MALARIA

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• MALARIA
• Four Plasmodium species are responsible for
  human malaria
• P. falciparum malignant tertian malaria
• P. vivax, benign tertian malaria
• P. ovale ovale tertian malaria
• P. malariae. quartan malaria

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• There are an estimated
• 200 million cases of malaria leading to
  mortality of more than one million people per
  year.

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• P.falciparum and P.malariae are the most
  common species and are found in Asia and Africa.
• P. vivax predominates in Latin America, India and
  Pakistan.
• P. ovale is almost found in Africa.

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• Malarial parasites are transmitted by female
  anopheline mosquito which injects sporozoites
  present in the saliva of the insect.
• Sporozoites infect the liver parenchymal cells
  where they may remain dormant (hypnozoites) or
  undergo stages of schizogony to produce schizonts
  (merogony) to produce merozoites (meronts).

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• When parenchymal cells rupture, thousands of
  meronts are released into blood and infect the
  red cells
• The liver cycle (extra-erythrocytic or pre-
  erythrocytic ) takes 5-15 days whereas the
  erythrocytic cycle takes 48 hours or 72 hours (P.
  malariae).
• Malaria can be transmitted by transfusion and
  transplacental.

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• In red cells, the parasites mature into
  trophozoites. These trophozoites undergo
  schizogony (merogony) in red cells which burst
  and release merozoites.
• Some of the merozoites transform into male and
  female gametocytes while others enter red cells
  to continue the erythrocytic cycle.

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sporozoites
Primary pre-erythrocytic cycle in liver
gametocytes
erythrocytic cycle
Hypnozoites
in P.vivaxP. ovale
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• The gametocytes taken by the female mosquito, the
  microgametes penetrate the macrogametes
  generating zygotes . 
• The zygotes become motile ookinetes which invade
  the midgut wall of the mosquito where they
  develop into oocysts . 
• The oocysts rupture, and release sporozoites ,
  which go to the mosquito's salivary glands
  (sporogony)
• Inoculation of the sporozoites into a new human
  host inchoate the malaria life cycle. (Infective
  stage)

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• Asexual cycle in vertebrate.
• Sexual cycle in invertebrate.
• .

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The malaria parasite life cycle involves two hosts

• - Intermediate host
• Vertebrate host Asexual cycle
• a-Exo-erythrocytic or pre-erythrocytic
• schizogony (merogony)
• b -Erythrocytic schizogony
• c -Gametogony
• - Definitive host
• Invertebrate host Sexual cycle
•  sporogony

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• Clinical features (fever)
• Cold stage rigor (cold and shivers)
• headache (half-1 hour)
• Fever (hot) stage
• temperature rises to maximum ,sever headache
  pain in back and joints vomiting and diarrhea
  (1-4 h)
• Sweating stage patient perspires temperature fall
  and patient relieved until the next rigor
  (1-4h).
• Cold- hot- sweating - normal

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• Incubation period
• Primary attack
• Malarial paroxysm
• cold -hot sweating normal
• Repeated attack
• Relapse
• recrudescence

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• Recrudescence of falciparum it is caused by
  parasites persisting in circulation at sub
  clinical level following previous attack.
• Malarial relapse due to delayed development of
  hypnozoites in liver
• There is no hypnozoites in falciparum

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Plasmodium falciparum
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• IN life cycle of P.falciparum
• There is No hypnozoite stage
• no relapse.
• Erythrocytic cycle takes 36-48 hours
• Schizont contain 8-32 merozoites .
• Large number of RBCs infected and
• many cell contain more than one
• trophozoite.
• only ring stage and gametocyte
• in peripheral blood.

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• Anemia can be sever and rapid
• Mainly due to mechanical distraction of
  parasitised RBCs.
• RBCs Phagocytosed in spleen and destroyed Due to
  lose of deformability .
• Aplastic anemia due to effect of malarial toxins
  on B.M.
• Hemolytic destruction (immune sensitization).

