Dear Friends and Professionals
I am sharing the Guest lecture on Covid 19 and Mucormycosis @ School of public health SRM University Sikkim on 28/052021
Thanking all the great support
Dr.T.V.Rao MD
Former professor of Microbiology
at present Adviser and Member associate Elsevier research Netherlands
Dear Friends and Professionals
I am sharing the Guest lecture on Covid 19 and Mucormycosis @ School of public health SRM University Sikkim on 28/052021
Thanking all the great support
Dr.T.V.Rao MD
Former professor of Microbiology
at present Adviser and Member associate Elsevier research Netherlands
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3. Mucormycosis (zygomycosis) is an emerging angioinvasive infection caused by the ubiquitous
filamentous fungi of the Mucorales order of the class of Zygomycetes.
The population at risk for this life-threatening fungal infection is growing worldwide, and tackling the
challenges of these pathogens should become a high priority.
Management of mucormycosis is traditionally multi-modal. It involves the reversal of underlying risk
factors, aggressive and often repeated debridement and prompt antifungal treatment.
In spite of active management, mortality due to invasive mucormycosis remains unacceptably high.
4. FUNGI
• Fungi - eukaryotic microorganisms
• Essentially aerobic (limited anaerobic
capacity)
• Morphology
• Yeasts - single-celled form - reproduce by
budding
• Molds form multicellular hyphae.
• Dimorphic fungi grow as yeasts at 37°C,
but as molds at 25°C
• Structure
• Characterized by a substance in cell walls
called “chitin”
• Plasma membranes containing
“Ergosterol”
• 80S rRNA
• Microtubules composed of tubulin
5. MYCOSIS- A fungal infection is known as “mycosis”
MYCOSIS
Superficial/
Cutaneous
Superficial infections
involves the outer layer
of the skin (stratum
corneum)
Subcutaneous
Involves subcutaneous
tissue (traumatic
inoculation of fungi)
Systemic (deep) or
invasive infections
Disseminated infection
involving the vital
organs
CLASSIFICATION BASED ON SITE OF INFECTION
6. MYCOSIS
Superficial/
Cutaneous
Systemic (deep) or invasive
infections
Subcutaneous
Superficial Mycoses :
black piedra, white piedra, pityriasis
versicolor (Malassezia furfur).
Cutaneous- Candida spp
• Epidermophyton infects : skin and
nails
• Microsporum spp. infect hair and skin
• Trichophyton spp. infect hair, skin,
and nails
3 GENERAL TYPES :
1. CHROMOBLASTOMYCOSIS
2. MYCETOMA
3. SPOROTRICHOSIS
Disseminated candidiasis,
aspergillosis, mucormycosis,
chronic mycetoma, cryptococcal
meningitis
7. PRINCIPAL SITES OF DEEP MYCOSES VS.
SUPERFICIAL/CUTANEOUS/SUBCUTANEOUS MYCOSES
8.
9. DEEP MYCOSES: CHALLENGES
• Superficial infections: affect 15% of the world’s population but rarely life threatening
• Invasive (Deep mycoses) fungal infections:
Responsible for deaths up to 1.5 million/year
Making these infections one of the most deadly among communicable diseases
High mortality rates (>50%)
Despite high mortality, experts estimate that 80% of these patients can be saved
with appropriate diagnostics & treatments
But diagnosing fungal infections is difficult, because of nonspecific symptoms
Many patients are misdiagnosed with bacterial and/or viral infections, delaying appropriate
treatment
Fungi are rapidly becoming resistant to the current arsenal of antifungal agents
10.
