The ‘primitive’ technique of healing wounds with maggots – 7/6/2023 – Science

By mail, tiny larvae have already been dispatched from a laboratory in Campinas, in the interior of São Paulo, towards hospitals in cities such as Natal, Rio de Janeiro, Petrópolis, Belo Horizonte and Porto Alegre.

They were larvae of two species of flies created, fed and sterilized by biologist Patricia Thyssen, from the State University of Campinas (Unicamp), with a very specific medical purpose: to treat wounds that are difficult to heal.

The reason is that these larvae feed on decaying human tissue.

Therefore, when placed on the skin in infected wounds —caused, for example, by diabetes or venous ulcers—, the larvae eat the dead tissue and secrete healing substances, preventing or reducing the use of antibiotics.

This technique, known as larval therapy, still in its infancy in Brazil, connects to ancient knowledge, albeit with a repulsive aspect: there are historical records that people such as the Mayans, in Central America, and Australian aborigines already used larvae to treat wounds, thousands of years ago.

The Mayans, for example, bathed fabrics in animal blood, left them exposed to the sun to attract flies, and then applied them to human wounds, where the larvae proliferated.

The technique has also been empirically documented by physicians in medieval Europe, the American Civil War (1861-65) and World War I (1914-18).

Until, in the 20th century, penicillin and the antibiotic revolution caused such treatments to be left aside.

The problem is that, nowadays, more and more antibiotics are losing their effectiveness in the face of resistant bacteria – something that the World Health Organization (WHO) treats as one of the ten biggest public health threats of today.

As a result, more health professionals have, in recent decades, returned to resorting to larvae to treat chronic and infected wounds, resistant to antibiotics and traditional dressings. (Read below about use in the UK public health system).

In Brazil, researchers want to validate this type of therapy at the National Health Surveillance Agency (Anvisa), which currently does not classify this type of treatment as a drug or medical device.

But it is a treatment that faces many obstacles —and that has associated risks—, as BBC News Brasil explains below.

Larvae that eat infected tissue

The first clinical study of larval therapy was carried out by the American physician William Baer, ​​based on his experience treating soldiers in France during the First World War in 1917.

At a battlefront hospital, Baer came across two patients who, at first glance, appeared to be in a particularly challenging situation: they were soldiers with open wounds in the leg and abdomen, who had spent days in the trenches without treatment, water or food. exposed to unhealthy conditions.

However, Baer noticed that the two soldiers’ wounds were infested with maggots. And that, despite the apparently bleak picture, the two men arrived at the hospital without fever or signs of septicemia or serious infections.

On the contrary, “when I looked at the extent of the wounds, particularly on the thigh, I couldn’t help but marvel at the good condition of the patients,” Baer wrote in his study.

From that episode, the American doctor decided to test the effect of the larvae on the wounds in the laboratory, identifying the healing capacity of some of them —although it is important to point out that the lack of sterilization of the larvae used by Baer ended up causing serious secondary infections, such as tetanus. , in some of his patients.

Sterilization

More than a century later, today’s larval therapy is very different —and much more hygienic— than that performed by Baer or the Mayan peoples, except that the basic input remains the same: flies.

Actually, very specific flies. Out of hundreds of thousands of fly species, the UK only uses one — the lucilia sericata— for medicinal treatment.

It is a species known to breed in garbage and decaying bodies. And that qualifies its larvae to treat chronic human wounds, explains to BBC News Brasil the doctor Yamni Nigam, professor of Biomedical Sciences at the University of Swansea (United Kingdom).

“They feed on these infected and necrotic tissues, clean the wound and stimulate the formation of good skin”, says Nigam.

The main use is in patients with diabetes – whose wounds, if left untreated, can lead to limb amputations or death.

“These are wounds that simply do not heal, and sometimes the patient is not even aware of it, because the nerves (in the injured area) are not working – there is a neuropathy. It is a classic case for the use of larvae”, explains Nigam.

the fly larva lucilia sericata it is a non-invasive species, incapable of parasitizing the human body, says the doctor. “And she doesn’t eat healthy tissue, so she’s perfect for the job.”

In the United Kingdom, the treatment is done with larvae disinfected in the laboratory and collected in small permeable biological bags, similar to a tea bag. Under medical guidance, these bags are placed for up to five days on top of the infected wound and then discarded as medical waste.

The porosity of the pouches allows the larva to come into direct contact with the wound – and, by feeding on this diseased waste, they can quadruple in size, from 3 to 12 millimeters.

“The larvae don’t have teeth: they just secrete a liquid that goes through the bag, digests it and cleans the wound. And then they swallow the liquid again – always inside the bag”, continues Nigam, citing studies that point out that the treatment is capable of prevent amputations and reduce the need for antibiotics.

Larval therapy began to be used by some British Public Health Service (NHS) hospitals from the 2000s onwards, at the same time it was approved by the US drug regulatory agency (FDA).

The British larvae are grown, sterilized and packaged by the Welsh company BioMonde, which tells BBC News Brasil it supplies more than 5,000 biological bags to the NHS annually. The company also has a unit in Germany that exports larvae to European countries.

