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Malaria treatment
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- 2. Chloroquine sensitive malaria Chloroquine 10mg/kgbw stat dose followed by 10mg/kg on 2nd day f/b 5mg/kg bw on 3rd day or Chloroquine 10mg/kg bw f/b 5mg/kg at 6hr,24 hrs & 48hrs Add Primaquine 0.25-0.5mg/kg bw/ day for 14 days only if G6PD levels are normal This chloroquine level resides for about 2-3 weeks in blood, thus prevents the first Relapse of P.vivax which generally occurs at 3wks after onset of primary illness. So relapses begin after 5-6wks of illness if not treated with Primaquine.
- 5. CHLOROQUINE S/E: - It isgenerally well tolerated in therapeutic doses of malaria - Large doses used in treatment of Rheumatoid Arthritis are usually associated with higher frequency of side effects - Pruritis is a common side effect and is more severe in darkly skinned individuals. - Other rare side effects : 1) elevated liver enzymes 2) GI disturbances 3) convulsions, retinopathy and arrhythmias Overdosages can be dangerous and can lead to death within hours. Pt. may progress from feeling dizzy and drowsy with headache and gi upset to sudden visual loss, convulsions, hypokalemia, hypotension and cardiac arrhythmias
- 6. The most importantside effect of Primaquine is hemolysis in G6PD deficient Patients Amount of hemolysis depends on dosage, duration of exposure and degree of G6PD Deficiency Primaquine is rapidly eliminated from the body. So hemolysis will stop once the drug is stopped. So Pt. being treated with Primaquine should be looked for anemia, red or black urine and should be stopped immediately if present. A single dose of 0.25mg/kg bw Primaquine as Gametocidal will not lead to hemolysis even in G6PD deficient pt. So it is not necessary to check G6PD status for single dose administration as given in Falciparum malariae.
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- 9. ACT should begiven for 3 days.
- 14. 1) Hypersensitivity reactions 2) GIDiturbances 3) Cough 4) Rash 5) Arthralgia 6) Delayed hemolysis
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- 16. SEVERE MALARIA Impaired consciousness Prostration Multipleconvulsions Acidosis Hypoglycemia Anemia Jaundice Pulmonary edema Significant bleeding Shock
- 18. ARTESUNATE > ARTEMETHER> QUININE irrespective of whether patient is A infant or pregnant or a lactating female. Mortality from untreated severe malaria is almost 100%. With effective treatment mortality reduces to 10-20% If a pt. presents with severe anemia , there are more chances of survival as compared to acidosis Therapeutic objective : is to prevent the patient from dying Artesunate Dosage : 2.4mg/kg Studies have shown that artesunate dosage between 1.5-4mg/kg dose is not associated with any toxicity
- 21. Artesunate and PostTreatment Hemolysis - Starts 7days after treatment with Artesunate - Between 2010 and 2012, there were 6 reports involving a total of 19 European travellers with severe malaria who were treated with artesunate injection and developed delayed hemolysis. Out of 6 , 1 was adult Artesunate rapidly kills ring stages parasites Taken out of RBCs by Spleen This infected RBCs have a shorter life span Leads to hemolysis
- 22. ARTESUNATE ARTEMETHER QUININE -Water soluble and can be given Intavenously - Oily solution - Should be given only I.M I.V or I.M both are equally effective Rapidly converts into Dihydroartemisnin, the active form. Converts slowly Loading dose : 20mg/kg f/b 10mg/kg every 8hrly Artesunate powder is diluted with 5ml of 5%D and given I.V or I.M Only I.M / Oral If no improvement in 48hrs, dose reduced to 10mg/kg every 12hrly 2.4mg/kg bw / dose 3.2mg/kg stat f/b 1.6mg/kg daily Shouldn’t be infused rapidly. - Dilute in 5%D and infuse over 4hrs ( not >5mg/kg/hour) Dose adjustment is not required for Artemisnin derivatives in Liver or Kidney diseases.
