Download Antiprotozoal drugs

Antiprotozoal drugs
Gábor Pozsgai
Pharmacology and Pharmacotherapy
University of Pécs
2012
Characteristics of protozoa
• single-cell organisms
• eukaryotic
• selective toxicity is complicated
– different metabolic pathways
– different amino acid sequences of otherwise
similar proteins
Characteristics of protozoa
• Life cycle includes insect and human hosts
– pest control through application of insecticids
– treatment of parasites in human hosts with
chemotherapeutics
Most frequent diseases caused by
protozoa
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Malaria
Amoebiasis
Trypanosomiasis
Leishmaniasis
Toxoplasmosis
Trichomoniasis
Giardiasis
Malaria
• The most frequent disease in the world
• It is spread by Anopheles mosquitos
• It is mostly imported from Africa to western
countries
Malaria
• Attacks of intermittent fever, shivering
– erythrocytic phase of the protozoa
• Head- and muscle aches
• Hemolytic anemia, splenomegaly
• It might be fatal within a couple of days
Malaria
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Plasmodium falciparum
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
Malaria
Plasmodium falciparum
• It might cause CNS malaria
• Infected red blood cells express PfEMP-1
protein
• That binds CD36, ICAM-1, ELAM-1 and
chondroitin sulfate
• Responsible for decreased elimination of red
blood cells in the spleen
Malaria
Plasmodium falciparum
• „Sludging” in blood vessels
• Ischemia and bleeding in the brain, lungs and
kidneys
• Lethal without treatment
• More than 20% of patients die despite therapy
Malaria
P. vivax und P. ovale
• They leave hypnozoites in the liver
• The disease might get reactivated after
months or years
• Hypnozoites have to be treated with special
medication
Antimalarial drugs
• Primary tissue schizontocidal effect
– pyrimethamine, primaquine, proguanil, atovaquone
• Blood schizontocidal effect
– chloroquine, quinine, proguanil, atovaquone
• Gametocidal effect
– pyrimethamine, primaquine
• Sporontocidal effect
– pyrimethamine
• Secondary tissue schizontocidal effect
– primaquine
Antimalarial drugs
• Symptoms might be healed by blood
schizontocidal drugs
– symptomatic therapy
• Hypnozoites in the liver can only be killed by
secondary tissue schizontocidal drugs
– radical therapy
• Sporontocidal and gametocidal drugs inhibit
transmission between hosts
– prophylactic therapy
Metabolic pathways of plasmodia
Heme metabolism
• Plasmodia cannot synthesize amino acids
• They degrade hemoglobin for amino acids
• These processes take place in food vacuoles
– aspartate proteases (plasmepsine)
– cysteine proteases (falcipain)
– metalloproteases (falcilysin)
Metabolic pathways of plasmodia
Heme metabolism
• Basic amino acids are released
• Toxic ferriprotoporphyrin IX is also produced
– damages lysosomal membranes and kills the
pathogen
– normally it is turned into harmless crystalline
hemozoin by heme polymerase
Metabolic pathways of plasmodia
Electron transport chain
• Not involved in ATP synthesis
• Important in pyrimidine synthesis and this way
in DNA synthesis
• Reactivation of dihydroorotate dehydrogenase
Inhibitors of heme metabolism:
4-aminoquinoline derivatives
Chloroquine
• Root or leaves of Dichroa febrifuga
• Bark of Cinchona trees
• Weak base that accumulates in food vacuoles
of plasmodia
• Binds ferriprotoporphyrin IX and inhibits
detoxification via polymerisation
• Effective in rheumatoid arthritis and SLE
Inhibitors of heme metabolism:
4-aminoquinoline derivatives
Chloroquine
• T1/2 5 days
• Loading dose is necessary
• Accumulates in various tissues
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lungs
liver
spleen
kidneys
leukocytes
etc.
