Molecular Diagnosis of Infectious Diseases — MCQs

10 questions

A healthcare worker develops fever, night sweats, and cough. Sputum shows acid-fast bacilli. What is the next diagnostic test?

A sexually active adolescent presents with cervicitis. Which specimen collection method has the highest sensitivity for detecting N. gonorrhoeae?

Which of the following statements about nucleic acid amplification tests (NAATs) for STIs is FALSE?

A patient with cough was sputum AFB negative but chest X-ray was suggestive of TB. What should be the next step according to RNTCP?

Species identification is done by:

False regarding Alzheimer's disease (AD) is:

Molecular genetic testing is used to detect all of the following except?

Dent's disease is characterized by all except:

Q10

A patient with native aortic valve disease presents with right hemiparesis. What is the most appropriate management to prevent further strokes?

Molecular Diagnosis of Infectious Diseases Indian Medical PG Practice Questions and MCQs

Question 1: A healthcare worker develops fever, night sweats, and cough. Sputum shows acid-fast bacilli. What is the next diagnostic test?

A. Gram stain
B. Serology for TB
C. NAAT for TB (Correct Answer)
D. Sputum culture

Explanation: ***NAAT for TB*** - Nucleic Acid Amplification Tests (**NAAT**) rapidly confirm the presence of **Mycobacterium tuberculosis** DNA or RNA, crucial after an **acid-fast bacilli (AFB) smear** is positive [1]. - This test offers high sensitivity and specificity and can also detect **drug resistance**, guiding immediate treatment decisions [1]. *Gram stain* - A **Gram stain** is not appropriate for **Mycobacterium tuberculosis** because these bacteria have a unique cell wall that makes them **acid-fast**, not readily stained by the Gram method. - The initial finding of **acid-fast bacilli** already indicates a general type of organism, making a Gram stain redundant and uninformative for TB. *Serology for TB* - **Serological tests for TB** (detecting antibodies to M. tuberculosis) are generally **not recommended** for the diagnosis of active pulmonary TB due to their **poor sensitivity and specificity**. - They have limited utility in diagnosing active disease and are not endorsed by major health organizations for this purpose. *Sputum culture* - **Sputum culture** is the **gold standard** for confirming TB diagnosis and for **drug susceptibility testing**, but it is a **slow process** (taking several weeks) [2]. - While essential for definitive diagnosis and resistance profiling, it is not the **"next" rapid diagnostic test** required given the positive AFB smear.

Question 2: A sexually active adolescent presents with cervicitis. Which specimen collection method has the highest sensitivity for detecting N. gonorrhoeae?

A. First-catch urine
B. Cervical gram stain
C. Clinician-collected endocervical swab (Correct Answer)
D. Self-collected vaginal swab

Explanation: ***Clinician-collected endocervical swab*** - A **clinician-collected endocervical swab** is the gold standard for detecting *N. gonorrhoeae* in cervicitis due to direct sampling and high cellularity. - This method ensures proper collection from the **likely site of infection**, maximizing the yield of bacterial DNA for NAATs. *First-catch urine* - While useful for screening, **first-catch urine** has lower sensitivity than direct cervical sampling for cervicitis. - It primarily detects urethral infections and may miss organisms localized in the endocervix. *Cervical gram stain* - **Cervical Gram stain** can identify gram-negative intracellular diplococci but has lower sensitivity and specificity compared to NAATs. - It is often reserved for initial rapid assessment but is not definitive for detecting *N. gonorrhoeae*. *Self-collected vaginal swab* - **Self-collected vaginal swabs** are less invasive and can be a good screening tool, but may not be as sensitive as a clinician-collected endocervical swab. - The patient may not properly access the **endocervical canal**, reducing the quality of the sample.

Question 3: Which of the following statements about nucleic acid amplification tests (NAATs) for STIs is FALSE?

A. They can be used for test of cure after 3 weeks
B. They can detect dead organisms after treatment
C. They can be used for pharyngeal gonorrhea screening
D. They are less sensitive than culture for rectal chlamydia (Correct Answer)

Explanation: ***They are less sensitive than culture for rectal chlamydia*** - This statement is **FALSE**. NAATs are generally **more sensitive** than culture methods for detecting *Chlamydia trachomatis* in all anatomical sites, including the rectum. - The high sensitivity of NAATs allows for the detection of very low bacterial loads, making them the preferred diagnostic method for many STIs. *They can be used for test of cure after 3 weeks* - This statement is generally **true**. While a "test of cure" (TOC) is not routinely recommended for uncomplicated *Chlamydia* or *Gonorrhea* infections due to high treatment efficacy, it can be considered in specific circumstances (e.g., persistent symptoms, pregnancy, or use of alternative regimens). - If a TOC is performed, it should ideally be done **no sooner than 3 weeks post-treatment** to minimize potential false positives from detecting residual nucleic acids from dead organisms. *They can detect dead organisms after treatment* - This statement is **true**. NAATs detect the **nucleic acids (DNA or RNA)** of the target organism. - These nucleic acids can persist in the body for a period even after the organism has been killed by treatment, leading to a positive NAAT result despite successful eradication of the infection. *They can be used for pharyngeal gonorrhea screening* - This statement is **true**. NAATs are the **recommended method** for detecting *Neisseria gonorrhoeae* in extragenital sites, including the pharynx. - Pharyngeal gonorrhea is often **asymptomatic**, making screening of at-risk individuals important for public health.

