Visit us at www drsarma in Falciparum Malaria

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Visit us at : www. drsarma. in Falciparum Malaria Dr. R. V. S. N.

Visit us at : www. drsarma. in Falciparum Malaria Dr. R. V. S. N. Sarma. , M. D. , M. Sc. , Consultant Physician & Chest Specialist Ph: 93805 21221, 3760 9993

Malaria Burden Malaria kills 1. 5 to 2. 7 m people world wide every

Malaria Burden Malaria kills 1. 5 to 2. 7 m people world wide every year n 95% are due to P. falciparum n In India P. falciparum up to 34% n Case fatality rate is up to 9% n Chloroquine resistance is major concern n Multi drug resistance emerged in India n

The Plasmodium species P. falciparum n P. vivax n P. malariae n P. ovale

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

Falciparum Malaria

Falciparum Malaria

What is the cause ? Inappropriate use of anti-malarials n Shot gun use of

What is the cause ? Inappropriate use of anti-malarials n Shot gun use of Chloroquine n Mass scale deployment of chloroquine n Almost always as monotherapy n Inadequate dose and duration n Continued use in spite of drug resistance n

Malaria Resurgence n Resistance of the parasite n Resistance of the vector n Resistance

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

Current WHO Call WHO Facts on ACTs – Jan 2006 Update

Current WHO Call WHO Facts on ACTs – Jan 2006 Update

Recent Recommendations n n International Conference on Malaria (125 Years of Malaria Research )

Recent Recommendations n n International Conference on Malaria (125 Years of Malaria Research ) New Delhi, November 4— 6, 2005 Organized by n Malaria Research Centre (Indian Council of Medical Research) 22 Sham Nath Marg, Delhi-110054 (India)

Why is falciparum malignant ? Each cycle releases 20 times more merozoites than vivax

Why is falciparum malignant ? Each cycle releases 20 times more merozoites than vivax n Multiple infestation of RBC n Early hemolysis and endotoxin release, cerebral toxicity n Bilirubin load affects kidneys, liver n Hypovolemia and shock occur n Usually resistant to Chloroquine n

Differentiation of falciparum P. falciparum trophozite P. vivax trophozite

Differentiation of falciparum P. falciparum trophozite P. vivax trophozite

Differentiation of falciparum P. falciparum shizont P. vivax shizont

Differentiation of falciparum P. falciparum shizont P. vivax shizont

Differentiation of falciparum P. falciparum gametocyte P. vivax gametocyte

Differentiation of falciparum P. falciparum gametocyte P. vivax gametocyte

Falciparum gametocytes Male Female

Falciparum gametocytes Male Female

Electron Micrographs P. falciparum EM P. vivax EM

Electron Micrographs P. falciparum EM P. vivax EM

Falciparum invading RBC

Falciparum invading RBC

Mangalore story

Mangalore story

Drug Rx. of falciparum Chloroquine is not the drug of choice n Should not

Drug Rx. of falciparum Chloroquine is not the drug of choice n Should not be treated with single drug n Combination therapy is a must n Weaker drugs like Proguanil are of no avail n Artemisinin based CT – ACT is the Rx. of choice n

The Anti-malarial Drugs Artesunate, Artether, Artemether n Mefloquine, Amodiaquine n Quinine, Chloroquine n Lumefantrine,

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

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

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

What is CT ? n Anti-malarial combination therapy (CT) is the simultaneous use of

What is CT ? n 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.

What is ACT ? n Artemisinin-based combination therapy (ACT) is an antimalarial combination therapy

What is ACT ? n 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.

Rationale for ACT n n n n Resistance to Chloroquine and SP Protect individual

Rationale for ACT n n n n 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

What are Artemisinins ? Artemisinin derivatives Dihydroartemi sin Methyl Ether Artemeth Ethyl Ether Arteether

What are Artemisinins ? Artemisinin derivatives Dihydroartemi sin Methyl Ether Artemeth Ethyl Ether Arteether Qinghaosu ("ching-howsoo") Hemisuccina te Artesunat e er

Why Artemisinins ? n n n n Short half-life; hence good for combination Rapid

Why Artemisinins ? n n n n 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.

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

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

ACT - WHO Guidelines Technical Consultation on Anti-malarial Combination Therapy: Geneva, April 2001 n

ACT - WHO Guidelines Technical Consultation on Anti-malarial Combination Therapy: Geneva, April 2001 n Guidelines for the treatment of Malaria WHO document – 266 page book – February 2006 n

Treatment of uncomplicated P. falciparum malaria

Treatment of uncomplicated P. falciparum malaria

Recommended Combinations 1. Artemether + Lumefantrine (Lumether) 2. Artesunate (3 days) + Amodiaquine 3.