• It is excreted better in acidic urine
Inhibitors of heme metabolism:
4-aminoquinoline derivatives
Chloroquine
• Ineffective against P. falciparum in Africa, Asia
and South-America
• It is not accumulated sufficiently in food vacuoles
• It is removed from the vacuoles by the PfCRT
transporter
– normally prefers basic amino acids
– plasmodia need another independent mutation to
mantain the pH of vacuoles
Inhibitors of heme metabolism:
4-aminoquinoline derivatives
Chloroquine
• Might be used for the treatment of P. vivax, P.
ovale, P. malariae and sensitive P. falciparum
• Suitable for prophylactic treatment
Inhibitors of heme metabolism:
4-aminoquinoline derivatives
Chloroquine
• Relatively safe in humans
– accumulates in infected red blood cells
– only high amounts might neutralize mammalian
lysosomes
Inhibitors of heme metabolism:
4-aminoquinoline derivatives
Chloroquine
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Itch in individulas of dark complexion
Might aggravate psoriasis and porphyria
Hair loss, white hair
Dizziness, confusion, psychosis, retinopathy,
deafness, neuropathy
• Vomiting
Inhibitors of heme metabolism:
4-aminoquinoline derivatives
Chloroquine
• Inhibits excitability of the heart
• Hypotension, shock
• Death (especially in suicide cases and
children)
• Teratogenic
Inhibitors of heme metabolism:
4-aminoquinoline derivatives
Mefloquine
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Unknown mechanism of action
Inhibits the formation of hemozoin lumps
Can only be administered orally
Strong plasma protein binding
Accumulation in erythrocytes
T1/2 13-33 days
Inhibitors of heme metabolism:
4-aminoquinoline derivatives
Mefloquine
• Therapy of chloroquine-resistant P. falciparum
and P. vivax
• Prophylactic treatment of sensitive plasmodia
Inhibitors of heme metabolism:
4-aminoquinoline derivatives
Mefloquine
• Bradycardia, QT elongation
• Insomnia, nightmares, anxiety, depression,
hallucination, psychosis, seizures
• Leukocytosis, thrombocytopenia
• Elevated liver enzymes
• Teratogenic
Inhibitors of heme metabolism:
Cinchona alkaloids
Quinine and quinidine
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Quinidine is an enantiomer of quinine
Pharmacological effects are similar
Inhibition of heme polymerase
Binding of the strands of DNA
Inhibitors of heme metabolism:
Cinchona alkaloids
Quinine and quinidine
• Therapy of acute malaria
• Especially in case of chloroquine-resistant P.
falciparum
Inhibitors of heme metabolism:
Cinchona alkaloids
Quinine and quinidine
• Cinchonism
– tinnitus, headache, nausea, visual disturbances
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Respiratory depression
Negative cardiac effects
Vasodilatation, hypotension
Perspiration
Inhibitors of heme metabolism:
Cinchona alkaloids
Quinine and quinidine
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Hemolysis, leukopenia, thrombopenia
Hepatotoxic
Hypoglycemia
Smooth muscle contraction
– contraindicated in pregnancy
– plasmodia released from the spleen might trigger
fever attack
Inhibitors of heme metabolism:
artemisinin and derivatives
Artemisinin, artesunate, artemether
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Activated by free or heme-bound iron
Production of a reactive radical
Alkylation of proteins and heme
Mechanism of selectivity is not fully
understood
– heme is necessary for the activation
– accumulation in plasmodia
Inhibitors of heme metabolism:
artemisinin and derivatives
Artemisinin, artesunate, artemether
• First choice drugs in case of acute malaria in
Africa and Southeast-Asia
• No resistant strains are known
– T1/2 only 1-11 hours
– always in combination
• Not suitable for prophylaxis
Inhibitors of heme metabolism:
artemisinin and derivatives
Artemisinin, artesunate, artemether
• Neurotoxicity, headache, dizziness
• Cardiotoxicity, elongated QT interval
Inhibitors of the respiratory chain:
8-aminoquinoline derivatives
Primaquine
• Secondary tissue schizontocidal effect
– hypnozoits of P. vivax and P. ovale
• No blood schizontocidal effect
– not suitable for the treatment of acute disease
• An active metabolite inhibits the function of
ubiquinone
• Other metabolites damage mitochondria of
plasmodia oxidatively
Inhibitors of the respiratory chain:
8-aminoquinoline derivatives
Primaquine
• Effective against exoerythrocytic forms of P.
