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Slide 1 - Falciparum Malaria Dr.R.V.S.N.Sarma., M.D., M.Sc., Consultant Physician & Chest Specialist Ph: 93805 21221, 3760 9993 Visit us at : www.drsarma.in
Slide 2 - Malaria Burden Malaria kills 1.5 to 2.7 m people world wide every year 95% are due to P.falciparum In India P.falciparum up to 34% Case fatality rate is up to 9% Chloroquine resistance is major concern Multi drug resistance emerged in India
Slide 3 - The Plasmodium species P.falciparum 15% of Malaria in India P.vivax Commonest in India P.malariae Africa & South America P.ovale African continent
Slide 4 - Falciparum Malaria
Slide 5 - What is the cause ? Inappropriate use of anti-malarials Shot gun use of Chloroquine Mass scale deployment of chloroquine Almost always as monotherapy Inadequate dose and duration Continued use in spite of drug resistance
Slide 6 - Malaria Resurgence Resistance of the parasite Resistance of the vector Resistance of the people Resistance of the community Resistance of the government
Slide 7 - Current WHO Call WHO Facts on ACTs – Jan 2006 Update
Slide 8 - Recent Recommendations International Conference on Malaria (125 Years of Malaria Research ) New Delhi, November 4—6, 2005 Organized by Malaria Research Centre (Indian Council of Medical Research) 22 Sham Nath Marg, Delhi-110054 (India)
Slide 9 - Why is falciparum malignant ? Each cycle releases 20 times more merozoites than vivax Multiple infestation of RBC Early hemolysis and endotoxin release, cerebral toxicity Bilirubin load affects kidneys, liver Hypovolemia and shock occur Usually resistant to Chloroquine
Slide 10 - Differentiation of falciparum P.falciparum trophozite P.vivax trophozite
Slide 11 - Differentiation of falciparum P.falciparum shizont P.vivax shizont
Slide 12 - Differentiation of falciparum P.falciparum gametocyte P.vivax gametocyte
Slide 13 - Falciparum gametocytes Male Female
Slide 14 - Electron Micrographs P.falciparum EM P.vivax EM
Slide 15 - Falciparum invading RBC
Slide 16 - Mangalore story
Slide 17 - Drug Rx. of falciparum Chloroquine is not the drug of choice Should not be treated with single drug Combination therapy is a must Weaker drugs like Proguanil are of no avail Artemisinin based CT – ACT is the Rx. of choice
Slide 18 - The Anti-malarial Drugs Artesunate, Artether, Artemether Mefloquine, Amodiaquine Quinine, Chloroquine Lumefantrine, Halofantrine, Proguanilchlor (chlorguanide) Sulfadoxin+Pyrimethmine, Dapsone Tetracyclines, Doxycyclin, Clindamycin
Slide 19 - Today’s Watch Word Combination Therapy (CT) Artemisinin based Combination Therapy (ACT)
Slide 20 - What is CT ? Anti-malarial combination therapy (CT) is the simultaneous use of two or more blood schizonticidal drugs with different biochemical targets in the parasites and independent modes of action.
Slide 21 - What is ACT ? Artemisinin-based combination therapy (ACT) is an antimalarial combination therapy with an artemisinin derivative as one component of the combination given for at least 3 days.
Slide 22 - Rationale for ACT Resistance to Chloroquine and SP Protect individual drug from resistance To decrease rate of decline in efficacy To interrupt spread of resistant strains To decrease transmission in a region The combination is often more effective In the rare event of resistance to one of the drugs during the course of the infection, the parasite will be killed by the other drug
Slide 23 - What are Artemisinins ? Artemisinin derivatives Methyl Ether Hemisuccinate Ethyl Ether Arteether Artemether Artesunate Dihydroartemisin Qinghaosu ("ching-how-soo")
Slide 24 - Why Artemisinins ? Short half-life; hence good for combination Rapid substantial reduction of the parasite biomass Rapid resolution of clinical symptoms Effective action against multi-drug resistant P. falciparum Reduction of gametocyte carriage No documented parasite resistance yet Few reported adverse effects.
Slide 25 - No Monotherapy No Chloroquine for P.falcipatum No Monotherapy with Artemisinin
Slide 26 - ACT - WHO Guidelines Technical Consultation on Anti-malarial Combination Therapy: Geneva, April 2001 Guidelines for the treatment of Malaria WHO document – 266 page book – February 2006
Slide 27 - Treatment of uncomplicated P.falciparum malaria
Slide 28 - Recommended Combinations Artemether + Lumefantrine (Lumether) Artesunate (3 days) + Amodiaquine Artesunate (3 days) + Mefloquine Artesunate (3 days) + SP Amodiaquine + SP (as interim option)
Slide 29 - WHO Recommendations Upto 1st Nov 2005 – ACT is adopted by total of 56 countries 34 Countries in Africa 22 Countries outside Africa India has adopted in 2005 14 countries AL as first line Rx. Indian Govt. chosen AS + SP – 1st line In five states it is available in NAMP
Slide 30 - β Artemether Methyl ether of Artemisinin Effective Schizonticidal and gametocidal drug Short half life 2 - 6 hours Interferes with the conversion of Haem to non toxic hemozoin in the parasite Not indicated in 1st trimester of preg.
