Epidemic in a pandemic
Although rising cases of mucormycosis are being attributed to diabetic conditions and steroid overuse, concerns around hygiene and unaffordability of drugs also demand urgent attention
This too shall pass. Yes, this is the four-word sentence that is, somehow, psychologically 'helping' people in distress by reducing their stress load at a time when the country is struggling hard to get over the second wave of the pandemic along with mucormycosis — popularly known as black fungus.
The outbreak of the second wave has abruptly exposed the Central and state government's lack of preparedness in dealing with the pandemic that has already claimed over three lakh lives in the country.
Due to the "ignorance" around imperative side-effects of COVID treatment, a rare fungal disease has surfaced and is now being declared as an epidemic by the states, just in a matter of a few days. Though black fungus affects only one in 10,00,000; its mortality rate is as high as 50 per cent. As a matter of fact, mucormycosis is not a new disease; it was there in the country much before the outbreak of COVID-19. The real cause of concern associated with the disease though is that experts and the medical fraternity have not yet been able to decode the reasons that led to the sudden spurt in cases in a short span of just over two months of time.
Most doctors and experts are attributing uncontrolled diabetes and irrational use of steroids during the COVID-19 treatment as the key reasons behind the unprecedented surge in black fungus cases. While it's true that overuse of steroids led to serious complications, but for black fungus upsurge, putting onus just on steroids and uncontrolled diabetics will not be justified as there are several other factors associated with the rise of black fungus cases among COVID-recovered as well as co-morbid patients.
Doctors say any procedure/disease that reduces immunity among patients is the key reason for the spread of black fungus. The major causes of the fungal infection are attributed to chemotherapy, use of industrial oxygen, unhygienic conditions, prolonged ICU stay, high sugar level etc. Despite having a high mortality rate, the relieving part of this rare disease is that, unlike the highly infectious COVID-19, it is non-communicable.
Responding about the causes of black fungus, NITI Aayog member (health) VK Paul said: "The occurrence of mucormycosis is natural and the correlation between mucormycosis and COVID-19 is not exclusive. The people having high blood sugar levels are more prone to the risk as the infection primarily affects them."
However, while holding irrational use of steroids responsible for the rise in black fungus cases among COVID-19 patients, Paul made it very clear that the use of steroids should not be stopped as these are 'wonder drugs' that help save lives. "Steroids are wonder drugs that help save lives, but administering them to COVID-19 patients before the appropriate time, giving unnecessarily high doses, administering it without its need, and continuing their use for undue time is not part of their appropriate and rational use in the treatment of COVID-19 patients," Paul said.
"When doses are given irrationally, steroids start having a negative impact instead of helping the patient. One of these negative impacts is being seen in the form of black fungus. Such use of steroids can also complicate existing diabetes," Paul further explained.
Agreeing with the views of Paul about the importance of steroids, Uma Kumar who heads the rheumatology department of AIIMS, New Delhi, said: "Use of steroids is not new. It's been routinely used in rheumatology patients, but they had never reported such high cases of mucormycosis. There may be several other reasons for its spread that need to be explored."
"It's been discussed that uncontrolled sugar level, over-staying in ICU and poor ventilation are playing major roles in the outbreak of black fungus cases, but all these things are not happening for the first time. If these were the reasons, then cases of black fungus should have been reported on earlier occasions too," Kumar said.
"We really need to find out the reasons behind its spread as use of industrial oxygen may also be one of the reasons for the spread of the fungal diseases as oxygen used in the industries is purer than medical oxygen and industrial cylinders are not as good as medical oxygen cylinders," she said.
"There are several micro leaks in industrial cylinders which are not maintained hygienically. Industrial oxygen cylinders with contaminated water and soil from inside could also lead to the growth of fungus. Still, a lot more research is needed in this area before coming to any conclusion," she stressed. Kumar has advised people living in rural areas to take all possible precautionary measures to avoid getting infected with the fungal disease. "The people living in rural areas should maintain proper hygiene of their place, dry the mask under the sun after every use, and keep surfaces dry among others," she said.
Apart from its rarity, the major cause of concern regarding the treatment of fungal infection is costly medicines. According to Yudhyavir Singh, who is managing COVID ICU at AIIMS-Delhi, the drugs used in black fungus treatment are beyond the reach of common people as the medicines like amphotericin B, injection posaconazole and syrup posaconazole cost around Rs 3,500 per vial, Rs 4,000-5,000 per vial and Rs 1,600-2,000 per bottle respectively.
Suggesting precautionary measures, Singh said, "The use of steroids must be supervised and there should be no self-medication through steroids. Blood sugar level must be in control and masks should be used to prevent inhaling of fungal spores. Also, cut or abrasion areas must be kept covered."
"Detection of black fungus is very difficult as tests are not done in small towns. Also, it is very difficult to treat the disease. Its treatment should start soon after diagnosis as the complications and death rate are high. If not treated on time, the patients may face complete vision loss, and eyeballs may have to be removed," Singh further added that if it affects the brain and can cause stroke, resulting in paralysis and even death.
