Mycoses due to yeasts

By
Dr Imran Jibril (MBBS, MSc, FWACP)
Introduction
• They are “opportunistic fungi” usually found as members of the
resident human microbiota or as saprophytes in the environment.
• They can cause infections ranging from skin/mucous membrane to
life-threatening, systemic disease following breakdown of host
defenses.
• Of the over 150 Candida species, fewer than 10 cause human
infections.
• Particular attention is given to the differentiation of C. albicans from
other species, because it is by far the most common cause of disease.
Introduction
• For serious infections, identifying Candida isolates to the species level
is important for prognostic and treatment decisions.
• Candida species are budding yeasts that readily grow in culture.
• Candidiasis occurs in localized and disseminated forms.
• Localized disease is seen as erythema and white plaques in moist
skinfolds (diaper rash) or on mucosal surfaces (oral thrush).
• It may also cause the itching and thick white (curd-like) discharge
seen in vulvovaginitis.
Introduction
• These fungi reproduce by budding.
• The buds, called blastoconidia, can remain attached to one another,
forming a chain called a pseudohypha (pleural pseudohyphae).
• Medically important yeasts belong to the following genera:
• Candida spp,
• Cryptococcus spp,
• Pneumocystis is a yeast‐like fungus, of medical significant.
WHO fungal priority pathogens list
Candida spp.
• The most important are:
• C. albicans
• C. auris
• C. dublinensis
• C. parapsilosis
• C. tropicalis,
• C. krusei, and
• C. glabrata
• Rare causes of human disease include:
• C. guillermondii and
• C. lusitaniae.
Candida spp.
• Candida albican – is the best characterised of the candida species
• C. glabrata – impt because of its increasing global incidence and
decrease susceptibility to antifungals . 2nd MC cause of candidemia.
• C. parapsilosis – 3rd MC esp. in patients with central venus catheter,
IV line, prosthetic devices, and IDU. MC cause of candidemia in
NICU. It produces slime as the VF enabling it to adhere to surfaces.
• C. tropicalis – 4th MC. Risk factors include leukemia, prolong
neutropenia, prolong ICU stay
Candida albicans
• Is a fungal pathogen of global distribution.
• Its part of the healthy human microbiome (mouth, throat, gut, vagina,
and skin) but may also cause infections of the mucosae or produce
invasive candidiasis.
• Invasive candidiasis is a life-threatening disease with high mortality.
• E.g. of invasive infections (invasive candidiasis): of the blood
(candidaemia), heart, CNS, eyes, bones and internal organs.
• Critically ill and immunocompromised patients are especially affected.
• Treatment is possible and antifungal resistance remains low.
• Invasive candidiasis has an overall mortality ranging from 20% to
50% despite the availability of active antifungal treatment.
• Length of stay in hospital is up to 2 months and is based on influenced
underlying comorbidities.
Pathogenesis of Candida albicans infections

