Writer: Chengzu Maxwell Xiang

Mother Nature has been trying to kill us for thousands and thousands of years, with everything big and spectacular and small and insidious alike, the loud and terrifying and the invisible and silent. We all know of the big predators and the invisible pathogens, but what about the things in-between? The slightly bigger, but no less deadly. I’m talking about parasites.

Parasites are organisms that survive within other organisms, leeching food off of the host or surviving at its expense. Parasites are divided into three disease causing classes: protozoa, helminths, and ectoparasites. Each of these classes has their own further subcategories which we will get into later. Protozoa are microscopic, single-celled organisms that can be free-living or parasitic. Parasitic protozoa multiply inside humans, allowing serious infections to develop from a single organism. Transmission of protozoa from human to human typically occurs through contaminated food or water, and arthropod vectors, such as mosquitos, contribute to the transmission of blood-borne protozoans.

Most parasitic protozoa in humans are less than 50 µm in size, with the smallest ranging from 1 to 10 µm in size, and all the way up to 150 µm for the largest known protozoa. Protozoa are unicellular eukaryotes, meaning that their nucleus is enclosed within a membrane. In protozoa other than ciliates, the nucleus is vesicular, with scattered chromatin giving diffuse appearance to the nucleus. In phylum Apicomplexa, the vesicular nucleus has one or more nucleoli that contain DNA. Ciliates have both a micronucleus and a macronucleus, which appear quite homogeneous in composition.

Protozoa organelles have similar functions to the organs of higher animals. The plasma membrane enclosing the cytoplasm also covers the projecting locomotory structures such as pseudopodia, cilia, and flagella. The outer layers of some protozoa, the pellicle, is both sufficiently rigid to maintain a distinctive shape, while remaining flexible enough to allow the organisms to readily twist and bend when moving through their environment. In most protozoa, the cytoplasm is differentiated into ectoplasm and endoplasm; the structure of the cytoplasm is most easily seen in species with projecting pseudopodia, such as the amoebas. Some protozoa have a cytostome or cell “mouth” for ingesting fluids or solid particles. Contractile vacuoles for osmoregulation occur in some species, such as Naegleria and Balantidium. Many protozoa have subpellicular microtubules; in the Apicomplexa, which have no external organelles for locomotion, these provide a means for slow movement.

Protozoans are classified into four categories based on their mode of transport. Sarcodina posses streaming cytoplasm and use temporary extensions called pseudopodia in locomotion and feeding. Sarcodinas are typically spherical or irregular in shape, and posses a thin and flexible pellicle. Sarcodinas also may have an external shell (foraminiferan), or a skeleton (radiolarian). They may also be multi-nucleated. Food adheres to the surface of the cell or trapped by pseudopodia, are digested internally within food vacuoles. Sarcodinas reproduce both sexually and asexually through the fusion of gametes and division or budding. Some Sarcodinas have flagella during certain stages of development; in other groups, flagellated and unflagellated generations alternate. Sarcodinas may be solitary or colonial, and despite some pathogenic species, most Sarcodinas are free-living, and feed on debris and other micro-organisms.

Mastigophora are protozoa characterized by their use of a flagella for movement. Many of them posses an outer pellicle or a jellylike coating for protection. Reproduction occurs asexually, typically through longitudinal splitting, or sexually, through the fusion of gametes. Mastigophra are divided into two classes, those that resemble plants, Phytomastigophorea, and those that resemble animals, Zoomastigophorea. Phytomastigophorea are chlorophyll-containing protists that can produce their own food photosynthetically, same as plants, leading to a difficult distinction between Phytomastigophorea and algae. Zoomastigophorea are colorless, animal-like protozoans. Mastigophora can be solitary, colonial, free-living, or parasitic. Parasitic forms often live in the intestines or bloodstream of the host.

Ciliophorans, also known as ciliates, are the most complex and evolved protozoans. Ciliates are identified by their use of cilia in movement and food gathering. The cilia are usually arranged in rows, called kineties, on the pellicle. Cilia also may fuse together near the cytostome, forming undulating membranes. Elsewhere on the pellicle, cilia may form limb-like tufts called cirri. Ciliates also have contractile vacuoles, and may contain toxicysts or other trichocysts, small organelles with thread or thorn-like structures that can be discharged for anchorage, defense, and hunting. Ciliates also have one or more macronuclei and micronuclei, controlling metabolic and developmental functions, as well as reproduction. Ciliate reproduction is typically asexual, although sexual reproduction does occur as well. Asexual replication takes place through transverse binary fission or budding, while sexual reproduction happens through conjugation or autogamy. Sexual reproduction in ciliates does not lead to an immediate increase in numbers; however, conjugation is typically followed by budding.

