How Unique Regional Factors Collided to Create the Mucormycosis Crisis in India — A Hypothesis
A Preface to the Reader
“When something is important enough, you do it even if the odds are not in your favor.” Elon Musk
Since taking a keen interest in the mucormycosis epidemic in India , I have been convinced of one fact: India’s ongoing mucormycosis problem cannot be explained away by simple general host factors like immunosuppression and diabetes, despite the repeated and emphatic pronouncements of most expert mycologists to this effect. There had to be unique regional factors that singled out Indians for such a fate. The more I read and researched about it, the more the facts seemed to zero in on one factor as the prime potential culprit: Cow dung. And the mode of transmission most likely causing the disproportionately high environmental count of Mucorales in India — fumes from the burning of dung.
I had my hypothesis. To take it further, I needed to have it researched and proven in the Indian setting — an arduous undertaking considering I am based in the United States. To get expert researchers and the medical fraternity seriously interested in the hypothesis, I also needed to present it in an academic format. Publication would then hopefully elicit discussions amongst experts, and could culminate in urgent warnings educating the general population about the safe use of cow dung, as a way of reducing the incidence of mucormycosis.
The stonewalling and obstruction I have faced in the above endeavors would take more than just a Medium post to cover. I am determined, however, to continue my efforts at validating the hypothesis, and to increase awareness of this issue among the academic fraternity. With a view to pursuing the latter, here I am — being a deliberate disruptor. In what is probably a first, I am publishing my hypothesis in academic format, here on Medium, hoping for a crowd-sourced peer-review process. My original submission to Elsevier’s Medical Hypotheses that was rejected for formal publication was dated July 20th. I am posting that same article here, with a few added points and updated statistics to emphasize the knowledge gained in these two months to further support my hypothesis.
I do believe in science and in humans with integrity. I believe that there are medical professionals and researchers who are focused on actual progress in science and medicine, in new ideas, and have the best interests of patients as their primary goal. I hope to catch the attention of such researchers, who will take this project to the next level of evidence-based medicine. And with that, thousands of potential patients could hopefully be saved from the unimaginable horrors of mucormycosis.
Please read this hypothesis and help — through research and republication — explore the possibilities raised herein. If the role of herbivore dung in transmitting mucormycosis to humans can be established beyond doubt, it would benefit not just Indians, but vulnerable patients everywhere.
Thank you.
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HYPOTHESIS
● Title: How Unique Regional Factors Collided to Create the Mucormycosis Crisis in India — A Hypothesis.
● Author: Jessy Skaria, MBBS
ABSTRACT
The root causes for the alarmingly disproportionate number of mucormycosis cases in India — an extant asymmetry in its global prevalence further markedly amplified during the COVID-19 pandemic — have never been fully explained. Mucorales are found abundantly in nature, in soil and organic substrates such as compost and animal excreta, and only cause opportunistic infections in a vulnerable host, commonly on a background of immunosuppression and/or hyperglycemia. While favorable conditions for mucormycosis exist relatively uniformly across the world, why was India home to more than 70% of the global cases prior to the pandemic, and a staggering 99% following its second wave in the country? This hypothesis proposes that the intersection of a slew of unique regional factors accounts for India’s disproportionate share — preeminent among them being the use of cow dung (known to harbor the “coprophilous”, or dung-loving Mucorales). The cow holds a revered, sacred status among many Indians, and cow excreta is typically incorporated in multiple facets of their everyday lives. Cow dung and urine are also considered medicinal and used habitually in the prevention and treatment of ailments ranging from common cold to cancer. Many religious rituals and prayers involve the burning of dried cow dung cakes. Dried cow dung is used as fuel for cooking in many parts of India, and also in funeral pyres which could typically burn for 2–5 hours. These practices potentially expose the Indian populace to a consistently high presence of fungal spores in their immediate environment. Unprecedented panic triggered by the COVID pandemic resulted in an escalated use of this trusted “cure-all”, and possibly contributed to the explosion in mucormycosis cases that resulted in India’s unique “black fungus” epidemic. This hypothesis posits that the Indian population — rendered vulnerable to opportunistic fungal infections by the SARS-CoV-2 infection and its corticosteroid treatment with the attendant effects of immunosuppression and hyperglycemia — succumbed readily to mucormycosis due to their unique exposure to large loads of Mucorales in their immediate environment, caused by the extensive and intimate use of products containing the fungi-rich cow excreta. The bi-annual agricultural practice of stubble-burning is also discussed as a potential cause for the widespread dispersal of the spores, and subsequently, the large Mucorales count in the Indian environment. The hypothesis also explores the possibility of fungal loads delivered through ablutions in contaminated river waters, since surface waters are known to harbor Mucorales. Additionally, the role of other untested and poorly tested medical remedies used exclusively in India during the pandemic are also scrutinized. India’s experience in eliminating neonatal tetanus — a condition that existed in the country on a similarly disproportionate scale, and also shared the use of cow dung as a causative factor — provides an uncannily similar precedent to bolster the hypothesis. Fundamentally, this paper suggests that the cultural use of cow excreta constitutes a key variable in India’s mucormycosis crisis, that burning cow dung causing the dispersion of fungal spores could possibly explain the inexplicably high Mucorales load in the Indian air, and calls for further research at the nexus of these unique regional factors.
