There are nearly 100 viruses of the herpes group that infect many different animal species. Official name of herpesviruses that commonly infect human is Humans herpesvirus (HHV) herpes simplex virus types 1 (HHV 1) Herpes simplex virus type 2 (HHV 2) Varicella-zoster virus (HHV 3) Epstein-Barr virus, (HHV 4) Cytomegalovirus (HHV 5) Human herpesvirus 6 (HHV 6) Human herpesvirus 7 (HHV 7) Human herpesvirus 8 (HHV 8) (Kaposi's sarcoma-associated herpesvirus). Herpes B virus of monkeys can also infect humans hELMINTHS#corona virus#Aspergillosis#BUGANDO#CUHAS#CUHAS#CUHAS

1. ASPERGILLOSIS, MUCORMYCOSIS
AND HISTOPLASMOSIS
DR.HAMISI MKINDI,MD.
TO DOWNLOAD CONTACT: hermyc@live.com

2. TABLE OF CONTENTS;
1. INTRODUCTION
2. EPIDEMIOLOGY
3. TYPES OF ASPERGILLOSIS
4. PATHOPHYSIOLOGY
5. DIAGNOSTIC TESTS
6. TREATMENT
7. REFERRENCES

3. ASPERGILLOSIS
• Aspergillosis is a disease caused by Aspergillus, a common
mold (a type of fungus) that lives indoors and
outdoors(decaying leaves, plants, trees, grain crops, compost).
• Most people breathe in Aspergillus spores every day without
getting sick.
• However, people with weakened immune systems or lung
diseases are at a higher risk of developing health problems due
to Aspergillus.

4. • Although more than 100 species have been identified, the
majority of human illness is caused by
1. Aspergillus fumigatus and Aspergillus niger
2. Aspergillus flavus and Aspergillus clavatus (less frequently)
• The transmission of fungal spores to the human host is via
inhalation.

5. EPIDEMIOLOGY
• In the United States in 1996, there were an estimated 10,190
aspergillosis-related hospitalizations (95% confidence interval [CI],
9000–11,380); these resulted in 1970 deaths (95% CI, 1659–2280),
176,272 hospital days (95% CI, 147,163–206,275. The average
hospitalization lasted 17.3 days (95% CI, 16.1–18.6).
• Although aspergillosis-related hospitalizations account for a small
percentage of hospitalizations in the United States, patients
hospitalized with the condition have lengthy hospital stays and high
mortality rates
Burden of Aspergillosis-Related Hospitalizations in the United States
Erik J. Dasbach, Glenn M. Davies, and Steven M. Teutsch

6. • The total number of patients with serious and chronic mycoses in
Russia in 2011 was three million.
• Most of these patients (2607 494) had superficial fungal infections
(recurrent vulvovaginal candidiasis, oral and oesophageal candidiasis
with HIV infection and tinea capitis).
• Invasive and chronic fungal infections (invasive candidiasis, invasive
and chronic aspergillosis, cryptococcal meningitis, mucormycosis and
Pneumocystis pneumonia) affected 69 331 patients.
• The total number of adults with allergic bronchopulmonary
aspergillosis and severe asthma with fungal sensitisation was 406 082
The burden of serious fungal diseases in Russia
N. Klimko,1 Y. Kozlova,1 S. Khostelidi,1 O. Shadrivova,1 Y. Borzova,1 E. Burygina,1 N. Vasilieva1 and D. W.
Denning2

7. TYPES OF ASPERGILLOSIS
• There are different types of aspergillosis. Some types are mild,
but some of them are very serious;
1) Allergic bronchopulmonary aspergillosis (ABPA):
- Occurs when Aspergillus causes inflammation in the lungs
and allergy symptoms such as coughing, Shortness of breath
and wheezing, but doesn’t cause an infection (act like allergen)

8. 2) Allergic Aspergillus sinusitis:
- Occurs when Aspergillus causes inflammation in the sinuses and
symptoms of a sinus infection (drainage, Reduced ability to smell,
stuffiness, headache).
3) Azole-Resistant Aspergillus fumigatus:
- Occurs when one species of Aspergillus, A. fumigatus, becomes
resistant to certain medicines used to treat it.
- Patients with resistant infections might not get better with
treatment.