Sporozoa, also known as Apicomplexan, is the only solely parasitic phylum of protozoan, lacking contractile vacuoles or any traditional locomotive structure in its adult form, instead using a unique form of “gliding motility” to traverse substrates and invade host cells. Apicomplexans live within the body cavities or cells of almost every kind of animal, including other Apicomplexans. Apicomplexans feed by absorbing dissolved food ingested by the host cell, or by directly absorbing the host’s cytoplasm and body fluids. Respiration and waste disposal occurs through diffusion through the cell membrane. Sexual and asexual reproduction alternate throughout the life cycle. Sexual reproduction takes place through a three-step process, sporogony, merogony, and gamogony. This process also includes four different basic cell types, sporozoite, merozoite, gamete (haploid), and zygote (diploid).

Reproduction begins with the release of sporozoites from the oocyst or sporocyst; the infection of a host cell, then transforms into a trophozoite and initiates merogony, resulting in the development of merozoites. Merozoites posses a similar biological and microscopic structure to sporozoites, and they go on to infect more cells, using asexual reproduction to produce new generations. This process of repeated invasion and replication of merozoites precedes the final stage, gamogony. In gamogony, some merozoites become female macrogametocytes (macrogamonts), while the majority transform into male microgametocytes (microgamonts). The life cycle now proceeds to the fusion of a motile flagellated microgamete with a large and immobile macrogamete, with fertilization leading to the formation of a diploid zygote. The zygote then finally develops into the sporozoite. This process is termed sporogony, and is characterized by variable amounts of cell division between taxa, along with several rounds of meiosis and mitosis, resulting in the formation of infectious haploid sporozoites. Upon the transmission of sporozoites to the next host, the life cycle is completed.

Protozoan parasites are transmitted to humans through a wide range of methods, including; contaminated water or food, undercooked meats, insect bites from infected insects, contaminated surfaces, unprotected sex, and contaminated dirt. Protozoal infections result in tissue damage that lead to serious illness. Tissue damage is often due to an immune response to the parasite, as well as changes in cytokine profiles. Alternatively, tissue damage may be caused through toxic protozoal products and mechanical damage.

Many protozoan infections that are inapparent or mild in normal individuals can be life-threatening in immunosuppressed patients, particularly patients with AIDS. Evidence suggests that many healthy people harbor low amounts of Pneumocystis carinii in their lungs. However, this parasite produces an often fatal pneumonia in immunosuppressed patients. Another example would be Toxoplasma gondii, a very common protozoan parasite which usually causes a rather mild initial illness which is then followed by a long-lasting latent infection. AIDS patients, however, can develop fatal toxoplasmic encephalitis. As more thorough studies of AIDS patients are conducted, it is likely that other rare or unusual protozoan infections will be diagnosed. Some examples would be Cryptosporidium, while non-threatening to healthy people, can produce serious complications in patients with AIDS.

Parasites also utilize a wide variety of escape mechanisms to avoid elimination from the immune system in an immunocompetent host. Some escape mechanisms include antigenic masking, the ability of a protozoa to evade detection by covering itself with host antigens, blocking serum factors, an antigen-antibody coating made up of complexes or noncytotoxic antibodies that sterically blocks the binding of specific antibodies or lymphocytes to the parasite’s surface antigens, antigenic variation, changing their surface antigen during the course of an infection, allowing protozoans carrying the new antigens to escape the immune response to the original, and immunosuppression, delaying detection of antigenic variants and reducing the ability of the immune system to inhibit growth of new parasites.

Resistance to parasitic protozoa appears to resemble resistance against other infectious agents, although the mechanisms of resistance in protozoan infections are not yet as well understood. Resistance can be divided into two main groups of mechanisms. Nonspecific mechanisms or factors, such as the presence of a nonspecific serum component that is lethal to the parasite, and specific mechanisms involving the immune system.

The most studied nonspecific mechanisms involved in parasite resistance are the ones that control the susceptibility of red blood cells to invasion or growth of plasmodia, the protozoa that cause malaria. Individuals that are heterozygous or homozygous for the sickle cell hemoglobin trait are considerably more resistant to Plasmodium falciparum than individuals with normal hemoglobin. Similarly, individuals who lack the Duffy factor on their red blood cells are not susceptible to Plasmodium vivax. There is a possibility that both the sickle cell trait and absence of the Duffy factor have become established in malaria-endemic populations as a result of selective pressure exerted by malaria. A second well-documented example of a nonspecific factor involved in resistance is the presence of a trypanolytic factor in human serum which confers resistance against Trypanosoma brucei brucei, the parasite that causes trypanosomiasis (sleeping sickness) in animals.

