Infection And Defence: Fungus, Parasites Structure And Function, Routes Of Transmission, Treatments

Front 1

How are fungi classified?

Back 1

>Fungi are Eukaryotes:
- sharing some characteristics with plants (and animals)
- possess their own kingdom
>Broadly divided into:
YEASTS:
- unicellular
- budding organisms
- e.g. Candida Albicans / Cryptococcus Neoformans

MOULDS:
- Organisms with branching hyphae
- e.g. Aspergillus fumigatus / Tricophyton Rubrum

DIMORPHIC FUNGI:
- Some species capable of displaying both morphologies in response to environmental triggers
- e.g. Histoplasma capsulatum / penicillium fungi

Front 2

Describe the growth characteristics of fungi.

Back 2

>Slow growing in the lab (days to weeks)
>Able to assimilate many different substrates, act as scavengers in the environment
- important in recycling biomaterial
- invasive species need to be able to grow at 37 degrees C but many grow at environmental temperatures

Front 3

What is the burden of fungal infection?

Back 3

>Superficial and mucosal infections are very common
- 10% of population will suffer dermatophyte infection (ringworm - skin/scalp/nails)
- 75% women episode of vulvovaginal candidiasis during lifetime
>Endemic or pathogenic fung causing invasive disease in immunocompetent hosts are restricted to certain parts of the world
- UK cases are caused from exposure elsewhere

Front 4

What are the big five causes of fungal infection?

Back 4

- Candida (esp. Albicans)
- Aspergillus (esp. Fumigatus)
- Pneumocystis Jirovecii
- Cryptococcus Neoformans
- Zygomycete species (esp. Rhizopus arrhizus)

Front 5

Describe the characteristics of yeasts.

Back 5

>Unicellular organisms
>Reproduce via budding
>Generally round or oval
- form pseudomycelium under certain conditions
>Medically important are candida and cryptococcus

Front 6

Describe the characteristics of Candida.

Back 6

>Principal pathogen is C. Albicans
- Tropicalis, Parapsilosis, Glabrata and Krusei also crop up occasionally
>Small numbers may be found in mouth, GI and genital tract without causing infection
- Larger numbers during or following broad spectrum antibiotic therapy
- Risk of superficial/systemic candidiasis
>Opportunistic infection
- occurs in immunosuppressed patients, broad spectrum antibiotic patients or extremes in age
- more common in diabetics, pregnant patients, steroid patients (e.g. asthmatics)
>Site of infection:
- Cutaneous candidiasis occurs particularly in moist skin
- Candidemia (blood infection) seen in TPN patients / drug abusers
- Recurrent oropharyngeal candidiasis infrequently encountered in normal healthy adults (should raise possibility of underlying disease / immunosuppression)
- Often commensal in origin, but cross infection occurs in healthcare setting
>Diagnosed via visualisation of yeast cells
- Can be grown on most agar 48-72h
- Saburaud's medium used to inhibit bacterial growth
- Chromogenic media available to differentiate species
- Rapid test - germ tube test (hyphae produced in human serum after incubation for 2-3 hours in human serum)

TREATMENT:
>Superficial infection: topical antifungals, or oral systemic therapy may be required for highly immunosuppressed patients (and nail infections - prolonged treatment required)
- Imidazoles (clotrimazole), polyenes (nystatin, amphotericin B)
>Systemic:
- Imidazoles (fluconazole, itraconazole, voriconazole)
- Polyenes can be used as oral suspensions for treatment of oropharyngeal candidiasis
- IV drugs include amphotericin B, flucytosine, caspofungin, imidazoles

Front 7

Describe the characteristics of Cryptococcus neoformans.

