Transcript Falciparum Malaria by Dr Sarma

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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
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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
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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 ?
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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
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Resistance of the parasite
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Resistance of the vector
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Resistance of the people
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Resistance of the community
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Resistance of the government
Current WHO Call
WHO Facts on ACTs – Jan 2006 Update
Recent Recommendations
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International Conference on Malaria
(125 Years of Malaria Research )
New Delhi, November 4—6, 2005
Organized by
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Malaria Research Centre
(Indian Council of Medical Research)
22 Sham Nath Marg, Delhi-110054 (India)
Why is falciparum
malignant ?
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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
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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
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Artesunate, Artether, Artemether
Mefloquine, Amodiaquine
Quinine, Chloroquine
Lumefantrine, Halofantrine,
Proguanilchlor (chlorguanide)
Sulfadoxin+Pyrimethmine, Dapsone
Tetracyclines, Doxycyclin, Clindamycin
Today’s Watch Word
Combination Therapy (CT)
Artemisinin based
Combination Therapy
(ACT)
What is CT ?
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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 ?
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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
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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
Qinghaosu
("ching-how-soo")
Ethyl Ether
Methyl Ether
Arteether
Artemether
Hemisuccinate
Artesunate
Why Artemisinins ?
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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
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No Chloroquine for P.falcipatum
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No Monotherapy with Artemisinin
ACT - WHO Guidelines
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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
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Artemether + Lumefantrine (Lumether)
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Artesunate (3 days) + Amodiaquine
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Artesunate (3 days) + Mefloquine
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Artesunate (3 days) + SP
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Amodiaquine + SP (as interim option)
WHO Recommendations
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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
β Artemether
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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.
β Artemether
side effects
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Very few and less troublesome
Cough
Body aches
Abd pain, Nausea, Vomiting, Anorexia
Palpitations
Dizziness, weakness
Skin rash, itching
Lumefantrine
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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 (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 – 3rd Day
AL v/s Q+DC – 28th Day
Second line Combinations
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Artesunate (7 days) + Tetracycline (7)
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Artesunate (7 days) + Doxycycline (7)
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Artesunate (7 days) + Clindamycin (7)
or
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Quinine in place of AS + any of the
above antibiotics for 7 days
What to give in
pregnancy ?
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In 1st trimester
– Quinine + Clindamycin 7 days
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In 2nd and 3rd trimesters
– Any ACT combination as per rec. or
– Artesunate + Clindamycin 7 days or
– Quinine + Clindamycin 7 days
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Lactating women same ACT
Warning
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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
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Chloroquine based combinations
(e.g CQ + SP; CQ + Artesunate)
2.
Artesunate (single dose) + SP
3.
Chloproguanil-Dapsone (LapDap)
Treatment of severe
P.falciparum malaria
Severe malaria is
a medical emergency
Complications of
falciparum malaria
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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
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αβ 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
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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
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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
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The costs of estimated global ACT requirements far
exceeds the current level of ACT financing by the GFA.
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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
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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.
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
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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
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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