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What causes malaria in humans
P. falciparum, P. vivax, P. ovale (curtisi and wallikeri), P. malariae, P. knowlesi
How is malaria transmitted
By the bite of infected female Anopheles mosquitoes
What happens during the inoculation stage of malaria
Plasmodial sporozoites enter the bloodstream and travel to the liver
What occurs in the liver during malaria infection
Sporozoites invade hepatic cells and undergo asexual reproduction (schizogony)
How many daughter merozoites are produced by one sporozoite in malaria
10,000 to >30,000 daughter merozoites
What happens when infected liver cells burst
Merozoites are released into the bloodstream and invade RBCs
What is the incubation period for P. knowlesi and P. malariae
P. knowlesi: 24 h, P. malariae: 72 h
What is the role of hypnozoites in malaria
They are dormant forms in P. vivax and P. ovale, causing relapses
How do P. falciparum merozoites invade erythrocytes
By binding to glycophorin A via erythrocyte binding antigen 175
What does the Duffy blood group antigen do in malaria
It plays a role in the invasion of erythrocytes by P. vivax
What is a schizont in malaria
A parasite that has grown inside an RBC and undergone nuclear divisions
What leads to the rupture of RBCs in malaria
Schizonts consume hemoglobin and release daughter merozoites
What stage of malaria causes disease in humans
The asexual blood-stage parasites cause RBC invasion and destruction
What is the role of gametocytes in malaria
They are sexual forms that transmit malaria to mosquitoes
How does the mosquito stage of malaria begin
Male gametocytes exflagellate and fuse with female gametocytes to form a zygote
Where does the zygote mature in the mosquito during malaria transmission
In the mosquito’s midgut, forming an ookinete
What completes the life cycle of malaria
Sporozoites migrate to the mosquito's salivary gland for inoculation into a new human host
How does the parasite detoxify toxic heme
By lipid-mediated crystallization to form inert hemozoin (malaria pigment)
What changes occur in the RBC membrane after parasite invasion
It alters transport properties, exposes cryptic antigens, and inserts parasite-derived proteins
What are "knobs" in P. falciparum infections
Protuberances on the RBC surface that extrude erythrocyte membrane adhesive protein (PfEMP1)
What is the role of PfEMP1 in malaria
It mediates cytoadherence to receptors on venular and capillary endothelium
What vascular receptors are important for cytoadherence in the brain and placenta
ICAM-1 and endothelial protein C receptor in the brain, chondroitin sulfate B in the placenta
What processes are central to the pathogenesis of falciparum malaria
Cytoadherence, rosetting, and agglutination
How do infected RBCs interfere with microcirculatory flow in malaria
They block capillaries and venules, causing sequestration in vital organs
Why do only young ring forms of the parasite circulate in falciparum malaria
Sequestered parasites develop out of reach of the spleen's filtration
How does malaria affect uninfected erythrocytes in severe cases
They become less deformable, impairing their passage through capillaries
How is parasite development in P. vivax and P. ovale different from P. falciparum
All stages of development are visible on peripheral blood smears in P. vivax and P. ovale
What type of erythrocytes do P. vivax and P. ovale prefer
They show a preference for young RBCs
What type of erythrocytes does P. malariae prefer
P. malariae prefers older erythrocytes
Why can P. falciparum cause higher parasite densities than other malaria species
It can invade erythrocytes of all ages
What contributes to high parasite densities in P. knowlesi infections
The shorter 24-hour asexual life cycle leads to rapid increases in parasite densities
How does the host initially respond to malaria infection
By activating nonspecific defense mechanisms, including splenic clearance of erythrocytes
What is "pitting" in malaria
The spleen removes damaged ring-form parasites from within RBCs and returns the cells to circulation
What triggers fever in malaria infections
Release of proinflammatory cytokines during schizont rupture
What effect do temperatures ≥40°C have on malaria parasites
They damage mature parasites and synchronize the parasitic cycle
What regular fever patterns were characteristic of untreated malaria
Quotidian (daily), tertian (every 2 days), quartan (every 3 days)
What genetic disorders provide protection against falciparum malaria
Thalassemias, sickle cell disease, hemoglobins C and E, hereditary ovalocytosis, and G6PD deficiency
How does sickle cell trait (HbA/S) reduce malaria severity
It impairs parasite growth at low oxygen levels and reduces cytoadherence
What protective effect does hemoglobin C have in malaria
It reduces cytoadherence of infected RBCs due to less surface PfEMP1 presentation
How does G6PD deficiency protect against malaria
It provides protection against severe P. falciparum and has a stronger effect against P. vivax infections
What is premunition in malaria
Asymptomatic parasitemia that provides protection from disease but not infection
What is the significance of PfEMP1 in malaria immunity
PfEMP1 is a key variant surface adhesin targeted by the immune system
How do maternal antibodies protect infants from malaria
They provide partial protection from severe malaria in the first months of life
Why does malaria immunity decline outside endemic areas
Immunity fades after several months of living away from transmission regions
How do malaria parasites evade the immune system
They lack MHC antigens on RBCs, induce immune unresponsiveness, and express variant antigens
How long can P. malariae persist without treatment
Parasites can persist for decades if left untreated
