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 Protozoans are more diverse than all

other eukaryotes.
 No longer classified in a single kingdom.
 Recently shown that there are at least

seven or more clades.
 May be more than 60 monophyletic
eukaryotic clades.

“Protozoa” is now used informally
without implying phyletic

 Can survive only within narrow environmental ranges.Protozoans  Protozoa  Lack a cell wall  Have at least one motile stage in life cycle  Most ingest their food  Carry on all life activities within a single cell.  Relationships may be mutualistic. . or parasitic.  At least 10.000 species of protozoa are symbiotic in or on other plants or animals.  Very important ecologically. commensalistic.

Cladogram ofthe M ajor D ivisions ofO rganism s .

Cryptosporidium. Leishmania. Acanthamoeba Sporozoea Plasmodium.Toxoplasma. Giardia. Isospora Kinetofragminopho rea Balantidium Naegleria.C lassif c iation Phylum: Sarcomastigop hora Apicomplexa Ciliophora Class Genera: Zoomastigophor a Trypanosoma. Trichomonas Lobosea Entamoeba. .

Life C ycle Stages
 The stages of parasitic protozoa

that actively feed and multiply are
frequently called trophozoites; in
some protozoa, other terms are
used for these stages. Cysts are
stages with a protective membrane
or thickened wall. Protozoan cysts
that must survive outside the host
usually have more resistant walls
than cysts that form in tissues.

EcologicalN iches in the H um an B ody:

 1. Skin: Leishmania
 2. Eye: Acanthamoeba
 3. Mouth: Amoebae and flagellates

(usually non-pathogenic)
 4.Gut: Giardia, Entamoeba
invasion to
liver), Cryptosporidium,
Isospora, Balantidium
 5. G.U. tract: Trichomonas


 Protozoans are an extremely diverse

assortment of unicellular eukaryotes.

leishm ania .

giardia .

trichom onas .

am oeba .


Malaria Pathogenesis and Clinical Presentation .

M alaria Burden  Malaria kills 1.falciparum In India P.5 to 2.falciparum up to 34% Case fatality rate is up to 9% Chloroquine resistance is major concern Multi drug resistance emerged in India .7 m people      world wide every year 95% are due to P.

technically the definitive host because of sexual reproduction  Vertebrates – reptiles. mammals or birds.Plasm odium  Causative agent of malaria “bad air”  Been around since ~3550 BC  General life cycle  2 hosts  Invertebrates – mosquitoes. so vertebrates are the definitive host . intermediate host  Gametocytes form in the blood of vertebrates but fertilization occurs in the gut of the mosquito in the blood of the vertebrate. asexual reproduction here.

releasing merozoites and produce clinical relapse .Relapsing m alaria  P. vivax and P. ovale hypnozoites remain dormant for months  They develop and undergoe preerythrocytic sporogeny  The schizonts rupture.

Life Cycle .

M alaria Transm ission Cycle Exo-erythrocytic (hepatic) Cycle: Sporozoites infect liver cells and develop into schizonts. vivax and P. which release merozoites into the blood Sporozoires injected into human host during blood meal Parasites mature in mosquito midgut and migrate to salivary glands MOSQUITO Parasite undergoes sexual reproduction in the mosquito HUMAN Some merozoites differentiate into male or female gametocyctes Dormant liver stages (hypnozoites) of P. ovale Erythrocytic Cycle: Merozoites infect red blood cells to form schizonts .

Com ponents ofthe M alaria Life Cycle Sporogonic cycle Infective Period Mosquito bites uninfected person Mosquito bites gametocytemic person Mosquito Vector Parasites visible Prepatent Period Human Host Symptom onset Recovery Incubation Period Clinical Illness .

plasm odium .


Life Cycle  Life Cycle (mosquito stages in orange): sporozoite in mosquito salivary glands  injected during feeding  sporozoite in blood  invades hepatocyte  trophozoite in hepatocyte  mitotic division  schizont in hepatocyte  hepatocyte bursts  merozoites in blood  invade RBC  trophozoite in RBC  mitotic division  schizont in RBC  RBC bursts  merozoites in blood  reinvade RBC  schizont or gametocyte in RBC  gametocytes ingested by mosquito  gametes in midgut  fertilization  zygote  elongation  ookinete  penetrates midgut epithelium. meiotic and mitotic division  oocyst containing sporozoites  sporozoite migration in hemolymph  sporozoites in salivary glands .

Anopheles H ead Female 200m Male .

O ocyst 500 m  Oocysts of Plasmodium sp. on the surface of an Anopheles sp. .

