infectiology

Parasite

Living organism dependen of another organism named host

Dependence can be transitory or definitive during the parasite life

Anthroponosis

Parasites only infect humans

Zoonosis

When animal parasites infect humans

Parasitism

Nutrient spoliation of the host towards the parasite

Unilateral physiological dependence

Parasite only gets the profit

Symbiosis

Mutual benefits

Parasite positions

• Taxonomic positions: belong to eukaryotes

• Anatomic location (ecto or endo parasites)

Protists

Unicellular eukaryotic cells

Helminths

Pluricellular eukaryotes → worms

Eumycytes

Fungi → eukaryotes uni or pluricellular

Ectoparasites

• On the host surface → provokes inconvenience (itching): lices

• Dwell in teguments → diseases: sarcoptic mange

Endoparasites

Different locations within the host:

• Cavities: intestine (taenia)

• Blood vessels (schistosomes)

• Muscular tissue (trichinella)

• Specific cells: erythrocyte (plasmodium), macrophage (leishmania)

Accidental parisitism

Fly larva within a wound

Optional parasitism

Normally saprophytes in the natural under certain conditions → parasites (fungi)

Obligatory parasistism

• Temporary: part of its life as a parasite and part as free-living organism (fasciola → liver fluke, strongyloides → anguillulosis)

• Permanent: parasite life in one or several hosts (filaria, plasmodium)

Erratic parasitism

Parasite in an unusual host (canin ascaris getting lost in human → larva migrans syndrome)

Parasite specificity

Degree of fidelity between parasite an hosts (stenoxenic or euryxenic)

Stenoxenic parasites

High fidelity degree to a host, only infects species hosts of taxonomically close to each other (plasmodium, anopheles sp.)

Euryxenic

Low fidelity degree to a host (trypanosoma brucei rhodesiense → in human and mammals)

Host

Living organism which harbours a pathogenic agent (parasite)

Final host

Host harbouring the sexual or adult form of the parasite

Intermediate host (IH)

Harbouring the asexual or larval form of the parasite

• The parasite should stay within the host

• Necessary to get transformations into the inefective form exhibiting contamination habilities

Passive intermediate host

When it harbours the ineffective form without performing any movement to get it or transmit it (molluscus for schistosomes)

Active intermediate host

Vector → when it carries and inoculates the inefective form of the parasite (anopheles sp. for plasmodium, sandflies for leishmania sp.)

Obligate host

When the parasite transforms/matures within a host

Facultative host

Optional host when there is no parasite transformation → paratenic host

Vector

Host for a pathogen and able to transmit it actively to another organism

• Hematophagous insect (arthropod) collecting the parasite in infected patients/animals, keeping it, carrying it, and inoculate it in naive patients/animals

Biological vectors

Ensure the parasite maturation or multiplication, essential to the parasite life cycle as an intermediate host (anopheles mosquito → malaria vector). Parasite transformation

Mechanical vectors

Only a role of parasite transport, no necessary to the life cycle (housefly carrying amoebal cysts). No transformation

Parasite reservoir

Animal, plant, or external environment ensuring the parasite's survival, making it available for the different hosts of the life cycle (sheep → parasite reservoir of the liver fluke)

Human parasite reservoir

When infection is strictly human, humans are reservoir (anthroponosis)

Accidental host

Some pathogens carried by animals can be transferred accidentally to humans, minor epidemiologic role (human trichinellosis and hydatidosis) → parasitic dead ends

Animal parasite reservoir

• Infection is common to humans and animals

• Animals are reservoir promoting transmission to humans, good tolerance and low clinical manifestations

Land based parasite rervoir

Soil, release through feces → intestinal parasite (cyst of amoeba/giardia, eggs of helminths, fungi)

Life cycle

Sequence of mandatory transformations occurring in a precise order for a parasite to get the next parasite generation

Monoxenic life cycle

Direct cycle. Parasite evolution takes place within the same host or partially in external environment, only 1 host