What are the first symptoms of malaria
Nonspecific symptoms like headache, fatigue, abdominal discomfort, muscle aches, and fever
What symptoms may suggest a diagnosis other than malaria
Prominent headache, chest pain, abdominal pain, cough, arthralgia, myalgia, or diarrhea
How does headache in malaria differ from meningitis
Malaria lacks neck stiffness and photophobia seen in meningitis
How does myalgia in malaria compare to dengue fever and leptospirosis
Myalgia is less severe in malaria than in dengue and muscles are not tender as in leptospirosis
What classic symptom is associated with P. vivax or P. ovale malaria
Classic malarial paroxysms with regular fever spikes, chills, and rigors
How does the fever pattern in falciparum malaria differ from other malarias
The fever in falciparum malaria may never become regular
What temperature changes are common in nonimmune individuals with malaria
Temperature often rises above 40°C (104°F) with tachycardia and sometimes delirium
What type of seizures are associated with falciparum malaria
Generalized seizures, potentially indicating cerebral malaria
What physical findings are common in uncomplicated malaria
Fever, malaise, mild anemia, and sometimes a palpable spleen
What causes anemia in young children in malaria-endemic areas
Frequent vivax malaria relapse and compromised antimalarial drug efficacy
How long does it take for the spleen to become palpable in nonimmune individuals with acute malaria
Several days after onset of the disease
What is a common sign of repeated malaria infections in endemic areas
Splenic enlargement in otherwise healthy individuals
What is a common finding in the liver in malaria, particularly among young children
Slight liver enlargement
What type of jaundice is associated with malaria
Mild jaundice, especially in adults, resolving in 1–3 weeks
Is malaria associated with a rash
No, malaria is not associated with a rash
What rare symptom may occur in severe falciparum malaria
Petechial hemorrhages in the skin or mucous membranes
What is the definitive diagnosis of malaria based on
Demonstration of asexual forms of the parasite in stained peripheral blood smears
What stain is preferred for diagnosing malaria
Giemsa at pH 7.2
What allows more rapid diagnosis of malaria but not speciation
Staining of parasites with fluorescent dye acridine orange
Why are both thin and thick blood smears examined for malaria diagnosis
To improve diagnostic sensitivity and accuracy
How is the density of parasitemia expressed in a thin blood smear
As the number of parasitized erythrocytes per 1000 RBCs
What is the advantage of thick blood films in malaria diagnosis
Concentrates the parasites, increasing diagnostic sensitivity
How are parasites and WBCs counted in thick blood films
By calculating the number of parasites per unit volume based on total leukocyte count
What is assumed WBC count for calculating parasitized erythrocytes per microliter
8000/μL
How many WBCs should be counted under oil immersion to confirm negative thick smear
A minimum of 200 WBCs
Why does low-density parasitemia have low specificity in high-transmission areas
Asymptomatic parasitemia is common, making it hard to identify malaria as the cause of illness
What rapid diagnostic tests (RDTs) are used for malaria diagnosis
Antibody-based tests detecting PfHRP2, lactate dehydrogenase, or aldolase antigens
What is a disadvantage of PfHRP2-based RDTs in high-transmission areas
Prolonged positivity after acute infection, potentially leading to false conclusions
Why is quantifying parasitemia important in malaria prognosis
High parasite densities (>105 parasites/μL) indicate an increased risk of death
What does the presence of phagocytosed malarial pigment in >5% of neutrophils indicate
Recent schizogony and a poor prognosis
When does gametocytemia peak in P. falciparum infections
One week after the peak of asexual parasite densities
Does persistent gametocytemia after treatment indicate drug resistance
No, it does not mean drug resistance if a full course of treatment was given
What does phagocytosed malarial pigment in monocytes suggest
Recent infection even if malaria parasites are not detectable
Why is PCR more sensitive than microscopy or rapid diagnostic tests for malaria
It detects malaria parasites and defines malarial species more accurately
How is PCR useful in epidemiologic surveys
Identifies asymptomatic infections as control and eradication programs reduce parasite prevalence
What is the role of serologic diagnosis in malaria
Useful for screening blood donors and measuring transmission intensity but not for diagnosing acute illness
What type of anemia is usual in acute malaria
Normochromic, normocytic anemia
What is the usual leukocyte count in acute malaria
Generally normal but may be raised in severe infections
What are the changes in white blood cell counts during acute malaria
Slight monocytosis, lymphopenia, eosinopenia
What happens to lymphocytes and eosinophils after acute malaria infection
Reactive lymphocytosis and eosinophilia
What is the typical platelet count in acute malaria
Usually reduced to ~105/μL
What happens to erythrocyte sedimentation rate, plasma viscosity, and C-reactive protein levels in acute malaria
Elevated
What are the coagulation abnormalities in severe malaria
Prolonged prothrombin and partial thromboplastin times, severe thrombocytopenia
What happens to Antithrombin III levels in malaria
Reduced even in mild infection
What are the typical plasma concentrations of electrolytes, BUN, and creatinine in uncomplicated malaria
Usually normal
What are common findings in severe malaria
Metabolic acidosis, low glucose, sodium, bicarbonate, phosphate, albumin, and elevated lactate, BUN, creatinine, urate, muscle and liver enzymes, bilirubin