Human Pathogens

As we have seen, a pathogen is anything that causes disease. Parasitic organisms live in or on a host organism and harm the organism. A small number of protists are serious pathogenic parasites that must infect other organisms to survive and propagate. For example, protist parasites include the causative agents of malaria, African sleeping sickness, amoebic encephalitis, and waterborne gastroenteritis in humans. Other protist pathogens prey on plants, effecting massive destruction of food crops.

Plasmodium Species

Figure 1. Red blood cells are shown to be infected with P. falciparum. In this light microscopic image, the ring-shaped P. falciparum stains purple. (credit: modification of work by Michael Zahniser; scale-bar data from Matt Russell)

In 2015 WHO reported over 200 million cases of malaria, mostly in Africa, South America, and southern Asia. However, it is not well known that malaria was also a prevalent and debilitating disease of the North Central region of the United States, particularly Michigan, with its thousands of lakes and numerous swamps. Prior to the civil war, and the drainage of many swamps, virtually everyone who immigrated to Michigan picked up malaria (ague as it was called in the late 1800s), and the pale, sallow, bloated faces of that period were the rule. The only healthy faces were worn by those immigrants who had just arrived. In fact, there were more deaths due to malaria in Michigan than those from the Civil War.

We now know that malaria is caused by several species of the apicomplexan protist genus Plasmodium. Members of Plasmodium must sequentially require both a mosquito and a vertebrate to complete their life cycle. In vertebrates, the parasite develops in liver cells (the exoerythrocytic stage) and goes on to infect red blood cells (the erythrocytic stage), bursting from and destroying the blood cells with each asexual replication cycle (Figure 1). Of the four Plasmodium species known to infect humans, P. falciparum accounts for 50 percent of all malaria cases and is the primary (and deadliest) cause of disease-related fatalities in tropical regions of the world. In 2015, it was estimated that malaria caused over 400,000 deaths, mostly in African children.

During the course of malaria, P. falciparum can infect and destroy more than one-half of a human’s circulating blood cells, leading to severe anemia. In response to waste products released as the parasites burst from infected blood cells, the host immune system mounts a massive inflammatory response with episodes of delirium-inducing fever (paroxysms) as parasites lyse red blood cells, spilling parasite waste into the bloodstream. P. falciparum is transmitted to humans by the African mosquito, Anopheles gambiae. Techniques to kill, sterilize, or avoid exposure to this highly aggressive mosquito species are crucial to malaria control. Ironically, a type of genetic control has arisen in parts of the world where malaria is endemic. Possession of one copy of the HbS beta globin allele results in malaria resistance. Unfortunately, this allele also has an unfortunate second effect; when homozygous it causes sickle cell disease.

Trypanosomes

Figure 2. Trypanosomes are shown among red blood cells. (credit: modification of work by Dr. Myron G. Shultz; scale-bar data from Matt Russell)

Trypanosoma brucei (Figure 2), transmitted by tsetse flies (Glossina spp) in Africa, and related flies in South America, is an flagellated endoparasite responsible for the deadly disease nagana in cattle and horses, and for African sleeping sickness in humans. This trypanosome confounds the human immune system by changing its thick layer of surface glycoproteins with each infectious cycle. (The glycoproteins are identified by the immune system as foreign antigens, and a specific antibody defense is mounted against the parasite.) However, T. brucei has thousands of possible antigens, and with each subsequent generation, the protist switches to a glycoprotein coating with a different molecular structure. In this way, T. brucei is capable of replicating continuously without the immune system ever succeeding in clearing the parasite. Without treatment, T. brucei attacks red blood cells, causing the patient to lapse into a coma and eventually die. During epidemic periods, mortality from the disease can be high. Greater surveillance and control measures lead to a reduction in reported cases; some of the lowest numbers reported in 50 years (fewer than 10,000 cases in all of sub-Saharan Africa) have happened since 2009.

In Latin America, another species of trypanosome, T. cruzi, is responsible for Chagas disease. T. cruzi infections are mainly caused by a blood-sucking “kissing bug” in the genus Triatoma. These “true bugs” bite the host during the night and then defecate on the wound, transmitting the trypanosome to the victim. The victim scratches the wound, further inoculating the site with trypanosomes at the location of the bite. After about 10 weeks, individuals enter the chronic phase but most never develop further symptoms. In about 30 percent of cases, however, the trypanosome causes further damage, especially to the heart and digestive system tissues in the chronic phase of infection, leading to malnutrition and heart failure due to abnormal heart rhythms. An estimated 10 million people are infected with Chagas disease, and it caused 10,000 deaths in 2008.

Plant Parasites

Protist parasites of terrestrial plants include agents that destroy food crops. The oomycete Plasmopara viticola parasitizes grape plants, causing a disease called downy mildew (Figure 3). Grape plants infected with P. viticola appear stunted and have discolored, withered leaves. The spread of downy mildew nearly collapsed the French wine industry in the nineteenth century.

Figure 3. Both downy and powdery mildews on this grape leaf are caused by an infection of P. viticola. (credit: modification of work by USDA)

Figure 4. These unappetizing remnants result from an infection with P. infestans, the causative agent of potato late blight. (credit: USDA)

Phytophthora infestans is an oomycete responsible for potato late blight, which causes potato stalks and stems to decay into black slime (Figure 4). Widespread potato blight caused by P. infestans precipitated the well-known Irish potato famine in the nineteenth century that claimed the lives of approximately 1 million people and led to the emigration of at least 1 million more from Ireland. Late blight continues to plague potato crops in certain parts of the United States and Russia, wiping out as much as 70 percent of crops when no pesticides are applied.