Amoebicidal Drugs Lecturer: Danica B
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Amoebicidal Drugs Lecturer: Danica B. Quijano, MD Date Lectured: November 20, 2015 DLSHSI – College of Medicine: PHARMACOLOGY ö Ariba amoeba! Greetings from the amoebas! Yes, ö Improper hygienic practices we’re gonna be talking a lot about the amoeba o Protozoal infections are common among people but only for the Entameoba histolytica , the in underdeveloped tropical & subtropical pathologic agent responsible for the famous countries, where sanitary conditions, hygienic “amoebiasis” we have all heard about. practices, and control of the vectors of ö We will focus our discussion in the transmission are inadequate. However, with pharmacological treatment for infection caused increased world travel, protozoal diseases are by the protozoa Entamoeba histolytica. But first, no longer confined to specific geographical let’s have a glimpse of the offending pathogen. locations. ö Amoebiasis is an infection caused by the E. ö Speaking of diarrhea and travel.. histolytica likewise amoebiasis is sometimes o Good to know: I believe you have heard the incorrectly used to refer to infection with other term Traveler’s diarrhea. Its diagnosis does not amoebae, but strictly speaking it should be imply a specific organism, but Enterotoxigenic E. reserved for E. histolytica infection. coli (ETEC) is the most commonly isolated pathogen. While Backpacker’s diarrhea is also ö Entamoeba is a genus of amoeboid protozoa that known as Giardiasis or Beaver fever because live in the human intestine. giardiasis, caused by the protozoan Giardia o Some species within this genus are harmless, lamblia, frequently infects persons who spend a while others are pathogenic. lot of time camping, backpacking, or hunting, so o One, especially, has the potential to become it has gained the nicknames. dangerous, the Entamoeba histolytica. ö Worth mentioning: ö Clinical features varies from asymptomatic to an o Traveler’s diarrhea (ETEC) infectious diarrhea and the most dreaded life- o Backpacker’s diarrhea (Giardiasis) threatening fulminant colitis. ö Entamoeba histolytica is the only specie that is ö The pathogenic Entamoeba histolytica definitely associated with pathological sequelae in o Amoebiasis – disease caused by E. histolytica humans; § It is estimated that up to 15% of the world's o the other entamoebas are considered population is infected by the pathogen nonpathogenic. Entamoeba histolytica. Every year, over ö The genus Entamoeba contains many species, six 100,000 people die of the disease caused of which, reside in the human intestinal lumen by E. histolytica, amoebiasis, making it the o Entamoeba histolytica, second most common parasitic cause of o Entamoeba dispar, death, after malaria. o Entamoeba moshkovskii, § 2nd most common parasitic cause of death o Entamoeba polecki, after malaria o Entamoeba coli, § Tropical countries with poor sanitation are o Entamoeba hartmanni often hit hardest by outbreaks. ö The lifecycle of Entamoeba histolytica is pretty typical for a protozoan parasite. Just remember, we have 2 forms of the parasite: the cyst & the trophozoite. Let’s simplify further. ö Infection occurs by ingestion of cysts on fecally contaminated food or hands. o The cyst is resistant to the gastric environment and passes into small intestine where it decysts. o The metacyst divides into four and then eight amoebae which move to the large intestine. o The organisms encyst for mitosis and are passed through with feces. o There are no intermediate or reservoir hosts. ö Cysts and trophozoites are passed in feces. o Cysts are typically found in formed stool, o Trophozoites are typically found in diarrheal stool. ö Infection by Entamoeba histolytica occurs by ingestion of mature cysts in fecally contaminated food, water, or hands. ö Excystation occurs in the small intestine and trophozoites are released, which migrate to the large intestine. ö The trophozoites multiply by binary fission and produce cysts, and both stages are passed in the feces. o Because of the protection conferred by their walls, the cysts can survive days to weeks in the external environment and are responsible for transmission. o Trophozoites passed in the stool are rapidly destroyed once outside the body, and if ingested would not survive exposure to the gastric environment. 