Table of Contents
Plasmodium Species – Malaria
This family of protozoan parasites is responsible for causing malaria, which is the number one cause of human death of all parasitic infections.
There are 5 species in the Plasmodium family: P. falciparum, P. vivax, P.malarie, P. ovale, and P. knowlesi. Humans are the only relevant reservoir. The parasite is transmitted by the female anopheles mosquito.
Endemic to Mexico, South America, Central America, Africa, and Southeast Asia. Globally, it is responsible for 2 billion infections and 3 million deaths per year.
Plasmodium life cycle
- Sporozoites are transferred from the mosquito’s salivary glands to a human via a blood meal
- Sporozoites enter the human’s liver cells within 30 minutes, becoming cryptozoites or schizonts
- Cryptozoites or schizonts multiply within the hepatic cells into merozoites which eventually burst the infected cell, being released into the bloodstream
- Notably, P. vivax and P. ovale can develop into a dormant stage (hypnozoites) which can persist in the liver for weeks or even years and cause relapses by invading the bloodstream.
- Merozoites infect human red blood cells and asexually reproduce into male and female gametocytes.
- Alternatively, merozoites can also transform into ring-shaped trophozoites, which mature into schizonts again and rupture, releasing more merozoites.
- This cyclic rupture of red blood cells is what causes the signs and symptoms of the disease.
- The gametocytes are taken up by another mosquito when it takes a blood meal of an infected human.
- The gametocytes reproduce sexually in the mosquito’s gut, making zygotes that mature into infective sporozoites.
Blood smears will show merozoites and sporozoites inside the red blood cells.
Patients present with cyclic bouts of fever, anemia, and episodes of shaking chills (related to red blood cell lysis) that repeat in approximately 48 to 72-hour intervals. It also presents with flu‑like symptoms, diarrhea, abdominal pain, nausea, jaundice, and vomiting.
Organ dysfunction can also occur including hepatomegaly, splenomegaly, oliguria, hemoglobinuria, heart failure, pulmonary edema, and cerebral malaria (especially with P. falciparum). Cerebral malaria is the most severe form and presents as hallucinations, confusion, impaired consciousness, or even coma.
Prevention and vector control are crucial to protect humans from mosquito bites.
- Cover exposed skin in endemic areas
- Use insect repellant, like DEET
- Sleep with mosquito nets
- Reduce mosquito breeding sites around the home/community, including pools of water, puddles, stagnant rainwater, etc.
- Chloroquine is the drug of choice for P.vivax, P.malarie, and P. ovale infections.
- P. falciparum has developed resistance to chloroquine. This drug cannot be used in Africa or Southeast Asia where P. falciparum is prevalent.
- P. falciparum infections are treated with artemether-lumefantrine, atovaquone‑proguanil, quinine in combination with doxycycline, tetracycline, or clindamycin, mefloquine, or artesunate.
- Quinine, artemether, atavaquone-proguanil, mefloquine, and pyrimethamin/sulfadoxine can be used as a prophylactic treatment in endemic regions for all 5 species of Plasmodium.
- Anti-Plasmodium vaccines are currently in development.
Toxoplasma species – Toxoplasmosis
Toxoplasma gondii is a single-celled protozoan that is present in undercooked pork and cat feces. Cats are the definitive hosts and acquire the parasite via consumption of infected animals.
Toxoplasma Life Cycle
- Humans become infected by ingesting Toxoplasma cysts via consumption of undercooked meat or food contaminated by cat feces.
- Cysts open in the human duodenum, enter the bloodstream, and release sporozoites.
- Sporozoites will infect human macrophages.
- Sporozoites can also form dormant cysts that remain within human tissues for years and decades or until the immune system is activated.
Serologic blood tests can detect antibodies to Toxoplasma to determine previous exposure. IgM antibodies will be present within the first week of acute infection, while IgG antibodies will be present from 2 weeks after the infection and remain positive for life. Tissue biopsies can also determine if a patient has an active infection.
The majority of patients (>90% of cases) with toxoplasmosis are asymptomatic carriers. Those who develop symptoms do so from 3 days to 3 weeks after the initial infection. Some patients will present with fatigue, malaise, and mononucleosis-like symptoms, which will spontaneously resolve in one month.