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• Erythrocytic schizogony take place in capillaries
  of deep organs.
• (Ring and gametocyte only that appeared in
  blood film).
• Adhererance phenomena lead to congestion ,hypoxia
  ,blockage and rupture of small blood vessels,
  (DIC) disseminated intravascular coagulation.
• High level of parasitaemia up to 30-40 of RBCs
  infected (5 considers sever).
• Cerebral malaria parasitized RBCS and fibrin
  block capillaries and small bl. Vessels (may
  causing un-arousable coma)

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• Black-water fever rapid and massive
  intravascular hemolysis of both parasitized and
  non-parasitized RBCs
• Urin appears dark red to brown-black Renal
  failure hemoglbinurea
• Diarrhea and vomiting
• Pulmonary edema
• Hypoglycemia
• Hyperpyrexia
• Pregnant women

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• Child with severe malaria, anemia, acidosis and
  respiratory distress

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• P. ovale and P. vivax infect immature red blood
  cells
• P. malariae infects mature red cells.
• P. falciparum infects both.

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• Laboratory Diagnosis
• microscopic identification of parasites in blood
  is most certain method of confirming infection
  with plasmodium.
• Examination of thick (large amount) and thin
  blood film relation of parasite to RBCs and rate
  of infection
• Serologloy used in epidemiology.

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• Thick smear should be examined in all suspected
  cases of malaria because of its ability to detect
  parasites even when the parasitemia is low.
• A thin film is used for species and stage
  identification and to provide information
  regarding erythrocytes, leukocytes, and
  platelets.

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• High parasitemia, growing stages of parasites
  (trophozoites and schizonts) and pigment-laden
  neutrophils indicate poor prognosis.
• In case of uncertainty in identification of the
  species in severe malaria patients, it should
  always be considered as
• P. falciparum.

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P.f. ring
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Plasmodium falciparum schizonte
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Plasmodium falciparum gametocyte
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• Plasmodiun vivax
• Rarely infected RBCs exceed 2
• infection less sever than P.f.
• P.v synchronized regular 48h pattern of fever
• All form of parasites trophozoites ,schizontes
  and gametocyte can be found in blood films.
• enlargement of RBCS, schuffners dotes
• Spleen enlargement and anemia
• Relapse are feature of P.vivax
• Patient must receive treatment both for attack
  and against relapsing form. (primaquine)

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Plasmodium vivax ring stage of trophozoite
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Plasmodium vivax schizontes
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Plasmodium vivax gametocyte
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• Plasmodium malariae
• Cycle synchronized every 72 h.(quarten)
• Spleen enlarge early.
• Nephrotic syndrome which progress to renal
  failure caused by damage to kidney following
  deposion of antigen-antibody complex on
  glomerular membrane of kidney (proteinuria ,low
  serum albumin oedema)
• Recrudescence can occur.

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Plasmodium malariae trophozoit
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Plasmodium malariae schizont
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Plasmodium malariae gametocyte
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Plasmodium oval ring, ameboid, schizont
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Plasmodium oval gametocyte
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Disease Severity and Duration

vivax ovale malariae falciparum
Initial Paraoxysm Severity moderate to severe mild moderate to severe severe
Average Parasitemia (mm3) 20,000 9,000 6,000 50,000-500,000
Maximum Parasitemia (mm3) 50,000 30,000 20,000 2,500,000
Symptom Duration (untreated) 3-8 weeks 2-3 weeks 3-24 weeks 2-3 weeks
Maximum Infection Duration (untreated) 5-8 years 12-20 months 20-50 years 6-17 months
Anemia
Complications renal cerebral
Modified from Markell and Voge's Medical Parasitology Modified from Markell and Voge's Medical Parasitology Modified from Markell and Voge's Medical Parasitology Modified from Markell and Voge's Medical Parasitology Modified from Markell and Voge's Medical Parasitology
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• High parasitemia, growing stages of parasites
  (trophozoites and schizonts) and pigment-laden
  neutrophils indicate poor prognosis.
• In case of uncertainty in identification of the
  species in severe malaria,it should always be
  considered as P. falciparum.

