fungal disease in children

1. FUNGAL DISEASES
IN
CHILDREN
1
BY:
DR. PRIYANKA GANANI

2. CONTENTS
 INTRODUCTIONTO FUNGI
 VARIOUS FORMS OF FUNGI
 TYPES OF FUNGAL INFECTION
 FUNGAL INFECTION
◦ Candidiasis
◦ Candida diaper rash
◦ Tinea infection
 Tinea capitis
 Tinea corporis
 Tinea pedis
 Tinea versicolor
◦ Aspergillosis
◦ Crytococcosis
◦ Coccidiodomycosis
◦ Blastomycosis
◦ Histoplasmosis
◦ Pneumocystis infection
2

3. INTRODUCTIONTO FUNGI
•They have a dense rigid cell wall made of glucan and
chitin.
•Their cell membrane contains sterols (ergosterol), making
them similar enough to human cell membranes to have
negative implications for the membrane destroying
properties of antifungal drugs.
3
•Fungi are eukaryotic, non-motile, and
usually aerobic.
• They can exist as parasites or free living
organisms and need organic sources of
nourishment.

4. • Yeasts – Round/oval, unicellular, and reproduce via budding
• Molds – Long, floppy, fluffy colonies that microscopically can be seen
as long tubular structures called hyphae and reproduce by forming
spore-forming structures at the end of hyphae called conidia.
• Dimorphs – Most medically important, can change from yeast to mold
and back, and grow in environment as molds and in humans as yeast.
4
Fungi come in many forms but only
three are of our interest as they may
cause disease in human being:

5. Types of Fungal Infections
Fungal infections in children are broadly classified into three types:
I. Superficial/cutaneous – present on skin, hair, nails (Candidiasis, Candida diaper rash,
Tinea infection)
II. Subcutaneous – infection in tissues under the skin (Sporotrichosis,
Chromoblastomycosis, Mycetoma)
III. Systemic – they are of two types:
1.True Pathogens –Which have the ability to cause disease in healthy host
(Histoplasmosis,Coccidiodomycosis, Blastomycosis)
2. Opportunists –Which cause disease exclusively in immunocompromised individuals
(Invasive candidiasis/candidemia, Zygomycosis, Pneumocystis infection )
5

6. Levels of Invasion by Fungal Pathogens
6

7. CANDIDIASIS
• Candidiasis occurs mostly as a superficial infection of the mucous
membrane or skin but the infection can involve deeper structures
(e.g. oesophagus, lungs) in severely debilitated or
immunosuppressed persons.
• It is also called oral thrush.
7

8. • Appears as white patches known as “plaques”
• If the surface of the plaque is scraped away, a sore and
reddened area will be seen underneath, which may
sometimes bleed.
• Occurs most commonly in babies, particularly in the first few
weeks of life.
• Outbreaks of thrush in older children may also be the result of
an increased use of antibiotics and steroids, which disturbs
the balance of microbes in the mouth. 8

9. • Candida normally inhabits the gastrointestinal tract, the female genital tract and the skin.
• The portal of entry is usually mucosal or skin.
• Intact epithelial barriers, normal neutrophils, lymphocyte and macrophage function,
adequate antibody and complement level, and normal bacterial flora are the host factors
which prevent invasion.
• During penetration of skin or mucous membrane, the yeast cells of Candida are
transformed into hyphal form. Hyphae being larger than the yeast are more resistant to
phagocytosis.
• It is believed that high concentration of phospholipase enzyme at the tip of the hyphae
may be related to the greater invasiveness of this form.
• They develop candidacidal activity following fungal penetration, which involve
myeloperoxidase and superoxide or cationic proteins.
• The phagocytic cell activity is crucial for protection against invasive candidiasis.
• Thus, increased incidence of invasive candidiasis is seen in neutropenic patients. 9

10. Acute pseudomembranous Candidiasis
• It is commonly known as “oral thrush” and it appears as a thick,
white soft and friable plaque (pseudomembrane) on the oral
mucosa
• The plaque can be easily wiped off by gentle scraping, which leaves
an erythematous, raw, bleeding surface in the affected area.
• The lesions may occour at any mucosal site
• They vary in size from small drop like areas to confluent plaques
covering a wide suface
11