9. 4) Aspergilloma:
Occurs when a ball of Aspergillus grows in the lungs or sinuses, but
usually does not spread to other parts of the body. Aspergilloma is also
called a “fungus ball. Sx; cough, hemoptysis, SOB

10. http://www.learningradiology.com/notes/chestnotes/aspergillomapage.htm

11. 5) Chronic pulmonary aspergillosis:
- Occurs when Aspergillus infection causes cavities in the lungs, and can be
a long-term (3 months or more) condition. One or more fungal balls
(aspergillomas) may also be present in the lungs. Sx; Weight loss,
Cough/hemoptysis, Fatigue, SOB.

12. https://www.slideshare.net/GTAtherton/management-of-chronic-pulmoanry-
aspergillosis-and-ige-for-the-layperson

13. • Pulmonary aspergillosis has been found to be present in approximately
25% of intubated patients with critical coronavirus disease 2019
(COVID-19), with increased 30-day mortality rates.
• A report from April 2021 stated that the incidence of COVID-19–
associated pulmonary aspergillosis ranged from 4% to 35% among ICU
patients.A comparison study from March 2021 maintains that whether
COVID-19–associated pulmonary aspergillosis is a distinct entity
remains under debate, but suggests the associated high mortality rate
(60-70%) among the putative ICU cases lends credence.

14. 6) Invasive aspergillosis:
- Occurs when Aspergillus causes a serious infection, and usually affects
people who have weakened immune systems, such as people who have
had an organ transplant or a stem cell transplant. Invasive aspergillosis
most commonly affects the lungs, but it can also spread to other parts of the
body. Such as heart, kidney, CNS, GIT, spleen, liver, thyroid gland and
pancreas.
- Fever, Chest pain, Cough/hemoptysis, Shortness of breath
- Other symptoms can develop if the infection spreads from the lungs to
other parts of the body.

15. 7) Cutaneous (skin) aspergillosis:
- Occurs when Aspergillus enters the body through a break in the skin (for
example, after surgery or a burn wound) and causes infection, usually in
people who have weakened immune systems. Cutaneous aspergillosis can
also occur if invasive aspergillosis spreads to the skin from somewhere else
in the body, such as the lungs.

16. https://www.researchgate.net/figure/Primary-cutaneous-aspergillosis-of-the-elbow-
Note-the-open-weeping-ulcers-black_fig1_23423587

17. PATHOPHYSIOLOGY
• Aspergillus causes a spectrum of disease, from colonization to
hypersensitivity reactions to chronic necrotizing infections to
rapidly progressive angioinvasion, often resulting in death.
• Rarely found in individuals who are immunocompetent,
invasive Aspergillus infection almost always occurs in patients
who are immunosuppressed by virtue of underlying lung
disease, immunosuppressive drug therapy, or
immunodeficiency.

18. • Aspergillus hyphae are histologically distinct from other fungi in
that the hyphae have frequent septae, which branch at 45°
angles. The hyphae are best visualized in tissue with silver
stains.

19. • Although many species of Aspergillus have been isolated in
nature, A fumigatus is the most common cause of infection in
humans. A flavus and A niger are less common. This difference
in frequency is probably related to the ability of A fumigatus, but
not most other Aspergillus species, to grow at normal human
body temperature

20. • Human host defense against the inhaled spores begins with the
mucous layer and the ciliary action in the respiratory tract.
Macrophages and neutrophils encompass, engulf, and
eradicate the fungus.
• However, many species of Aspergillus produce toxic
metabolites that inhibit macrophage and neutrophil
phagocytosis.

21. Some of the virulence factors identified are;
i. Proteases – allergic reactions ie asthma
ii. Phospholipase –key enzyme in pathogenic fungi that cleave host
phospholipids, resulting in membrane destabilization and host cell
penetration
iii. Ribonucleases – cleaves a single phosphodiester bond in a highly
conserved region of the ribosomal RNA, So they scavenge nucleic acids
of host
iv. Restrictocin – enzymatic inactivation of the ribosome by cleaving 28S
RNA of the large ribosomal subunit. Consequently, elongation
factor binding is disrupted, and protein synthesis is suppressed
v. Catalases – a putative virulence to this fungal pathogen against the toxic
effects of human hydrogen peroxide(from phagocytes), which they cleave
into water and molecular oxygen.
vi. Mycotoxins – inhibit the function of leukocytes in terms of migration,
superoxide production and fungicidal activity

22. • Corticosteroids also impair macrophage and neutrophil function.
• Underlying immunosuppression (eg, HIV disease, chronic
granulomatous disease, pharmacologic immunosuppression)
also contributes directly to neutrophil dysfunction or decreased
numbers of neutrophils. In individuals who are
immunosuppressed, vascular invasion is much more common
and may lead to infarction, hemorrhage, and necrosis of lung
tissue. Persons with CNPA typically have granuloma formation
and alveolar consolidation. Hyphae may be observed within the
granulomata.