Plasm odium Species  4 human plasmodium  P falciparum  P vivax  P malariae  P ovale .

vivax malaria or tertian ague – fever every 48 hours Found in temperate zones. mostly in Asia – 40% of American soldiers in Vietnam had this type Blacks in tropical Africa are resistant May remain as hypnozoites in the liver. not     usually life threatening Causes benign tertian malaraia. relapse of up to 8 years later .Plasm odium vivax  43% of the malaria world wide.

P vivax (cont. they become active amoeba Schüffner’s dots are stippling in the RBCs Hemozoin accumulated in RBC when trophozoite is present 12-24 nuclie in mature schizont Some merozoites develop into gametocytes     Ratio of 2 macrogametocytes to 1 microgametocyte Macrogametocyte is almost is large as RBC Microgametocyte is not nearly as large Mature in about 4 days .)  Merozoites only infect young RBC called      reticulocytes because they contain the right receptors on the surface After the ring stage.

migrate in the hemolymph to the salivary glands  Several thousand may be injected into the host by one mosquito during feeding  In host liver. each will penetrate into an hepatocyte and develop into an exoerythrocytic schizont by way of a trophozoite .Sporozoites of Pl asm odium  Squash prep of an oocyst from an infected vivax mosquito  Sporozoites develop in 10 m oocysts.

Exoerythrocytic Schizonts  Liver cells  Exoerythrocytic schizont. which is a single multinucleate cell  Cytokinesis occurs. some schizonts develop into dormant hypnozoites  May become active and cause a 10 m relapse of the disease years after a supposed cure . vivax and P. and thousands of merozoites burst from the hepatocyte within 1-2 weeks post infection  Merozoites then infect erythrocytes  P. ovale.

vivax by the following features:  Enlarged. 10 m decolorized infected erythrocytes  Prominent Schüffner’s dots  Amoeboid shape of the troph .vivax  Identified as P.Trophozoites of P.

Erythrocytic Schizonts of P. causing a rapid rise in body temperature at 48-hour intervals .vivax  Merozoites invade 10 m host erythrocytes. most undergo schizogony  New merozoites burst out of the cell and immediately infect new cells  Large numbers of infected erythrocytes burst more or less simultaneously.

Plasm odium falciparum  50% of malaria world wide. more irregularly shaped No relapse but can have recrudescence – develop symptoms years later due to resurgence of previously low. subtertian or estivoautumnal malaria Concentrated in the tropics and subtropics Exoerythrocyte stage in liver. most     virulent strain Causes malignant tertian. nondetectable levels of parasitemia (not to be confused with relapse) .

)  Merozoites can infect any RBC.falciparum (cont. can be hard to find in blood smears  RBC develop irregular blotches called Mauer’s clefts that are larger than Schüffner’s granules  Mature schizont is less symmetrical than others  Gametocytes take 10 days to develop and then can be seen in large numbers  Cresent shaped and very distinct . not age dependent  Usually see early ring stage/gametocytes in the blood smear  Smallest ring stage of the 4  Can also bind uninfected RBC – forming a rosettes.P.

falciparum  Young signet ring stage  Diagnostic features are:  High parasitemia  Presence of only signet ring trophozoites.  Double chromatin dots  Multiple infections in some cells  Absence of Schüffner’s dots 10 m  Schizogony results in new infected erythrocytes .Troph of P.

with an average of 20 to 24. every 48 hours  Hemozoin pigment is clumped in the center of the infected RBC  Note that the merozoites are very small. This Erythrocytic schizont s of P. and that the schizont usually does not fill up the RBC .usually is stage not observed in peripheral blood. falciparum 10 m except in very heavy infections  Each schizont produces from 6 to 32 merozoites.

nucleus that is greater than one-half the length of the cell Gametes not produced until in the midgut of a mosquito . lighter blue cytoplasm.G am etocytes of P.falciparum          10 m Macrogametocytes are elongate. nucleus less than one-half the length of the cell Microgametocytes may be shorter and more blunt-ended.

falciparum gametocyte P.D iff erentiation offalciparum P.vivax gametocyte .

falciparum shizont P.D iff erentiation offalciparum P.vivax shizont .

vivax trophozite .falciparum trophozite P.D iff erentiation offalciparum P.

vivax gametocyte .falciparum gametocyte P.D iff erentiation offalciparum P.

Falciparum gam etocytes Male Female .

Electron M icrographs P.falciparum EM P.vivax EM .

Falciparum invading RBC .

of choice .offalciparum  Chloroquine is not the drug of choice  Should not be treated with single drug  Combination therapy is a must  Weaker drugs like Proguanil are of no avail  Artemisinin based CT – ACT is the Rx.D rug Rx.

