Falciparum Malaria Visit us at : www.drsarma.in Dr.R.V.S.N.Sarma., M.D., M.Sc., Consultant Physician Tiruvallur 602 001 Ph: 93805 21221

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

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

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

Electron Micrographs P.falciparum EM P.vivax EM

Falciparum invading RBC

Mangalore story

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 Artemesinin based CT – ACT is the Rx. of choice

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

What is CT ? Antimalarial 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 ? 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 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 Dihydroartemesin Ethyl Ether Methyl Ether Arteether Artemether Hemisuccinate Qinghaosu ("ching-how-soo") Artesunate

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.

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

Treatment of uncomplicated P.falciparum malaria

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

Artemether-Lumefantrine (Coartem) AL 6 dose regimen

Course of Rx blister packs

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

Artesunate + Mefloquine AS + MQ

Artesunate + Amodiaquine AS + AQ

Artesunate + sulfadoxine –pyrimethamine – AS + SP

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

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 Lactating women same ACT

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 over 3 days AQ or MQ or SP should never be used alone - lest drug resistance occurs

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

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

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

Artemisinins parenteral Artesunate 2.4 mg/kg bw i.v. or i.m. given on admission (time = 0), then at 12 h and 24 h, then once a day is the recommended 1 choice Artemether 3.2 mg/kg bw i.m. given on admission then 1.6 mg/kg bw per day is an acceptable alternative to quinine i.v infusions Rectal artemisinins are not as effective

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

Trade names Arteether Falcy inj, E Mal 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

AM

Momentum is high to ensure access to effective antimalarial treatment 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.

The time of poor drugs for poor people is over Africa has therefore arrived at a critical point in the struggle against a disease that saps its development and kills some 3000 of its children every day. Left to its present course, malaria is a crisis that can only deepen. But if national commitments and global support for the Roll Back Malaria initiative can be translated into action on the ground, then the gains being made by malaria can be reversed. Unique opportunity to do something about the burden and make an impact on both the health and economic strength of the African region... in light of funding now available through GFATM And especially in light of the US commitment to AIDS, TB & Malaria (new bill) The time of poor drugs for poor people is over