falciparum, P. vivax and P. ovale
• Gametocidal against all plasmodia
Inhibitors of the respiratory chain:
8-aminoquinoline derivatives
Primaquine
• Leukopenia
• Methemoglobinemia, hemolysis
– especially in individuals lacking glucose-6phosphate dehydrogenase activity
– enzyme activity has to be checked every time
before initiation of therapy
– might lead to life-threatening hemolysis of the
fetus in pregnancy
Inhibitors of the respiratory chain:
ubiquinone analogues
Atovaquone
• Inhibition of pyrimidine synthesis
• Other metabolic pathways are probably
inhibited, too
• Hundred fold higher affinity to cytochrome bc1
protein of plasmodia
• A single point mutation renders the pathogen
resistant
Inhibitors of the respiratory chain:
ubiquinone analogues
Atovaquone
• Always in combination with doxycycline or
proguanil
• Synergistic effects of proguanil and
atovaquone
– not related to inhibition of folic acid synthesis by
proguanil
– proguanil might induce uncoupling in plasmodia
Inhibitors of the respiratory chain:
ubiquinone analogues
Atovaquone
• Suitable for both treatment and prophylaxis of
malaria
• Effective against Toxoplasma and P. jirovecii
Inhibitors of the respiratory chain:
ubiquinone analogues
Atovaquone
• Lipophilic, poor absorption
– better absorption when taken with a fatty meal
• Strong plasma protein binding
• T1/2 2-4 days
Inhibitors of the respiratory chain:
ubiquinone analogues
Atovaquone
• Headache, dyssomnia
• Nausea, diarrhoea
• Rash
Inhibitors of protein synthesis
Doxycycline
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Tetracycline antibiotic
Inhibition of protein synthesis of apicolpasts
Delayed effect
Effective against erythrocytic schizonts
Unsuitable for monotherapy
Inhibitors of protein synthesis
Doxycycline
• In case of suspected multiresistance it might
be combined with quinine
• Suitable for prophylaxis of malaria even in
case of chloroquine resistance
• Not licenced for malaria prophylaxis in some
European countries
Inhibitors of protein synthesis
Clindamycin
• Active against erythrocytic schizonts
• In pregnancy and for children because they
cannot be administered tetracycline
antibiotics
• After treatment with quinine, quinidine or
artesunate
Inhibitors of folic acid synthesis
Proguanil, pyrimethamine
• Inhibitors of protozoal dihydrofolic acid reductase
• Only in combination due to fast development of
resistance
• Delayed effect
• Synergistic effects with some other medications
– pyrimethamine + sulfadoxine (fansidar)
– proguanil + atovaquone (malarone)
Inhibitors of folic acid synthesis
Proguanil, pyrimethamine
• Pyrimethamine is also active against
Toxoplasma
• Pyrimethamine might be administered once
weakly for prophylaxis due to its long half life
• Therapy has to be continued for 6 weeks after
the journey
• Unsuitable for acute treatment
Inhibitors of folic acid synthesis
Proguanil, pyrimethamine
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Abdominal distress, diarrhoea
Hematuria
Macrocytic anemia
Might be prevented by administration of folic
acid
Table 53-2. Summary of drugs used for treatment and chemoprophylaxis of malariaa
Infections
Infection with chloroquine-resistant
Plasmodium falciparum or with
unknown or mixed organisms
Typical drug choices for acute
attacks
Oral quinine plus: proguanil +
atovoquone;b or artemether +
lumefantrinec
Typical drug choices for
chemoprophylaxis
Short term (weeks):
atovoquone + proguanil or doxycycline
Long term (months/years):
chloroquine + proguanil or atovoquone
+ proguanil
a
It must be appreciated that this is only a summary, not a definitive guide to prescription, as the recommended drug combinations vary depending
on the patient, the area visited, the overall risk of infection, the presence of resistant forms of the disease and so on. This information is based on
current UK recommendations (source: British National Formulary 2008).
b Malarone is a proprietary combination of atovoquone and proguanil hydrochloride.
c Riamet is a proprietary combination of artemether and lumefantrine.
Rang et al: Rang & Dale’s Pharmacology, 7e
Copyright © 2011 by Churchill Livingstone, an imprint of Elsevier Ltd. All rights reserved.
