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Transcript of MALARIA TEACHING BASICS By Dr.T.V.Rao MD
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MalariaTeaching Basics
Dr.T.V.Rao MD
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History of Malaria• One of the oldest known diseases.• King Tut died of malaria.• Malaria has been infecting humans for over 50,000 years.
• References to malaria have been recorded for nearly 6000years, starting in hina.
• !sed to be common in "uro#e and $orth %merica.
• &irst advances in malaria 'ere made in 1((0 by a &rencharmy doctor named harles )averan.
• *e loo+ed into infected red blood cells and discovered the#arasite 'as a #rotist. This 'as the rst time a #rotist 'asdiscovered to cause a disease.
• arlos &inlay discovered that mos-uitoestransmitted diseases.
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Lavern and Ronald Ross/ioneered the "vents on
Malaria
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Malaria – Historywho made it
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Patrick MansonSirAlphonse Laveran
Sir Ronald Ross Giovanni Grassi
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A French armydoctor in Algeriaobserved parasitesinside red bloodcells of malariapatients and
proposed for thefirst time that aprotozoan causeddisease
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more than 100 years
ago
harles )ouis %l#honse )avera
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Ronald Ross discoers the role ofmos!uitos and transmission
• Ronald Ross discoeredthat mos!uitoestransmitted malaria in"#$#.
• %irst e&ectie medicine
was discoered 'y (ierre(elletier and )ose*h+aentou. This medicineis called !uinine, whichcomes from the 'ark of
cinchona trees in (eru.• -o e&ectie accine only
immunity is a result ofmulti*le infections.
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-ature of *arasite asDrawn 'y /aern
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Malaria – Hot s*ots0eogra*hic
distri'ution
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(resentgeogra*hical distri'ution of malaria
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MALARIA• 40% of the world’s population lives in
endemic areas• !"00 million clinical cases per #ear• $"!&' million deaths ()0% Africa*• increasin+ pro,lem (re!emer+in+ disease*
•resur+ence in some areas
• dru+ resistance (
mortalit#*
•P falciparum•P viva-•P malariae•P ovale
• causative a+ent . Plasmodium
species
• proto/oan parasite• mem,er of Apicomple-a• 4 species infectin+ humans
• transmitted ,# anopholine
mosuitoes Dr.T.V.Rao MD 11
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asmo um s*ec eswhich
infect humans
Plasmodium vivax (tertian) Plasmodium ovale (tertian)
Plasmodium falciparum (tertian)
Plasmodium malariae (quartian)
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1hat is Malaria2• Malaria is a #arasite that enters the
blood.
• This #arasite is a #roto2oan called#lasmodium.
• 3 to 400 million #eo#le get malariaeach year, but only +ills 1 to million
• 0 of the 'orlds #o#ulation lives inmalaria 2ones
• Malaria 2ones are %frica, 7ndia, Middle"ast, 8outheast %sia, entral and 8outh%merica, "astern "uro#e, and the 8outh/acic 9slide 13:.
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1hat determines the s*read ofmalaria2
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?
Malaria s*readde*ends on
•Rainfall *attern
3How does thisa&ect mos!uito'reeding24
• Ty*es of mos!uitoes in the area
•
How close are *eo*le to the 'reedingsites2
5ome areas constantly hae a highrate of malaria.
Other areas hae 6malaria seasons7
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Exo-erythrocytic(hepatic) cycle
Sporozoites
Mosquito SalivaryGland
Malaria LifeCycleLife Cycle
Gametocytes
ocyst
ErythrocyticCycle
!y"ote
Schizogony
Sporogony
#ypnozoites(for P. vivax and P. ovale )
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";oygote
%da#ted from
?ocyst
8tomach @all
/re
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Malaria
Transmission +ycle
Parasite undergoes
sexual reproduction in
the mosquito
Some merooites
di!!erentiate into male or
!emale gametocyctes
"rythrocytic #ycle$
Merooites in!ect red
%lood cells to !orm
schionts
&ormant liver stages
'hypnooites( o! P.
