Transcript Malaria Endemic Areas and Drug Resistance Chloroquine

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.
Blood schizonticides: (A
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?
Absence of effective immune response. .1
Exposure to repeated mosquito bites and .2
re-infection.
Incomplete treatment. .3
Relapse. .4
Recrudescence. .5
Malaria Endemic Areas and Drug Resistance
Chloroquine resistance
SP resistance
Multi-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 pretreatment level in 48 hours, but
reappears between 2-4 weeks.
RI, Early Recrudescence: The asexual
parasitemia reduces to < 25% of pretreatment 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.
Definition of drug resistance
14 days test for assessing the
efficacy of antimalarial drugs using
clinical and parasitological criteria:
early treatment failure.1
Late treatment failure.2
Adequate clinical response.3
What causes drug resistance ?
Parasite with a degree of resistance to antimalaria drug
are:
Spontaneously produced by mutations..1
Selected for by subtherapeutic concentrations of the .2
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•
Molecular genetics
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 •
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:
Physiological adaptation.
Single mutation for resistance.
Longer half –life.
Host immunity.
Number of people using these drugs.
Poor compliance.
.1
.2
.3
.4
.5
.6
Prevention of drug
resistance:
Selection of drugs.
Avoid drugs with longer half – life if possible.
Avoid basic antimalarias for non malarial
indications.
ensure compliance.
Monitoring for resistance and early treat of
these cases to prevent their spread.
.1
.2
.3
.4
.5
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