Amoebiasis
• Caused by Entamoeba hystolytica
• E. dispar is similar, but it is not a human pathogen
• Cysts reach the gastrointestinal tract with
contaminated beverages or food
• Occurance of invasive disease depends on
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the number of ingested cysts
the strain of the pathogen
intestinal motility
presence of bacteria serving as food for the parasite
Amoebiasis
• Cysts are inactive, but infectious
• Excystation and ripening of trophozoites
occurs in the intestine
• Trophozoites are able to move with
pseudopodia and consume bacteria, other
protozoa, intestinal cells and erythrocytes
Amoebiasis
• Trophozoites turn into binuclear, then
quadrinuclear cysts excreted with the feces
• Trophozoites spread sideways
• Trophozoites sometimes penetrate deeper
into the colon, perforation might occur
• This way the parasite might enter the portal
circulation and induce the formation of
hepatic abscesses
Amoebiasis
• Diarrhoea, abdominal cramps, dysentery
• Hepatic abscess
• Symptoms often occur days or even years
after infection
• Patients are frequently asymptomatic, but
infectious
Amoebiasis
• E. hystolytica lacks the following enzymes
– enzymes of fermentation
– enzymes of ative phosphorylation
– enzymes of the Krebs cycle
– pyruvate dehydrogenase
• The parasite depends on the metabolism of
glucose to ethanol
Amoebiasis
• Some enzymes are specific for luminal
protozoa and anaerobic bacteria
• Pyruvate-ferredoxin oxidoreductase (PFOR)
and alcohol dehydrogenase E are of
significance
• They contain ferredoxin
Amoebiasis
Metronidazole
• Prodrug
• Activated by
– reduced ferredoxin
– specific nitroreductase
• Proteins, membranes and DNA are damaged
by radicals produced
Amoebiasis
Metronidazole
• Only active against tissue trophozoites
• Distributed in the intracellular compartment,
bones and adscesses
• Inactive against luminal parasites
– absorbed in the samll intestine
– only small amount reaches the colon
• Invasive amoebiasis is first treated with
metronidazole, then with drugs that are active
against luminal trophozoites
Amoebiasis
Metronidazole
• Resistance
– mutated nitroreductase
– lowered expression of ferredoxin
– decreased PFOR activity
– decreased permeability of parasites
Amoebiasis
Metronidazole
• Resistance is rare amongst luminal protozoa
– diploid genetic material
– no alternative pathways for PFOR
– metronidazole is a substrate of P-glycoprotein
Amoebiasis
Metronidazole
• Headache, neuropathy, encephalopathy,
seizures, metallic taste
• Nausea, abdominal discomfort, pancreatitis
• Dark urine
• Disulfiram-like effect
• Contraindicated in pregnancy
Amoebiasis
Tinidazole
• Similar mechanism of action
• Longer half life
• Fewer side effects
Amoebiasis
Emetine, dehydroemetine
• Active against tissue trophozoites
• Only used if metronidazole is contraindicated
due to severe side effects
• Dehydroemetine is favoured for its fewer side
effects
Amoebiasis
Emetine, dehydroemetine
• Binds 40S ribosome subunits and inhibits
eukaryotic protein synthesis
• Administered s.c. or i.m.
Amoebiasis
Emetine, dehydroemetine
• Sterile abscesses
• Arrhythmia, cardiac failure, hypotension
• Hepatotoxic, nephrotoxic, cardiotoxic and
damages skeletal muscles
• Myopathy, cardiomyopathy
• Unsuitable for children and pregnant women
Amoebiasis
Diiodohydroxyquinoline (iodoquinol)
• Luminal amoebicidal effect
• Low absorption
• Forms complexes with iron that is essential for
parasites
Amoebiasis
Diiodohydroxyquinoline (iodoquinol)
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Optic and peripheral neuropathy
Enlarged thyroid
Nausea, diarrhoea, abdominal discomfort
Itch, rash
Amoebiasis
Diloxanide furoate
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Luminal amoebicidal effect
Hydrolized into diloxanide and furoate
90% of diloxanide is absorbed
Diloxanide remaining in the colon is
responsible for the amoebicidal effect
Amoebiasis
Diloxanide furoate
• Nausea, flatulence
• Unsuitable for children and pregnant women
Amoebiasis
Paramomycin
• Aminoglycoside antibiotic
• Low intestinal absorption
• Used only orally
– systemic administration would induce severe side
effects
Toxoplasmosis
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The pathogen is Toxoplasma gondii
Animal hosts are mammals and birds
Transferred by food
Disease progression depends on host
immunity
