Parasitology

TOXOPLASMOSIS (caused by Toxoplasma gondii)

Written by MicroDok

Toxoplasmosis is a protozoan disease which occurs in both humans and animals, and affecting many cell types in its host. It is an asymptomatic infection in adult individuals, but toxoplasmosis can be a wasting disease in children when the parasite is acquired congenitally following infection during pregnancy. It can result in stillbirth and other anomalies in the unborn child. The parasite that causes toxoplasmosis (which usually causes a covert infection in humans) also occurs in birds but rarely produce a disease in them. The protozoan that causes toxoplasmosis can be transmitted to humans via the ingestion of undercooked or contaminated food, meat or water. Hands contaminated with feaces harbouring the parasite can also serve as route via which the protozoan infects humans. It can also be transmitted through blood transfusion, and congenitally from mother to an unborn child. Toxoplasmosis is one of the major causes of death in AIDS patients, thus the disease is opportunistic in HIV infected individuals.

Toxoplasmosis is caused by Toxoplasma gondii in the genus Toxoplasma. T. gondii has a worldwide distribution, and has been reported in almost all countries of the world including the USA except for some selected nations. Though T. gondii is known as an intestinal coccidian in the Apicomplexa phylum, the parasite affects other organs and tissues of its host than it does the intestine; and T. gondii is a very successful parasite in that it affects a wide variety of animals more than other protozoan’s in the same phylum with it.

Type and morphology of Toxoplasma gondii

Toxoplasma gondii is a member of parasites in the subclass Coccidia and phylum Apicomplexa. It is in the same class (Sporozoa) as the Plasmodium parasite that causes malaria infection. Protozoa in the Coccidia subclass are group of parasites which are known to infect pets (e.g. cats), and they are of veterinary importance. Isospora belli and Cryptosporidium parvum are other examples of parasites in the subclass Coccidia and they cause opportunistic parasitic infections in AIDS patients and other immunocompromised individuals. T. gondii can exist in three morphological forms: the tachyzoites (trophozoites) which are the rapidly multiplying cells of the parasite, bradyzoites (cysts) which multiply slowly and are termed the resting stage of the parasite, and the oocysts (which are shed in the host’s feaces). Tachyzoites initiate the acute stage of toxoplasmosis while bradyzoites only cause chronic disease. It is noteworthy that any of these three infective forms of T. gondii can cause infection once ingested. Mature T. gondii oocysts contain eight infective sporozoites. Bradyzoites are the tissue cyst forms of T. gondii, and they remain in the muscle cells (without causing any form of harm) throughout the life span of its animal host and can infect susceptible host from their when meat is not properly cooked.

Vector, reservoir and habitat of Toxoplasma gondii

T. gondii does not have an insect vector. Domestic cats are the only known definitive host of gondii. Toxoplasmosis cannot be transmitted to human hosts through invertebrates. Cats in the family Felidae are the definitive hosts of T. gondii, and they are required for the completion of the sexual stage of the parasite’s life cycle. T. gondii also have a wide range of intermediate hosts including humans, birds, chicken, pigs and many other warm-blooded animals. The oocysts of T. gondii can develop in cats and other related members in the Felidae family. Both asexual and sexual stages of T. gondii occur in cats of the Felidae family. But only asexual stage occurs in humans and other intermediate hosts of the parasite.

Clinical signs and symptoms of toxoplasmosis

Toxoplasmosis is usually an asymptomatic infection in humans. However, myocarditis, pneumonitis and meningoencephalitis are usually some of the signs and symptoms of toxoplasmosis in normal individuals. In congenital toxoplasmosis, an abortion or stillbirth may occur. A mononucleosis-like condition can result after some weeks of T. gondii infection, and the syndrome is usually characterized by lymphocytosis, fever, malaise, lymphadenopathy (abnormality of the lymph nodes), and headache. Inflammation of the retina (retinitis), sore throat, rashes, convulsion and muscle pains can also occur in addition to the previously mentioned syndromes in immunocompromised patients. In some cases of congenital toxoplasmosis, syndromes may be delayed to appear years later after birth, and this can cause a number of nervous anomalies in the child, and this may include difficulty in learning and other mental defects. However, the period of gestation in the mother determines the severity of the infection and the rate of placental transmission of T. gondii. Neurologic damage in toxoplasmosis usually occurs in foetuses that survive the stillbirth associated with the congenital episodes of the disease. Toxoplasmosis is usually self-limiting, thus the condition resolves in normal individuals (but can persists in immunocompromised patients) after some weeks of T. gondii infection.

