Pharmacotherapy of Malaria v.1
Pharmacotherapy of Malaria v.1
Pharmacotherapy of Malaria v.1
Malaria
Dr. Sumit Ourasang
Senior Resident
Department of Pharmacology
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• Malaria is an acute febrile illness caused by Plasmodium parasites, which are
spread to people through the bites of infected female Anopheles mosquitoes.
Organization WH. World malaria report 2022. World Health Organization; 2022. 2
MAGNITUDE OF THE PROBLEM :: National Center for Vector Borne Diseases Control (NCVBDC) [Internet]. [cited 2021Oct19].. Available from:
https://ncvbdc.mohfw.gov.in/index4.php?lang=1&level=0&linkid=420&lid=3699
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Life cycle
P.vivax 50%
P.falciparum >40%
P.malariae and P. ovale (rare)
• Conventional method
• PCR
• Detects 1 parasite/microlitre
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Mosquito (sexual phase)
sporozoite
PRIMAQUINE
PRIMAQUINE hypnozoite
PRIMAQUINE schizont
PROGUANIL
ARTEMISININ
derivatives PRE-ERYTHROCYTIC
STAGE
Gametocytes
Blood schizont
Merozoites
ERYTHROCYTIC STAGE
Late trophozoite
CHLOROQUINE SULFONAMIDES
ARTEMISININ TETRACYCLINES
LUMEFANTRINE CLINDAMYCIN RBC
MEFLOQUINE PYRIMETHAMINE
PROGUANIL Early trophozoite (ring form)
QUININE 9
Anti-malarial agents
Erythrocyctic schizonticides Chloroquine
Artemisinin
Lumefantrine
Mefloquine
Proguanil
Quinine
Sulfonamides
Tetracyclines
Clindamycin
Pyrimethamine
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Brunton LL, Knollmann BC, Hilal-Dandan R, editors. Goodman & Gilman’s the pharmacological basis of therapeutics. Thirteenth edition. New York: McGraw Hill Medical; 2018. 1419 p. page no.973
Principles of malaria management
3. Combination therapy
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1.WHO Guidelines for malaria, 14 March 2023. Geneva: World Health Organization; 2023 (WHO/UCN/GMP/ 2023.01).
Objectives and use of antimalarial drugs
Tripathi KD. Essentials of medical pharmacology. Eighth edition. New Delhi: Jaypee Brothers Medical Publishers; 2019. 1064 p. page no.874 12
Chloroquine
• 4-aminoquinoline
• Targeting the Food VacuolePrevents polymerization of
heme to hemozoinLysis
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Chloroquine
Extensive tissue binding A loading dose is required to achieve
effective concentrations in plasma
Complex pharmacokinetics Plasma levels of the drug are
determined primarily by the rate of distribution rather than the rate
of elimination
Narrow safety margin
Peak plasma levels ~3-5 hours after oral dose
ADR – Oral therapy GI upset, headache, visual disturbances,
and urticaria
High cumulative doses - irreversible retinopathy and
ototoxicity
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Quinine
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Artemisinin
Endoperoxide bridge of
artemisininCleaved by
hemeRadicalsInhibit ER
based Ca ATPase of parasite
Generate free
radicals that alkylate
and oxidize proteins
and lipids in
parasitized
erythrocytes
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Artemisinin
Potent and fast-acting antimalarials rapid parasite clearance
and fever resolution
Blood schizonticide
Short t1/2
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Rationale for ACT(Artemisinin Combination
Therapy)
Enhanced efficacy and reduced likelihood of resistance.
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Advantages of ACT
The advantages of ACT relate to the unique properties and mode of
action of the artemisinin component –
World Health Organization [WHO]. Antimalarial Drug Combination Therapy . Report of a WHO Technical Consultation. 2001.
