Life Cycle Of The Malaria Parasite And Sites Of Drug Action

The incubation period of malaria is 10-35 days. The principal features of the life cycle (Fig. 14.1) of the malaria parasite must be known in order to understand its therapy. Female anopheles mosquitoes require a blood meal for egg production and in the process of feeding they inject salivary fluid containing

1 Charles Louis Alphonse Laveran (1845-1922), Professor of Military Medicine, Paris (France); Nobel prize winner 1907.

sporozoites into humans. Since no drugs are effective against sporozoites, infection with the malaria parasite cannot be prevented.

Hepatic cycle (site 1 in Fig. 14.1)

Sporozoites enter liver cells where they develop into schizonts which form large numbers of merozoites which, usually after 5-16 days but sometimes after months or years, are released into the circulation. Plasmodium falciparum differs in that it has no persistent hepatic cycle.

Primaquine, proguanil and tetracyclines (tissue schizontocides) act at this site and are used for:

• Radical cure, i.e. an attack on persisting hepatic forms (hypnozoites, i.e. sleeping) once the parasite has been cleared from the blood; this is most effectively accomplished with primaquine; proguanil is only weakly effective

Female mosquito bites human and infects the blood

All forms except

P. falciparum

Sexual forms develop and leave red blood cells

Clinical attack when cells burst

Sexual forms conjugate in mosquito stomach and migrate to Its salivary glands

Mosquito bites human and sucks up parasite

Female mosquito bites human and infects the blood

Sexual forms develop and leave red blood cells

Clinical attack when cells burst

All forms except

P. falciparum

Sexual forms conjugate in mosquito stomach and migrate to Its salivary glands

Mosquito bites human and sucks up parasite

Fig. 14.1 Life cycle of the malaria parasite.The numbers are referred to in the text.

• Preventing the initial hepatic cycle. This is also called causal prophylaxis. Primaquine has long been regarded as too toxic for prolonged use but evidence now suggests it may be used safely and it is inexpensive; proguanil is weakly effective. Doxycycline may be used short-term.

Erythrocyte cycle (site 2 in Fig. 14.1)

Merozoites enter red cells where they develop into schizonts which form more merozoites which are released when the cells burst giving rise to the features of the clinical attack. The merozoites reenter red cells and the cycle is repeated.

Chloroquine, quinine, mefloquine, halofantrine, proguanil, pyrimethamine, and tetracyclines (blood schizontocides) kill these asexual forms. Drugs which act on this stage in the cycle of the parasite may be used for:

• Treatment of acute attacks of malaria.

• Prevention of attacks by early destruction of the erythrocytic forms. This is called suppressive prophylaxis as it does not cure the hepatic cycle (above).

Sexual forms (site 3 in Fig. 14.1)

Some merozoites differentiate into male and female gametocytes in the erythrocytes and can develop further only if they are ingested by a mosquito where they form sporozoites (site 4 in Fig. 14.1) and complete the transmission cycle.

Quinine, mefloquine, chloroquine, artesunate, artemether and primaquine (gametocytocides) act on sexual forms and prevent transmission of the infection because the patient becomes noninfective and the parasite fails to develop in the mosquito (site 4). In summary, drugs may be selected for:

• treatment of clinical attacks

• prevention of clinical attacks

Drugs used for malaria, and their principal actions are classified in Table 14.3.

Dealing With Asthma Naturally

Dealing With Asthma Naturally

Do You Suffer From ASTHMA Chronic asthma is a paralyzing, suffocating and socially isolating condition that can cause anxiety that can trigger even more attacks. Before you know it you are caught in a vicious cycle Put an end to the dependence on inhalers, buying expensive prescription drugs and avoidance of allergenic situations and animals. Get control of your life again and Deal With Asthma Naturally

Get My Free Ebook


Post a comment