1. A 32-year-old business traveler returns from Nigeria and presents with 3 days of fever, headache, and myalgia. A blood smear confirms Plasmodium falciparum with a parasitemia of 1.5 percent. He is alert, hemodynamically stable, tolerating oral fluids, and has no organ dysfunction. What is the most appropriate treatment?
A) Oral chloroquine
B) An oral artemisinin-based combination therapy such as artemether-lumefantrine, taken with food
C) Intravenous artesunate
D) Oral primaquine alone
E) Oral atovaquone-proguanil at prophylactic dosing
ANSWER: B
Rationale:
This patient has uncomplicated Plasmodium falciparum malaria acquired in West Africa (a chloroquine-resistant region), is clinically stable, and can take oral medication. The appropriate treatment is an oral artemisinin-based combination therapy such as artemether-lumefantrine, given with food to ensure adequate lumefantrine absorption. This is correct.
Option A: Option A is incorrect because chloroquine-resistant falciparum predominates in Nigeria, so chloroquine would fail.
Option C: Option C is incorrect because intravenous artesunate is reserved for severe malaria; this patient has no severity criteria and can take oral therapy.
Option D: Option D is incorrect because primaquine does not treat the acute blood-stage falciparum infection and falciparum forms no hypnozoites requiring radical cure.
Option E: Option E is incorrect because prophylactic-dose atovaquone-proguanil is not a treatment regimen; treatment requires full treatment dosing, and an ACT is preferred first-line here.
2. A 5-year-old child is brought from a malaria-endemic region with high fever, deep unresponsiveness (unable to localize pain), and repeated seizures. The blood smear shows Plasmodium falciparum at 8 percent parasitemia, and laboratory studies reveal a lactate of 6 mmol/L and a blood glucose of 45 mg/dL. What is the most appropriate immediate antimalarial treatment?
A) Oral artemether-lumefantrine once the child can swallow
B) Oral chloroquine via nasogastric tube
C) Intravenous artesunate, because the child has severe malaria (cerebral involvement, hyperparasitemia, and acidosis)
D) Intramuscular primaquine
E) Oral atovaquone-proguanil
ANSWER: C
Rationale:
This child meets multiple criteria for severe malaria: impaired consciousness with seizures (cerebral malaria), hyperparasitemia (8 percent), and metabolic acidosis (elevated lactate), along with hypoglycemia. Severe malaria requires immediate parenteral therapy, and intravenous artesunate is first-line, reducing mortality compared with intravenous quinine; glucose should also be corrected. This is correct.
Option A: Option A is incorrect because an unresponsive, seizing child cannot safely take oral medication and severe disease demands parenteral treatment.
Option B: Option B is incorrect because chloroquine is inappropriate for severe falciparum disease and oral/nasogastric dosing is unsafe in an obtunded child.
Option D: Option D is incorrect because primaquine is an 8-aminoquinoline for radical cure and transmission blocking, not a treatment for acute severe malaria.
Option E: Option E is incorrect because oral atovaquone-proguanil is not appropriate for a child with severe disease requiring parenteral therapy.
3. A 27-year-old man returns from Papua New Guinea with fever and is found on smear to have Plasmodium vivax malaria. He is clinically well and able to take oral medication. The team plans to treat the acute infection and to prevent relapse. Before which step is a quantitative glucose-6-phosphate dehydrogenase (G6PD) level specifically required?
A) Before starting primaquine for radical cure, because primaquine causes dose-dependent hemolysis in G6PD-deficient patients
B) Before starting the blood schizonticide for the acute infection, because blood schizonticides cause hemolysis in G6PD deficiency
C) Before obtaining the diagnostic blood smear
D) Before administering antipyretics
E) Before discharging the patient, but only after primaquine has already been given
ANSWER: A
Rationale:
Radical cure of Plasmodium vivax requires an 8-aminoquinoline (primaquine or tafenoquine) to eradicate dormant liver hypnozoites, and these drugs cause dose-dependent oxidative hemolysis in G6PD-deficient patients. A quantitative G6PD level is therefore mandatory before starting primaquine. This is correct.
Option B: Option B is incorrect because the standard blood schizonticides used for the acute infection do not require G6PD testing; the requirement is tied specifically to the 8-aminoquinoline.
Option C: Option C is incorrect because the diagnostic smear has nothing to do with G6PD status.
Option D: Option D is incorrect because antipyretics do not require G6PD testing.