KEYWORDS
Mucormycosis; Mucorales; black fungus; India; cow dung; cow urine; stubble-burning; pyroaerobiology
TEXT
How Unique Regional Factors Collided to Create the Mucormycosis Crisis in India — A Hypothesis
Introduction and background
The devastating effects of the second wave of the Coronavirus Disease of 2019 (COVID-19) pandemic in India [1] have been significantly amplified by an explosion of mucormycosis cases in the country, with the government declaring it an epidemic and a notifiable disease on May 20, 2021[2]. Even preceding the second wave, India was home to a disproportionate share of this comparatively rare infection. 70 percent of all global cases of mucormycosis prior to 2019 [3], and also during the first wave of the pandemic between December 2019 and April 2021[4], were reported from India. The Leading International Fungal Education (LIFE) portal has estimated the annual prevalence of mucormycosis to be around 10,000 cases in the world, not including the ones from India. Following the inclusion of Indian data, the estimate of mucormycosis rises to 910,000 cases globally [5]. The number of Indian cases is significantly and disproportionately higher even when compared to India’s subcontinental neighbours — countries with largely similar climatic, ethnic and sociocultural milieus. Further alarmingly, official statistics indicate that since the onset of the second wave of the pandemic, India’s share of mucormycosis cases has soared to 99% of all global cases and fatalities (Figure 1) [6].
Mucormycosis, formerly known as zygomycosis and commonly alluded to as black fungus in India [7], refers to a constellation of varied conditions caused by infections with fungi belonging to the order Mucorales [8]. Mucorales are thermotolerant molds that are known to be ubiquitous in nature, widely found in the soil and on organic substrates including rotting fruits and vegetable matter, compost piles and animal excreta [9]. Due to their widespread presence in nature, most human beings are exposed to the fungus on a routine, everyday basis. The fungi are opportunistic pathogens, with mucormycosis typically only resulting in at-risk individuals, most importantly the immunocompromised and those with uncontrolled hyperglycemia. Host risk factors hence include diabetes mellitus (especially undiagnosed and those with poorly controlled blood sugar levels), neutropenia, post-infectious states, immunosuppressive therapy including corticosteroid use, transplant patients, severe malnutrition, and disruption in the integrity of the cutaneous barrier, as with trauma or burns [10]. Based on its anatomic localization, the condition can be classified into: (1) rhino-orbital-cerebral (ROCM), (2) pulmonary, (3) cutaneous, (4) gastrointestinal, (5) disseminated, and (6) uncommon presentations, including renal mucormycosis [11]. The major mode of infection is through the inhalation of the fungal spores — deposition of the spores on the nasal turbinates in a vulnerable host can result in the most common rhino-orbital-cerebral form of the disease [12], while their transport into the distal airways can cause the pulmonary form. Other modes include ingestion and traumatic inoculation leading to gastrointestinal and cutaneous presentations respectively. The condition is remarkable for its high mortality and morbidity. Mucormycosis is characterized by extensive infarction and necrosis of host tissues resulting from invasion of the vasculature by the fungal hyphae [11], and carries an overall mortality rate of 50–85%. While 50–70% of the rhinocerebral cases are lethal, pulmonary and gastrointestinal presentations carry an even higher mortality rate, since these forms are typically diagnosed late. Mortality rate in disseminated disease approaches 100% [13]. Survivors are often left with the debilitating and disfiguring sequelae of the condition and the mutilating surgeries — including orbital exenteration — that may be required for its treatment [14].
Hypothesis
There is no evidence to suggest that the accepted risk factors for mucormycosis such as immunosuppression, diabetes and post-transplant states are prevalent at a disproportionate enough scale in India to account for its staggering share of global cases of the condition. What is it then about the country that accounts for these extraordinarily high numbers? Indeed, the question of other unknown “missing links” has been raised by well-known mycologists in India, although the query has not yet generated any scientifically validated answers [15].
This hypothesis grapples with the question, particularly as it pertains to the country’s second wave of COVID-19, and ultimately posits that multiple regional factors unique to India potentially contributed to the problem. Cow excrement is proposed as a major factor — that its reported presence in multiple rituals (including spreading dung on the body and the burning of dung), and in untested ingested or topically applied remedies for COVID-19 — ensured a heavy load of Mucorales in and around predominantly vulnerable, immunocompromised, and diabetic COVID patients, thus creating the perfect storm of mucormycosis in India.
The above conclusions are drawn from the following:
1. Cow excrement is rich in the spores of Mucorales. The fungi are often referred to as coprophilous (dung-loving) and are known to have an affinity for herbivore dung [16] [17] [18] [19] [20].
2. There is a longstanding tradition in large parts of India of incorporating cow excreta into multiple facets of daily life [21] [22] — significantly and disproportionately more so than in most other parts of the world. Hinduism, the religion practiced by 80 percent of India’s population, accords a sacred and venerated status for the cow [23]. Panchagavya, for instance, ingested as an Ayurvedic medicine by many Indians, contains five ingredients derived from the cow: dung, urine, milk, ghee and curd [24]. Rituals, including applying cow dung on bodies and imbibing cow urine, and the burning of cow dung in sacred ceremonies routinely, and especially so during major religious festivals like Diwali and Holi, are common practices [25]. Herbivore dung is also burnt for cooking fuel. The dispersal of viable fungal spores in biomass fires is well documented [25a, 25b]. The burning of cow dung for varied purposes — including cooking, fumigation, havans and cremations is likely to spread the fungal spores through the fumes, which might then be inhaled by those exposed to them. It would then be logical to assume that any population that engages in such practices would harbor a heavy load of Mucorales spores in their bodies and immediate environment. Topical application, inhalation and consumption of products containing cow-excreta [26] [27] could then routinely offer entry points to large loads of the fungus, and could result in mucormycosis in an at-risk host.