Immunocompromised patients, such as individuals with congenital or acquired immunodeficiency, long-term steroid use, or cancer, can develop cerebral and ocular toxoplasmosis. Ocular toxoplasmosis presents with a retinal lesion and marked vitreous reaction, leading to defects in the visual field at the site of inflammation. Cerebral toxoplasmosis is the most common neurological disorder associated with AIDS. It presents with fever, headache, mental status changes, seizures, and focal neurological deficits.
Pregnant women, especially in the first trimester are advised to stay away from cats because of risk of congenital toxoplasmosis for their child.
- The parasite can cross the placenta and cause stillbirth, chorioretinitis, intracerebral calcifications, psychomotor disturbances, and hydro- or microcephaly.
- Manifestations of this disease can occur after childbirth.
- Symptoms in the child are not as severe if the infection occurs in the second or third trimester.
People can prevent acquiring the parasite by eating meat that is cooked through and avoiding contact with cat feces. Pregnant women are advised to avoid cat feces during pregnancy.
Pharmacological treatment includes pyrimethamine and sulfadiazine.
Leishmania – Cutaneous and Visceral Leishmaniasis
Leishmania is a single-celled protozoan parasite. There are 4 species (L. donovani, L. tropica, L. mexicana, and L braziliensis) that can cause visceral leishmaniasis, cutaneous leishmaniasis, and mucocutaneous leishmaniasis.
There are 1.3 million new cases a year with 20 to 30 thousand deaths annually. These parasites are found in Central America, South America, Africa, the Middle East, and India.
They are zoonotic parasites that are found in dogs, rodents, and foxes. The transmission vector is the phlebotomous sandfly.
Leishmania life cycle
- The sandfly acquires amastigote forms of the parasite from zoonotic hosts.
- In the sandfly’s gut, the amastigotes develop into flagellated promastigotes and multiply.
- When the sandfly bites a human, the promastigotes exit via the salivary gland into the skin.
- The promastigotes are taken up by macrophages and multiply within until the macrophages rupture.
Leishmaniasis can be diagnosed in several ways:
- PCR of a blood sample can identify Leishmania DNA
- Microscopy of a skin biopsy will visualize macrophages with amastigotes
- ELISA test will show Leishmania antibodies, confirming infection
- Blood tests will also show hemolytic anemia, neutropenia, eosinopenia, and thrombocytopenia as a result of the infection.
L.mexicana and L. tropicana cause cutaneous leishmaniasis. When the sandfly bites a human, the parasite infects local macrophages. This will lead to macrophage lysis at the site of the bite causing a dermal lesion and ulceration.
The incubation period can extend weeks to months. The lesion is characteristically solitary, but can also be multiple. It is represented by reddish macules and/or papules around the initial sandfly bite that can quickly increase in size and develop central ulceration.
L. braziliensis causes mucocutaneous leishmaniasis. In this case, once the sandfly bites a human, the infected macrophages travel to the nasopharynx or genitals, where the parasite can lay dormant for years. Eventually, macrophage destruction will occur and there will be lesions and ulcerations in the infected area; can also cause mucosal bleeding and nasal blockage.
L. donovani causes visceral leishmaniasis, also known as kala-azar. The parasite will spread from the site of inoculation to the liver and spleen. Here, the parasite will lay dormant for months and eventually multiply resulting in hepatosplenomegaly and anemia. Additionally, there can be edema, weight loss, ascites, systemic lymphadenopathy, fever, and flu-like symptoms. There is also an associated darkening of the skin in the infected region. L. donovani is able to cross the placenta and cause congenital leishmaniasis. In 20% of patients, there is an associated dermal inflammation that persists after the disease subsides. Patients will have soft nodules on their faces that are asymptomatic (non-tender and non-pruritic) and will spontaneously resolve.
Prevention and Treatment
Prevention of leishmaniasis is performed with the use of bed nets, long clothing, and destruction of the habitat of the sandfly.
Amphotericin B and sodium stibogluconate are effective treatments against leishmaniasis.
