INDEX

Sr.no. Name Page no.

1. Abstract

2. Introduction

3. History

4. Types

5. Pathogenesis

6. Epidemiology

7. Mechanism

8. Risk Factor

9. Signs and symptoms

10. Mucormycosis affects various type of diaseases

● mucormycosis in diabetic patients

● mucormycosis in asthma

● mucormycosis in bones and joints

● mucormycosis in malaria, acute kidney

injury and gastrointestinal bleeding

●mucormycosis in children’s

●mucormycosis in cirrhosis

11. Overall treatment of mucormycosis

12. References

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 A review on progess and challenges of
black fungus - Mucormycosis
Abstract:

Black fugus is a angioinvasive infection caused by non fungi Order mucorales.mucormycosis

is also called such as zygoMycosis. The most underlying risk factors for development of
Mucormycosis are immunosupression therapy, ketoacidosis ,Use of corticosteroid ,
overweight,cancer like lymphomas, Kidney failure, AIDIS, and also organ transplant and
disruption Of mucocutaneous barrier by cathereters and other.anatomic Area of intacellular
mucormycosis is classified in six variants are: Rhinocerebral (2) cutaneous (3) pulmonary (4)
gastrointestinal (5) disseminated (6) idiosyncratic form like such as osteomyelitis,
endocarditis, peritonitis, and nephrological diseases .Mucormycosis most commonly
manifests in sinuses (39%) ,lungs (24%),Skin(19%), brain (9%), GIT (7%), in the form of
disseminated disease (6%) And other sites (6%). treatment of mucormycosis requires a rapid
diagnosis Correction of predisposing factor ,surgical resection, and appropriate antifungal
Therapy. Only 10% cases occur in subjects with no underlying disease. These fungi often
occur in nature, especially on leaves, soil, manure, and animal droppings and can enter the
body by breathing, smelling and exposing skin lesions. It caused creatures of the subphylum
Mucormycotina, including category such as Absidia, Mucor, Rhizomucor, and Rhizopus. The
incidence of mucormycosis is approximately 1.7 cases per 1,000,000 people each year.
Surgical reduction and anti-rot treatment are the cornerstone of the fight against non invasive
mucormycosis. However, the severity and unusual diagnosis of the disease make comparative
clinical trials exploring treatments that kill children in children difficult to move.

Keywords: Mucormycosis , Mucorales , infection, zygo Mycosis.

Introduction:
Black fungus is a way of fungal infections caused by non-fungi or Mucerales [1]. The
varieties are Mucorrhyzupus, Absidia and Cunnnighamella, genera are which is often
involved. Mcormycosis is also called such as Zygomycosis. The main source of infection
(dams) is soil, dumps, ancient walls buildings etc [2]. Still zygomycota is identified as
polyphelitic and not included in modern fungal classification systems.it often affects the
sinuses,lungs,skin and brains. Black fungus infections are widespread and During the period
1992-1993, the number of infected people in the San Francisco Bay Area was estimated at
1.7 million people.

India is one of the countries with the highest prevalence of the disease, and this it is due to
the high number of people with diabetes,as these diseases are the most vulnerable groups
[3,4]. It may also be due to high humidity, which increases the spread of mold through it [5].

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About 3,200 cases were registered in five provinces, Maharashtra, Madhya Pradesh, Haryana,
Telangana and Gujarat. The province of Maharashtra is considered one of the world's most
populous countries, with an estimated 2,800 cases and 90 deaths [6]. As this fungus affects
the sinuses, brain and lungs, in addition to being the most dangerous substance that can lead
to death if the mortality rate due to fungal infection reaches about 50%, especially in patients
with diabetes and immunodeficiency diseases [7].

Mucormycosis is a rare, dangerous disease that kills most of the immune system in
developing countries. Mucormycetes or Zygomycetes a group of filamentous fungi is
responsible for this unique angioinvasive disease [8,9]. The anatomic area of intracellular
mucormycosis is classified as a variety of clinical methods. The six clinical variants are:

(a)rhinocerebral
(b)cutaneous
(c)pulmonary
(d)gastrointestinal
(e)disseminated
(f)idiosyncratic

form,such as osteomyelitis, endocarditis, peritonitis, and nephrological diseases [10].

Mucormycetes species are found all over the environment and further human infection can
occur by inhaling fungal sporangiospores or direct application of the fungus to the mouth,
eyes, mucosa or irritation of the epidermis. Symptoms of intestinal mucormycosis include:
intestinal bleeding, abdominal pain, nausea and vomiting. Patients with mucormycosis that
are spread to the brain may develop cerebral plasma or coma [11]. Characteristics of violence
of molds rapid growth and distribution in the host due to cell wall formation and genetic
modification. The expression of CotH proteins in spores and hyphae facilitates angioinvasion,
avoids detection, and suppresses the bacterial response that leads to disease manifestations
[12].