3. To bolster the above point, it merits note that the personal and community use of cow excreta amongst Indians increased manifold during the COVID pandemic. Under the patronage of political and religious leaders, many Indians actively utilized cow dung and urine regularly and in copious amounts, in the hopes of preventing and treating COVID, despite warnings from the scientific community [28] [29][30]. Ritual mass fumigations (havans) that involve the burning of cow dung cakes and ghee — and potentially facilitating large airborne spore dispersal — were claimed to have virucidal effects [31], and were conducted in the open in multiple urban and rural localities throughout India [32][33][34]. Crematoriums, unable to cope with the pace of unprecedented deaths, were encouraged to use cow dung as a substitute fuel for fast depleting wood [34a]. Gomutra Arka or Cow urine distillate is claimed to have been “used successfully” on COVID patients [35]. These practices, again, possibly paved the way for unusually large fungal loads, and, syllogistically, markedly elevated chances of systemic fungal infections amongst the Indians, especially the vulnerable, immunocompromised and diabetic COVID patients, exposed directly or indirectly to these practices. Cow dung could also potentially explain the instances of mixed fungal infections, such as concomitant mucormycosis and aspergillosis, reported in many Indian patients [35a], since dung has been shown to harbor multiple different fungal species [17].
4. In a country as large and diverse as India, a federation of 28 states and 8 centrally administered union territories, the above practices are not uniformly observed. Veneration of the cow and use of products containing cow excreta are known to be more concentrated in states that have larger rural populations with relatively lower levels of literacy and stricter adherence to religious practices. These states — collectively referred to as “cow-belt states” [36] in colloquial parlance — typically also have strict laws against cow-slaughter within their jurisdictions [37]. A review of the state-wise distribution of mucormycosis within the country shows a remarkable aggregation of the cases within the states that ban cow slaughter (and by extension, consider the cow sacred and are more likely to use cow excreta), like Maharashtra, Gujarat, Madhya Pradesh, Uttar Pradesh, Haryana, Andhra Pradesh, Telangana, Rajasthan and Karnataka, while relatively sparing states like Kerala and West Bengal where cow slaughter is allowed (which in turn, translates as a populace less likely to use cow dung and cow urine therapies). (Figure 2). This is especially noticeable in the case of Kerala, which leads in the number of COVID positivity rates and Diabetes but has one of the smallest caseloads of mucormycosis, with 128 cases and 10 deaths [6] [37] [38] [38a].
Several striking incidents reported in the media of mass rituals involving the use of cow dung have been followed by reports of clusters of mucormycosis in the same areas. Examples include Kurnool [38b] [38c], Meerut [38d] [38e], Rohtak [32] [38f] and Belgaum (Belagavi) [34] [38g].
While on the topic of geographical variations based on differences in the usage of cow dung within India, the rising mucormycosis cases in Iran also merit mention. Similar to the medicinal properties attributed to cow dung and its fumes in India, parts of Iran attribute therapeutic qualities to female donkey dung. Anbarnesa smoke derived by burning donkey dung is used as a traditional medicine, and was used extensively during COVID [38h]. The number of cases of mucormycosis in Iran has now crossed 500 [38i], and it would be useful to evaluate if a correlation exists between the use of anbarnesa and mucormycosis. Similarly, the higher rates of mucormycosis in countries with greater herbivore-human interactions like Iraq, Pakistan, Bangladesh, Central and South American countries are also worthy of further scrutiny.
5. Following on from the above, the role of other untested remedies in the prevention and treatment of COVID-19 cannot be discounted:
● Coronil, a purported herbal remedy has been widely used in India as an “alternative cure/prophylactic” for COVID-19 [39]and even exported as an “immunity booster” [40]. The product which has not undergone animal or human trials has been touted, in a solitary paper of dubious academic merit [41], as an immunomodulator that prevents SARS-CoV-2 S-protein mediated viral entry into animal cells. Human testing is indicated to ensure that the purported immunomodulator effects do not actually increase the predisposition of the user to opportunistic infections. Similarly, the potential presence of steroids [42]and/or cow excreta [43] [27]in various other indigenous remedies used in India, including herbal and homeopathic ones[44], and their possible role in the mucormycosis crisis [45], cannot be excluded without further studies.
● 2-Deoxy-D-Glucose (2DG) was approved for emergency use by Indian authorities in the treatment of COVID-19 in May 2021 [46], and has so far been used exclusively in India for the purpose. Several health experts have, however, questioned the approval, based on a lack of published data on the drug’s performance in human trials [47]. If its reported potential to cause hyperglycemia [48] is accurate, the drug could actually contribute to the patient developing mucormycosis, analogous to the role of steroids and Diabetes Mellitus in rendering the host vulnerable to the infection.
