Introduction
According to WHO, malaria is a disease that is caused by a plasmodium parasite and transmitted by the bite of infected mosquitoes. April 25th every year is WHO World Malaria Day to sensitize people on dangers of malaria.
The Mosquito is the female of the genus Anopheles. It can also be transmitted through blood transfusion from an infected donor. Unborn babies can get it through the placenta of an infected mother.
On 20th Aug 1897 in Secunderabad, India, Sir Ronald Rose discovered that Anopheles mosquitoes were responsible for transmission of malaria parasites in humans.
The causative unicellular parasite – Plasmodium is a protozoon. There are up to 50 species but only four species of plasmodium are known to cause malaria in man. They are Plasmodium ‘P’ Falciparum, P- malaria, P ovale, and P – vivax. These four species are responsible for the distribution of malaria disease all over the world. However, their distribution are affected by the different climates. In the tropical and subtropical part of the world like West Africa, the plasmodium Falciparum is most common. Other factors such as stagnant water, bushes, dirt, high density human population provide breeding environment for these mosquitoes.
For us to understand the drug treatment of Malaria, let us understand the stages the plasmodium undergo in the body to cause the symptoms we describe as malaria.
LIFE CYCLE OF PLASMODIA
There are 3 Stages of life cycle of plasmodium namely Gametocytes, Sporozoites and Merozoites.
GAMETOCYTES
Microgametocytes are male gametocytes while female gametocytes are macrogametocytes. These sexual phase of the plasmodium take place in the female mosquitoes. With the presence of male and female gametocytes, fertilization takes place in the mosquitoes gut and the fertilized Zygote develops in the gut wall.
This development process is called Sporogony and leads to the formation of an infective Sporozoites which migrate to the tissues of the mosquitoes salivary gland.
The next stage is when the infected female mosquito bites a human being. It injects the infective sporozoites into the blood stream of the person from there the sporozoites rapidly migrate to the hepatic (liver parenchymal cells, and remained undetected for about 30 minutes. While in these liver cells they develop into tissues Schizonts. All these while the host is assymptomatic and are the exoerythrocytic stage. The length of time differs depending on the specie of Plasmodium involved. For P- Vivax and P – Falciparum, It can be between 10 and 14 days while 18 days to 6 weeks in the case of P – Malariae.
The next stage is the symptomatic stage – erythrocytic stage when the matured schizonts now merozoites are released after the rupture of the tissue Schizonts into the blood stream. They continue invading other red blood cells, with more asexual cycle and multiplication. Occasionally, the infected erythrocytes or red blood cell burst and release of merozoites into the blood stream that manifest, the feverish symptoms of malaria and the length of time for its occurrence depends on the species. It can take 48 hours for P.Falciparum, P –Vivax and P – ovale while 72 hours in P – Malaria.
To repeat the sexual process, some of infected erythrocytes develop into gametocytes and when mosquitoes bite such people they pick the gametocytes and stores them in their guts where the processes of fertilization re occurs when eventually the whole processes regenerated.
TYPES OF MALARIA
Basically we have 5 types of Malaria due to Causative Plasmodia Parasites. They are :
Plasmodium Falciparum or P- Falciparum – malignant tertian malaria
P – Malariae – Quartan malaria,
P – Vivax – Benign tertian malaria
P – Ovale – Ovale malaria
P – Knowlesi – common in Southeast Asia E.g. Malaysia. It can also cause malaria in other primates.
In man P – Vivax is most prevalent of type and shows characteristic period acute attacks involving chills, fever, profuse sweating, enlarged spleen and liver, anemia, abdominal pains, headaches and lethargy.
P – Falciparum is the most serious and lethal form of malaria and is responsible for 90% of deaths from malaria especially cerebral malarial.
DRUG TREATMENT OF MALARIA
I want to group the drug treatment of malaria into 6 (six) groups namely.
Causal Prophylaxis
Suppressive treatment
Clinical cure
Radical cure
Gametocytocidal
Miscellaneous
Causal Prophylaxis
These class of drugs are used to attack the parasite before it is released into the blood stream where it causes a lot of symptoms. They act on the exoerythrocytic stage of plasmodia. They are useful in prophylaxis.
