Parasitic Infections: Protozoans

Parasitic Infections

• Parasites are either protozoans (microscopic, single-celled eukaryotes) or helminths (macroscopic, multicellular worms).
• Disease-causing parasites rely on their host to survive.
• Parasitic infections are a significant global health issue.
• More than 200 million people have malaria.
• Malaria causes more than half a million deaths per year, mainly in children.
• Over 500 million individuals are affected by amebiasis.

Parasitic Protozoans: Morphology and Pathogenesis

• Protozoans range from 2–100 μm
• Protozoans have membrane-bound nuclei and cytoplasm
• Protozoans possess a trophozoite and a cyst stage.
• Trophozoites are the active, metabolically active, growing, and reproducing stage.
• Cysts are the dormant stage and protect from harsh conditions.
• Protozoans are classified by how they move.
• Ameboids feature pseudopods.
• Ciliates have cilia.
• Flagellates have flagella.
• Sporozoans have motile structures during the gamete stage only.
• Many protozoan organisms reproduce asexually via binary fission.
• Infectious protozoans are often facultative anaerobes and heterotrophs.
• They have highly developed reproductive systems.
• Some protozoans form cysts for protection and transmission between hosts.

Parasitic Helminths: Morphology and Pathogenesis

• Helminths are worms that are elongated, cylindrical, or flat.
• Helminth sizes range from 1 mm to over 10 mm.
• Helminth bodies are covered by a tough cellular cuticle that may be smooth or have ridges, spines, or nodules.
• The anterior end of helminths features suckers, hooks, or plates for attachment.
• Helminths contain primitive nervous and excretory systems along with a highly developed reproductive system and no circulatory system.

Three Classes of Helminth

• Nematodes (roundworms) come in gastrointestinal forms which use one host and blood/tissue forms which use multiple hosts.
• Cestodes (tapeworms) are flat, ribbon-shaped organisms.
• Cestodes have heads with suckers and often hooks.
• Cestodes generate proglottids, which are reproductive segments with male and female gonads.
• Cestodes absorb nutrients across their cuticle, lacking a digestive tract.
• Some cestodes use one host, while others use two.
• Trematodes (flukes) have leaf-shaped bodies and two suckers.
• The oral sucker in trematodes takes in nutrients and regurgitates waste.
• Distal suckers on trematodes are used for attachment.

Life Cycles and Transmission Pathways of Protozoans and Helminths

• Life cycles and transmission mechanisms are organism-dependent.
• Single-host parasites complete their life cycle in one host, requiring environmental survival.
• Multiple-host parasites require more than one host to complete the life cycle.
• Sexual reproduction occurs in the definitive host.
• Asexual reproduction occurs in the intermediate host.

Malaria (Plasmodium Species)

• Malaria is a febrile illness caused by parasitic infection of human red blood cells.
• Malaria exists throughout the world, mainly in warmer climates.
• Malaria is transmitted by the bite of the Anopheles mosquito.
• Disease spread relies on mosquito density and feeding habits.
• Populations most at risk include children and immunocompromised adults.

Life Cycle of Plasmodium (Sexual Life Cycle)

• Female mosquitoes ingest male and female Plasmodium gametocytes from an infected host.
• Male gametocytes fertilize female gametocytes in the mosquito's gut.
• A zygote forms an oocyst and sporozoites then develop inside.
• The oocyst ruptures, releasing sporozoites into the mosquito's body.
• Sporozoites penetrate the salivary glands.
• The cycle takes 1-3 weeks.
• Higher temperatures and humidity accelerates the process.

Life Cycle of Plasmodium (Asexual Life Cycle)

• The cycle begins when a mosquito bites a new host.
• Sporozoites are introduced to the mosquito’s saliva.
• Sporozoites move to the liver and attach to hepatocytes.
• Each sporozoite produces 2,000 to 40,000 daughter cells (merozoites).
• Infected hepatocytes rupture, releasing the merozoites after two weeks.
• Merozoites infect red blood cells.

Life Cycle of Plasmodium

• Infected red blood cells rupture within 72 hours.
• Merozoites are released.
• Some merozoites infect other red blood cells, while some transform into the gametocyte form.
• Gametocytes are then taken up by the next mosquito.