11. •The plaque consists of fungal organisms, keratotic debris,
inflammatory cells, desquamated epithelial cells and fibrin etc.
•Oral thrush commonly occurs among children, debilitated
elderly persons and AIDS patients
•In neonates, the diseases is contracted from birth canal of an
infected mother
12

12. Acute Atrophic Candidiasis
• It occurs when the pseudomembranous covering of oral thrush is
lost.
• The lesion prevents a generalised red, painful area over the
mucosa, which often causes tenderness, dysphagia and burning
sensation etc.
• The condition is commonly seen on the dorsum of the tongue in
patients receiving long term antibiotic or steroid therapy
13

13. Candida-Associated Angular Chelitis
• An important form of chronic atrophic candidiasis is “angular cheilitis”. It
occurs at the angle of the mouth among persons having deep
commissural folds secondary to over closure of mouth.
• The infection starts due to the colonization fungi in the skin folds
following deposition of saliva due to repeated lip-licking
• Clinically the patients often have soreness, erythema and fissuring at the
corner of the mouth. In some cases the defect can extend over the
adjoining skin surfaces
14

14. • It can occur among persons with lip-licking habits, denture wearing
or deficiency of riboflavin, vitamin B-12 and folic acid deficiency
etc.
• Under favourable conditions (vitamin deficiency, malnutrition and
antibiotic therapy etc.) lesions similar to angular chelitis could be
produced by other organisms like staphylococcus aureus or
streptococcus-β hemolyticus etc
15

15. Chronic Atrophic Candidiasis
• This form of candidiasis is commonly seen in palatal mucosa of the
denture wearing elderly persons
• The condition is more often seen in females than males
• The lesion clinically appears as a bright red, erythematous, velvety areas
with little keratinization
• It is regarded as secondary candidal infection of oral tissues modified by
continous wearing of ill-fitting dentures and associated poor oral hygiene
• Most of the lesions of chronic atrophic candidiasis are clinically
asymptomatic
16

16. Chronic Hyperplastic Candidiasis
• It appears as a slightly elevated, indurated, persistent, white plaque
or patch on the oral mucosa that often resembles oral leukoplakia.
• /
• The lesions could be bilateral and are mostly seen on the buccal
mucosa near the commisure. Some lesions may also develop over
the tongue or palate etc.
• The patchy areas are of irregular thickness and density and they
have a rough, nodular surface
17

17. • These lesions cannot be removed by scraping and in some cases
there may be presence of erythematous areas within the patch
• Development of chronic hyperplastic candidiasis is often favoured
by certain conditions like smoking, denture wearing and occlusal
friction.
18

18. Localised Mucocutaneous Candidiasis
• This is characterised by long standing and persistent candidal
infections in the oral cavity, skin, nails and vaginal mucosa, etc.
19

19. Familial Mucocutaneous Candidiasis
• It is believed to be transmitted genetically as autosomal recessive
trait and most of the patients are mildly affected.
20
Syndrome Associated Candidiasis
Several candidiasis (both acute and chronic variety) are
well recognised opportunistic infections in
immunosuppressed patients, particularly those suffering
from AIDS. Depressed cell-mediated immunity is
believed to be the cause for development of these lesions

20. Gastrointestinal candidiasis
• Gastrointestinal candidiasis Candidiasis may involve esophagus and rarely stomach, in immunosuppressed
children.
• Esophagitis may be asymptomatic or it may cause burning sensation in throat and suprasternal area of chest,
dysphagia, and anorexia.
• UpperGI endoscopy reveals white plaques on the mucosal surface, notably in the distal third of esophagus.
• Nausea and vomiting are common in young children. Many may not have associated oral thrush. Stomach or
intestinal ulcers may occur. Atrophic glossitis, chronic hyperplastic candidiasis may occur in critically ill
children.A syndrome of mild diarrhea occurs in normal individuals.
• Candida is not considered as a true enteric pathogen, its presence mostly in stool likely reflects recent
antimicrobial therapy.
• Retrograde migration from GI tract into biliary tract may cause gallbladder infection.
21

