HC15: Fungi and parasites

Definition

Parasites and fungi are eukaryotes. They are a mixture of single-cell and multi-cellular species and are more complex than viruses and bacteria.

Fungi:

A fungus is a eukaryotic organism that normally lives in the environment. It is an opportunistic pathogen. It has a more plant-like structure than a parasite.

Fungi are very common in the community. They are an important cause of disease and mortality in patients with an impaired immune system.

Parasites:

A parasite is a eukaryotic organism that lives in or on, and takes its nourishment from, another organism (for example a human host). It cannot complete its life cycle independently. It has a more animal-like structure than a fungus.

Parasites are globally still an important cause of disease and mortality. Travel-related infections are often parasitic → some parasites have a geographically limited occurrence. Parasitic infections are often related to socio-economic circumstances → there are many opportunities for prevention and control.

There are 2 types of parasites:

• Protozoa
• Helminths

Fungi

Structure:

A fungal (yeast) cell is a eukaryotic cell, which consists of:

• Cell membrane
• Nucleus
• Cytoplasm
• Cell organelles
• Special components
  • In the rigid cell wall: mannan, flucan and chitin
    • Both bacteria and fungi can have a cell wall
  • In the cell membrane: ergosterol
    • An important target for anti-fungal drugs

Reproduction:

Fungi have different ways of reproducing:

• Yeast: budding → one cell separates from the other
• Molds
  • Sexual: in the form of spores
  • Conidia: asexual

Pathogenesis:

The cellular immune system is very important to combat fungi:

• Yeasts
  • Granulocytes and macrophages
  • T-cells
  • Normal commensal bacterial population
• Molds
  • Granulocytes and macrophages
  • T-cell immunity

Species:

There are many important types of fungi, of which 2 are relevant for this course:

• Candida albicans → stomatitis, vaginitis
• Aspergillus fumigatus → pneumonia in patients with granulocytes

Parasites

Parasites have a very complex structure. Their life cycle depends on hosts:

• Parasites that depend on 1 host
  • The parasite can either stay in the host for the whole cycle or exit and enter the host repeatedly
• Parasites that alternate between 2 different host species
  • Malaria alternates between human hosts and mosquito hosts
• Parasites that alternate between many hosts

Parasites can be divided into 2 groups:

• Ecto-parasite: scabies mite (headlice)
• Endo-parasite
  • Protozoa: entamoeba histolytica
    • 1 cell
    • Lives in the intestines
    • Multiplies within the host
  • Helminths: strongyloides stercoralis
    • Multicellular
    • Only transmitted in the tropics
    • Stable population
      • Strongyloids form an exception
    • Inoculation dose determines the outcome

Diagnosis:

The diagnosis of a parasitic infection can be made directly or indirectly:

• Direct: stage of the parasite
  • Feces
  • Blood
  • Urine
  • Other
• Indirect: via serology
  • Entamoeba
  • Toxoplasma
  • Strongyloides
  • Schistosoma

Protozoa

Structure:

A protozoa is a eukaryotic cell containing the following structures:

• Cell membrane
• Nucleus
• Cytoplasm
• Cell organelles

Relevant protozoa are:

• Entamoeba histolytica and entamoeba dispar → amoebiasis
• Toxoplasma gondii → toxoplasmosis
• Plasmodium vivax and plasmodium falciparum → malaria
• Giardia lamblia → intestinal infection

Classification:

Protozoa can be classified systemically or enterically:

• Enteric
  • Non-invasive: giardia lamblia
    • Sticks to the intestinal wall
    • Causes diarrhea
  • Invasive: entamoeba histolytica
    • Can migrate from the intestines to different organs
    • Effects the liver
• Systemic
  • Plasmodium species
  • Toxoplasma gondii

Giardia:

Giardia is a very common disease which causes diarrhea. It is an intestinal protozoa. People can get infected by giardia because they have an oral exposure to a state of the parasite, usually called a cyst. A cyst is a very rigid state of a parasite:

• External cyst wall
• No multiplication
• Decreased metabolism
• Resistance to the environment
• Transmission

Cysts are responsible for transmission from one person to another, but not for the disease. When someone has swallowed the cysts, some of the parasites change into a different form → trophozoites.  A trophozoite is very lively:

• Lipid bilayer
• Metabolically active
• Motile: migrates to the liver and other organs
• Asexual reproduction
• Disintegrates easily: not resistant to the environment → disappears after 30 minutes
• The trophozoite sticks to the intestinal wall and causes malabsorption.

