17-Jun-2021: Steps taken by Government to ensure drug availability for treatment of Mucormycosis

A sudden increase in the demand has been observed in some States for Amphotericin-B, which is being actively prescribed by the physicians to the patients suffering from Mucormycosis, which has been seen as a post COVID complication. Through active measures to augment production, and import and ensure equitable distribution, Government has been able to mobilise over 6.67 lakh vials of the Amphotericin B for patients in the states and UTs and Central Health Institutes, in addition to other drugs such as Amphotericin Deoxycholate and Posaconazole being used for treatment of this disease.

The Department of Pharmaceuticals (DoP) along with inputs from CDSCO has been continuously assessing the availability of drugs for treating Mucormycosis - both through domestic manufacturing and import. Since early   May, 2021 the details of production, stock, supplies made and purchase orders were obtained from the manufacturers and their co-operation sought to overcome the gap between supply and demand. An inter-departmental meeting was held on 10th May, 2021 with Department of Pharmaceuticals, Ministry of Health & Family Welfare (MoHFW), Central Drugs Standard Control Organisation (CDSCO) and Directorate General of Health Services (DGHS)to take stock of the situation. A view emerged that allocation of limited stocks among the States/UTs would ensure that all States get a fair chance of accessing a share of the available supplies, till the supply demand gap is overcome.

Production enhancement

In order to augment the domestic manufacture, the Government is continuously engaging with the manufacturers to resolve their issues related to raw materials. Department of Pharmaceuticals and the Drug Controller General of India (DCGI) have actively coordinated with the industry for identification of manufacturers, alternate drugs and expeditious approvals of new manufacturing facilities. The manufacturing firms were contacted and have been sensitized about the need to increase production. The existing manufacturers have also been called upon to increase production of Liposomal Amphotericin-B. Ramping up production of alternative drugs/forms for treating the disease is also being actively pursued with the manufacturers. Various concerns of manufacturers and importers, including those related to licensing and availability of raw material issues, import license are being speedily addressed.

The existing five manufacturers of Liposomal Amphotericin B are Bharat Serums and Vaccines Limited, Cipla, Sun Pharma, BDR Pharmaceuticals and Lifecare Innovations.  The expected release by them for the month of June is about 2.63 lakh vials. Manufacturing of liposomal formulation involves a complicated process and can only be done by industries having advanced technology. DCGI, after consultation with the association of Drugs manufacturers, has issued manufacturing / marketing permission of Amphotericin B Liposomal Injection to six firms, viz., Emcure, Gufic, Alembic,  Lyka,  Natco Limited and Intas Pharma. The expected release by the six new manufacturers for the month of June is about 1.13 lakh vials.

The domestic production capacity of Amphotericin B Liposomal Injection has increased from about 62000 in April 2021, to 1.63 lakh vials in May 2021 and is expected to cross 3.75 lakh vials in June, which is a fivefold increase in a short time span.

Regular Monitoring of production is being carried out by the Government and several meetings held with the manufacturers to identify the issues involved in the augmentation of the production. Companies manufacturing APIs have also been contacted by the Government and asked to ensure increased and continuous supplies for augmenting production.

Import facilitation

Ministry of External Affairs (MEA) is playing an important role in reaching out to various players abroad. Through its missions all over the world, MEA has identified new sources of Amphotericin B/ Liposomal Amphotericin B injections and alternative drugs for treatment of Mucormycosis. Out of the identified sources, the MoHFW has called upon MEA to take steps to procure Liposomal Amphotericin-B from Australia, Russia, Germany, Argentina, Belgium and China. MEA has also been actively working on ensuring supplies of key excipient, HSPC and DSPG-NA from sources abroad for production of Liposomal Amphotericin B in India.

