malaria

Parasitism

Ecological terms that define way of life - symbiotic relationship between species.

Commensalism

Sharing the table - one partner benefits - but other is not hurt.

Mutualism

Special form of commensalism - both benefit.

Obligate parasites

Most parasites are obligate (permanent).

Facultative parasites

In some species only some life cycle stages: larvae - parasitic, and free-living generations can alternate depending on environment.

Protozoa

Greek for first (proto), zoa (animals).

Eukaryotic organelles

Protozoa possess eukaryotic organelles + exhibit features of other eukaryotic cells.

Apicoplast

Unique organelle in malaria parasites; derived non-photosynthetic plastid found in most apicomplexa, thought to have originated through algae through secondary endosymbiosis - contains 35kb circular genome.

Trophozoite

Life cycle stage that is vegetative; feeding, mostly motile.

Cyst

Life cycle stage that is dormant; protective thick wall.

Amoeba

Classified by motility - move by pseudopods.

Flagellates

Classified by motility - move by flagella.

Ciliates

Classified by motility - move by cilia.

Sporozoa (apicomplexan)

Classified by motility - complex life cycle - actin myosin motor complex (AMMC).

Apicomplexan parasites

Either invade or attach to host cells by unique organelles localized to one end of parasite - apical organelles.

Main biosynthetic pathways in apicoplast

FA biosynthetic pathway, isoprenoid biosynthetic pathway (DOXP pathway), haeme biosynthesis pathway.

Host invasion of apicomplexa

1. Merozite attachment 2. Reorientation + junction formation 3. Sequential discharge rhoptry and microneme 4. Penetration parasite in RBC 5. Pinching off junction.

Malaria

Derived from Italian word mal

Causative agent

Plasmodium species

Type of organism

Protozoan parasite

Classification

Member of apicomplexa

Species infecting humans

5 species

Transmission

Transmitted by Anopholes Mosquitoes

Clinical cases per year

3-500 million

Deaths per year

1.5-2.7 million (90% Africa)

Disease status

Re-emerging disease

Drug resistance

Drug resistant

P.vivax

Most common human plasmodium parasite

P.falciparum

Most strongly pathogenic, causes cerebral malaria and majority of mortality

RBC invasion by P.vivax + P.ovale

Invade young RBC

RBC invasion by P.malariae

Invade old RBC

RBC invasion by P.falciparum

Invade all RBC

Incubation period for P.falciparum

7 to 14 days

Incubation period for P.vivax + P.ovale

8 to 18 days

Incubation period for P.malariae

7 to 40 days

Sporozoites injection

Injected into saliva and enter circulation

Liver trapping

Trapped by liver via Ephrin receptor A2

Relapse

Appearance of clinical signs of malaria: 3 to 6 months or longer after primary disease/attack

Types of sporozoites in P.vivax + P.ovale

2 types: sporozoites induce primary attack, hypnozoites result in relapse

Sporozoites in P.malariae and P.falciparum

Only sporozoites without hypnozoites, no relapse

Intermittent period of malaria attacks

Determined by length of asexual erythrocytic cycle

Paroxysm attack frequency for P.vivax + ovale

About every 48 hours

Paroxysm attack frequency for P.malariae

Every 72 hours

Paroxysm attack frequency for P.falciparum

36-48 hours, may be irregular

Mild form of malaria

Symptoms milder and persistent time is shorter

Malaria immunity

Species specific, strain specific, lasts for a short time only

Cross-protective immunity

Immunity to P.falciparum does not protect from P.vivax

Pathogenesis and pathology

Includes hepatocellular lesions, hepatomegaly, abnormal liver functions, anaemia, and splenomegaly

Types of malaria

Asymptomatic, mild or uncomplicated, severe

Cerebral malaria

Most serious type, generally caused by P.falciparum

Diagnostic tests for malaria

Blood smear, PCRs, Serology (ELISA or IFA), Rapid diagnostic test

Malaria rapid diagnostic tests

Detect antigens such as HRP-2 and pLDH

Protozoan Parasites

Single-celled organisms including classes such as Lobosea (Amoebas), Zoomastigophorea (Flagellates), Ciliophora (Ciliates), and Sporozoa (Apicomplexa).

Metazoan Parasites

Multicellular organisms including Helminths (worms) and Arthropods (ectoparasites).

Helminths

Worms that include Nematodes (roundworms), Trematodes (flatworms), Cestoda (tapeworms), and Metacanthocephala (spiny-headed worms).

Arthropods

Insects, Arachnids, and Crustaceans that act as ectoparasites like ticks, mites, and lice.

Direct Life Cycle

A simpler pathway where the parasite goes directly from host to eggs/cysts to larval stages and back to host.

