Black fungus: The deathly infection

The incidence of black fungus, the fatal opportunistic infection, underscores the need for significant public health investment in disease control and puts India’s national health security challenges on high alert.

An ENT specialist performs an extended functional endoscopic sinus surgery on a mucormycosis patient at a hospital in Ghaziabad in Uttar Pradesh on May 29.

Black fungus, or mucormycosis, is an opportunistic infection in COVID-19 patients. It is caused by a fungus that is omnipresent in our environment and affects only when a person’s immunity is sufficiently compromised. The disease may emerge as a result of compromised immunologic milieu relating to the underlying precipitating factors such as diabetes, or as an adverse effect of medications, including steroids, that suppress a person’s immunity. When hospital infection control procedures are suboptimal, hospitals that cater to a high number of such patients may also harbour the fungus. Early diagnosis, avoidance or minimisation of the underlying cause, and anti-fungal treatment can reduce the impact of the disease. Hospital infection control procedures, including adequate ventilation and cross ventilation, need to be strengthened to avoid the growth of the fungus. Control of diabetes and rational use of medications are important. Case control studies are urgently needed to discern the necessary co-factors in COVID-19-related increase in mucormycosis. In the long run, boosting India’s national spending on health (which is currently 1.3 per cent of gross domestic product GDP) to improve the health system in areas of surveillance, disease control and preparedness, infection control procedures, and addressing the health care access issues in India will complement efforts to minimise the emergence of such opportunistic infections. As disease emergence is a threat everywhere, India’s proactive efforts to ensure health security can be useful for other countries to achieve health security.

Reports about “black fungus” amid the second and deadliest wave of the ongoing pandemic in India have fuelled confusion and panic among citizens and health care providers. Although COVID-19, caused by the novel virus SARS-CoV-2, is a new disease among humans, mucormycosis is not a new disease. The condition was first described in 1885 by the German pathologist Arnold Paltauf as “mucormycosis mucorina” in the Virchows archives of pathology and anatomy. In 1957, the American pathologist R.D. Baker coined the term mucormycosis. COVID-19, its precursor MERS-CoV, as well as other disease outbreaks such as acquired immune deficiency syndrome (AIDS) all tend to exacerbate and dwell on pre-existing human fragilities. In fact, AIDS was first suspected in 1981 as a new disease by the United States Centers for Disease Control and Prevention (CDC) epidemiologists as an immunodeficiency underlying four persons with a known disease called Pneumocystis Carinii Pneumonia . Later, it was another rare disease named Kaposi’s sarcoma that helped the diagnosis of many patients with AIDS. In fact, it is this unique survival partnerships between old and new germs that help them go undetected for a while and mask their identify, giving them ample time to spread among humans.

Mucormycosis serves as a perfect example to remind us of the basic thesis on health as a balancing game between the agent (fungus), host (human), and the environment. Any imbalance in one of these triads leads to an adverse health outcome. The COVID-19-related mucormycosis resurgence underscores a sufficiently altered balance between the host and the environment to the advantage of the germ.

The human body and health systems share one thing in common. Both show symptoms of hidden deficiencies when exposed to stress. When health systems get stressed or overburdened due to a sudden increase in patients, the system will expose the inherent weaknesses and underlying issues. Similarly, there are some infections that show up when the human body’s immunity goes down.

What do we know about black fungus occurrence?

While the fungus is omnipresent, the prevalence of the disease mucormycosis varied from 0.005 to 1.7 per million population. Like all diseases, there are countries where they appear in higher and lower frequencies. In India, the most recent reported prevalence (for 2019–2020) is nearly 80 times higher (0.14 per 1,000) compared with high-income countries. Before COVID-19, diabetes was the leading risk factor associated with mucormycosis globally, with an overall mortality of 46 per cent. Even a short course of corticosteroids has recently been linked to mucormycosis, especially in people with diabetes. Just as the link between high prevalence of metabolic disorders (diabetes, obesity) and camel populations with MERS COV in Saudi Arabia resulted in high MERS-COV burden in that country, India has the second largest population with diabetes mellitus globally that can both compound the COVID-19 crisis and accompanying opportunistic infections. Diabetes is the most common risk factor linked with mucormycosis in India, while patients with blood diseases and organ transplants take the lead in Europe and the U.S. Steroid risk for mucormycosis is well documented. Half of the patients had received corticosteroids within the month before the diagnosis of mucormycosis in the European Confederation of Medical Mycology study.