Pathogenesis of Toxoplasma gondii infection

Human toxoplasmosis is initiated following the ingestion of materials (undercooked meat or raw vegetables) contaminated with feaces of cats (in the Felidae family) containing infective cysts of T. gondii (Figure 1). The feacal-oral-route is usually the most important channel via which the parasite is acquired. Upon ingestion of T. gondii cysts, the infective and resistant cysts undergo asexual reproduction in the host’s intestine to release sporozoites that pass through the gut wall and circulate in the body to invade macrophages and other cells. Inside the macrophages, the sporozoites transforms to tachyzoites that initiate acute toxoplasmosis in the host. Trophozoites also invade mononuclear leucocytes and phagocytes, thus stimulating immunological reactions in the host. T. gondii is known to elicit cell-mediated (T-cells) and antibody (B cells) immune response in its animal and human host. After multiplication of the tachyzoites in the host cells, trophozoites rupture to release many bradyzoites that initiate chronic toxoplasmosis. Bradyzoites are slowly multiplying forms of T. gondii, and they invade the brain cells, muscle and nerve cells and even the eye where they multiply intracellularly. T. gondii majorly produce four forms of clinical disease in infected human host, and this include:

  • Congenital (pre-natal) toxoplasmosis: Pre-natal toxoplasmosis occurs in children when non-immune mothers are infected during pregnancy.
  • Post-natal toxoplasmosis: This type of toxoplasmosis occurs after childbirth, and it is less severe than pre-natal toxoplasmosis. It is acquired via eating food or drinking water contaminated with feaces of cats harbouring the parasite.
  • HIV-associated toxoplasmosis: HIV-associated toxoplasmosis occurs in individuals with dysfunctional immune system. The disease is more severe in such individuals, and it is associated with a plethora of syndromes.
  • Asymptomatic toxoplasmosis: Asymptomatic toxoplasmosis occurs in normal individuals whose immune system is still intact. This form of toxoplasmosis usually resolves on its own following some weeks of gondii infection.

The level of injury caused by T. gondii to some vital organs of its host including the heart, eyes and the nervous system determines the severity and extent of the infection in an individual. Severe toxoplasmosis is usually experienced in HIV-infected patients, congenitally infected children and people with incompetent immune systems.       

Figure 1: Life cycle of Toxoplasma. 1. Unsporulated oocysts of T. gondii are shed in the cat’s feces (oocysts are less dense than water and thus remain in the upper part of the soil where they may contaminate skin and may be ingest via raw vegetables or directly through hand-to-mouth transmission). 2. Although oocysts are usually only shed for 1-2 weeks, large numbers may be shed. Oocysts take 1-5 days to sporulate in the environment and become infective. Intermediate hosts in nature (including humans, birds and rodents) become infected after ingesting soil, water or plant material contaminated with oocysts. 3. Oocysts transform into tachyzoites shortly after ingestion. These tachyzoites localize in neural and muscle tissue and develop into tissue cyst bradyzoites. 4. Cats become infected after consuming intermediate hosts (e.g. rats) harboring tissue cysts of T. gondii. 5. Cats may also become infected directly by ingestion of sporulated oocysts. Animals bred for human consumption and wild game may also become infected with tissue cysts of T. gondii after ingestion of sporulated oocysts in the environment. 6. Humans can become infected through eating undercooked meat of animals harboring tissue cysts of T. gondii. 7. Consuming food or water contaminated with cat feces or by contaminated environmental samples (such as fecal-contaminated soil or changing the litter box of a pet cat) can also transfer the parasite to humans. 8. Blood transfusion or organ transplantation is another route via which humans can contact T. gondii. 9. Transplacental transmission of the parasite   from mother to foetus can also occur. 10. In the human host, the parasites form tissue cysts, most commonly in skeletal muscle, myocardium, brain, and eyes; these cysts may remain throughout the life of the host. Diagnosis is usually achieved by serology, although tissue cysts may be observed in stained biopsy specimens. 11. Diagnosis of congenital infections of T. gondii can be achieved by detecting the parasite’s DNA in amniotic fluid using molecular methods such as polymerase chain reaction (PCR).  CDC

Laboratory diagnosis of T. gondii infection

The identification of the parasite’s tachyzoites from clinical specimens (tissues) establishes T. gondii infection in a human host. However, toxoplasmosis is primarily diagnosed in the laboratory by a number of serological tests including ELISA, IFA and the Sabin-Feldman dye test. Blood, CSF, sputum, lymph node aspirates, bone marrow and tissue biopsies are usually choice specimens in the laboratory diagnosis of toxoplasmosis. T. gondii is a protozoan that affects a wide variety of its host’s cells including the central nervous system (CNS), fibroblasts, myocytes, endothelial cells, macrophages, and hepatocytes unlike other intracellular parasites such as Leishmania species amongst others which are known to infect only a single type of cell in the host. Microscopical investigation is also employed to demonstrate the parasite’s trophozoites in dry smear preparations using staining techniques such as Giemsa staining. Molecular characterization using PCR amplification of T. gondii genes and tissue cultures can also be employed in T. gondii identification, but these are normally employed in research institutions.