Short direct cycle

Eggs or larvae are directly infectious without necessity of passage within the external environment

Long direct cycle

Eggs or larvae should follow a development in external environment under specific conditions to become infectious

Heteroxenous life cycle

Indirect cycle. Parasite transformation take place in several successive hosts

Polyembryonny

Two or more embryos developing from a single fertilized egg (trematodes)

Forms of resistance

• Eggs (worms)

• Encysted larvae (nematodes, trematodes)

• Cysts (protists)

Types of worms

• Nematodes: round

• Cestodes: flat, segmented

• Trematodes: flat, unsegmented

Quiescent eggs

Require maturation in the environment, not directly infectious (ascaris lumbricoides)

Embryonated eggs

Infectious as soon as eliminated in the stools (enterobius vermicularis)

Encysted larvae

Resealed, larvae mobile encyst and attach, infectious when ingested (metacercarie of liver fluke)

Cysts

• Cysts of resistance (entamoeba histolytica)

• Vegetative or division cysts: involved in the parasite's life cycle and reproduction

  • Plasmodium sp.: gametocyte, which undergoes gametogenesis and fertilization.

  • Toxoplasma:

    • Forms oocysts that are released into the environment, acting like an "encapsulated egg." Oocysts contain two smaller sacs called sporocysts, and each sporocyst contains four infective sporozoites.

    • Can also form tissue cysts in the brain that contain slow-growing forms called bradyzoites

• Spores (microsporidiae)

Modes of transmission

• oral route

• muco-cutaneous route

• respiratory route

• vectorial origin

• sexual route

• congenital route

• transfusion route

• transplantation

Oral transmission

By external environment through contaminated water and food

Oral transmission of monoxenous protists via contaminated food and water

• Entamoeba hystolytica (amoebosis)

• Giardia intestinalis (giardiasis)

• Cryptosporidium parvum (cryptosporidiosis)

• Enterocytozoon bieneusi (microsporidiosis)

• Cyclospora cayetanensis (cyclosporosis)

• Isospora belli (isosporose)

Giardiasis

• Giardia intestinalis, lamblia or duodenalis

• Ingestion of mature cysts in water and food

• Diarrhea

• Oral transmission

Oral transmission of monoxenous helminths via contaminated food and water

• Ascaris lumbricoides (ascaridiosis)

• Enterobius vermicularis (oxyurosis)

• Toxocara canis (toxocariasis) → human paratenic host

• Trichuris trichiura (trichocephalosis)

Oral transmission of heteroxenous helminths via contaminated food and water

• Hymenolepis nana (hymenolepiasis)

• Echinococcus granulosus (hydatidosis) → human dead-end host

Oral transmission of heteroxenous helminths via contact with animals or plant supports

• Toxoplasma gondii (toxoplasmosis)

• Angiostrongylus cantonensis (angiostrongylosis) → human accidental host

Toxoplasmosis

• Toxoplasma gondii

• Heteroxenous life cycle

• Human contamination:

  • Eating uncooked meat

  • Blood transfusion and organ transplant

  • Congenital (mother-child)

• Able to penetrate nervous and muscular tissues

• The cat is the definitive host

• Zoonotic disease

Oral transmission through cyclops

• Dracunculus medinensis (dracunculosis)

• Passive aquatic intermediate host

• Worm lysis can cause alergia if not extracted completely

Muco-cutaneous transmission through water and moist soil

• Strongyloides stercoralis (strongyloidiasis)

• Intestinal hookworm (ancylostomiasis)

• Schistosoma spp. (schistomiasis)

• Larva migrans → human dead end host

Intestinal hookworm

• Ancylostoma duodenale

• Humans are the principal host

Muco-cutaneous transmission through dry environment

• Dermatobia hominis (myiases)

• Tunga penetrans (tungiasis)

Muco-cutaneous transmission through human contact

• Saecoptes scabiei (scabies)

• Contagious dermatitis

• Sexually transmitted

• Sick person or asymptomatic carrier

Vector-borne transmission by flying evening and night insect vectors

• Malaria (anopheles)