Favourable conditions for mucormycosis

The mucormycosis outbreak in India appears to be an opportunistic infection precipitated by the COVID-19 crisis. The COVID-19 situation in India exacerbates at least five favorable conditions for the emergence of mucormycosis. They include (1) immunologic alterations induced by SARS-CoV-2 infection, (2) high burden of persons with metabolic disorders such as diabetes, (3) high prevalence of steroid use as an emergency treatment for COVID-19-related respiratory distress, (4) challenges with maintaining hospital infection control procedures amid COVID-19 caseload, leading to the possibility of potential high prevalence of the fungus in hospital settings, and (5) lack of early adequate care for COVID-19 patients and suboptimal proactive control measures for people potentially at higher than normal risk for acquiring the disease, including people who have diabetes, in severe respiratory distress, and under immuno-suppressive treatment.

Opportunistic infections are diseases that do not occur in healthy individuals but occur when a person’s disease defense mechanisms are inadequate to avert the challenges of microbes around them or within them. This is also a widely used survival strategy by microbes to conquer their host (the human body). The microbes create immunologic challenges that help them get established in the human body (the stage when we observe signs and symptoms). The most widely known among such ‘opportunistic infections’ are the ones that have been associated with HIV/AIDS. These opportunistic infections are caused by organisms that are otherwise not harmful. These organisms are usually present in the natural environment, and they do not produce any symptoms even if we inhale or ingest them if our immunity is strong. However, whenever immunity is impaired, including when people use anti-rejection medications after transplant or treatment for cancer, then these organisms can produce symptoms in human beings. Some of these opportunistic infections are so severe that they will lead to sudden death, as in the case of AIDS.

While high diabetic burden is contributed by genetic susceptibility, lifestyle and dietary factors, much of diabetes-related adverse health events can be minimised by adequate control measures. In high-income countries, diabetes is often detected during routine medical check-ups affording early interventions. Such early diagnosis and intervention opportunities are suboptimal in India. Superimposed on this suboptimal care opportunities is the onset of SARS COV-2-related immunological challenges, lack of early care for COVID-19, and a health system that is challenged by excess COVID-19 cases.

GDP spent on health care in India

A pandemic is not the time to revamp the health care system. However, the success of pandemic mitigation is dependent on a functioning fully funded health care system. At 1.28 per cent of GDP spent on health care, India ranks 186th out of 200 countries in terms of government spending. In 2004, the Government of India made a commitment to raise public spending on health to at least 2-3 per cent of GDP over the next five years. That did not happen. A similar commitment was reiterated in the 2017 National Health Policy, which commits to increasing public spending on health to 2.5 per cent of GDP by 2025. The health system is a complex ecosystem of many players, including preventive programmes, care delivery, workforce development, surveillance and control, oversight bodies, and the manufacturing sector. While India exports health manpower and pharmaceutical products, deficits prevail in many essential areas with spotty distribution of care services.

First and foremost is the absence of credible institutions such as Public Health England and the CDCs of China, U.S. and Europe or the National Institutes of Health in other countries. Institutions that have national recognition and mandate to perform ‘all things public health’—collect data, inform policy and develop national guidelines and advisories. Data-driven understanding of the epidemiology of the disease, followed by case control studies of occurrences of concern, and provider guidance—these functions require substantial infrastructure, credible institutions, funding and autonomy. Absence of credible institutions can lead to misinformation that spreads faster during crisis. Universities, professional bodies and other non-profit entities may not be a substitute for governmental intuitions that can coordinate functions across many interconnected entities and ministries.

Although India has the second highest number of COVID-19 cases in the world, it still does not have a systematic way to collect and analyse COVID epidemiological data. There is no centralised functioning system with appropriate mandates to have the clinical details of patients at least from a selected number of hospitals or specialised care centers. Such a system would have been useful to have a quick analysis of data to understand the clinical characteristics of “black fungus” patients. In the absence of a centrally recognised agency to provide treatment and control guidance, there is a plethora of clinical guidance and control practices, and they vary substantially. A case control study is the most useful way to understand the risk factors of rare but emerging diseases such as mucormycosis in an epidemic situation. Such studies should have been conducted early during the outbreak so that timely advisories are available to practitioners. With half-baked knowledge and information passed down through WhatsApp and other social media platforms, these practitioners might have inappropriately used steroids in patients coming to them with fever and other symptoms, probably cases of COVID infection. Early on, long-term and indiscriminate use of steroids at high doses might have reduced the immunity of the patients resulting in mucormycosis becoming an opportunistic infection in them.

