Selected Diseases - Part 3
I Fungal Infections
1) General 2) Histoplasmosis
II Protozoan Infections
1) Amebic Dysentery 2) Trypanosomes
3) Malaria
I Fungal Diseases
1. General
Most fungal infections are opportunistic or accidental. Generally fungi digest host cells by enzymes. Sometimes they cause allergies and sometimes they make toxins (mycotoxin = fungal toxin).
Lysergic acid is made by ergot, a fungus that grows on rye. The drug LSD is a derivative of lysergic acid. Poisoning from ergot/lysergic acid was quite common in the Middle Ages. The ergot fungus spread in cold wet conditions and infected the rye which was made into bread.
Aflatoxin is made by Aspergillus, a mold that grows on a variety of foods, especially peanuts. Aflatoxin damages the liver and is also a carcinogen.
2. Histoplasmosis (Talaro pages 670-672)
Caused by Histoplasma capsulatum, a dimorphic fungus which alternates between two forms depending on the temperature. It lives as a single-celled yeast at 37o in animal tissue but forms filaments below 35o in soil. The filaments form spores which may be blown around and breathed in.
It is considered a true pathogen and not just an opportunist. Carried by bats, and also lives in the soil, especially where there are bat and bird feces. It seems to flourish in high nitrogen content.
Other names = reticulo-endotheliosis, Ohio Valley fever, Darling's disease. Identified in 1905 but has been around through the ages. Has been suggested it was the cause of the sudden deaths of several people who participated in the archeological projects at the tomb of King Tut - the "mummy's curse."
If we did antibody tests, probably over half of us would be positive in this region (the Mississippi Valley region). Also prevalent in other river valleys.
Usually causes a mild respiratory infection not recognized as anything special but maybe 0.1% of the time it will progress and can be very serious. About 50 people die in the US each year from histoplasmosis.
Transmission by spores that are spread by the wind and inhaled. The lungs are infected and then other organs can be infected also. Treatment is with intravenous amphotericin B daily for several days to weeks.
Most at risk: individuals working with soil or cleaning up in areas contaminated by bird or bat feces in areas where histoplasmosis is endemic. Especially the young, the very old, those with lowered resistance.
II Protozoan Diseases
1. Amebic Dysentery
Caused by the ameba Entamoeba histolytica. Often just lives in the intestine without doing any damage. May be asymptomatic (90%) or cause mild to serious diarrhea. Sometimes invades tissue of the intestines and may move on to other internal organs such as the liver where it causes dangerous abscesses.
Only infects humans. Reservoir is people who carry it without showing disease (or who have very slow and mild disease). 50-100,000 deaths per year world-wide (3rd highest for a parasite).
Life cycle:
Trophozoite (i.e. the ameba form or "feeding form") is 0.1 to 0.6 mm long. This lives inside humans, especially in the small intestine. It produces cysts that exit in the feces. Cysts are distributed and may contaminate water or food etc. If they are swallowed, they hatch out and this starts another infection. Most common in tropical and subtropical regions, especially in areas with poor sanitation.
Treatment:
Metronidazole and emetine act against amebas in tissues but not free in the intestine. Paromomycin and diiodohydroxyquin (iodoquinol) act against amebas free in the intestine but not in tissues. Generally give one of each.
2. Trypanosomes
Trypanosomes are protozoan parasites with flagella. They have complex life cycles that alternate between vertebrates and insects. Most do not harm their hosts. A few cause serious diseases. They live in the blood (mostly) and are sometimes known as "hemoflagellates" because of this.
Trypanosoma cruzi causes Chagas disease in Latin America. Carried by kissing bugs that live among humans and domestic animals. Parasites come out in bug feces and may infect wounds when the bug bites someone. Treatment is difficult. Bug control is reasonably effective.
Trypanosoma brucei causes sleeping sickness in Africa. Shared by humans, wild animals and domestic animals. Carried by tse-tse flies (Glossina).
