1. A 34-year-old missionary returns from rural Democratic Republic of Congo with weeks of fever, posterior cervical lymphadenopathy, daytime somnolence, and a personality change noted by family. Blood smear shows trypomastigotes, and lumbar puncture reveals 40 white blood cells per microliter with trypanosomes in the cerebrospinal fluid. The infecting organism is Trypanosoma brucei gambiense. Which treatment is most appropriate?
A) Pentamidine intramuscularly
B) Suramin intravenously after a test dose
C) Nifurtimox-eflornithine combination therapy
D) Benznidazole orally for 60 days
E) Liposomal amphotericin B intravenously
ANSWER: C
Rationale:
Cerebrospinal fluid pleocytosis with trypanosomes establishes stage 2 (encephalitic) Trypanosoma brucei gambiense disease, which requires a central-nervous-system-penetrating regimen; nifurtimox-eflornithine combination therapy is the standard of care for stage 2 gambiense infection.
Option A: Option A is incorrect: pentamidine treats stage 1 gambiense only and does not reliably reach the central nervous system.
Option B: Option B is incorrect: suramin is for stage 1 rhodesiense and does not cross the blood-brain barrier, so it would fail in stage 2 disease.
Option D: Option D is incorrect: benznidazole treats Chagas disease (Trypanosoma cruzi), not African trypanosomiasis.
Option E: Option E is incorrect: liposomal amphotericin B treats visceral leishmaniasis, not trypanosomiasis.
2. A 28-year-old woman with Trichomonas vaginalis infection returns after a 7-day metronidazole course with persistent symptoms. She reports that on the second day she developed flushing, palpitations, and vomiting after a glass of wine and stopped taking the medication. Which intervention best addresses both her treatment failure and its underlying cause?
A) Prescribe single-dose tinidazole and counsel that nitroimidazoles cause a disulfiram-like reaction, so all alcohol must be avoided during therapy and for about 72 hours afterward
B) Switch to intravenous metronidazole to bypass the alcohol interaction
C) Add oral fluconazole, since the reaction indicates a resistant fungal coinfection
D) Reassure her that the reaction confirms the drug is working and restart the same regimen with alcohol
E) Begin desensitization immediately, since the symptoms indicate high-level metronidazole resistance
ANSWER: A
Rationale:
Her "failure" reflects nonadherence caused by a disulfiram-like reaction after alcohol, not drug resistance. Single-dose tinidazole improves adherence, and explicit counseling to avoid alcohol during therapy and for about 72 hours afterward (tinidazole's longer half-life) addresses the cause.
Option B: Option B is incorrect: the interaction is systemic and not avoided by the intravenous route; route is not the problem.
Option C: Option C is incorrect: the symptoms are an alcohol-acetaldehyde reaction, not evidence of fungal coinfection.
Option D: Option D is incorrect: the reaction is an adverse interaction, not a marker of efficacy, and combining with alcohol would repeat it.
Option E: Option E is incorrect: there is no evidence of resistance here; the issue is the alcohol interaction and incomplete therapy.
3. A 67-year-old man on chronic warfarin (a vitamin K antagonist) for atrial fibrillation is treated with metronidazole for a dental abscess. Eight days later he presents with gum bleeding and easy bruising; his international normalized ratio, previously therapeutic at 2.4, is now 6.8. Which mechanism best explains this development?
A) Metronidazole induced CYP2C9, accelerating warfarin clearance and paradoxically raising the international normalized ratio
B) Metronidazole displaced vitamin K from hepatic stores, enhancing clotting-factor synthesis
C) The dental infection alone caused the international normalized ratio to rise independent of any drug interaction
D) Metronidazole chelated warfarin in the gut, increasing its systemic absorption
E) Metronidazole inhibited CYP2C9, reducing clearance of the potent S-enantiomer of warfarin and potentiating its anticoagulant effect
ANSWER: E
Rationale:
Metronidazole inhibits CYP2C9, the enzyme that clears the more potent S-enantiomer of warfarin; reduced clearance raises warfarin exposure, elevates the international normalized ratio, and increases bleeding risk, exactly the picture here.