Treatment of toxoplasmosis

Toxoplasmosis is treated using a combination of antimetabolite agents including sulphonamide (e.g. sulfadiazine) and pyrimethamine which targets the folic acid (folate) synthesizing pathway of T. gondii that cannot produce its own folic acid. Folic acid is required for the organisms own DNA synthesis. Thus if T. gondii’s folate synthesis pathway is inhibited or obstructed by an antimetabolite, the organism can no longer continue in its DNA synthesis because purines and pyrimidines (which are produced in this pathway) required for this very important process in the parasite’s metabolism will not be produced. Consequently, the parasite will be short-lived in the human host upon proper therapy using these agents. Macrolides (azithromycin, clindamycin, and spiramycin), dapsone, and minocycline are some examples of drugs used for the treatment of toxoplasmosis.

         Control and prevention of toxoplasmosis

Toxoplasmosis is a protozoal disease that has a worldwide distribution. T. gondii that causes the infection is transmitted via three major routes: through feacal route, through consumption of raw or undercooked infected meat or raw vegetables, and transplacentally (from mother to child). Public awareness is necessary to increase advocacy and inform the general public about these routes of transmission and how the infection can be prevented. Hand washing using detergents especially after coming in contact with cats and other source of contamination is very necessary in preventing infection with T. gondii cysts. Body contacts with cats should be minimized as much as possible, and feaces and other litters from them should be disposed properly and floors disinfected as well. Since cats feeds on rodents (which are intermediate hosts of T. gondii), keeping cats indoors (and feeding them with commercially available foods) in order to prevent them from birds and rats harbouring the parasite will help in preventing the spread and transmission of the parasite amongst human population. Cautious practices in husbandry practices and in the handling of meats, vegetables and other materials that may transmit the parasite can help to contain the infection in a given population. Though human vaccine for toxoplasmosis is still distant, vaccines for animals in husbandry practices are available in some parts of Europe and the United Kingdom.

REFERENCES

Taylor LH, Latham SM, Woolhouse ME (2001). Risk factors for disease emergence. Philos Trans R Soc Lond B Biol Sci, 356:983–989.

Stedman’s medical dictionary, 27th edition. Philadelphia: Lippincott, Williams and Wilkins.

Summers W.C (2000). History of microbiology. In Encyclopedia of microbiology, vol. 2, J. Lederberg, editor, 677–97. San Diego: Academic Press.

Schneider M.J (2011). Introduction to Public Health. Third edition. Jones and Bartlett Publishers, Sudbury, Massachusetts, USA.

Roberts L, Janovy J (Jr) and Nadler S (2012). Foundations of Parasitology. Ninth edition. McGraw-Hill Publishers, USA.

Rothman K.J and Greenland S (1998). Modern epidemiology, 2nd edition. Philadelphia: Lippincott-Raven.

Principles and practice of clinical Parasitology. Edited by Stephen H. Gillespie and Richard D. Pearson. John Wiley and Sons Ltd. Chichester, New York.

Nelson K.E and Williams C (2013). Infectious Disease Epidemiology: Theory and Practice. Third edition. Jones and Bartleh Learning

Mandell G.L., Bennett J.E and Dolin R (2000). Principles and practice of infectious diseases, 5th edition. New York: Churchill Livingstone.

Molyneux, D.H., D.R. Hopkins, and N. Zagaria (2004) Disease eradication, elimination and control: the need for accurate and consistent usage. Trends Parasitol, 20(8):347-51.

Lucas A.O and Gilles H.M (2003). Short Textbook of Public Health Medicine for the tropics. Fourth edition. Hodder Arnold Publication, UK.

MacMahon   B.,   Trichopoulos   D (1996). Epidemiology Principles and Methods.   2nd ed. Boston, MA: Little, Brown and Company. USA.

Leventhal R and Cheadle R.F (2013). Medical Parasitology. Fifth edition. F.A. Davis Publishers,

Lee JW (2005). Public health is a social issue. Lancet. 365:1005-6.

John D and Petri W.A Jr (2013). Markell and Voge’s Medical Parasitology. Ninth edition.

Gillespie S.H and Pearson R.D (2001). Principles and Practice of Clinical Parasitology. John Wiley and Sons Ltd. West Sussex, England.

About the author

MicroDok

2 Comments

Leave a Comment