Environmental Pathogens Flashcards

Question

what are some of the malarial species?

Answer 1

There are some differences among the four species of Plasmodium. Note that P. falciparumis the most devastating. The repeating fevers/merozoiterelease from erythrocytes may not be synchronized with the multiple-stage infections of P. falciparum. Furthermore, P. falciparumtriggers increased adhesion of infected rbcsto endothelial cells, hence triggering obstruction and inflammation. Falciparum-doesn’t cycle multiples so quickly doesn’t get syncrhonizationas it multiples frantically w/in red cells developing stickiness to endothelium and can develop a cerebral malaria. Most at risk are young indivdiauslw/ this not constantly exposed that would prevent that proliferation (stroke-like) Vivax- loves to hang out inside the liver (hyponzoite)

Answer 2

Chloroquine, along with the other quinineproducts, accumulates in the food vacuole of the parasite, and shuts down heme polymerase, and so will lead to a toxic accumulation of the heme. Chloroquineaffects the erythrocyte stages of malaria only. In contrast, primaquinekills the liver forms of malaria, but not the rbcstages. While chloroquine can be appropriate prophylaxis against P. falciparum in those regions of the world with sensitive strains, e.g., Central America and the Middle East, regions of the world with resistant strains, e.g., South America, sub-Saharan Africa, and Southeast Asia, typically require a different strategy: atovaquoneinterferes with the electron transport chain in malarial mitochondria. It is taken in combination form (as Malarone®) with proguanil(a dihydrofolatereductase inhibitor) that enhances the atovaquoneeffect on mitochondrial membranes. This is an effective, but expensive,combination. Sickle cell anemia, G6CPDH, thalasemia- resistances create stress on the red cell as the malaria parasite is eating it making it less likely for the bacteria to eat it. Eat heme and have reactive iron, heme molecule to hold these together and not make it dangerous all quinindrugs inhibit heme polymerase activity oxidative stress killing off parasite. Quinine- primaquinineprophylaxis. Chloroquine- resistant in the 60s in the vietnamewar to US troops led to resistance Malarone- combo drug atovaquoneand proguaniltargettingshould start before travel

Answer 3

Babesiamicrotiis another erythrocyte infection particularly affecting asplenicpatients, that is spread by the Ixodestick, (deer tick) particularly in the Northeast US (often a co-infection with Lyme disease). Atovaquoneand azithromycin are primary considerations for treatment. Multiples in redcells and persists. Asplenic- no hematologic survalenaceof the liver are at higher risk. Need Atoquovone(malaronecomponent). Babesiamicroti Pathogen category: sporozoanparasite(apicomplexan) Source: ticks (Ixodes) withwild mice reservoir Virulence factors: intracellularexistence, rapid invasion of merozoiteinto RBC (similar to Plasmodium) Clinical: babesiosis Immune response: splenicremoval of infected RBCs; complement activation triggers TNF-alpha and IL-1 from macrophages Treatment and/or prevention:tick avoidanceand early removal; atovaquoneand azithromycin

Answer 4

Leishmaniaspecies Pathogen category: flagellates Source: sandflies Virulence factors: superoxidedismutase; triggering of (ineffective) Th2-humoral response Clinical: leishmaniasis,cutaneousor visceral Immune response: Th1-mediatedcell mediated response Treatment and/or prevention:avoidanceof insect bites; amphotericin B, paromomycin, miltefosine, sodium stibogluconate Leishmaniais a flagellategenus with a number of different species, some preferring skin and others preferring visceral targets (presumably reflecting temperature preferences, like those seen in leprosy vs. TB). Spread is via bites of sandflies. The flagellates are taken up by phagosomes, but the superoxide dismutase produced by the non-flagellated amastigotes is protective, and barring a successful cell-mediated immunity response, will continue to spread through the reticuloendothelial system. Diagnosis is via biopsy that can be examined by histology, culture, and PCR. Flagellate form- travel Amastagoatform- infected macrophages that transfer and multiple and spread. Cell-mediated immunity should be able to clear since protozoan more elusive. Cutaenousforms are most and some internal Why this is on the list: * Common worldwide (1.5 million) * Seen in travelers (e.g., Central America) and military personnel (e.g., from Iraq and Afghanistan) * Refugees or tours of duty * Some suggestion that it could be endemic in parts of Texas where the appropriate sandflyspecies can persist Treatment is a challenge. Standard therapy has included antinomy (i.e., heavy metal) containing compounds such as sodium stibogluconateavailable through the CDC. In March 2014, the FDA approved miltefosine(oral drug with a long fatty acid-like chain inhibits a major [protein kinase B or Akt] kinase-activated set of intracellular pathways). Topical paramomycincan be used for cutaneous disease, and amphotericin B is also used for visceral disease.

Answer 5

Trypanosomacruzi Pathogen category: flagellate Source: reduviidbug from multiple mammalian reservoirs Virulence factors: surfaceproteins that avoid complement; antioxidant enzymes when phagocytosed Clinical: Chagasdisease Immune response: lymphocytosisand accompanying fibrosis Treatment and/or prevention:insectbite avoidance; benznidazole Trypanosomacruziis a flagellate spread by reduviidbugs (kissingbugs-beak while sleeping and defecates in the wound) in Central and South America. A painful ulcer (chagoma) may be present at the site of the bite. Blood-borne spread can occur. In pregnant women, this can lead to placental crossing and stillbirths. In adults, one can have the concern of dilatedcardiomyopathy and megacolon(lossof contractile function full of backed up feces) as they lose their flagella and become amastigotes, triggering an inflammatory response in the targeted tissues (cardiac and intestine). The current drug of choice is available from the CDC in the form of benznidazole, which can form DNA-damaging metabolites like metronidazole.