21. Pulmonary infection Candida
• Pulmonary infection Candida is commonly isolated from respiratory
secretions as it frequently colonizes the respiratory tract.
• Demonstration of tissue invasion is essential to diagnose Candida
pneumonia or tracheitis.
• It is a rare condition seen in immunosuppressed children and in
those intubated for long periods, and on broadspectrum antibiotics.
• The pulmonary infection may cause fever, cough, abscesses,
reticulonodular infiltrates, and effusion.
22

22. Urinary tract infection
• Urinary tract infection Candiduria may reflect colonization or may be
the only manifestation of urinary tract disease.
• Most of the patients are asymptomatic.
• More often, candiduria is associated with instrumentation, in situ
catheter, abnormality of the urinary tract or immunosuppressed host
especially in diabetics.
• Rarely, masses of Candida (fungal balls) may obstruct ureters and
cause obstructive nephropathy. Candida casts in the urine suggest
renal tissue infection
23

23. Candidal Endocarditis
• Patients who have undergone prosthetic heart valve replacement
and those who are using long time venous catheters are at risk for
developing candidal endocarditis.
• Clinically the patients often develpes fever, dyspnoea, edema and
congestive cardiac failure, etc.
• Candidial growth in the valve may result in the development of
major venous embolism
24

24. Candidal Meningitis
• Spread of candidal organism into the brain results in meningitis,
which could be a consequence of oral candidiasis and in such cases,
the organism can be detected from the CSF.
• Patients often develop fever, headache, stiffness in the body and
hemiplegia.
• The condition is often fatal.
25

25. Candidal Septicaemia
• It occurs due to disseminated spread of candidal organisms
throughout the body and it can be secondary to serve oral or
oropharybgeal candidiasis.
• Clinically the patients often develop fever, chill, nausea, vomiting,
shock, coma etc.
• The condition can be fatal if not treated in time.
26

26. Disseminated candidiasis
• This occurs in neonates, especially in premature infants, in an
intensive care setting, and should be suspected when the baby
fails to respond to adequate dose of antibiotics.
• These infants have unexplained feeding intolerance,
cardiovascular instability, apnea, new or worsening respiratory
problems, fluctuating glucose levels, thrombocytopenia, or
hyperbilirubinemia.
• Disseminated candidiasis is also common in children with
hematological malignancies, and in those undergoing bone
marrow or organ transplantation. 27

27. Treatment
• Suspensions of nystatin, held in contact with the oral
lesions.
• Other drugs of value are clotrimazole, amphotericin B and
miconazole.
28
Drugs Dose and route Comment
Amphotericin B
deoxycholate
1–1.5 mg/kg/day, IV Broadspectrum,
nephrotoxic
Liposomal amphotericin B 3–5 mg/kg/day, IV Broadspectrum
Fluconazole 6–12 mg/kg/day, IV and
oral
Most commonly used
Voriconazole 6–8 mg/kg/day, IV and oral Multiple drug interaction
Caspofungin 50 mg/m2/day, IV Broadspectrum

28. Candida Diaper Rash
• It is sometimes called napkin dermatitis, a rash which occurs
in the buttocks. Nappy rash will occur when the skin is
sensitive and there is a presence of a trigger factor which
includes prolonged exposure to urine
• It tends to be in the deepest part of the creases in the groin
and buttocks. The rash is usually red with a clearly defined
border and consists of small red spots close to the large
patches 29

29. • Any diaper rash that lasts for 3 days or longer may be
candidiasis. A Candida diaper rash can be accompanied
by Candida infection of the mouth (thrush).
• A breastfeeding infant with a thrush infection may
inadvertently infect the mother’s nipple/areola area. If such
an infection is suspected, simple topical medications may be
prescribed by her doctor. 30

30. TINEA INFECTION
It is called “ringworm” because the infection may produce ring-shaped
patches on the skin that have red, wavy, worm-like borders.
Some of the ways of catching Tinea is by direct skin-to-skin contact with an
infected person, by sharing items with an infected person, or by touching a
contaminated surface
31

31. • Tinea capitis results in a diffuse,
itchy, scaling of the scalp that
resembles dandruff. It can cause
patches of hair loss on the scalp.
• It is especially common among
children aged 3–9, particularly
children who live in crowded
conditions in urban areas.
32