Pathogenesis of Malaria

• Fever is a malaria symptom and is initiated by the rupturing of red blood cells.
• The condition causes anemia because of the destruction of red blood cells and is accompanied by a depression of marrow function and an enlarged spleen.
• Severe red blood cell destruction causes hemoglobinuria (dark urine).
• Circulatory changes can include hypotension (low blood pressure).
• High fever causes blood vessels to dilate.
• Thrombocytopenia (low levels of platelets) is common because of the shortened life span of platelets.
• Clinical manifestations depend on the species of Plasmodium.
• Malaria can cause Cold, hot, and sweating stages.
• The cold stage includes a drop in body temperature lasting 20-60 minutes.
• Shaking and chills occur.
• The hot stage includes a temperature increase for about 3-8 hours and shaking/chills subside.
• The Sweating stage consists of profuse sweating and rapidly dropping fever for 2-4 hours.
• The recurrent hot and cold stages cause exhaustion in patients.
• Paroxysms are synchronized by the third week.
• Weeks 1-2 represent different stages of parasite development, leading to irregular paroxysms.
• Week 3+, parasite populations reach the mature stage leading to regular intervals of paroxysms.
• Paroxysms diminish and disappear when the parasites in the blood disappear.

Treatment of Malaria

• Species of Plasmodium needs to be considered.
• Immune status of the infected individual must be considered.
• Successful treatment necessitates destroying all forms of the parasite.
• This breaks the transmission cycle of the parasite.
• Artemisinin-based combination therapy is currently the best treatment.
• Chemoprophylaxis completes routine malaria control measures (vector control).
• The WHO recommended the first malaria vaccine in 2021 for children in areas with high Plasmodium transmission.

Toxoplasmosis (Toxoplasma gondii)

• Toxoplasma gondii is an obligate intracellular sporozoan.
• Domestic cats are the definitive host.
• Transmission occurs by ingesting oocysts in fecal material, eating raw meat, or unwashed fruit.

Life Cycle Of Toxoplasma

• The life cycles begins in the intestines of cats.
• Trophozoites enter the epithelium cells.
• Trophozoites undergo schizogony and then merozoites form.
• Ruptured epitelial cells release parasites.
• Merozoites differentiate into female and male gametocytes.
• Gametogony starts and oocysts are formed and released.
• Oocysts mature in the external environment for months.
• Sporozoites form during this maturation.
• Humans are intermediate hosts
• Mature oocysts are ingested and sporozoites are released.
• Sporozoites enter macrophages and travel to all organs, rupturing and then releasing new parasites.
• A new asexual cycle starts.
• The parasites are resilient in the brain, heart, and skeletal muscles.
• Cysts hold 1000+ organisms and can persist for the life of a host.

Pathogenesis of Toxoplasmosis

• During the primary infection, trophozoites proliferate, cause cell death, and initiate an immune response in the host, resulting in mild symptoms.
• Tissue death can be continuous in immunocompromised patients with a delayed or reduced immune response.
• Serious disease can lead to the inhibition of cell mediated immunity, leading to host defenses becoming overactive.
• Treatment includes pyrimethamine and sulfonamides.

Trypanosomiasis (Trypanosoma Species)

• Trypanosmomiasis is caused by the flagellated protozoan Trypanosoma
• Trypanosomiasis is transmitted to humans via Insect vectors
• African and American forms
• The african form, sleeping sickness, is spread by the tsetse fly, and is caused by Trypanosoma brucei, new cases are now < 1000/year (due to control efforts), but is not eradicated because humans are the reservoir
• The american form, chagas disease, is spread by kissing bugs, caused by Trypanosoma cruzi, and most cases are in Latin America

Life Cycle of Trypanosoma

• All species reproduce by binary fission.
• The cycle includes both insects and humans.
• They multiply extracellularly in mammalian hosts.
• All species have the ability to change their antigens, expressing dozens to hundreds of variations, which makes it difficult for the host’s immune system to respond effectively.

Pathogenesis of Trypanosomiasis

• Trypomastigotes are deposited by the bite of the vector, which reproduce and cause localized inflammation.
• A chancre develops, allowing the organism to spread into the blood and lymph nodes, which causes swollen lymph nodes and recurrent parasitemia.
• The host responds by producing antibodies to destroy the parasite, but they reappear with different antigenic markers.
• Reappearances become less frequent, but the condition may persist for years.