Department of Pharmaceuticals and the Indian Embassy in the USA are working continuously with the Mylan Labs for increasing import and ensuring early delivery from M/s Gilead Inc. USA. Out of total Orders placed with Gilead for 9,05,000 vials, the stocks of 5,33,971 vials have already been received till 16th June by M/s Mylan, the main importer. The remaining deliveries are being expedited.

Making allocation

In order to ensure equitable distribution of the limited stocks, it was decided to make allocation of limited stocks among states, which would ensure that all states with patients of Mucormycosis would get a fair chance of accessing a share of the supplies.  The allocation by the Central Government is being done only in respect of Lyposomal Amphotericin-B, barring one manufacturer Bharat Serum, which produces Lyposomal, Lipid and emulsion form of the drug. The allocation of Conventional Amphotericin is also being done since 14th June 2021, after assessing the demand and availability.

For equitable distribution, allotments are being made to the States/ UTs in accordance with the proportion of their reported case load in respect of the entire country. The number of patients in a particular State is derived from the portal of Ministry of Health and Family Welfare, in which the States themselves enter the figures of patient load in their respective states. This allocation regime is an interim arrangement till the supply of the drug stabilises vis a vis the demand.

Physical distribution and availability of the drug in a particular city/ hospital is managed by the State Governments concerned. Liposomal Amphotericin-B is directly procured by State Governments from the manufacturers based on the allocation made and the drug is subsequently made available to the Hospitals. Through allocations made till 14th June, 2021, a total 6,67,360 vials have been allocated by Department of Pharmaceuticals to States / UTs. In addition, 53,000 vials of Conventional Amphotericin B were also allocated to States / UTs on 14th June.

Ensuring supply

Supply arrangements are being monitored by the National Pharmaceuticals Pricing Authority (NPPA) under the Department so as to ensure expeditious availability of the drug to the needy. NPPA has put in place a strongly responsive system to ensure timely supplies of allocated volumes and maintains continuous contact with States / UTs and suppliers to trouble shoot any issues in reaching the drugs to the Health Departments of States/ UTs.

On 7th June, 2021, MoHFW has circulated the advisory of the National Task Force on COVID-19 for treatment and management of Covid related Mucormycosis (CAM), which explains in detail, the manner and conditions under which various Mucormycosis drugs like Amphotericin B lipid complex, liposomal Amphotericin B, Amphotericin deoxycholate form, Posaconazole etc. are to be used. Department of Pharmaceuticals has also on 10th June, 2021 issued an advisory to the Health Secretaries of all State governments/UTs reiterating the need of ensuring judicious use of allocated drugs and efficient distribution within their State/UTs.

Government continues to closely monitor in contact with state governments and manufacturers, the production, import, supplies and availability of the drugs required for treatment of Mucormycosis.

3-Jun-2021: Mucormycosis mostly seen in people with decreased immunity, diabetes

The cases of Mucormycosis we are witnessing are a tiny fraction of COVID-19 cases, informed Gastroenterologist Dr. Rajeev Jayadevan during a webinar on 'Mucormycosis and Dental Health in relation to COVID-19', organized by the Press Information Bureau today. The other expert panelist in the webinar was Prosthodontist Dr. Neeta Rana.  The doctors’ advice and knowledge imparted in the webinar are presented in form of key points below.

What makes people prone to Mucormycosis?

Explaining what makes COVID-19 patients prone to Mucormycosis, Dr. Jayadevan said, "Having COVID-19 in the background of diabetes and steroid use, is a classic setting for triple immune suppression. COVID-19 affects many segments of our body, including our immune system". Stating that there is a link between diabetes and Mucormycosis, the doctor informed, " Many people in our country have diabetes. Given this and our population, the number of people who fall sick is higher than in any other country. So, it is understandable that some of them will catch Mucormycosis."

Dr. Jayadevan, who has written several articles for doctors, policy makers and the general public during the pandemic, opined, "The way I see it, a tiny proportion of the large number of people getting infected with COVID-19 are getting infected with Mucormycosis, so this proportion becomes a large number".

