Download P. vivax

Glass sporozoa
Genus plasmodium
There are 4 species of plasmodium responsible for human malaria
P.vivax-benign tertian malaria.
P.malariae-quartan malaria.
P.falciparum-malignant tertian or sub tertian malaria.
P. ovale-tertian or benign tertian malaria
Morphology
The earliest form after the invasion of the R.B.C by the malarial parasite. is the
trophozoite stage.
The early trophozoite form rings usually with a single nucleus .As the
troph.growsIt will metabolize the haemoglobin of the R.B.C. and produce a
darkly staining malarial pigment-hemozoin.
The nucleus of the trophozoite divides and it is now called immature schizont
then each nuclear division surrounded by piece of cytoplasm forming mature
schizont.Merozoitsform&rupturesRBCs,then it infect other RBCs.
Some merozoites develops into gametocytes or sexual stage which have
compact cytoplasm and no nuclear division.
P. vivax
The infected R.B.C. is enlarged because the parasite invade the reticulocytes –
immature R.B.C. which is larger than other R.B.C. as the trophozoite grows, it
form ring stage then the cytoplasm become irregular in shape with
amaeboidextention forming amaeboid stage .Fine pink or reddish granules
appear all over the infected R.B.C. these are schuffners dotes-believe to be an
allergic reaction from the host to the presence of the parasite.
Malarial pigment in the cytoplasm of the parasite is fine light brown in colour
1
In immature schizointes nucleus start division then.
The schizont matures in about 48 hrs. after the invasion of the R.B.C. and
becomes segmented into12- 16 merozoites .Gametocytes are round and nearly
filling the R.B.C. all these stages are seen in the peripheral blood.
P.malariae
The infected R.B.C. is not enlarged because the parasite invade the old or
mature R.B.C. ring are smaller than those of vivax and more compact, no
schuffners dotes malarial pigments are coarse dark brown or black, trophozoite
assume band shape across the infected R.B.C.matureschizont need 72 hrs.to
develops contain 6-10 merozoits mostly 8 in No. which may be arranged in a
rosette form with merozoits at the periphery and dark malarial pigments at the
center,gametocytes are round, all these stages are seen in peripheral Bl
P.falciparum
The parasites infect all ages of R.B.C.rings are small,multiple infection in one
R.B.C.is common,ring may have double chromatin dots-2 N- Schizonts are rarly
seen at the peripheral Bl. Except insever infection with high parasitemia,
schizogony take place in the capillaries of muscles and viscera,matureschizont
has 8-32 merozoit .gametocytes are cresent in shape, only ring and
gametocytes are ordinarily seen in the peripheral Bl.
P. ovle
Commonly seen in west Africa.The infected R.B.C.is slightly enlarged and oval
in shape and show schuffnersdots,it has irregular or fimbriatedappearace of
the edges of the infected R.B.C. mature schiz.cotains 8 meroz.malarial
pigments is coarse and brown.
Life cycle
Vertebrate host-asexual cycle-schizogony.
Invertebrate host-sexual cycle-sporogony
2
Human infection result from the bite of an infected female anophyline
mosquito in which sporozoites are injected into the human Bl. Stream during
feeding Within 30 min.sporozoites move rapidly to the liver, invade
hepatocytes and undergoexoerythrocytic development 8-15 days depend on
the species leading to the formation of liver schizots.Rupture of each liver
schizont releases thousands of meroz.into the peripheral Bl.where they invade
the R.B.C.&theerythrocytic stages started.forming the erythrocytic cycle.
In P. vivax and P .ovale some parasites remain dormant in the liver cells as
hepatic sch. which are later released as merozoites.such parasites persisting in
the liver cells and called hypnozoites which responsible for late relapses.
In P.falciparum and P.malariae true relapse does not occur and hepatic
sch.survive only a short time.
There is no return of merozoit from R.B.C.to the liver cells.
In the infected R.B.C.the early trophozoits form –ring stage-develop into late
troph.with an enlarged cytoplasm and accumulation of hemozoin pigment.
Mature sch .ruptures releasing meroz.There are reinvasion of R.B.C.by
meroz.and repeat the schizogony cycle
Some meroz.that invades R.B.C.does not go into schizogony but goes into
gametogony cycle forming male and female gametocytes.
