Lecture Notes on Parasites and Protozoa of Clinical Importance PDF

This document consists of lecture notes for two lectures: Parasites and Protozoa of Clinical Importance and Fungi of Clinical Importance. Parasites and Parasitology A parasite is defined as an organism that lives on or in a host and gets its food from or at the expense of its host. M...

This document consists of lecture notes for two lectures: Parasites and Protozoa of Clinical Importance and Fungi of Clinical Importance. Parasites and Parasitology A parasite is defined as an organism that lives on or in a host and gets its food from or at the expense of its host. Medical parasitology is the study of parasites that are capable of causing disease in humans and animals. Host: The organism the parasite lives on/in. o There can be more than one host during a life cycle. o Often the life cycle includes larval stages and adult stages in diDerent hosts. Life Cycle: Describes how an organism develops from the immature stage to the adult. Vector: An animal that carries a parasite to the host. Reservoir: Non-human “host” where the parasite can live. General Characteristics of Parasitic Diseases Parasitic diseases are usually chronic and there are no e>ective vaccines or practical chemotherapy treatments for them. They typically a>ect the young and underprivileged and are vector-borne. Host Responses to Parasites Nonspecific Immunity o Macrophage endocytosis o Inflammation o Hyperplasia – causes host cell proliferation o Neoplasia (cancer) – rarely parasites have been associated with cancer Specific Immunity o Humoral response o Cell mediated response Parasite Responses Antigenic variation: change surface glycoproteins regularly Being poorly antigenic: don’t induce a response, or only a mild one Hide within host cells: host can’t kill what it can’t find Camouflage: use bits of host cells and attach to parasite’s surface Depress host’s immune response: modulate production of host T cell production Classification of Parasites The parasitic organisms important to human health are eukaryotes with a well defined chromosome in a nuclear membrane. They are functionally classified as: 1. Protozoa 2. Helminths 3. Arthropods Protozoa Protozoa are single-cell eukaryotes ranging in size from 2 to 100 µm. Protozoa that are infectious to humans are classified into four groups based on their mode of movement:  1. Sarcodina – the ameba, e.g., Entamoeba (they “slither”) 2. Mastigophora – the flagellates, e.g., Giardia, Leishmania 3. Ciliophora – the ciliates, e.g., Balantidium 4. Sporozoa – organisms whose adult stage is not motile, e.g., Plasmodium, Cryptosporidium Protozoa can invade the lumen (intestinal and urogenital protozoa) or tissues (blood and tissue protozoa). General Characteristics of Protozoa Nutritional requirements are simple and require the assimilation of organic nutrients. Many protozoa can exist in a trophozoite form or in a cyst form when under adverse conditions. Many have developed elaborate immuno-evasive mechanisms to respond to attack by host immune system (by continuously changing their surface antigens or hijacking host molecules). Trophozoite: any stage in a protozoan’s life cycle which can ingest food. Also used to refer to the motile form. Cyst: the non-motile form which is protected by a distinct membrane or cyst well --- facilitate host to host transmission. Excystation: the process of emergence of the trophozoite from the cyst. Examples of Pathogenic Protozoa Intestinal Protozoa: Entamoeba histolytica --- Worldwide (Sarcodina) o Transmission occurs through the fecal/oral route: cysts passed in feces are ingested, the cyst wall disintegrates in the small bowel, amebas go to the colon and live on red blood cells and bacteria. o Causes necrosis, ulceration (bloody diarrhea), flatulence and cramping that can last for years. o Treatment: metronidazole, iodoquinol, paromomycin o Found worldwide in most mammals; especially bovine, cattle, cats and dogs. Giardia lambia --- Worldwide (flagellate) Cryptosporidium species --- Worldwide (Sporozoa) o The leading cause of outbreaks of diarrhea linked to water and the third leading cause of diarrhea associated with animal contact in the United States. o Leading causes of infection include swallowing contaminated water in pools or water playgrounds, contact with infected