Back 7

>Encapsulated yeast
>Found in dried pigeon droppings or contaminated soil
- inhaled into lungs
>Opportunistic infection
- occurs in immunocompromised patients, particularly those with HIV
>Patients present with meningitis (acute or chronic), +/- pulmonary signs
- Can occur in skin, eyes and musculoskeletal system (via haematogenous spread)
>Diagnosed via CSF / blood stain (india ink)
- Cultures take up to 10 days
- Latex agglutination can be used
>High mortality
>Treated with high dose systemic anti fungal drugs
>Combination of amphotericin B or fluconazole + flucytosine for 4-6 weeks
- Recurrent infection common in HIV+, maintenance therapy of oral fluconazole may be given

Front 8

What is Malassezia furfur?

Back 8

>Lipophilic commensal yeast
>Cause of common pityriasis versicolor
- disfiguring skin condition with development of numerous brown scaly patches
- hypo pigmentation of skin
- Treat with topical anti fungal or oral itraconazole
>May cause central venous catheter associated fungemia (in patients receiving fat emulsions)

Front 9

What is Trichosporum beigelii?

Back 9

>Causes mild infection of hair in tropical countries (white piedra)
>Rare opportunistic infection in immunosuppressive disease e.g. leukaemia, causing disseminated infection

Front 10

Describe the characteristics of Aspergillus.

Back 10

>Abundant in environment
>Airborne spores common, infections follow inhalation of Aspergillus
>Several species can cause infection:
- fumigatus
- niger
- flavus
>Risk factors = immunosuppression (e.g. bone marrow transplant recipients)
>Outbreaks occur during building demolition or construction occurs in vicinity of high risk units, releasing aspergillus spores
>Infections:
ALLERGIC ASPERGILLOSIS:
- Uncommon condition caused by hypersensitivity to inhalation of aspergillus spots
- Asthma-like symptoms, mucus plug formation, Farmer's lung
ASPERGILLOMA:
- Fungus ball occurring in patients with lung cavities (result of TB)
- Patients may be asymptomatic or have cough / malaise
INVASIVE PULMONARY ASPERGILLOSIS
- Rapidly progressive and life threatening
- Highly immunosuppressed patients
- Persistent fever, shortness of breath and pleuritic chest pain
- Cause widespread necrosis and hemoptysis
- Haematogenous spread
>Diagnosed via Aspergillus precipitins in serum (Ab test)
- Difficult in immunosuppressed as immune response not mounted
- Treatment sometimes given on empiric basis
- Radiologic investigation may be used (e.g. CT)
>Definitive diagnosis ONLY by HISTOLOGICAL DETECTION OR CULTURE
>Treatment:
- Allergic aspergillosis: steroids
- Aspergillomas: surgical excision / installation of antifungals
- Invasive Aspergillosis: high dose systemic antifungal therapy

NB. Prophylaxis may be used for at risk patients e.g. HEPA filtered positive pressure rooms, itraconazole.

Front 11

Describe the characteristics of mucorales.

Back 11

>Group of moulds causing a variety of infections called mucormycosis (or zygomycosis)
- Rhizopus
- Rhizomucor
- Absidia
>Infection caused by spore inhalation or inoculation
>Risk factors:
- Diabetes
- Immunosuppression
- Burns
>Common infection 'rhinocerebral mucormycosis'
- starts paranasal sinuses
- spreads to eye, palate and brain
>Diagnosed by clinical, radiological and histological features (showing browad nonseptate hyphae within tissue)
>Fungus can be grown occasionally from clinical specimen
>Treatment by resection of necrotic tissue / high dose antifungal therapy
- High mortality

Front 12

Describe the characteristics of dermatophytes.

Back 12

>Filamentous fungi commonly causing superficial infection of skin, nails and hair:
- tinea / ringworm (skin/hair)
- onychomycosis (nails)
>Clinical diagnosis by microscopy and fungal culture
>Treatment with topical anti fungal preparations
- systemically for nail and hair

Front 13

What are dimorphic fungi? Which diseases are dimorphic fungi associated with?