Without treatment,falciparum infection ordinarly will terminate spontaneously
in less than than 1 year unless it ends fatally.InP.vivax and P.Ovale some
parasite will stay in the liver cells after the initial Bl.streaminvasion,these are
known as hypnozoites which later will develop into mature liver schiz.then
invade the R.B.C.later causing parasitemia and relapse after original infection.
Relapses in P.vivax is up to 3-4 years.
Relapses in P.ovale is up to 4-5 years.
Sporogony
3
Is the sexual stage take place in the mosquito, the gametocytes ingested with
the Bl. Meal of the mosquito not digested, they are ;
Male microgametocyte-its chromatin dots [nucleus] divided into 6-8 divisions
that migrate to the periphery with cytoplasmic projections forming whip like
actively motile filaments [microgamets] detached from the parent cell, this
process called exflagellation which lasts 10-20 min.occur in the stomach of
mosquito.
Female macrogametocyte become mature into macrogamete its nucleus shift
to the periphery .
Fertilization occurs in the stomach of mosq. Results in the formation of zygote,
which will change into worm like body after 12-24 h.of the Bl. Meal and now it
is called ookinete which penetrates the wall of the gut and develops into
oocyst between the epithelium and the basement membrane. Oocyst increase
in size become rounded, projects into the body cavity of the mosq. And will
develop thousands of sporpzoites inside it.after rupture of the
oocyst,sporozoites are librated into the body cavity and migrate to the salivary
gland.the cycle in the mosq. Lasts 10-17days,whenmosq.feedssporoz.are
injected to the host T.
________________________________________
Terms:Prepatent period:
Is the time between the infection by the sporoz.and the first appearace of
erythrocytic parasites in the Bl. It is usually 6-9 days except in P.malariae 13-16
days usually no clinical findings are present.
Incubation period :Is the time between the infection and the first appearance
of fever with erythrocytic parasite in the Bl.,
In non immune hosts i. p. usually 10-15 days it may prolonged by
administration of anti malarial drugs in small doses.
4
Latent malaria:
Is acondition in which P.parasites are found in peripheral Bl. Of the host who
has no acute symptoms of malaria ,they are important as they have
gametocytes in the peripheral Bl. [silent carrier] and infectious to mosq.
Relaps:
Renewed manifestations of malaria due to parasites in the Bl., derived from
hypnozoites from the liver it occurs only in sporozoite induced infection and in
plasmodium species who develops hypnozoites in the liver ,after the Bl. Is
invaded by [p.vivax or p. ovale ]it does not occur in Bl. Transfusion induced
malaria.
Recrudescence:
Re newed manifestation of malaria subsequent to the primary attack duo to
multiplication in the Bl. Of an existing population of parasites surviving from
the original infection ,it may occur in Bl. Transfusion induced malaria and it
may occur in all types of P. Infections.
Tropical spleenomegaly:
Seen in area endemic with malaria ,not related to particular species there is
hypersplensim ,it is an immune complex disorder.
____________________________________________
Epidemiology
Malaria generally is widespread in tropics, subtropics and to a lesser extend in
temprate zones.
The most common sp.found in Iraq is vivax and to a lesser extend P.falciparum
.mixed infection of P.vivax and P. falciparum may occur P. malariae is less
common than vivax
P.falciparum and ovale are rare except in west Africa.
5
Reservoir host : -mosquitois the only important reservoir host .
Transmission : 1. Bite of female anophiline mosquito
2. Blood transfusion , using contaminated syringes (addicts)
3. Across the placenta (it means some placental defect .
Transfusion mal , initiate only erythrocytic cycles , therefore it is easily
eradicated and relapse does not occur .
Malaria is regarded as endemic in an area where there is measurable incidence
and natural transmission over the years .
To study the endemicity of mal. The following points should be considered : 1.
2.
3.
4.
5.
Collection of statistics about past and present morbidity and mortality .
Spleenicindex .
Parasite index .
Mosquito density and infection rate .
Environmental factors affecting transmission .