The doctor further explained: "Mucormycosis cases have been seen in people with decreased immunity, predominantly either due to diabetes or after some organ transplant. In the last month or two, we have seen a rise in Mucormycosis in those without these conditions. It is a new development. But we need studies need to confirm reasons for increased cases in those without traditional risk factors."

Diabetes and Mucormycosis: Dr. Jayadevan says, "For diabetic patients, when the blood glucose of sugars cannot be controlled, the immune system is not able to work properly. In case of severe diabetes, the function of pathogen-fighting cells like neutrophils gets impaired. Factors such as this make us prone to contracting Mucormycosis. High sugar level in itself is conducive to fungal growth. Fungus loves sugar, it loves trace metals like zinc, it also grows on dead tissue and until the body repairs the dead tissue, fungus may grow on it".

In the next stage, "The fungus invades our blood cells, our tissues don't get oxygen supply and die, and when the tissues die, they become black in colour. This is the reason why the name black fungus is used for Mucormycosis", explained the gastroenterologist in simple terms for the benefit of lay people.

Dental Health and Mucormycosis: The dental expert Dr. Neeta Rana explains, "There is definitely a link between good dental health and COVID-19 infection. When teeth, gums and palette are maintained well, naturally present microorganisms will function well and viral infection is less likely to occur. If wound after tooth-extraction is not maintained well, if good oral hygiene is not observed, then we increase chances of catching Mucormycosis".

Brushing of teeth, flossing, mouth-washing and rinsing will also help in maintaining good dental health, advised Dr. Neeta.

Vaccination and Mucormycosis: Dr. Jayadevan says, "If you get COVID-19 after vaccination, it will be mild in vast majority of cases". The doctor further suggested that medicines are not necessary in mild cases of COVID. Hence, in cases of mild COVID-19, the chance of catching steroid-related Mucormycosis will be low, opined the doctor. "But if instead of letting the mild COVID case cure by itself, if the person starts self-medication, taking medicines which are not required, it may set the stage for a fungal infection that would have never happened in the first place", he cautioned.

Post-COVID and Mucormycosis: Dr. Jayadevan says, "Effects of immuno-suppression and COVID-19 treatment will remain in body for some time, just like we see ripples in a river, long after a boat goes through the river". Hence, his advice is to 'Remain Vigilant for a few weeks after recovering and not do anything adventurous or experimental with your body'. In the context of immuno-suppression causing patients to become prone to Mucormycosis, Dr. Jayadevan informs, "So many studies have conclusively shown that good healthy bacteria living in our body improve our body's defence against invading bad bacteria. So, prolonged and unnecessary use of antibiotics is a strong risk factor for fungal and bacterial infections". In this connection, Dr. Jayadevan reflected that vast majority of people in our country engage in some form of self-treatment. The doctor strongly discouraged this practice. His advice in this regard: "Just follow the basic instructions given by the doctor you are in touch with and stay away from unnecessary medicines".

Whether Mucormycosis infection comes from surroundings?

Dra. Jayadevan says, "Fungus is there all around us. Do not be excessively scared of venturing out due to fear of catching fungal infection. Fungi have existed for centuries, and Mucormycosis is a rare infection, occurring in very few cases".

Dental Care in times of a pandemic: Dr. Neeta advises, "Be in touch with your dental doctor, teleconsultation will help in many cases. If guidelines are followed at dental clinics, there should not be reason for fear of catching any infection, but don't be overzealous too. Follow doctor's advice about physical visit to a dental clinic".

How long vaccines can provide immunity against COVID-19?

Dr. Jayadevan explains, "When we encounter repeat infection or infection after vaccination, memory cells introduced in previous infection will swing into action immediately. Studies show that memory cells last at least an year". Explaining the function of vaccines, the doctor said, "What vaccines do predominantly is to prevent severe disease or death on getting infected; a good number of scientists believe that immunity from vaccination is reasonably long-lasting, likely to protect us for many years".