Option A: Option A is incorrect: metronidazole inhibits rather than induces CYP2C9, and induction would lower, not raise, the international normalized ratio.
Option B: Option B is incorrect: metronidazole does not mobilize vitamin K to enhance clotting-factor synthesis, which would oppose the observed rise.
Option C: Option C is incorrect: while acute illness can perturb anticoagulation, the temporal link to metronidazole and the magnitude point to the CYP2C9 interaction.
Option D: Option D is incorrect: the interaction is hepatic enzyme inhibition, not gut chelation enhancing absorption.
4. A 41-year-old man with untreated HIV and a CD4 count of 30 cells/mm3 presents with headache, right-sided weakness, and confusion. Brain magnetic resonance imaging shows multiple ring-enhancing lesions with surrounding edema, and Toxoplasma gondii serology is positive. Which regimen is the appropriate first-line treatment?
A) Liposomal amphotericin B plus flucytosine
B) Pyrimethamine plus sulfadiazine plus folinic acid
C) Metronidazole plus a luminal agent
D) Suramin followed by melarsoprol
E) Benznidazole plus nifurtimox
ANSWER: B
Rationale:
The presentation is classic toxoplasmic encephalitis in advanced HIV: multiple ring-enhancing lesions, positive serology, and CD4 below 100. First-line therapy is pyrimethamine plus sulfadiazine with folinic acid (leucovorin) to prevent pyrimethamine marrow toxicity. If there is no clinical or radiologic response by about 2 weeks, brain biopsy is considered to exclude central nervous system lymphoma, which can mimic this appearance.
Option A: Option A is incorrect: amphotericin-flucytosine treats cryptococcal disease, not toxoplasmosis.
Option C: Option C is incorrect: metronidazole plus a luminal agent treats amebiasis, not cerebral toxoplasmosis.
Option D: Option D is incorrect: suramin and melarsoprol treat African trypanosomiasis.
Option E: Option E is incorrect: benznidazole and nifurtimox treat Chagas disease.
5. A 52-year-old woman is receiving intravenous pentamidine for cutaneous leishmaniasis. Thirty minutes after the third dose she becomes diaphoretic, tremulous, and confused. A fingerstick glucose is 38 mg/dL, and her symptoms resolve promptly with intravenous dextrose. Which mechanism explains this event?
A) Pentamidine-induced QTc prolongation causing cerebral hypoperfusion
B) An anaphylactic reaction to the pentamidine infusion
C) Pentamidine-induced nephrotoxicity producing uremic encephalopathy
D) Pentamidine toxicity to pancreatic beta cells, causing unregulated insulin release and hypoglycemia
E) Pentamidine-induced hypothyroidism lowering the metabolic rate
ANSWER: D
Rationale:
Pentamidine is directly toxic to pancreatic beta cells; early injury triggers unregulated release of stored insulin, producing hypoglycemia, which is why glucose is monitored before and after each dose. The neuroglycopenic and adrenergic symptoms with a glucose of 38 mg/dL that reverse with dextrose fit this mechanism.
Option A: Option A is incorrect: QTc prolongation can cause arrhythmia but would not produce documented hypoglycemia reversed by dextrose.
Option B: Option B is incorrect: anaphylaxis presents with urticaria, bronchospasm, and hypotension, not isolated hypoglycemia.
Option C: Option C is incorrect: nephrotoxicity develops over time and does not cause acute hypoglycemia.
Option E: Option E is incorrect: hypothyroidism is not an acute pentamidine effect and would not cause this rapid hypoglycemic episode.
6. A 30-year-old man with stage 2 Trypanosoma brucei rhodesiense infection is being treated with melarsoprol. On the fifth day of therapy he develops rapidly declining consciousness, fever, and a generalized seizure. Which complication is most likely, and what is the appropriate co-treatment?