Spleenicindex : -represents the percentage of children 2 – 9 yrs age with
enlarged spleen .
w.h.o classify the endemicity according to spleenic index into :a) Holo endemic – spleenic index is constantly over 75% , adult spl , rate is
low .
b) Hyperendemic – spl. index is constantly over 50% , adult spl . rate is high .
c) Mesoendemic – spl .index11 – 50% .
d) Hypoendemic – spl .indexnot exceeding 10% .
With repeated exposure to malaria adult spleen become fibrotic and shrink to
near a normal size , so in areas with heavy transmission , the spleen size in
adult may be normal .
6
Parasite index or parasite rate- is the percentage of children 2-9 yrs of age
with detectable plasmodium in single thick bl.smear .
Mosquito density and infection rate– it is determined by dissection of stomach
of mosquito for oocyst, and salivary glands for sporozoites, the percentage of
infected mosq. Is usually 0-10% in endemic areas .
Environmental factors– includesclimate , socioeconomic state of population .
A temp between 16-34 c. and relative humidity over 60% are suitable for
breeding of mosq. And development of sporogeniccycle .
Socioeconomic state includes housing,nutritional state .
Agricultural practice – water and wastage provide good breeding sites .
____________________________________________
Immunity :-natural and acquired
Innate resistance – natural immunity .
Insusceptibilty of most black people to vivax most of them lack the duffy
antigen on R.B.C. because merozoite receptors of p.vivax are associated with
duffy factor on red cells .
Sickle Hb trait show resistance to P.falciparum . it does not prevent infection ,
but limits high degree of parasitemia that might be fatal .
G6pd , deficiency of red cells (glucose 6 phosphate dehydrogenase deficiency )
this condition will limit parasitemia
Acquired immunity :Appears within few days of establishment of erythrocytic parasite, it is
stimulated by eryth. Parasite only and last few monthes after eradication of
erythrocytic parasite.
Immunity is specific for species and strain .
7
Pathology :Pathological changes occur in all types of malaria , but they are mainly
seen in P. falciparum infection . it is the erythrocytic phase alone which
is responsible for the clinical and pathological disturbances in the host .
In P. falciparum the late trophozoite and schizonts will precipitate high
molecular weight protein in the erythrocytic membrane containing it ,
which causes the infected RBC to adhere to the vascular endothelium –
that is why these stages of the life cycle do not circulate in the
peripheral blood .
There is activation of reticuloendothelial system duo to the rupture of
infected RBC and intravascular release of parasites , malaria pigment
and cellular debris .
Anemia and tissue anoxia are the main pathological changes .
Anemia
1- destruction of red cells by the parasite
2-Haemolysis of non infected RBC possibly duo to autoimmune
process .
3-Hyperplenism lead to destruction of RBC .
4.-bone marrow depression .
5-Increase fragility of RBC .
Tissue anoxia
In P. falciparum there is vascular obstruction due to :
1. Tendencyof infected R.B.C. to stick to the endothelium of vessels
and to each other (development of knoblike structure on the
infected red cell membrane as the parasite matures and the
8
infected RBC become more rigid than normal RBC leading to
congestion and reduced blood flow , stasis of blood , thrombi
obstruction of small blood vessels , petechial hemorrhage , with
anoxia of the affected organ .
2. The ability of P. falciparum to infect RBC of all ages leading to high
parasitemia .
So changes in P.falciparum are basically vascular in nature and may
affect any organ , liver , spleen , brain , kidnies , heart , lung , gut ….
Liver and spleen show:- deposition of mal. pigment , hyperplasia of
kupffer cells and macrophages resulting in enlargement of liver and
spleen .
In acute infection, the soft enlarged spleen is susceptible to
spontaneous or traumatic rupture , fixed macrophages in spleen and
liver phagocytose infected and some non infected RBC and. malarial
pigment , with increase red cell destruction excess iron deposited as
hemosiderine in the paranchymatous cells .
-In chronic infection, liver, spleen and also other organs become grey
or black in colour due to deposition of malarial pigment.Spleen later
become hard fibrotic and shrinks.
Brain-oedematous and, congested, cortex grey, petechial hemorrhage,
capillaries packed with infected R.B.C. and pigments.
Lungs-interstitial pneumonitis.