Advice for those exposed to COVID-19

Dr. Jayadevan says, "Never take it lightly. There is no need to panic. But, after 5-6 days, if your symptoms are worsening, if you are getting tired, short of breath, unable to eat, chest pain or simply not feeling well, then go to a hospital and see a doctor. Alternatively, you can do teleconsultation with a doctor also".

14-May-2021: Stay Safe from Mucormycosis - a Fungal Complication being Detected in COVID-19 Patients

Even as we try our best to protect ourselves from and cope with COVID-19, there is another threat being posed by a fungus, which we must know and act upon. Mucormycosis, a fungal infection, is being reported in a few COVID-19 patients during or post recovery. As per a statement given by the Health Minister of Maharashtra two days ago, more than 2000 people had already been affected by this fungal infection in the state; 10 people had even succumbed to it. Some patients even lost their eyesight.

What causes Mucormycosis?

Mucormycosis or black fungus is a complication caused by fungal infection. People catch Mucormycosis by coming in contact with the fungal spores in the environment. It can also develop on the skin after the fungus enters the skin through a cut, scrape, burn, or other type of skin trauma.

The disease is being detected among patients who are recovering or have recovered from COVID-19. Moreover, anyone who is diabetic and whose immune system is not functioning well needs to be on the guard against this.

According to an advisory issued by the Indian Council of Medical Research, the following conditions in COVID-19 patients increase the risk of mucormycosis infection:

1. Uncontrolled diabetes
2. Weakening of immune system due to use of steroids
3. Prolonged ICU/hospital stay
4. Co-morbidities / post organ transplant / cancer
5. Voriconazole therapy (used to treat serious fungal infections)

How it is related with COVID-19?

The disease is caused by a set of micro-organisms known as mucormycetes, which are present naturally in the environment, seen mostly in soil and in decaying organic matter like leaves, compost and piles.

In normal course, our body’s immune system successfully fights such fungal infections. However, we know that COVID-19 affects our immune system. Moreover, the treatment of COVID-19 patients involves intake of drugs like dexamethasone, which suppress our immune system response. Due to these factors, COVID-19 patients face a renewed risk of failing the battle against attacks mounted by organisms such as mucormycetes.

In addition, COVID patients undergoing oxygen therapy in ICU, where humidifier is used, are prone to fungal infection because of exposure to moisture.

But this does not mean that every COVID patient will get infected by Mucormycosis. The disease is uncommon in those not having diabetes but can be fatal if not treated promptly. Chances of recovery depend upon early diagnosis and treatment.

What are the common symptoms?

Mucormycosis begins to manifest as skin infection in the air pockets located behind our forehead, nose, cheekbones, and in between the eyes and teeth. It then spreads to eyes, lungs and can even spread to the brain. It leads to blackening or discoloration over the nose, blurred or double vision, chest pain, breathing difficulties and coughing of blood.

The Indian Council of Medical Research has advised that not all cases of blocked nose should be considered as cases of bacterial sinusitis, particularly during/after the treatment of Covid-19 patients. One must seek medical help for detecting fungal infection. 

How is it treated?

While the infection may just begin with a skin infection, it can spread to other parts of the body. Treatment involves surgically removing all dead and infected tissue. In some patients, this may result in loss of upper jaw or sometimes even the eye. Cure may also involve a 4-6 weeks course of intravenous anti-fungal therapy.  Since it affects various parts of the body, treatment requires a team of microbiologists, internal medicine specialists, intensivist neurologists, ENT specialists, ophthalmologists, dentists, surgeons and others.

Controlling diabetes is one of the foremost prevention methods suggested by ICMR. Hence, COVID-19 patients who are diabetic need to take utmost care.