 Proguanilchlor (chlorguanide)  Sulfadoxin+Pyrimethmine. Dapsone  Tetracyclines. Halofantrine. Clindamycin . Artemether  Mefloquine. Artether. Amodiaquine  Quinine. Chloroquine  Lumefantrine.The Anti-m alarialD rugs  Artesunate. Doxycyclin.

Today’s W atch W ord Combination Therapy (CT) Artemisinin based Combination Therapy (ACT) .

.W hat is CT ?  Anti-malarial combination therapy (CT) is the simultaneous use of two or more blood schizonticidal drugs with different biochemical targets in the parasites and independent modes of action.

.W hat is ACT ?  Artemisinin-based combination therapy (ACT) is an antimalarial combination therapy with an artemisinin derivative as one component of the combination given for at least 3 days.

W hat are Artem isinins ? Artemisinin derivatives Dihydroartemisin Qinghaosu ("ching-how-soo") Ethyl Ether Methyl Ether Arteether Artemether Hemisuccinate Artesunate .

W hy Artem isinins ?  Short half-life. hence good for      combination Rapid substantial reduction of the parasite biomass Rapid resolution of clinical symptoms Effective action against multi-drug resistant P. falciparum Reduction of gametocyte carriage No documented parasite resistance yet .

N o M onotherapy  No Chloroquine for P.falcipatum  No Monotherapy with Artemisinin .

April 2001  Guidelines for the treatment of Malaria WHO document – 266 page book – February 2006 .ACT -W H O G uidelines  Technical Consultation on Anti- malarial Combination Therapy: Geneva.

Artesunate (3 days) + Amodiaquine 3. Amodiaquine + SP (as interim option) .Recom m ended Com binations 1. Artesunate (3 days) + Mefloquine 4. Artemether + Lumefantrine (Lumether) 2. Artesunate (3 days) + SP 5.

.β Artem ether  Methyl ether of Artemisinin  Effective Schizonticidal and gametocidal drug  Short half life 2 .6 hours  Interferes with the conversion of Haem to non toxic hemozoin in the parasite  Not indicated in 1st trimester of preg.

Nausea. itching .β Artem ether side eff ects  Very few and less troublesome  Cough  Body aches  Abd pain. Anorexia  Palpitations  Dizziness. weakness  Skin rash. Vomiting.

AL D osage Schedule .


Artesunate (7 days) + Doxycycline (7) 3. Artesunate (7 days) + Clindamycin (7) or 4.Second line Com binations 1. Quinine in place of AS + any of the above antibiotics for 7 days . Artesunate (7 days) + Tetracycline (7) 2.

W hat to give in pregnancy ?  In 1st trimester   In 2nd and 3rd trimesters     Quinine + Clindamycin 7 days Any ACT combination as per rec. or Artesunate + Clindamycin 7 days or Quinine + Clindamycin 7 days Lactating women same ACT .

Coagulopathy. severe bleeding Hypovolemic shock. convulsions  Renal failure – black water fever  Hyperpyrexia.cerebral malaria. Severe anaemia. hyperparasitemia .Com plications offalciparum m alaria  Coma . Hypoglycemia Metabolic acidosis. acute pulmonary     edema Hemolytic Jaundice.

v infusions  Rectal artemisinins are not as effective .m. then once a day  Artemether 3.m.2 mg/kg i.m od x 3 days or 3 mg/kg od i. given on admission (time = 0). then at 12 h and 24 h.Artem isinins parenteral  αβ Arteether – 150 mg (2ml) i. given on admission then 1. or i.4 mg/kg i.6 mg/kg per day is an acceptable alternative to quinine i. x 3 days  Artesunate 2.v.m.

v infusion Rate-controlled i. infusion is the preferred route of quinine admin. Rectal admin. 10 mg/kg 8th hrly i.m.Q uinine parenteral  A loading dose of quinine of 20 mg     salt/kg bw. injection is a satisfactory alternative.v. then i. is not effective Quinidine can substitute quinine . If this cannot be given safely.

is not effective Quinidine can substitute quinine .m. then i. injection is a satisfactory alternative. If this cannot be given safely.v. 10 mg/kg 8th hrly i. Rectal admin.v infusion Rate-controlled i.Q uinine parenteral  A loading dose of quinine of 20 mg     salt/kg bw. infusion is the preferred route of quinine admin.

The time of poor drugs for poor people is over .

M .αβ ARTEETH ER 150 mg (2 ml amp. intramuscular x 3 days = Total 3 ampoules in a box To be given I.D.) O.