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From Forests to Deserts: Analyzing the Global Environmental Impact of Widespread Deforestation

Shradha Bisht¹*, Anubhuti Juyal¹, Mamta F Singh² and Anupam Bisht²

¹Amity University, India

²COER University, India

Submission: July 09, 2024; Published: July 16, 2024

*Corresponding author: Shradha Bisht, Amity Institute of Pharmacy, Amity University, UP, Lucknow Campus, India, Email: itsshradha30@gmail.com

How to cite this article: Shradha Bisht*, Anubhuti Juyal, Mamta F Singh and Anupam Bisht. From Forests to Deserts: Analyzing the Global Environmental Impact of Widespread Deforestation. Int J Cell Sci & Mol Biol. 2024; 7(5): 555723. DOI: 10.19080/IJCSMB.2024.07.555723

Abstract

Mucormycosis emerges as a swift-moving fungal assailant, exploiting the vulnerabilities of a compromised immune system triggered by medications, illnesses, or other exigencies. A disconcerting revelation surfaces, unveiling a threefold to fourfold increase in infection rates among Covid patients, where the insidious role of steroid medication, a double-edged sword inhibiting the immune system, comes to light. The eye, our delicate ocular outpost, becomes the epicenter of Mucormycosis’ impact. Consequently, clinicians navigating this medical terrain must don the mantle of suspicion, as early detection becomes pivotal when dealing with patients harboring these risk factors. This comprehensive overview unveils the intricacies of Mucormycosis, unraveling the symphony of symptoms, assessment protocols, therapeutic strategies, and management approaches. Delving into the intricate dance between host functions and the fungal invader’s tropism post-invasion, this narrative aims to illuminate the multifaceted facets of this elusive adversary.

Keywords: Mucormycosis; Immune system vulnerability; Covid-19 connection; Steroid medication impact; Ocular impact; Cellulolytic; Ligninolytic

Introduction

Opportunism is the broad term for the practice of exploiting situations, sometimes where the enemy is vulnerable. When our immune systems are compromised, some organisms also take advantage of these openings and enter, multiply, and mutate on the side of our bodies to produce deadly diseases. Among these species, there is a group of fungus that only affect immune-compromised patients and do not harm healthy people. A person is susceptible to these opportunistic infections because of several predisposition characteristics. Patients are more susceptible to these infections because of long-term use or high dosages of immune-suppressing medications like steroids and illnesses like diabetes, cancer, and HIV. Another stark example of a pandemic situation that makes people more vulnerable to opportunistic fungal infections is the current COVID-19 disease brought on by SARS-CoV 2. A new epidemic was observed in individuals who were not only feverish and breathless but also experiencing pain in their eyes and other facial regions during the second wave of COVID-19, when all hospitals were filled with COVID patients. The infection of a rare group of fungi called mucormycosis, which is brought on by individuals from the order Mucorales, which is now widely referred to as “black fungus” among COVID-19 patients, was eventually found to be the source of this illness [1].

Mucormycosis can infect the sinuses and facial bones, enter the brain, or harm the eyes to the point that individuals lose their vision. Mucormycosis can kill up to 50% of individuals who contract it if it is left untreated or treated slowly. According to one population-based study, there are roughly 500 cases of mucormycosis in the United States per year, or 1.7 cases per million individuals [2]. According to autopsy series, mucormycosis occurs in 1 to 5 instances out of every 10,000 autopsies, which is 10- to 50-fold less frequently than invasive Candida or Aspergillus infections [3,4,5].

Mucormycosis can be classified into at least six clinical categories, including rhinocerebral, pulmonary, cutaneous, gastrointestinal, disseminated, and miscellaneous, depending on the clinical presentation and the involvement of a specific anatomic site. It should be mentioned that certain kinds of invasive mucormycosis are more common in people with specific host defense weaknesses. For example, the rhinocerebral form of diabetic ketoacidosis is more common in patients than in the pulmonary or disseminated versions. [6-9].