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Other anti-malarials
Drug MOA/Class Use
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CHLOROQUINE
No of tablets
Age Day1 (10mg/kg) Day 2 (10mg/kg) Day 3 (5 mg/kg)
<1 ½ ½ ¼
1-4 1 1 ½
5-8 2 2 1
9-14 3 3 1½
>15 4 4 2
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Treatment of Uncomplicated malaria
Non-falciparum P.falciparum
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Non-falciparum malaria treatment (uncomplicated)
Atovaquone-proguanil
Quinine sulfate +
Doxycycline/
tetracycline/ clindamycin
mefloquine
• Yellow conjunctiva
• Abdominal pain
• Nausea
• Vomiting
• Breathlessness
Tefanoquine • Pregnant Chloroquine Adult dosing (>16 years): Not Not Not
300 mg single dose
• Lactating recommended recommended recommended
• ≤2 years of Pediatric dosing:
age
Children >2 years of age
and >10 kg to 20 kg: 100
mg (two 50 mg
dispersible tablets)
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Falciparum malaria
North-eastern states
All over India except North eastern states
Artemether- Lumefantrine
• Artesunate 4mg/kg for 3 days
• Sulfadoxine (25mg/kg) +
pyrimethamine (1.25mg/kg) on day 0
1.WHO Guidelines for malaria, 14 March 2023. Geneva: World Health Organization; 2023 (WHO/UCN/GMP/ 2023.01). 38
Principles of management
• ACT more preferable than quinine
• Management of complications
• Anti-emetics causes sedation which should be distinguished from the patient progressing towards
severe malaria
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Pre-referral treatment
If NA
If NA
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Management in tertiary centre IV artesunate
Evalaute after 4 weeks for
2.4mg/kg
Delayed hemolytic anemia
0,12,24 hrs
If NA
Artemether IM
3.2mg/kg,
Followed by 1.6mg/kg x 3 days
If NA
Quinine IV IV infusion
20mg/kg in 5% dextrose over 4 hours No bolus
Cardiac monitoring
Followed by 10mg/kg IV over 4 hours at 8-12 hrs interval Glucose monitoring
Once patient
tolerate orally
Oral regimen
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• Monitoring with parasite density
• Every 12hrs
• Completing therapy
• If parasite density ≤ 1 % plan for oral regimen
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Malaria in Pregnancy
• High risk group
• VAR2CSA
• Low transmission area – acute lung injury, severe hypoglycemia, coma, pregnancy loss
Rogerson SJ. Management of malaria in pregnancy. Indian J Med Res. 2017 Sep;146(3):328–33.
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Treatment
Uncomplicated P.falciparum 1st AM-L
Chloroquine-resistant trimester ACT (without antifolates)
Quinine + Clindamycin
2nd & 3rd ACT
trimester Quinine + Clindamycin
Chloroquine-sensitive Any Chloroquine/HCQ
P.falciparum trimester
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• ACTs in Pregnancy
• Artemether- Lumefantrine
• Artesunate-amodiaquine
• Artesunate- mefloquine
• Dihydroartemisinin- piperaquine
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• Anti-relapse therapy (non-falciparum)
• Primaquine/tafenoquine are CI in pregnant women
• Following delivery after G6PD status (mother and infant) initiate primaquine
• In 1st trimester – AM-L can be used rather than quinine based regimen
(DP) -Dihydroartemisinin-piperaquine
Saito M, McGready R, Tinto H, Rouamba T, Mosha D, Rulisa S, et al. Pregnancy outcomes after first-trimester treatment with artemisinin derivatives versus non-artemisinin antimalarials:
a systematic review and individual patient data meta-analysis. Lancet. 2023 Jan 14;401(10371):118–30.
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• Severe malaria
• IV artesunate
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Algorithm for diagnosis and treatment
Clinically suspected malaria
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National Vector Borne Disease Control Programme (NVBDCP): Guidelines – Malaria.2013
When microscopy not available
Perform RDT
Positive Negative
Pf RDT positive Pf RDT negative
Treat acc. to
ACT 3 days CQ 3 days and wait species
for microscopy
PQ day 2
• Long-term
• More than 6 weeks
• RTS,S/AS01
• Pre-erythrocytic recombinant protein vaccine
• 0.5ml IM
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• G6PD assessment before primaquine is needed
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Thank
You
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