6. Another unique factor that needs to be considered in the Indian context is the millions of Indians who come in contact with river waters routinely, and especially during religious festivals like the Kumbh Mela [49]. In 2021, the Mela was held in April, and preceded the second wave of COVID-19 in India [50]. Mucorales are known to exist in surface waters [51], and probably more so in polluted waters, and increased incidence of mucormycosis has been reported after natural disasters like tsunamis [52], thus pointing towards a potential water-borne route of entry. This factor gains additional importance in the Indian context since water from the River Ganga has also been touted as a ‘cure’ for COVID [53].
7. The low vaccination rates, and flouting of Covid norms in large religious and election gatherings had potentially resulted in a large cohort of Indians that was vulnerable to the SARS-CoV-2 infection [54]. The treatment of COVID with steroids markedly compounded the susceptibility of these patients to systemic fungal infections [56]. Widespread overuse of steroids in the treatment of COVID in India has been reported in the Indian media [57]. The above risks were amplified manifold in a diabetic patient, due to the possibility of uncontrolled hyperglycemia caused by the combination of diabetes and steroids. The conjunction of steroid abuse with India’s enormous diabetic population [58] has been attributed as the major cause for its large numbers of mucormycosis infections [59] [60]. As host factors they remain relevant. However, as mentioned earlier, there is no evidence to suggest that the scale of steroid abuse and prevalence of diabetes in India are disproportionately high enough in comparison to the rest of the world to account for the country’s overwhelming share (99%) of global cases of mucormycosis [6] during this particular epidemic. The above host factors do not take into account unique environmental factors, especially considering the fact that Mucorales have been isolated at disproportionately high rates in the Indian environment [60a]. This would again point to as yet unidentified factors unique to India, the ‘missing links’, working in tandem with other known and globally existent host risk factors such as diabetes and steroid use, in the causation of mucormycosis. The “environmental factor” in all likelihood , hence, provides the “missing link”. Burning of Mucorales rich substrates could potentially explain India’s increased environmental load of the fungus. In India’s case, as pointed out earlier, cow dung burnt extensively for various purposes, stands out as the most likely cause, especially during the COVID pandemic.
Stubble burning — the burning of harvested fields biannually, especially during the autumn-winter season, a common farming practice in northern India — could similarly be a cause of the high environmental load, potentially transmitting spores from both the vegetation and the manure-rich agricultural soil. This could also explain the seasonal variations — higher incidence during the autumn months — in Indian mucormycosis that have been pointed out by some mycologists [60b] [60c].
Medical Precedent
The natural history — and potentially the elimination — of mucormycosis has parallels to the Indian experience with neonatal tetanus.
In the 1980s, more than two hundred thousand newborns died every year in India due to neonatal tetanus [61]. This, when the preventable disease was already only of academic interest in the developed world. The World Health Organization (WHO) and the Indian government collaborated to identify and address the issues linked to the disproportionately high rates of this infection and neonatal fatalities in India, as compared to the rest of the world. Questions of a “missing link” in relation to India were raised, since the condition is caused by a spore-forming anaerobic bacterium (Clostridium tetani) that is present all around, especially in soil and animal manure — in India and the rest of the world. But what caused the high asymmetric prevalence of infections in India? Studies identified low antenatal vaccination rates, in conjunction with the high rates of home deliveries under unhygienic conditions, as the predominant causes [62]. In relation to the latter, the presence of cow dung in the immediate vicinity of childbirth — especially the application of cow/goat dung on the newborn’s umbilical cord stump was identified as a main factor. This finding made sense due to the abundant presence of tetanus spores in animal dung [63]. These core issues were focused on and tackled by India’s health workers, and ultimately led to the country successfully eliminating the condition in 2015 [64] [65].
Evaluation of the Hypothesis
The following methods of observational and experimental testing of the hypothesis are proposed:
● Further microbiological testing to confirm the presence of the fungi in cow excreta, with emphasis in evaluating whether particular species of Mucorales isolated from affected patients are also identified in cow dung and urine. The role of fungal spores spread through smoke from burning cow dung and stubble could be crucial in establishing the causative factor for the large Mucorales load in the Indian environment. Pyroaerobiology experts could play a pivotal role in establishing this connection.
● Detailed retrospective analysis of clinical histories of mucormycosis patients with emphasis on potential direct or indirect exposure to the spores — particularly the use of cow excreta in personal or communal daily use and rituals, including those involving burning of cow dung and inhaling the fumes, topical application and medications — needs to be performed. Occupational exposure — as in agriculture, manual scavenging, crematorium workers, priests — could be elucidated. History of contact with river waters, such as regular bathing or ritual dips, and the use of indigenous remedies also needs to be obtained.
● In patients with mucormycosis and known exposure to cow excreta, an attempt to correlate the mode of exposure to the form of the disease could be made. For example, if the hypothesis is accurate, those exposed to airborne spores through fumigation (havan) or extensive topical applications would contract rhinocerebral, pulmonary or cutaneous mucormycosis, while those who ingested them directly or through quack remedies would likely present with gastrointestinal or renal mucormycosis. Indeed, it is notable that isolated renal mucormycosis in an immunocompetent host is a clinical entity that is unique to India [3].
