Management of Malaria

this lecture will help students from any medical field to learn more about the five species of Plasmodium Malaria, the clinical presentation of malaria, various strategies of malaria diagnosis, management of both complicated and non-complicated malaria, and management of malaria during pregnancy according to the recommendation of WHO.
https://www.youtube.com/watch?v=Tmk71zeydbw&t=12s

1. Parasitic Diseases
(Malaria)
A.Halboup
M.Pharm(Clinical)

2. LEARNING OBJECTIVES
Upon completion of the chapter, the reader will be able to:
1.Describe the presenting signs and symptoms of malaria.
2.List some specific toxicities of mefloquine.
3.Identify the monitoring parameters for quinidine gluconate in severe malaria.
4.Define the major complicationsof falciparum malaria.
5.Identify thediagnosticstrategiesofmalaria
6.Design treatment planfor complicated and uncomplicated types of malaria
7.Propose treatment plan for pregnant patientwith sever and non-sever malaria
8.Consequencesofmalariaduringpregnancy

3. parasites
GI parasites
(giardiasis and
amebiasis)
protozoan infections
(malaria and
trypanosomiasis)
helminthic diseases
(nematodes and
cestodes)
Ectoparasites
(lice and
scabies)

4. MALARIA
•WHOestimatesthat228millioncasesofmalariaoccurredworldwidein2018(confidence
interval:206–258million)andabout405000peoplediedfromthedisease,mostlychildren
under5yearsofageinsub-SaharanAfrica.
❑Theprimaryreasonsformorbidityanddeathinmalariaare:
❖failuretotakerecommendedchemoprophylaxis,
❖inappropriatechemoprophylaxis,
❖delayinseekingmedicalcareorininitiatingtherapypromptly,and
❖misdiagnosis
•Evaluationofapatientshouldinclude:specifictravelhistory,detailsofchemoprophylaxis,
andphysicalfindings(eg,splenomegaly).

5. •MalariaistransmittedbythebitesoftheAnophelesmosquitoes,whichintroduceintothe
bloodstreamoneoffivespeciesofsporozoitesoftheplasmodia.
Plasmodia
P.
falciparum
P. OvaleP. vivax
P.
malariae
P.knowlesi

6. •Initialsymptomsofmalariaarenonspecificandmayresembleinfluenzaandincludechills,
headache,fatigue,musclepain,rigors,andnausea.Theonsetofthesymptomsisbetween1
and3weeksfollowingexposure.
•Fevermayappear2to3daysafterinitialsymptomsandmayfollowapatternandoccur
every2or3days(P.vivax,P.ovale,andP.malariae).
•FeverwithP.falciparumcanbeerraticandmaynotfollowspecificpatterns.
–Falciparummalaria(orP.knowlesi)mustalwaysberegardedasalife-threatening
medicalemergency.

7. Pathophysiology
•WithinminutesafterthebiteoftheAnophelesmosquito,thesporozoitesinvadehepatocytes
andbeginanasexualphasecalledschizonts.
•patientmaybeasymptomaticduringthisperiod.Afteralapseof5and15days(depending
onthespecies),schizontsrupturetoreleasedaughtercells(merozoites)intotheblood,which
theninvadeerythrocytes.
–Thisasexualphaseisabout48hoursforP.falciparum,P.vivax,andP.ovale,and72
hoursforP.malariae.

8. •UnlikeP.falciparumandP.malariae,whichonlyremainintheliverforabout3weeks
beforeinvadingerythrocytes,P.ovaleandP.vivaxcanremainintheliverforextended
periodsinalatentstage(ashypnozoites);thiscanresultintherecurrenceoftheinfection
afterweeksormonths.
–primaquinefor14daystherapyisnecessarytoeradicatethisstageoftheinfection.

9. Clinical Presentation and Diagnosis
•Normally,theappearanceofaprodromewithheadache,anorexia,abdominalpain,fatigue,
fever,chills,andmyalgiawhichcoincideswiththeerythrocyticphaseofmalaria,occurs
frequentlybetween10and21daysafterbeingexposed.
•Thisphasecausesextensivehemolysis,whichresultsinanemiaandsplenomegaly.
•ThemostseriouscomplicationsarecausedbyP.falciparuminfections.Thisattributedto
–(a)itsabilitytoproducehighparasitism(upto80%)ofredcellsofallages;and
–(b)thepropensitytobesequesteredinpostcapillaryvenulesofcriticalorganssuchas
brain,liver,heart,lungs,andkidneys.Asresults,P.falciparumContributestosevere
ischemiaandmetabolicderangements.
•P.malariaeisimplicatedinimmune-mediatedglomerulonephritisandnephroticsyndrome