- 23. FOLLOW ON TREATMENT -24hrs parenteral f/b complete ACT - In ACT, Artemisnin + Mefloquine should be avoided in Pt. presenting with unconsciousness or altered consciousness. - If ACT not available : Artesunate/Quinine + Doxycycline(7d) or Artesunate/Quinine + Clindamycin(preferred in Pregnancy)
- 24. MANAGEMENT OF COMPLICATIONSOF SEVERE FALCIPARUM MALARIA Coma Hypoglycemia Convulsions Hyperpyrexia Pulmonary edema Severe anemia Acute kidney injury Coagulopathy Metabolic acidosis shock
- 26. TREATMENT OF SEVERE FALCIPARUMMALARIA IN PREGNANCY - Artesunate > artemether > quinine - 2nd & 3rd trimester > 1st trimester - Hypoglycemia and pulmonary edema - Risk of mortality 50% more in pregnant > non pregnant - Fetal demise and premature labor - Teratogenic effects : decreases embryonic erythroblasts, cardiac myopathy delay in limb and tail development
- 27. SEVERE VIVAX MALARIA -Very rare - Anemia, thrombocytopenia , acute pulmonary edema are common TREATMENT Parenteral Artesunate > Artemether > Quinine for 24hrs f/b ACT or Chloroquine
- 29. 1) There isno liver stage since parasite directly enters blood 2) Hypnozoites are not found 3) Hence there is no relapse 4) No need for Primaquine
- 30. 1) Infective formto man = Sporozoites present in salivary glands of Mosquito 2) Infective form to man in case of blood transfusion 3) Infective form to mosquito = Gametocytes - To infect mosquito, Gametocyte must be mature, viable, count >12per cubic mm. merozoites
- 31. P.Vivax P.Falciparu m P.Malariae P.Ovale Relapse(Hypn ozoites) seenNot seen Not seen Seen Recrudescene ce Not seen seen seen Not seen Incubation period 14days 12days 28days 17days Erythrocytic cycle 48hrs 48hrs 72hrs 48hrs
- 32. Recrudescence is dueto persistence of drug resistant parasite. In Falciparum : Disease appears after 2-3weeks of completion of treatment In Malariae ; Disease appears very late almost after 60yrs. -due to hypnozoites -May reappear after2-3yrs -Seen in P.vivax and ovale.
- 33. Species Disease Periodicity P.VivaxBenign tertian 48hrs P.Falciparum Malignant tertian 48hrs P.Ovale Ovale tertian 48hrs P.Malariae Quartian 72hrs P.Knowlesi Quotidian 24hrs
- 34. Plasmodium spcies Typeof RBC P.Vivax Young RBCs P.Falciparum RBCs of all age P.Ovale Reticulocytes /Young RBCs P.Malariae Old RBCs
- 35. Sickle cell traitProtective from P.falciparum Thallasemia trait Protective from P.falciparum Fetal Hb Protective from P.falciparum G6PD deficiency Protective from P.falciparum Ovalocytosis Protective from P.falciparum Duffy negative RBCs Protective from P.vivax
- 36. -It is aparasite of monkey but can also affect humans -Early trophozoite resembles to P.falciparum -Late trophozoite resembles to P.malariae -Quotidian malariae
- 37. P.Vivax P.Falciparu m P.Malariae P.ovale Formsseen in peripheral blood smear Early and late trophozoites, gametocytes and schizonts Ring forms (early trophozoites) and gametocytes Similar to that of vivax Ring forms are known as Band forms. Similar to that of vivax Gametocye Spherical, almost occupies RBC Banana shape, larger than RBC Similar to that of vivax Similar to that of vivax RBC size Enlarged Normal Normal enlarged Stippling Schuffner’s dots ( small red dots) Maurer’s cleft( large red spots) Ziemann’s dots James dots
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- 41. Thin smear =for species identification Thick smear = for quantification
- 42. -pLDH and Aldolase= common to all plasmodium species -HRP-2 Ag detection = specific for P.falciparum
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- 44. -Most potent andfastest acting schizonticidal drugs -But have short duration of action, hence cant be used singly and has to be combined with slower acting drugs - Acts by producing free radicals and toxic heme products -Since they produce free radicals, free radicals have teratogenic effect. Hence C.I in 1st trimester. Can be given in 2nd and 3rd trimester -Oral drugs : Artesunate, Artemether, Dihydroartemisnin -Only i.v drug : Artesunate ARTEMISNISNIN GROUP DRUGS
- 45. -I.V Artesunate isDOC in severe falciparum malaria -Oral artesunate 200mg for 3 days is preferred in Chloroquine resistant malaria -Not used for prophylaxis since it has short duration of action -S/E: GI side effects: Nausea, vomiting, Diarrehea ARTEMISNISNIN GROUP DRUGS
- 46. -Enters vacuole ofplasmodium and binds with haem and produces toxic heme products which is cidal for plasmodium -Resistance is due to efflux of drug from vacuole -DOC for treatment and prophylaxis of malaria except falciparum -It has high volume of distribution and hence loading dose has to be given. -Other uses : Giardiasis Amebiasis, Infectious mononucleosis, SLE, RA CHLOROQUINE
- 47. S/E: C - Convulsions H- Hemolysis in G6PD deficient pt. L - Low blood pressure O -Ocular : Bull’s eye maculopathy R - qRs and T wave abnormalities CHLOROQUINE
- 48. •Fast acting schizonticidaldrugs •Used in severe falciparum malaria and chloroquine resistant malaria •Derived from bark of cinchona plant QUININE and QUINIDINE
- 49. •Cinchonism : headache+ tinnitus +Visual disturbance •Hypotension : Due to Alpha-1 blocking effect •Hypoglycemia : Due to insulin release. Hence given with dextrose •Black water fever : Inadequate therapy leads to hypersensitivity QUININE and QUINIDINE S/E
- 50. •Used in treatmentand prophylaxis of vivax •Used along with artesunate in severe falciparum malaria •S/E : Neuropsychiatric MEFLOQUINE
- 51. •Hemolysis in G6PDdeficiency •Methemoglobinemia •Anemia • Leukocytosis PRIMAQUINE S/E
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