23. LAB TESTS
In the appropriate clinical setting of pulmonary infiltrates in a patient who
is neutropenic or immunosuppressed, visualization of the characteristic
fungi using;
1. Gomori methenamine silver stain or Calcofluor
https://webpath.med.utah.edu/INFEHTML/INFEC005.html

24. 2. positive culture result from sputum
https://www.123rf.com/stock-photo/aspergillus_fumigatus.html?sti=m4w0ohdrtaqscvpsq3|&oriSearch=aspergillus

25. 3. Needle/Tissue biopsy, or bronchoalveolar lavage (BAL) fluid
- Histopathology and silver staining for persons with invasive
aspergillosis demonstrate the characteristic septate hyphae,
branching at acute angles, and acute inflammatory infiltrate and
tissue necrosis with occasional granulomata and blood vessel
invasion
4. Imaging studies

26. MANAGEMENT
Allergic bronchopulmonary aspergillosis
• Oral corticosteroids (inhaled steroids are not effective)
• Adding oral itraconazole to steroids in patients with recurrent or
chronic ABPA may be helpful.
• Patients who have associated allergic fungal sinusitis also
benefit from surgical resection of obstructing nasal polyps and
inspissated mucus; nasal washes with amphotericin or
itraconazole have also been employed

27. Aspergilloma
• Treatment is considered when patients become symptomatic, usually
with hemoptysis
• Oral itraconazole may provide partial or complete resolution of
aspergillomas in 60% of patients
• Intracavitary treatment, using CT-guided, percutaneously placed
catheters to instill amphotericin alone or in combination with other
drugs (eg, acetylcysteine, aminocaproic acid), has been successful
in small numbers of patients [12]
• Surgical resection is curative and may be considered for massive
hemoptysis if pulmonary function is adequate
• Bronchial artery embolization may be used for life-threatening
hemoptysis in patients unlikely to tolerate surgery or in patients with
recurrent hemoptysis (eg, patients with CF in whom hemoptysis may
be related to underlying bronchiectasis with or without aspergilloma)

28. Invasive aspergillosis
• Preventive therapy and rapid institution of therapy for suspected
cases may be lifesaving
• Prophylactic antifungal therapy and the use of laminar airflow (LAF)
or high-efficiency particulate air (HEPA) filtration of patient rooms can
be effective
• Voriconazole – Drug of choice [14]
• Posaconazole, amphotericin B, or amphotericin B lipid formulations –
May be considered as empiric therapy in critically ill patients with
possible mucormycosis
• Caspofungin – In patients who are unable to tolerate, or are resistant
to, other therapies [15]
• If possible, the level of immunosuppression should be decreased

29. Chronic necrotizing pulmonary aspergillosis
• Antifungal therapy is with voriconazole or with itraconazole (if
expense is an issue), caspofungin, or amphotericin B or
amphotericin lipid formulation
• A prolonged course of therapy with the goal of radiographic
resolution is needed
• Reduction or elimination of immunosuppression should be
attempted, if possible
• Surgical resection may be considered when localized disease
fails to respond to antifungal therapy

30. BREAK TIME
RELAX

31. MUCOMYCOSIS
1. INTRODUCTION
2. EPIDEMIOLOGY
3. RISK FACTORS
4. PATHOPHYSIOLOGY
5. SYMPTOMS
6. DEFINITIVE DIAGNOSIS
7. MANAGEMENT

32. MUCORMYCOSIS
• Mucormycosis (previously called zygomycosis) is a serious but rare
fungal infection caused by a group of molds called
mucormycetes(Mucor, Cunninghamella, Apophysomyces, Lichtheimia
(formerly Absidia), Saksenaea, Rhizomucor)
• These molds live throughout the environment.
• Mucormycosis mainly affects people who have health problems or
take medicines that lower the body’s ability to fight germs and
sickness.
• It most commonly affects the sinuses or the lungs after inhaling fungal
spores from the air. It can also occur on the skin after a cut, burn, or
other type of skin injury.