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Clinical symptoms
Patent parasitemia
Subpatent parasitemia
Exoerthrocytic shizogony ( Liver)
Primary hepatic form and hypnozoites
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• Geographical Distributions
• p.vivax widespread in tropical and subtropical
  areas
• range extends into temperate areas
• relatively uncommon in Africa
• P falciparum. widespread, but primarily in
  tropics and subtropics
• P malariae broad, but spotty geographical
  distribution
• P. ovale
• primarily tropical Africa, especially western
  coast

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• Diagnosis
• history of being in endemic area
• symptoms fever, chills, headache, malaise
• splenomegaly, anemia
• microscopic demonstration of parasite (blood
  smear)
• antigen detection PCR amplification of parasite
  DNA

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• Treatment
• Blood stages
• erythrocytic stages (Asexual schizogony)
• Chloroquine
• Quinine
• pyrimethamine sulfadoxine
• (fansidar)
• Mefloquine, halofantrine
• Gametocytes primaquine
• Liver stages (in vivax, ovale species)
• primaquine

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• In malignant malaria all is right except
• black water fever.
• Relapse .
• disseminated intravascular coagulation (DIC).
• Adhesion phenomena.
• Cerebral malaria.
• Acute renal failure

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• In benign tertian malaria all can occur except
• attack every 48 hours.
• Relapse
• Splenomegaly
• Un arousable coma
• High parasitamia

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• In Erythrocytic cycle of P.vivax
• Enlargement of RBCs.
• schuffners dots.
• DIC.
• Splenomegaly anaemia
• recrudescence

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• In P.falciparum
• High parasitemia
• Multiple infection.
• Enlargement of RBCs
• Erythrocytic tertian or sub tertian schizogony.
• Maurers dots
• Adhesion phenomena (DIC)

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• In P. malariae
• Splenomegaly
• Band shape trophozoites.
• Recrudescence
• Antigen antibodes complex depostion in glomeruli
  with nephrotic syndrome
• relapse

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• Inoculation of the sporozoites into a new human
  host lead to inchoation of
• 1 Exo-erythrocytic cycle (Tissue cycle)
  Pre-erythrocytic cycle
• 2 -Erythrocytic cycle.
• 3 -Sporogonic cycle.
• 4 -Sexual cycle.

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• Malarial releapse is due to
• Merozoite.
• Sporozoite.
• Hypnozoite.
• trophozoite
• schizonte

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• The clinical manifestations of the disease is due
  to
• Erythrocytic cycle.
• Exo-erthrocytic cycle.
• Sporogonic cycle.
• Rupture of infected RBC and release malarial
  pigments and toxin.

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• Infective stage in saliva of female Anopheles is
• Merozoite.
• Schizonte.
• Trophozoite.
• Sporozoite.

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• Feature of intestinal and tissue
• protozoa
• Entamoeba histolytica, G.lamblia are motile
  organisms that multiply and encyst in intestinal
  tract. they form cyst which excreted in faces.
  Invasive strains of
• E histolytica multiply in intestinal wall.
• Cryptospordium multiply intracellular in cells.
  It produces oocysts which are excreted in feces.
• T.gondii muliply intracelluler in
  reticuloendothelial cell and cell of brain and
  other organs of body.
• T.vaginalis is motile and multiplies in the
  urogenital tract cyst forms are unknown

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• Infection is by ingesting
• cysts (E.histolytica, G.lamblia) or
• oocyst (Cryptosporidium,T.gondii)
• in food,water,or from hands contaminated with
  infected feces.
• T.gondii can also be transmitted congenitally
  and by ingesting the parasites in under-cooked
  meat of intermediate hosts.
• T.vaginalis is transmitted sexually (no cyst).
• Humans are important hosts of E. histolytica,
  G.lamblia and T.vaginalis.
• Animal are natural definitive hosts of
  Cryptosporidium and T.gondii .

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• Laboratory confirmation of E.histolytica
  infection is by finding amoebae or cysts in feces
  or by detecting antibodies in serum (invasive
  amoebiasis)
• Giardiasis diagnosed by finding motile
  flagellates or cysts in feces or flagellates in
  duodenal aspirates.
• Infection with Cryptosporidium is diagnosed by
  finding oocyst in feces
• Toxoplasmosis is usually diagnosed
  serologically.
• T. vaginalis infection is usually confirmed by
  detecting flagellates in vaginal or uretheral
  discharge or urine.

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