FUNGAL DISEASES in children by dr priyanka.pptx

fungal disease in children

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

2. CONTENTS INTRODUCTION TO 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. INTRODUCTION TO 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: Superficial/cutaneous – present on skin, hair, nails ( Candidiasis, Candida diaper rash, Tinea infection) Subcutaneous – infection in tissues under the skin (Sporotrichosis, Chromoblastomycosis, Mycetoma) 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. Types of Oral Candidiasis Acute Candidiasis Pseudomembranous type (ORAL THRUSH) Atrophic type Chronic Candidiasis Candida-associated angular chelitis Atrophic type (ADULT) Hypertrophic type (RARE) Mucocutaneous candidiasis Localised type Familial type Syndrome associated Systemic Candidiasis Gastrointestinal candidiasis Pulmonary infection Candida Urinary tract infection candida Candidial meningitis Candidial endocarditis Candidial septicaemia 10

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

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

20. 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

21. 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. Upper GI 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

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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

30. 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

31. 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

32. 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

33. 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

34. 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

35. Tinea corporis – Body Ringworm 35

36. 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

37. Tinea Pedis – Athlete’s Foot Infection 37

38. 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

39. 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

40. 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: Hypersensitivity (e.g., allergic bronchopulmonary aspergillosis (ABPA); Aspergillus mediated asthma and hypersensitivity pneumonia; and malt worker’s disease), Saprophytic ( noninvasive e.g., aspergilloma) Invasive disease [e.g., invasive aspergillosis (IA)] ABPA is an important and common disease caused by Aspergillus species. 40

41. 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

42. 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 Stage V: Fibrotic stage which responds poorly to steroids and may lead to pulmonary hypertension and cor pulmonale. 42

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44. 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 inhaled Aspergillus. 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

45. 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

46. 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

47. 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

48. Events in Coccidioides infection 48

49. 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

50. 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

51. Cutaneous Blastomycosis in the Hand and Wrist 51

52. 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

53. HISTOPLASMOSIS : Ohio Valley 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 by Amphotericin B. 53

54. Events in Histoplasmosis 54

55. 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

56. 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 in TB patients with granulomatous disease who do not respond to antituberculous treatment (ATT). Antifungal therapy leads to excellent outcome in most patients.

57. 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

58. 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

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60. 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.

61. PRECAUTIONS TO 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

62. 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