32. • Scalp ringworm spreads via contaminated
combs, brushes, hats, and pillows.
Treatment
• Topical treatments are ineffective
• Fungistatic agents are somewhat effective
(miconazole, clotrimazole) in combination to
systemic administration of griseofulvin.
• Vigorous daily scrubs of scalp help removal of
infectious debris. 33

33. Tinea corporis means “ringworm of the body”; it involves the
non-hairy skin of the face, trunk, arms, or legs.
 This would produce the classic ring-shaped patches with
worm-like borders which may occur singly or in groups of
threes and fours.
It can occur in persons of all ages.
Tinea Corporis normally resolves itself in several months
Widespread tinea corporis may require systemic griseofulvin
treatment (about 6 weeks for effective treatment)
34

34. Tinea corporis – Body Ringworm
35

35. • Tinea Pedis (athlete’s foot) produces area of redness,
scaling, or cracked skin on the feet, especially between the
toes. The affected skin may itch or burn, and the feet may
have a strong odor.
• It is often acquired by walking barefoot on contaminated
floors.
• Treatment of Tenia pedis includes topical antifungal
agents – tolnaftate, miconazole applied for several weeks
36

36. Tinea Pedis – Athlete’s Foot Infection
37

37. • Tinea versicolor or more commonly known as “white spots” is
caused by a fungus known as Malassezia furfur.
• This fungus is present on the skin of utmost of the people but
will only cause infection in some of them.This infection is
common round the year in hot and humid climate. It occurs
more often in older children and young adults.
38

38. • The infection causes a rash which may appear on the back, neck,
upper chest, shoulders, armpits, and upper arms.
• The skin rash consists of peeling, oval patches with sharply defined
borders, and pimple-like bumps.
• The patches appear white or
black on dark-skinned people
and are usually pink or tan on
the more fair-skinned.
• It does not cause itching unless the person is hot or sweaty. The
patches may be more prominent after the skin has been exposed to
the sun, because the patches do not tan. 39

39. ASPERGILLOSIS
• Very common airborne soil fungus
• A. fumigatus most commonly
• Serious opportunistic threat to AIDS, leukemia, and
transplant patients
• Aspergillus may cause three separate groups of diseases:
1. Hypersensitivity (e.g., allergic bronchopulmonary
aspergillosis (ABPA); Aspergillus mediated asthma and
hypersensitivity pneumonia; and malt worker’s disease),
2. Saprophytic (noninvasive e.g., aspergilloma)
3. Invasive disease [e.g., invasive aspergillosis (IA)]
ABPA is an important and common disease caused by
Aspergillus species.
40

40. Allergic Bronchopulmonary Aspergillosis
• Inhaled A. fumigatus spores germinate into hyphae within bronchi and release various proteins (e.g.,
proteases, superoxide dismutases, hemolysin, etc.) and toxins which induce production of inflammatory
cytokines and chemokines, such as IL-6, IL-8 that leads to disruption of pulmonary epithelium and
persistent abnormal immunological inflammatory response.
• People with asthma and CF that develop ABPA are found to have some genetic susceptibility factors.
• Infection usually occurs in lungs – spores germinate in lungs and form fungal balls; can colonize sinuses, ear
canals, eyelids, and conjunctiva
• Invasive aspergillosis can produce necrotic pneumonia, and infection of brain, heart, and other organs
• Management of ABPA includes use of steroids for control of inflammation; and itraconazole to suppress
Aspergillus colonization. 41

41. Clinical Features Allergic bronchopulmonary aspergillosis(ABPA)
• The ABPA presents with worsening cough and wheezing which may be accompanied by fever, malaise,
and expectoration of brown plugs.
• The ABPA may be in chronic form with intermittent acute exacerbations.
• Chest examination may reveal findings of underlying disease, i.e., asthma or CF along with wheeze and/or
crepitations, clubbing, weight loss,
• The ABPA should be suspected in asthmatics that are difficult to control or inadequately treated with
marked eosinophilia.
• Clinical staging of ABPA (Patterson staging)
Clinical stages for allergic bronchopulmonary aspergillosis (ABPA)
• Stage I: Acute exacerbation of disease with most of the classical features
• Stage II: Remission
• Stage III: Recurrence of exacerbation with two times increase in IgE levels
• Stage IV:Where patients need continuous steroids to control the disease
• StageV: Fibrotic stage which responds poorly to steroids and may lead to pulmonary hypertension and cor
pulmonale.
42