Option E: Option E is incorrect because the test must precede primaquine, not follow it; checking after the drug has been given defeats its protective purpose.
4. A 24-year-old traveler started weekly mefloquine for prophylaxis 10 days before a planned trip. After the second dose she reports vivid, disturbing nightmares, new anxiety, and difficulty concentrating. She has not yet departed. What is the most appropriate management?
A) Continue mefloquine, since these effects always resolve with continued use
B) Increase the mefloquine dose to overcome breakthrough symptoms
C) Reassure her that mefloquine has no neuropsychiatric effects and continue
D) Discontinue mefloquine and switch to an alternative prophylactic agent such as atovaquone-proguanil or doxycycline, because these neuropsychiatric symptoms reflect mefloquine intolerance
E) Add a benzodiazepine and continue mefloquine unchanged
ANSWER: D
Rationale:
Mefloquine carries a boxed warning for neuropsychiatric effects, and vivid disturbing dreams, new anxiety, and impaired concentration are recognized signs of intolerance. The standard reason prophylaxis is begun 2 to 3 weeks before travel is precisely so intolerance can be detected while still at home; this patient has not departed, so the correct action is to discontinue mefloquine and switch to an alternative such as atovaquone-proguanil or doxycycline. This is correct.
Option A: Option A is incorrect because these symptoms are warning signs that may worsen, not effects that should be pushed through.
Option B: Option B is incorrect and dangerous because a higher dose would intensify neuropsychiatric toxicity.
Option C: Option C is incorrect because mefloquine does have well-described neuropsychiatric effects.
Option E: Option E is incorrect because masking the symptoms while continuing the offending drug ignores the intolerance and risks progression to severe neuropsychiatric events.
5. A 30-year-old woman who is 20 weeks pregnant must travel for 3 weeks to a rural area with chloroquine-resistant Plasmodium falciparum. She has no psychiatric history and no seizure history. Which prophylactic regimen is most appropriate?
A) Doxycycline for the duration of travel
B) Mefloquine, started in advance of travel, because it is acceptable in pregnancy and effective against chloroquine-resistant strains, and she has no contraindication to it
C) Chloroquine weekly
D) Primaquine daily as causal prophylaxis
E) No chemoprophylaxis; rely on bed nets alone
ANSWER: B
Rationale:
For a pregnant traveler to a chloroquine-resistant area, mefloquine is considered acceptable in pregnancy and is effective against chloroquine-resistant strains; this patient has no psychiatric or seizure contraindication, so mefloquine is the most appropriate choice and should be started in advance of travel. This is correct.
Option A: Option A is incorrect because doxycycline is avoided in pregnancy owing to effects of tetracyclines on fetal bone and teeth.
Option C: Option C is incorrect because chloroquine would be ineffective against a chloroquine-resistant strain.
Option D: Option D is incorrect because primaquine is avoided in pregnancy because the fetal G6PD status is unknown and hemolysis cannot be excluded, and it is not used as routine prophylaxis here.
Option E: Option E is incorrect because relying on bed nets alone leaves a pregnant traveler dangerously unprotected against falciparum malaria, which is especially severe in pregnancy.
6. A patient with severe Plasmodium falciparum malaria is being treated with intravenous quinine in a setting where artesunate is unavailable. Several hours into therapy the patient becomes diaphoretic, tremulous, and acutely confused. What is the most important immediate step?
A) Stop all antimalarial therapy permanently, assuming an allergic reaction
B) Administer intravenous potassium, assuming hyperkalemia
C) Order an urgent head CT before any other intervention, assuming intracranial hemorrhage
D) Give intravenous antihypertensives, assuming hypertensive encephalopathy
E) Check the blood glucose immediately and treat hypoglycemia, because quinine stimulates insulin secretion and severe falciparum infection increases glucose consumption, making hypoglycemia a common and reversible cause of these symptoms
ANSWER: E
Rationale:
Quinine stimulates pancreatic insulin secretion, and severe falciparum malaria itself increases glucose consumption; together these make hypoglycemia a common, dangerous, and readily reversible complication of quinine therapy. New diaphoresis, tremor, and confusion should prompt an immediate bedside glucose check and treatment of hypoglycemia. This is correct.
Option A: Option A is incorrect because these features are characteristic of hypoglycemia, not an allergic reaction, and stopping malaria therapy in severe disease without addressing glucose would be harmful.