Histroy:

The first case of mucormycosis is probably the one described by Friedrich in the Chenmiester
in 1855 [13]. Furbringer first described the disease in the lungs in 1876 . In 1884 Lichtheim
introduced the development of diseases in rabbits and described two species; Mucor
corymbiafera and Mucor rhizopodiformis, later known as Lichtheimia and Rhizopus
respectively. In 1943 its association with well-controlled diabetes was reported in three cases
with severe sinus, mental and facial involvement . In 1953, Sassenarae vasiformis, found in
several cases, was separated from the soil of the Indian forest, and in 1979, P.C Misra
examined soil in an Indian orchard where they separated Apopysomyces, later found to be a
major cause of mucormycosis .Arnold Paltauf coined the name Mycosis. Mucorina ”in 1885
after describing the case with a systemic system affecting the sinus, brain and intestinal tract,
following which the term mucormycosis became popular [14].

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These deaths have been reported in natural and man-made disasters; (2004) in the Indian
ocean tsunami and the 2011 Missouri hurricane [15]. A series of diseases occurred after
Hurricane Joplin in 2011. As of July 19, 2011, 18 cases of suspected mucormycosis have been
identified, and 13 have been confirmed. In 2014 details of the deadly outbreak of
mycormycosis in 2008 emerged after television and newspaper reports responded to an article
in the medical medical Journal [16]. The 2018 study found several lines of newly cleaned
hospital delivered to implant hospitals in the U.S. They were contaminated with Mucorales
[17]. In addition to human cases of mucormycosis have been described in cats, dogs, cattle,
horses.

Types:

It is of different types depending on the organ infected:

• A. Rhinocerebral Mucormycosis
• B. Pulmonary Mucormycosis
• C. Cutaneous Mucormycosis
• D. Gastrointestinal Mucormycosis
• E. Disseminated Mucormycosis

• A. Rhinocerebral (skin and brain ) mucrormycosis:

These types of mycormycosis are infections of the sinuses that can spread to the brain. This
type of infection is more common in people with uncontrolled diabetes and in people who
have had a kidney transplant.

• B. Pulmornary (lungs) mucormycosis:

This is the most common type of infection in people with cancer and in people who have had
organ transplants or stem cells.

• C.Cutaneous (Skin) mucormycosis:

This type of infection occurs when the fungus enters the body through the skin; it can be after
surgery, burns, skin rash or some other form of skin trauma. This type of mucormycosis is
found in people with good immune systems.

• D. Gastrointestinal mucormycosis:
This mucormysis is more common in young children than adults especially infants born
prematurely and infants born less than 1 year old, less than 1 month old, with antibiotics,
surgery or antimicrobials.

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• E. Disseminated mucormycosis:
It occurs when an infection spreads through blood vessels to another part of the body.
Infections often affect the brain, but can also affect other organs such as the spleen, heart and
skin [19].
Pathogenesis:
Due to its ubiquitous nature, the Mucorales are found mainly in the surrounding environment.
People with autoimmune conditions such as diabetes mellitus that are poorly controlled or
(especially with ketoacidosis), glucocorticid treatment, neutropenia in hematologic or severe
malignancy, implants, have too much iron, and suffer from burns are at greater risk of
developing infectious disease inhaling conidia, ingestion of food and harmful ingestion of the
virus is a common form of infection.
In terms of space placement, disease manifestations occur, for example, when bullets are
inserted into the turbinate of the nasal cavity, rhino-cerebral disease develops; when you
inhale, pulmonary ; when inserted, it develops GI disease; and when agents are introduced to
damaged skin, a growing disease develops. When the fungus mucormycosis enters the tissues
from nature, it turns into hyphal forms. Fungal hyphae invade blood vessels and produce
tissue infarction, necrosis, and thrombosis. Neutrophil enters the field as the primary defense,
and as a result, neutropenia or neutrophil dysfunction occurs. For this reason, people with
neutropenia or neutrophil dysfunction (e.g., diabetes, steroid use) are at greater risk [20].

The disease begins as an infection of the skin in the thighs found on the back of the forehead,
nose, bones, and between the eyes and teeth. After that the infection spreads to the eyes, then
the lungs, and the spread can reach the brain. It is possible that black fungus has overstated
blood circulation as it damages organs due to the inability of blood to reach it, so it loses its
function and dies and this is known as necrosis. This is when the organ becomes black and
must be removed to prevent the infection from spreading to all parts of the body. In some
serious injuries, it circulates in the bloodstream to the brain, causing blurred vision and
creating gaps in the face. If left unchecked, the mortality rate rises tbetween 20-50%. The
mortality rate depends on the type of mold and the affected organ, so sinus infection is mild
compared to severe injury in the event of a lung injury [21]

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 Fig.1 Pathogenesis of pulmonary mucormycosis. (Lewis, 2013)

The most common types of Mucorales that cause mucormycosis are:

• Rhizopus Oryzae

• Rhizopus Microsporus

• Lichtheimia Corymbifera

• Lichtheimia Ramosa

• Rhizomucor Pusillus

• Mucor Circinelloides

• Apophysomyces Elegans

• Saksenaea Vasiformis

• Cunninghamella Bertholletiae

Epidemiology:

Mucormycosis is a rare but life-threatening serious infection caused by a fungal group called
mucormycetes [22]. It is a saprophytic non septate or fungal fungus of the order Mucorales
[23]. It causes angio attacks and is associated with high morbidity and mortality [24,25].
Previous Mucormycosis known as 'zygomycosis'. After the proposed removal of the
Zygomycota phylum, a fungus associated with mucormycosis is now taxed under phylum
Glomeromycotan. Therefore, tax-or clinically, 'mucormycosis' is a more appropriate term for
zygoMycosis of these diseases [26,27].