Plasmodium:

Malaria is a systemic protozoa. It is an infection made by the plasmodium parasite. Malaria is a tropical disease → it is transmitted via mosquitoes, mainly occurring in Africa, South America and southeast Asia. Malaria deaths are greatly underestimated:

• 438.000 deaths in 2015
• Mainly children under the age of 5
• 90% in Sub-Saharan Africa

A plasmodium parasite constantly has a life cycle between 2 hosts:

• Definitive host: anopheles mosquito
  • Sexual reproduction takes place
• Intermediate hosts: human

The parasite has to develop itself into a new stage within the mosquito. This takes about 10 days → if the life cycle of a mosquito is shortened, malaria can be prevented.

Toxoplasma gondii:

A toxoplasma gondii is a common parasite in the Netherlands. The parasite can be acquired in 4 different ways. The parasite constantly switches between a definitive host and different intermediary hosts:

• Definitive host: the cat
• Intermediate hosts: humans and other animals

The infection stays in the human host for the rest of its life. If the patient is healthy, the parasite hardly causes any symptoms. However, if the patient is immunosuppressed the parasite can cause a life-threatening situation.

Pathogenesis:

The mechanisms of protozoan pathogenesis are different for different protozoa:

• Entry → via vectors or oral
• Adhesion
• Invasion → host cell tropism
• Injury
  • Direct: entamoeba histolytica
  • Indirect: through host response
• Persistence: toxoplasma gondii

Most protozoa are primary pathogens → no host defense disorder is needed. In case of toxoplasmosis, there is an asymptomatic infection or mild disease in a healthy host. In case of an impaired T-cell immunity, there is a risk of a more severe course or reactivation.

Helminths

Classification:

Helminths are known as "worms". Biologically, they can be divided into 3 different groups:

• Roundworms/nematodes
  • Strongyloides stercoralis
• Tapeworms/cestodes
  • Taenia saginata
• Flukes/trematodes
  • Schistosoma mansoni

Structure and life cycle:

Helminths have several distinguishing characteristics:

• Start as an egg or larvae
• Adult worms have multiple organs → very animal like
• Some species have separate sexes → 2 different sexes are needed to reproduce
• Some species are hermaphrodite → 1 hermaphrodite is enough to reproduce
• Reproduction consists of the production of eggs or larvae
• Eggs/larvae need to leave the human host before they can continue the lifecycle
• No multiplication within the host occurs
  • The eggs/worms have to be excreted to multiply

Several relevant helminths are:

• Shistosoma haemotobium and shistosoma mansomi → shistosomiasis (Bilharzia)
• Strongyloides stercoralis → strongyloidiasis
• Taenia saginata and taenia solium → taeniasis and cysticercosis
• Echinococcus granulosus → echinococcosis
• Ascaris lumbricoides → ascariasis
• Trichuris trichiuria → trichuriasis
• Hookworm → anemia

Strongyloides stercoralis:

Strongyloides is a very harmful parasite, even more than malaria. Strongyloides larvae can be found in the stool and can reside in the lungs and other organs. Infection occurs in the tropics when soil comes into contact with bare skin:

1. Strongyloides stercoralis eggs penetrate the skin and migrates into the human host
2. The eggs travel to the intestines
3. The eggs become adult worms in the intestines
4. When the eggs arrive in the intestines, they almost immediately become larvae and larvae become worms
   • After 3 years the worm usually dies off
5. The larvae are excreted and travel to organs
6. In case of immunosuppression hyperinfection occurs
7. Auto-infection can occur → the larvae can re-infect the same individual
   • This usually is low-grade → there hardly are any symptoms

In case of an impaired T-cell immunity, there is an increased risk of a severe course or reactivation of strongyloides.

Pathogenesis:

Most helminths are primary pathogens → no host defense disorder is needed. Symptoms are dependent on the worm load.