Some 250,000 to 300,000 people in 36 countries of sub-Saharan Africa are infected. There are two forms of African sleeping sickness, caused by two related parasites:
Trypanosoma brucei gambiense causes a chronic infection lasting years in countries of western and central Africa
Trypanosoma brucei rhodesiense causes acute illness lasting several weeks in eastern and southern Africa
Parasites are taken in by a blood sucking insect when it sucks blood from an infected animal. Parasites multiply in the intestines and move to the salivary glands. Next time the insect bites, the parasites are injected with the saliva into the wound.
Trypanosomes constantly change their surface proteins. They have hundreds of different but related copies of the gene for the main surface glycoprotein and they switch from one to another every few days. The immune system never manages to keep up. Infections goes in waves as one variant is killed off by the immune system but another replaces it.
Symptoms:
Early phase - bouts of fever, headaches, pains in the joints and itching. Second phase (neurological phase) - begins when the parasite crosses the blood-brain barrier and infests the central nervous system. Characteristic symptoms of the disease appear: confusion, sensory disturbances and poor coordination. Disturbance of the sleep cycle is the most important feature.
Without treatment, the disease is fatal. If the patient does not receive treatment before the second phase starts, neurological damage is irreversible even after treatment.
Treatment:
Most drugs are old, difficult to administer and not always successful. If disease is diagnosed early, chances of a cure are high.
Early phase &emdash; pentamidine (best) or suramine.
Neurological phase &emdash; Melarsoprol, invented in 1949, is the last arsenical derivative in use. Drastic side effects are often fatal and include reactive encephalopathy (an allergic hyperacute neurological complication) in 3% to 10% of cases. Widespread resistance to the drug, up to 30%, in parts of central Africa. Eflornithine (difluoromethylornithine) is the less toxic alternative but only works against the West African version of the disease.
3. Malaria
Malaria is caused by protozoans of the genus Plasmodium. It may be acute and/or chronic and varies greatly in severity. Transmitted by mosquito bites and infects red blood cells. Every so often the red cells burst and release a new crop of parasites. The result is a cyclic pattern of fever that occurs every 2 or 3 days.
Malaria affects 300-500 million people per year and 1.5 to 3 million per year die from malaria. 1 million of these are children under 5 years old
At any given time, only about 20% of infected individuals show symptoms, although many more will go on to have symptoms
Life cycle:
Asexual stage occurs in human red blood cells (or liver cells).
Sexual stage occurs in the mosquito.
The Vector is the female Anopheles mosquito. Only the females bite, mostly between dusk and dawn. The male mosquitoes do not consume blood, they live on nectar from flowers and therefore do not carry malaria.
Symptoms include anemia, jaundice, enlarged spleen and fever. The fever goes through malaise, cold stage (chills and shaking) hot stage (fever up to 102-104 for several hours with headache, nausea and delirium) sweating stage (fever goes, severe fatigue, sleep).
Four species of Plasmodium cause the disease in humans (others cause malaria in other animals and birds).
Plasmodium falciparum
Causes the most deadly and severe infections
It infects all ages of red blood cells (therefore more parasites)
Causes infected red blood cells to bind to blood vessel walls a) may block small blood vessels and b) the red blood cells avoid the spleen where the immune system is concentrated
Varies its surface proteins to avoid immune recognition
It does not have a latent form
There is widespread drug resistance
Plasmodium vivax and Plasmodium ovale
Usually do not cause life-threatening infections
Only infect developing red blood cells ("reticulocytes")
May give rise to special cells ("hypnozoites") that live in the liver in a latent form. Therefore disease may re-emerge up to 5 years later
Plasmodium malariae
Usually do not cause life-threatening infections
Only infects mature red blood cells
Relatively mild but may last on and off up to 40 years
Treatment:
Traditional treatment is quinine (relatively expensive)
Synthetic aminoquinoline drugs that act similarly to quinine:
Chloroquine was the most common but many parasites have now become resistant.
Mefloquine
Primaquine kills malaria stages found in the liver
Artemisinin (Qinghausu) from the Chinese wormwood, Artemisia annua is an ancient herbal remedy.
Quinine comes from the Cinchona tree from South America. It fluoresces blue under near UV (black light). Quinine is found in tonic water. Gin and tonic was drunk in India by British colonists to prevent malaria.
