Falciparum Malaria Introduction PowerPoint Presentation

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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

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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

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The Plasmodium species P.falciparum 15% of Malaria in India P.vivax Commonest in India P.malariae Africa & South America P.ovale African continent

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Falciparum Malaria

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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

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Malaria Resurgence Resistance of the parasite Resistance of the vector Resistance of the people Resistance of the community Resistance of the government

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Current WHO Call WHO Facts on ACTs – Jan 2006 Update

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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)

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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

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Differentiation of falciparum P.falciparum trophozite P.vivax trophozite

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Differentiation of falciparum P.falciparum shizont P.vivax shizont

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Differentiation of falciparum P.falciparum gametocyte P.vivax gametocyte

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Falciparum gametocytes Male Female

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Electron Micrographs P.falciparum EM P.vivax EM

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Falciparum invading RBC

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Mangalore story

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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

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The Anti-malarial Drugs Artesunate, Artether, Artemether Mefloquine, Amodiaquine Quinine, Chloroquine Lumefantrine, Halofantrine, Proguanilchlor (chlorguanide) Sulfadoxin+Pyrimethmine, Dapsone Tetracyclines, Doxycyclin, Clindamycin

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Today’s Watch Word Combination Therapy (CT) Artemisinin based Combination Therapy (ACT)

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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.

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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.

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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

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What are Artemisinins ? Artemisinin derivatives Methyl Ether Hemisuccinate Ethyl Ether Arteether Artemether Artesunate Dihydroartemisin Qinghaosu ("ching-how-soo")

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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.

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No Monotherapy No Chloroquine for P.falcipatum No Monotherapy with Artemisinin

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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

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Treatment of uncomplicated P.falciparum malaria

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Recommended Combinations Artemether + Lumefantrine (Lumether) Artesunate (3 days) + Amodiaquine Artesunate (3 days) + Mefloquine Artesunate (3 days) + SP Amodiaquine + SP (as interim option)

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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

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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.

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β Artemether side effects Very few and less troublesome Cough Body aches Abd pain, Nausea, Vomiting, Anorexia Palpitations Dizziness, weakness Skin rash, itching

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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

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AL Peak Plasma concentrations

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Artemether-Lumefantrine - AL (Coartem, Lumether, Riamet) 6 dose regimen of Lumether

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AL Dosage Schedule

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Low Resistance areas

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Course of Rx blister packs

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COARTEM® PREFERENTIAL PRICING FOR PUBLIC SECTOR: PRICE CHANGES BY 2005

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FCT in hours with AL FCT (Hours)

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PCT in days with AL

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Artesunate + Mefloquine AS + MQ

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Artesunate + Amodiaquine AS + AQ

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Artesunate + sulfadoxine –pyrimethamine – AS + SP

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ACT trend worldwide

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Comparative Efficacy

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AL v/s Q+DC – 3rd Day

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AL v/s Q+DC – 28th Day

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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

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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

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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

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Combinations not recommended Chloroquine based combinations (e.g CQ + SP; CQ + Artesunate) Artesunate (single dose) + SP Chloproguanil-Dapsone (LapDap)

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Treatment of severe P.falciparum malaria Severe malaria is a medical emergency

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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

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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

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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

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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

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AM

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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

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The time of poor drugs for poor people is over

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αβ ARTEETHER 150 mg (2 ml amp.) O.D. intramuscular x 3 days = Total 3 ampoules in a box To be given I.M

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Let us give Colour to their Lives

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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.

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A Practical Approach to Anemia This session will be after tea break How to efficiently and accurately work up an anemic patient ?

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www.drsarma.in This is time for Tea The Next part our CME is on Anaemia Let us quickly come back after Tea