A) Hypoglycemia from beta-cell toxicity; treat with intravenous dextrose
B) Post-treatment reactive encephalopathy; manage with corticosteroids such as prednisolone, which reduce but do not eliminate this risk
C) A disulfiram-like reaction; administer intravenous fluids and antiemetics
D) Acute pancreatitis; begin bowel rest and analgesia
E) Torsades de pointes; give intravenous magnesium
ANSWER: B
Rationale:
Melarsoprol causes post-treatment reactive encephalopathy in roughly 5 to 10 percent of patients, an inflammatory syndrome that is fatal in about half of those affected and presents with depressed consciousness, fever, and seizures during treatment; concurrent prednisolone reduces but does not eliminate the risk.
Option A: Option A is incorrect: hypoglycemia from beta-cell toxicity is a pentamidine effect, not the cause of this melarsoprol-associated encephalopathy.
Option C: Option C is incorrect: the disulfiram-like reaction is an alcohol-nitroimidazole interaction and does not cause seizures and coma.
Option D: Option D is incorrect: pancreatitis is an antimonial toxicity and does not explain the neurologic picture.
Option E: Option E is incorrect: torsades de pointes is a pentavalent antimonial concern and would present as arrhythmia, not encephalopathy.
7. A 26-year-old woman at 12 weeks gestation is found to have acute Toxoplasma gondii seroconversion on routine screening. Amniocentesis and fetal imaging show no evidence of fetal infection at this time. Which agent is most appropriate now to reduce the risk of transmission to the fetus?
A) Spiramycin, which concentrates in placental tissue and reduces vertical transmission
B) Pyrimethamine plus sulfadiazine plus folinic acid as definitive fetal treatment
C) Metronidazole to clear the maternal infection
D) Liposomal amphotericin B to prevent dissemination
E) Benznidazole to interrupt transmission
ANSWER: A
Rationale:
When maternal infection is confirmed but the fetus is not yet infected, spiramycin is used because it concentrates in placental tissue and reduces vertical (mother-to-fetus) transmission without the teratogenic concern of pyrimethamine in early pregnancy.
Option B: Option B is incorrect: pyrimethamine-sulfadiazine-folinic acid is reserved for confirmed fetal infection (and pyrimethamine is generally avoided in the first trimester), not for transmission prophylaxis when the fetus is uninfected.
Option C: Option C is incorrect: metronidazole has no activity against Toxoplasma.
Option D: Option D is incorrect: liposomal amphotericin B treats leishmaniasis, not toxoplasmosis.
Option E: Option E is incorrect: benznidazole treats Chagas disease and has no role here.
8. A 19-year-old man from Bihar, India, has visceral leishmaniasis with months of fever, weight loss, and massive splenomegaly. He was treated with sodium stibogluconate at a local clinic without improvement. Considering the regional resistance pattern, which agent is the most appropriate next choice?
A) A higher dose of sodium stibogluconate
B) Suramin
C) Liposomal amphotericin B
D) Pyrimethamine plus sulfadiazine
E) Melarsoprol
ANSWER: C
Rationale:
In Bihar, antimonial resistance in Leishmania donovani is extremely high (60 percent or more), so antimonial failure is expected and liposomal amphotericin B (or miltefosine) is the appropriate next agent.
Option A: Option A is incorrect: escalating the dose of a drug to which regional resistance is widespread is unlikely to succeed and increases toxicity.
Option B: Option B is incorrect: suramin is an antitrypanosomal agent with no role in leishmaniasis.
Option D: Option D is incorrect: pyrimethamine-sulfadiazine treats toxoplasmosis, not visceral leishmaniasis.
Option E: Option E is incorrect: melarsoprol treats stage 2 African trypanosomiasis and is not used for leishmaniasis.
