Treatment for Malaria: The activity of Chloroquine


Malaria is a disease characterized by high fever, severe anemia, and respiratory distress. The organism responsible for this condition belongs to the unicellular group of organisms– Plasmodium. The causative organism of Malaria disease is
Plasmodium falciparum. The primary target cells are liver cells. The parasite rapidly multiples in the liver cells before attacking the erythrocytes. Usually, treatment for Malaria focuses on attacking the parasite at the liver stage.

Moreover, it is also capable of producing glycophosphatidylinositol, which acts as a potential malaria toxin. The release of pro and anti-inflammatory factors along with cytokines and chemokines determine the severity of the disease.

Arginine therapy for Malaria treatment

Low Arginine levels is a feature of Malaria. Arginine is the precursor of Nitric Oxide. Low levels can cause endothelial dysfunction, and eventually, cell death. Hence, Arginine therapy is among the treatments of Malaria. According to studies, the levels of nitric oxide and retinoic acid are inversely proportional. In other words, low Arginine is a sign of high retinol. Arginine therapy can inhibit retinoic acid activity, reverting endothelial dysfunction.

What is the possible treatment of retinopathy in Malaria?

Vitamin A deficiency- Retinopathy

The parasite can alter the retinoids affecting its concentration, leading to retinopathy. It is a characteristic sign of Vitamin A deficiency.

Vitamin A (retinoid) plays a vital role in host growth and development. It is also essential for vision, gene expression, tissue differentiation, growth factor release, and immune response. Besides, more than 80% of the body’s retinoids are present in the liver cells, which are the primary target of the parasite.

The parasite takes up all the retinoids present in the liver and converts it into retinal via alcohol dehydrogenase. After that, aldehyde dehydrogenase aids in the conversion of retinal to retinoic acid, which is a vital substance for the nutrition of the parasite. Later, it releases all the retinoic acid into the system, resulting in high concentration. This process simultaneously depletes retinoids (Vitamin A) in the surrounding cells. The host, simultaneously, loses the potential of an immune response.

Conclusively, low retinol concentration in the serum and more parasite-derived retinoic acid in the cells characterize the condition.

Quinolone treatment for Malaria

Research suggests that drugs that block the expression or metabolism of retinoic acid can serve as a proper treatment of retinopathy in Malaria. Quinolones (like Chloroquine and Fluoroquinolone) were the first choice. They inhibit the dehydrogenase enzymes, altering the synthesis and release of retinoic acid into the system. Aldehyde dehydrogenase inhibitors also prove lethal to P.falciparum

Moreover, high retinoid concentrations act as pro-oxidants and destabilize the cell membrane, resulting in death. They are also cytotoxic, mutagenic, and teratogenic. The liver saturated with retinoic acid spills the retinyl into the blood circulation. Retinyl reacts quickly. High doses can also cause acute toxicity. Nausea, vomiting, headache, vertigo, and muscular coordination characterize the condition.

How Chloroquine inhibits RNA/DNA synthesis?

Chloroquine primarily acts by inhibiting DNA synthesis. The target enzyme is the DNA primer. Although it attacks RNA synthesis too, the efficiency is less comparatively. In a study comparing its activity on both RNA and DNA synthesis, the researchers found that it can block the synthesis upto 50% of RNA and almost entirely in DNA.

The study also proved that its inhibitory reduces with the presence of more primer concentration and bivalent ion concentration. When the bivalent ions bind to Chloroquine, reducing its inhibitory effect on DNA polymerase enzyme. Moreover, structural alterations of the molecule can also affect its activity. 

Although chloroquine inhibition activity decreased with increasing Magnesium ion concentration, 8-aminoquinoline was insensitive to the Mg level. At a low Mg+2 level, the activity of Chloroquine was high, whereas at high Mg+2 8-aminoquinoline exceeded the inhibition activity of Chloroquine. 

Tips to prevent contracting the infection

  • Try to stay in air-conditioned rooms. If it is not available, prefer sleeping under the net treated with insecticide. Close the doors and windows entirely with drapes down.
  • Use insect repellent creams on your skin– also available as roll-ons, sprays, and ointments.
  • Prefer light and full clothing rather than shorts. Cover your skin to prevent mosquito bites.

Malaria prophylaxis

Malaria prophylaxis includes weekly oral intake of the drug. The reason behind this use is that the drug accumulates in the cell, and after a week will start expressing its activity of inhibiting RBC cell death. Start taking medicine 1-2 weeks before visiting the malarious area. Continue the usage weekly–same day each week– while you are in the area; and four weeks after leaving the place. It also includes the suppressive treatment, which starts two weeks before exposure, or take-in 1gm of the drug in two doses, six hours apart.

Make sure to share your personal history with your doctor. The medications can have side-effects if you already have HIV, AIDS, depression, heart or kidney problems, contraceptive pills, and remedies for blood clots. Immediately seek medical care at the onset of unusual symptoms.

Related: Ebola virus: What actually happens in the infected system

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