cattle, and contact with infected persons in child care settings. Urogenital Protozoa: Trichomonas vaginalis --- Worldwide (flagellate) o Only exists in trophozoite form. o Transmission is by intimate sexual contact. o Worldwide, 10% to 25% adult women become infected sometime and 2% to 10% in adult men. Blood and Tissue Protozoa: Plasmodium species --- Tropic & subtropical areas (Sporozoa) o Causes malaria, which kills 1-3 million people per year, mostly in the tropic region (Africa). o Transmission occurs through mosquitoes. Naegleria fowleri --- Worldwide (Sarcodina) o Known as the “brain eating amoeba”. o Infections are rare and only occur through the nose when people swim in warm water (e.g., summer) lakes, ponds, rivers and hot springs. o Infections are essentially 100% fatal. Toxoplasma gondii --- Worldwide (flagellate stage) o Infects both humans and domestic animals worldwide. o Transmission is by inhalation/ingestion of infective oocysts by grazing animals or from infected cat litter or by ingestion of animal muscle tissue containing pseudocysts. o Felines are the definitive hosts. o Pregnant women are advised to avoid handling cat litter to prevent congenital infection. Trypanosoma species --- America and Africa (flagellate) o Trypanosoma brucei: Causes African trypanosomiasis (sleeping sickness). § Transmitted by bloodsucking tsetse fly. § Limited to central Africa. § Multiplies at the site of the bite. § Spreads through bloodstream to CNS. o Trypanosoma cruzi: Causes American trypanosomiasis (Chagas’ disease). § Infects 15-20 million in South and Central America. § Kills 50,000 every year (especially children). § Transmitted by reduviid bug (kissing bug), which bites sleeping hosts around the mouth and on the face. Helminths and Arthropods Helminths (worms) possess elaborate attachment structures and don’t have a circulatory system. o Nematodes (roundworms) o Cestodes (tapeworms) o Trematodes (flukes) Arthropods (insects, etc) can directly cause diseases (or indirectly as intermediate hosts and as vectors of many infectious agents). General Characteristics of Helminths Adults are usually large enough to be seen by the naked eye (tapeworms can be up to 25 meters). Many worms are quite prolific, producing as many as 200,000 oDspring (eggs) each day. Many have mouth-like attachment structures, such as hooks, suckers or plates. Nutritional requirements are met by active ingestion of host tissue or fluids.  May also secrete enzymes to destroy host cells and neutralize immunologic and defense mechanisms. Possess the ability to alter antigenic properties to evade the host immune response. Examples of Pathogenic Helminths Nematodes (round worms): Ascaris lubmricoides --- Worldwide o The most common helminthic infection worldwide (-1 billion). o Prevalent in areas where human faeces are used as fertilizer. o Adult female may lay up to 200,000 eggs per day for as long as a year. o Infection occurs through ingestion of food contaminated with the eggs. Necator americanus --- Tropic & subtropical areas o Known as hookworms. o Infects -20% of the world’s population. o Transmission requires high rainfall and a warm climate. o Infection occurs when larvae in the soil penetrate the skin of people walking barefoot. o Larvae are transported to the lungs and then swallowed. o Mature into adults that lay eggs in the intestines. o Adult worms live in the small bowel and suck blood from mucosa. o Can cause iron-deficiency anemia. o May cause rash, abdominal pain and reduced development in children. Toxocara species --- Worldwide o Ascaris-like parasite of dogs. o High infection rate in dogs in US. o People are dead-end hosts. o Infected when eggs are ingested. o Larvae invade tissues and make granulomas. o May cause rash, asthma and neurological defects. Trematodes (flat or worm-like / small / flukes): Schistosoma species --- Africa, Asia, Latin America o 200m people in 74 countries are infected, 85% of whom live in sub-Saharan Africa. § S. haematobium – Africa, middle east § S. mansoni - Africa and Latin America § S. japonicum – Pacific region o Transmission occurs in fresh water. o Cercariae released from snails penetrate the skin of people. o Adult worms live in the veins and release eggs into water. o Eggs develop into miracidia which then infect snails. o Liver failure occurs