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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: Treatment of acute attack malaria. e.g chloroquine, qunine, artimisinin. B) Tissue schizonticides:
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Treatment: Based on the knowledge of the anti malarial drugs effects on the parasite at various stages of the life cycle.
Blood 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? • Absence of effective immune response. • Exposure to repeated mosquito bites and re-infection. • Incomplete treatment. • Relapse. • Recrudescence.
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 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.
Definition of drug resistance 14 days test for assessing the efficacy of antimalarial drugs using clinical and parasitological criteria: • early treatment failure • Late treatment failure • Adequate clinical response
What causes drug resistance ? Parasite with a degree of resistance to antimalaria drug are: • Spontaneously produced by mutations. • Selected 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
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.
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.
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