Indirect Life Cycle

A more complex pathway requiring a definitive host for sexual reproduction and an intermediate host, going through multiple larval stages.

Contact and Penetration of Eyes

An entry route for parasites such as Acanthamoeba.

Inhalation

An entry route for parasites including Acanthamoeba, Enterobius, and Naegleria.

Fecal-Oral/Ingestion

An entry route for multiple parasites including Ascaris, Giardia, Toxoplasma, and Cryptosporidium.

Sexual Contact

An entry route for parasites such as Entamoeba, Giardia, and Trichomonas.

Vector-Borne

Parasites transmitted through bites, such as Trypanosoma by kissing bugs, Plasmodium and Wuchereria by mosquitoes, and Leishmania by sandflies.

Helminth Entry

Entry through skin penetration by parasites like Ancylostoma, Necator, and Schistosoma.

Apicomplexan Parasites

Parasites characterized by the presence of an apicoplast, which is essential for survival but has lost the ability to photosynthesize.

Key Genera of Apicomplexan Parasites

Plasmodium, Babesia, Toxoplasma, Cryptosporidium, Eimeria.

Malaria Symptoms - Central/Systemic

Headache and Fever.

Malaria Symptoms - Skin

Chills and Sweating.

Malaria Symptoms - Respiratory

Dry cough.

Malaria Symptoms - Muscular

Fatigue and Pain.

Malaria Symptoms - Spleen

Enlargement.

Malaria Symptoms - Back

Pain.

Malaria Symptoms - Stomach

Nausea and Vomiting.

Malaria Life Cycle - Key Stages

Stages include mosquito injecting sporozoites, liver stage development, asexual reproduction in red blood cells, and formation of gametocytes.

Hypnozoites

Dormant forms of P. vivax and P. ovale in the liver that can cause relapse months or years later.

Plasmodium falciparum Blood Stage Development

A highly synchronized 48-hour cycle including red cell invasion, ring stage, trophozoite, and schizont formation.

Merozoite release

Cell bursts, releasing new parasites (40-48 hours)

Clinical Impact

When RBCs rupture (hemolysis), they release parasite debris, pigments, and metabolites.

Periodic paroxysm

Causes shaking chill, high fever, and heavy sweating - the classic malaria attack pattern.

P. vivax / P. ovale

48-hour cycle (fever every other day) - 'tertian malaria'

P. malariae

72-hour cycle (fever every 3rd day) - 'quartan malaria'

P. falciparum

Irregular fever pattern (most dangerous species)

Rosetting Types

Types of rosetting include Type I (basic adhesion), Type II (host-derived factor), and Type III (parasite-derived proteins).

Type I Rosette

Basic adhesion of infected RBC to uninfected RBCs.

Type II Rosette

Host-derived rosette-stimulating factor involved.

Type III Rosette

Parasite-derived proteins (non-RBC membrane-associated) create larger clusters.

Clinical significance of rosetting

Helps parasites avoid splenic clearance, evade immune detection, and contribute to severe disease.

Sequestration in blood vessels

Causes severe complications like cerebral malaria (brain blood vessels blocked) and organ damage.

Molecular Interactions

Complex protein interactions at the cell membrane level between modified infected RBC membrane and endothelial cells.

Hemozoin Problem

Parasite converts 25-50% of free heme into insoluble crystalline hemozoin (malaria pigment).

Antimalarial Drug Action

Chloroquine and Artemisinin inhibit hemozoin formation, causing toxic heme to accumulate and kill the parasite.

Clinical impact of hemolysis

Severe anemia occurs because 1% of people die from sickle cell anemia alone; non-immune hemolysis contributes significantly.

Gametocyte Development Timing

P. falciparum takes about 10 days, P. ovale takes 2-3 days, and P. vivax takes 6-7 days to develop mature gametocytes.

Traditional Antimalarial Drugs

Includes Chloroquine, Sulfadoxine/Pyrimethamine, Quinine, Mefloquine, Atovaquone-Chloroguanide, and Antibiotics.

Artemisinin Combination Therapies (ACTs)

Includes Artemether-lumefantrine (Coartem), Artemisinin-piperaquine, Dihydroartemisinin-piperaquinir, Artesunate-mefloquine, Artesunate-pyronaridine, Artesunate-sulfadoxine/pyrimethamine, and Artesunate-amodiaquin.

Primaquine

Targets the liver stages (hypnozoites) in the malaria life cycle.

What is the goal of pre-erythrocytic stage vaccines?

To block infection of the liver.

Who is the target population for pre-erythrocytic stage vaccines?

Non-immune travelers in low transmission areas, infants, and pregnant women in high transmission areas.

What is the purpose of blood stage vaccines?

To reduce disease severity and death.

Who benefits from blood stage vaccines?

Children and pregnant women in high transmission areas.