11 Malaria Revision
Transcript of 11 Malaria Revision
A vector-borne disease is one in which the pathogenic microorganism is transmitted from an infected individual to another individual by an agent
The name comes from the Italian mal (bad) and aria (air) – it was originally thought the disease was spread by the damp air from swamps
The link between the disease and the Anopheles Mosquito was first made by Ronald Ross, a Scottish army doctor, working in India
Malaria
Plasmodium falciparum is responsible for most morbidity and mortality
4 distinctive species
P. vivax P. falciparum P. malariae P. ovale
Malaria
Malaria - deadly disease
Malaria kills 1.5-2.7 million people every year
Additional 300-500 million people suffer from malaria attacks but survive
Malaria is a major cause of death equal with AIDS and tuberculosis
The mortality and morbidity associated with malaria have a crippling effect on the economies of endemic countries
-100 nations at risk
- 1 death every 30 seconds
- 2.7 millions death / year
- 1 in 3 below five years
- 10 times killer than AIDS
Malaria – global scenario
NVBDCP - 2 million cases
WHO estimate – 70 million cases
45-50% falciparum cases
2 lakh deaths / year
Increasing drug resistance
Malaria – Indian scenario
NVBDCP – National Vector Borne Disease Control Programme
Malaria triad
AGENTAGENT
(Plasmodium)(Plasmodium)
VECTORVECTOR(Female anopheles (Female anopheles
mosquito)mosquito)
HOSTHOST
(Man)(Man)
Eleven Steps in ‘Slow Motion’
Life Cycle of
A Malarial Parasite
Why Falciparum Malaria is serious?
Vivax malaria seldom kills, Falciparum does
In Falciparum life cycle, each liver schizont can release upto 40,000 merozoites (only 10,000 in Vivax)
In Falciparum life cycle, merozoites attack young RBC, and even older RBC (Vivax merozoites preferentially attack immature RBC).
In Falciparum life cycle, a large number of infected RBC get sequestered i.e. get secluded by leaving the general circulation and move to peripheral circulation (microvascular circulation), causing multiple organ damage.
Falciparum parasitizes upto 35 per cent of RBCsWHEREAS
Parasitization with Vivax rarely exceeds 5% 0f RBCs
Parasitemia in Vivax ranges between 20,000 to 50,000 RBCs per
micro-litre (1/1000th of a liter) whereas in Falciparum it can go upto 20,000,000 RBCs per micro-litre
Why Falciparum Malaria is serious?
PCT & FCT
Parasitic clearance time is the time between beginning antimalarial treatment and the first negative blood slide.
Fever clearance time is the time taken by an antimalarial drug to bring down the body temperature of a patient with malarial fever to normal temperature (i.e. 37.5oC or below).
Other common terms
Tissue schizontocide
Kills hypnozoites or tissue schizonts which leads to relapse. e.g. Primaquine
Blood schizontocide
Acts on malaria parasites (which are in various stages like trophozoites, schizonts, merozoites) inside RBCs. e.g. Chloroquine,Quinine, Artemisinins
Gametocytocidal
Kills gametocytes & hence prevents spread of disease
Resistance
R1
(Low grade)
Recrudescence of infection (i.e. reappearance of malaria) between 7 and 28 days of completing treatment following initial resolution of symptoms and parasite clearance
R2
(High grade)
Reduction of parasitaemia by >75% at 48 hours, but failure to clear parasites within the 7 days
R3 Parasitaemia does not fall below >75% within 48 hours
Improper treatment and inadequate dosage of antimalarials lead to development of resistance
Antimalarial therapy
Vivax malaria
LARIAGO (Chloroquine Tablets/Suspension/Injection)
Drug of choice in the treatment and prophylaxis of malaria caused by P. vivax
Rapid schizontocidal effect
No effect on malarial parasites present in the liver cells
Mode of Action
Accumulates selectively in parasitized erythrocytes
Alters the pH of the food vacoules of the parasites, resulting in severe metabolic disturbances
Also interferes with the parasites’ ability to utilize haemoglobin
These disturbances ultimately leads to destruction of the membrane of the parasite, causing its death
MALIRID(Primaquine Tablets )
Tissue schizonticidal agent for radical cure of vivax malaria
Acts at liver stage of vivax parasite
Exact mechanism of action is not known but the drug appears to interfere with the function of plasmodial DNA
Gametocytocidal against gametocytes of P. falciparum
Falciparum malaria- traditional antimalarials
LARIDOX (Sulphadoxine and Pyrimethamine Tablets/Susp.)
Effective against P. falciparum
As a single dose of therapy
Should not be used alone for the treatment of malaria having P. vivax presence
Ineffective in P. vivax infection
Lariago to be added along with Laridox in cases of mixed malaria
LARIMEFMefloquine Tablets
Blood schizontocidal
Active against all forms of malaria parasites including multidrug resistant strains of P. falciparum
Ensures both suppression and cure of infections with multidrug resistant P. falciparum.
