Malaria and Plasmodium Species

Plasmodium Species

• Plasmodium vivax: causes benign tertian malaria, most widely distributed
• Plasmodium ovale: causes ovale tertian malaria, confined to West Africa
• Plasmodium malariae: causes quartan malaria, rare except in Africa
• Plasmodium falciparum: causes malignant tertian malaria, most predominant in Africa

Global Distribution of Malaria

• Mode of infection: infective female Anopheles mosquito injects sporozoites with its saliva at the site of bite

Life Cycle of Malaria

• Infective stage: when a female Anopheles mosquito bites a patient, it ingests infected RBCs
• Liver phase: hypnozoites (P.vivax & P.ovale) present, patient is asymptomatic
• Blood phase: rupture of infected red blood cells occurs every 3rd day in P.vivax & P.ovale, 4th day in P.malariae, and irregularly in P.falciparum

Pathogenesis of Malaria

• Incubation period followed by influenza-like symptoms
• Malaria paroxysms (clinical attack) appears: symptoms coincide with rupture of infected RBCs, release of parasite metabolites, and host immunologic response

Clinical Picture of Malaria

• Patient passes through three consecutive stages:
  • Cold stage: sudden chill, extreme cold, and temperature rises (15 minutes)
  • Hot stage: headache, high fever, and hot, dry, and flushed skin (2-6 hours)
  • Sweating stage: profuse sweating and temperature falls (few hours)
• Clinical attacks gradually decrease and finally disappear as patients' immune cells clear the circulation from most of blood merozoites, Plasmodium metabolites, and Malaria pigment
• Clinical attacks reappear due to presence of hypnozoites in the liver (relapse) or presence of low-grade parasitaemia when the patient becomes immunosuppressed (recrudescence)

Clinical Picture of Malaria (continued)

• Hemolytic anemia: severity of anemia varies according to the invading Plasmodium species
  • P.vivax & P.ovale: prefer to invade young RBCs, less severe anaemia
  • P.malariae: prefers to invade old RBCs, less severe anaemia
  • P.falciparum: invades RBCs of any age, severe anaemia
• Hepatosplenomegaly: due to enhanced phagocytosis of remnants of ruptured red cells, blood merozoites, Plasmodium metabolites, and Malaria pigment

Complications

• Chronic P.malariae infection: complicated by Nephrotic syndrome
  • P.malariae parasite produces excess amount of antigen
  • Patient's immune system produces excess amount of antibody
  • Immune complexes are produced and circulate to deposit on glomerular wall, leading to kidney tissue damage
• P.falciparum infection: complicated by:
  • Knob formation on the surface of infected RBCs, adherence to receptors on endothelium of blood capillaries, leading to blood supply and death of organ tissue
  • Examples of affected organs and tissues: brain (cerebral malaria), intestine, lungs, liver, and kidney

Laboratory Diagnosis of Malaria

• 1- Giemsa-stained thin & thick blood film examination to demonstrate the parasite stages
• 2- Detection of circulating parasite antigen using monoclonal antibodies
• 3- Detection of parasite DNA and RNA in patient's blood using PCR

Treatment of Malaria

• Groups of drugs used to treat malaria: tissue schizonticides, blood schizonticides, and blood gametocytes
• Recommended regimen for treatment of malaria:
  • During clinical attack: Chloroquine
  • Radical treatment after clinical attack: Primaquine (for P.vivax and P.ovale)
  • Treatment of drug-resistant cases: combination of drugs (recently artimisinin)
  • Chemoprophylaxis: for healthy human entering an endemic area

Epidemiology of Malaria

• Circumstances responsible for existence of malaria in a certain locality:
  • Infected human (gametocyte carrier)
  • Suitable species of Anopheles mosquito vector
  • Human (susceptible to infection)

People Naturally Resistant to Malaria Infection

• Those having the following medical problems:
  • Absence of Duffy antigen: resistant to P.vivax infection
  • Haemoglobin S (in sickle-cell disease): shape of RBC and type of haemoglobin are not suitable for P.falciparum parasite growth
  • Deficiency of G6PD enzyme: P.falciparum parasite needs this enzyme for its growth

Control of Malaria

• Treatment of cases
• Mosquito control
• Chemoprophylaxis
• Vaccination trials: RTS, S/AS01 was engineered using genes from the outer protein of P.falciparum