Pathogenesis of Trypanosomiasis

• During parasitemia, trypomastigotes localize in small blood vessels of the heart and the central nervous system.
• Encephalopathy, peripheral neuropathy, convulsions, and gastrointestinal issues can be caused in the brain.
• Patients can experience fever, tenderness in the lymph nodes, skin rash, headache, and impaired mental status during recount bouts of parasitemia.
• Fever can last for years, gradually causing problems with the CNS, diminishing alertness, wavering attention, tremors, speech problems, loss of sphincter control, coma, and death.

###Treatment of Trypanosomiasis.

• Agents that cross the blood–brain barrier are needed if the CNS is involved.
• Melarsoprol (arsenic compound) may be used if the CNS is involved, but is very toxic and may lead to Encephalopathy, peripheral neuropathy, convulsions, gastrointestinal issues, hypertension, kidney damage and liver damage.
• There is no CNS involvment present Pentamidine or eflornithine are options and have less severe side effects.

Helminthic Infections: Nematodes

• Nematodes are all roundworms
• The two subgroups are defined by
  • Intestinal nematodes live within the intestines of their hosts (humans and animals), having a fusiform body with a tough cuticle, and come in male and female forms which produce thousands of offspring
  • Tissue nematodes live within tissues, blood, and lymph systems of their hosts (definitive host), and can live for years in subcutaneous tissues and lymph vessels

Intestinal Nematodes

• Intestinal nematode infection can produce malnutrition, discomfort, anemia and occasionally death.
• Severity of disease is directly correlated to worm load, where a small worm load is generally asymptomatic, while having a large worm load is symptomatic.
• Host immune defenses are slow to develop

Enterobiasis (Enterobius Vermicularis)

• Pinworm (Enterobius vermicularis) is a ubiquitous parasite of humans
• More than 200 million people are infected each year, mostly children
• Enterobiasis is mostly found in temperate climates of Europe and North America.
• The disease is readily transmitted where large numbers of children gather such as in nurseries, child care facilities, and orphanages

Pathogenesis of Enterobiasis

• Eggs can be ingested directly (fingers to mouth) or indirectly (swallowed or inhaled)
  • Eggs hatch in the upper intestine and the larvae travels to the large intestine
  • Females migrate down the colon and through the anal canal, where they deposit about 20,000 sticky eggs to the perianl skin, or the eggs can fall off onto bedsheets or clothes
  • Eggs become mature once they are exposed to oxygen, and the infection cycle takes about 2 weeks
• The main symptom is an itching in the anal region, where - Scratching can lead to bacterial infection
  • Eggs can be skaen into the air and inhaled and swallows always

Treatment of Enterobiasis

• Effective treatments include mebendazole and pyrantel pamoate
• Recurrence is common, especially when Sanitation is not crucial

Ascariasis (Ascaris Lumbricoides)

• Ascaris lumbricoides is the largest intestinal nematode (up to 40cm)
• Female parasites can lay 250,000–500,000 eggs per day
• The eggs are very resistant to environmental pressure, remaining viable for 6+ years
• Transmission of eggs occurs where eggs are Picked up from the soil, come from contaminated foods or inhaled or swallowed
• Infection is often maintained by small children picking up mature eggs from soil while playing

Life Cycle of Ascaris

• Adult worms live in small intestines
  • Eggs are passed via feces.
  • Eggs require approx 3 weeks in the soil before the eggs can become infectious.
• Once ingested, eggs produce a larval stage
  • Larvae penetrate intestinal mucosa and invade the liver
  • Exit liver through the hepatic vein and then enter the heart and progress to the lung
  • Larvae rupture into the alveolar spaces to get Coughed up, swallowed, and arrive in the intestine

Pathogenesis Of Ascariasis

• Infections can be asymptomatic when the worm load is small
• If the worm load is large, symptoms can include fever, coughing, wheezing, and shortness of breath.
• Patients may experience malnutrition, abdominal pain, and obstruction of the bile and pancreatic ducts when suffering from prolonged infection with heavy worm loads.
• Worms can pass out of the body through Vomiting , in stool, and they can move out of anus, nose, mouth, and ears.
• Treatment can be achieved with Albendazole or Mebendazole.

