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Saturday, 19 June 2021

INTERVIEW: Confronting the lethal black fungus disease

Dr. Ashraf Ibrahim of the Lundquist Institute and Professor of Infectious Disease at UCLA explains to Ahram Online causes behind spread of mucormycosis (black fungus) across India and precautionary measures to reduce infection

Ashraf Amin, Tuesday 25 May 2021
Dr. Ashraf Ibrahim
Dr. Ashraf Ibrahim, a lead investigator at Lundquist Institute and Professor of Infectious Disease at UCLA
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With the growing fear of the fatal fungal infection, Dr. Ashraf Ibrahim, a lead investigator at Lundquist Institute and Professor of Infectious Disease at UCLA, explains to Ahram Online the causes behind the spread of mucormycosis (black fungus) across India and the precautionary measures to reduce infection.

Born and raised in Kuwait to Arab Expatriates parents, Dr. Ibrahim spent 30 years of his career microbial physiology and pathogenesis in the US.

Over the last seven years, Dr.Ibrahim has been developing an antibody that stems the spread of the black fungus.

Based on the animal trials, the new therapy showed promising effects. Still more studies and trials on humans should be pursued before approving the drug.

Ahram Online: You have been working the past few years on a new black fungus drug. Based on the animal trials, what is its efficacy compared to the approved therapies? 

Dr. Ashraf Ibrahim: We are developing a humanized monoclonal antibody (immunotherapy) to treat black mold infection, which is better known in the scientific community as Mucormycosis. It is a lethal infection with 50-100% lethality (depending on the site of infection and the status of the patient). In mice, the immunotherapy outperforms any antifungal drug currently approved for treating the infection. 

More importantly, the combination therapy of antifungal drug and immunotherapy is highly superior to antifungal therapy in mice. We get almost complete protection against the disease with the combination therapy vs. 10-40% protection with antifungal drug therapy alone. In such a lethal disease, it is important to realize that the immunotherapy is not intended to be administered alone but rather as a combination therapy with antifungal drugs.    

AO: What are the causes behind the spread of the black fungus and white fungus in India?

AI: India has been known to have a very high number of mucormycosis cases prior to COVID-19. One population-based study estimated the number of mucormycosis cases to be more than 200,000 patients per year. Compare this to few thousand cases in the US or Europe. The increased number of cases in India is probably due to the large number of uncontrolled diabetes among Indian citizens.

Another important factor predisposing for black fungus is immunosuppression with cortisone. In COVID-19 patients, the combination of uncontrolled diabetes with high dose cortisone to control the exuberant inflammatory immune response resulting from COVID-19 infection represents a perfect storm for black fungus infection and worst outcome. 

Another thing to keep in mind is the tropical environment present in India with high humidity. Fungi in general thrives in humid environments and this make for high load of fungal spores in the environment including those causing black fungal infection.     

Some health authorities in India have called to declare the rise of black fungus an epidemic. What is your comment on that?

With more than 7000 confirmed cases in two months, absolutely this is an epidemic and very concerning. I am hearing that they are running into shortage of critical antifungal drugs to treat the infection. This is a disease that if not attended to immediately with a combination of surgical removal of infected tissues when possible and antifungal therapy is often 100% lethal.

What are the measures that should be taken to avoid black fungus and white fungus infection?

Controlled diabetes is a must and caution in administering corticosteroids (cortisone in dosing and duration) is advisable. Trying to figure out the source of infection in these patients is also important. It could be happening from humidifiers or contaminated air cylinders. It is hard to tell what is the source of infection but this needs to be looked at since the numbers are alarming.

 Would you please explain the mechanism of the new antibody? 

The antibody is designed to target a cell surface protein that is critical in allowing the fungus to bind and invade human cells. In other words, the antibody prevents the fungus from invading human tissues and cause widespread infection. The antibody also allows the human immune cells --white blood cells -- to better recognize the invading fungus and attack it.

What other infectious diseases could this new drug overcome? Could it be used to treat the white fungus (aspergillosis)?

This is a monoclonal antibody specific to (black fungus) since the target molecule is only present in fungi that cause mucormycosis. However, we are working on another antibody that is in an animal model is effective in treating white fungus.

 When do you expect the trials on humans to start and the approval of the medicine?

It all depends on how soon we are able to raise USD 5-10 M. If we are reliant on NIH funding, I expect another 4 years to finish manufacturing and start a Phase I clinical trial. It will be another 4-5 years to finish a Phase II clinical trial and approval (again due to funding issues). If we have the money upfront, we can be in Phase I clinical trial within one year and another 2 years for a Phase 2 and approval.

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