• Leishmaniases (sandflies)

• Lymphatic filariases (culex, anopheles, aedes, mansonia)

Vector-borne transmission by flying diurnal insect vectors

• Trypanosomiases (Tse-tse fly)

• Loasis (Chrysops)

• Onchocercosis (Blackflies)

• Mansonellosis (Culicoides)

Vector-borne transmission by terrestial insect vectors

• Chagas disease (bug)

• Babesiosis (tick)

Malaria

• Plasmodium vivax

• Heteroxenous life cycle

• Cyclic fever, anemia

• Provoked by protists

• Congenital transmission, blood transfusion

• Humans are the intermediate host

Airborne transmission

Pneumocystis jirovecii (fungi)

Sexual transmission

Uro-genital trichomoniasis

Human final host

Taenia saginata (taeniasis)

Human secondary host

Dipylidium caninum

Fungi

• Uni or multicellular eukaryotes

• Heterotroph (no photosynthesis)

• Sexual and asexual reproduction (spores)

• Thallophyte (constituted of filaments)

• Cell wall made up of chitin

Classification by modes of nutrition

• Symbionts

• Saprobes (yeast, mold)

• Parasites (dermatophytes)

Classification by pathologies

• Cutaneous (candida albicans)

• Sub-cutaneus (madurella)

• Invasive (coccidioides)

• Diverse clinical forms (fusarium)

Phylogenic classification

• Chytridiomycota

• Sygomycota

• Glomeromycota

• Ascomycota

• Basidiomycota

Classification as a function of cellular organization

• Moulds: filamentous multicellular fungus

  • Aseptate hyphae: hyphae divided by cross walls

    • Zygomycetes

  • Coenocytic hyphae: hyphae lacking cross walls

    • Dematiaceous moulds: mold with pigmented hyphae

    • Hyaline moulds: lack of hyphae pigmentation

      • Hyaline septate moulds

      • Dermatophytes

      • Dimorphic moulds

• Yeasts: unicellular fungus →

Yeast identification method

Candida species

• Yeast

• Ascomycota (septate hyphae, unflagellated spores)

• Saprobe in the digestive, respiratory or vaginal mucosa

• Can cause candidiasis when it multiplies uncontrollably

• Ovoid cells → blastoconidia with multipolar budding

• Pseudohyphae

• Chromogenic color change on chromagar

• Germ tube for C. albicans

Cryptococcus neoformans

• Yeast

• Basidiomycota

• Ubiquitous, saprophyte in the environment

• Ovoid cells → blastoconidia with unipolar budding

• Presence of a capsule

• No pheusohyphae, no germ tube

• Production of melanin

• Contamination by inhalation of spores

• Cause cryptococcosis

• + Urease, 37ºC

Cryptococcosis

Is a potentially fatal fungal infection of mainly the lungs, presenting as a pneumonia, and in the brain, where it appears as a meningitis. Mostly in immunocompromised patients

Aseptate molds

• Entomophtorales:

  • Insect pathogenic fungi

  • Production of a single conidium forcibly ejected upon maturation

  • Waxy, folded, and compact mycelium

• Mucorales:

  • Numerous spores in a sporangium

  • Flucose aerial mycelium

Rhizopus sp.

• Zygomycete

• R. oryzae

• Ubiquitous saprobes in soils, decaying foo

• Spherical sporangium; columella +; apophysis-; rhizoid +; unbranched sporangiophores

• Transmission via the respiratory, percutaneous, or oral routes

• Risk factors: diabetes, immunosuppression

• Can cause: rhino cerebral, pulmonary and cutaneous infections, gastric ulcers and peritonitis

Alternaria sp.