Trypanosoma Species – African sleeping sickness and Chagas disease
A flagellated, single-celled protozoan parasite. There are 3 species that have human pathology (T. brucei gambiense, T. brucei rhodesiense, and T. cruzi).
The transmitting vector is the tsetse fly in the African species (T. gambiense and T. rhodesiense). In the American species (T. cruzi), the vector is the reduviid bug.
Reservoirs for T. rhodesiense are game animals; while for T. gambiense, the reservoir is humans and domesticated animals. There is no animal reservoir for T.cruzi.
Trypanosoma Life Cycle
The African and American species of the parasite have different life cycles. In the African species, T. gambiense and T. rhodesiense:
- An infected tsetse fly bites a human and injects the parasite in the form of metacyclic trypomastigotes.
- A chancre forms at the site of the bite while the metacyclic trypomastigotes turn into trypomastigotes and infiltrate the bloodstream.
- The parasites make their way to the lymphatic and nervous tissues over the course of months to years.
- The body cannot clear the parasite due to antigenic variation, and these multiply by binary fission in the blood and lymph.
- Another tsetse fly will bite an infected human and draw up the parasite into its gut with the blood.
In the American species, T.cruzi:
- An infected reduviid bug will bite a human. As they take blood in, the bug will defecate, and the parasite is located within the feces.
- As humans scratch after being bitten, the parasite will enter the skin through the wound or nearby mucosal membranes and proceed to cells.
- The metacyclic trypomastigotes transform into amastigotes, which multiply via binary fission.
- Intracellular amastigotes transform into more trypomastigotes, which burst the cells and are released into the bloodstream.
- The parasite will then reinfect other cells and continue this destructive cycle for years.
- The final destination of the parasite will be the cardiac muscle and gastrointestinal nerves, where the parasite can lay dormant for years.
|The African trypanosomes can be identified histologically via a blood smear.||American trypanosomes are identified by blood smear. Another diagnosis method consists of free reduviid bugs are allowed to bite a potential carrier of trypanosomes. One month later, the bugs are analyzed to see if they are infected with the parasite.|
In the African species, patients develop African trypanosomiasis, also called the African sleeping sickness. First, they develop a chancre at the site of the infection within 2 weeks of the bite. As the parasite enters the lymphatic and nervous tissue over the course of months to years, patients will develop intermittent fevers and painless lymph node enlargement. Eventually, the patients develop anorexia, headaches, neurological symptoms, and apathy. Over the course of the disease, the neurological symptoms worsen and the patient has sleep disturbances. Patients will decompensate further resulting in convulsions, coma, and death.
Patients with American species of trypanosomes will develop American trypanosomiasis, also called Chagas disease. The first clinical sign of infection is a chagoma, which is an inflammatory nodule present at the site of the bite of the reduviid bug about 1-2 weeks after the bite. If the bite is near the eye, Romana’s sign can also occur, unilateral painless edema of the eyelids and periocular tissue. Primary infection is characterized by fever, malaise, anorexia, and lymphadenitis. These symptoms usually resolve within 1 month.
Patients with chronic Chagas disease, will undergo an indeterminate latent phase for 10 to 20 years.
Then, the parasite will enter the cardiac muscle and lead to arrhythmias, dilated cardiomyopathy, and even stroke. The parasite can also enter gastric nervous tissue, destroy nerve plexuses, and create megacolon and megaesophagus.
Prevention requires the limiting of contact with the tsetse fly and the reduviid bug vectors, usually by wearing long clothing and using bug nests while sleeping to preventing inoculation.
Pharmacologically, eflornithine, pentamidine, and suramin can be given to treat the African species of the parasite. However, once neurological symptoms are present, the drugs lose their effectiveness.
Regarding the American species of trypanosome, benznidazole and nifurtimox can be used for treatment.
Multi-celled organisms that can reproduce sexually or are hermaphroditic, and are commonly called “worms”. They have the ability to develop into dormant cysts. Helminths can be transmitted via fecal-oral contact, fecal-skin contact, or ingestion. The disease burden is directly related to the number of worms that are in the host.
