Relative cost of antimalrial drug

Treatment:

Based on the knowledge of the anti malarial drugs effects on the parasite at

various stages of the life cycle.

)ABlood schizonticides:

Treatment of acute attack malaria.

e.g chloroquine, qunine, artimisinin.

B) Tissue schizonticides:

only primaquime.

C) Gametocyticides:

Chloroquine and amodiaquine, are effective against the gametocytes of

P.vivax P.ovale, P.malaria and immature gametogytes of P.falciparum.

Primaquine is gametocyticidal for all four species of human malaria parasites.

Recurrent malaria:

Why dose malaria recur?

.1Absence of effective immune response.

.2Exposure to repeated mosquito bites and re-infection.

.3Incomplete treatment.

.4Relapse.

.5Recrudescence.

Malaria Endemic Areas and Drug Resistance

Chloroquine resistanceSP resistanceMulti-drug resistance

Drug resistance:

•Definition:

is the ability of the parasite species to survive and/or multiply despite the

administration an absorption of a drug.

Degree of resistance:

WHO has developed a simple scheme for estimating the degree of the resistance that involves studying the parasitemia over

28 days.

Smears on day 2 , 7 and 28 are done to grade the resistance as RI to RIII.

Sensitive (S): The asexual parasite count reduces to 25% of the pre-treatment

level in 48 hours after starting the treatment and complete clearance after

7 days, without subsequent recrudescence - Complete Recovery.

RI, Delayed Recrudescence: The asexual parasitemia reduces to < 25% of pre-

treatment level in 48 hours, but reappears between 2-4 weeks.

RI, Early Recrudescence: The asexual parasitemia reduces to < 25% of pre-

treatment level in 48 hours, but reappears earlier.

RII Resistance: Marked reduction in asexual parasitemia )decrease >25%

but <75%) in 48 hours, without complete clearance in 7 days.

RIII Resistance: Minimal reduction in asexual parasitemia, )decrease <25%)

or an increase in parasitemia after 48 hours.

14 days test for assessing the efficacy of antimalarial drugs using clinical and parasitological criteria:

.1early treatment failure

.2Late treatment failure

.3Adequate clinical response

Definition of drug resistance

What causes drug resistance?

Parasite with a degree of resistance to antimalaria drug are:

.1Spontaneously produced by mutations.

.2Selected for by subtherapeutic concentrations of the drug

Exposure of parasite to such concentrations can follow:

•Inadequate treatment with any antimalarial•Monotherapy with a drug with a long elimination time•Rapid reinfection after treatment, while some drug remains

The malaria parasite:

•Is haploid for most of the cycle•It diploid at the time of gamete

fusion•Undergoes meiosis within few our

hours of the fertilization .

This allow genetic recombination:•Reassortment of parent

chromosomes•Crossing over events

Molecular genetics

It is necessary to lock in metabolism of the parasite, and the mode of action of

the anti malaria drug in order to appreciate the physical nature of

resistance.

Artemisinin:

The newest and most effective of all anti malarial drugs and seem to effect the

protein synthesis .

Important factors that are associated with resistance:

.1Physiological adaptation.

.2Single mutation for resistance.

.3Longer half –life.

.4Host immunity.

.5Number of people using these drugs.

.6Poor compliance.

Prevention of drug resistance:

.1Selection of drugs.

.2Avoid drugs with longer half – life if possible.

.3Avoid basic antimalarias for non malarial indications.

.4 ensure compliance.

.5Monitoring for resistance and early treat of these cases to prevent their spread.

Control of malaria:

•Involve three living beings: Man , parasite and mosquito.

Man: treat the affected protect the unaffected.

Parasite: 1 \kill the asexual forms….prevent the

progression of the diseases. 2 \kill the sexual forms….prevent the spread of

mosquitoes. 3 \ensure full treatment.

Mosquito :

1 \prevent breeding.

2 \prevent entry.

3 \prevent bites.

Sources of initial treatment for young and children with fever, Nigeria