Malaria Overview and Understanding

Malaria Overview

• Malaria is a deadly disease caused by the parasite Plasmodium
• Four species cause malaria in humans, but P. falciparum causes most deaths (97% of global cases)
• P. vivax is the most prevalent species outside Africa (~50% of cases in SE Asia)
• Malaria is characterized by cyclical fever bouts (every other day) linked to parasite division/release. It is often followed by anaemia.
• The parasite's complex lifecycle involves both humans and mosquitoes.
• Malaria incidence has shown a decrease since 2010, but numbers remain high. Around 249 million cases globally in 2022, a slight increase over 2021, possibly due to COVID.

Learning Objectives

• Understanding that malaria is caused by different species of Plasmodium.
• Understanding the pathology (disease process) of malaria is linked to the parasite's immune evasion (sequestration).
• Understanding the complex life cycle of the Plasmodium parasite.
• Identifying the human host cells Plasmodium colonizes.
• Understanding how sickle cell anaemia can protect against malaria.
• Understanding chloroquine's mode of action and how parasite resistance arises.
• Understanding the geographical distribution of malaria.

Malaria Epidemiology

• 94% of malaria cases and deaths globally occur in Africa.
• Six countries (Nigeria, Democratic Republic of Congo, Uganda, Côte d'Ivoire, Mozambique, and Niger) account for over half the world’s cases.
• 41% of the global population live in areas where malaria transmission occurs.

Plasmodium Species

• P. falciparum: causes the majority of deaths globally (99.7% cases in Africa, 97% global)
• P. vivax: usually less severe but accounts for ~75% of cases in the Americas and a similar proportion in Southeast Asia
• P. ovale: uncomplicated form of malaria, less than 1 % of all cases.
• P. malariae: uncomplicated form of malaria, less than 1% of all cases.

Malaria Pathogenesis

• Infected red blood cells (RBCs) change shape, developing knobs.
• These knobs contain the protein PfEMP1, allowing them to adhere to host blood vessel walls.
• This process, sequestration, prevents the spleen from eliminating infected RBCs.
• This can lead to cerebral malaria due to the blockage of blood vessels in the brain.
• Characteristic symptom patterns in malaria are often linked to the timing of parasite division and release.

Apicomplexa

• Plasmodium belongs to the phylum Apicomplexa.
• Apicomplexa parasites have complex organelles like apicoplasts and micronemes.
• Several genera infect humans, causing human diseases like malaria, diarrhea, and neurological pathology.

Plasmodium Lifecycle

• The lifecycle has two hosts: humans and mosquitos
• The disease progresses through the liver and red blood cells (RBCs) in the human.
• The parasite infects the mosquito to complete its lifecycle.
• Infectious sporozoites are injected into the blood stream.
• Once inside the liver, the parasites divide and mature to merozoites.
• Merozoites infect red blood cells causing symptoms.
• Merozoites develop into gametocytes which are transmitted to mosquitoes through human blood.
• Mosquitoes feed on human blood and sporozoites develop in their digestive systems, infecting the salivary glands.
• As infections spread, they release the sporozoites to infect new humans.
• During the parasite's lifecycle, it shows intricate strategies for evading the host immune system during reproduction and transmission.

Malaria Resistance and Sickle Cell Anemia

• Sickle cell anemia is a genetic disorder where beta hemoglobin can form abnormal polymers and cause the RBCs to become abnormally shaped (sickled).
• This abnormality makes them more susceptible to destruction by the immune system (slower life cycle than normal RBC).
• Individuals with sickle cell trait (one copy of the HbS gene) have protection against malaria.
• The reason for susceptibility and resistance is related to the life cycle, parameters and parasite physiology.
• Other hemoglobin disorders, like thalassemia, confer a similar protective effect.

Chloroquine Mechanism of Action

• Chloroquine prevents the formation of hemozoin from hemoglobin inside the parasite.
• Chloroquine uptake reduces hemozoin concentration lowering parasite proliferation.

Chloroquine Resistance

• Resistance to chloroquine has developed in many regions.
• Resistance mutations in the parasite protein PfCRT interfere with chloroquine transport and accumulation, making infections much more difficult.
• Chloroquine remains a first-line treatment for some Plasmodium species, but resistance renders it less effective or useless for others.

Video Plasmodium Lifecycle in the Mosquito

• The lifecycle in the mosquito midgut involves multiple steps leading to sporozoite production.
• Gametocytes develop into different haploid forms (male and female)
• Fusion forms a zygote.
• Develop into sporozoites after several stages in the midgut.
• Sporozoites enter the salivary glands and are transmitted to humans.

Additional Concepts

• The Plasmodium parasite relies on immune evasion mechanisms for survival in the host.
• The parasite's ability to evade the host's immune response is critical to its success.
• Understanding the parasite's methods of immune evasion is essential for developing effective treatment and preventive strategies.
• There are multiple mechanisms of parasite evasion; cytoadhesion, sequestration, and various other processes all contribute to the parasite immune evasion strategies.
• These factors play a role in the disease progression; understanding them is essential for treatment and prevention strategies development.
• There are now several different approaches to malaria treatment and prevention strategies.

This quiz explores the deadly disease malaria, which is caused by various species of the Plasmodium parasite. It delves into the complex life cycle of Plasmodium, the pathology of the disease, and the relationship between sickle cell anaemia and malaria resistance. Test your knowledge on key concepts in malaria and its impact on human health.