How does antimalarial drug resistance happen?

Several factors facilitate the emergence of resistance to existing antimalarial drugs. To mention some factors, the parasite mutation rate, the overall parasite load, the strength of drug selected, the treatment compliance, and poor adherence to malaria treatment guidelines.

What is the mechanism of chloroquine resistance?

The major action of chloroquine is to inhibit the formation of hemozoin (Hz) from the heme released by the digestion of hemoglobin (Hb). The free heme then lyses membranes and leads to parasite death. Chloroquine resistance is due to a decreased accumulation of chloroquine in the food vacuole.

What is antimalarial drug resistance?

Antimalarial resistance in malaria parasites spreads because it confers a survival advantage in the presence of the antimalarial and therefore results in a greater probability of transmission for resistant than for sensitive parasites.

How does malaria become resistant to chloroquine?

In P. falciparum, the cause of the most lethal human malaria, chloroquine resistance is linked to multiple mutations in PfCRT, a protein that likely functions as a transporter in the parasite’s digestive vacuole membrane.

What is the role of drug resistance in the control of malaria transmission?

The development of resistance to drugs poses one of the greatest threats to malaria control and results in increased malaria morbidity and mortality. Resistance to currently available antimalarial drugs has been confirmed in only two of the four human malaria parasite species, Plasmodium falciparum and P. vivax.

Why do antimalarial drugs become ineffective?

Over the last century, almost every frontline antimalarial drug – chloroquine, sulfadoxine, pyrimethamine – has become obsolete because of defiant parasites that emerged from western Cambodia. From this cradle of resistance, the parasites gradually spread west to Africa, causing the deaths of millions.

What does chloroquine do to Plasmodium?

Similar to the case of the DV of Plasmodium parasites, chloroquine accumulates in any low-pH (i.e. a pH of less than 4–5) organelle such as lysosomes due to its weak base property and reduces the organelle’s acidification.

How does drug resistance occur in parasites?

The factors that can explain the emergence of resistance are: Reduction of drug concentration within the parasite, either by decreasing drug uptake or by increasing efflux of the drug; inhibition of drug activation; inactivation of active drug; and gene amplification [70].

What type of mutation is malaria resistance?

The sickle-cell allele is widely known as a variant that causes red blood cells to be deformed into a sickle shape when deoxygenated in AS heterozygotes, in which A indicates the non-mutant form of the β-globin gene, and also provides resistance to malaria in AS heterozygotes.

What is the mechanism of action of quinine?

Mechanism of Action: Quinine inhibits nucleic acid synthesis, protein synthesis, and glycolysis in Plasmodium falciparum and can bind with hemazoin in parasitized erythrocytes.

What gene is the key to malaria resistance?

Roberto Amato: kelch13 is one of the ‘nicknames’ of a gene officially known as ‘PF3D7_1343700’ in the malaria-causing parasite Plasmodium falciparum.