People get the disease mainly by inhaling sporangiospores and occasionally by ingesting food
contaminated with fungus or painful inoculation. Morphologically the fungus under
Mucorales are wide, aseptate or spseely septate ribbon-like hyphae, and is ubiquitous.
The most common etiological agent is Rhizopus arrhizus. Diseases caused by Rhizopus
microsporus, Apophysomyces variabilis, and Rhizopus homothallicus are on the rise. Other
rare agents are Saksenaea erythrospora, Mucor irregularis, and Thamnostylum

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lucknowense.There are differences in the prevalence of mucormycosis between western
International Fungal Education (LIFE), a website that measures the global burden of serious
fungal infections, the annual outbreak of this disease could be about 10,000 cases worldwide
outside of India. If India is included, the number will be 910,000 cases worldwide[32,33]. The
exact cause of mucormycosis in India is unknown due to a lack and Asian countries [28-31].
Due to the low sensitivity of diagnostic tests and the difficulty in collecting a sample from
deep tissue, the incidence / increase of mucormycosis is challenging to quantify. According to
the Leadingof human-based research[34]. Bangladesh has no information on the prevalence
or incidence of mucormycosis at present. Mucormycosis most commonly manifests in sinuses
(39%) ,lungs (24%),Skin(19%), brain (9%), GIT (7%), in the form of disseminated disease
(6%) And other sites (6%).

Mechanism:
Most people are exposed to Mucorales without contracting the disease. It is usually spread by
eating spoiled food, or by obtaining mucorales from the open wound. It is not transmitted
between humans [33]. In people with uncontrolled diabetes, high blood sugar provides the
necessary conditions for the development of filamentous stiffness that begins to invade blood
vessels and then enter them, thereby blocking them and causing tissue death [34].

Risk factors :

Mucormycosis is more common in such people who are unable to fight infection
(Precautionary measures) [35]. These include organ transplants, AIDS, uncontrolled
diabetes,overweight, cancer-like lymphomas, kidney failure, chronic corticosteroid and
immunosuppressive therapy, cirrhosis and mal nutrition [36] .
People with low neutrophil counts are also at risk of infection, other risks include tuberculosis
(TB). Increased iron deficiency due to deferoxamine treatment in kidney disease has also
been reported to increase the risk of Mucormycosis [37].

Use of a common steroid in the treatment of Covid -19 also reduced the decrease in energy
caused by the immune system itself during coronavirus infection. These corticosteroids
suppress the immunosuppression and raise blood sugar levels in both diabetic and non
diabetic patients, and as a result both of these effects may contribute to cases of
mucormycosis [38].

There are several risk factors and indications for diseases associated with mucormycosis.
Diabetes with or without complications, e.g., Diabetes Ketoacidosis (DKA), is one of the
leading causes of mucoromycete infection. Haematological lesions (especially acute myeloid
leukemia) and organ transplants are also common as risk factors after DM [23,31].

The most common risk in Asian and African countries is diabetes, and in western countries
(including Europe, United States, Australia and New Zealand), hematological and
reconstructive trauma are high risk factors [31,39,40].

One of the most important risk factors is corticosteroid therapy, and perhaps steroid
intolerance is one of the most common causes of increased mucormycosis in COVID-19 [24].

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Other risk factors are chronic kidney disease (CKD), tuberculosis and chronic obstructive
pulmonary disease (COPD). Iatrogenic trauma to the surgical or injection site, contaminated
intramuscular injections, adhesive tapes and endo-bronchial tubes were the sources of
infection in nosocomial mucormycosis. and dangerous features [23].

Signs and symptoms :

Fig.2: symptoms of various types of Mucormycosis.

The symptoms of mucormycosis depend on where in the body the fungus is growing.

Symptoms of rhinocerebral (sinus and brain) mucormycosis include:

• One-sided facial swelling

• Headache
• Nasal or sinus congestion
• Black lesions on nasal bridge or upper inside of mouth that quickly become more
severe
• Fever

Symptoms of pulmonary (lung) mucormycosis include:

• Fever
• Cough
• Chest pain
• Shortness of breath

Symptoms of cutaneous (skin) mucormycosis include:

It can look like blisters or ulcers, and the infected area may turn black.
Other symptoms include pain, warmth, excessive redness, or swelling around a wound.