42. 43

43. IN A NUTSHELL
• Aspergillus may cause hypersensitivity, saprophytic, or invasive disease in human.
• Disease pattern of Aspergillus is determined by immune status of the individual, genetic
susceptibility, and quantity and virulence of inhaledAspergillus.
• Allergic bronchopulmonary aspergillosis (ABPA) occurs in settings of asthma and cystic
fibrosis.
• High index of suspicion with early diagnosis of ABPA is crucial to start aggressive treatment
for prevention of irreversible lung damage.
• Oral prednisolone is the mainstay of treatment for ABPA in asthma and CF with itraconzole
being a useful adjuvant therapy.
• Invasive aspergillus is a notorious disease among immunosuppressed individuals, that needs
early diagnosis and treatment
44

44. CRYPTOCOCCOSIS
• Cryptococcosis is caused by fungi that belong to the genus Cryptococcus.Cryptococcus is
found in the soil throughout the world, usually in association with large amounts of bird
droppings.
45

45. • Cryptococcosis is a fungal infection which predominantly involves the CNS, lungs,
skin, and bones, but other organs can also be affected.
• It usually affects immunocompromised children but can occur in immunocompetent
children.
• Subacute or chronic meningitis is most common manifestation of disseminated
cryptococcal disease in children.
• Cryptococcal antigen tests on CSF have a high sensitivity and specificity for diagnosis
and now considered point-of-care tests.
• Amphotericin B remains the drug of choice for induction followed by fluconazole for
completion of therapy. 46

46. COCCIDIOIDOMYCOSIS:Valley Fever
Coccidioides immitis – causative agent
Distinctive morphology – block like
arthroconidia in the free-living stage and
spherules containing endospores in the
lungs
Lives in alkaline soils in semiarid, hot
climates and is endemic to southwestern
U.S.
Arthrospores inhaled from dust, creates
spherules, and can form nodules in the
lungs
47

47. Events in Coccidioides infection
48

48. • The lesions of skin and oral mucosa are proliferative, granulomatous, ulcerated and non specific
in their clinical appearance
• Most coccidioidal infections are asymptomatic or minimally symptomatic and resolve without
treatment.
• Coccidioides species can cause severe pulmonary and extrapulmonary infections including
pneumonia, adult respiratory distress syndrome (ARDS), fungemia, septic shock, meningitis,
osteomyelitis and, septic arthritis.
• Diagnosis of coccidioidal infection entails a high index of suspicion, clinical evaluation,
appropriate radiologic studies, appropriate laboratory studies such as serologic testing for IgG
and IgM of blood or CSF, fungal stain and culture of clinical specimens, in some cases polymerase
chain reaction (PCR) or other molecular techniques.
• Treatment of coccidioidal infection entails antifungal therapy with azole antifungals or
amphotericin B preparations, respiratory and hemodynamic support in severe cases, and
judicious surgical intervention
49

49. BLASTOMYCOSIS
• Dimorphic
• Free-living species distributed in soil of a large section of the midwestern and southeastern
U.S.
• Inhaled 10-100 conidia convert to yeasts and multiply in lungs
• Symptoms include cough and fever
• There are 3 clinical forms: pulmonary, disseminated and primary cutaneous.
• The most common organs involved are the lungs, skin, bone and CNS, in that order.
• Diagnosis is by demonstration of fungus in the tissue, sputum and exudates by potassium
hydroxide (KOH) mounts and culture.
• Amphotericin B is the drug of choice in severe cases and oral itraconazole for mild cases
50

50. Cutaneous Blastomycosis in the Hand andWrist
51

51. Oral Manifestations
• Proliferative, ulcerated lesions developing over the palate, lips,
tongue, gingiva and maxilla or mandible
• Loosening of teeth and draining sinuses.
• Oropharyngeal pain and cervical lymphadenopathy.
52