Option B: Option B is incorrect because quinine toxicity is associated with hypoglycemia, not hyperkalemia, and empiric potassium could be dangerous.
Option C: Option C is incorrect because, although cerebral malaria is a consideration, the immediate, reversible, and far more likely cause to check first is hypoglycemia.
Option D: Option D is incorrect because the picture is hypoglycemia, not hypertensive encephalopathy.
7. A 40-year-old traveler returns from the Thailand-Cambodia border region with falciparum malaria and is treated with a full course of an artemisinin-based combination therapy. On day 3 of treatment, a blood smear still shows persistent parasites, and the parasite count has fallen only slowly over the preceding days. What is the most appropriate interpretation and next step?
A) Suspect artemisinin partial resistance with possible partner-drug failure; manage as treatment failure with an effective alternative regimen (for example intravenous artesunate plus a different partner drug) and send samples for resistance genotyping
B) Conclude the patient is adequately treated, because persistent day-3 parasitemia is expected and benign
C) Add chloroquine, because it restores artemisinin susceptibility
D) Switch to primaquine monotherapy to clear the blood-stage parasites
E) Stop all therapy and observe, because the parasites will clear spontaneously
ANSWER: A
Rationale:
The Greater Mekong region (including the Thailand-Cambodia border) is the epicenter of artemisinin partial resistance, characterized by delayed parasite clearance, and clinical failure occurs when partner-drug resistance coexists. Persistent parasitemia with slow clearance at day 3 should be treated as treatment failure: switch to an effective alternative regimen (such as intravenous artesunate with a different partner drug) and send samples for resistance genotyping. This is correct.
Option B: Option B is incorrect because adequate ACT response normally produces marked parasite reduction by day 3; persistent slow-clearing parasitemia is abnormal in this context.
Option C: Option C is incorrect because chloroquine does not restore artemisinin susceptibility and has no role here.
Option D: Option D is incorrect because primaquine does not treat acute blood-stage falciparum infection.
Option E: Option E is incorrect because falciparum malaria is potentially fatal and persistent parasitemia will not be safely left to clear on its own.
8. A 58-year-old woman has taken hydroxychloroquine for rheumatoid arthritis for the past 7 years. She reports new difficulty reading and subtle changes in her central vision. What is the most appropriate interpretation and action?
A) Reassure her that hydroxychloroquine cannot affect the eyes and continue unchanged
B) Attribute the symptoms to oxidative hemolysis and order a G6PD level
C) Suspect hydroxychloroquine retinopathy and refer urgently for ophthalmologic evaluation, recognizing that cumulative, duration-dependent retinal toxicity can be irreversible and that the drug may need to be stopped
D) Attribute the symptoms to a neuropsychiatric effect of the drug and obtain psychiatric evaluation
E) Conclude the symptoms are unrelated and simply increase the hydroxychloroquine dose
ANSWER: C
Rationale:
Chloroquine and hydroxychloroquine can cause cumulative, dose- and duration-dependent retinopathy that may be irreversible, and risk rises with years of use. New central visual disturbance in a long-term user should prompt suspicion of retinopathy and urgent ophthalmologic referral, with consideration of stopping the drug. This is correct.
Option A: Option A is incorrect because hydroxychloroquine has a well-recognized ocular toxicity that requires monitoring.
Option B: Option B is incorrect because oxidative hemolysis is the hallmark of the 8-aminoquinolines, not the chronic ocular toxicity of hydroxychloroquine.
Option D: Option D is incorrect because the prominent neuropsychiatric toxicity belongs to mefloquine, and the visual symptoms point to retinopathy.
Option E: Option E is incorrect because increasing the dose would raise cumulative exposure and worsen the very toxicity suspected.
9. A 64-year-old man with congenital long QT syndrome and a baseline QTc of 480 ms is diagnosed with uncomplicated falciparum malaria. He can take oral medication. Which principle should most guide antimalarial selection in this patient?
A) Halofantrine should be chosen first because it is the least cardiotoxic antimalarial
B) Agents that markedly prolong the QT interval — quinine, quinidine, and halofantrine in particular — should be avoided or used only with caution and ECG monitoring, and an effective regimen with a more favorable cardiac profile should be selected with electrolyte correction
C) Quinidine should be chosen because its antiarrhythmic action will protect the heart
D) Cardiac status is irrelevant because no antimalarial affects the QT interval
E) Quinine is the safest option because it does not affect cardiac repolarization
ANSWER: B
Rationale:
Several antimalarials prolong the QT interval, with halofantrine being especially arrhythmogenic and quinine and quinidine also QT-prolonging. In a patient with long QT syndrome, these agents should be avoided or used only with caution and ECG monitoring, electrolytes should be corrected, and an effective regimen with a more favorable cardiac profile should be selected. This is correct.