33. EPIDEMIOLOGY
WORLD WIDE
• The exact incidence of mucormycosis in India is unknown due
to the lack of population-based studies. The estimated
prevalence of mucormycosis is around 70 times higher in India
than that in global data. Diabetes mellitus is the most common
risk factor, followed by haematological malignancy and solid-
organ transplant.
Epidemiology of Mucormycosis in India
Hariprasath Prakash 1,* and Arunaloke Chakrabarti 2

34. EAST AFRICA
• No reliable data exist on blastomycosis, mucormycosis or fungal keratitis.
Burden of serious fungal infections in Tanzania, First published 09, October 2015
• Diana Faini,Werner Maokola,Hansjakob Furrer,Christoph Hatz,Manuel Battegay,Marcel
Tanner,David W. Denning,Emilio Letang

35. RISK CONDITIONS
1. Immunocompromising conditions
2. Patients with uncontrolled diabetes mellitus, especially those with
ketoacidosis, are at high risk.
3. Other high-risk groups include patients with cancer, especially
those who are neutropenic and those receiving broad-spectrum
antibiotics.
4. Individuals receiving immunosuppressive agents, including oral
or intravenous steroids and tumor necrosis factor (TNF)-alpha
blockers (patients with rheumatoid disorders).

36. 5. Extreme malnutrition is also linked to mucormycosis,
especially the gastrointestinal (GI) form.
6. Iron is a growth stimulant for Mucorales; older iron chelators
such as deferoxamine and all causes of iron overload are
additional risk factors for mucormycosis.
7. Trauma and the use of contaminated medical supplies over
wounds are associated with cutaneous mucormycosis.
8. Patients with burns and those who use intravenous drugs are
at a higher risk.

37. PATHOPHYSIOLOGY
• Mucorales are ubiquitous fungi that are commonly found in soil
and in decaying matter
• The major route of infection is via inhalation of conidia; other
routes include ingestion and traumatic inoculation
http://dxline.info/img/new_ail/mucormycosis_1.jpg

38. • Ingestion leads to GI disease and occurs primarily among
malnourished patients but can also occur after ingesting non-
nutritional substances (pica).
• Mucoraceae are molds in the environment that become hyphal
forms in tissues

39. • Once the spores begin to grow, fungal hyphae invade blood
vessels, producing tissue infarction, necrosis, and thrombosis.
• When spores are deposited in the nasal turbinates, rhinocerebral
disease develops (see Rhinocerebral Mucormycosis);
www.bing.com/images/search?q=Mucormycosis+Infection+Nose&form=IRTRRL&first=1&tsc=ImageBasicHover

40. • When spores are inhaled into the lungs, pulmonary disease
develops;.
https://pathos223.com/en/image/086/1.jpg

41. • When Taken orally/ingested, oral/GI disease ensues;
https://www.apollomedicine.org/articles/2018/15/1/images/ApolloMed_2018_15_1_6_229050_f1.jpg

42. • When the agents are introduced through interrupted skin,
cutaneous disease develops
https://www.mold-help.org/wp-content/uploads/2004/10/1220-Mucormycosis-642x361-slide2.jpg

43. • When the agents are introduced in the eyes
https://emedicine.medscape.com/article/222551-overview#a5

44. The virulence factor involved in the pathogenesis of
Mucorales
1. High affinity iron permease (FTR1), allowing Mucorales
survival in iron-poor environments.
2. Spore coat protein (Cot H) present on the surface of
Mucorales results in impaired host defense.
3. ADP-ribosylation factor plays a significant role in the growth of
Mucorales.
4. Neutrophils are the key host defense against these fungi;
thus, individuals with neutropenia or neutrophil dysfunction
(eg, diabetes, steroid use) are at highest risk.
Few cases of mucormycosis have been reported in patients with
acquired immunodeficiency syndrome (AIDS).

45. • Mucormycosis should be considered in the differential diagnosis
of a necrotic-appearing wound or one with an inadequate
response to antibiotic treatment.