Epidemiological Data

One-fourth of the COVID-19 patients had been found to have mucormycosis, a rare but dangerous fungal infection. The disease was declared notifiable by the government in the third week of May 2021, and all states were required to report cases—both suspected and confirmed—to the Integrated Disease Surveillance Programme (IDSP) [10].

There were 388 occurrences of mucormycosis between 2013 and 2015, and roughly 56% of those cases had uncontrolled diabetes, according to an Indian study. Trauma was the secondlargest risk factor; however, it was only mentioned in 10% of cases, highlighting how important it is to manage risk factors [1- 3]. In Southern India (Tamil Nadu), an investigation over a tenyear period reported 18.4 new cases year between 2005 and 2015 [4].

Between 2015 and 2019 there were 9.5 new instances reported annually in Tamil Nadu, according to another study. 465 recent cases were recorded annually in a study conducted over 21 months at 12 India-based clinics. The top 12 centers saw about 38 of these cases. Although mucormycosis is less common than infections caused by invasive Aspergillus, it nonetheless affects a significant number of patients (14%) according to multicenter research conducted in Indian intensive-care units (ICUs). With a mean of 171,504 (SD: 12,365.6; 95% CI: 195,777-147,688) cases and mean attributable mortality of 65,500 (38.2%) deaths per year, the cumulative burden varied between 137,807 and 208,177 cases. According to data, India has a mucormycosis incidence that is about 70 times higher than the 0.02 to 9.5 cases (with a median of 0.2 cases) per 100,000 people estimated for the global prevalence of the disease.

Habitat with the macroscopic and microscopic appearance

A Mucorales is a type of saprophyte organism that lives in a range of environments, such as soil, plants, manure, and organic waste products like rotting fruits and vegetables. It is a member of the Kingdom Fungi, Phylum Zygomycota, and Order Mucorales. Mucorales are primarily found in plants, soil (rotten, dead, dead), manure, and dead organic detritus. Inhaling Mucorales spores, which are commonly present in the air, can cause SARS-CoV-2, a potentially fatal infection. They could be inhaled by anyone with a robust immune system, but if someone’s immunity is weakened, the effects could be disastrous. Another option to stop fungus spore inhalation is to wear a mask. But the masks must never be worn and discarded once more. The masks’ frequent use can cause them to grow fungus spores. Because mold and mildew thrive in humid environments, it’s crucial to properly air the house, dust the carpets and screens, and keep the place dry. Avoid going near a construction site or an area that is heavily polluted with dust [1].

On Sabouraud or potato dextrose agar, Mucorales colonies develop at room temperature (25–30°C). The growth, which is very rapidly, immediately covers the agar surface. It appears fluffy or cotton candy-like. The colony is originally white when viewed from the front, changing from grayish to brown as sporangia develops. A mucor’s sporangia are normally rounded or pear-shaped. A mucor’s sporangia are normally rounded or pear-shaped. The sporangia in Mucor are made up of wellformed, subtending columellae. The hyphae might seem simple or branching [1].

Transmission

The organism that causes mucormycosis, Muscorales, is a spore-forming fungus that creates spores that are 3-11 micrometers in diameter, yellow or brown, and are simple to aerosolize. The most efficient method of transmission is through contact with decaying objects and an unclean environment. When blood oxygen levels are insufficient, fungi can swiftly multiply and become ensconced in the sinuses and lungs. They can withstand the elevated body temperature linked to most infectious illnesses, including COVID-19, since they are thermo-tolerant. Additionally, SARS-CoV-2 is a known mucormycosis risk factor. The Mucorales have a dietary supply that is comparable to diabetes and have rapid growth. They also absorb simple carbs. Due to the fungal’s sequential behavior, Garrett’s theory of succession for the decomposition of sugar by fungi may be applicable. The sugar fungi come first, followed by the cellulolytic, ligninolytic, and then the secondary sugar fungi. Any other blackish staining, nasal blockage, or swelling in the periorbital region should prompt the doctor to do an emergency biopsy and start therapy right once.

Symptoms

The most prevalent type of mucormycosis is rhino-orbitalcerebral mucormycosis, which affects 45-74% of people. Other common forms include cutaneous (10-31%), pulmonary (3- 22%), renal (0.5-9%), gastrointestinal (2-8%), and disseminated infections (0.5-9%). Breast, ear, spine, heart, and bone infections are other odd sites of infection mentioned in the literature from India.

