RECENT DRUG THERAPY IN MALARIA:

Objectives and Use of Antimalarials

To prevent and treat clinical attack of malaria

To completely eradicate the parasite from the body

To reduce the human reservoir of infection

Classification of Antimalarial drugs (AMD’s)

Cinchona alkaloids: Quinine, quinidine

Quinoline derivatives: Chloroquine, primaquine, mefloquine, halofantrine

Antifolates: Sulfadoxine, dapsone, proguanil, pyrimethamine

Naphthoquinone derivative: Atovaquone

Artemisinin compounds: Artesunate, artether, artemether

Antimicrobials: Tetracycline, doxycycline, clindamycin

Life cycle of malarial parasite where drugs act on

Acute attack of malaria

‘Chloroquine sensitive Falciparum malaria’

1st day - Chloroquine phosphate 600mg base  (1gm salt = 600mg base) followed  by 300mg base 8hr later 

2nd & 3rd day – chloroquine 300mg base

4th-18th day – primaquine 7.5mg bid  (p.vivax & p.ovale).  

Chloroquine resistant malaria

Single drug therapy:

 Quinine 600mg t.i.d for 7 days

 Mefloquine 750mg followed by 500mg 12hr later

 Artesunate 100mg b.d on 1st day followed by 100mg o.d  for 5 days.

Combination drug therapy:

Quinine 600mg t.i.d. for 7days, Tetracycline 250mg q.i.d ‘or’ Doxycycline 100mg o.d for 7 days             ‘OR’

Pyrimethamine75mg + Sulfadoxine 1500mg 3 tab single dose on the last day of treatment                          ‘OR’

Artesunate 4mg/kg/d for 3days + Mefloquine750mg followed by 500mg 12hr later

‘OR’

Mefloquine 750mg followed by 500mg 12hr later

‘OR’

Clindamycin 900mg t.i.d. for 5days

‘OR’

Atovaquone 1000mg/day (2 tab b.d.) + Proguanil 400mg/day for 3 days.

Treatment in severe complicated malaria:

Chloroquine sensitive areas:                                                                                                                  Chloroquine phosphate  (Max.dose 25mg base /kg/day ): I.M route: 3.5mg base/kg every 6hr, I.V.route: 10mg base/kg slow infusion over 8hr, followed by 5mg/kg base on every 12hr.

Chloroquine resistant areas:

Quinine 20mg/kg by i.v. infusion over 4hr &10mg/kg 8th hr thereafter

Artesunate 120mg i.v/ i.m on 1st day, followed by 60mg daily for 4 days 

Artemether 1.6mg/kg b.d. by i.m on 1st day, then o.d for next 5 days.

Treatment of malaria in Pregnancy:

Chloroquine remains the drug of choice in pregnancy.

Drug should be avoided in 1st trimester and it’s safer to give in 2nd and 3rd trimester.

Chemoprophylaxis of malaria:

Chloroquine sensitive areas: Chloroquine phosphate 300mg base weekly

Chloroquine resistant areas : Mefloquine 250mg weekly, ‘OR’ Doxycycline 100mg daily                      ‘OR’ Atovaquone 250mg + Proguanil 100mg (MALARONE) 1 tab daily.

Antimalarial drug Resistance:

WHO definition: “Ability of a parasite strain to survive and/or multiply despite the administration and absorption of a drug given in doses equal to or higher than those usually recommended but within tolerance of the subject”.

Later modified to specify that the drug, must “gain access to the parasite or the infected red blood cell for the duration of the time necessary for its normal action”  

Factors which contribute to treatment failure:     

Non-compliance with duration of dosing regimen

Poor drug quality, Drug interactions, Poor or erratic drug absorption, Misdiagnosis, Lack of guidelines/poor drug treatment policies, Irrational prescribing, Irrational drug use.  

Mechanism of antimalarial drug resistance:

Spontaneous mutations:

    - Single point mutation

    - Multiple mutations

Biochemical mechanism of resistance:

Chloroquine resistance: In P. falciparum malaria, resistance is related to increased chloroquine efflux mechanism.

Antifolate combinations: Specific gene mutations encoding for resistance to both DHPS & DHFR have been identified.

Atovoquone: Resistance is conferred by single point mutations in the cytochrome b-gene.

TOGETHER WE CAN DEFINITELY BEAT MALARIA!