• The disease is mostly asymptomatic
Toxoplasmosis
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Infection often occurs transplacentarily
Meningitis, encephalitis
Intraocular infection
Lymphadenopathy
Immunocompetent patients with
lymphadenopathy only do not need
pharmacotherapy
Toxoplasmosis
• Pharmacotherapy is required in the following
situations:
– disease affects organs
– chorioretinitis
– acute infection during pregnancy
– connatal toxoplasmosis in children
Toxoplasmosis
Pyrimethamine + sulfadiazine
• Synergistic inhibition of folic acid synthesis
• Folic acid has to be administered to prevent
myelosuppression
Toxoplasmosis
Spiramycin
• Macrolide antibiotic
• Therapy of children and pregnant women with
acute infection
• Does not totally prevent fetal infection, but
lowers its incidence
Trypanosomiasis
African trypanosomiasis
• Sleeping sickness
• Trypanosoma brucei gambiense, T. brucei
rhodesiense
• Intermediate hosts are tsetse flies
• At the site of the bite a primary chancre might
occur
• From the primary chancre protozoa reach the
circulation and lymphatic organs
Trypanosomiasis
African trypanosomiasis
• Generalized lymphadenopathy, fever
• Parasites reach the CNS through the
circulation
• Meningoencephalitis and narcoleptic state are
induced
• High mortality
Trypanosomiasis
African trypanosomiasis
• West-African sleeping sickness is more
dangerous
– early CNS involvement
– cardiomyopathy
– fast disease progression
Trypanosomiasis
Pentamidine
• Treatment of early phase of T. brucei
gambiense infection
• In combination with suramin
• T. brucei rhodesiense might be sensitive, too
• Second choice drug for P. jirovecii pneumonia
Trypanosomiasis
Pentamidine
• Positively charged molecule
• Transported actively into parasites
• Binds negatively charged molecules
Trypanosomiasis
Pentamidine
• Synthesis of DNA, RNA, proteins and
phospholipids are inhibited
• High affinity to DNA of kinetoplasts
• Dihydrofolic acid reductase and
topoisomerase II are inhibited, too
Trypanosomiasis
Pentamidine
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Administered slowly i.v.
Might also be given i.m. or inhaled
Accumulates in various tissues
T1/2 10 days
Very slow elimination
Trypanosomiasis
Pentamidine
• Frequent and potentially fatal side effects
• Nephrotoxic
• Sterile abscess at the site of i.m.
administration
• Dizziness, headache, nausea, dispnoea,
tachycardia
– due to histamine release
Trypanosomiasis
Pentamidine
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Elongated QT interval
Pancreatitis
Diabetes, hypo- or hyperglycemia
Hepatitis
Changes of blood counts
Trypanosomiasis
Suramin
• Also known as Germanin
• Tretament of early phase of african
trypanosomiasis
• High electronegativity, poor absorption
• Strong plasma protein binding
• Administered i.v.
Trypanosomiasis
Suramin
• Interaction with various macromolecules
• Inhibition of the following enzymes
– glycerolphosphate dehydrogenase
– RNA polymerase
Trypanosomiasis
Suramin
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Fatigue, unconciousness
Headache, joint aches, ocular irritation
Neuropathy
Nausea
Seizures, shock
Nephrotoxic
Hemolytic anemia, agranulocytosis
Trypanosomiasis
Melarsoprol
• First choice drug for the treatment of late
phase of sleeping sickness
• Lipophilic and reaches the CNS
• Contains arsenic and only soluble in propylene
glycol
• Damages plastic bottles
Trypanosomiasis
Melarsoprol
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Inhibits protozoal pyruvate kinase
Inhibits the uptake of adenine and adenosine
mammalian cells less permeable for the drug
Treatment is fatal in 5% of the cases
Trypanosomiasis
Melarsoprol
• Phlebitis
• Reactive encephalitis
– mortality is over 50%
– risk might be lowered by steroid administration
• Polyneuropathy
– necessitates thiamine administration
Trypanosomiasis
Tryparsamide
• Treatment of T. brucei gambiense infection
• Crosses the blood-brain barrier
Trypanosomiasis
Eflornithine
• Treatment of early and late phases of WestAfrican trypanosomiasis
• Only slowly degraded by T. brucei gambiense
• Faster eliminated by T. brucei rhodesiense and
human cells renders these less sensitive to the
drug
Trypanosomiasis
Eflornithine
• Selective irreversible inhibitor of ornithine
decarboxylase
– the enzyme produces putrescine from ornithine
– this is the rate limiting step in the synthesis of