Mucormycosis manifests differently depending on which regions of the body the fungus has infected. If you exhibit any of the symptoms listed below, you should be suspected of having mucormycosis. nasal discharge, nasal congestion, and sinusitis (blackish or bloody). a single-sided facial pain, numbness, swelling, or black discoloration over the forehead, along with localized pain in the cheekbone. teeth loosening, jaw involvement, painful double vision or hazy vision, thrombosis, necrosis, and skin lesions. discomfort in the chest, pleural effusion [6].

Pathogenesis

Mucor produces millions of spores, which are tiny, darkcolored globular structures that most fungi make and release into the atmosphere. The spores start to germinate and create threadlike structures called mycelia when they touch wettish shells, such as soil or manufactured material. The mycelia spread out, eat the nearby sugars to feed on, and develop. Spore counts are often higher in the summer than they are during the monsoons in tropical regions like India. However, the number of spores per cubic meter inside residences is often about 100-250 as opposed to 1,000-5,000 outside. More than 90% of the total spore density in the air is made up of five to ten species. Unfortunately, these spores can also be found in hospitals. Patients with end-stage renal failure in the pre-erythropoietin era provided the original data on the involvement of iron in the etiology of mucormycosis. Due to their chronic renal failure-related anemia, these individuals experienced iron excess. Deferoxamine therapy used to decrease iron levels in these patients came with a substantial risk of rapidly lethal, disseminated mucormycosis. Deferoxamine is an iron chelator for the human host, but it functions as a siderophore for fungus, providing iron directly to the Mucorales. The availability of host iron has since been discovered to be essential for the Mucorales’ capacity to spread infection. Indeed, greater baseline blood iron levels were associated with a higher risk of mortality in the sole randomized, controlled clinical study ever done for the treatment of mucormycosis.

The subsequent investigation into the role of diabetic ketoacidosis (DKA) in why diabetes mellitus is predisposed to mucormycosis initially focused on this issue. Even though not all diabetes patients with mucormycosis are in DKA,8 diabetic people in DKA are more likely to develop mucormycosis than diabetic patients who are not in DKA. According to pathogenesis studies, the blood’s acidic environment causes iron to separate from proteins that are securing it, delivering free iron to the fungus [7].

Over time, even in the absence of acidosis, hyperglycemia increases the risk of mucormycosis by approximately 4 probable components

i. Upregulation of a mammalian epithelial receptor (GRP78) that ties to Mucorales, enabling tissue entrance;

ii. Upregulation of a contagious protein, CotH, that ties to the mammalian receptor to start attack into have tissue;

iii. Upregulation of a contagious protein, CotH, that ties to the mammalian receptor to start infection into have tissue;

iv. Initiating inadequately described flaws in phagocytic function.

Reduced immunity and a higher risk of developing mucormycosis include symptoms of COVID-19, HIV/AIDS, and other viral infections, congenital bone marrow disease, severe burns, malignancies, and untreated or inconsistently treated diabetes. Individuals with COVID-19 who have taken steroids are especially at risk because steroids weaken the immune system, which increases the likelihood of mucormycosis infections in these patients. Because of this, it’s best to avoid using steroids unless it’s absolutely required. (Figure1)

Prognosis and morbidity rate

The forecast is dependent on the degree of illness association and the moment that the illness-related therapy begins. According to Chamilos et al. research’s patients with hematological malignancies who delayed successful amphotericin B-based treatment for more than five days saw a roughly twofold increase in 12-week mortality (82.9% as opposed to 48.6% for those who started treatment right away). Rhino-cerebral infection has a 75% survival rate in patients without basic disorders, drops to 20% with other diseases, and is dangerous and fatal in situations of pneumonic infection The focus of the contamination determines the survival rate, which is supposedly 45% in cases of rhino cerebral mucormycosis, 33% in cases of central cerebral mucormycosis, and 36% in cases of pneumonic structures. Sinusitis without cerebral inclusion has a superior survival rate of 87%, cutaneous segregation has a survival rate of 90%, and its lowest or considered lethal in cases of dispersed illness is 16%, with a contribution from the gastro digestive system of 10% Neutropenia, threatening cases unrelated to disease, and low gauge serum iron/ferritin grouping all have better survival rates.