Back 13

>Exhibit mycelial growth at 22C but form yeasts at 35-37C

SPOROTRICHOSIS:
>Infection of subcut. tissue with Sporothrix Shenckii
- Arms hands after inoculation injury
>Histoplasma capsulatum (causes histoplasmosis)
- Mild self-limiting chest infection
- Chronic pulmonary infection (resembling TB) can occur in immunosuppressed)
>Reservoir - bird or bat droppings

COCCIDIOIDES IMMITIS:
>Soil fungus found in SW USA, Central and South America
- Inhalation of airborne spores can cause asymptomatic pulmonary infection
- Occasionally chronic pulmonary or disseminated disease occur

Front 14

What is pneumocystis jirovecii?

Back 14

>Found worldwide, natural reservoir unknown.
>Humans exposed via airborne route
- Infection normally only occurs in patients with depressed cell mediated immunity (e.g. HIV infection)
>Principally causes PCP
>AIDS defining illness in HIV+ patients
>Other patients include bone marrow and solid organ transplant recipients
Lab diagnosis is by microscopic exam of sputum or broncho-alveolar lavage fluid (using immunofluorescence)
>Treatment principally with high dose trimethoprim sulfamethoxazole

Front 15

Describe the characteristics of moulds.

Back 15

>Or filamentous fungi
>Group of saprophytic (feeds on dead matter) eukaryotic organisms
>Form mycelia in vegetative state
>Many moulds found in the environment, few capable of causing human disease
>Important filamentous fungi causing human infection:
- Aspergillus
- Mucorales
- Dermatophytes

Front 16

Identify this fungus.

Back 16

>Aspergillus fumigatus

Front 17

Identify this fungus.

Back 17

Rhizopus

Front 18

Identify this fungus.

Back 18

Penicillium

Front 19

What are the three forms of asexual spore?

Back 19

Front 20

Describe the basic nomenclature of fungi.

Back 20

Front 21

Describe the structure of the fungal cell wall.

Back 21

>Cell membrane contains ergosterol as the main sterol (c.f. cholesterol in mammalian cell membrane)
>Cell wall consists of several polysaccharides (glucans, manna's), proteins and chitin
>Some fungi have melanin in the cell wall
>Some fungi have a polysaccharide capsule e.g. Cryptococcus neoformans

Front 22

What is unusual about candida opthalmitis?

Back 22

It lights up in the retina.

Front 23

Define parasitism.

Back 23

The activity of an organism that spends any portion of its life in direct contact with a host species at the expense of the host.
>Protozoa:
- exist in all body compartments
- intra and extracellular
- cause a spectrum of disease (e.g. malaria, presents with symptoms such as diarrhoea and blastocystis)
>Helminths:
- multicellular
- highly organised
- complex lifecycles

Front 24

Describe the burden of parasitic disease.

Back 24

>Parasites cause chronic invasive illnesses
- often overlooked
- affect people's daily lives
- prelude to worse disease
>Parasites are associated more with DALYs (disability adjusted life years)
- significantly impact society as people's contribution is affected
>Due to parasite coevolution with man; not in the parasite's interest to kill the host
>Malaria an exception - causes a significant number of deaths annually in developing world

Front 25

How do parasites tend to be transmitted?

Back 25

>Environmental / behavioural:
- Associated with resistant cyst or ova (survives in the environment)
- e.g. Giardia, Toxoplasma, Tapeworms, geohelminths; Trichomonas vaginalis directness of contact precludes need for cyst formation
>Consumption of resistant stages with food
- e.g. tissue cyst of toxoplasma
>Direct invasion
- e.g. schistosomes and hookworms invade host via the skin
>Via insect vectors
PROTOZOA
- E.g. Malaria (Anopheles mosquito; interestingly can be infected with fungus as a means of controlling spread))
- Leishmania (Sandflies)
- Trypanosomes (African = Tsetse fly, American = Triatomid bugs)
HELMINTHS - FILIARIASIS
- Blood sucking flies
Onchocerca - Simulium blackflies
Loa Loa - Chysops
Wucheria bancrofti - Culex, Anopheles and Aedes
Brugia malayi - Mansonia

Front 26

What are the typical mechanisms of parasite pathogenesis?