According to NHS hospitals, the risks of treatment, in some cases, are increased local pain, skin irritation or bleeding – a situation in which the larvae have to be removed.

“The larvae produce anticoagulants, so we cannot use them in patients with a high risk of bleeding”, says Dr. Nigham.

Finally, it is important to highlight that a treatment of this type should never be carried out outside the medical scope, necessarily with sterilized larvae in the laboratory, warns Brazilian Patricia Thyssen.

“You should never use a wild larva, because (a layperson) has no way of knowing whether it is a harmless and safe species of larva, nor the amount of bacteria that this larva can bring”, he clarifies.

But when it comes to manageable risks compared to the potential benefits —to prevent amputations and generalized infections, for example—, why is the therapy so restricted?

‘Disgust’

“It is an underutilized treatment”, believes Yanni Nigham.

“We’ve only used it on very difficult, otherwise untreatable wounds. And that’s something we’re trying to change. Why do we leave larval therapy only as a last resort? Why do we expect some patients to suffer for years, sometimes trying different types of dressings?” and ointments, when it would be enough to use the larvae for four days?”

Last year, Nigam and his colleagues conducted an opinion poll in the UK, in which only 36% of 412 respondents said they would be okay with using maggots to treat a hypothetical painful wound.

“The overriding concern is disgust associated with therapy,” the survey says.

Other difficulties listed by Nigham are that, unlike traditional medicines and ointments, the larvae are not as easily produced and stored — and are often met with resistance among doctors and nurses.

But the advance of superbugs has, according to the doctor, given impetus to new research.

“Bacteria are very intelligent beings. There are few antibiotics left that work against certain diseases. In addition, bacteria settle in wounds and form a wall, which we call bacterial biofilm, something very resistant to antibiotics and very difficult to treat”, he explains Nigham.

“But we were able to demonstrate, in the laboratory and in patients, that larvae not only manage to break through this biofilm, but their liquid also prevents it from forming.”

As this knowledge advances, says the doctor, it may be possible in the future to use the liquid secreted by the larvae to waterproof human prostheses before surgery, for example, in order to prevent infections.

In Brazil

At the University Hospital Onofre Lopes, of the Federal University of Rio Grande do Norte, nurse Julianny Barreto Ferraz, coordinator of the wound team, started to put larval therapy into practice in 2012.

She uses larvae created at the university’s Laboratory of Insects and Vectors, in addition to those sent from Campinas by Patricia Thyssen.

In the hot climate of Brazil, explains Thyssen, the fly lucilia sericataused in Europe, is not so easily found, so it was necessary to identify other common species considered safe for medicinal use: the Cochliomyia macellaria and the chrysomya megacephala.

They are carefully nurtured to reproduce in the laboratory, with ingredients such as powdered milk, dairy flour, fish meal and brewer’s yeast — before their larvae are disinfected and released to patients.

Except that, in the absence of a company that packs the larvae in a permeable bag, as is the case in the United Kingdom, the Brazilian larvae are applied directly to the open wound, covered with gauze and surrounded by zinc sulfate ointment, whose smell prevents them from ” escape”, explains Julianny Barreto.

The procedure was filed and validated by an ethics committee at the UFRN hospital, but, without being able to rely on a constant supply of larvae, Barreto was only able to treat 23 patients over ten years.

“We don’t have a specific employee for larval therapy, nor a laboratory technician dedicated to that alone. So we can only produce larvae when we have students (from the university who get involved in the project)”, says Barreto.

“If we had more incentive, we would have treated thousands of cases. (…) But we had to choose those of people (diabetics) who already had a limb amputated, who were losing first a finger, then another finger, then half of the foot. We opted for these cases to give these patients a better chance of cure.”

In the other hospitals in Brazil to which biologist Patricia Thyssen dispatched her disinfected larvae, use was punctual and ended up paralyzed by the Covid-19 pandemic —according to her, with good results in wound healing, but still awaiting publication in scientific journals. It also provides inputs for veterinary larval treatment.

But, today, the hospital in Natal is the only one where supplies for human use continue.

Thyssen’s objective, now, is to carry out randomized clinical studies that allow the therapy to be validated by the National Health Surveillance Agency, Anvisa, and to implement broader use.

So far, the agency informs BBC News Brasil that “it has not received a product registration request of this nature”. Therefore, “this type of therapy does not fit as a medicine or a medical device”.

But Thyssen, who has been dedicated to the study of flies for almost 30 years, sees the future potential of the treatment with optimism.

“In terms of logistics, I already produce disinfected larvae and I already have good production and transport practices. Our larvae arrive ready for use, and manage to survive at room temperature, via Post Office, (in journeys that last) 3 to 4 days”, affirm.

“So I’m really excited about this work. We’ve been trying to look at the insect with this perspective of investigating its antimicrobial action and its potential for new antibiotics.”

In the UK, Yamni Nigam also talks about changing the way we see these creatures.

“I think that (larval therapy) will never be massified, because of the disgust factor, the reluctance”, she says. “But I think the negative perception associated with maggots needs to change. We have to think of them as medicine or medical equipment, and not as a repulsive being that we see in the garbage.”

This report was originally published here.