Symptoms of gastrointestinal mucormycosis include:

• Abdominal pain
• Nausea and vomiting

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 • Gastrointestinal bleeding

Symptoms of Disseminated Mucormycosis :

It occurs in people who are already sick from other medical conditions, so it can be difficult to
know which symptoms are related to mucormycosis. Patients with disseminated infection in
the brain can develop mental status changes or coma [41,42,43,44].
Mucormycosis in various type of diasease:

(1) Mucormycosis in Diabetic patient :

Introduction :

Mucormycosis (phycomycosis, zygomycosis) it is a rare disease caused by a fungus with a

non-order mold of Mucorales Injured the third most common angioinvasive fungal infections
follow candidiasis and aspergillosis [47] . it Is affect the immune system individually nor
does it seem that way individually [48]. To the stranger, the infection of mucormycosis is
caused by mutations immune system when it increases rapidly again the attack on biological
fungal ensue is deep tissue [49].
The Various to put forward features because mucormycosis there is uncontrolled diabetes
(especially in four patients ketoacidosis), bad such as lymphomas and leukemias, kidney
failure, transplantation, long-term corticosteroid and immune therapy, cirrhosis, burning,
protein –energy malnutrition, and found immune system lack disease [50].
However, some patients with has no significant risk features [51]. Successful management of
this fatal infections require early detection the disease is also aggressive and immediate
medical and surgical interventions to prevention of high morbidity and mortality associated
with this disease process [52].

Fig. 3: (a) Extraoral photograph showing diffuse swelling on the right middle third of the face
(red circle). (b) Intraoral photograph showing necrotic bone (black arrow) and oroantral
communication in the palate (red circle)

Treatment:
The patient is presented with a suggestion that is centralized in the brain and cavernous sinus
hrombosis with a low level of ability to movement and after that a constant outburst of mind
and respiratory function. Insulin insertion, hydration, antibiotic and heparin was immediately
started in the patient.

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On the second day despite treated he had a dark blue color on the left on the side of his nose at
the time biopsy samples were also found Amphotericin B 1mg / kg / day was started
depending on the dosage An indication of suspicion without waiting for a microbiological
diagnosis. Serum potassium and creatinine levels have been tested giving him Amphotericin
B. On the same day the patient grew up hypernatremia, hypokalemia, polyuria and
coagulopathy with multiple mucosa wounds in his mouth. Liquid and electrolyte and blood
sugar disorders were strictly controlled.

On the third day the patient had Otorrhagia from the right ear and at the same time to him. The
family gave us a history of the patient's ears two weeks ago. The the color change of the face
was spread from left to right in dots of necrosis. Without effective antifungal treatment and
rapid modification of diabetic ketoacidosis, the patient experienced further deterioration. he
had quadriplegia and died on the fourth day of admission due to contraindicated hypotension.
Unfortunately we did not access to MRI or MR Venography and therefore the cause of
quadriparesis could not be suggested for sure. Negative neurological failure can it may be due
to the involvement of vascular structures, or the cavernous sinus and internal contents
(especially cranial nerves 3 and 5) lesion.

(2) Mucormycosis in asthma :

Introduction :
Fungus can cause a variety of infectious diseases, including incurable mycosis and
non-invasive mycosis, as well as physical diseases. Different types of mycosis are often
described as independent, non-independent organizations, with a few definitions of scattered
cases. Mucormycosis the third most common mycosis attack. In depressed patients, this
condition can cause uncertainty symptoms including cough, shortness of breath, and chest
pain. The fungus can grow very aggressively, destroying tissues in cases of angioinvasive
infection, leading to in the distribution of system organs [53, 54]. Still, no a case that
introduces the problem of allergen disease to The course of incurable mycosis caused by
mucormycetes has reported. Here, we describe the first reported.case of induction of
pulmonary pulmonary mucormycosis with pulmonary eosinophilia.

Case report :
A 74-year-old Japanese man with good control asthma-COPD overlap (ACO) as comorbidity
and who was treated with inhaled corticosteroid and not a long acting beta agonist was adopted
emergency surgery to treat aortic rupture aneurysm. The surgery was successful, but the flu
was also worsening dyspnea developed and persisted from the day before surgery (POD) 10.
Chest discovery revealed.The end of the end of time. Complete blood count in POD 15
showed leukocytosis (12.7 × 109 / L) with neutrophilia (10.2 × 109 / L) and eosinophilia (1.0
× 109 / L). Chest X-ray showed stiffness of the upper extremity.lungs. The patient produced
mucopurulent sputum in.which was resistant to methicillin Staphylococcus aureus found.

