Pathogenesis, Diagnosis and treatment of Malaria - Plasmodium spp, a malarial parasite

                  Pathogenesis, Diagnosis, and treatment of Malaria

Malaria :
- It is a disease caused by the bite of a mosquito that carries the parasitic protozoa called Plasmodium species
- The disease can be fatal and life-threatening for humans
- Plasmodium species comes under the parasite group called "Sporozoa"
- Malaria is one of the major zoonotic diseases that cause millions of human deaths each year
- More than 75% of deaths occur in the African region of the world, over a million people mostly children die from malaria each year worldwide

Plasmodium species:
- Malaria is a vector-borne infection that is spread through the bite of the mosquito, thus the term given for this type of infection is a 'zoonotic disease'. The infected vector, the mosquito injects the parasite into the bloodstream of humans.
- Malaria in humans is known to cause primarily by four species of Plasmodium, they are Plasmodium vivax, Plasmodium falciparum, Plasmodium malariae and Plasmodium ovale 
- A new species P. knowlesi has also been found to cause malaria in humans
- P. vivax and P. falciparum are the most common, P. falciparum is the most pathogenic of all four
- The parasite is transmitted to humans via the vector female Anopheles mosquito

General characteristics of Plasmodium species (blood)
P. vivax:
-Infects reticulocytes, usually, young cells, has 48 hour incubation period
- Could remain inactive in the liver as hypnozoites
- Ring formation with the enlarged RBCs
- Amoeboid shape trophozoites within 10 hours and into mature schizont containing merozoites in RBC's

P. ovale:
- Infects young cells, has 48 hours of the incubation period
- Could remain inactive in the liver as hypnozoites
- Smaller ring than P. vivax with the enlarged RBCs having oval-shaped edges 
- Less amoeboid trophozoites than P. vivax
- Mature schizonts has fewer merozoites than that of P. vivax

P. falciparum:
- Infects young and old cells, has 36 to 48 hour incubation period
- Different sizes of RBCs develop with multiple rings
- Formation of crescent-shaped gametocytes 
- More severe and life-threatening than other Plasmodium species

P. malariae:
Infects old cells, has 72 hours of the incubation period
- Normal size RBCs, the formation of thick rings 
- Trophozoites with the band formation and mature schizonts consists of the merozoites  

P. knowlesi:
-Infects young and old cells, has 24 hours of the incubation period
- Different sizes of RBCs with multiple rings
- Trophozoites with the bands and mature schizonts consists of the merozoites
- Formation of gametocytes
- More fatal and life-threatening than other Plasmodium species

  • A female Anopheles mosquito with sporozoites in its salivary glands bites a person
  • Within a few hours, the sporozoites are carried to the liver via the blood
  • The parasite enters the hepatocytes and starts to grow, the process is known as the "pre erythrocytic cycle"
  •  Merozoites are formed in the liver which ultimately invades the RBCs and reticulocytes, thus "erythrocytic cycle" begins
  • Develops into trophozoites, takes up the hemoglobin, and further develops into mature schizont which consists of several merozoites
  • Merozoites are released into the bloodstream invading RBCs, this is known as the "erythrocytic schizogony cycle"
  • Some merozoites can develop into male and female gametocytes after undergoing several generations of the erythrocytic cycle 
  • The incubation period of the Plasmodium spp is usually one to two weeks except for P. malariae from two weeks to six weeks. Although it may be extended from months to years.

Symptoms of malaria:

Fever is common, a person may experience headaches, chills, and muscle pain within a few days after the infection. Here are the types of symptoms shown by the different types of Plasmodium spp.

P. vivax-
Mild fever within 48 hours of infection, paroxysm, parasitemia may occur resulting in anemia. In rare cases, it may invade the central nervous system(CNS). If untreated infection may last up to 5 to seven years

P. ovale
Mild fever within 48-hour infection, mild paroxysm occurs, parasitemia and anemia develop. CNS infection may occur. If untreated the infection may last up to 12 months

P. falciparum
Mild continuous fever, severe paroxysm occurs, parasitemia, and severe anemia develops. CNS involvement is very common, if untreated infection may last up to 6 to 18 months

P. malariae- 
Mild to moderate continuous fever, severe paroxysm occurs, parasitemia, mild anemia. CNS involvement is rare, if untreated infection may last up to more than 20 years.

P. knowlesi
Mild and regular fever, moderate to severe paroxysm, severe anemia may occur. CNS infection is possible, the lasting duration of the infection is not known

Laboratory diagnosis:
Blood is used as a standard specimen 
  • Microscopic examination- Blood specimen with Giemsa stain, other stains such as Wright-Giemsa and Rapid Field stain. A Finger-stick blood test is recommended where thin and thick blood smears are taken on the glass slides and observed under a microscope. Fluorescent microscopy is also done for the parasite detection
  • Rapid Antigen Test and Antibody tests are commercially available 
  • Serological tests: IFA, ELISA. Not very helpful
  • Molecular diagnosis- Nucleic acid amplification test(DNA or RNA) from blood specimen by PCR method
Treatment of Malaria:
  • Drugs- Recommended according to the species of the Plasmodium and the infection type. Chloroquine, mefloquine, quinine, artemisinin, sulfadoxine-pyrimethamine is effective to reduce the symptoms. P. falciparum and P. vivax have become more resistant to these drugs. In serious and severe cases of malaria, the drugs are very less or non-effective
  • Classification of antimalarial drugs- tissue schizonticides, blood schizonticides, gametocytocidal and sporontocidal compounds
  • Recently, in 2021 WHO (World Health Organization) have recommended a newly discovered vaccine for malaria. RTS, S/AS01, (RTS, S) have shown effective results in the African parts of the world where malaria is prevalent and deaths due to the infection are highest.
Prevention and Control:
- Protective clothing, full sleeve t-shirts, full length trousers etc. will help to protect exposed skin
- Use of bed nets, insect repellent ointments and topical creams in mosquito prevalent regions
- Use of antimalarial drugs in endemic regions
- Awareness programs in endemic areas focusing on health and hygiene
- Staying inside during evening and night in mosquito prevalent regions
- Clearing the stagnant water areas, which could be the site for the breeding of the mosquitoes