Lecture 9 — Malaria & Genetic Control

What organism causes malaria?

Protozoan parasites of the genus Plasmodium (phylum Apicomplexa).

Which five Plasmodium species infect humans?

P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi.

Which species causes the most severe form of malaria?

Plasmodium falciparum.

What mosquito transmits malaria?

Female Anopheles mosquito.

What kind of transmission occurs in mosquitoes carrying malaria?

Cyclopropagative transmission (parasite develops and multiplies inside the vector).

What are other, non-mosquito forms of malaria transmission?

Blood transfusion, congenital infection, and contaminated needles or syringes.

How long is the incubation period for malaria?

Usually 7 – 30 days (shorter for P. falciparum, longer for P. malariae).

How can antimalarial prophylaxis affect the incubation period?

It can delay symptom onset, masking or postponing disease.

Which species can relapse due to dormant liver stages?

P. vivax and P. ovale (form hypnozoites that reactivate months or years later).

Why can malaria be misdiagnosed in returned travelers?

Symptoms may appear long after infection because of liver relapse or delayed diagnosis.

What are the three stages of a classic malaria attack?

Cold stage (chills), Hot stage (fever, headache, vomiting), Sweating stage (sweats, fatigue).

How long does a classical malaria attack last?

About 6 – 10 hours.

Which malaria parasites have a “tertian” (48 hr) fever pattern?

P. falciparum, P. vivax, and P. ovale.

Which malaria parasite has a “quartan” (72 hr) fever pattern?

P. malariae.

What symptoms characterize uncomplicated malaria?

Fever, chills, sweats, headache, body aches, nausea, vomiting, malaise.

What physical findings are common in malaria?

Fever, weakness, perspiration, splenomegaly, mild jaundice, hepatomegaly, increased respiratory rate.

What lab findings support malaria diagnosis?

Mild anemia, low platelets (thrombocytopenia), ↑ bilirubin, ↑ aminotransferases, parasites on blood smear.

What is the gold standard for malaria diagnosis?

Microscopy of thick and thin blood smears.

What defines severe malaria?

Organ failure or blood/metabolic abnormalities due to high parasite load.

What are the major complications of severe malaria?

Cerebral malaria, severe anemia, hemoglobinuria, ARDS, DIC, hypotension, renal failure, acidosis, hypoglycemia, hyperparasitemia (>5% RBCs infected).

Why does P. falciparum cause severe disease?

It infects RBCs of all ages → very high parasitemia and massive hemolysis.

What is cerebral malaria?

A form of severe malaria causing seizures, coma, and neurologic damage from RBC blockage in brain vessels.

What neurologic defects may remain after cerebral malaria?

Ataxia, palsy, speech, hearing, or vision impairment.

How can malaria affect pregnancy?

P. falciparum infection can cause maternal anemia, premature birth, and low-birth-weight infants.

Which malaria species can cause splenic rupture?

Plasmodium vivax.

Which species can cause nephrotic syndrome from chronic infection?

Plasmodium malariae.

What is tropical (hyperreactive) splenomegaly syndrome?

Excessive immune reaction to repeated malaria → huge spleen/liver, anemia, and immunologic abnormalities.

Why do relapses occur in P. vivax and P. ovale malaria?

Reactivation of dormant liver forms (hypnozoites) months or years after infection.

What drug eliminates dormant hypnozoites to prevent relapse?

Primaquine (tissue schizonticide).

What are the three main goals of malaria treatment?

Relieve symptoms, prevent relapse, and prevent transmission.

What drug classes correspond to those goals?

Blood schizonticides (chloroquine, quinine, artemisinin combos);

tissue schizonticides (primaquine);

gametocytocides (primaquine or chloroquine).

When is “presumptive” malaria treatment used?

Only in emergencies when lab confirmation is unavailable and severe disease is suspected.

What vaccine is available for malaria?

Mosquirix (RTS,S) – the first approved malaria vaccine.

What is the target antigen of Mosquirix?

P. falciparum circumsporozoite protein (CSP) from the pre-erythrocytic stage.

How does Mosquirix work?

Stimulates antibodies that block sporozoite entry into liver cells and cell-mediated destruction of infected hepatocytes.

Why is the malaria vaccine only partially effective?

CSP is antigenically weak and elicits limited immunity.

Why is P. falciparum more dangerous than other species?

It infects RBCs at all ages → higher parasitemia and severe anemia or organ failure.

What is the difference between Zika and West Nile virus transmission?

Zika uses Aedes aegypti mosquitoes with no bird reservoir; WNV uses Culex mosquitoes with bird reservoirs, allowing spread in temperate regions.

Why won’t Zika spread like West Nile in North America?

It lacks a large animal (bird) reservoir for local amplification and overwintering.

What does RIDL stand for?

Release of Insects Carrying a Dominant Lethal gene.

What is the purpose of RIDL technology?

To genetically suppress mosquito populations by releasing engineered males whose offspring die in larval/pupal stages.

How is the RIDL lethal gene controlled?

By a tetracycline-repressible switch – gene is off in lab (rearing with tetracycline) and on in the wild (no tetracycline).

What gene system is used in RIDL?

The tTAV (tetracycline-repressible transcriptional activator) system – over-expression without tetracycline is toxic.

How are RIDL mosquitoes identified in the field?

They carry a fluorescent marker gene expressed in the eyes to distinguish GM from wild mosquitoes.

What happens when RIDL males mate with wild females?

Offspring inherit the lethal gene and die before adulthood, reducing vector populations.