Implications of the Hypothesis
● Mucormycosis, once contracted, is a distressing, debilitating, mutilating and often lethal condition that is extremely difficult to treat. It can destroy patients and their families mentally, physically and financially. It is hard to overemphasize the importance of identifying the causes for the disproportionate prevalence of mucormycosis in India, since preventing the condition offers significantly better clinical and cost-effective outcomes for the general population.
● If the hypothesis is accurate, the reduction of risk could, in theory, be relatively simple by limiting exposure to the fungal spores. (Limiting exposure to fungal spores is known to reduce risk of systemic fungal infections, as multiple studies have shown increased risk and clustering of cases with unprotected exposure to fungus-laden dust during renovation and construction activities [66] [67], and even contaminated hospital linen [68].) While methods to achieve this in the Indian setting are potentially broader than with the aforementioned precedent of neonatal tetanus, the results of the exercise could be no less dramatic.
○ Educating the public on reducing the personal use of cow excreta in all forms, especially limiting burning of dung in open fires, would likely provide the highest clinical yield in attempts to eliminate the condition. Guidelines on precautions (protective equipment including gloves, shoes, long sleeved dress, masks) while handling animal excreta, including its agricultural use, could further help reduce the risk. The dangers of spreading the spores by burning of herbivore dung for fuel and in rituals should be made widely known to the public so that alternate, safer methods would be employed. Awareness on water-borne mucormycosis and the potential effect of polluted rivers also need to be stressed. While these attempts are likely to face resistance due to religio-cultural implications, the country’s success in achieving a similar objective with neonatal tetanus shows that it is not an impossible undertaking.
○ Curbing misinformation on all platforms, especially on social media, involving non-validated claims of success and usefulness of untested remedies should be undertaken alongside the above efforts.
Conclusions
This hypothesis proposes that the intersection of multiple causative factors unique to India account for the inordinate prevalence of mucormycosis in the country, particularly in relation to the second wave of the COVID-19 pandemic (Figure 3).
The most likely of these factors are:
● The widespread and varied use by Indians of cow excreta (especially dung) that is known to harbor Mucorales spores, thus exposing vulnerable, immunocompromised, and diabetic patients to heavy loads of the fungus in their immediate environment. The burning of cow dung as fuel and in rituals, and the practice of post-harvest stubble burning could potentially be of particular importance in the widespread dispersal of the spores, and likely contribute to the consistently high Mucorales count in the Indian environment.
● The large-scale use by Indians of untested and poorly tested remedies such as Coronil and 2-DG, that could have the potential for accentuating immunosuppression and hyperglycemia, thus increasing their susceptibility to the opportunistic fungal infection.
● Potential waterborne mucormycosis in the context of bathing in polluted rivers routinely and during rituals and festivals, and the ingestion of contaminated water, could also contribute to India’s disproportionate prevalence of the condition.
● If validated, the hypothesis that herbivore dung is linked to the causation of mucormycosis, would have global implications that can affect herbivore-human interactions across the world.
REFERENCES
[1] Kumar S. Second wave of COVID-19: Emergency situation in India. J Travel Med 2021. https://doi.org/10.1093/jtm/taab082.
[2] Sarda R, Swain S, Ray A, Wig N. COVID-19 associated Mucormycosis: An epidemic within a pandemic. QJM 2021. https://doi.org/10.1093/qjmed/hcab165.
[3] Prakash H, Chakrabarti A. Epidemiology of Mucormycosis in India. Microorganisms 2021;9. https://doi.org/10.3390/microorganisms9030523.
[4] Raut A, Huy NT. Rising incidence of mucormycosis in patients with COVID-19: another challenge for India amidst the second wave? Lancet Respir Med 2021. https://doi.org/10.1016/S2213-2600(21)00265-4.
[5] Prakash H, Chakrabarti A. Global Epidemiology of Mucormycosis. J Fungi (Basel) 2019;5. https://doi.org/10.3390/jof5010026.
[6] [No title] n.d. https://governmentstats.com/mucormycosis/index.html (accessed September 3, 2021).
[7] Gandra S, Ram S, Levitz SM. The “Black Fungus” in India: The Emerging Syndemic of COVID-19-Associated Mucormycosis. Ann Intern Med 2021. https://doi.org/10.7326/M21-2354.
[8] Kwon-Chung KJ. Taxonomy of fungi causing mucormycosis and entomophthoramycosis (zygomycosis) and nomenclature of the disease: molecular mycologic perspectives. Clin Infect Dis 2012;54 Suppl 1:S8–15. https://doi.org/10.1093/cid/cir864
[9] Richardson M. The ecology of the Zygomycetes and its impact on environmental exposure. Clin Microbiol Infect 2009;15 Suppl 5:2–9. https://doi.org/10.1111/j.1469-0691.2009.02972.x
[10] Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease. Clin Microbiol Rev 2000;13:236–301. https://doi.org/10.1128/CMR.13.2.236
[11] Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis 2012;54 Suppl 1:S23–34. https://doi.org/10.1093/cid/cir866
[12] Gamaletsou MN, Sipsas NV, Roilides E, Walsh TJ. Rhino-orbital-cerebral mucormycosis. Curr Infect Dis Rep 2012;14:423–34. https://doi.org/10.1007/s11908-012-0272-6
[13] Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA, Schaufele RL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 2005;41:634–53. https://doi.org/10.1086/432579
[14] Hargrove RN, Wesley RE, Klippenstein KA, Fleming JC, Haik BG. Indications for orbital exenteration in mucormycosis. Ophthal Plast Reconstr Surg 2006;22:286–91. https://doi.org/10.1097/01.iop.0000225418.50441.ee
[15] COVID-19: Did India read mucormycosis right? n.d. https://www.downtoearth.org.in/news/health/covid-19-did-india-read-mucormycosis-right--77537 (accessed July 4, 2021).