vivax and P. ovale
"xo)erythrocytic 'hepatic( #ycle$
Sporooites in!ect liver cells and
develop into schionts* which release
merooites into the %lood
MOSQUIO !UMA"
Sporooires in+ected
into human host during
%lood meal
Parasites
mature in
mosquito
midgut and
migrate to
salivary
glands
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+om*onents of the Malaria /ife+ycle
Mosquito Vector
Human Host
Sporogonic cycle
Infective Period
Mosquito ites
gametocytemic
person
Mosquito ites
uninfected person
Prepatent Period
Incuation Period
Clinical Illness
Parasites visile
!ecovery
Symptom onset
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Malaria Burden +linical Manifestations
8nfectedMos!uito
8nfected
Human
+hronic
e&ects
;nemia-eurolog
ic<cognitieDeelo*mental
8m*airedgrowth
anddeelo*m
ent
Malnutrition
;cutefe'rileillness
5eereillness
Hy*oglyce
mia;nemia
+ere'ralmalaria
Death
Res*iratory
distress
(regnancy
%etus
Maternal
;cute
illness;nemia
8m*aired*roducti
ity
/ow 'irthweight
8nfantmortality
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Malaria *arasite 3*lasmodium4
• Pathogen o! malaria
• P,vivax - P,!alciparum -P,malariae -
P,ovale• P.vivax ; P.falciparum are morecommon
• Plasmodium is a wide distri%utionin many tropical or su%tropicalregions o! the world
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Malaria – Vectors
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Anopheles ,ala,acensis
A free,orni
A +am,iae
A stephensi
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+haracteristic of life cycle
• 7ntermediate host human
• &inal host mos-uito
• 7nfective stage s#oro2oite
• 7nfective 'ay mos-uito bite s+in of human• /arasitic #osition liver and red blood cells
• Transmitted stage gametocytes
• 8chi2ogonic cycle in red cells ( hrsA/.v
• 8#oro2oite tachys#oro2ite andbradys#oro2ite
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Mos!uitoes and Malaria
• The s#read of malariade#ends on the life cycleof the mos-uito.
• %dult mos-uitoes lay their
eggs on 'ater.• The eggs hatch to become
larvae and then #u#ae,before turning into adults.
• %dult females mos-uitoesonly live to 'ee+s.
• 8o you can reduce malariaby attac+ing any of thesefour stages of themos-uito.Dr.T.V.Rao MD 3
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Li!e #ycle• sporooites in+ected during
mosquito !eeding• invade liver cells• exoerythrocytic schiogony
'merooites(• merooites invade R.#s•
repeated erythrocyticschiogony cycles
• gametocytes in!ective !or
mosquito• !usion o! gametes in gut• sporogony on gut wall in
hemocoel• sporooites invade salivary
glands
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1nvasive Sta+esMero/oite• er#throc#tes
Sporo/oite•
salivar# +lands• hepatoc#tes
2okinete• epithelium
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5*ecies +haracteristics
(V (O (M (%
/eriodicity9hrs.: ( 50 4(
/arasitesAMl 0
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Morphology
• Malarial parasite trophozoites are generally ring
shaped, 1-2 microns in size, although other
forms (ameboid and band) may also exist.
• The sexual forms of the parasite (gametocytes)
are much larger and -1! microns in size.
• P. falciparum is the largest and is banana
shaped, "hile others are smaller and round.
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3R56R27517
6P8292153S S
GAM352753S
3:2!3R56R27517
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9=oerythrocytic 3tissue4
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9=oerythrocytic 3tissue4*hase
• Blood is infected 'ith s#oro2oites about30 minutes after the mos-uito bite
• The s#oro2oites are eaten by
macro#hages or enter the liver cells'here they multi#ly E
#re
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9=oerythrocytic 3tissue4*hase
• P. malariae or P. falciparums#oro2oites do not formhy#no2ites, develo# directly into
#re
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"xoerythrocytic Schiogony
• hepatoc#te invasion• ase-ual replication• ;!$" da#s• $000!$0
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/yponooite orms• some 33 forms e-hi,it dela#ed
replication (ie< dormant*• mero/oites produced months after
initial infection• onl# P. vivax and P. ovale
relapse . h#pno/oite
recrudescence .