46. SYMPTOMS
• Based on anatomic localization
(1) Rhinocerebral - unilateral, retro-orbital headache, facial pain,
numbness, fever, hyposmia, and nasal congestion, which
progresses to black discharge. Initially, mucormycosis may
mimic bacterial sinusitis. Late symptoms that indicate invasion
of the orbital nerves and vessels include diplopia and visual
loss
(2) Pulmonary - manifests nonspecifically as fever, dyspnea, and
cough. Hemoptysis may occur in the presence of necrosis.

47. (3) Cutaneous - manifests as cellulitis, which progresses to
dermal necrosis and black eschar formation. The progressive
black necrotic lesion of cutaneous mucormycosis reflects the
vascular invasion characteristic of all forms of the disease.
(4) Gastrointestinal - usually affects severely malnourished
individuals. This infection may occur throughout the GI tract but
most commonly affects the stomach, ileum, and colon. Again, the
presentation is nonspecific, with abdominal pain, distention,
nausea, and vomiting. Hematochezia or obstruction may occur.
Some patients have tenderness to palpation or a mass. Rupture
may lead to signs of peritonitis.

48. (5) Disseminated disease - Other disseminated forms of
mucormycosis may involve the kidneys, bones, heart, and other
locations, with symptoms attributed to these organ systems.

49. DEFINITIVE DIAGNOSTIC TEST
• Definitive diagnosis is based on laboratory methods of direct examinations of
clinical specimens, fungal cultures, and histopathology.
• Specimens vary according to the type of infection and clinical presentations.
Most commonly used samples include skin scrapings from cutaneous lesions,
nasal discharges, scrapings and aspirates from sinuses in patients with
rhinocerebral lesions, bronchoalevolar lavages and needle biopsies from
pulmonary lesions, and biopsy tissue from patients with gastrointestinal and/or
disseminated disease

50. 1. Direct microscopic examination - fungal hyphae will be seen
by fluorescent microscope
https://microbeonline.com/mucormycosis-diagnosis/

51. 2. Histopathological examination - reveal broad-based, ribbon-
like, non-septate hyphae with wide-angle branching
(approximately 90°).
https://microbeonline.com/mucormycosis-diagnosis/

52. 3. Culture methods - Culture is a best diagnostic method of mucormycosis
and allows both identification to the genus and species level, and antifungal
susceptibility testing.
https://microbeonline.com/mucormycosis-diagnosis/

53. 4. Molecular methods - Recent advances in molecular biology have
contributed to the development of rapid, accurate, and sensitive methods for
pathogen detection. Most commonly used are conventional PCRs.

54. MANAGEMENT
• In current practice, Amphotericin B and Isavuconazole are the 2
antifungal agents licensed by the US Food and Drug
Administration (FDA) for the primary therapy of mucormycosis.
• First-line treatment is with an amphotericin derivative.
• In patients with extensive disease or rapid progression, the
addition of posaconazole or isavuconazole to amphotericin B
may be considered.
• Surgical removal of dead tissues

55. THANKS 4 UR ATTENTION..
BY PRESENTERS

56. REFERRENCES
1. Centers for Disease Control and Prevention
https://www.cdc.gov/fungal/diseases/aspergillosis/index.html
2. Learning radiology - Aspergilloma
http://www.learningradiology.com/notes/chestnotes/aspergillomapage
.htm
3. Chronic pulmonary aspergillosis radiology
https://www.slideshare.net/GTAtherton/management-of-chronic-
pulmoanry-aspergillosis-and-ige-for-the-layperson

57. 4. Primary Cutaneous Aspergillosis – skin lesions
https://www.researchgate.net/figure/Primary-cutaneous-aspergillosis-of-
the-elbow-Note-the-open-weeping-ulcers-black_fig1_23423587
5. Infectious Diseases Society of America (IDSA)
https://academic.oup.com/cid/article/31/6/1524/373166?login=true
6. Wiley online library – Russia based article
https://doi.org/10.1111/myc.12388
7. The Journal of Infection in Developing Countries (JIDC)
https://jidc.org/index.php/journal/article/view/27580321

58. 8. Wiley online library – Tanzania based article
https://onlinelibrary.wiley.com/doi/epdf/10.1111/myc.12390
9. Laboratory diagnosis of mucomycosis . Microbe Online
https://microbeonline.com/mucormycosis-diagnosis/
10. Medscape
https://emedicine.medscape.com/article/222551-overview