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Malaria

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Alternative names: Quartan malaria Falciparum malaria

Blackwater fever Tertian malaria

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A vector-borne infectiousdisease caused by protozoanparasites.It is widespread in tropical andsubtropical regions

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A bite from an infective female Anopheles mosquito.

Anopheles must be infectedthrough a previous blood mealtaken on an infected person to

transmit malaria

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At risk for malaria:

40% of the worlds population

more than 500 million are ill of malaria

yearlyIf treated in the early stages, malaria can becured.

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IV , malaria and TB are among the most important infectious agents in the world.

There are no vaccines against them, and all have the

same property of establishing chronicinfection without an effective immune

response

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Plasmodium falciparum - most

common and deadly type of malariainfection - can lead to cerebral malaria

P.vivax - most common - causes relapse if treatment was notcompleted.

P.malaria

P.ovale.

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Female Anopheles are:

Anthropophilic : from humansZoophilic : from animalsEndophagic : prefer to bite indoorsExophagic : prefer outdoor biting

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Liver Stage. Human infection is initiated when sporozoites areinjected with the saliva during mosquito feeding. The sporozoitesenter the circulatory system and within 30-60 minutes will invade aliver cell. Host cell entry, as in all apicomplexa, is facilitated by theapical organelles. After invading the hepatocyte, the parasiteundergoes an asexual replication. This replicative stage is oftencalled exoerythrocytic or pre-erythrocytic) schizogony .

PATHOPHYSIOLOGY:

In P. vivax and P. ovale some of the sporozoites donot immediately undergo asexual replication, butenter a dormant phase known as the hypnozoite .This hypnozoite can reactivate and undergoschizogony at a later time resulting in a relapse.

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Blood Stage. Merozoites released from theinfected liver cells invade erythrocytes. Themerozoites recognize specific proteins on the

surface of the erythrocyte and activelyinvade the cell in a manner similar to otherapicomplexan parasites.

After entering the erythrocyte the parasite undergoes atrophic period followed by an asexual replication. Theyoung trophozoite is often called a ring form due to itsmorphology in Geimsa-stained blood smears. As theparasite increases in size this 'ring' morphologydisappears and it is called a trophozoite . During the

trophic period the parasite ingests the host cellcytoplasm and breaks down the hemoglobin into aminoacids. A by-product of the hemoglobin digestion is themalaria pigment, or hemozoin. These golden-brown toblack granules have been long recognized as adistinctive feature of blood-stage parasites.

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Nuclear division marks the end of thetrophozoite stage and the beginning of theschizont stage. Erythrocytic schizogongyconsists of 3-5 rounds (depending on species)of nuclear replication followed by a budding

process. Late stage schizonts in which theindividual merozoites become discernableare called segmenters . The host erythrocyteruptures and releases the merozoites. Thesemerozoites invade new erythrocytes andinitiate another round of schizogony. The

blood-stage parasites within a host usuallyundergo a synchronous schizogony.

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Sexual Stage. As an alternative to schizogony some ofthe parasites will undergo a sexual cycle and terminallydifferentiate into either micro- or macrogametocytes .

Gametocytes do not cause pathology in the human hostand will disappear from the circulation if not taken up by

a mosquito.

Gametogenesis, or the formation of micro- andmacrogametes , is induced when the gametocytes are

ingested by a mosquito. After ingestion by the mosquito,the microgametocyte undergoes three rounds of nuclear

replication. The macrogametocytes mature intomacrogametes.

The highly mobile microgametes will seek out and fuse witha macrogamete. Within 12-24 hours the resulting zygote develops into an ookinete . The ookinete is a motile invasivestage which will transverse both the peritrophic matrix and

the midgut epithelium of the mosquito.

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Sporogony. After reaching the extracellular space betweenthe epithelial cells and the basal lamina, the ookinete

develops into an oocyst . The oocysts undergo an asexualreplication, called sporogony, which culminates in theproduction of several thousand sporozoites . This generallytakes 10-28 days depending on species and temperature.Upon maturation the oocyst ruptures and releases thesporozoites which cross the basal lamina into the hemocoel

(body cavity) of the mosquito.