Surface glucomannan receptor(s) on the yeast may bind to fibronectin covering the
epithelial cell or to elements of the extracellular matrix (ECM) when the epithelial
surface is lost or when the Candida cells have invaded beyond it.
Invasion is associated with formation of hyphae and production of proteinases, which
may digest tissue elements
Pathogenesis of Candida albicans infections
• Shift from yeast to hyphae is associated with invasion
• Switch is triggered by environmental conditions (serum pH,
temperature, amino acids).
• Opsonized yeast forms are killed by PMNs
• Compromised CMI is associated with progressive infection
• Balance between TH1 and TH2 cytokines is necessary – coffee.
Oropharyngeal candidiasis (OPC) – thrush
• It is most prevalent in infants, the elderly, and compromised hosts and
occurs in association with serious underlying conditions including
diabetes, leukemia, neoplasia, steroid use, antimicrobial therapy,
radiation therapy, and HIV infection.
• Persistent OPC in infants may be the first manifestation of childhood
AIDS or chronic mucocutaneous candidiasis.
• It present as raised, white plagues on the mucosa, tongue, or gums
often spreads to the oesophagus.
Esophageal Candidiasis
• Now common due to increased prevalence of AIDS, transplant
recipients, cancer and other severely immunocompromised patients.
• Predisposing factors: irradiation, recent cytotoxic chemotherapy,
antibiotics, corticosteroids, and neutropenia.
• May be the first manifestation of AIDS among HIV-positive patients
• Clinical presentations: dysphagia, odynophagia, retrosternal pain,
and occasionally fever.
Gastric Candidiasis
• Since normal gastric microbial flora is derived from oropharyngeal
secretions, saliva and food, Candida organisms are normal
components of gastric flora.
• Factors that enhance oral carriage of Candida similarly increase gastro
duodenal colonization with Candida species.
Cutaneous Candidiasis
• Candida can invade any body surface and cause superficial infection of
the skin, hair, and nails.
• Symptomatic mucocutaneous candidiasis occur when dysfunctional host
resistance promotes an overgrowth of indigenous flora and there is a
breach in the anatomical barriers (skin and mucosa).
• Dry intact skin is a potent barrier to fungal invasion, and hydration of the
epidermis decreases resistance.
• Candida albicans and C. tropicalis are the most common causes of
superficial infections of the skin and the nails.
• These organisms favor growth in warm, moist areas such as the skin
folds of obese individuals, between the fingers and toes, perineal areas,
and genitocrural folds.
Vulvovaginal Candidiasis
• Candida vaginitis is the second MC vaginal infection in the United
States.
• During the childbearing years, 75% of women experience at least one
episode of vulvovaginal candidiasis (VVC), and 40%–50% of these
women experience a second attack.
• Candida is isolated from the genital tract of approximately 10%–20%
of asymptomatic, healthy women of childbearing age.
• Candida albicans adheres to vaginal epithelial cells in significantly
greater numbers than non-albicans Candida species.
Vulvovaginal Candidiasis
• Presentations include itching, burning pain of the vulva and vagina,
and whitish, curd-like discharge.
• RFs include pregnancy (30%– 40%), corticosteroids, antimicrobial
therapy, intrauterine devices, oral contraceptives with a high estrogen
content, uncontrolled DM and high frequency of coitus.
• The hormonal dependence of VVC is illustrated by the fact that
Candida is seldom isolated from premenarchial girls, and the
prevalence of Candida vaginitis is lower after the menopause, except
in women taking hormone replacement therapy.
Pathogenesis of recurrent vulvovaginal
candidiasis
VVC
• During pregnancy, the incidence of clinical episodes is highest in the
third trimester, but symptomatic recurrences are common throughout
pregnancy.
• The high levels of reproductive hormones are thought to increase the
glycogen content of the vaginal environment and provide a carbon
source for Candida germination and growth.
• Estrogens enhance vaginal epithelial cell avidity for Candida
adherence
• In addition, estrogens enhance yeast-hyphae transformation.
VVC
• Diets high in refined sugar may precipitate symptomatic Candida
vaginitis.
• Environmental factors that predispose to Candida vaginitis may
include tight, poorly ventilated clothing and nylon underclothing,
which increase perineal moisture and temperature.
• Chemical contact, local allergy (to vaginal deodorants, washes,
perfumed feminine hygiene products, etc) and hypersensitivity
reactions may also predispose to symptomatic vaginitis.
Systemic candidiasis
• Neonatal candidiasis – neonatal systemic candidiasis or congenital
cutaneous candidiasis.
• Candida bloodstream and urinary tract infections are especially
common among hospitalized patients with intravenous and urinary
catheters.
• Deep tissue and disseminated infections are limited almost exclusively
to the immunocompromised.
Laboratory diagnosis
• Exudate or epithelial scrapings examined by KOH preparations
demonstrate abundant budding yeast cells;
• If associated hyphae are present, the infection is almost certainly caused
by C. albicans.
• Germ tube test for C. albicans confirmation.
• Antigen detection: latex agglutination test (Cand-Tec).
• Candida species are readily grown in routine cultures media.
• Blood agar, Sabouraud Dextrose agar (SDA), Potato Dextrose Agar (PDA)
or broth, CHROMagar Candida, Yeast Nitrogen Base (YNB), Yeast Potato
Dextrose (YPD) agar or broth.
 Pseudohyphae of C. albicans in pus from a
perivenous abscess caused by an IV catheter
 Perivenous abscess at an intravascular
catheter site, caused by Candida albicans
Colonies and Germ tube production by
Candida albicans
Characteristic blue colonies of Candida
tropicalis on CHROMagar®.
Treatment
• Depends on the severity and extent of candida infection:
• Azole drugs (orally or IV) – ketoconazole, fluconazole, & itraconazole
• Amphotericin B +/- Flucytosine in systemic disease
• Echinocandins (caspofungin, micafungin, anidulafungin) – active against most
Candida, including spp resistant to azoles.
• C. auris, Candida glabrata and Candida krusei are often resistant to azoles.
• Treatment of invasive candidiasis usually includes echinocandins followed by a
step-down to azoles when appropriate.
• Removal of an infected catheter, control of diabetes, or an increase in peripheral
leukocyte counts can be important aspects of the complete treatment of infection.
Cryptococcus spp.
• These are environmental yeasts that grow on organic material such as bird
or bat guano.
• The two main species are C. neoformans and C. gatti.
• Cryptococcus neoformans is a well‐recognized cause of chronic meningitis
in individuals with deficiencies in cell‐mediated immunity e.g. AIDS.
• Following inhalation of fungal cells from the environment, C. neoformans
can infect humans.
• Human-to-human transmission does not occur
• Cryptococcosis first affects the lungs and spread to the CNS (cryptococcal
meningitis) and blood (cryptococcaemia).
• The meningitis can have a very insidious progression over months.
• Cryptococcus gatti is much less common than C. neoformans.
• Recently, infections in normal hosts were documented in the
northwestern USA and British Columbia.
• C. neoformans cryptococcosis is a very serious disease, with mortality
ranging from 41% to 61%, especially in patients with HIV infection.
Cryptococcus spp.
• Lab diagnosis
• The organism can be detected in cerebrospinal fluid by Gram stain, but
it is best seen by India ink preparation, which demonstrate its large
capsule
• The most sensitive test for detecting the organism is the antigen test
which can be performed on CSF and on serum.
• It can be cultured on blood and other agars
• Treatment of patients with cryptococcal meningitis consists initially of
amphotericin B plus 5‐flucytosine, followed by step-down to long‐term
fluconazole.
Indian ink and Gram stain of CSF showing
Cryptococcus neoformans. Note budding
Cryptococcus neoformans growing on agar
Pneumocystis jirovecii
• This genus was considered to belong to the protozoan parasites for
many years, but is now classified as a fungus, related to yeasts.