su,patentt
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Rela*sing malaria
• P. vivax and P. ovale hy#no2oitesremain dormant for months
• They develo# and undergoe #re<
erythrocytic s#orogeny• The schi2onts ru#ture, releasing
mero2oites and #roduce clinical
rela#se
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85 8T %;/+8(;R>M2• 1H;T DO95 TH9 5M9;R 5HO12
# ?@A (;R;58T9M8;
# MO-OTO-O>5 5M;// R8-05
# -O TRO(HOO8T95 OR 5+H8O-T5 # B;-;-; 5H;(9D 0;M9TO+:T95
# M>/T8(/: 8-%9+T9D +9//5
# ;((/8C>9 %ORM5
# +9//5 O% ;// 5895 8-%9+T9D
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How the *arasite a**ears in'lood smear
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P f l i Bl d t
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P. falciparum – Blood stages
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=ninfected R>7
& hr
4 hr
$& hr
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9=oerythrocytic 3tissue4 *hase
• P. vivax and P. ovalehy#no2oites remain dormantfor months
• They develo# and undergoe#re
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9rythrocytic *hasestages of *arasite in RB+
• Tro#ho2oites are early stages 'ith ringform the youngest
• Tro#oho2oite nucleus and cyto#lasm
divide forming a schi2ont• 8egmentation of schi2ontFs nucleus and
cyto#lasm forms mero2oites
• 8chi2ogeny com#lete 'hen schi2ont
ru#tures, releasing mero2oites into bloodstream, causing fever
• These are ase;ual forms
9rythrocytic *hase
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9rythrocytic *hasestages of *arasite in RB+
• Mero2oites invade other RBsand schi2ongeny is re#eated
• /arasite density increases untilhostFs immune res#onse slo'sit do'n
• Mero2oites may develo# intogametocytes, the se;ual formsof the #arasite
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gametocytes
erythrocytic schiogony• 2 hr in Pf, Pv, Po• 34 hr in Pm
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5ametocytogenesis•
alternative to ase-ual replication• induction factors not known• dru+ treatment ?@s• immune response ?@s
• rin+ +ametoc#te• Pf B$0 da#s• others Bsame as schi/o+on#
• se-ual dimorphism• micro+ametoc#tes• macro+ametoc#tes
• no patholo+#• infective sta+e for mosuito
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0ametocytes
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Male gametocyte &emale gametocyte
$ote com#act cyto#lasm and absence ofnuclear division.
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0ametocyte of P. falciparum
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banana shaped gametocyte( P. falciparum)
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5ametogenesis•
occurs in mosuito +ut• Ce-fla+ellation’ most
o,vious• : nuclear replication•
D micro+ametes formed• e-posure to air induces
•↓
temperature (&!o7*•
p6 (D!D*
• result of↓
p72&
• +ametoct#e activatin+
factor in mosuito• -anthurenic acid
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Sporogony•occurs in mosuito ()!&$ d*•
fusion of micro! andmacro+ametes
•/#+ote ookinete (B&4 hr*•ookinete transverses +ut
epithelium (@trans!invasion@*
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Sporogony•ookinete ooc#st
•
,etween epithelium and,asal lamina
•ase-ual replication
sporo/oites•
sporo/oites released
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Sporogony
• sporo/oites mi+rate
throu+h hemocoel• sporo/oites @invade@
salivar# +lands
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8 ' ti ( i d
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8ncu'ation (eriod
&ollo'ing the infective bite by the Anopheles mos-uito a #eriod of time9the Gincubation #eriodG: goes by
before the rst sym#toms a##ear. The incubation #eriod in most casesvaries from 4 to 30 days.
The shorter #eriods are observedmost fre-uently 'ith P. falciparum andthe longer ones 'ith P. malariae.
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5chiogenic *eriodicity and feer *atterns
• 8chi2ogenic #eriodicity is length ofase;ual erythrocytic #hase # ( hours in P.f., P.v., and P.o. 9tertian:
# 4 hours in P.m. 9-uartian:• 7nitially may not see characteristic fever
#attern if schi2ogeny not synchronous
• @ith synchrony, #eriods of fever or
febrile #aro;syms assume a moredenite 3 9tertian:< or 9-uartian:< day#attern
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#linical eatures• characteri/ed ,# acute fe,rile attacks (malaria
paro-#sms*• periodic episodes of fever alternatin+ with s#mptom!free
periods
• manifestations and severit# depend on species and host
status• immunit#< +eneral health< nutritional state< +enetics
• recrudescences and relapses can occur over months or
#ears
• can develop severe complications
(especiall# P. falciparum*
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Malaria
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• paro-#sms associated with
s#nchron# of mero/oite
release• ,etween paro-#sms temper!