Back 26

>Disruption of normal physiological function:
- e.g. Giardia deconjugates bile salts causing malabsorption and consequent steatorrhea
>Invasion of host tissues:
- Disruption of metabolism: trypanosome induced cardiac failure
- Disruption of host immune responses e.g. Toxoplasma and Leishmania invade macrophages
- Physical disruption e.g. granuloma formation leading to necrosis
>Physical presence
- Plasomodium aggregation in cerebral malaria, Ascaris blockage of gut (foot long worm, between 10 and 100 will physically obstruct the gut)
>Induction of immune responses:
- Leishmania lesions associated with protective immune responses
- Toxoplasma encephalitis associated with cyst reactivation
- Schistosome granuloma formation

Front 27

Give five examples of protozoa and their common hosts/route of transmission.

Back 27

1. Malaria (Anopheles mosquito, bite)
2. Trichomonas vaginalis (Sexually transmitted)
3. Trypanosomiasis (Tsetse fly = Africa, Triatomine bug = USA, bite)
4. Leishmaniasis (Sandflies, bite)
5. Toxoplasmosis (Domestic cat, oral)

Front 28

What are the 4 main species of malaria?

Back 28

Plasmodium...
- ...falciparum (most deaths, subsaharan Africa, S.E. Asia, S/C America)
- ...vivax
- ...ovale
- ...malaria

Front 29

What is the epidemiology of malaria?

Back 29

- Tropical disease
- 40% of world's population, mostly those living in the poorest countries, are at risk of malaria.
- 2.5 billion are at risk
- >500 million become severely ill with malaria each year
- >1 million die from malaria
- Africa:
- 20% childhood deaths
- African child has on average between 1.6 and 5.4 episodes of malaria fever each year
- Every 30 seconds a child dies from malaria

Front 30

Give an overview of Toxoplasmosis.

Back 30

>Toxoplasma gondii
>Obligate intracellular parasite (apicomplex)
>Sexual cycle only occurs in cats but all vertebrates are susceptible
>Non-feline hosts 2 critical phases of infection
- Acute flu like disease
- Establishment of chronic latent cysts
>UK seropositivity 30-40% (60% in France due to rare lamb etc.)
>Reactivation of cysts associated with immunosuppression; HIV or transplantation
- AIDS defining illness
>Risk of congenital transmission during pregnancy
- spontaneous abortion / adolescent eye disease

Front 31

Give an overview of Trichomonas.

Back 31

>3 species:
- T. hominis (caecum / large intestine
- T. Tenax (mouth)
- T. Vaginalis (vagina, urethra, seminal vesicles and prostate)
>T. vaginalis results in inflammation and discharge and affects ~180 million women

Front 32

Give an overview of Trypanosomiasis.

Back 32

African vs. South and central American
>Trypanosoma cruzi
- S. American
- Intracellular; macrophages, muscle and nerve cells
- Chagas disease (common in Southern and Central America)
- Cardiac failure (hypertrophy)
- Loss of nervous control of gut
>Trypanosoma brucei
- 2 sub species
- T.b. Gambiense
- T.b. Rhodesiense
SYMPTOMS:
>Fever, malaise, anorexia; invasion of CNS results in sleeping sickness phase of disease
>Both sub-species demonstrate variable surface coats associated with avoidance of host immune response
- Variable surface glycoproteins
>Treatment = antibiotics which are toxic to the host

Front 33

Give an overview of Leishmaniasis.