Slide 31 - β Artemether side effects Very few and less troublesome Cough Body aches Abd pain, Nausea, Vomiting, Anorexia Palpitations Dizziness, weakness Skin rash, itching
Slide 32 - Lumefantrine Schizonticidal; Safe in pregnancy AMMS – China discovered it 1970 Registered for use in 1987 Half life 3-6 days Acts on the food vacuole of parasite Inhibition of Nucleic acid and Protein synthesis in the parasite
Slide 33 - AL Peak Plasma concentrations
Slide 34 - Artemether-Lumefantrine - AL (Coartem, Lumether, Riamet) 6 dose regimen of Lumether
Slide 35 - AL Dosage Schedule
Slide 36 - Low Resistance areas
Slide 37 - Course of Rx blister packs
Slide 39 - FCT in hours with AL FCT (Hours)
Slide 40 - PCT in days with AL
Slide 41 - Artesunate + Mefloquine AS + MQ
Slide 42 - Artesunate + Amodiaquine AS + AQ
Slide 43 - Artesunate + sulfadoxine –pyrimethamine – AS + SP
Slide 44 - ACT trend worldwide
Slide 45 - Comparative Efficacy
Slide 46 - AL v/s Q+DC – 3rd Day
Slide 47 - AL v/s Q+DC – 28th Day
Slide 48 - Second line Combinations Artesunate (7 days) + Tetracycline (7) Artesunate (7 days) + Doxycycline (7) Artesunate (7 days) + Clindamycin (7) or 4. Quinine in place of AS + any of the above antibiotics for 7 days
Slide 49 - What to give in pregnancy ? In 1st trimester Quinine + Clindamycin 7 days In 2nd and 3rd trimesters Any ACT combination as per rec. or Artesunate + Clindamycin 7 days or Quinine + Clindamycin 7 days Lactating women same ACT
Slide 50 - Warning Artemisinins should never be used as monotherapy Artesunate combinations always given for 3 days; never single dose of AS. For AL six doses must be over 3 days AQ or MQ or SP should never be used alone - lest drug resistance occurs
Slide 51 - Combinations not recommended Chloroquine based combinations (e.g CQ + SP; CQ + Artesunate) Artesunate (single dose) + SP Chloproguanil-Dapsone (LapDap)
Slide 52 - Treatment of severe P.falciparum malaria Severe malaria is a medical emergency
Slide 53 - Complications of falciparum malaria Coma - cerebral malaria, convulsions Renal failure – black water fever Hyperpyrexia, acute pulmonary edema Hemolytic Jaundice, severe bleeding Hypovolemic shock, Hypoglycemia Metabolic acidosis, Coagulopathy, Severe anaemia, hyperparasitemia
Slide 54 - Artemisinins parenteral αβ Arteether – 150 mg (2ml) i.m od x 3 days or 3 mg/kg od i.m. x 3 days Artesunate 2.4 mg/kg i.v. or i.m. given on admission (time = 0), then at 12 h and 24 h, then once a day Artemether 3.2 mg/kg i.m. given on admission then 1.6 mg/kg per day is an acceptable alternative to quinine i.v infusions Rectal artemisinins are not as effective
Slide 55 - Quinine parenteral A loading dose of quinine of 20 mg salt/kg bw. 10 mg/kg 8th hrly i.v infusion Rate-controlled i.v. infusion is the preferred route of quinine admin. If this cannot be given safely, then i.m. injection is a satisfactory alternative. Rectal admin. is not effective Quinidine can substitute quinine
Slide 56 - Some brand names Arteether E Mal inj, Falcy inj Artemether Larether caps, inj Artesunate Falcigo, Falcynate tab, inj Mefloquine MQF, Meflotas, Mefque –tab Quinine Quinarsol, Cinkona inj, tab SP Pyralfin, Laridox, Amalar Primaquine Malirid, Primacip, PMQinga
Slide 57 - AM
Slide 58 - The costs of estimated global ACT requirements far exceeds the current level of ACT financing by the GFA. An enhancement of the financial resources for purchasing ACTs is, therefore, urgently required to both encourage endemic countries to adopt these effective treatment policies and to control malaria mortality Malaria is a highly treatable disease, and very effective treatment is available in the form of ACTs. WHO calls on all member countries to unite in a global coalition to enable countries accelerate access to ACTs and make these life-saving medicines affordable to the people in need. Momentum is high to ensure access to effective antimalarial treatment
Slide 59 - The time of poor drugs for poor people is over
Slide 60 - ppt slide no 60 content not found
Slide 61 - αβ ARTEETHER 150 mg (2 ml amp.) O.D. intramuscular x 3 days = Total 3 ampoules in a box To be given I.M
Slide 62 - Let us give Colour to their Lives
Slide 63 - www.drsarma.in Points Ponder If we find a person’s Hb is say 8 g% - What shall we do ? It is imperative to identify the type of anaemia and treat ! In middle age or elderly – anemia is the clue to Ca !! Thorough examination for occult or chronic bleeding- a must All cases of anaemia are not IDA – Tonics aren’t the answer Anaemia – 1. Under production 2. Hemolytic 3. Hemorrhagic Reticulocyte count is the first test that is needed RDW – RBC indices will classify the type of anaemia Peripheral smear examination is invaluable in the Dx.
Slide 64 - A Practical Approach to Anemia This session will be after tea break How to efficiently and accurately work up an anemic patient ?
Slide 65 - www.drsarma.in This is time for Tea The Next part our CME is on Anaemia Let us quickly come back after Tea