This is a roundworm that lives in the human intestinal tract. It can reach a length of 30 centimeters and up to 25% of the world’s population is infected with this helminth.
The lifecycle of this worm begins by the human ingestion of eggs through contaminated food. The eggs will hatch in the intestine and make their way into the bloodstream and into the alveoli of the lungs. The worms will become lodged in these air sacs. They pierce the alveoli and migrate up the bronchus into the trachea. Via coughing and swallowing, the parasites enter the GI system where they mature and lay eggs that leave the body through feces.
Infection by these helminths causes malabsorption of nutrients for their human hosts. They also have the potential to obstruct the biliary tract and cause peritonitis.
Diagnosis involves an analysis of the patient’s stool looking for adult worms and/or eggs with a characteristic “knobby appearance”.
Treatment consists of an antihelminthic drug: mebendazole, albendazole, ivermectin, or nitazoxanide.
Patients should also avoid eating food contaminated with feces by maintaining good hygiene in the kitchen and with their food.
This helminth is a hookworm. The larvae live in the soil and can infect humans when they step on infected soil without wearing shoes. These helminths will penetrate the skin, enter the bloodstream, and travel directly to the alveoli, where they can later escape and enter the GI tract via the bronchus and trachea.
Once in the intestinal system, the helminths will attach to the lumen of the GI tract and feed off human blood. These organisms will lay eggs that will be excreted by the human host via their feces.
Patients will present with symptoms depending on the phase of the life cycle the parasites are going through. After the penetration of the skin, patients will develop pruritus, erythema, and a maculopapular rash. Sometimes this rash can have a very particular pattern, with serpiginous marks representing the larval tracks, which is called cutaneous larva migrans.
When the parasite is found within the lungs, the patient can develop a dry cough or wheezing (Löffler syndrome). During the intestinal phase, the patient develops symptoms of iron deficiency anemia and failure to thrive. Abdominal pain, weight loss, nausea, vomiting, and diarrhea can also occur.
Diagnosis involves inspection of human feces for larvae and eggs, while blood tests can show eosinophilia and microcytic anemia. Treatment is with mebendazole or pyrantel pamoate. The cutaneous phase can be treated with bendazoles or ivermectin.
A nematode that is present in undercooked pork and other wild types of meat or rarely through the fecal-oral route. The larvae are consumed, enter the body, and mature in the intestines within the mucosa of the small bowel. Once the worms become adults, they will release larvae that can invade muscle cells. At this point, the parasites become encapsulated within the muscle.
Patients present with diarrhea, abdominal pain, muscle pain, and headaches. Additionally, fevers, rashes, splinter hemorrhages, retinal and conjunctival hemorrhages can occur.
Treatment is with albendazole or mebendazole. However, once the helminth enters the muscle cells, pharmacological treatment will not work. Most commonly, mild cases are self-limiting and only require analgesics.
These are a family of helminths that include 4 species (S. manconi, S. japancoium, S. haematobium, and S. mekongi). Globally, there are between 200 and 300 million infections per year. A specific freshwater snail is the intermediate host to this trematode.
Schistosoma larvae in the form of miracidia enter the snail where they mature into cercaria. They can come into contact with human flesh in contaminated waters. Once mature, they will penetrate human flesh and enter the bloodstream. In the blood, they mature into adult schistosomes and migrate to the veins of their target organs, which include the intestines, liver, and bladder (most commonly, the liver). The Schistosoma organisms will mate within the organ, and the female will lay eggs that leave the body via feces.
Humans infected with schistosomes will firstly develop a pruritic maculopapular rash in the area where cercaria penetrated the skin. Then, after 3 to 6 weeks, the patient will present fever, fatigue, cough, myalgia, and angioedema from the immune response to antigens released by the helminths. Eventually, they will suffer from portal hypertension because the eggs laid by the females will impede the blood flow to and from the liver. The eggs also produce granuloma formation as a result of the body’s chronic inflammatory immune response. Esophageal varices and ascites can occur as a result of portal hypertension.
Diagnosis is based on direct visualization of schistosome eggs via stool or urine analysis. Blood tests will show eosinophilia. Treatment is with praziquantel which will prevent egg production by the females.