1 ö In many cases, the trophozoites remain confined to the intestinal lumen (: noninvasive infection) of individuals who are asymptomatic carriers, passing cysts in their stool. ö In some patients the trophozoites invade the intestinal mucosa (: intestinal disease), or, through the bloodstream, extraintestinal sites such as the liver, brain, and lungs (: extraintestinal disease), with resultant pathologic manifestations. ö It has been established that the invasive and noninvasive forms represent two separate species, respectively E. histolytica and E. dispar. o These two species are morphologically indistinguishable unless E. histolytica is observed with ingested red blood cells (erythrophagocystosis). ö Transmission can also occur through exposure to fecal matter during sexual contact (in which case not only cysts, but also trophozoites could prove infective) -- o These protozoa are transmitted by the fecal–oral route; high rates of oral–anal sex by MSM are considered the reason for increased rates of carriage. o Because E. histolytica is also transmitted by the fecal–oral route, MSM may also have an increased risk for E. histolytica carriage. ö Cysts, which are the round, dormant, resistant and infectious stage, are acquired by the fecal-oral route.u o Usually by drinking contaminated water. ö Once in the intestine, excystation occurs, with trophozoites emerging from the cyst. ö Trophozoites are the motile, feeding stage of Entamoeba histolytica. ö They are amorphous cells containing prominent round vacuoles that move via oozing pseudopod motion through the length of the intestine, until they reach the large intestine. o Once there, they multiply by binary fission and begin to form new cysts. ö The cyst serves as the protective coat. o These cysts are excreted in the feces, can survive outside the body for several weeks and are capable of infecting new hosts. ö The diagnosis is established by isolating E. histolytica from the feces. ö When exposed to new environments (such as temperature changes, or transit down the intestinal tract, or exposed to a chemical agent), the protozoa can secrete a protective coat and shrink into a round, armored form called the cyst. o It is this cyst form that is infective when ingested by humans. o Following ingestion, it converts back into the motile form, called the trophozoite. ö The cysts can live outside the hosts or be carried asymptomatically in the stool, while trophozoites, passed by people with invasive disease, cannot survive outside the host. ö Only ten percent of those infected with Entamoeba histolytica ever develop amoebiasis and its associated symptoms, most of which are very mild. o Within two to four weeks of exposure, you may experience brief bouts of diarrhea, accompanied by stomach cramping and abdominal pain. o During this time, you can be shedding millions of cysts ö In rare cases, without treatment, the symptoms can become more severe. ö Entamoeba histolytica is able to survive in the intestinal tract, but can also invade the cells of the intestinal lining. o The trophozoites release proteases, which are enzymes that break down protein, causing deep, painful lesions and ulcers in the intestinal lining. o What results is a more severe form of amoebiasis, called amoebic dysentery. o A patient with amoebic dysentery can experience intense abdominal pain, periodic loose stools with blood and mucus, and fever. o Weight loss and fatigue can also occur. ö If the amoebic dysentery goes untreated, it can progress to extraintestinal amoebiasis, although this is rare. o The trophozoites can migrate out of the large intestine, travel through the blood and invade other tissues, causing the same lesions found in the gut. 2 ö The liver receives blood from both systemic and portal circulations. Increased susceptibility to infections would be expected given the increased exposure to a pathogen. o However, Kupffer cells lining the hepatic sinusoids clear bacteria so efficiently that infection rarely occurs. o The predilection for the right hepatic lobe can be attributed to anatomic considerations. § The right hepatic lobe receives blood from both the superior mesenteric and portal veins, § Whereas the left hepatic lobe receives inferior mesenteric and splenic drainage. § Also the right hepatic lobe contains a denser network of biliary canaliculi and, overall, accounts for more hepatic mass. o Untreated, pyogenic liver abscess remains uniformly fatal. Sepsis, Multi-organ failure. Polymicrobial involvement is common. o Gross pathology of amebic abscess of liver. Tube of "chocolate" pus from abscess. ö E. histolytica is the causative agent of amebic dysentery. Dysentery - in Parasitology, you’ve discussed 2 bacterial agents of dysentery namely EIEC and Shigella dysenteriae. o And this one is dysentery, an amebic dysentery. o A patient infected may get the famous flask shaped ulcers in the GIT mucosa and may also have extensions into the liver although that would be a very severe complication from Entamoeba. o One of the things that you could also see in this disease is Pseudoappendicitis (you can also get pseudo appendicitis-like disease in infections caused by Yersinia enterocolitica). The characteristic “flask-shaped ulcers” of intestinal amoebiasis (enzymatic degradation)