9. An 8-year-old child in rural Bolivia presents with fever, periorbital swelling (Romana sign), and a chagoma at the site of a triatomine bug bite. Blood smear shows Trypanosoma cruzi trypomastigotes, confirming acute Chagas disease. Which statement about treatment is correct?
A) Treatment should be deferred until the chronic indeterminate phase
B) Suramin is the agent of choice for acute Chagas disease
C) Melarsoprol should be given because of central nervous system risk
D) No antiparasitic therapy alters outcome in the acute phase
E) Benznidazole is first-line, and acute-phase treatment, especially in children, achieves high cure rates
ANSWER: E
Rationale:
Acute Chagas disease should be treated promptly; benznidazole is the first-line agent, and cure rates in the acute phase, particularly in children who tolerate the drug better than adults, exceed 80 percent.
Option A: Option A is incorrect: deferring treatment forgoes the highest-cure window; acute disease is treated immediately.
Option B: Option B is incorrect: suramin treats African trypanosomiasis, not Chagas disease.
Option C: Option C is incorrect: melarsoprol is an African trypanosomiasis agent and is not used for Chagas disease.
Option D: Option D is incorrect: acute-phase treatment markedly improves cure, so therapy clearly alters outcome.
10. A 45-year-old man is receiving suramin for stage 1 Trypanosoma brucei rhodesiense infection. Before the next scheduled dose, his routine urinalysis shows 3+ proteinuria, increased from a trace level at baseline. What is the most appropriate action?
A) Proceed with the scheduled dose, since proteinuria is an expected benign effect
B) Switch to oral pentamidine to complete the course
C) Double the next suramin dose to ensure parasite clearance before stopping
D) Withhold further suramin, because new significant proteinuria signals nephrotoxicity and proteinuria above 2+ contraindicates further dosing
E) Add a loop diuretic and continue suramin at the same dose
ANSWER: D
Rationale:
Suramin is nephrotoxic, and urinalysis is checked before each dose precisely to detect early renal injury; new proteinuria above 2+ contraindicates further suramin and mandates holding the drug.
Option A: Option A is incorrect: worsening proteinuria is not benign and is the specific trigger to stop.
Option B: Option B is incorrect: pentamidine treats stage 1 gambiense, not rhodesiense, and switching does not address the renal injury appropriately for this subspecies.
Option C: Option C is incorrect: increasing the dose of a nephrotoxic drug in the face of renal injury is dangerous.
Option E: Option E is incorrect: a diuretic does not treat suramin nephrotoxicity, and continuing the drug ignores the contraindication.
11. A 38-year-old man with advanced HIV (CD4 45 cells/mm3) has been treated successfully for visceral leishmaniasis with liposomal amphotericin B but has relapsed twice within a year despite completing each course. In addition to optimizing antiretroviral therapy, which strategy is most appropriate to prevent further relapse?
A) Switch permanently to sodium stibogluconate monotherapy
B) Begin secondary prophylaxis with periodic (for example, monthly) liposomal amphotericin B infusions and continue until immune reconstitution
C) Discontinue all antileishmanial therapy once each acute episode resolves
D) Give a single dose of oral metronidazole at each relapse
E) Treat each relapse with suramin
ANSWER: B
Rationale:
In HIV-coinfected visceral leishmaniasis, relapse rates are very high while immunosuppression persists, so secondary prophylaxis with periodic liposomal amphotericin B (commonly monthly) is recommended, continued until immune reconstitution on antiretroviral therapy.
Option A: Option A is incorrect: antimonial monotherapy is limited by resistance and toxicity and is not the maintenance strategy of choice.
Option C: Option C is incorrect: stopping all therapy after each episode is what permits the recurrent relapse; ongoing prophylaxis is needed.
Option D: Option D is incorrect: metronidazole has no activity against Leishmania.
Option E: Option E is incorrect: suramin is an antitrypanosomal agent and does not treat leishmaniasis.
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