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We suspect nosocomial pneumonia together with the promotion of the ACO. So, we gave up
meropenem with teicoplanin and bronchodilator therapy. However, the symptoms did not
improve, and eosinophilia increased significantly (2.0 × 109 / L) however.the number of
leukocytes decreased (7.2 × 109 / L). Chest X-ray.and CT showed worse left upper extremity
stiffness lobe in POD 25 (Fig. 1a, b). To diagnose the cause of acute pneumonia and to
determine appropriate empiric therapy antibiotic, performed bronchoscopy in POD 26.
Bronchoalveolar lavage (BAL) fluid.the analysis showed an increase in eosinophils (82% of
the total.cells) and fungal fibers in the skin of papanicolau.

We started to suspect bronchopulmonary mycosis (ABPM) caused by Aspergillus based on

published conditions [3] provided that the patient indicated i) bronchial asthma as
comorbidity; ii) increase of eosinophils in both serum and BAL fluid; iii) increase in total
serum IgE volume (2,092 IU / mL); iv) readiness for certain IgE antibodies against the fungus,
including Aspergillus and certain IgG antibodies against Aspergillus in serum; and v)
filamentous mold in BAL fluid. Therefore, we corticosteroid therapy (prednisolone; 1mg /.kg
with intravenous administration of voriconazole e.POD 27. However, a BAL fungal culture
test.the liquid reveals mucormycetes, which are identified over time such as Cunninghamella
bertholletiae with PCR and DNA sequence. After that we switched to anti-lethal treatment
liposomal amphotericin B in the treatment of pulmonary mucormycosis in POD 29. Without
replacement voriconazole with liposomal amphotericin B, patient he suffered severe shock
and died at POD 39.

An autopsy revealed macroscopically extensive necrosis with severe emphysema in both

lungs . The Histopathological studies have shown significant infiltration of inflammatory
cells, which consist mainly of.neutrophils and eosinophils, with extensive necrosis and
destruction of alveoli and artery walls .A fungus with a lot of unusual fibrous tissue.A branch
of hyphae was foundon the broad sides inside wounds The fungus also attacked the.heart,
thyroid glands, kidneys, and spleen.

Fig. 4 : a, b Chest X-ray (a) and computed tomography (b) on POD 25 showed massive
consolidation in the left upper lobe and a nodular shadow in the right upper lobe. c
Eosinophilic infiltration (arrow) was confirmed by BAL fluid cytology using Diff-Quik stain.

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Discussion:
Mucormycosis is an infection caused by mucormycetes and emerges as life threatening
mycosis, especially in defenseless patients [53, 54]. Cunninghamella bertholletiae is a genus
of the genus Cunninghamella of mucormycetes is also the most common human virus in this
genus, including about 7% of all infections caused by mucormycosis. Cunninghamella
infections have been reported to be a major risk factor for death compared with Rhizopus
species [53]. Similar to the diagnosis of mucormycosis with other types of mucormycete,
diagnosis of Cunninghamella infection depends on biological identification by pathological
examination, confirmation by cultural examination. The common traditional methods of
identifying these fungi are cultural, macroscopic morphology of the colonies, and the
microscopic morphology of the organisms [55].

Cunninghamella bertholletiae is a fast-growing fungus that can grow at room temperature.

However, Cunninghamella bertholletiae can grow at temperatures above 40 ° C, which
separates it from Cunninghamella elegans, which are found in laboratory specimens.as
polluting the environment. Microscopically, The morphology of this fungus is seen as the
branches of sporangiophores that end up in the inflamed, final area round, ovoidal, or
ellipsoidal sporangioles. However, it recently reported the use of PCR and DNA sequencing
using quoted and new specimens or.specimens of structured tissue are more sensitive and
specific compared to conventional methods based on culture [56].

Cunninghamella bertholletiae can infect various human tissues. Icon angioinvasive and can
grow very aggressively, causing.tissue destruction. According to the PubMed Search for the
relationship between mucormycosis and eosinophilia, only one case of paranasal
mucormycosis brought on by serum eosinophilia can be identified; however, the case was
there negative for certain IgE antibodies in mucormycetes [57].

(3) Mucormycosis in bonds and joints :

Introduction :
Osteoarticular mycoses are rare diseases. Several years ago, several systematic reviews.
Specify important human variables, diagnosis, treatment, and outcomes of osteoarticular
malformations.mycoses [58-68]. However, it still has to be fulfilled a.the full analysis focuses
only on osteoarticular mucormycosis. So we took a systematic approach.a review of
epidemiological features, clinical, diagnostic, and treatment of these serious
diseases.Emphasis on the state of the immune system, the result.age, various mechanisms of
infection, anatomical distribution, and outcome.

Clinical manifestation and mechanisms of infection:

The most frequently reported clinical manifestations.limited movement (62%), local pain,
tenderness, and / or inflammation (59%), and cellulitis / abscess (24%). The flu was rarely

Page 12
reported. Suggested inflammatory markers were obtained by ESR and WBC; active C-data
protein was not available. Direct inoculation was the main mode of infection.in 56% of cases,
mainly in preterm patients.trauma, injury, or previous surgery. Hematogenous hemorrhage
occurs in 24% of cases, mainly in patients with hematological and other immune disorders,
disability. The volatile spread was observed in the remaining 21%.