There is evidence that other nonspecific factors, such as fever and the sex of the host, may also contribute to the host’s resistance to various protozoan parasites. Although nonspecific factors can play a key role in resistance, they usually work in conjunction with the host’s immune system.

For example, cellular immunity is believed to be the single most important defense mechanism in leishmaniasis and toxoplasmosis. In animals infected with Toxoplasma, the activated macrophage has been shown to play an important role in resistance. Accordingly, resistance to protozoan parasites most likely involves nonspecific factors as well as specific humoral and/or cellular mechanisms. In malaria and trypanosome infections, antibodies appear to play a major role in immunity, however, recent evidence suggests that the survival time of infected mice does not necessarily correlate with the ability of the animal to produce the trypanosome-specific antibody. In other words, resistance measured by survival time may not be determined entirely by a single system, with recent data suggesting that successful immunization against malaria with an active sporozoite antigen requires both an active cellular response and a sporozoite specific antibody.

The treatment of protozoan diseases depends heavily on the severity of the infection, with varying doses and treatments required. The common protozoan infections include; malaria, amebiasis, toxoplasmosis, and trichomoniasis. The pharmacological treatment of malaria can include chemoprophylaxis, or antimalarial medications, taken before a person travels to a geographic area at high risk for malaria. Chemoprophylaxis drugs are taken one week before travel to an endemic area, during the stay, and continually taken for one to four weeks after return from travel. The primary medication prescribed for chemoprophylaxis is chloroquine (Aralen), and if the patient is unable to take this drug, combinations of drugs such as atovaquone-proguanil (Malarone); mefloquine (Lariam), which is used by pregnant women; doxycycline and primaquine may also be prescribed. The newest malaria treatment recommended by the CDC is artemether-lumefantrine (Coartem), which has become popular due to its fast onset of action. However, Coartem is only approved for the treatment and not for the prevention of malaria.

Amebiasis is a protozoan disease that usually occurs in the human digestive system. However, amebiasis can spread through colon ulcers to other parts of the body, including the liver. Treatment for amebiasis includes combination therapies of two or more drugs to ensure effective treatment. Metronidazole is the drug of choice, taken with an opioid to control diarrhea. Other antibiotics such as chloroquine and tetracycline may also be given. Paromycin and iodoquinol can be used when the infection is limited to the intestine. Therapy is continued until consecutive stools test negative for the protozoa.

Toxoplasmosis is transmitted by cat feces, and poses a significant threat to developing babies in the first two trimesters of pregnancy. Treatment includes four to five weeks of pyrimethamine, given in combination with sulfadiazine. These drugs must be used cautiously around people with megaloblastic anemia because these drugs are folic-acid inhibitors. 

Trichomoniasis, or trich, is a sexually transmitted protozoan disease caused by T. vaginalis. As many as 50% of infected people are asymptomatic. A single dose of metronidazole (Flagyl) is an effective treatment. If the patient experiences any gastrointestinal upset, a lower dose can be used for seven days. The same treatment should also be given to any sexual partners of the infected person.

Bibliography:

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CDC. 2024. “CDC – Parasites – about Our Division.” Www.cdc.gov. November 14, 2024. https://www.cdc.gov/parasites/about/index.html.

Cleveland Clinic. 2023. “Parasitic Infection: Causes, Symptoms & Treatment.” Cleveland Clinic. 2023. https://my.clevelandclinic.org/health/diseases/24885-parasitic-infection.

John Richard Seed. 2014. “Protozoa: Pathogenesis and Defenses.” Nih.gov. University of Texas Medical Branch at Galveston. 2014. https://www.ncbi.nlm.nih.gov/books/NBK8043/.

“Sarcodine | Definition, Characteristics, & Facts.” n.d. Encyclopedia Britannica. https://www.britannica.com/science/sarcodine.

Sibley, L David. 2010. “How Apicomplexan Parasites Move in and out of Cells.” Current Opinion in Biotechnology 21 (5): 592–98. https://doi.org/10.1016/j.copbio.2010.05.009.The Editors of Encyclopaedia Britannica. 2019a. “Ciliate | Protozoan.” In Encyclopædia