Recommended Combinations 1. Artemether + Lumefantrine (Lumether) 2. Artesunate (3 days) + Amodiaquine 3. Artesunate (3 days) + Mefloquine 4. Artesunate (3 days) + SP 5. Amodiaquine + SP (as interim option)

WHO Recommendations Upto 1 st Nov 2005 – ACT is adopted by total of

WHO Recommendations Upto 1 st Nov 2005 – ACT is adopted by total of 56 countries n 34 Countries in Africa n 22 Countries outside Africa n India has adopted in 2005 n 14 countries AL as first line Rx. n Indian Govt. chosen AS + SP – 1 st line n In five states it is available in NAMP n

β Artemether Methyl ether of Artemisinin n Effective Schizonticidal and gametocidal drug n Short

β Artemether Methyl ether of Artemisinin n Effective Schizonticidal and gametocidal drug n Short half life 2 - 6 hours n Interferes with the conversion of Haem to non toxic hemozoin in the parasite n Not indicated in 1 st trimester of preg. n

β Artemether side effects Very few and less troublesome n Cough n Body aches

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

Lumefantrine Schizonticidal; Safe in pregnancy n AMMS – China discovered it 1970 n Registered

Lumefantrine Schizonticidal; Safe in pregnancy n AMMS – China discovered it 1970 n Registered for use in 1987 n Half life 3 -6 days n Acts on the food vacuole of parasite n Inhibition of Nucleic acid and Protein synthesis in the parasite n

AL Peak Plasma concentrations

AL Peak Plasma concentrations

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

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

AL Dosage Schedule

AL Dosage Schedule

Low Resistance areas

Low Resistance areas

Course of Rx blister packs

Course of Rx blister packs

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

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

FCT (Hours) FCT in hours with AL

FCT (Hours) FCT in hours with AL

PCT in days with AL

PCT in days with AL

Artesunate + Mefloquine AS + MQ

Artesunate + Mefloquine AS + MQ

Artesunate + Amodiaquine AS + AQ

Artesunate + Amodiaquine AS + AQ

Artesunate + sulfadoxine – pyrimethamine – AS + SP

Artesunate + sulfadoxine – pyrimethamine – AS + SP

ACT trend worldwide

ACT trend worldwide

Comparative Efficacy

Comparative Efficacy

AL v/s Q+DC – 3 rd Day

AL v/s Q+DC – 3 rd Day

AL v/s Q+DC – 28 th Day

AL v/s Q+DC – 28 th Day

Second line Combinations 1. Artesunate (7 days) + Tetracycline (7) 2. Artesunate (7 days)

Second line Combinations 1. Artesunate (7 days) + Tetracycline (7) 2. Artesunate (7 days) + Doxycycline (7) 3. Artesunate (7 days) + Clindamycin (7) or 4. Quinine in place of AS + any of the

What to give in pregnancy ? n In 1 st trimester – Quinine +

What to give in pregnancy ? n In 1 st trimester – Quinine + Clindamycin 7 days n In 2 nd and 3 rd trimesters – Any ACT combination as per rec. or – Artesunate + Clindamycin 7 days or – Quinine + Clindamycin 7 days n Lactating women same ACT

Warning n Artemisinins should never be used as monotherapy n Artesunate combinations always given

Warning n Artemisinins should never be used as monotherapy n Artesunate combinations always given for 3 days; never single dose of AS. n For AL six doses must be over 3 days n AQ or MQ or SP should never be used alone - lest drug resistance occurs

Combinations not recommended 1. Chloroquine based combinations (e. g CQ + SP; CQ +

Combinations not recommended 1. Chloroquine based combinations (e. g CQ + SP; CQ + Artesunate) 2. Artesunate (single dose) + SP 3. Chloproguanil-Dapsone (Lap. Dap)

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

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

Complications of falciparum malaria Coma - cerebral malaria, convulsions n Renal failure – black

Complications of falciparum malaria Coma - cerebral malaria, convulsions n Renal failure – black water fever n Hyperpyrexia, acute pulmonary edema n Hemolytic Jaundice, severe bleeding n Hypovolemic shock, Hypoglycemia n Metabolic acidosis, Coagulopathy, n Severe anaemia, hyperparasitemia n

Artemisinins parenteral n αβ Arteether – 150 mg (2 ml) i. m od x

Artemisinins parenteral n αβ Arteether – 150 mg (2 ml) i. m od x 3 days or 3 mg/kg od i. m. x 3 days n 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 n 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 n Rectal artemisinins are not as effective

Quinine parenteral n n n A loading dose of quinine of 20 mg salt/kg

Quinine parenteral n n n A loading dose of quinine of 20 mg salt/kg bw. 10 mg/kg 8 th 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

Some brand names Arteether n Artemether n Artesunate n Mefloquine n Quinine n SP

Some brand names Arteether n Artemether n Artesunate n Mefloquine n Quinine n SP n Primaquine n E Mal inj, Falcy inj Larether caps, inj Falcigo, Falcynate tab, inj MQF, Meflotas, Mefque –tab Quinarsol, Cinkona inj, tab Pyralfin, Laridox, Amalar Malirid, Primacip, PMQinga

AM

AM

Momentum is high to ensure access to effective antimalarial treatment 1. The costs of

Momentum is high to ensure access to effective antimalarial treatment 1. The costs of estimated global ACT requirements far exceeds the current level of ACT financing by the GFA. 2. 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 3. 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

αβ ARTEETHER 150 mg (2 ml amp. ) O. D. intramuscular x 3 days

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

Let us give Colour to their Lives

Let us give Colour to their Lives

Points Ponder • If we find a person’s Hb is say 8 g% -

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 www. drsarma. in • Anaemia – 1. Under production 2. Hemolytic 3.

A Practical Approach to Anemia How to efficiently and accurately work up an anemic

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

This is time for Tea The Next part our CME is on Anaemia Let

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