[16] Richardson MD, Rautemaa-Richardson R. Biotic Environments Supporting the Persistence of Clinically Relevant Mucormycetes. J Fungi (Basel) 2019;6. https://doi.org/10.3390/jof6010004.
[17] Obire O, Okigbo RN, Ojim CF, Others. Fungal population and diversity in partially digested cellulose from the abomasum of beef cows. J Agric Sci Technol 2010;6:783–92. http://www.ijat-aatsea.com/pdf/October_v6_n4_10/16-112-IJAT2009_92R.pdf
[18]Coprophilous Mucorales (ex Zygomycota) from three areas in the semi-arid of Pernambuco, Brazil: https://www.sciencedirect.com/science/article/pii/S1517838216309054
[19] McGranaghan P, Davies JC, Griffith GW, Davies DR, Theodorou MK. The survival of anaerobic fungi in cattle faeces. FEMS Microbiol Ecol 1999;29:293–300. https://doi.org/10.1111/j.1574-6941.1999.tb00620.x
[20] Khiralla AAI. A study on the ecological group coprophilous (dung) fungi in Khartoum. UOFK, 2015.
[21] Pathak S. Cow Dung Soap Is Cleaning Up In India. NPR 2018. https://www.npr.org/sections/goatsandsoda/2018/10/03/653739760/cow-dung-soap-is-cleaning-up-in-india
[22] Notermans C. Prayers of Cow Dung: Women Sculpturing Fertile Environments in Rural Rajasthan (India). Religions 2019;10:71. https://doi.org/10.3390/rel10020071
[23] Brown WN. The sanctity of the cow in Hinduism. éditeur non identifié; 1964. https://www.epw.in/system/files/pdf/1964_16/5-6-7/the_sanctity_of_the_cow_in_hinduism.pdf
[24] Raut AA, Vaidya ADB. Panchgavya and cow products: A trail for the holy grail. J Ayurveda Integr Med 2018;9:64–6. https://doi.org/10.1016/j.jaim.2017.12.005
[25] Singh PK, Mohanta N. A REVIEW ON HAVAN: DRUG DELIVERY BEYOND SCIENCE. Journal of Biological & Scientific Opinion 2020;8:21–5. https://doi.org/10.7897/2321-6328.082122.
[25a] Mims, Sarah & Mims III, Forrest. (2004). Fungal spores are transported long distances in smoke from biomass fires. Atmospheric Environment. 38. 651–655. 10.1016/j.atmosenv.2003.10.043. http://dx.doi.org/10.1016/j.atmosenv.2003.10.043
[25b] A deadly fungal disease on the rise in the West has experts worried (2021): https://grist.org/health/valley-fever-rising-us-west-wildfires-cocci-fungus/ (accessed September 20, 2021).
[26] Bhattacharya DP. Gujarat centre relies on cow urine, herbs, homeopathy to treat mild cases. Economic Times 2021. https://economictimes.indiatimes.com/news/india/gujarat-centre-relies-on-cow-urine-herbs-homeopathy-to-treat-mild-cases/articleshow/82513198.cms (accessed July 18, 2021).
[27] Mahajan SP, Chavan SA, Shinde SA, Narkhede MB. Miraculous Benefits of Cow Urine: A Review. Journal of Drug Delivery and Therapeutics 2020;10:275–81. https://doi.org/10.22270/jddt.v10i4-s.4267
[28] Panchagavya, Gaumutra and Yoga: Re-inventing Hinduised Medical Practices in Times of Pandemic — Asia Research Institute, NUS 2020. https://ari.nus.edu.sg/20331-38/ (accessed July 4, 2021).
[29] Indian doctors warn against cow dung as COVID cure. Reuters 2021. https://www.reuters.com/world/india/indian-doctors-warn-against-cow-dung-covid-cure-2021-05-11/
[30] As coronavirus spreads around the world, so too do the quack cures. The Guardian 2020. https://www.theguardian.com/world/2020/apr/16/as-coronavirus-spreads-around-the-world-so-too-do-the-quack-cures
[31] Kumar N, Tripathi N, Kanchibotla D. Virucidal Effect of Medicinal Smoke for Mass Fumigation using Hawan Techniques during SARS-CoV-2 Pandemic: A Review. (ISSN: 2394–6539 … 2394. https://journals.indexcopernicus.com/api/file/viewByFileId/1159543.pdf
[32] Tribune News Service. Rohtak residents turn to havan to cleanse air of coronavirus. The Tribune India 2021. https://www.tribuneindia.com/news/haryana/rohtak-residents-turn-to-havan-to-cleanse-air-of-coronavirus-251403 (accessed July 4, 2021).
[33] News18. BJP Leader in Jammu & Kashmir Performs “Havan” to Beat Covid-19. News18 2021. https://www.news18.com/news/india/bjp-leader-in-jammu-kashmir-performs-havan-to-beat-covid-19-3742334.html (accessed July 4, 2021).