Diagnostic image:
Osteoarticular abnormalities found in a variety of diagnostic methods include osteolytic
lesions, bone destruction / erosion, inclination and increased radionuclide capture. Magnetic
resonance imaging showed low signal intensity in T1 with weight and dots with high signal
strength in T2-weighted images.

Treatment and outcome :

Patients with osteoarticular mucormycosis were more common treated with a combination of
medical and surgical interventions..Surgical intervention and / or treatment was reported in 33
(97%) of the 34 patients.Among the 33 patients who received treatment, the majority. 28
patients (85%) treated with a combination of.pain management and surgery, four (12%) with
antifungal agents, and one (3%) with only surgical treatment. One the patient died before the
start of any treatment intervention. All cases treated with amphotericin B. Posaconazole was
used as a nutritional treatment after amphotericin B treatment in 4 cases.

The average duration of treatment was 45 days (5-573). The demolition was the worst.Regular
surgical intervention (38%) followed by orthopedic surgery Connection / repair procedures
(21%), disconnection (15%), and full discharge (15%) A total response rate of 76% was
reached at treatment of 34 viral mucormycetes and joint infections complete response by 41%
and incomplete response by 35%. One patient died before starting treatment. The overall
mortality rate was 24% for 6 (75%) of these deaths due to advanced bone infection and
treatment failure with amphotericin B, while both are related to development dangerous
substances and infections.

(4) Mucormycosis in malaria , acute kidney injury, lower gastrointestinal

bleeding :

Introduction:
Plasmodium knowlesi (P. Knowlesi) is a malaria parasite. monkeys, transmitted by
mosquitoes of the Anopheles leucosphyrus group [69]. Previously, infectious diseases of P.
knowlesi existed thought to be rare, but following numerous reports from Southeast Asian
countries, it is now widely known as the fifth dose of malaria [70]. It happens naturally P.
Knowlesi infection, randomly diagnosed as Plasmodium malariae (P. malariae), accounted for
more than half of all malaria cases in a study conducted in Sarawak [71]. However, the
infection of P. thesesies often have severe parasitemia therefore had a more severe clinical
presentation than P. malaria infection [70].

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Patients with a mild illness can be treated with chloroquine, quinine or
artemether-lumefantrine, and those with a serious illness can be treated quinine injected into
the vein or artesunate. [72]. Stomach mucormycosis is rare and only reported 7% of all
mucormycosis [73]. In a study [74] of 87 four patients.intestinal mucormycosis, the most
affected sites were 57.5% stomach, colon 32.2%, small intestine 10.4%, and esophagus 7%.
The symptom of mucormycosis is Inflammation of the blood vessels leading to endarteritis
thrombosis, leading to tissue ischemia and infarction. Therefore, ischemic Colitis-like
presentation is common in colonic mucormycosis. However, the clinical presentation of
colonic mucormycosis may be unclear, from an unexplained stomach pain of diarrhea and
nausea [74] .

Discussion:
Literature reports on P-related kidney damage. thesesies are rare. A series of recent cases in
Sabah, Malaysia [72]. It have revealed.that 12 of the 22 patients with WHO separated
P..knowles malaria suffered severe kidney damage; 11 out of 12. patients needed dialytic
support, intermediate duration.dialysis 3 days (range 1-6 days). Cyrus Daneshvar et al. [75]. 3
cases of severe kidney injury (serum creatinine> 265) were reported.micromol / l, without
liquid rehydration) from a series of cases of.8 Severe Diseases P. knowlesi. Cox-Singh et al.,
[76] reported case of severe kidney injury in a patient with P. this is an infection, with
evidence of autism with acute tubular necrosis..Studies in monkeys have shown that infection
reduces the level of glomerular filtration and increases glomerular permeability in albumin
[77]. Other studies show that P. The virus significantly reduced kidney blood flow in
monalbumi [78].

There are also very few reported cases of minor intestinal bleeding due to mucormycosis. One
is made by a mixed infection of mucormycosis and cytomegalovirus in a kidney transplant
patient [79]. reported the same.bleeding case from colonic mucormycosis in our facility.
Diagnosis of both cases was made only after histopathological examination. Intestinal
mucormycosis that affects the intestines carries a high mortality rate of more than 90%.
Mucormycosis as well occurs more frequently in patients with kidney disease [80].

This perhaps related to the defensive nature of birth. many kidney patients also appear to have
no direct link between mucormycosis and internal renal disease disease. Many kidney injuries
are related to intestinal injuries from septicemia rather than direct damage to the glomeruli,
vessels, or interstitium. Our patient has P infection. knowlesi with mucormycosis and
experienced complete recovery from both acute.

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 Fig.5 : Mucormycosis in gastrointestinal bleeding

resection specimen of the infected kidney transplant. Gross inspection of the

specimen showed extensive areas with necrosis (arrows) and purulent fluid
(asterisk) (A). Histological examination (PAS stain) showed acute purulent,
necrotizing extended inflammation with localization of thick hyphae, consistent
with mucormycosis, in arteries (B) and veins (C).