• Dematiaceous molds

• Large dark septate muriform (bricks) conidia in chains

• Cause allergic reactions, cutaneous/sub-cutaneous mycosis

• Risk factors: immunosuppression

• Ubiquitous saprobes in soil or decaying vegetation

• Transmission: breakdown of the skin or mucous membrane (ex: nasal, ocular) or inhalation

• A. alternata

Phaeohyphomycosis

General term designating infections caused by dematiaceous fungi other than chromoblastomycosis or eumycetoma

Penicillium sp.

• Hyaline septate molds

• very large and ubiquitous genus

• Production of chains of conidia, in basipetal succession (basocatenate: youngest conidia at the basal end of the chain), on flask-shaped phialides via metulae and branches giving a brush-like appearance (penicillus)

• Production of different forms of unicellular conidia

• Associated with allergic reactions: allergic rhinitis, asthma,

• Many species are potential mycotoxin producers

• P. citrinum

Histoplasma sp.

• Dimorphic fungi

• H. capsulatum var. capsulatum and H. capsulatum var. duboisi

• Histoplasmosis: acute pulmonary infection to chronic pulmonary or fatal disseminated disease

• Grow as molds in the natural environment at 25-30°C and as yeasts at 37°C

Microsporum sp.

• Dermatophytes: skin disease

• Thick-walled macronidia with a terminal knob

• Causing frequently ringworm in

  humans (tinea corporis, tinea capitis) and rarely onychomycosis.

Family of antifungals drugs

• Polyenes

• Azoles

• Echinocandins

• Pyrimidine

• Allylamines

Polyenes

Amphiphilic molecules combining with ergosterol to produce holes in fungal plasma membrane, hydrophilic and hydrophobic

Polyenes mechanism of action

• Pore formation in the fungal plasma membrane

• Increase of permeability → uncontrolled exchange of electrolytes

• Lead to cell death

Amphotericin B (AmB)

• Polyenic antifungal

• Large spectra: yeast (Candida spp, crypt. neoformans), filamentous (alternaria spp, aspergillus, hyalohyphomycetes), dimorphic (histoplasma, blastomyces)

• Lack of activity in dermatophytes, C. lusitanie, trichosporon sp.

• Activity on cholesterol of human cells → toxicity

• Formulation: Fungizone (old, highly toxic), AmBisome

Nystatin

• Polyene for local administration

• Cutaneous and mucosal application

• Fungal sterilization of the digestive tract (Candida sp.)

• Mycostatine

Pymaricin

• Polyene

• Treatment of keratomycoses

• Ophthalmic formulation

Azoles

Inhibition of ergosterol biosynthesis (fungistatic). Di or triazoles

Diazoles

• Topical administration

• Miconazole, econazole, tioconazole, ketoconazole

Triazoles 1st generation

• Fluconazole: IV, good oral biodisponibility, crosses BBB

• Itraconazole: larger spectra

Triazoles 2nd generation

• Voriconazole

• Posaconazole

• Ravuconazole

• Isavuconazole

Mechanism of action of azoles

14α-demethylase is a cytochrome P450 enzyme that allows the conversion of lanosterol to ergosterol by interacting with oxygen

Azoles inhibit 14α-demethylase by interacting with its active site → block oxygen → prevent conversion of lanosterol to ergosterol → accumulation of toxic methylated sterols → membrane alteration → prevent fungal cells from building new membranes to grow and divide

Azoles toxicity

Lack of specificity. Cross-inhibition of hepatic cytochrome p450 enzymes in sexual hormones, corticoid biosynthesis, and hepatic metabolism

Fluconazole Triflucan

• Against C. albicans and C. neoformans

• C. krusei resistant

• C. glabrata decreased sensitivity

Itraconazole

• Godd activity: aspergillus, dimorphic fungi, phaehyphomycetes, dermatophytes, yeast

• Lacj of activity: fusarium sp, mucorales

Voriconazole

• Candida resistant to fluconazole

• Rare infections: fusarium, penicillium marneffei, scedosporium

• Low activity in zygomycetes

Posaconazole

• Zygamycetes

• Dimorphic fungi

• Aspergillys fumigatus

• Candida sp

• Fusarium sp

• Scedosporium