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Exoerythrocytic schizogony andprepatent and incubation periods

P.falciparu

mP. vivax P. oval e P. malar iae

Prepatentperiod

(days)

6-9 8-12 10-14 15-18

Incubation period(days)

7-14 12-17 16-18 18-40

Merozoite

maturation (days) 5-7 6-8 9 12-16

Merozoitesproduced

40,000 10,000 15,000 2000

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P. falciparum P. vivax P. ovale P. malar iae H ypnozoite -- + + --Size of RBC normal normal normal normalParasi te size 1/3 1/3 1/3 1/6

M ulti parasite -- -- + --Schff nr s duts -- -- + --* Tr ophzoite:Size of RBC normal enlarge enlarge normalParasi te size 67% 100% 67% 100%Parasi te shape ameboid band ameboid compact

Suf fner duts -- + + --M aure duts + -- -- --

not seen i nP.B

malari a pigment

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P. falciparum P. vivax P. ovale P. malar iaeSchizont :size of RBC nor mal enl arge enl arge nor malParasi te size 67% 100% 67% 100%Suf fner duts -- + + --# of merozoite 16-24 12-24 6-12 6-12(r ostte s

not seen inP.B hpe)Gamitosite:Size of RBC crecent shape enl arge enl arge nor malParasi te size hall cell 100% 67% 100%Age of cel l any young young oldDi sease malegnant beni gn beni gn benign

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Signs & symptoms:

The pathology and clinical manifestationsassociated with malaria are almostexclusively due to the asexual erythrocyticstage parasites. Tissue schizonts andgametocytes cause little, if any, pathology.

Plasmodium infection causes an acutefebrile illness which is most notable for itsperiodic fever paroxysms occuring at either48 or 72 hour intervals. The severity of theattack depends on the Plasmodium speciesas well as other circumstances .

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Sometimes the incubation periods can be prolongedfor several months in P. vivax, P. ovale, and P.malariae . All four species can exhibit non-specific

prodromal symptoms a few days before the firstfebril attack. These prodromal symptoms aregenerally described as 'flu-like' and include:headache, slight fever, muscle pain, anorexia andnausea. The symptoms tend to correlate withincreasing numbers of parasites.

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Disease Severity and Duration

vivax ovale malariae falciparum

Initial ParaoxysmSeverity

moderate tosevere

mild moderate tosevere

severe

AverageParasitemia(mm 3)

20,000 9,000 6,000 50,000-500,000

MaximumParasitemia(mm 3)

50,000 30,000 20,000 2,500,000

SymptomDuration(untreated)

3-8weeks 2-3 weeks 3-24 weeks 2-3 weeks

MaximumInfectionDuration(untreated)

5-8 years12-20

months20-50 years 6-17 months

Anemia ++ + ++ ++++

Complications renal cerebral

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In contrast to the other three species, P. falciparum canproduce serious disease with mortal consequences. Thisincreased morbidity and mortality is due in part to the highparasitemias associated with P. falciparum infections.These potentially high parasitemias are due in part to thelarge number of merozoites produced and the ability of P.falciparum to invade all erythrocytes.

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Other Physical symptoms:

Fever: Fever can be very high from the first day.

Temperatures of 40

C and higher are often observed.Fever is usually continuous or irregular. Classic periodicity

may be established after some days.

Hepatomegaly: The liver may be slightly tender.

Splenomegaly: Splenomegaly takes many days, especiallyin the first attack in nonimmune children. In children froman endemic area, huge splenomegaly sometimes occurs.

Anemia: Prolonged malaria can cause anemia, andmalarial anemia causes significant mortality.

Jaundice: With heavy parasitemia and large-scaledestruction of erythrocytes, mild jaundice may occur. This

jaundice subsides with the treatment of malaria.

Dehydration: High fever, poor oral intake, and vomiting allcontribute to dehydration.

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Black water fever

Massive intravascular hemolysis Due to P. falciprum Severe acute hemolytic anemia

RBC=1-2*106 /ml Hemoglobinuruia Increase bilirubin Acute tubcular necrosis& Hb casts

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Examine blood under microscope(geimsa stain)

chest x-ray : helpful if respiratory symptoms arepresent

CT scan : to evaluate evidence of cerebral edema orhemorrhage

Medical intervention:

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Polymerase chain reaction (PCR)

-determine the species of plasmodium Dipstick test- not as effective when parasite levels

are below 100 parasites/mL of blood

Blood examination: Thick and thin blood film

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Other tests:

CBC:-Lukopenia-Thrombocytobenia-Esinophilia-monocytosisQuntitative buffy coat techniqeUrinalysisIncrease ESR

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Thank you