Pharma gyan Pandit

Malaria

Most important parasitic disease of humans, causing hundreds of millions of illnesses and probably over a million deaths each year. It is, however, pertinent to observe here that the Anopheles mosquito happens to be a nocturnal feeder ; and, therefore, it is relatively much easier to control than the corresponding Aedes aegypti mosquito which is a day feeder and is responsible solely for carrying dengue as well as yellow fever (prevalent in the African continent).

Causative agent

4 species

P. vivax (tertian)

P. falciparum (tertian)

P. ovale (tertian)

P. malariae(quartian)

Life-cycle of Plasmodium

Malaria is transmitted by the bite of infected female anopheles mosquitoes.

During feeding, mosquitoes inject sporozoites, which circulate to the liver, and rapidly infect hepatocytes, causing asymptomatic liver infection. Merozoites released from the liver, rapidly infect erythrocytes to begin the asexual erythrocytic stage of infection that is responsible for human disease. Multiple rounds of erythrocytic development, with production of merozoites that invade additional erythrocytes, lead to large numbers of circulating parasites and clinical illness. Release of merozoites subsequent to rupture of erythrocytes causes the clinical attack of malaria. Some erythrocytic parasites also develop into sexual gametocytes, which are infectious to mosquitoes, allowing completion of the life cycle and infection of others.

In P vivax and P ovale parasites also form dormant liver hypnozoites, which are not killed by most drugs, allowing subsequent relapses of illness after initial elimination of erythrocytic infections

Signs and symptoms

Initial manifestation of malaria are non-specific and resembles to flu like symptoms. The presentation includes headache, fever, shivering, arthralgia, myalgia. The paroxysm which includes fever spikes, chills and rigors  are classical for malaria.

The typical paroxysmal attack comprises of three distinct stages:

a) Cold stage- The onset is with lassitude, headache, nausea and chilly sensation followed by rigors. The stage lasts for ¼ - 1 hour

 b) Hot stage- The patient feels burning hot, the skin is hot and dry to touch. Headache is intense. Pulse rate is high. The stage lasts for 2-6 hours

c) Sweating stage- Fever comes down with profuse sweating. The pulse rate gets slower, patient    feels relieved. The stage lasts  2-4 hours

These paroxysms have different frequencies in different species of malarial parasites

•      In P. vivax and P. ovale after every 2 days- Tertian fever

•      In P. malariae after every 3 days- Quartan fever

•      While in P. falciparum  it recurs in every 36-48  hours

These paroxysmal attacks coincide with the release of successive broods of merozites into the blood stream.

Relapse Vs Recrudesence

•      Depending upon the cause , recurrence can be classified either as recrudescence or relapse

•      Recrudescence is when symptoms return after a symptoms free period. It is due to parasites surviving in the blood as a result of inadequate or ineffective treatment.

•      Relapse is when symptoms reappear after the parasites have been eliminated from blood but persist as dormant hypnozites in liver cells.

•      Relapse is common in P.ovale and P.vivax infection

•      Recrudescence is commonly seen in P.falciparum

Classification of antimalarial drugs

S.N	Category	Drugs
1	4-Aminoquinoline	Chloroquine , Amodiaquine
2	Quinoline methanol	Mefloquine
3	Cinchona alkaloid	Quinine, Quinidine
4	Biguanides	Proguanil  (Chloroguanide)
5	Diaminopyrimidines	Pyrimethamine
6	8-Aminoquinoline	Primaquine, Tafenoquine
7	Sulfonamides & sulfone	Sulfadoxine , Sulfamethopyrazin , Dapsone
8	Antibiotics	Tetracyclins, Doxycycline
9	Sesquiterpine lactones	Artesunate, Artemether, Arteether
10	Amino alcohols	Halofantrine, Lumefantrine
11	Naphthyridine	Pyronaridine
12	Naphthoquinone	Atovaquone

       

                                                                

Tissue schizonticides:  That eliminate pre erythrocytic/exo-erythrocytic  stages in liver

Erythrocytic schizonticides: It  acts on erythrocytic parasites

Gametocides : kill gametocytes in blood and prevent transmission to mosquitoes

Tissue schizonticides:

Primaquine: 15 mg/kg/day  X 2 weeks(hypno)

Proguanil

Doxycycline 

Gametocides: 

Primaquine

gametocidal for all species.

45 mg single dose. Immediately after clinical cure .Cuts down transmission to mosquito.

Clinical cure

Erythrocytic schizonticide is used to terminate the episode of malarial fever

a)     High efficacy

b)     Low efficacy

High efficacy	Low efficacy
Artemesinin	Proguanil
Chloroquine	Pyrimethamine
Amodiaquine	Sulfonamides
Quinine	Tetracyclins
Mefloquine	Clindamycin
Halofantrine
Lumifantrine
Atovaquone

Radical cure 

Eliminates both hepatic and erythrocytic stages in Vivax & ovale

Erythrocytic schizonticide + Tissue schizonticide

Chloroquine + primaquine

Chloroquine resistance

Quinine + Doxycycline/clindamycin + Primaquine

Artemesinin based combination therapy + Primaquine

Causal prophylaxis

Pre-erythrocytic phase which is the cause of malarial infection and clinical attacks is the target for this purpose Primaquine is the causal prophylactic for all species of malaria.

Supressive prophylaxis

Schizonticides which suppress the erythrocytic phase and thus attacks of malarial fever can be used as prophylactics. Clinical disease does not appear. For Supressive prophylaxis Chloroquine: NOT used in INDIA.

•      Mefloquine

•      Doxycycline

These protozoa have complex life cycles embodying both the female anopheles mosquito and the liver and the erythrocyte of the human host. Hence, an ideal antimalarial must be able to exert an effect on two fronts simultaneously, namely : to eradicate the microzoan from the blood and also from the tissues, in order to produce an effectife ‘radical cure’.

In actual practice, there are three well recognized and predominant manners to control malaria effectively, namely ;

(a) Elimination of the vector
(b) Drug therapy, and
(c) Vaccination.