Examples are Pyrimethamine which is popularly known as Sunday – Sunday medicine as it is taken 1 tablet once a week.
Primaquine is also effective but unpopular due to serious side effects.
Proguanil hydrochloride popularly Known as paludrine is prophylactic and administered one tablet orally every day.
Suppressive Treatment
These group of drugs act on the erythrocytic stage of the parasite. They inhibit malaria symptoms but do not affect the exoerythrocytic stage. As such they suppress the manifestation of the symptoms. When the drug is stopped symptoms can appear.
Examples include pyrimethamine which act as prophylactic and suppressive.
In combination with sulfadoxine, it was effective against Chloroquine resistant Falciparum malaria.
Clinical Cure
The drugs here are meant to interfere with the asexual erythrocytic stage on the hepatic parachymal cells preventing the formation of the Schizonts.
Chloroquine and Amodiaquine are good examples that work on both Falciparum and Vivax malarial infections.
Radical Cure
This is the group of drugs which can eliminate both the exoerythrocytic and erythrocytic stages of a malarial infection. A good example is 8 aminoquinolines, which have also good gametocytocidal activities against all four species of Plasmodium.
To prevent drug resistance by any of the species, Chloroquine is administered in conjuction.
Gametocytocidal Therapy
These group attack the gametocidal stage of the parasite while they are still in the erythrocytic stage before mosquitoes bite the host to pick them up for another sexual cycle in which they will go round to repeat total cycle. Again. Primaquine can destroy both Vivax and Falciparum gametocytes when other anti malarial are effective more on Vivax rather than falciparum sexual stages.
Miscellaneous
Quinacrine was blood Schizonticides but no longer in use as anti malarial. Quinine is a good blood Schizonticide and has no effect on exoerythrocytic stages but gametocytocidal for P –Vivax and P – Malariae.
Note: Also ensure that you use insecticide treated net and maintain clean environment.
WHO CURRENT STANDARD TREATMENT FOR MALARIA
Due to resistance to a monotherapy for malaria therapy especially involving Falciparum specie of plasmodium WHO came up with combination therapy called Artemisinin based combination Therapies (ACTS). This offer a good solution to failures in Chloroquine – resistant malaria. Examples of such combination therapy are: 1. Artemeter – lumefantrine as it is in lonart, Coartem, Coatal etc. others include 2. Artesunate + Mefloquine, 3. Artesunate + Sulfadoxine – Pyrimethamine and 5. Dihydroartemisinin + Piperaquine e.g.Waipa
Note: There are many other combinations of ACT
ADVERSE DRUG REACTIONS OF DRUGS USED FOR TREATMENT OF MALARIA.
Chloroquine Based Therapy; blurred vision, nausea, vomiting, abdominal or stomach cramps, headache, diarrhea, temporary hair loss, changes in hair color, dizziness, sleep disturbances (insomnia and vivid dreams), psychiatric reactions e.g. anxiety, depression, panic attacks, and hallucinations, rashes, pruritus.
Artemisinin – Based Combination Therapics (ACTS): anorexia, nausea, abdominal pain, diarrhea, headache, dizziness, sleep disorders, palpitation, arthralgia, myalgia, cough, asthenia, fatigue, pruritus, rash.
DRUG INTERACTIONS WITH ANTI MALARIA DRUGS
ACT
You are advised not to take the following drugs at the same time with ACT drugs: Azithromycin, chloroquine, Ciprofloxacin, Erythromycin, Fluconazole, Mefloquine, Ofloxacin, Primaquine, Proguanil, Quinine, pyrimethamine, Quinidine, Grapefruit juice.
It is not advisable to take grape juice, orange or Vitamin c when you are on ACT, Artesunate or amodiaquine as the efficacy and potency will be diminished since they can interfere with the metabolism of the anti malarial drugs.
Do not take folic acid with malaria drug as it supplies the plasmodium with cellular folate to survive the inhibitory effect from anti malarial drugs.
ACKNOWLEDGEMENT
Geneith Pharm. Ltd.
Wikipedia
WEBMD
Emdex
Medical Micrbiology 26th Edition – Jawetz, Melnick and Adelberg