Cestodes

• Most patients know them as tapeworms
• Largest of the intestinal parasites
• Lack a vascular and respiratory system
• Lack a gut or body cavity
• Nutrients are absorbed across the cuticle
• The adult body has three sections:
  • Head—the scolex which may have a rostellum
  • Regenerative neck
  • Segmented body

Cestodes

• Sexual reproduction occurs as the segments move further from the neck
• Distal proglottids eventually rupture and release eggs.
• All except one form of cestode require at least one intermediate host.

Pathogenesis of Cestode Infection

• severity of infection depends on whether the patient is the definitive or intermediate host
  • definitive host infections stay in the lumen of the gut, cause only minor symptoms
  • Larval stages of intermediate host worm infections cause tissue invasion associated with serious disease

Pathogenesis of Cestode Infection

• Most common cestode if Taenia (beef tapeworm)
• Can live in human jejunum for 25 years
• Mature taenia can have 6-9 terminal groglottids, each containing 100,000 eggs
• Proglottids can break free and exit through the anal canal of the host
• Once they reach the soil, the eggs are released and Can survive for months
• Can ingest by cattle where the larvae can penetrates the intestinal wall and get carried by the blood, and the eggs are transformed into a cysticercus

Pathogenesis of Cestode Infection

• Humans are infected when they eat improperly prepared meat.
• Most patients are asymptomatic
• May see visable proglottids in stool or on clothes
• If symptoms occur: gastric discomfort, nauseam diarrhea, and weight loss (DO NOT USE IT FOR WEIGHT LOSS)
• Treatment
  • Praziquantel and niclosamide. -- Peristalsis then pushes the worm out of the digestive system

Trematodes (Flukes)

• Consist of Main features
• Have a bilateral symmetry.
• have two deep suckers, one in the oral cavity and one on the ventral side of the worm
• Trematodes can live for decades in human tissue and blood vessels , and produce progressive damage to vital organs
• There are two major categories of trematodes: Hermaphrodites & Schistosomes

Life Cycle Of Trematodes

• Eggs are excreted from the human host, must reach water in order to hatch, and hatching eggs release larvae called miracidia.
• Miracidia then penetrate snails (intermediate host), and develop into cercarie who are released from the snail
• In hermaphrodite species:
  • Cercariae encyst in or on animals or plants, which then Develop into metacercariae which can then be eaten by humans
• In schistosome species:
• Cercariae can invade skin of humans.

Flukes

• Lung flukes: Paragonimus species
• Liver flukes: Clonorchis species
• Blood flukes: Schistosoma species

Pathogenesis Of Paragonimiasis

• Infections are frequently caused by consuming infected undercooked shellfish.

• -Infections cause eosinophilia and inflammation, where After infection, a capsule forms around the fluke.

• Patient may have as many as 25 capsules, and those Capsules eventually swell and erode into the bronchioles of the lungs, Causing expectoration of brownish eggs, blood, and inflammatory exudate.

• Capsules form cystic rings and become calcified, and Can resemble tuberculosis lesions on an X-ray

Pathogenesis Of Paragonimiasis

• Adult flukes in the intestine cause: Pain, and Bloody diarrhea Adult flukes in the CNS cause: Epilepsy, and Paralysis
• Treatment is with: Praziquantel, and Triclabendazole

###Life Cycle of Clonorchis

• Utilizes 3 hosts
• Infection caused by eating freshwater fish contained Clonorchiasis -- Larvae released into the duodenum and ascend to the common bile duct Adult liver flukes can live up to 50 years in the human host and also infect cats, dogs, rats, and pigs. liver larvae mature (approx 30 days -eggs then passed in the feces and ingested by freshwater snails -snails develop into cercariae who develop further in freshwater fish who can infect fish.

####Pathogenesis of Clonorchiasis

• Migration of larvae from duodenum can cause fever and chills, mild jaundice, eosinophilia, and englarfed liver.
• Symptoms of adult worms may include Epithelial hyperplasia, inflammation, and fibrosis around the bile ducts,however Low worm loads may be asymptomatic .
• Repeated infections can produce worm loads of up to1000, Leading to bile stones and bile duct carcinoma, or to Worms can migrate to the pancrease and cause obstruction, and acute pancreatitis.
• -Treatment is with: Praziquantel, and Albendazole

###Pathogenesis Of Schistosomiasis

• Male and female forms Copulate and stay conjoined for life
• Schistosoma first mate in the portal vein of the host and and Use their suckers to ascend the mesenteric vessels untilthey reach the ascending colon. They then Lay eggs in the submucosal venules in masses of(300-3000 eggs) every day for the remainder of their life which can last for35) years.