ature is normal and patientfeels well
• falciparum ma# not e-hi,it
classic paro-#sms
(continuous fever*
Malaria
Paroxysm
tertian malaria
uartan malaria
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+linical manifestations
1 %nemia
8#lenomegaly
3 erebral malaria
Malariane#hro#athy
5 ongenital malaria
usually fatal6 blac+ 'ater feverH
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+linical *resentation
• %cute febrile illness, may have #eriodicfebrile #aro;ysms every ( E 4 hours 'ith
• %febrile asym#tomatic intervals
• Tendency to recrudesce or rela#se overmonths to years
• %nemia, thrombocyto#enia, Iaundice,he#atos#lenomegaly, res#iratory distress
syndrome, renal dysfunction,hy#oglycemia, mental status changes,tro#ical s#lenomegaly syndrome
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+linical *resentation
• "arly sym#toms # *eadache
# Malaise
# &atigue # $ausea
# Muscular #ains
# 8light diarrhea
# 8light fever, usually not intermittent• ould mista+e for inJuen2a or
gastrointestinal infection
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1hat are the signs and sym*toms of malaria2
8ym#toms of malaria include fever andJu
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>ncom*licated Malaria
The classical 9but rarely observed:malaria attac+ lasts 6
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85 8T %;/+8(;R>M2
• 1H;T DO95 TH9 5M9;R 5HO12
# ?@A (;R;58T9M8;
# MO-OTO-O>5 5M;// R8-05
# -O TRO(HOO8T95 OR 5+H8O-T5
# B;-;-; 5H;(9D 0;M9TO+:T95
# M>/T8(/: 8-%9+T9D +9//5
# ;((/8C>9 %ORM5
# +9//5 O% ;// 5895 8-%9+T9D
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Rela#se
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Malignant malaria Malaria caused by /.falci#arum. is
more severe than that caused by other#lasmodia.
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/a'oratory diagnosis
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Blood collected with steriletechni!ue
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Making of Thick smear
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How a thick smear looks
;**earance of Thick and
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**Thin
5mears
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Microsco*y
• Malaria #arasites can be identied bye;amining under the microsco#e adro# of the #atientLs blood, s#read
out as a Gblood smearG on amicrosco#e slide. /rior toe;amination, the s#ecimen is stained
9most often 'ith the =iemsa stain: togive to the #arasites a distinctivea##earance. This techni-ue remainsthe gold standard for laboratory
Microsco*ic demonstration still
http://www.cdc.gov/malaria/biology/parasites/index.htmhttp://www.cdc.gov/malaria/biology/parasites/index.htm
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Microsco*ic demonstration stillthe 0old standard in Diagnosis
Blood smear
stained with0iemsaFs
stain
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;ntigen Detection methods
• Various test +its areavailable to detect antigensderived from malaria#arasites. 8uchimmunologic
9Gimmunochromatogra#hicG:tests most often use adi#stic+ or cassette format,and #rovide results in
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C yra*id and *recise method
in Diagnosis• The NB Malaria method is the sim#lest
and most sensitive method for diagnosing
the follo'ing diseases. # Malaria # Babesiosis
# Try#anosomiasis 9hagas disease, 8lee#ing
8ic+ness: # &ilariasis 9"le#hantiasis, )oa
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(rinci*le of CB+ 5ystem
;**earance of Malarial
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;**earance of Malarial*arasite in CB+ system
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5erology in Malaria
• 8erology detectsantibodies againstmalaria #arasites,using either indirect
immunoJuorescence97&%: or en2yme
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Molecular Diagnosis of malaria
• /arasite nucleic acids aredetected using #olymerasechain reaction 9/R:.%lthough this techni-uemay be slightly more
sensitive than smearmicrosco#y, it is of limitedutility for the diagnosis ofacutely ill #atients in thestandard healthcaresetting. /R results areoften not available -uic+lyenough to be of value inestablishing the diagnosisof malaria infection.
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-ewer Diagnostic methods
Molecular Diagnosi
• /arasite nucleic acids aredetected using #olymerase chain
reaction 9/R:. This techni-ue ismore accurate than microsco#y.*o'ever, it is e;#ensive, and
re-uires a s#eciali2ed laboratory9even though technical advances'ill li+ely result in eld
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(+R is useful in s*eciesdetection
• /R is most usefulfor conrming thes#ecies of malarial
#arasite after thediagnosis has beenestablished byeither smear
microsco#y or RDT.
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Other /a'oratory %indings
• $ormocytic anemia of variableseverity.