Heart-petechialhaemorrhages, partially blocked capillaries.
Kidneys-ischamia to the cortex ,malaria pigments in the interstitial
tissue. In complicated P.falciparummalaria,when there is acute massive
hemolysis it may result in acute tubular necrosis
In chronic infection with P.malariae, an immune complexes are formed
and deposited in the kidney ,glmerular deposits of Ab-Ag complex.
9
____________________________________________
Clinical picture:The clinical manifestations of malaria arise from the invasion of
erythrocytes and the progress of asexual erythrocytic stages.
P.falciparum infection differs from other species in that it causes an
acute and rapidly progressive disease and may be fatal if not
treated,While other species give more benign illness in which
complications are unusual, fatality is rare and the disease itself is selflimited.
Incubation period: 9-30-days
First there aregeneral symptoms which are non specific, mistaken for
influenza as headache, joint pain, chills and irregular fever. This stage
lasts few days. Then malaria paroxysms start.
The beginning of paroxysm corresponds with the ruptureof schiz. And
the liberation of merozoites, pigments and residue of debris into the Bl.
Stream.
Intervals between febrile paroxysms represent the time required for
development of schizonte , from the entery of meroz. Into R.B,C. until
rupture of schiz.
 Paroxysms of malaria:
 Cold stage:Up to 1hr. with chills, peripheral Bl.vessels
are
constricted ,lips and nails are cyanotic with skin is pale and cold.
 Hot stage:It last6-12 hrs . suddenly replaces the cold stage , temp
high skin flushed hot and dry , rapid pulse , rapid respiration ,
headache , convulsions in children
10
 Sweating stage:sweating all over the body , temp falls , headache
disappear , pulse return to normal pt. feels better , become
exhausted and go to deep sleep .
Then interval follows , patient feels well but deteriorates rapidly once
next paroxysm begins .
Such paroxysms are self -limited , usually last 6-8 wks , then paroxysms
tend to become less severe and stop .
In untreated cases the quiescent stage lasts weeks or months , then
when paroxysms occur at regular intervals , it means that the parasites
reach maturity at the same time , that is why fever at the beginning of
the primary attack does not have regular periodicity , because several
hepatic schizonts did not develop exactly at the same time – multiple
broods of parasites go to blood , but with time , the broods tend to
become synchronous their development .
P. vivax ,falciparum&ovalschizogony lasts about 48 hrs, and febrile
paroxysms occur every third day – tertian periodicity .
P.malariaschizogony last about 72 hrs , and febrile paroxysms occurs
every fourth day – quartan periodicity .
P.vivax rarely causes death ,relapses are common in untreated cases
or with incomplete treatment , and relapses are usually milder than
primary attacks and shorter duration (immunity)
Complications :Without treatment all species of human malaria end in spontaneous
self-cure but with P.falciparum it may progress to increasing
parasitemia and ends fatally .
In complicated falciparum malaria , the complications may appear at
any stage in a primary attack or in a recrudescence , usually the
patient is not treated or had repeated inadequate treatment .
11
complications usually occur in the second or third week of the
acuteprimary attack .
Cerebral malaria :severe headache , drowsiness , confussion ,
convulsion , coma (duo to anoxia of brain,cerebral edema and increase
intracranial pressure) .
Hyperpyrexia :- the body temp , rises rapidly above 41 c , skin flushed
and dry , usually accompanied by signs of CNS disturbances .
Gastrointestinal complications :abdominal pain , watery stool ,
vomiting , intestinal hemorrhagesever dehydration may develop with
jaundice .
Algid malaria or medical shock – patient suddenly suffers from
circulatory collapse , and rapidly passes into coma (sunken eyes , cold
skin , pale,fast shallow breathing and hypotention] .
Acute renal failure:- duo to acute tubular necrosis resulting from renal
anoxia .
In all previous complications – parasitemia is high (more than 5%)
Multiple infection in the RBC is common
Troph, and schizonts appear in periph blood
Nephrotic syndrome:-is a complication of quartan malaria, there are
glomerular deposites of antibody compliment and antigen .