Self-medication and over-dosage of steroids can result in fatal events and hence doctor’s prescription should be strictly followed. Speaking about the adverse effects of inappropriate use of steroids, Member (Health), NITI Aayog, Dr. V.K. Paul says: “Steroids should never be administered at an early stage of COVID-19. It should be taken only after sixth day of infection. Patients should stick to appropriate doses of the drugs and take the drug for specific number of days as advised by the doctors. Rational use of medicines should be ensured to avoid adverse side effects of the drug.”

“Other than steroids, use of COVID-19 drugs such as Tocilizumob, Itolizumab also suppresses the immune system. And when these drugs are not used appropriately, it increases the risk, as our immune system fails to fight the fungal infection.” Dr. Paul adds.

ICMR in its guidelines has also advised COVID-19 patients to discontinue immunomodulating drugs, a substance that stimulates or suppresses immune system. The National COVID-19 Task Force has revised the dosage of Tocilizumab to prevent any such adverse effects. Maintaining proper hygiene can also help keep the fungal infection away.

For patients on oxygen therapy, it should be ensured that the water in the humidifier is clean and is refilled regularly. Attention should be paid to ensure there is no leakage of water (to avoid wet surfaces where the fungus can breed). Patients should maintain proper hygiene by keeping their hands as well as body clean.

Be on guard after COVID Recovery as well: After recovering from COVID-19, one should closely monitor and should not miss any warning signs and symptoms mentioned above, as the fungal infection is found to emerge even weeks or months after recovery. One should make judicial use of steroids as per doctor’s advice to avoid risk of infection. Early detection of the disease can ease the treatment of the fungal infection.

17-Jun-2021: Study Explored Benefits of Yoga in Chronic Low Back Pain

Most of the yoga-based studies so far have relied on patient’s experience and rating of pain and disability as an indicator of recovery and better quality of life. Researchers who measured pain, pain tolerance and body flexibility have found that yoga leads to pain relief, increases tolerance of pain and improves flexibility in patients of chronic low back pain.

Dr Renu Bhatia, Additional Professor, Department of Physiology, AIIMS, New Delhi conducted research to measure the impact of yoga on Chronic Low Back Pain (CLBP) along with Dr Raj Kumar Yadav (Professor, Department of Physiology, AIIMS, New Delhi), Dr Sri Kumar V (Associate Professor, Department of Physical Medicine & Rehabilitation, AIIMS, New Delhi).

The study conducted on 100 Chronic Low Back Pain (CLBP) patients of 50 years with 3 years of history of the disease.  After systematic Yogic intervention of 4 weeks, Quantitative sensory testing (QST) showed increase in thresholds for cold pain and cold pain tolerance. Corticomotor excitability and flexibility improved significantly in the patients.

They recorded objective measures for pain (electrophysiology), sensory perception (quantitative computerized sensory testing) and cortical excitability parameters. (using Transcranial Magnetic Stimulation of motor cortex).They found significant changes between all the parameters in CLBP patients compared to healthy controls at baseline. Significant improvement in all parameters was found after yoga.

This research supported by the Science and Technology of Yoga and Meditation (SATYAM) funded by the Department of Science and Technology, GoI has been recently published in the ‘Journal of Medical Science and Clinical Research’.

Assessment of pain and corticomotor excitability parameters shall help in establishing strong ground with scientific evidence for yoga to be prescribed as therapeutic intervention for chronic low back pain relief with or without standard therapy depending on the pathology. Also these parameters can be used for prognosis and follow-up of patients during recovery phase.

The team also developed yoga protocol for CLBP patients and for fibromyalgia patients in Pain Research and TMS laboratory, AIIMS, New Delhi.

In patients with Chronic Low Back Pain, 4 weeks of yoga intervention improved pain status and pain-related functional disability, increased spinal flexibility and corticomotor excitability significantly more than standard care.

The study suggests that in long term Yoga can be performed at home, and hence is an inexpensive therapeutic intervention. It not only relieves pain but also improves overall quality of life and bestows other health benefits.