. Twenty-five forms of agricultural azoles are in use, compared to just three forms of medical azoles. Obviously, the medical use of azole-based antifungals is ineffective. Azoles are increasingly failing as frontline therapies, with patient mortality approaching 100 per cent. The rate of emergence of fungicide resistance is greater than the pace of fungicide discovery. This situation parallels the situation for antibiotics

But, instead of intervening in the interests of public health to limit azoles, government policy in recent years has promoted their expansion, fostering conditions for virulent drug-resistant fungi. Global sales have tripled since 2005, from $8 billion to $21 billion in 2017.

As climate change brings higher overall temperatures and vacillation between drought and heavy rainfall, fungi will spread outside their current ranges. Aspergillus flavus, the producer of a cancer-causing aflatoxin thrives in drought conditions and large crop-water deficits.

Instead of government blaming farmers for illiterate overuse, or using this opportunity to get more GMO gene manipulated seeds, or looking at different drug cocktails that will spew more poison into the environment, agricultural practices will have to be modified to bring back organic food, sustainable crop rotation, and intercropping. There is enough evidence to show that this can greatly reduce fungal diseases. For instance, intercropping soya with flax removed all pathogenic fungi. Researchers in India find that if, instead of using azole fungicide to control potato blight, silica is applied to the leaves, disease infestation comes down sharply. Surrounding crops, with wild non-crop vegetation, also control fungal pathogens.

We are in a vicious spiral. As we use more fungicides, more resistant pathogenic fungi emerge. The first case of resistance against the benzimidazoles (MBCs) was reported in 1969, and now MBC resistance occurs in more than 90 plant pathogens. Azole resistance in a plant pathogen was first reported in 1981. Resistance to strobilurins was reported in field trials even before commercial introduction, and in wider field populations within two years of release.

A new generation of succinate dehydrogenase inhibitors was introduced in 2007, but by 2017 resistance were found in 17 pathogen species. Today, crop-destroying fungi account for annual yield losses of 20 per cent worldwide, with a further 10 per cent loss post harvest.

To avoid a global collapse in our ability to control fungal infections, and to avoid critical failures in medicine and food security, we must put public health before company fiscal health.

The global mortality rate for fungal diseases now exceeds that for malaria or breast cancer, and is comparable to those for tuberculosis and HIV. But no Indian government has applied its mind to this huge problem.

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