Mucormycosis and body’s defense

By the age of oxidative metabolites and the cationic peptides defensins, mononuclear and polymorphonuclear phagocytes of normal hosts destroy Mucorales. Clinical evidence demonstrates that these phagocytes are the key component of the host’s defense mechanism against mucormycosis. In any case, normally harmless parasites that assault human tissues when the immune system has been compromised by another disease. They are referred to as sharp illnesses. Overall, unlike their pathogenic bacterial counterparts, growths rarely result in dangerous illnesses. Occasionally, a few growths, such the Candida yeast, can lead to actual contamination. For instance, mucormycosis is more likely to develop in neutropenic patients. Patients who have damaged phagocytes are also more likely to develop mucormycosis. The ability of phagocytes to go toward and kill live things via both oxidative and nonoxidative processes is known to be impaired by hyperglycemia and acidosis. The ability of mice broncho-alveolar macrophages to prevent spore germination in vitro or later in vivo contamination brought on by intranasal immunization is also affected by corticosteroid treatment. It is yet unknown exactly how ketoacidosis, diabetes, or steroids reduce the ability of these phagocytes. Recently, the disease known as mucormycosis has afflicted many people who were recovering from coronavirus. Attacking the sinus, the growth spreads to the intra-orbital and cerebral regions. 50 to 80 percent of patients could pass away if its mobility is not restrained in the middle.

Management and Treatment

Utilize steroids sensibly, following the appropriate timing, dosage, and duration. If the patient is still taking them, lower the dosage with the goal of stopping them quickly. Stop using immunomodulating medications. Antibiotics should be used wisely to address the disease. Amphotericin B therapy must start right away. strict blood glucose monitoring and control for patients who have just been admitted and those who have just been discharged. Control diabetes and diabetic ketoacidosis. Keep a high index of suspicion in presence of risk factors, daily examination of eyes, nose, and mouth for detecting signs. Using clean sterile water for humidifiers may help manage mucormycosis [8].

Drugs

A prescription antifungal medication, generally one of the following: amphotericin B, Posaconazole, or isavuconazole, is required to treat the dangerous infection known as mucormycosis. Amphotericin B, Posaconazole, and isavuconazole are given intravenously, whereas the other medications are taken orally (posaconazole, isavuconazole). Strongly advised first-line therapies include high-dose liposomal amphotericin B, while moderately advised first-line therapies include intravenous isavuconazole and intravenous or delayed-release tablet posaconazole. Liposomal amphoterecin B can be safely supplied at higher doses for a longer period than amphotericin B deoxycholate because it is much less nephrotoxic.

Amphotericin B deoxycholate is not advised due to its high level of toxicity, but in environments with limited resources, it might be the only choice. Recognizing disease patterns and receiving an early diagnosis are essential for managing mucormycosis. Other medications, such as echinocandins, voriconazole, and fluconazole, are ineffective against the fungi that cause mucormycosis. Quick correction of metabolic abnormalities is necessary in patients with uncontrolled diabetes, as well as the use of sodium bicarbonate (with insulin) to reverse ketoacidosis. Whether the acidosis is mild or severe, this will help with a better outcome because it reduces Mucorales’ ability to attack the host tissues. There should be a swift reduction in the use of corticosteroids and immunosuppressive drugs, to the absolute minimum. The European Confederation of Medical Mycology (ECMM) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) have published guidelines that advise using defenselessness testing to guide mucormycosis therapy and compile epidemiological data. The ESCMID/ECMM guidelines and the European Conference on Infections in Leukemia (ECIL-6) advocate the use of a lipid plan of amphotericin B as the first-line therapy for mucormycosis. For liposomal amphotericin B (AmB), the recommended dose is 5 mg/kg/day, and it can go as high as 10 mg/kg/day for contamination that affects the focal nervous system. Spellberg et al. suggested a more practical method for “Blend Therapy” for Mucormycosis because current monotherapy has a high mortality rate, particularly in patients with haematological malignancies. Dexycholate, Liposomal AmB (5–10 mg/kg), AmB lipid complex, AmB colloidal scattering, Posaconazole (400 mg bid), and the board of hidden centre conditions are all antifungal treatments. One other mixture of antifungal drugs that is suggested as a second line of treatment combines caspofungin and lipid AmB, lipid AmB and Posaconazole, and excludes Deferasirox [9].

