Different anti-malarial drugs are designed to target different steps in life cycle of plasmodium.
Malaria is cause by four species of protozoa:
- Plasmodium malariae.
- P. falciparum.
- P. vivax.
- P. ovale.
The plasmodium transmitted to human is by the bite of an infected female anopheles mosquito.
Plasmodium is an obligate intracellular protozoa. Within human race infection may become chronic, involving CNS and death might occur due to unawareness or development of resistance. It is the most devastating parasitic infection existing so far. More than 5 million deaths occur, and high mortality rate is seen among pregnant females and young children. Mortality is increased in children of less than 5 years of age, in economically burdened developing countries.
Infection leads to:
- If not treated, death
The type of febrile illness is specific for specific plasmodium.
Caused by P. vivax and ovale. Illness occurs on every third day with 48 hours interval.
Infection by P. vivax is of chronic type. Illness by P. ovale is of moderate type.
Caused by P. malariae. Febrile illness after every 4th day with 74 hours interval, relapsis may occur.
Tertian malignant malaria
Caused by P. falciparum. Interval of 48 hours with febrile illness after every 3rd day. Chronic form, chances of mortality are more. Relapsis is very rare.
Infection in humans is rare, as bite of female anopheles mosquito is required. Infection present in salivary glands (sporozoites) is transferred through saliva.
2 stages of life cycle:
- Asexual stage –within human beings
- Sexual stage –within mosquito
When female anopheles mosquito bites human beings, it transfers sporozoites in circulation. As soon as they enter liver cells, they are deposited in hepatocytes. Within liver replication occurs, cells are affected and sporozoites mature into schizonts. When converted into mature merozoites, cells rupture and merozoites are released in circulation. This is known as pre erythrocytic stage.
As outside erythrocytes, also known as tissue stage of replication. Most of it occurs within tissues.
They quickly invade human RBCs, resulting in beginning of erythrocytic stage. It begins with febrile illness with clinical signs and symptoms. Depending on different species, different time period is taken for the appearance of signs. They invade erythrocytes quickly. Mature tropozoites develop.
Once schizonts have converted into merozoites, 6-24 merozoites are released in circulation and become available to infect more RBCs. Merozoites may invade human liver cells specifically P. vivax, ovale. Relapsis does not occur with falciparum and rarely with malariae.
May be transformed into gametocytes, capable of transmitting into mosquito, when it takes blood from humans.
This marks the beginning of sexual stage. Gametocytes mature into male and female gametes (macro and microgametes). Fertilization occurs, ookinite are formed, when convert into oocyst, which are transported from gut to salivary glands. Now becomes ready for asexual cycle.
Causal prophylactics: (drugs that kill the pre-erythrocytic forms of parasite)
Clinical curatives (blood schizontocides)
Radical curtives (tissue schizontocides) (for p. Vivax & p. Ovale)
Primaquine –drug of choice for P. Falciparum
Sporontocides: (drugs that inhibit the life cycle of malarial parasite in mosquitoe)
Most effective ones are the agents which target asexual cycle, most rapidly acting are the blood schizontocides.
|4-Quinoline- Methanol Mefloquine||++||0|
|Quinoline-containing Cinchona Alkaloids QuinineQuinidine||++||0|
P. vivax, P. ovale & P. malariae
NB: It is also allowed in pregnancy.
P. Falciparum (most cases are chloroquine-resistant):
- Quinine 600 mg salt/8h till patient become better and blood is free of parasites (usually in 3-5 days).
- Followed by a single dose of fansidar (3 tablets).
- In pregnancy 7-day course of quinine alone should be given.
- Mefloquine 20 mg base/kg up to a maximum of 1.5 g in two divided doses 8 hours apart.
- Mefloquine is contraindicated in pregnancy.
- Quinine 10 mg/kg i.v infusion over 4 h. could be repeated at intervals of 8-12 h. until patient can take drug orally.
- Or Halofantrine: orally only
- Or Qinghaosu (Artemisinin): oral & i.v
Chemoprophylaxis of malaria
- Chloroquine 150 mg base ( 2 tab/week)
- Chloroquine ( 2 tab/week) plus proguanil100 mg (one or two tab/ day) or
- Mefloquine 250 mg (one tab./ week)