Rapidly absorbed and long elimination half life of 21 days
Add on to Artemisinin injection as a follow up to prevent recrudesence
Falciparum malaria
Increasing incidences Rising resistance Fast progression towards complicated malaria Morbidity & mortality
NEED - new treatment approach
ARTEMISININS
Potent antimalarial activity
Immediate onset and rapid reduction of parasitaemia with complete clearance in most cases within 48 hours
Clinical recovery of the patient, e.g. defervescence is faster than with other antimalarials
Efficacy is high even in areas with multi-drug resistant strains
Well tolerated and efficacious in adults and children
Artemisinin
Dihydroartemisinin
Methyl ether Hemisuccinate Ethyl ether
Artemether Artesunate Arteether
Parameter Artemether Artesunate Arteether
Solubility Oil soluble Water soluble Oil soluble
Dosage forms Oral/Inj Oral/inj Inj
Route of admin. Oral/IM Oral/IM/IV IM
Blood/tissue schizonticidal
Blood Blood Blood
Action on rosetting & cytoadherence
Reduces Faster action than others
Reduces
Plasma half life Rapidly eliminated
3-6 hrs 23 hrs
Stability Stable Unstable Stable
Mechanism of action
Drug is concentrated in parasitized erythrocytes
The functional group responsible for antimalarial activity of drug is endoperoxide bridge
Iron from the digested haemoglobin of the parasite’s victim reduces this bridge, releasing a highly reactive free radical iron species, which causes lysis of the parasitic cell
It is also proposed that artemisinins inhibit the protein synthesis and alters the ribosomal organization and endoplasmic reticulum.
A
A
A
A
A
MPMP
MP
MPMP
MP MPMP
A
MP
RE
MP
Hb Hb Hb Hb Hb
Intracellular Mechanism of Action
of Artemisinin compounds
A Artemisinin derivatives MP Malaria ParasiteHb HaemoglobinRE Reticular Endothelial Cells
Concept of ACT
Lumerax Larinate kit
WHO initiative
Combinations of drugs
First line tratment for uncomplicated falciparum malaria
The aim is to improve efficacy and to retard the development of resistance to the individual components of the combination
Fixed-combination and multiple-drug therapies are used to exploit the synergistic and additive potential of individual drugs
Ideal ACT features
Drugs having unrelated mode of action on the parasite
Fast acting & Long acting
No negative pharmacological interactions
Short duration & well tolerated
WHO Initiative
Artesunate + amodiaquine
• Artemether/lumefantrine
Artesunate + SP
Artesunate + mefloquine
FDC
KIT
Amodiaquine + SP
Lumerax represents a new approach in Antimalarial treatment called Artemisinin-based Combination Therapy (ACT)
Lumerax is fixed dose combination of Artemether with Lumefantrine
Lumerax is the first ACT introduced in the Indian market
LUMERAX
Larinate Kit is a combo-pack of an artemisinin derivative, Artesunate, along with a separate strip of Sulfadoxine and Pyrimethamine (‘SP’) tablets
Larinate Kit is the WHO-endorsed combination for Uncomplicated Falciparum Malaria
Larinate Kit also serves as a ‘switch oral therapy’ when patients on injectable Artemisinins (injectable artesunate, artemether or arteether who are able to swallow an oral dosage form)
LARINATE KIT
RAPITHER-AB
Combination of alpha and beta isomers (A and B) of Arteether, the ethyl ether of artemisin. Hence Rapither AB
Rapither AB is recommended for Falciparum Malaria, including drug-resistant Malaria
Short 3-dose treatment
Larither contains Artemether and belongs to the Artemisinin group of Antimalarial drugs.
Larither is recommended for the treatment of severe Falciparum Malaria, as a complete 7-day IM injection therapy especially in area where falciparum cases are on rise
The elimination half-life is approximately 1 hour, but following intramuscular administration the elimination phase is prolonged because of continued absorption.
LARITHER
Complicated Malaria Treatment
Hospital settings
OPD, Casualty
Ward care
ICU care
Criticality of disease
Why complications?
High degree of parasitemia
Severity of illness
Cytoadherence - rosseting
One to multi organ failure
Predisposing factors for complications
Extremes of age
Pregnancy
Immunosuppressed - patients on steroids, anti-cancer drugs, immunosuppressant drugs
Lack of previous exposure to malaria (non-immune)
Pre-existing organ failure.
Complications of Malaria
Cerebral malariaSevere anemiaJaundiceRenal failurePulmonary edemaHypoglycemiaBleeding and clotting disturbancesHyperpyrexia
HyperparasitemiaComplicating or associated infectionsVomiting of oral drugsImpaired consciousnessExtreme weakness
CINKONA(Quinine Tablets/Injection)
A cinchona alkaloid that is a time tested drug
Mode of action: May interfere with nucleic acid synthesis in the malaria parasite
Activity against all four forms of malaria
Rapidly acting blood schizontocide
Effective against resistant strains
Adverse effect - Hypoglycemia, Cinchonism i.e. tinnitus, headache, nausea and diarrhoea
LARINATE INJECTION(Artesunate inj.)
The primary objective of antimalarial treatment in severe malaria is to prevent death
IV artesunate is more rapidly acting than IV quinine in terms of parasite clearance, is safer, and is simpler to administer
Reduces mortality in complicated malaria cases
Larinate for injection is available as a combi-pack containing:
a) 5 ml vial containing sterile Artesunate powderb) Sodium Bicarbonate 1 ml. for reconstitutionc) Sodium Chloride 5 ml
All the three components i.e. one vial and two ampoules are embedded in a specially designed three-compartment tray
LARINATE INJECTION(Artesunate inj.)
MANAGEMENT OF MALARIA
Management of clinical malaria (febrile episode)
Prevention of relapse in vivax and spread in falciparum
UncomplicatedComplicated
P. Vivax / P. falciparum Chloroquine Sulphadoxine/Pyrimethamine Mefloquine ACT Inj. Artemisinin derivatives
P. falciparum Inj. Artemisinin derivatives Inj. Quinine
Primaquine
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