spermine and spermidine
– these are involved in nucleic acid synthesis and
regulate protein synthesis of the parasite
– inhibited polyamine synthesis
Trypanosomiasis
Eflornithine
• Nausea
• Seizures
• Hair loss
– used in the treatment of hirsutismus
• Fever
• Anemia, thrombocytopenia, leukopenia
Trypanosomiasis
American trypanosomiasis
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Chagas disease
Caused by T. cruzi
Intermediate hosts are triatomine bugs
Human infection is caused by rubbing the
insect feces into bite wounds or naïve
conjunctiva
Trypanosomiasis
American trypanosomiasis
• Transplacentar infection might occur and
breastmilk might also spread the disease
• Site of infection becomes swollen (Romana sign
in the ocular area)
• Acute phase only occurs in immunocompromised
patients
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–
–
–
fever, lymphadenopathy, edema
diarrhoea, abdominal discomfort
seizures
enlarged heart
Trypanosomiasis
American trypanosomiasis
• Latent phase might take years
• Chronic disease
– dilated cardiomyopathy
– megaesophagus, megacolon
– intestinal occlusion, penetration, peritonitis
Trypanosomiasis
Nifurtimox
• Prodrug
• Yields nitroaryl radicals if reduced
• These produce superoxide and hydrogen
peroxide if oxidized
Trypanosomiasis
Nifurtimox
• Trypanosomes are sensitive because they lack
catalase
• Mammalian cells contain catalase, superoxide
dismutase and glutathione peroxidase
• Oral administration
• Progression of intestinal and cardiac disease
frequently fails to respond to therapy
Trypanosomiasis
Nifurtimox
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•
•
•
Nausea, abdominal discomfort
Rash
Dyssomnia, agitation, damaged memory
Neuropathy, seizures
Leishmaniasis
Three different presentations of the disease
• Kala azar (visceral leishmaniasis)
– spleen and liver involvement
• Oriental sore (cutaneous leishmaniasis)
– skin symptoms
– spontaneous improvement
• Espundia (mucocutaneous leishmaniasis)
– involvement of mucous membranes of the upper
airways and gastrointestinal tract
Leishmaniasis
•
•
•
•
Intermediate hosts are sand flies
Disease is pread by the saliva of the insect
Parasites are taken up by phagocytes
Disease progression depends on
– the strain of the pathogen
– the distribution of infected macrophages
– the state of the immune system
Leishmaniasis
Sodium stibogluconate, meglumine antimonate
• Contain antimony
• Mechanism of action is not fully understood
• Glycolysis and fatty acid oxidation of the
parasite might be inhibited
• Antimony reacts with sulfhydryl moieties
Leishmaniasis
Sodium stibogluconate, meglumine antimonate
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•
•
•
•
•
Myelosuppression
Disorders of circulation, shock
Elongated QT interval
Hepatotoxic
Pancreatitis
Rash
Leishmaniasis
Amphotericin B
• In case of resistance for stibogluconate
• Frequent in India
Leishmaniasis
Paramomycin
• Only applied topically due to severe side
effects
• Except systemic administration in case of
visceral leishmaniasis
• Ototoxic
• Hepatotoxic
• No nephrotoxicity has been reported
Leishmaniasis
Miltefosine
• Synthetic ether analogue of phospholipids
• Mechanism of action is unknown
• Antineoplastic, immunomodulatory and
antiprotozoal effects
• Administered orally
Leishmaniasis
Miltefosine
• Inhibition of enzymes in the plasma
membrane
– protein kinase C
• Inhibited phosphatidylcholine synthesis
• Inhibited PAF production
• Inhibited inositol phosphate synthesis
Leishmaniasis
Miltefosine
•
•
•
•
Enhanced T cell activation
Increased INF-γ release
Increased expression of IL-2 receptors
Increased expression of MHC molecules
Leishmaniasis
Miltefosine
•
•
•
•
Nausea, diarrhoea
Hepatotoxic
Nephrotoxic
Teratogenic
Trichomoniasis and giardiasis
• Trichomoniasis affects vaginal and urethral
mucous membranes
• Often asymptomatic, but activated in case of
immunosuppression or mixed infection
• T. vaginalis is transmitted sexually
• Sexual partners of the patient have to be
treated, as well
Trichomoniasis and giardiasis
• Giardiasis is the most frequent protozoal
infection in developing countries
• Often asymptomatic
• Resides in the duodenum
• Malabsorption, steatorrhoea and weight loss
might occur
• Transmitted by feces
• Intermediate hosts might be animals or
humans
Trichomoniasis and giardiasis
Metronidazole, nimorazole, tinidazole
• Resistance is rare