Black water fever :- an acute intravascular hemolysis may occur in
P.falcipP.vivax&P.malariae
causing
hemoglubinemia
and
hemoglubinurea,
,hemolysis is rapid and severe, severe anemia may
result , urine become dark and contain sediment of epith .cells,casts
and protein, it represents an autoimmune phenomenon with the
development of antibodies to infected RBC .
12
In hyperendemic area:Infantsdo not become infected during the first 3_4 months of age duo
to transplacental immunity from their mothers and because of reduced
ability of fetal Hb. To support development of the parasite.
Young children suffer repeated infections .
Late childhood become immune .
Premunition – concomitant immunity – infection immunityIs a protection against super infection duo to continued antigenic stimulus of
the same parasitic strain in the host .this resistance dose not completely
prevent reinfection , but limits it and considerably modifies the clinical picture.
Individuals who have acquired such resistance are known as semi-immune , the
imm. is not absolute , there are occasional attacks of clinically modified mal.
Diagnosis:
Identification of asexual erythrocytic parasites in the blood. ,if only
gametocytes in the blood. ,it is not sufficient because gamt. May be present for
long period after cure .
 Thick film for detecting parasites.
 Thin film to differentiate the spesies.
 Serodiagnosis.as PCR.
Treatment :It includes general supportive and chemotherapy
Ceneral measures- include rest in bed , cold sponging , aspirin or sedative for
headache and general symptoms , regulation of fluid intake , blood transfusion
if severely anemic .
13
The species of the parasite should be determined before starting treatment in
order to choose the proper drugs and to be aware of the complications of P.
falciparum.
Durgs acting on asexual eryth. Parasites – schizontocides
Used for clearance of schizonts from the blood in all forms of malaria
-quinine
-4aminoquinoline (chloroquine, nivaquine, amodiaquine)
-mefloquine
-mepacrine
-proguanil
-pyrimrthamine
-sulphonammide and sulphones – usually used in combination with other
drugs.
Durgs acting on tissue forms
-proguanil and pyrimethamine
-8 aminoquinoline(primaquine, has also gametocidal activity) ,primaquine is
the only drug effective against persisting exoeryth. Liver stages in P. vivax and
P. ovale .
Treatment of all uncomplicated attacks
Chloroquine phosphate orally :10 tablets(250mg.) over 3 days.
Day 1 1 gm.(600 mg base ) 4 tablets.
After 6h. 0.5 gm ( 300 mg base) 2 tablets.
Day 2 0.5 gm ( 300 mg base).
Day 3 0.5 gm (300 mg base ).
14
In case of P.vivax and P.ovale we have to do radical cure to prevent relapses ,
so we use drugs acting on tissues to destroy hypnozoites in the liver .
Primaquinephosphate 15mg. base orally / day for 14 days .
Treatment of severe illness (for all plasm. Except resist. P falciparum)
Chloroquine hydrochloride 250 mg ( 200 mg base ) i.m. every 6 hrs. (maximum
dose 1 mg/ day) until oral therapy with chloroquinephosph. Is possible.
In P. falciparum infection , if the patient does not show any response to the
usual chloroquine doses , parasite resistance is considered .
Treatment of p. falciparum resistant to chloroquine
(resistance. is mainly found in south east Asia)
Combined therapy with
Quinine sulfate orally 650 mg. tid. For 3-10 days .
Pyrimethamineorally 25 mg. bid. For 3days .
Sulfadiazine orally 500 mg. for 5 days .
Severe resistant P.falciparum with coma or vomiting should be treated Withi.v.
Quinine dihydorchloride 600 mg. in saline repeated every 6-8 hrs. until quinine
therapy is possible .
Steroidemay be given in cerebral malaria in addition to antimalarials to
decrease cerebral edema.
Toxicity of some antimalarial drugs
Quinine - tinnitus , visual disturbance , dizziness, headache , nausea , skin
rashes , asthma , hemolytic anemia .
Chloroquine-pruritis, mild visual disturbances ,retinopathy.
15
Primaquine – haemolysis in RBC deficient in glucose 6 phosphate
dehydrogenase , abdominal cramps,leucopenia.
Prevention
1- Reduction of gametocyte carriers.
2- Mosquito control – insecticides , eradication of breeding places.
3- Protection of people – use repellants , nets, screening windows, vaccine.
16