because the parasites release millions of eggs, which remain trapped in liver tissue causing extensive damage, including liver fibrosis. Fasciola hepatica --- Worldwide Cestodes (ribbon shape multi-segment flatworms): Taenia saginata --- Worldwide o Common name: beef tapeworm o One of the most common causes of cestode infections in the US. o Infection occurs through consumption of insuDiciently cooked beef. o Adult size: 4-6 meters Diphyllobothrium latium --- Worldwide Echinococcus granulosus --- Sheep-raising countries Echinococcus multilocularis --- Canada, US, Europe Arthropods Usually ectoparasites. Worldwide distribution. Usually no vector. Usually temporary. Reservoirs are variable. Pathologies: itching, scabs at the site if the bite, rashes, redness, etc. Often carriers of bacterial infections. Examples: body, head, and pubic lice; bed bugs; ticks Fungi & Mycology Basic Fungal Biology Fungi are eukaryotic, heterotrophic organisms devoid of chlorophyll that obtain their nutrients by absorption and can reproduce by spores. Most fungi have hyphae (singular hypha) that can be elongated by tip growth. There are over 2.2 million species of fungi but only 300 are associated with human disease and only a small handful are frequently encountered in the clinic. Most fungi enhance our quality of life by degrading organic debris, contributing to food preparation (breads, cheeses) and facilitating beer and wine production. Basic Concepts: o Eukaryotes o No locomotion structures o Cell membrane contains ergosterol instead of cholesterol o Cell wall contains chitin, a long chain polymer of N-Acetyl Glucosamine, a derivative of glucose o Some species have capsules composed of polysaccharides (mannans and glucans) complexed with surface proteins o Yeasts: grow as single cells and reproduce by budding o Molds: multicellular, filamentous hyphae (with or without septa) forming a mass (mycelium) that reproduce sexually and asexually via spores o Dimorphic fungi: can switch between yeast and mold form in response to diDerent environmental stimuli Host Response to Fungi Humans are naturally resistant to most invasive fungal infections due to a highly sophisticated innate and adaptive immune systems.  Neutrophils function in phagocytosis but capsular polysaccharides of some fungi are anti-phagocytic. Fungal proteins elicit strong T- and B-cell responses. T-cell mediated immunity is key determinant in protection. Fungal Pathogenicity Only a small minority of fungi are capable of establishing invasive human infections because they meet the four criteria required to do so: 1. The ability to grow at or above 37°C 2. The ability to reach internal tissues by penetrating or circumventing host barriers, e.g., through small airborne cells that directly enter air-filled spaces of lungs and sinuses. 3. The ability to digest and absorb components of human tissues. 4. The ability to withstand the human immune system. Fungal Pathogens Primary fungal pathogens: can cause disease in any individual, regardless of their health status. Opportunistic fungal pathogens: not suDiciently pathogenic to cause infection in healthy individuals, but are known to cause disease in individuals with a weak or depleted immune system. In rare cases, opportunistic fungi can cause infection in healthy individuals if a suDicient quantity is inhaled. Fungal Pathogenesis Adhesion to mucosal surfaces Invasion of host tissues Production of extracellular products Evasion of the immune system Classification of Mycoses Mycoses are classified by the tissues they infect: Superficial: outside layers of skin or hair only o Example: pityriasis versicolor § Chronic, superficial infection of the outer skin due to Malassezia furfur. § Causes hypo- or hyperpigmented scaly lesions. § Inflammation is limited and it is primarily a cosmetic problem. § Treatment: keratinolytic agents (salicylic acid) and topical imidazoles (miconazole). Cutaneous: invade skin, hair and nails (dermatophytes) o Caused by three genera of fungi known as dermatophytes: Microsporum sp., Trichophyton sp., and Epidermophyton sp. o Common features: § Only grow within the dermis at the body surface. § Make enzymes that degrade keratin, elastin and collagen of skin, hair and nails. § Mostly troublesome, not serious.  § Millions of dollars are spent annually to treat them. o Also called tineas or ringworms: § Tinea corporis – non-hairy body parts § Tinea capitis – scalp § Tinea pedis – athlete’s foot § Tinea barbae – beard § Tinea cruris – jock itch § Tinea unguium – nails o The only really contagious fungal infections. o Examples: § Tinea corporis: typical “ringworm” lesions with clearing, scaly center with raised red edges. § Treatment: topical antifungals for 2-4 weeks (miconazole, clotrimazole) or oral antifungals as necessary (itraconazole, terbinafine). § Tinea pedis (athlete’s foot): the most prevalent dermatophytosis in the US. § Uncommon in children. § Primarily occurs in adults who wear shoes. § Chronic infection of toe webs and soles. § Fluid-filled lesions dry to itch, crack and peel. § Treatment: keep areas dry and treat with topical or oral antifungals (terbinafine, azoles). Subcutaneous: localized, enter by trauma o Example: sporotrichosis § Generally introduced by trauma. § Caused by Sporothrix schenckii, which is found in soil and decaying vegetation. § Most common in agricultural workers and gardeners. § Also known as “rose-handler’s” disease. § Initial lesion usually on extremities. § Multiple lesions develop along lymphatic tracts. § Usually few systemic signs of illness. § Treatment: newer azole, e.g. itraconazole for 3-6 months. Systemic: aDects multiple organs/tissues or whole body o Often initially an infection of the lungs, spreads to other parts of the body. o More virulent, can cause disease in healthy hosts. o Dimorphic Systemic Mycoses: § Involves virulent fungi capable of causing infection in healthy people. § Fungi overcome physiological and cellular defenses of the normal human host by changing form (mold to yeast form). § Primary site of infection: pulmonary following inhalation but can disseminate to other (systemic) sites. § Geographically restricted. § Examples: § Histoplasmosis: caused by Histoplasma capsulatum, which is endemic in the Ohio and Mississippi River valleys. § Most infections are asymptomatic and self limiting, however, immunocompromised patients can experience problems. § Forms localized granuloma, can disseminate, and can mimic tuberculosis. § Blastomycosis: caused by Blastomyces dermatitidis, which is endemic in the Ohio and Mississippi River valleys and Missouri and Arkansas River basins. § Disease is also seen in horses and dogs. § Similar to histoplasmosis and can mimic tuberculosis or lung cancer. § Symptomatic infection is common. § Coccidioidomycosis: caused by Coccidioides immitis, which is endemic in the southwest US, Mexico, and South America. § Infection is usually asymptomatic but mortality of untreated disseminated disease is ~ 50%. § Paracoccidioidomycosis: caused by Paracoccidioides brasiliensis, which is restricted to Central and South America. § Asymptomatic infections are common. § General symptoms are similar to histoplasmosis and blastomycosis. § Disseminated disease is rare, usually oral, nasal and facial nodular ulcerative lesions and lymphadenopathy. o Opportunistic and Systemic Fungal Infections: § Increasing due to: § Increase in the number of people who have become immunocompromised due to transplants, chemotherapy, etc. § Emergence of HIV/AIDS. § Medical advances, including the elderly living longer, increasing survival of premature neonates, use of artificial heart valves and indwelling catheters. § An important issue is the emergence of opportunistic pathogenic fungi which were thought to be non-pathogenic. § The more immunosuppressed the host, the more susceptible they are to infection from more obscure fungi. § Examples: § Aspergillosis: § Caused by over 150 species of Aspergillus. § Ubiquitous in soil and plants worldwide. § Infection requires profound immunosuppression. § Generally due to inhalation of spores. § Patients: gardeners and farmers with underlying disease; cancer and transplant patients (90% have had chemotherapy or steroids); people with low neutrophil counts. § Not particularly common in AIDS patients. § In immunocompromised hosts, spores germinate and hyphae invade tissues. § Cutaneous infections usually occur at catheter sites and wounds. § Disseminated infections invade tissues and fill them with hyphae.  § Treatment is IV amphotericin B, posaconazole, or echinocandin. § Rarely successful unless suppression is reversed. § Cryptococcosis: § Most common species is Cryptococcus neoformans. § Not dimorphic – always a yeast. § Encapsulated yeast. § Forms titan cells that have undergone huge ploidy increase. § Isolated from soil (bird droppings). § Hallmark infection of AIDS patients. § Mild infection begins in the lungs. § May go systemic with a predilection for the CNS. § Slowly-developing meningitis that may mimic brain tumor, abscess, or multiple sclerosis. § Symptoms include headaches, dizziness, irritability and confusion that increase in intensity over time. § Treatment: § Mortality rate if untreated is ~100%. § 80-90% cure rate with treatment. § Amphotericin B IV ± 5-flucytosine. § Sometimes can switch to oral azole. § Relapse rate is significant, especially in AIDS patients. § Candidiasis: § Candida is present in the mouth/gut of ~60% of healthy people. § Can colonize almost every niche in the human body and is a commensal of the mucosal microbiota, where maintenance of a stable host-fungus relationship is crucial for avoiding disease. § The most prevalent opportunistic human fungal pathogen and the 3rd leading cause of all bloodstream infections. § Infection is associated with immunosuppression, diabetes, broad-spectrum antibiotics, corticosteroid use, and denture use. § Systemic candidiasis is deadly – causing mortality in >40% of individuals, despite state-of-the-art antifungal therapies. § Over 20 species of Candida yeasts can cause infection in humans, including mucosal and bloodstream infections. § Candida albicans is the most common. § There is an increasing incidence of other species, including: § Candida glabrata § Candida parapsilosis § Candida tropicalis (higher incidence in diabetics) § Source of infection is usually endogenous. § Oral candidiasis (“thrush”): § C. albicans is part of the normal mouth microbiota, but illnesses, stress or medications can disturb this balance. § Medications include steroids and antibiotics.  § Symptoms usually develop suddenly and include: § Creamy white, slightly raised lesions in the mouth — usually on the tongue or inner cheeks, occasionally the roof of the mouth, gums, tonsils or back of the throat. § Redness and soreness inside and at the corners of the mouth. § Loss of sense of taste (ageusia). § Cottony feeling in the mouth. § Lesions can hurt and may bleed a little during tooth brushing. § In severe cases, the lesions can spread into the esophagus and cause pain and the feeling that food is stuck in throat. § Candida albicans is a polymorphic fungus that can alter its physiology and morphology during infection. § It diDers from the dimorphic fungi in that it forms hyphae at 37°C. § Candida auris: § A serious global health threat because: § It is resistant to multiple antifungal drugs commonly used to treat Candida infections. § It is diDicult to identify with standard laboratory methods, and it can be misidentified in labs without specific technology. § It has caused outbreaks in healthcare settings. § Important to quickly identify C. auris in a hospitalized patient so that appropriate infection control measures can be taken. § Black fungus (Mucor) infections in COVID patients (India): § The source notes that there is a recognition of diagnostic gaps for laboratory diagnosis of fungal diseases. § Fungal biofilms: § Candida commonly adheres to implanted medical devices, growing as a resilient biofilm capable of withstanding extraordinarily high antifungal concentrations. § A variety of biomaterials used in clinical practice are able to support biofilm formation by Candida (eg. catheters and dentures). § A key feature of mature biofilms is the production of extracellular matrix, a polymeric material that promotes adherence and protects biofilm cells from environmental insults. § This material is also thought to aid in the retention of nutrients, water and enzymes. § Since common drug therapies do not eradicate Candida biofilms, removal of the infected device is almost always necessary to cure the infection. § Candida biofilm infections, if not successfully treated, can have devastating consequences, progressing to bloodstream infections and invasive fungal infections with high risks of mortality. Antifungal Drugs There is a limited number of antifungal drug targets that do not also cause host toxicity. Antifungal drug resistance, including multidrug resistance, is increasing.