52. HISTOPLASMOSIS: OhioValley Fever
• Histoplasma capsulatum – most common true pathogen; causes
histoplasmosis
• Typically dimorphic
• Distributed worldwide, most prevalent in
eastern and central regions of U.S.
• Grows in moist soil high in nitrogen content
• Pulmonary histoplasmosis resolves itself while severe forms of disease
are usually treated byAmphotericin B.
53

53. Events in Histoplasmosis
54

54. Oral Manifestation
• Oral lesions occurs in the form of nodules over the mucosa, which
frequently undergoes ulceration with raised, rolled borders and
induration of the surrounding tissue.
• Most of the oral lesions develop in the gingiva, tongue, palate and
buccal mucosa, etc.
• Some lesions may be popular, verrucous or plaque-like
• Sore throat, pain during chewing, hoarseness of voice and
dysphagia are common
55

55. • Granulomatous lesions often cause destruction of the alveolar bone
with loosening or exfoliation of teeth
• Oral lesions of histoplasmosis may occur secondary to HIV
infections and in many cases they resembles carcinoma or
tuberculous ulcers.
56
Histoplasmosis should be considered in the differential
diagnosis of prolonged fever, oral ulcers and adrenal
enlargement.
Histoplasmosis should be considered as differential
diagnosis inTB patients with granulomatous disease who
do not respond to antituberculous treatment (ATT).
Antifungal therapy leads to excellent outcome in most
patients.

56. PNEUMOCYSTIS (CARINII) JIROVECI AND
PNEUMOCYSTIS PNEUMONIA
• A small, unicellular fungus that
causes pneumonia (PCP), the most
prominent opportunistic infection
in AIDS patients
• This pneumonia forms secretions in
the lungs that block breathing and
can be rapidly fatal if not controlled
with medications like Pentamidine
and cotrimoxazole 57

57. • The 5–7 mm cyst contains up to eight pleomorphic intracystic bodies (sporozoites).
• Once excysted, sporozoites become trophic forms (trophozoites).
• Once inhaled, all these forms reside in the alveoli of the lung.
• The trophic form of Pneumocystis organisms attach to the alveoli.
• Multiple host immune factors, importantly,CD4+T-cells and macrophages, hinder
uncontrolled replication of Pneumocystis organisms and subsequent development of
illness, in immunocompetent hosts.
• Therefore in immunocompromised hosts, when activated alveolar macrophages and CD4+
T-cells are unable to eradicate Pneumocystis organisms, pneumonia and other
manifestations of the disease ensue.
• Lung injury is directly related to the Pneumocystis jirovecii-specific inflammatory response
rather than to the organism burden per se.
• Thus, there seems to be a role of steroids to control the inflammation and hypoxia in these
patients. 58

58. 59

59. 60
PREVENTION
Patients at risk of PCP must receive chemoprophylaxis.
In patients with HIV, PCP prophylaxis is recommended in following situations:
• All HIV exposed infants from 4 weeks of age (infants born to HIV infected mothers) till
proven to be HIV negative
• All HIV infected asymptomatic infants till 1 year of age
• All symptomatic HIV infected children (WHO stage 2 and above)
• After initial treatment for PCP
• All HIV infected children with CD4 less than 200 cells/cumm in children above 5 years of
age and less than 25% in children below 5 years of age irrespective of symptoms.

60. PRECAUTIONSTO PREVENT FUNGAL
DISEASES
• Washing your feet every day.
• Drying your feet completely, especially between your toes.
• Wearing sandals or shower shoes when walking around in
locker rooms, public pools, and public showers.
• Wearing clean socks. If they get wet or damp, be sure to change
them as soon as you can.
• Using a medicated powder on your feet to help reduce
perspiration (sweating). Ask a parent first.
61

61. Wearing clean cotton underwear and loose-fitting pants.
Keeping your groin area clean and dry.
Changing out of wet swimsuits instead of lounging around in them.
Wearing clean cotton underpants.
Trying not to let your skin get too hot or sweaty.
Using an anti-dandruff shampoo to wash your skin once a month.
Make sure shoes fit correctly and are not too tight.
62

62. 63