Answer 6

Trypanosoma brucei Pathogen category: flagellate Source: tsetse flyfrom multiple mammalian reservoirs Virulence factors: antigenic variation Clinical: sleeping sickness Immune response: antibodies andlymphocytosis Treatment and/or prevention:insectbite avoidance/vector control (difficult); early disease: suramin(possible inhibition of NADH-associated enzymes); late disease: eflornithine (irreversible inhibition of ornithine decarboxylase) and nifurtimox (oxygen radical formation). These would all be CDC specialist medications in the USA. (may not need to know he said we would be looking up these meds) Trypanosomabrucei, the sleeping sickness trypanosome, is spread via biting tsetse flies(wildlife reservoir- hard to clear and swimming around as trypanomsomehematogenouslynot just at bite but CNS). In contrast to T. cruzi, this African trypanosome uses 1000+ genes for antigenic variation of its glycoprotein coat, so that it can effectively evade the immune system. After local proliferation marked by swollen local nodes, hematogenousspread can lead to fever, splenomegaly, and subsequent CNS penetration. 10% of genome changing surface features to change its appearance (Hib, HIV, and influenza- variability in proofreading) deliberately spends a lot of genetic effort in order to get variation that by the time you establish immune response can shift and present w/ a different immune profile. (similar to malaria (go to next river and might be immune to local malaria but not nearby one) and wildlife and grazing oppurtunitiescontinuous reservoir).

Answer 7

Onchocercavolvulus Pathogen category: nematode with microfilarialstage Source: Simuliamblack fly Virulence factors: immune response to microfilarialworms dying; adult worms with surface features that can lessen immune response. Clinical: river blindness Immune response: antibodies and cell-mediated Treatment and/or prevention:ivermectin for months, followed by doxycycline (that addresses the endosymbiont Wolbachia). Onchocercavolvulus, river blindness from the bite of a Simuliamblack fly that lives near flowing water (hence the name of the disease). Onchocercais a filarial worm that has both microfilarialand adult stages. The adult worms become enclosed in subcutaneous fibrous nodules (skin snips are the gold standard for diagnosis), but when the microfilarialworms are born (by the thousands) and die, a strong inflammatory response generates overall pruritus and corneal clouding, in addition to microfilarialinvasion of vessels such as those in the cornea. Live in connective tissue causing disease, black fly can trigger another spread w/out an animal reservoir. Ivermectintriggers chloride influx on ion channels with invertebrate nerves, so leading to hyperpolarization, paralyzing and causing their death (killing adults before they reproduce- killing massive dieoffwill speed up process of autoimmune response). It preferentially kills the microfiliariae. A human population would need to be treated for years to make sure the adults are dead (as they can last 10-15 years within people). While widespread dosing of ivermectin has helped to decrease the parasite load, particularly in the Americas, as of 4/2018 the WHO was reporting transmission still occurring in Brazil and Venezuela.

Answer 8

Schistosomaspecies Pathogen category: fluke (class of flatworm) Source: human andsnail hosts; water spread by penetration of skin by cercarialworm form Virulence factors: incorporation of host proteins onto teguments to minimize immunesurveillance Clinical: chronic inflammation depending on where eggs lodge Immune response: granulomas and eosinophils to the eggs Treatment and/or prevention:sewagecontrol to avoid infecting water; praziquantel l(calcium influx contracting muscle of worms and contraction of things hidden away from outer surface of integument and showing up on radar screen targettingw/ eosinophils-treating over and over again to break the cycle) Trematoda(bloodflukes), e.g., Schistosoma(split body-male permanent honeymoon inside you )or blood flukes requirean intermediate host (snail). The blood flukes are tropical parasites, with millions affected; species distribution depends on where the preferred snail lives. The life cycle of Schistosomainvolves: 1) Skin exposure and penetrance by worm 2) Worm travels through the bloodstream 3) Settles into the liver (preferentially)- fresnutrient food 4) Adult worms live in venous system of liver or around bladder, depending on species, reproducing and laying eggs for decades (Coats in firbonectinto hide) ● 5) Eggs are released into fresh water and hatch into a ciliated form (granulomatous response) 6) Ciliated form swims to snails. 7) Invade snail (all flukes have a snail stage) 8) Increases in snail as other form number as another form 9) Worm form is released to into the water ● There is a strong eosinophilic response to the embedded eggs, which can lead to cirrhosis or bladder cancer, depending on the species and where the eggs are lodging.

Answer 9

Naegleriafowleri Pathogen category: sarcodine(ameba)protozoan Source: warmerfresh waters Virulence factors: cyst form for persistence; mucolytic proteinproduction and subsequent ability to invade cribriform plate to olfactorylobes; complement avoidance Clinical: primary amoebic meningoencephalitis Immune response: neutrophils activatedby TNF-alpha; death occurs before substantive adaptive response generated Treatment and/or prevention:avoidance of nasalexposure; multidrug regimen very rarely effective (once established as lethal as rabies) Naegleriafowleriis a free-living amoeba that is thrives in warm fresh water, and can enter the CNS via the cribriform plate in the ethmoid bone to generate a nearly uniformly fatal primary amoebic meningoencephalitis(PAM). It can encyst under unfavorable conditions or temporarily shift to a flagellated form. Given the very unfavorable prognosis, a variety of agents have been tried. Given the experience of two survivors in 2013, a combination of amphotericin B, fluconazole, rifampin, azithromycin, dexamethasome, and miltefosinehas been used.