10. Diagnosis
•Genotyping ofmalaria parasites (PCR)
–Innovations for detecting malaria include DNA or RNA probes by PCR and monoclonal
antibody testing (not widely available for clinical use.).
•Microscopic test (the “gold standard”):blood smears were stained with 2.5% Giemsa for
45min and examined at a magnification of 1000×.
•A P. falciparum–specific monoclonal antibody test, histidine-rich protein 2 (HRP-2), is fairly
sensitive for P. falciparum and is recommended by the World Health Organization as an
alternative for microscopic test.
–rapid malaria diagnostic tests (RDTs) are restricted from wide use by cost, regulatory
standards, operative expertise, and availability.

11. Treatment
•Theprimarygoalinthemanagementofmalariaistherapididentificationofthe
Plasmodiumspeciesbybloodsmears(boththickandthinsmearsrepeatedevery12hours
for3days).
•Antimalarialtherapyshouldbeinitiatedpromptlytoeradicatetheinfectionwithin48to
72hoursandavoidcomplicationssuchashypoglycemia,pulmonaryedema,andrenal
failure.
•The presence of parasites in the blood 3
to 5 days after initiation of therapy
suggests resistance to the drug regimen.

12. Pharmacologic Therapy
•Inanuncomplicatedattackofmalaria(forallplasmodiaexceptchloroquine-resistantP.
falciparumandP.vivax),therecommendedoralregimenischloroquine600mg(base)
initially,followedby300mg(base)6hourslater,andthen300mg(base)dailyfor2days.?
•Insevereillnessorfalciparummalaria,patientsshouldbeadmittedtoanacutecareunit,
andquinidinegluconate10mgsalt/kgasaloadingdose(maximum600mg)in250mL
normalsalineshouldbeadministeredIVslowlyover1to2hours.
•Thisshouldbefollowedbycontinuousinfusionof0.02mg/kg/minofquinidineforatleast24
hoursuntiloraltherapycanbestarted.
–Inpatientswhohavereceivedeitherquinineormefloquine,theloadingdoseof
quinidineshouldbeomitted.
•Oralquininesalt(650mgevery8hours)plusdoxycycline100mgtwicedailyshouldfollow
theIVdoseofquinidinetocomplete7daysoftherapy.

13. Pharmacologic Therapy
cont…
•In patients who cannot tolerate quinidine or if quinidine is not readily available,
IV artesunate 2.4 mg/kg/dose for 3 days, at 0, 12, 24, 48, and 72 hours may be used, followed by
oral therapy.
–Oral therapy may include doxycycline, mefloquine , clindamycin, or atovaquone/proguanil,
•AcuteP.falciparummalariaresistanttochloroquineshouldbetreatedwithIVquinidine.
•Hypoglycemia,thatisassociatedwithbothP.falciparumandquinidineadministration,
shouldbecheckedevery6hoursandwhennecessary,correctedwithdextrose(5%–10%)
infusions.
–Complication of falciparum malaria include : pulmonary edema, hypoglycemia,
jaundice, renal failure, confusion, delirium, seizures, coma, and death,

14. Pharmacologic Therapy
cont…
•Quinidineinfusionsshouldbeslowedorstoppedif
–theQTintervalisgreaterthan0.6second,
–theincreaseintheQRScomplexisgreaterthan25%,or
–hypotensionunresponsivetofluidchallengeresults.
•Quinidinelevelsshouldbemaintainedat3to7mg/dL.
•Monitor(ECG,BP,BS)whenQuinidineisused.
•In P. falciparum, P. vivax, P. ovale, or P. malariae (chloroquineresistant) infections, a dose of 750 mg
of mefloquine followed by 500 mg 12 hours later is recommended.
–Mefloquineis associated with sinus bradycardia, confusion, hallucinations, and psychosisand
should be avoided in patients with a history of epilepsy, cardiovascular problems or depression.

15. Pharmacologic Therapy
cont…
•InpatientswhohaveP.vivaxorP.ovalemalaria,followingthetreatmentoftheacute
phaseofmalariaandscreeningforglucose-6-phosphatedehydrogenase(G6PD)deficiency,
patientsshouldreceivearegimenofprimaquinefor14daystoensureeradicationofthe
hypnozoitestageofP.vivaxorP.ovale.
•Themainadverseeffectofprimaquineishaemolyticanaemiainindividualswithglucose-
6-phosphatedehydrogenasedeficiency(G6PDd).