Option A: Option A is incorrect because halofantrine is among the most cardiotoxic antimalarials, not the least.
Option C: Option C is incorrect because quinidine is strongly QT-prolonging (a class IA antiarrhythmic) and would be hazardous here.
Option D: Option D is incorrect because several antimalarials clearly affect the QT interval, so cardiac status is highly relevant.
Option E: Option E is incorrect because quinine does affect cardiac repolarization and can prolong the QT interval.
10. A 35-year-old man is started on primaquine for radical cure of Plasmodium vivax. Two days later he develops dark (cola-colored) urine, fatigue, lower back pain, and jaundice; his hemoglobin has fallen sharply and the laboratory reports an elevated reticulocyte count and low haptoglobin. A G6PD level had not been checked before the drug was started. What is the most likely cause and the appropriate action?
A) Acute hepatitis from primaquine; continue the drug and add a hepatoprotective agent
B) Acute interstitial nephritis; continue primaquine and start high-dose steroids
C) Expected benign discoloration; reassure and continue primaquine unchanged
D) Acute oxidative hemolysis precipitated by primaquine in an undiagnosed G6PD-deficient patient; stop primaquine immediately and provide supportive care, with transfusion if hemolysis is severe
E) A new malaria relapse; double the primaquine dose
ANSWER: D
Rationale:
Dark urine (hemoglobinuria), back pain, jaundice, a sharp hemoglobin drop, reticulocytosis, and low haptoglobin after starting primaquine are classic for acute oxidative intravascular hemolysis in a G6PD-deficient patient — exactly the event that pre-treatment quantitative G6PD testing is meant to prevent. The correct action is to stop primaquine immediately and provide supportive care, including transfusion if the hemolysis is severe. This is correct.
Option A: Option A is incorrect because the laboratory pattern (reticulocytosis, low haptoglobin, hemoglobinuria) indicates hemolysis, not hepatitis, and continuing the drug would worsen it.
Option B: Option B is incorrect because the picture is hemolysis, not interstitial nephritis, and continuing primaquine is harmful.
Option C: Option C is incorrect because cola-colored urine with a falling hemoglobin is dangerous hemolysis, not benign discoloration.
Option E: Option E is incorrect because this is drug-induced hemolysis, not relapse, and increasing the dose would intensify the hemolysis.
11. A 29-year-old traveler returns from a malaria-endemic region with fever and chills. The clinical suspicion for malaria is high, but the first thick and thin blood smear is reported as negative for parasites. What is the most appropriate next step?
A) Exclude malaria definitively, because a single negative smear rules it out
B) Start empiric broad-spectrum antibiotics and discharge without further malaria testing
C) Begin primaquine presumptively for radical cure while awaiting other results
D) Order serologic antibody testing as the definitive method to exclude acute malaria
E) Repeat thick and thin blood smears every 12 to 24 hours for a total of three negative smears before excluding malaria, because a single negative smear does not rule it out (parasitemia fluctuates and may be low at the time of sampling); a rapid diagnostic test can be used in parallel
ANSWER: E
Rationale:
A single negative blood smear does not exclude malaria, because parasitemia fluctuates with the synchronized replication cycle and may be below the detection threshold at the moment of sampling. The standard approach in a patient with high clinical suspicion is to repeat thick and thin smears every 12 to 24 hours until three are negative before excluding malaria, often with a rapid diagnostic test used in parallel. This is correct.
Option A: Option A is incorrect because one negative smear is insufficient to rule out malaria.
Option B: Option B is incorrect because abandoning malaria evaluation in a high-suspicion febrile returnee is unsafe; falciparum can deteriorate rapidly.
Option C: Option C is incorrect because presumptive primaquine does not treat acute blood-stage malaria, must not be given without G6PD testing, and is not a diagnostic strategy.
Option D: Option D is incorrect because serology reflects past exposure and is not used to diagnose or exclude acute malaria; microscopy (and rapid antigen testing) are the diagnostic tools.
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