"Steroids such as Dexamethasone, Betamethasone Prednisolone, Methylprednisolone, Fludrocortisone, Deflazacort, Budecort, Fluticasone etc. are commonly used in the treatment of COVID-19 patients. Excessive use of these steroids reduces immunity among patients due to which they get infected with black fungus," he said.
Explaining the characteristics of black fungus, AIIMS director Randeep Guleria said that fungal diseases are not communicable and they don't spread from one person to another. However, he added that it is better to identify mucormycosis by its name rather than by the colour, as labelling the same fungus with names of different colours can create confusion.
"Many patients taking treatment at home, who were not on oxygen therapy, have also been found to be infected with mucormycosis. So, there is no definite link between oxygen therapy and catching the infection," he said, adding that about 90-95 per cent of patients getting infected with mucormycosis are found to have been either diabetic and/or were taking steroids. This infection is seen very rare among those who are neither diabetic nor are taking steroids.
"In general, there are various types of fungal infections such as candida, aspergillosis, cryptococcus, histoplasmosis and coccidioidomycosis. Mucormycosis, candida and aspergillosis are the ones observed more in those with low immunity," the AIIMS director said.
Speaking about the prevalence of these infections, he pointed out: "Candida fungal infection can manifest with symptoms such as white patches in the mouth and oral cavities. It can infect private parts and can also be found in the blood (in that case it can become serious)."
"Aspergillosis, which is relatively uncommon, affects and invades lungs by creating cavities in the lungs. What is observed in COVID-19 patients is mostly mucormycosis; aspergillosis is observed occasionally, and candida in some people," he explained.
On the challenges being faced in treating mucormycosis, Guleria said: "Anti-fungal treatment goes on for many weeks so it is proving to be challenging for hospitals since COVID-19 positive and negative patients who catch mucormycosis need to be housed in separate hospital wards. Surgery also needs to be done judiciously since aggressive surgery for mucormycosis could have adverse outcomes for COVID-19 patients."
"Maintaining proper hygiene is very important for diabetic patients since the chances of opportunistic infection are very high in such patients. Those using oxygen concentrators should ensure cleaning of humidifiers regularly," Guleria said.
Slamming regulatory authorities for their laxity in checking the misuse of steroids, Ravi Wankhedkar, treasurer of World Medical Association, said: "Unethical and rampant use of steroids and other immunosuppressants by unqualified doctors led to the rise of fungal diseases in the country."
"Since India is called the diabetes capital of the world, and diabetic patients are very prone to fungal diseases, the cases are rising. A severe shortage of drugs is further compounding the crisis. The government should have anticipated the need for drugs and managed accordingly", Wankhedkar said.
As per the Indian Council of Medical Research (ICMR) guidelines, the symptoms of the disease include pain and redness around the eyes and nose, fever, headache, coughing, shortness of breath, blood vomiting, altered mental status etc. If patients notice sinusitis-nasal blockade or congestion, nasal discharge (blackish/bloody), pain on the cheekbone, one-sided facial pain, numbness or swelling, toothache, blurred or double vision etc. then it could be a sign of black fungus.
As per the ICMR advisory, people should not miss these warning signs but should also not consider all cases with a blocked nose as black fungus infection. Tests like KOH staining, microscopy and MALDI TOF can be done to detect fungal infection and people should not lose crucial time by hesitating to initiate the treatment.
As per the former president of the Indian Medical Association (IMA), Rajeev Jayadevan, excessive usage of steam, intake of zinc supplement and a combination of antibiotics used to treat Coronavirus is responsible for the black fungal outbreak. Jayadevan, in his tweet, mentioned that the cocktail of antibiotics — azithromycin, doxycycline and carbapenem — can increase the risk of fungal infection.
What is mucormycosis?
Mucormycosis, caused by a group of moulds called mucormycetes, is more common among people whose immunity has been lowered due to COVID-19, diabetes, kidney disease, liver or cardiac disorders, age-related issues, or those on medication for auto-immune diseases like rheumatoid arthritis. The disease begins to manifest as a skin infection in the air pockets located behind the forehead, nose, cheekbones and in between the eyes and teeth. It then spreads to the eyes, lungs and can even spread to the brain. It leads to blackening or discolouration over the nose, blurred or double vision, chest pain, breathing difficulties and coughing of blood.
The brain behind a life-saving drug
The life-saving drug Liposomal Amphotericin-B was developed in 2010-11 by B Srikantha Annappa Pai, who was the head of the research and development team at Bharat Serums and Vaccines Limited in Mumbai.
Pai, who is a native of Gangoli village in Kundapura Taluk of Karnataka's Udupi district, got a Bachelor degree in Pharma from the Government Pharmacy College in Bengaluru and completed his post-graduation from Manipal.
As there were lesser job opportunities in Karnataka, Pai moved to Mumbai and got a job with Bharat Serums after several rounds of interviews in other pharma firms. Gilead Sciences, an American company, was having the patent of the drug used for the treatment of mucormycosis, which expired in 2008.
With minimum available resources, Pai and his team took two years to develop the formula of the drug. After meeting all the research requirements, the drug got permissions from the FDA and European Medical Agency before the trials and it was finally released in 2010-11.
Views expressed are personal