[34] Dwarakanath N. Fumes fill Belgaum streets as Karnataka BJP MLA carries out havan to ward off Covid-19 2021. https://www.indiatoday.in/coronavirus-outbreak/story/fumes-fill-belgaum-streets-karnataka-bjp-mla-abhay-patil-carries-out-havan-ward-off-covid-19-watch-1807061-2021-05-26 (accessed July 18, 2021).
[34a] 2 Delhi civic bodies approve use of cow dung for cremation of bodies amid surge in COVID deaths (2021). https://www.outlookindia.com/newsscroll/2-delhi-civic-bodies-approve-use-of-cow-dung-for-cremation-of-bodies-amid-surge-in-covid-deaths/2075958 (accessed September 20, 2021).
[35] Tijare P, Ambatkar N, Tiwari V. Clinical Improvement In COVID19 Patients With Timely Intervention Of Panchagavya Medicine: A Preliminary Finding. Int J of Pharmc Res 2020;10:e5449–e5449. https://www.ssjournals.com/index.php/ijpr/article/view/5449
[35a] Singh V, Prasad A, Panda PK. Mixed invasive molds among COVID-19 patients. medRxiv 2021.08.09.21261555. https://doi.org/10.1101/2021.08.09.21261555
[36] Mandal DK. Buffalo nationalism and dalit aesthetics- a subaltern study of dhouli by mahasweta Devi. International Journal Of All Research Writings 2019;2:1–2. http://ijciras.com/PublishedPaper/IJCIRAS1367.pdf
[37] ANNEX II (8) n.d. https://web.archive.org/web/20131029185034/http://www.dahd.nic.in/dahd/reports/report-of-the-national-commission-on-cattle/chapter-ii-executive-summary/annex-ii-8.aspx (accessed July 18, 2021).
[38] Chapter ii executive summary n.d. https://web.archive.org/web/20131109002416/http://www.dahd.nic.in/dahd/reports/report-of-the-national-commission-on-cattle/chapter-ii-executive-summary.aspx (accessed July 18, 2021).
[38a] https://twitter.com/Lalitha_Ranjani/status/1421786773076643840?s=20
[38h] https://headtopics.com/mx/remedios-extranos-de-ir-n-contra-el-coronavirus-11813090
[38i] https://iranintl.com/en/iran/lethal-%E2%80%98black-fungus%E2%80%99-hits-500-iran-covid-patients
[39] Menon S. Coronavirus: The misleading claims about an Indian remedy. BBC 2021. https://www.bbc.com/news/56172784
[40] Patel K. Covid-19: Fake “immunity booster” found on sale in London shops. BBC 2020. https://www.bbc.com/news/uk-england-london-55318095
[41] Balkrishna A, Haldar S, Singh H, Roy P, Varshney A. Coronil, a Tri-Herbal Formulation, Attenuates Spike-Protein-Mediated SARS-CoV-2 Viral Entry into Human Alveolar Epithelial Cells and Pro-Inflammatory Cytokines Production by Inhibiting Spike Protein-ACE-2 Interaction. J Inflamm Res 2021;14:869–84. https://doi.org/10.2147/JIR.S298242
[42] Paudyal B, Thapa A, Sigdel KR, Adhikari S, Basnyat B. Adverse events with ayurvedic medicines- possible adulteration and some inherent toxicities. Wellcome Open Res 2019;4:23. https://doi.org/10.12688/wellcomeopenres.15096.3
[43] Dhillon A. Cow dung cocktails: why India can’t get enough of quack Covid-19 “cures.” South China Morning Post 2021 https://www.scmp.com/week-asia/health-environment/article/3134352/cow-dung-cocktails-why-india-cant-get-enough-quack (accessed July 4, 2021).
[44] Binder U, Maurer E, Lass-Flörl C. Mucormycosis — from the pathogens to the disease. Clin Microbiol Infect 2014;20 Suppl 6:60–6. https://doi.org/10.1111/1469-0691.12566
[45] Bhowmick N. Indian doctors protest herbal treatments being touted for COVID-19. National Geographic 2021. https://www.nationalgeographic.com/science/article/indian-doctors-protest-herbal-treatments-being-touted-for-covid-19
[46] Borana R. India’s Drug Regulator Has Approved DRDO’s New COVID Drug on Missing Evidence — The Wire Science 2021. https://science.thewire.in/the-sciences/dcgi-drdo-2-dg-covid-19-treatment-phase-2-3-trials-shoddy-evidence/ (accessed July 6, 2021).
[47] Koshy J. Questions remain on DRDO’s COVID drug. The Hindu 2021. https://www.thehindu.com/news/national/questions-remain-on-drdos-covid-drug/article34537596.ece (accessed July 4, 2021).
[48] Pascoe WS, Smythe GA, Storlien LH. 2-deoxy-D-glucose-induced hyperglycemia: role for direct sympathetic nervous system activation of liver glucose output. Brain Res 1989;505:23–8. https://doi.org/10.1016/0006-8993(89)90111-X
[49] Sridhar S, Gautret P, Brouqui P. A comprehensive review of the Kumbh Mela: identifying risks for spread of infectious diseases. Clin Microbiol Infect 2015;21:128–33. https://doi.org/10.1016/j.cmi.2014.11.021
[50] Pandey G. India Covid: Kumbh Mela pilgrims turn into super-spreaders. BBC 2021. https://www.bbc.com/news/world-asia-india-57005563
[51] Novak Babič M, Zupančič J, Brandão J, Gunde-Cimerman N. Opportunistic Water-Borne Human Pathogenic Filamentous Fungi Unreported from Food. Microorganisms 2018;6. https://doi.org/10.3390/microorganisms6030079.