5) Mucormycosis in children :

Introduction:
Mucormycosis affects adults and children and is associated with significant illness and death
from recurrence they do not know the helpless. Here, we review the literature on
mucormycosis in children and use evidence to provide management recommendations..

Epidemiology:

As a group, the Mucoraceae represents the third most common the cause of the incoming
fungal infection after Candida and Aspergillus species [81]. The increased incidence of
mucormycosis has recommended epidemiologic studies [82]. Many features may contribute to
this increase, including selective pressure from antifungal prophylaxis by agents without
mucormycosis function [83]. Voriconazole use in patients who are depressed identified as an
important part of independent risk of mucormycosis (rate of inequality, 10.37 [95%
confidence interval (CI), 2.76–38.97]; P <.001) [84]. Still, there is evidence that the levels of
mucormycosis were growing before spreading the use of voriconazole, which shows that other
substances, such as The additional use of antidepressant medications, too, is helpful [85].

Diagnosis :

Diagnosis of mucormycosis is often made on a regular basis.Histopathologic features (broad,

hyaline, hyposeptated hyphae, concert and angioinvasion and tissue necrosis) in.appropriate
clinical condition. Cultures are not sensitive to the harshness of the Mucorales hyphae, which
remains so damaged during sample collection. As a result, only about a third of all
microscopic positive models cause a positive culture [86]. What is clear is also a problem,

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because.Isolation from illegal areas sometimes shows more pollution than disease. The culture
of clinical compliance.classification enables identification and detection of pathogen [87].
Histopathology and culture form the basis of diagnosis.in many cases, even though cellular
methods are used increasingly complementary to traditional methods [88]. Molecules testing
improves the accuracy of species identification in comparison phenotypic identification of
differentiated cultures [86]. Nuclear acid enhancement techniques target ribosomal DNA
genetic targets 18S, 28S, and Internal Transcribed Spacer (ITS) the whole region is used.
Sensitivity and specificity of cells diagnoses performed directly on new or frozen tissues are
dependent in the DNA-extraction method used [86]. New things are like that prefers tissues
embedded in paraffin, because it is formalin damages DNA [87].

Treatment:
Surgical reduction and anti-rot treatment are pillars Treatment of non-invasive mucormycosis.
Both are associated with improved outcomes for adults and children, and for in most cases, an
integrated approach is indicated [88, 87]. Combined children data showed that children
received anti-rot treatment and surgery with 18.5% CFR, compared to 60% of those receiving
painkillers alone [89]. A review of 255 cases of pulmonary mucormycosis (including cases
involving distribution) the operation was performed. The intervention reduced the CFR level
to 11% compared to 68% in those treated medically only (P = .0004) [90]. Survival benefits
are provided by those who undergo surgery of diseases of the lungs [91-93].

Distribution occurs several times before respiratory failure begins, and surgery works to
reduce the risk of fungus sepsis and protect against respiration function. Patients with a
positive initial response to antifungal treatment can be treated properly, but in the absence of
clinical development and if operational risk is considered acceptable, consideration should be
given to wedge removal, lobectomy, or pneumonectomy, depending on the severity of the
disease [92]. Significant surgical reduction is thought to be important in to treat short-term
mucormycosis, and repeated surgery is common needed to ensure adequate mitigation and
disease control continuity [94, 95].

Similarly, aggressive stimulation is important in the management of rhinocerebral

mucormycosis, i.e. is associated with high CFR in vulnerable individuals without intervention
[90, 96]. Surgery is not yet shown.completely improve the effects of neonates with intestinal
mucormycosis, which are often fatal despite aggressive treatment [97]. If possible, combined
surgery once the medical method is recommended anyway, because it is it may provide a
better chance of survival [98, 99].Amphotericin B (AmB) has anti-Mucorales activity in in
vitro [100, 101]. Both normal AmB (cAmB) and AmB lipid Complex (ABLC) is associated
with improved survival rates (324 [61%] of 532 and 80 [69%] of 116, respectively) compared
to 18% survival (59 of 333) among those who could not be treated with antifungal therapy
[88]. Children's analysis of ABLC (median dose, 4.92 mg / kg per day) in the treatment of
invasive fungus infection involves a very small number (n = 4) of four children mucormycosis
[102]. ABLC administered at 5 mg / kg per day is safe and tolerable by children; however, it
is not recommended for those with a central nervous system (CNS) involvement [87].

Page 16
(6) Mucormycosis in cirrhosis:

Introduction:
Rhinocerebral mucormycosis is also uncommon. if it is unknown or mistreated, it is the most
dangerous fatal infection known to man [103]. The clinical presentation and prediction of
oculo-rhino-cerebral Mucormycosis in patients with cirrhosis is not appropriate known.
Available books are hidden in a few cases reports or case series only. The purpose of the
current study determine the clinical presentation and outcome of rhinocerebral mucormycosis
in patients with cirrhosis.

