Falciparum Malaria

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Falciparum Malaria
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• Dr.R.V.S.N.Sarma., M.D., M.Sc.,
• Consultant Physician Chest Specialist
• Ph 93805 21221, 3760 9993

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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 46, 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)
• SulfadoxinPyrimethmine, Dapsone
• Tetracyclines, Doxycyclin, Clindamycin

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Todays 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
Dihydroartemisin
Methyl Ether
Ethyl Ether
Artemether
Arteether
Hemisuccinate

Qinghaosu ("ching-how-soo")
Artesunate
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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

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)

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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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ß 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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ß 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 MefloquineAS MQ
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Artesunate AmodiaquineAS 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 QDC 3rd Day
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AL v/s QDC 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

1. Chloroquine based combinations (e.g CQ SP CQ
   Artesunate)
2. Artesunate (single dose) SP
3. 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

• aß 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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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
   accelerate access to ACTs and make these
   life-saving medicines affordable to the people in
   need.

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The time of poor drugs for poor people is over
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(No Transcript)
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aß 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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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

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This is time for Tea

• The Next part our CME is on Anaemia
• Let us quickly come back after Tea