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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

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

The Plasmodium species


P.falciparum P.vivax P.malariae P.ovale

15% of Malaria in India Commonest in India Africa & South America African continent

Falciparum Malaria

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

Malaria Resurgence

Resistance of the parasite


Resistance of the vector

Resistance of the people


Resistance of the community Resistance of the government

Current WHO Call

WHO Facts on ACTs Jan 2006 Update

Recent Recommendations

International Conference on Malaria (125 Years of Malaria Research ) New Delhi, November 46, 2005
Malaria Research Centre (Indian Council of Medical Research) 22 Sham Nath Marg, Delhi-110054 (India)

Organized by

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

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 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

The Anti-malarial Drugs

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

Todays Watch Word


Combination Therapy (CT)

Artemisinin based Combination Therapy (ACT)

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.

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
Dihydroartemisin Ethyl Ether Arteether
Qinghaosu ("ching-how-soo")

Methyl Ether
Artemether Hemisuccinate 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.

No Monotherapy

No Chloroquine for P.falcipatum


No Monotherapy with Artemisinin

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

Treatment of uncomplicated P.falciparum malaria

Recommended Combinations
1. 2.

Artemether + Lumefantrine (Lumether) Artesunate (3 days) + Amodiaquine

3.
4. 5.

Artesunate (3 days) + Mefloquine


Artesunate (3 days) + SP

Amodiaquine + SP (as interim option)

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

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.

Artemether side effects

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

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

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 in hours with AL

FCT (Hours)

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 3rd Day

AL v/s Q+DC 28th Day

Second line Combinations


1. 2.

Artesunate (7 days) + Tetracycline (7) Artesunate (7 days) + Doxycycline (7)

3.

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 Quinine + Clindamycin 7 days

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 be over 3 days

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. 3.

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

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

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

Some brand names

Arteether Artemether Artesunate Mefloquine Quinine SP Primaquine

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.
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 lifesaving medicines affordable to the people in need.

2.

3.

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 persons 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 arent 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


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

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