Method:
Health records for the past five years are searched of cirrhotic patients allowed concurrent
diagnosis of mucormycosis or fungal infection. Six patients four the infection of
mucormycosis has been proven by histology or culture and patients at Aga Khan University
Hospital were confirmed. In addition to a detailed clinical examination, basic parameters such
as full blood count, liver and kidney functional Examination, diagnostic ascitic paracentesis
and abdomen ultrasound was performed to test the hepatic function again by scoring goals for
Child-Pugh.

Computed tomography (CT) of the head performed, a tissue examination was required by
biopsy obtained endoscopically below the surface anesthesia or by surgical removal.
Important too custom sent. Amphotericin B was started right there clinical diagnoses were
suspected or post-radiological as well Histopathological diagnosis. These patients were treated
by gastroenterologists in consultation with a specialist in infectious diseases, ophthalmology,
and ear, nose and throat (ENT).

Case report :
A 57-year-old man with hepatitis C virus (HCV) cirrhosis and hepatocellular carcinoma
(HCC) presented with shortness of breath, pedal edema, decreased urination discharge, dual
ear infection and parotid inflammation of five days. He had a history of oesophageal variceal
bleeding with the latest band ligation. Clinically, he had jaundice, high fever, moderate to
severe ascites, and swelling on the right side of the face below the ear.
On the basis of clinical and laboratory data, diagnostics for automatic bacterial peritonitis
(SBP), hepatic encephalopathy and mucormycosis are formed, i.e. Confi was reduced by the
custom of septate hyphae from ear cutting. He had Child's C renal disease insuffi ciency. It
was started on amphotericin B however surgical interventions were not possible because of
the poor clinical condition. He died a few days later.

Discussion:

Known risk factors for rhinocerebral mucormycosis diabetes, systemic steroids,

neutropenia,malnutrition, immunodefe ciency, leukemia, paralysis bone marrow
transplantation [104,105]. Cirrhosis of the liver it is an acquired condition of the immune defi

Page 17
ciency state and patients with chronic liver disease (CLD) is very common developing various
diseases [106,107]. All hosting plans are in danger, e.g. negative class response, once
macrophage, neutrocyte, and lymphocyte functions. Many they also show glucose intolerance
or diabetes mellitus, while some patients also take steroids for automatic hepatitis.
Dyshomeostasis and malnutrition they also have an effect. In the rotten CLD, SBP is the most
common infection. Patients taking prophylactic antibiotics for SBP tend to improve and other
rare diseases. There are only a few case reports of rhinocerebral mucormycosis in four
cirrhotic patients with or without liver transplantation [108,109]. Amphotericin B is a
pharmacological chamber stone treatment. Due to the negative side effects of kidney toxic
effects and electrolyte imbalance, it is a diffi religion to handle this drugs in patients with
cirrhosis.

Overall treatment of mucormycosis:

According to guidelines from 3 European Leukemia Infection Conference, four corner stones
management is:

1) early detection or prompt diagnosis,

2) rapid implementation of effective treatment regimens,
3) appropriate and major surgical removal of infected tissue (especially for rhino-cerebral or
skin diseases), and
4) managing priorities and causative diseases (immediate modification where possible)[
110,111,112].

Early diagnosis is probably the most influential factor patient survival. Any initial delay is
antifungal. The treatment allows more time for the mold to get inside deep tissue and blood
vessel and as a result spread vital organs [113 ].

In antifungal treatment, the most effective drugs are available amphotericin B (and lipid
composition), posaconazole, or still acuconazole. Amphotericin B, posaconazole,
isavuconazole can be administered in an IV route and posaconazole ne isavuconazole is
available in both IV and oral methods. Usually use lethal drugs, including fluconazole,
voriconazole, and echinocandins, which are not found to be effective in fighting fungus that
causes mucormycosis [26,114] .

As a delay in starting treatment associated with increasing death, it is important to start one of
these antifungal very quickly. Amphotericin B is so often used as a first-line
treatment[112,113,114]. IV use of Posaconazole is more beneficial than oral preparation for
increased disease prevalence in patients with lower kidney disease dysfunction that may not
tolerate lipid amphotericin B composition . The new triazole, saucuconazole, is mild impact
on Mucorales in vitro, so in the future, as an alternative, this is not the case it can be a
potential drug of some kind of affected [116].

Recommended wound healing is recommended any patient with a progressive autoimmune or

sinus disease of an aggressive state of infection. A disease of fierce sin, complete removal,

Page 18
including eye enucleation, perhaps required [4,32,33] . In some recurring cases, better survival
has been observed when patients underwent surgical removal internally in combination with
systemic therapy antifungal [117-120].conventional therapies for mucormycosis include iron
chelation, hyperbaric oxygen, cytokine therapy and more other drugs. However, due to a lack
of available metal data chelation, is rarely found in the role of hyperbaric oxygen of these
combined therapies is subject to active investigation [110].

Page 19
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