11. RISK FACTORS FOR DEEP MYCOSES
• Impaired immune systems –Diabetics with ketoacidosis, Elderly patients
• People taking prolonged steroids (glucocorticoids)
• Cancer- Leukaemia
• Prolonged neutropenia from various causes
• Cancer (Cytotoxic) chemotherapy – leads to neutropenia
• AIDS/HIV
• Organ transplantation- Kidney, Liver, Bone marrow/stem cell
• Intensive care unit patients
• Major Surgery
• Prolonged courses of broad spectrum antibiotic administrations
• Intra-vascular catheters
13. • The most common causes attributed to the rise of mucormycosis in COVID-19
1. Patients are uncontrolled diabetes
2. The excessive use of corticosteroids for immunosuppression, and
3. long-term stays in the ICU
14. Rising Mucormycosis in Patients with COVID-19: another challenge for
India amidst the 2nd wave?
• Incidence risen more rapidly during 2nd vs.1st wave in India
• 14872 cases as of May 28, 2021
• India contributed to approximately 71% of the global cases (published literature from
Dec, 2019 to April, 2021)
• Gujarat, Maharashtra contributing mostly followed by other states such as Rajasthan,
Andhra Pradesh, Karnataka, Haryana, MP, Uttarakhand & Delhi have also shown a steady
rise
• A steady rise in the number cases & deaths related to Mucormycosis
• Several states already having declared it as an epidemic and a notifiable disease to the
national health authorities
15. Overall Patients with Risk Factors
• Patients with
• Uncontrolled diabetes mellitus
• Taking immunosuppressant drugs
• Acquired immunodeficiency syndrome
• Iatrogenic immunosuppression and
• Haematological malignancies
• Those who have undergone organ transplantation
• Mucormycosis is characterised by the presence of hyphal invasion of
sinus tissue and a time course of < 4 weeks
16. • Thermotolerant
• Mucor Species are thermotolerant i.e., they are efficiently able to survive at temperature above 37 ◦C,
thus, they can survive the raised body temperature seen in most infection diseases including COVID-
2019
• Known risk factors for mucormycosis
• Provided by SARS-COV-2 infection, including raised ferritin, immunosuppressed condition, diabetes
like state and endothelial damage
• Diabetes
• The mucorales grow fast and utilize simple carbohydrates. Diabetes like state with raised glucose levels
may act as a good source of nutrition for the organism
• Dysregulation of ACE-2 expression
• Dysregulation of ACE-2 expression not only in lungs but also in bounty in esophagus, pancreas, ileum,
colon, cardiovascular and renal tissues and how this leads to a cascade of pathways that craft a
suitable microenvironment for opportunistic infections like mucormycosis
Does COVID 19 generate a milieu for propagation of mucormycosis?
25. Types of Mucormycosis
• Rhinocerebral (sinus and brain) mucormycosis
• An infection in the sinuses that can spread to the brain
• This form of mucormycosis is most common in people with uncontrolled diabetes and in people who have had a kidney transplant
• Pulmonary (Lung) mucormycosis
• The most common type of mucormycosis in people with cancer and in people who have had an organ transplant or a stem cell
transplant.
• Gastrointestinal mucormycosis
• It is more common among young children than adults, especially premature and low birth weight infants less than 1 month of age,
who have had antibiotics, surgery or immunosuppressant
• Cutaneous (skin) mucormycosis
• Fungi enter through a break in the skin (e.g. after surgery, a burn, or other type of skin trauma)
• Most common form of mucormycosis among people who do not have weakened immune systems
• Disseminated mucormycosis
• Infection spreads through the bloodstream to affect another part of the body
• Most commonly affects the brain, but also can affect other organs such as the spleen, heart, and skin
26. Rhino-Orbito-Cerebral Mucormycosis
(ROCM)
a. Initially – nasal blockade or congestion, nasal
discharge (bloody or brown/ black), local pain
b. Facial pain or numbness or swelling
c. Headache, orbital pain
d. Toothache, loosening of maxillary teeth, jaw
involvement, Blurred or double vision with pain;
paresthesia, fever, skin lesion, thrombosis &
necrosis (eschar)
Pulmonary Mucormycosis
a. Fever, cough, chest pain, pleural effusion,
hemoptysis
b. Worsening of respiratory symptoms
c. Lung CT – confused with COVID-related
shadows; suspect Mucormycosis in patients
with thick-walled lung cavity (Need to
differentiate from COVID-associated pulmonary
Aspergillosis), reverse halo sign, multiple
nodules, pleural effusion
d. Repeated negative galactomannan & β-glucan
tests
COVID19-associated mucormycosis (CAM)
Common Presentations
Patients with COVID-19 illness (Active/Recovering/Post-discharge)
27. Other Presentations
• Cutaneous (skin) mucormycosis
• 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
• Gastrointestinal mucormycosis
• Abdominal pain
• Nausea and vomiting
• Gastrointestinal bleeding
• Disseminated mucormycosis
• Typically 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
29. This patient presented to us with history of nasal bleeding, and
swelling of the right eye with proptosis with lid drooping &
blackish discoloration of the skin around the right eye associated
with diminished vision and restricted movement in right eye in a
k/c/o COVID19 pneumonia with uncontrolled type-2 diabetes
mellitus, who was being administered injectable corticosteroids
and moist O2 during treatment for COVID19 pneumonia.
