MALARIA TEACHING BASICS By Dr.T.V.Rao MD

8/20/2019 MALARIA TEACHING BASICS By Dr.T.V.Rao MD

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MalariaTeaching Basics

Dr.T.V.Rao MD

Dr.T.V.Rao MD 1


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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.

Dr.T.V.Rao MD


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Lavern and Ronald Ross/ioneered the "vents on

Malaria


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Malaria – Historywho made it

Dr.T.V.Rao MD

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

Dr.T.V.Rao MD (


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(resentgeogra*hical distri'ution of malaria

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Dr.T.V.Rao MD 10


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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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Dr.T.V.Rao MD 1

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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Dr.T.V.Rao MD 6


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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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Dr.T.V.Rao MD 3(

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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S


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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@*

Dr.T.V.Rao MD (

S


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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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S


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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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+li i l i


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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

+li i l t ti


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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

Dr.T.V.Rao MD 60

l


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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

MALARIA TEACHING BASICS By Dr.T.V.Rao MD

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Transcript of MALARIA TEACHING BASICS By Dr.T.V.Rao MD