###Pathogenesis of Schistosomiasis

• Eggs rupture into the lumen of the colon or in the bladder
  • eggs Eventually excreted to the outside, but Will hatch into miracidia form once reach water if they leave the host
• -Miracidia invade snails where inside they transform into cercariae and Cercarieae can penetrate human skin, Stay in the skin for 1-3 days, then enter the small blood vessels, and Ultimately move into systemic circulation where they reach -Intestinal capillaries to the portal vein which iswhere the mature

###Pathogenesis Of Schistosomiasis

• Schistosomiasis infections are widespread worldwide
• Most individuals with low worm loads are asymptomatic
• Heavy worm loads can serious disease leading to , Bladder infection. abdominal pain , Epilepsy and paralysis if found in the CNS and potentially Death

-Symptoms may be relieved and disease treated when administering Praziquantel

###Fungal Infection

• Fungi are eukaryotes and Have nucleus-bound and membrane-bound organelles
• Fungi associated with the body are mostly commensal organisms, and play important roles in the environment and food creation
• From a clinical perspective, fungi are opportunistic pathogens where Fungal infections are either subactue or chronic with being acute is uncommon

###Fungal Structure And Growth

• The plasma membrane contains sterol ergosterol which makes the plasma membrane stronger.
• Fungal cells are surrounded by a cell wall with components different than bacteria, and contains mannan,glucan , and chitin.

###Fungal Structure And Growth

• Fungi are heterotrophic and can not create their own food, needing to Obtain nutrients nutrients from decaying organic matter
• Most are obligate aerobes but some are facultative anaerobes, yet No fungi are obligate anaerobes
• Fungi reproduce either sexually or asexually, where Asexual reproduction proceeds through conidia in a process that Involves mitotic division and budding, but Sexual reproduction involves spores

###Yeasts And Hyphae

• Fungi can manifest in two forms such as being Hyphae who aremulticellular _Tube-like extensions of cytoplasm Some have septae—cross walls and Wide variety of shapes andsizes—used to identify fungi. In some , Then form aerial hyphae and containing reproductive structures like Connidia & Spores -Also be Yeast: unicellular, so presenting simplest form of growth iswhich is Budding, making Buds are called blastoconidia

###Dimorphism

• Some fungi can grow both in hyphae or yeast form(called Dimorphism) _where Yeast form is a function of In vivo temperature (35-37C), and also to facilitate Enriched nutrient source
• But Hyphae form in Ambient temperature (20-25C in location appropriate ranges), then needs to limit the Minimal nutrients source

###Fungal infections (Mycoses) -classified

• Superficial mycoses
• Subcutaneous mycoses
• Mucocutaneous mycoses
• Deep mycoses

###Superficial Mycoses _Fungal infections can occur in the nonliving outer skin, hair, and nails with

• Piedra: colonization of the hair shaft , and can then cause the the development of black or white nodules. -Tinea nigra is described by a brown or black superficial and is a skin lesions Tinea capitis creates a folliculitis on the scalpand eyebrows Farvus causes destruction to the hair follicle -Pityriasis a dermatitis which can have a distinct dermatitis is characterized, by redness of the skin and itching, it is then Caused by a hypersensitivity in to reactions with fungi whom normally are found and exist on skin, but also Mostly is seen in immunocompromised patients.

###Cutaneous and Mucocutaneous Mycoses

• Fungal infections are seen on:Skin, in Eyes,in their Sinuses, Orpharaynx, External ears, and inside the Vagina
• Hyperkeratosis is characterized by extended scaly areas on the hands and feet
• Onychomycosis an infection is a chronic infection that manifests on the nail bed which is Commonly seen in toes.