There may also be associated invasion
into the maxilla leading to palatal
perforation, which may warrant an
emergency total/partial maxillectomy
All the other departments such as
ENDOCRINOLGY, CHEST MEDICINE,
GENERAL MEDICINE,
OPHTHALMOLOGY,
RADIODIAGNOSIS, PLASTIC
SURGERY & MAXILLOFACIAL
SURGERY (PROSTHODONTICS),
PATHOLOGY & MICROBIOLOGY are
also informed and involved for their
respective role in the management
33. HISTOLOGICAL FEATURES
Histological features include: Mycotic infiltration of blood vessels, vasculitis with
thrombosis, tissue infarction, haemorrhage and acute neutrophilic infiltrate.
34. • Collection and transportation of the sample:
• Specimen should be collected in 2 containers:
• Container 1: NORMAL SALINE: for KOH stain and culture
• Container 2: 10% FORMALIN: for HPE
• Specimens should be collected aseptically in sterile containers and transported
to the laboratory within 2 hours.
• Sending swabs should be avoided if pus or sterile body fluid can be aspirated or
when tissue can be obtained. Swabs may give false negative reports.
• Dry swabs should not be used to collect specimen.
36. 1. Amphotericin B deoxycholate (D-AmB)- 1.0-1.5 mg/kg/day
2. Liposomal amphotericin B (L-AmB) (preferred treatment)- 5-10mg/kg/day
3.Inj. Amphotericin B Lipid Complex- 5mg/kg/day
ADEQUATE HYDRATION
MONITOR RENAL FUNCTION AND SERUM POTASSIUM
• Patients who are intolerant to Amphotericin B----------
CAPSOFUNGIN
POSACONAZOLE (300mg twice on day 1, followed by 300mg daily)
After 3-6 weeks of Amphotericin B therapy, consolidation therapy (posaconazole) for 3-6 months
MEDICAL
MANAGEMENT
37. • SIDE-EFFECTS:
ANEMIA
MUSCLE SPASMS
PHLEBITIS
HEADACHE
HYPOTENSION
HYPOKALEMIA
THROMBOCYTOPENIA
EMESIS
ENCEPHLOPATHY
RESPIRATORY STRIDOR
FEVER WITH CHILLS
NEPHROTOXICITY
BRONCHOSPASM
ANAPHYLACTIC REACTIONS
MECHANISM OF ACTION:
Amphotericin B binds with ergosterol, a component
of fungal cell membranes, forming pores that cause
rapid leakage of monovalent ions (K+, Na+, H+ and
Cl−) and subsequent fungal cell death.
AMPHOTERICIN-B
40. DNE was done and guided
debridement done by doing
MMA, anterior & posterior
ethmoidectomy and
sphenoidotomy and this
sample is sent for KOH
mount & C/S and HPE
Repeated endoscopies
are done thereafter to
review the status of the
cavity and for regular
suction & clearance and
for crust removal
After confirming it to
be invasive
mucormycosis by KOH
mount & C/S and HPE