• )iver function tests may be abnormal
• /resence of #rotein and casts in the!rine of children 'ith /.malariae issuggestive of Nuartan ne#hrosis.
• 7n severe &alci#arum malaria 'ithrenal damage may cause oliguria anda##earance of casts, #rotein, and redcells in the !rine
T t t
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Treatment
Dr.T.V.Rao MD 4
Faciparum$
%es
Fansidar or
Artemeter&'umefantrine
"o
(iva) or Ovale
*hloro+uine
*hec, -./0
/rima+uine
Malariae
*hloro+uine
TR9;TM9-T
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TR9;TM9-T• *%)?&%$TR7$"
• M%)%R?$"
# %T?V%N!?$"A/R?=!%$7)
• T%&"$?N!7$"• N!7$7$" based regimens
• *)?R?N!7$"A/R?=!%$7) 78 %$ INFERIOR
REGIMEN AND !O"#D NO$ %E "ED
Dr.T.V.Rao MD (0
1hat are ways to
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1hat are ways to*reent mos!uito 'ites2
• !se mos-uitore#ellants.
• @ear long #ants
and longsleeves.
• @ear light<
colored clothes.• !se 'indo'
screens
• !se bed nets. Dr.T.V.Rao MD (1
7nsecticide
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97T$s:
• 1hat is ha**ening here2• 1hat needs to ha**en within si= months2
• +an you think of any *ractical challenges2
Dr.T.V.Rao MD (
ource: HEPFDC,
2009.
O i i l 9 di ti (l
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Original 9radication (lans
• 7nterru#tion oftransmission ofmain s#eciesinfecting humansby DDT s#raying
• Malaria
disa##earss#ontaneously inunder 3 years
Dr.T.V.Rao MD (38ource =abaldon
Other 1ays to (reent Malaria
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Other 1ays to (reent Malaria @ho is at the highest ris+ of malariaO
# Travelers to an area high in malaria• Travelers often ta+e #ro#hylactic9#reventive: medicines to #reventmalaria.
# /regnant 'omen 9es#ecially those 'ith *7V:• /regnant 'omen are given intermittent#reventive treatment. They are given atleast doses of a malaria drug during
their #regnancy. # Coung children
• *o' can you #rotect young childrenO
Dr.T.V.Rao MD (
M l i V i
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Malaria Vaccine
• 8cientists are 'or+ing on a ne'malaria vaccine.
• The vaccine 'ould hel# #rotectchildren from deadly malaria.
• The vaccine boosts the immune
res#onse against malaria.• *o'ever, the vaccine is still
being tested.Dr.T.V.Rao MD (5
V i f M l i
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Vaccines for Malaria
• This degree of #rotection 'ould bee;tremely diPcult to achieve and mightnot be technically feasible 'ith currentvaccinology art and science. Many vaccine
develo#ers have therefore focused theireorts on creating a vaccine that limits theability of the #arasite to successfully infectlarge numbers of red blood cells. This
'ould not #revent infection but 'ould limitthe severity of the disease and hel##revent malaria deaths.HVaccine hallenges
+ t 8 iti ti
http://www.malariavaccine.org/mal-vac2-challenge.htmhttp://www.malariavaccine.org/mal-vac2-challenge.htm
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+urrent 8nitiaties
The /%T* Malaria Vaccine 7nitiativeand #artner, =la;o8mithlineBiologicals, #ublished recent /hase
trial results sho'ing that the vaccinecandidate, RT5,5, has a #romisingsafety and tolerability #role and
reduces malaria #arasite infectionand clinical illness due to malaria. This 'as the rst RT8,8 vaccine trialin %frican infants.
1orld Malaria Da
http://www.malariavaccine.org/files/101707/RTS_S_fact_sheet_Oct15_FINAL%20version%202.pdfhttp://www.malariavaccine.org/files/101707/RTS_S_fact_sheet_Oct15_FINAL%20version%202.pdf
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1orld Malaria Day
• @orld Malaria Day 9#reviously %fricaMalaria Day: 'ill no' becommemorated every year on 5
%#ril. The declaration of the 00( 1st@orld Malaria Day reJects theem#hasis the 'orld no' attaches to
the burden of this disease and itsim#act on the lives of those 'ho livein malaria endemic countries,es#ecially children under ve years
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+reated for >niersal
9ducation on MalariaDr.T.V.Rao MD
"mail
doctortvraoSgmail.com