Back 33

>Multiple species
>Cutaneous diseases, deeper tissue may be implicated
>Old World vs. New World
>L. donovanii (OW)
- Most severe form Kala azar
>Simple cutaneous lesion localises at the site of the bite resulting in a granulomatous response
>Epidermis fragile and prone to further physical damage, ulceration and secondary infection

NB. Many Africans self inoculate with Leishmania and may be unsuccessful.

Front 34

Describe the pathogenesis of Leishmaniasis.

Back 34

>Insect takes a blood meal and injects protozoa
>Protozoa invades macrophages
>Immune response leads to granulomatous reaction and fragile skin
>Patients prone to secondary bacterial infections

Front 35

What classes of worm are there?

Back 35

>2 groups:
- Platyhelminthes or 'flatworms'
- Cestodes; tapeworms
- Digeneans; flukes
- Nematodes or 'roundworms'

Front 36

Give an overview of Cestodes.

Back 36

>Complex parasites, invade tissues, immune responses to larval stages
>Pathogenesis can be classified by lifecycle stage
>Larval cestodiasis
- Larvae in organs results in disease
- Spirometra spp. Invasion of deep tissues
- Taenia solium cysticercosis, invasion of range of tissue but predilection for brain (may cause epilepsy)
- Echinococcus granulosus, hydatid disease (cysts cannot be penetrated by drugs, full of larvae), liver and lung infections
>Humans not obligate hosts, heavy infections are found in communities with close contact to reservoir species

Front 37

What are Digeneans?

Back 37

>Flutelike worms
- Flattened oral sucker, ventral sucker
>Alternate asexual and sexual cycles between molluscan and vertebrate hosts
>6000spp. ~12 significant in man
>Human infective stage is the cercariae which emerges from the snail
>Swimmers itch

Front 38

What is Schistosomiasis?

Back 38

>Occurs in the rural tropics:
- S. Mansoni (intestinal)
- S. Haematobium (urinary)
- S. Japonicum (intestinal)
- S. Intercalatum (intestinal)
>Located in the lumen of blood vessels
>Female permanently in ventral groove of male
>Adaptations to evasion of host immunity
>Pathology associated with granulomatous lesions

Front 39

What are Nematodes?

Back 39

>Free living and parasitic
>Egg-L1-L4 adult
>Resistant cuticle
>Multi organ systems
>Broad classification
- Intestinal
- Filarial
- others

Front 40

What is Filariasis and a potential pathology in humans?

Back 40

>Long lived roundworm
>Requires larval passage through insect vector
>4 major species
- Lymphatic disease (Wucheria bancrofti, Brugia malayi)
- Blindness (Onchocerca volvulus, Loa loa)

LYMPHATIC FILARIASIS:
>Adults: afferent lymphatics
>Juveniles: blood dwelling, sheathed micro filariae
>Pathology associated with adults:
- Inflammation and immune responses to worms
- Lymphatic inflammation, pain, fever
- Elephantiasis (chronic lymphodaema, fibrous infiltration, thickening of the skin)

Front 41

What are two examples of intestinal nematodes?

Back 41

>Ascaris lumbricoides
>Hookworms
- Ancyclostoma duodenale
- Necator americanus

Front 42

What is onchoceriasis?

Back 42

>Causes river blindness / onchodermatitis
- Result due to immune response to microfilariae
- Unsheathed microfilariae found in skin leading to nodular formation
- Skin changes; increased pigmentation, loss of elasticity, hanging groin, pouches under eye
- High vector density with 30% blindness
>Immune response to treatment = Mazotti reaction

Front 43

Identify this microbe and describe its characteristics.

Back 43

>Taenia Saginata
- beef tapeworm
- found in lumen of small intestine
- 5-20m long
- 60M cases world-wide
- competes for nutrients and space!

Front 44

Identify this microbe and its characteristics.

Back 44

>Taenia solium scolex
- pork tapeworm
- found in small intestine
- disease associated with nutrient competition and physical blockage

Front 45

Identify this disease and its cause.

Back 45

Elephantiasis; filariasis (nematode / round worm)