Visit us at www drsarma in Falciparum Malaria
- Slides: 65
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 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 n 15% of Malaria in India Commonest in India Africa & South America African continent
Falciparum Malaria
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 of the people n Resistance of the community n Resistance of the government
Current WHO Call WHO Facts on ACTs – Jan 2006 Update
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 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 shizont P. vivax shizont
Differentiation of falciparum P. falciparum gametocyte P. vivax gametocyte
Falciparum gametocytes Male Female
Electron Micrographs P. falciparum EM P. vivax EM
Falciparum invading RBC
Mangalore story
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, 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)
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 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 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 Qinghaosu ("ching-howsoo") Hemisuccina te Artesunat e er
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
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
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 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 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 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 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
Artemether-Lumefantrine - AL (Coartem, Lumether, Riamet) 6 dose regimen of Lumether
AL Dosage Schedule
Low Resistance areas
Course of Rx blister packs
COARTEM® PREFERENTIAL PRICING FOR PUBLIC SECTOR: PRICE CHANGES BY 2005 PUBLIC SECTOR PRIVATE SECTOR
FCT (Hours) FCT in hours with AL
PCT in days with AL
Artesunate + Mefloquine AS + MQ
Artesunate + Amodiaquine AS + AQ
Artesunate + sulfadoxine – pyrimethamine – AS + SP
ACT trend worldwide
Comparative Efficacy
AL v/s Q+DC – 3 rd Day
AL v/s Q+DC – 28 th Day
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 + 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 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 + Artesunate) 2. Artesunate (single dose) + SP 3. Chloproguanil-Dapsone (Lap. Dap)
Treatment of severe P. falciparum malaria Severe malaria is a medical emergency
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 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 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 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
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 = Total 3 ampoules in a box To be given I. M
Let us give Colour to their Lives
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 patient ? This session will be after tea break
This is time for Tea The Next part our CME is on Anaemia Let us quickly come back after Tea www. drsarma. in
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