Malaria Biology and Erythrocytic Cycle Quiz

Pharmacology of Antiparasitic Agents and Parasite Diseases

• The presentation covers the pharmacology of antiparasitic agents and parasite diseases, specifically focusing on malaria and amebiasis.

Outline

• Antiprotozoal Drugs:
  • Antimalarial drugs
  • Drugs for treatment of amebiasis
• Anthelmintic drugs

Introduction of Malaria

• Malaria is a protozoan disease transmitted by infected Anopheles mosquitoes.
• It's transmitted in 106 countries, with 300-500 million cases annually.
• Approximately 2000 deaths occur each day.
• Mortality rates have decreased due to effective control programs.
• Malaria was eliminated from many western countries in the late 20th and early 21st centuries, but its prevalence has increased in many tropical regions.
• Malaria poses a threat to non-endemic countries and travelers.

Epidemiology

• The precise geographic distribution of malaria species is not fully documented.
• Plasmodium vivax is more prevalent in India, Pakistan, Bangladesh, Sri Lanka, and Central America.
• P. falciparum is the dominant species in Africa, Haiti, the Dominican Republic, the Amazon region of South America, and New Guinea.
• Plasmodium ovale is found in Africa.
• Plasmodium malariae is considered to have a worldwide distribution.
• In the United States, most malaria cases are reported in immigrants and American travelers from endemic areas.
• Thailand: Plasmodium vivax accounts for 56.8% and P. falciparum comprises 42.5%

Life Cycle

• The life cycle involves the mosquito injecting sporozoites into a human host, followed by asexual multiplication in the liver and RBCs, and ultimately, gametocyte production, which allows transmission back to the mosquito.
• Asexual phase in the liver is called exoerythrocytic schizogony.
• Asexual production of merozoites in RBCs is called erythrocytic schizogony.
• Gametocyte stage is necessary for transmission to a mosquito.

Primary Attack

• The presentation highlights that relapses can occur due to P. vivax or P. ovale exoerythrocytic infections where these parasites can persist in the liver and causes later erythrocytic infections.

Immunity/Antibodies

• Antibodies against sporozoites block liver invasion.
• Antibodies to merozoites block RBC invasion.
• Antibodies to parasite antigens on infected RBCs block cytoadherence.
• Cell-mediated immunity and antibody-dependent cytotoxicity kill intraerythrocytic parasites.
• Antibodies block fertilization, development, and invasion.

Drugs that eliminate developing or dormant liver forms

• Tissue schizonticides
• Erythrocytic parasites (blood schizonticides)
• Drugs that kill sexual stages and prevent transmission to mosquitoes (gametocides)
• No single anti-malaria drug provides a complete cure.

Pathology

• The erythrocytic phase of malaria results in extensive hemolysis, anemia, and splenomegaly.
• Severe complications predominantly associate with P. falciparum infections.
• Infants and children, and non-immune pregnant women are especially at risk for severe malaria.
• The high parasitemia and ability of parasites to sequester in capillaries and postcapillary vessels of organs like the brain and kidney are largely responsible for the severe complications in malaria.

Characteristics of Indicated Species

• Table summarizing key characteristics (e.g., duration of intrahepatic phase, number of merozoites released per infected hepatocyte, duration of erythrocytic cycle, red cell preference, morphology, pigment color, ability to cause relapses). This table also contains essential data on different species of malaria parasite (P. falciparum, P. vivax, P. ovale, P. malariae).

Clinical Presentation of Malaria

• Initial presentation often involves nonspecific symptoms like fever, chills, rigors, diaphoresis, and malaise.
• The erythrocytic phase often presents with prodromal symptoms like headache, anorexia, malaise, fatigue, and myalgia, followed by specific symptoms like high fever, chills, and rigors.
• A variety of more serious complications including severe anemia, lactic acidosis and hypoglycemia, and splenomegaly may also arise.

Classification of Antimalarial Drugs

• Table showing the different classes of antimalarial drugs and their activity against specific stages of parasite development.

Treatment of Malaria

• Detailed information on the treatment of malaria, including different clinical settings, drugs, dosages, and alternative drugs.

Antimalarial Drugs

• Chloroquine, Piperaquine, Artemisinin &its derivatives, Mefloquine, Primaquine, Atovoquone

Drugs for the treatment of helminthic infections

• Detailed tables providing a list of infecting organisms, the drugs of choice, and any alternative drugs. This includes different groups like roundworms, flukes, and tapeworms.

Amebiasis

• Amebiasis is an infection with Entamoeba histolytica.
• Classification is based on symptomatology.
• The presentation discusses symptomatic and asymptomatic intestinal infection, amebic colitis, and extraintestinal infections.

Drugs of choice

• Listing specific drugs, dosages, and formulations for the treatment of amebiasis, based on the severity.

Metronidazole

• A drug of choice for various infections with particular considerations depending on disease severity.
• Metronidazole has various uses and is often paired with other medicines.

1. Albendazole

• A broad-spectrum oral antihelminthic.
• Effective against pinworms, hookworms, ascariasis, trichuriasis, and strongyloidiasis.
• MOA: inhibits microtubule synthesis, depletion of ATP production and leads to worm death.

2. Mebendazole

• Wide-spectrum antihelminthic agent.
• Effective against ascariasis, trichuriasis, hookworms and pinworms.
• Absorption is low, but increases with high-fat meals.

3. Diethylcarbamazine citrate

• Used against filarial nematodes.
• Kills microfilariae rapidly but adult parasites are killed more slowly.

4. Ivermectin

• Drug of choice in strongyloidiasis and onchocerciasis.
• MOA: strongly binds to glutamate-gated chloride channels (GABA) leading to paralyzation and death for invertebrate helminths.

5. Niclosamide

• Second-line drug for tapeworms.
• Effective for killing most adult tapeworms.

6. Praziquantel

• Effective against schistosomes, clonorchiasis, opisthorchiasis, paragonimiasis, and some kinds of tapeworms.
• MOA: increases the cell permeability to calcium in schistosomes causing strong contractions and paralysis of the worm musculature leading to detachment of suckers from the blood vessel walls.

7. Pyrantel pamoate

• Broad spectrum antihelminthic (for roundworms).
• Effective against various helminths such as pinworms, roundworms.
• MOA: causes the release of acetylcholine and inhibition of cholinesterase ultimately leading to paralysis.