Another adjuvant treatment that creates a more oxygenimproved cell climate in combination with the organisation of cytokines concurrently with the antifungal treatment is the use of hyperbaric oxygen. Interferon- has shown to improve the resistance reaction against Mucorales in vitro and in some preclinical studies, and these findings could potentially aid in the treatment of the condition as there is no clinical data available demonstrate their adequacy, these treatments ought to be utilized with caution (Figure 2).

Surgical Intervention

Mucormycosis is typically quickly mild, and antifungal therapy alone frequently falls short of controlling the contamination. The various mucormycosis specialists have a wide range of antifungal specialist susceptibilities; certain strains may be profoundly resistant to amphotericin B. In addition, the characteristic angioinvasion, apoplexy, and tissue putrefaction of this infection cause the defence less entry of infectious specialists to the contaminated area. Therefore, even if the causative organic entity is incapable of being treated by an antifungal specialist in vitro, the antifungal may not be effective in vivo. Finally, medical intervention is essential due to the enormous amount of tissue putrefaction that occurs during mucormycosis and cannot be prevented by killing the organism [10].

Conclusion

It is still necessary to investigate the pathogenesis of mucormycosis to significantly reverse the course of infection caused by mucormycosis. Although there has been a noticeable improvement in the outcomes of mucormycosis infections because of the development of more effective antifungal treatments and a focus on earlier diagnosis, further pathogenesis research, including infection caused by other species, including those outside the family Mucoraceae, will enable future management and treatment of the infection.

References

1. Gokulshankar S, Mohanty BK (2021) COVID-19 and black fungus. Asian Journal of Medicine and Health Sciences 4(1): 137-140.
2. Rees JR, Pinner RW, Hajjeh RA, Brandt ME, Reingold AL (1998) The epidemiological features of invasive mycotic infections in the San Francisco Bay area, 1992–1993: results of population-based laboratory active surveillance. Clin Infect Dis 27: 1138-1147.
3. Hotchi M, Okada M, Nasu T (1980) Present state of fungal infectionsin autopsy cases in Japan. Am J Clin Pathol 74: 410-416.
4. Tietz HJ, Brehmer D, Ja¨nisch W, Martin H (1998) Incidence of endomycoses in the autopsy material of the Berlin Charite´ Hospital. Mycoses 41(2): 81-85.
5. Yamazaki T, Kume H, Murase S, Yamashita E, Arisawa M (1999) Epidemiology of visceral mycoses: analysis of data in annual of the pathological autopsy cases in Japan. J Clin Microbiol 37: 1732-1738.
6. Khor BS, Lee MH, Leu HS, Liu JW (2003) Rhinocerebral mucormycosis in Taiwan. J Microbiol Immunol Infect 36: 266-269.
7. McNulty JS (1982) Rhinocerebral mucormycosis: predisposing factors. Laryngoscope 92: 1140-1143.
8. Nithyanandam S, Jacob MS, Battu RR, Thomas RK, Correa MA (2003) Rhino-orbito-cerebral mucormycosis. A retrospective analysis of clinical features and treatment outcomes. Indian J Ophthalmol 51: 231-236.
9. Peterson KL, Wang M, Canalis RF, Abemayor E (1997) Rhinocerebral mucormycosis: evolution of the disease and treatment options. Laryngoscope 107: 855-862.
10. Balwan KW, Saba N, Rasool N (2021) Epidemiology of Mucormycosis in India: A Notifiable Disease. Saudi J Pathol Microbiol 6(6): 187-191.