###Cutaneous And Mucocutaneous

• Mycoses like Ringworm create distinct skin lesions that is and characterized by red margins, scales, and itching to form a Classified based on location of infection as : _Tinea pedis: presenting on the feet or between the toes
• Tinea corporis: presentation between the fingers,in wrinkles on the palms
• Tinea cruris: formation oflesions on the hairy skin and around the genitalia

###Cutaneous And Mucocutaneous Mycoses Mucocutaneous candidiasis:

• A Candida albicans colonization of the mucous membranes is Often associated with to a loss of immunocompetence Two clinical types of the above can be shown a: Thursh which are and fungal growth in the oral cavity that, which presents as a distinct Indicator of having immunodeficiency, but can also manfest as Vulvovaginitis which create fungal growth in the vaginal canal, associated to a hormonal imbalance

###Cutaneous And Mucocutaneous -Mycoses Keratitis is a colonization or infiltration of the corneal epithelium and occurs to often patients who just underwent surgery

• Other causes: from corticosteroid use & from using contact lenses.
• These affected eyes can become ulcerated or scarred

###Subcutaneous Mycoses

• They are Localized primary infections into the subcutaneous tissue:.
  • In these situations Can the to the development of cysts and granulomas , or Provoke an innate immune response—eosinophilia

-Several Types include: __Sporotrichosis—traumatic implantation of fungal particles ___Paranasal conidiobolomycosis —Infection of the paranasal sinuses which Causes the formation of granulomas ____Zygomatic rhinitis—An infestation when fungus invades tissue through arteries Causes thrombosis an infection andcan involve to invade the CNS

###Deep Mycoses -These are Usually seen in highly immunosuppressed patients suffering many disease such a AIDS, from Cancer,. or with Diabetes users, or in or Intra venous drug.

• • The infection Can be acquired by a distinct act of: Infection of fungi or fungal spores, and also from the Use of contaminated medical equipment. This is important due to being about to Cause a systemic infection where being able to(or are) spread disseminated mycoses from . - and if able to do so they Can spread to a the skin & are Very hard to treat and often impossible.

###Deep Mycoses Coccidiomycosis: caused by species of the genus Coccidioides, its Primary effect is a respiratory infection. *

• Other symptoms or causes Can lead to fever, also erythema, and bronchial pneumonia But Can then Usually resolves spontaneously due to an immune defense, or unfortunately Some may be fatal
• Then also Histoplasmosis: a disease caused by Histoplasma capsulatum to:
  • Often associated with immunodeficiency, or ++ Cause the formation of granulomas if they Can necrotize and can become calcified, or if ++ +If disseminate, or if histoplasmosis is fatal

Deep Mycoses

• Aspergillosis: infection caused by several species of Aspergillus. -- This is an Infection which presents itself with immunodeficiency -- These infections Can be highly invasive and in severe situations may disseminate to the blood and lungs leading to acute pneumonia +The disease if contracted has ah Mortality is very high, and - Death can occur in a matter of weeks when this infection arises.

###Pathogenesis Of Fungal Infections Thousands of fungal spores are inhaled or ingested from everyday actions, where Most fungi are then adapted to be part of our normal skin or bodily flora Clinical for an infection to properly occur and spread, usually fungal infections are very uncommon in immun ocompetent individuals, where More common however in infections in Immunode ficient patients

For any Fungal infections the ability to be acquired will take through inhalation or ingestion of infectious conidia

• But only A limited small number will even infect*

###Pathogenesis Of Fungal Infections

• Pathogenesis of any proper fungal infection is divided into three stages: A:Adherence where; _ Several fungal species, especially yeasts, can adhere to mucosal surfaces _ Usually will requires a surface adhesion molecule on the fungi , but will also need to locate a receptor on the -Target organ of that cell to perform B:Invasion is when : Some certain fungi are introduced through breaches to the skin ++The small size of any spores Can evade the host's defenses within to the lungs. ++ +When some Dimorphic fungi Can become highly invasive when or, They actively are involved with the process to which ,Switch from the host's yeast form to the hyphae form or use it,
• to make The hyphae then invade tissues and is what may disseminates that damage or effect further then before C:Tissue injury -- In the host, the most critical element is that fungi will do and is that - they do not produce extracellular virulence factors to cause more ,but are more such highly deadly toxins
• Primary tissue to injury is usually then due and caused from of that high host inflammatory response and how that impacts bodily functions