• Originally, the organism infecting humans was called P. carinii. It is

now known to be the species infecting rats.

• The human species is called P. jirovecii. It exists as a trophozoite, a

precyst, and a cyst.

• It is transmitted by inhalation from other infected individuals.

Pneumocystis jirovecii
• Almost all humans become infected within the first few years of life,
and disease is largely confined to premature and malnourished
children, and individuals of any age with severe impairment of cell‐
mediated immunity.
• Pneumocystis jirovecii pneumonia (PCP) is a serious disease with
mortality ranges from 0% to 100%.
• Hospital length of stay in patients with P. jirovecii infection ranged
from 0–123 days (median of 6.6–30 days).
Pneumocystis jirovecii
• It is a very important opportunistic infection in individuals with AIDS.
• Diffuse pneumonitis with insidious or fairly acute in onset
• Occasionally it spreads to organs other than the lung.

• Presentation: Fever, nonproductive cough, dyspnea, chest pain, chills,

fatigue and cyanosis develop later
• Extrapulmonary lesions are seen in AIDS
Pneumocystis jirovecii
• Complications include respiratory failure, long-term graft failure and
renal failure.
• Preventability of PJP is high. No vaccine is available.
• Drug prophylaxis, which is highly efficacious
• Antifungal resistance is unknown.
Diagnosis
• The diagnosis is made by demonstration of the organism in material
from the lung, such as sputum, bronchoalveolar lavage fluid, or lung
biopsy.
• When stained by the Gomori silver impregnation stain, the cyst wall
stains black.
• When stained with Giemsa stain, the cyst wall is not seen, but the
intracystic bodies can be seen.
• Immunofluorescent stains are available.
• Histologically the lung tissue shows interstitial infiltration of
mononuclear cells and the alveoli are filled with foamy material
The cysts of Pneumocystis jiroveci, in lung tissue from
a child with AIDS, stained with Gomorri silver
impregnation stain
Pneumocystis pneumonia

A silver stain of this material from the lung reveals folded cysts some of which contain
comma-shaped spores.
Treatment
• Therapy consists of respiratory support and antimicrobial therapy.
• Mainstay of therapy: trimethoprim/sulfamethoxazole (cotrimoxazole).
• Alternative drugs are atovaquone/proguanil, pentamidine, or
primaquine plus clindamycin.
• Chemoprophylaxis is indicated for patients who have:
• CD4+ lymphocyte counts lower than 200/mm3,
• unexplained fever, or
• a previous episode of PCP
• solid-organ