Second, the lack of preparedness was evident with the second wave. Although the country had enough time to prepare its infrastructure, including expanding the availability of oxygen and intensive care facilities, many States were unprepared to deal with the second wave. Oxygen shortage and multiple incidents of patients dying in intensive care units owing to lack of oxygen were reported. With the spread of infection to rural areas, which have a weak and unprepared public health system, patients were forced to seek care from less-than-fully-qualified and unqualified practitioners who indiscriminately use medications. Two decades ago, a study by Noble laurates Abhijit Banerjee and Dr Esther Duflo found that 41 per cent of those in the private sector who called themselves doctors did not have a medical degree while 17 per cent of them did not even have a high school degree. Analysis based on Census data in 2012 showed that 37 per cent of doctors (63 per cent in rural areas) were unqualified, while a 2016 WHO report says that 60 per cent of Indian “doctors” are “quacks”. Steroids have been much misused by unqualified medical practitioners as they give immediate results and alleviate pain, fever, breathlessness and other symptoms with which many patients go to such practitioners in rural areas and in urban slum areas. Even without any definitive diagnosis these practitioners use steroids, both injection and tablets, in most cases.

A third factor that is missing in the discourse is related to the quality of care in hospitals. Health care associated outbreaks of mucormycosis have been well documented in the past. We did not see many cases of mucormycosis in the initial wave when the hospital systems were not much overburdened. But in the second wave, with hospitals being overburdened, there is enough reason to suspect the deficiencies within the health care facilities as an important factor that contributed to the increase in the incidence of the disease. Outbreaks of mucormycosis in hospitals have been linked to hospital linens, negative pressure rooms, poor air filtration, increased humidity, non-sterile medical devices, and building construction related issues.

To understand and to confirm whether the current outbreak of black fungus is a hospital-acquired infection, we need more data like the difference in the incidence of the disease among COVID patients treated in hospitals and at home or on outpatient basis, and the time duration between hospitalisation and the emergence of such infections. If the fungal infection is more among patients who were treated for longer duration within hospitals—after adjusting for use of steroids or blood sugar levels—then it points to a system issue rather than the use of steroids or uncontrolled diabetes. A comprehensive and scientific analysis of both clinical and epidemiological data is essential to understand the complete picture.

Shortage of drugs

To treat these patients, clinicians need Amphotericin B, or the liposomal Amphotericin B. Reports indicate that these drugs are in shortage in States where there are more requirements. A sudden shortage of the drug may not be coincidental, given the regulatory environment in India which has many loopholes that permit hoarding of drugs and other essentials, as was the case of oxygen cylinders in Delhi in the recent period. Regulations and rules cannot be changed overnight, but all these point to the need to have more systems in place to enforce the regulations that already exist. Governments can use the provisions within the existing rules, and regulate the storage, distribution, and use of costly and essential medications like Amphotericin B so that clinicians get access to the medicine through a centralised system.

Finally, although mucormycosis may have received attention due to the high mortality rate during the pandemic, it underscores the need for significant public health investments in disease control—both infections and chronic diseases. Although the list of public health interventions needed is long, control of chronic diseases such as obesity and diabetes and improving dietary education should be as important as preparing for the next disease outbreak. Much of India’s urban areas developed through a haphazard development trajectory and urban population density is a reality. The potential of the three megacities (population >10 million) and 46 cities with over one million population is high both for emerging infectious diseases outbreaks and chronic diseases endemicity—a perfect disaster during diseases such as COVID-19. India’s rural areas face different health challenges—lack of access to critical care and sparse distribution of preventive services, in addition to socio-economic challenges—that exacerbate the outcome of these determinants of health.

Unless India’s leadership proactively and systematically addresses these foundational health system issues, these recurrent national health security challenges will undermine success in other development areas. Black fungus should be considered as another warning sign, in addition to the second wave of COVID-19. Such opportunistic infections cannot be fully eliminated when the underlying conditions prevail, however the frequency at which they occur can be minimised with adequate checks and balances in the health system. Mucormycosis is just the tip of the iceberg of future challenges to India’s health security.

Dr Shahul Hameed Ebrahim is professor, University of Sciences, Techniques and Technology, Bamako, Mali.

D r Muhammed Shaffi  Fazaludeen Koya is Research Analyst, Boston University, U.S.

Dr N.M. Mujeeb Rahman is Medical Superintendent (on leave), MES Medical College, Perintalmanna, Malappuram, Kerala.