16. Pregnant Women with malaria
•Pregnantwomenarethreetimesmorelikelytodevelopseverediseasethannon-pregnant
women.
•Malariainfectionduringpregnancycanleadto:
–miscarriage,prematuredelivery,lowbirthweight,congenitalinfection,and/orperinatal
death.
•ForpregnantwomendiagnosedwithuncomplicatedmalariacausedbyP.malariae,P.vivax,
P.ovale,orchloroquine-sensitiveP.falciparuminfection,prompttreatmentwith
chloroquine(treatmentscheduleaswithnon-pregnantadultpatients)isrecommended.
–Alternatively,hydroxychloroquinemaybegiveninstead.
•Forwomenintheirsecondorthirdtrimesters,artemether-lumefantrineisanadditional
option.

17. •Quininetreatment should continue for 7 days for infections acquired in Southeast Asia
and for 3 days for infections acquired elsewhere; clindamycintreatment should continue
for 7 days regardless of where the infection was acquired. (1
st
trimester :quinine
+clindamycin for 7 days )
•For pregnant women diagnosed with uncomplicated malaria caused by chloroquine-
resistant P. vivax infection, prompt treatment with artemether-lumefantrine(second and
third trimesters) or mefloquine(all trimesters) is recommended.
•IV artesunateis safe in infants, children, and pregnant women in the second and third
trimesters(used only for severe malaria).

18. Treatment: Severe Malaria
Allpatientswithseveremalaria,regardlessofinfectingspecies,shouldbetreatedwith
intravenous(IV)artesunate.
•OralmedicationscanbeusedtillarrivingofIVartesunate
–Artemether/lumefantrine(Coartem®):
–Atovaquone/proguanil(Malarone®):
–Quinine:Adults:650mg(salt)every8hours.
–WhenIVartesunatearrives,discontinuetheoralmedication.
•ThedosingofIVartesunateisasfollows:Adultsandchildren≥20kg:2.4mg/kgat0hour,12
hours,and24hours;and48hours
–IVartesunateissafeininfants,children,andpregnantwomeninthesecondandthirdtrimesters.

20. Literature

21. Dose and duration of tttregimens
•In the AS+SP studies the patients received a dose of 4mg/kg/day artesunateonce a day
for 3days and a single administration of 25/1.25mg/kg SP on day 0.
•In studies on AL, the patients were given AL (Coartem®, Novartis) according to body weight
bands.
–Patients weighing 5–14kg received one tablet (20mg artemetherplus 120mg lumefantrine)
per dose,
–those weighing 15–24kg received two ,
–those weighing 25–34kg three tablets, and
–those weighing≥35kg received four tablets.
•In total, six doses were administered at hours 0, 8, 24, 36, 48, and 60

22. Malaria prophylaxis
•Chloroquine: 300 mg base (500 mg salt), once/week.
–Begin 1-2 weeks before travel, once/week during travel, and for 4 weeks after leaving.
•Mefloquine 250 mg weekly
–1 tablet weekly. Begin 1-2 weeks before travel, weekly during travel, and for 4 weeks
after leaving.
•Doxycycline : 100 mg daily.
–Begin 1-2 days before travel, daily during travel, and for 4 weeks after leaving.
•Primaquine 30 mg base, daily (NOT recommended in (G6PD) deficiency.
–Begin 1-2 days prior to travel, daily during travel, and for 7 days after leaving

23. Summary
•Malaria is transmitted by the bites of the Anopheles mosquitoes(female)
•There are five species of malaria (P. falciparum
99%
, P. ovale, P. vivax, P. malariae, and P.knowlesi).
•Falciparum malaria must always be regarded as a life-threatening medical emergency.
•Clinical presentation (headache, anorexia, abdominal pain,fatigue, fever, chills,and myalgia, occur 10-21 day
after exposure)
•Diagnosis: microscopic test, PCR, RDT(hrp-2)
•Treatment : complicated (IV:artesunate2.4mg/kg/dose for 3days(0,12,24,36,72) or quinidine (loading and
continuous dose ), all tttshowed by followed by oral therapy for 7 days . Oral therapy: doxycycline, mefloquine ,
clindamycin, or atovaquone/proguanil,.
–Monitor (ECG, BP, BS) when Quinidine is used.
•Uncomplicated cases : orally (coartum, chloroquine, hydroxychloroquine, mefloquine, quinine plus doxycycline).
•In patients who have P. vivax or P. ovalemalaria , following the treatment of the acute phase, a regimen of
primaquine for 14 days. Why ?
•Sever cases of malaria : artesunate for 3 days (0, 12, 24, 48, 72) followed by ordaltherapy for 7 days.
•Malaria in pregnant woman: mefloquine for all semester , artesunate or artemether with lumefantrine for 2
nd
and
3
rd
trimester.

24. Case study

25. Continue