[52] Benedict K, Park BJ. Invasive fungal infections after natural disasters. Emerg Infect Dis 2014;20:349–55. https://doi.org/10.3201/eid2003.131230
[53] Mishra VN, Kumari N, Pathak A, Chaturvedi RK, Gupta AK, Chaurasia RN. Possible Role for Bacteriophages in the Treatment of SARS-CoV-2 Infection. Int J Microbiol 2020;2020:8844963. https://doi.org/10.1155/2020/8844963
[54] Frayer L. India Is The World’s Biggest Vaccine Maker. Yet Only 4% Of Indians Are Vaccinated. NPR 2021.
[55] Mishra GP, Mulani J. Corticosteroids for COVID-19: the search for an optimum duration of therapy. Lancet Respir Med 2021;9:e8. https://doi.org/10.1016/s2213-2600(20)30530-0
[56] Tandon A, Pandey L. COVID-19, steroids, and mucormycosis: What an ophthalmologist should know. Indian J Ophthalmol 2021;69:1970. https://doi.org/10.4103/ijo.ijo_1143_21
[57] Use of steroids in Covid-19 treatment: What experts have warned so far. Hindustan Times 2021. https://www.hindustantimes.com/india-news/use-of-steroids-in-covid-19-treatment-what-experts-have-warned-so-far-101621184470534.html
[58] Editor. Diabetes in India 2019. https://www.diabetes.co.uk/global-diabetes/diabetes-in-india.html (accessed July 4, 2021).
[59] Moorthy A, Gaikwad R, Krishna S, Hegde R, Tripathi KK, Kale PG, et al. SARS-CoV-2, Uncontrolled Diabetes and Corticosteroids-An Unholy Trinity in Invasive Fungal Infections of the Maxillofacial Region? A Retrospective, Multi-centric Analysis. J Maxillofac Oral Surg 2021:1–8. https://doi.org/10.1007/s12663-021-01532-1
[60] Patel A, Agarwal R, Rudramurthy SM, Shevkani M, Xess I, Sharma R, et al. Multicenter Epidemiologic Study of Coronavirus Disease-Associated Mucormycosis, India. Emerg Infect Dis 2021;27. https://doi.org/10.3201/eid2709.210934.
[60a] Chakrabarti A. The recent mucormycosis storm over Indian sky. Indian J Med Microbiol. 2021;39(3):269–270. https://doi.org/10.1016/j.ijmmb.2021.06.010
[60b] Muhammad Isa Abdurrahman, Sukalpaa Chaki, Gaurav Saini. Stubble burning: Effects on health & environment, regulations and management practices,Environmental Advances,
Volume 2,2020,100011,ISSN 2666–7657. https://doi.org/10.1016/j.envadv.2020.100011
[60c] https://pubmed.ncbi.nlm.nih.gov/12161726/
[61] Sokhey J, Bhargava I. Control of neonatal tetanus in India. Indian Pediatr 1984;21:515–9. https://pubmed.ncbi.nlm.nih.gov/6519778/
[62] Bairwa M, Sk S, Rajput M, Khanna P, Malik JS, Nagar M. India is on the way forward to maternal and neonatal tetanus elimination! Hum Vaccin Immunother 2012;8:1129–31. https://dx.doi.org/10.4161%2Fhv.20262
[63] Roper MH, Vandelaer JH, Gasse FL. Maternal and neonatal tetanus. Lancet 2007;370:1947–59. https://doi.org/10.1016/s0140-6736(07)61261-6
[64] Annadurai K, Danasekaran R, Mani G. Elimination of Maternal and Neonatal Tetanus in India: A Triumph Tale. Int J Prev Med 2017;8:15. https://doi.org/10.4103/ijpvm.IJPVM_392_15
[65] editorial@tribune.com. India declared free of neonatal tetanus, Yaws. The Tribune India 2016. https://www.tribuneindia.com/news/archive/nation/india-declared-free-of-neonatal-tetanus-yaws-266162 (accessed July 4, 2021).
[66] Krasinski K, Holzman RS, Hanna B, Greco MA, Graff M, Bhogal M. Nosocomial fungal infection during hospital renovation. Infect Control 1985;6:278–82. https://doi.org/10.1017/s0195941700061750
[67] Kanamori H, Rutala WA, Sickbert-Bennett EE, Weber DJ. Review of fungal outbreaks and infection prevention in healthcare settings during construction and renovation. Clin Infect Dis 2015;61:433–44. https://doi.org/10.1093/cid/civ297
[68] Alexander J Sundermann, Cornelius J Clancy, A William Pasculle, et al. Remediation of Mucorales-contaminated Healthcare Linens at a Laundry Facility Following an Investigation of a Case Cluster of Hospital-acquired Mucormycosis, Clinical Infectious Diseases, 2021;, ciab638, https://doi.org/10.1093/cid/ciab638