Question 4: A patient with cough was sputum AFB negative but chest X-ray was suggestive of TB. What should be the next step according to RNTCP?

A. Nucleic acid amplification test (Correct Answer)
B. Tuberculin test
C. Line probe assay
D. Culture

Explanation: Nucleic acid amplification test - According to the and Revised National Tuberculosis Control Program (RNTCP) guidelines, if sputum AFB microscopy is negative but clinical suspicion and chest X-ray point towards TB, NAAT (Nucleic Acid Amplification Test) is recommended as the next confirmatory step [1]. - NAATs like CBNAAT (Cartridge-Based Nucleic Acid Amplification Test) or TrueNat provide rapid detection of Mycobacterium tuberculosis and resistance to Rifampicin, aiding in early diagnosis and appropriate treatment initiation. Tuberculin test - The Tuberculin Skin Test (TST), also known as the Mantoux test, indicates past exposure to TB or latent infection, but it cannot differentiate between active disease, latent infection, or past treated infection [2]. - A positive TST in an adult with a suggestive chest X-ray still requires further investigation for active disease, as it does not confirm active pulmonary TB [2]. Line probe assay - Line Probe Assay (LPA) is a molecular test used for rapid detection of MDR-TB (multi-drug resistant TB) by identifying mutations associated with resistance to Rifampicin and Isoniazid. - While useful for resistance testing, it typically requires a positive culture or direct sputum sample with a higher bacterial load and is not the primary diagnostic test for initial confirmation of TB when sputum AFB is negative. Culture - Mycobacterial culture is the gold standard for TB diagnosis, providing definitive confirmation and enabling drug susceptibility testing (DST) [1]. - However, culture results can take several weeks (typically 3-6 weeks), which delays treatment initiation, making it a less immediate next step compared to rapid molecular tests like NAAT in cases of strong clinical suspicion.

Question 5: Species identification is done by:

A. Precipitin test (Correct Answer)
B. Benzidine test
C. Spectroscopy
D. Takayama test

Explanation: ***Precipitin test*** - The **precipitin test** is the **gold standard method for species identification** in forensic serology. - It is based on the principle of **antigen-antibody reaction**, where species-specific antisera (e.g., anti-human serum) react with corresponding antigens in the biological sample. - When positive, a visible **precipitate forms at the interface**, confirming the species origin of the bloodstain or bodily fluid. - This test is **highly specific** and can differentiate human blood from animal blood. *Benzidine test* - The **benzidine test** is a **presumptive test for blood** that detects the presence of hemoglobin through a color change reaction. - It is **not species-specific** and cannot differentiate between human and animal blood. - It only indicates the **likely presence of blood**, requiring further confirmatory testing. *Spectroscopy* - **Spectroscopy** involves analyzing the interaction of electromagnetic radiation with matter to identify chemical composition. - While useful for identifying various compounds, it is **not the standard method for species identification of biological samples** in forensic practice. - Other specialized techniques are preferred for determining species origin. *Takayama test* - The **Takayama test** (haemochromogen crystal test) is a **confirmatory test for blood** that detects hemoglobin derivatives by forming characteristic pink crystals. - Like the benzidine test, it confirms blood presence but **does not determine species origin**. - It is used to confirm that a stain is blood, not to identify whether it is human or animal.

Question 6: False regarding Alzheimer's disease (AD) is:

A. Number of neurofibrillary tangles is associated with the severity of dementia
B. Number of senile (neuritic) plaques correlates (increases) with age
C. Presence of tau protein suggest neurodegeneration
D. Extracellular inclusion (lesion) can occur in the absence of intracellular inclusions to make pathological diagnosis of AD (Correct Answer)

Explanation: ***Extracellular inclusion (lesion) can occur in the absence of intracellular inclusions to make pathological diagnosis of AD*** - A definitive pathological diagnosis of **Alzheimer's disease** requires both the presence of **extracellular amyloid plaques** and **intracellular neurofibrillary tangles** [1]. - Neither inclusion type alone is sufficient for the diagnosis, as amyloid plaques can be found in non-demented elderly individuals [1]. *Number of neurofibrillary tangles is associated with the severity of dementia* - The **density and distribution of neurofibrillary tangles** (NFTs) directly correlate with the severity of cognitive impairment and **dementia** in AD [1]. - Tangles are composed of hyperphosphorylated **tau protein** and disrupt neuronal function, leading to neurodegeneration [2]. *Number of senile (neuritic) plaques correlates (increases) with age* - The accumulation of **senile (neuritic) plaques**, composed primarily of **beta-amyloid protein**, generally increases with age, even in cognitively normal individuals [1]. - While plaques are a hallmark of AD, their mere presence is not always diagnostic of clinical dementia [1]. *Presence of tau protein suggest neurodegeneration* - The presence of **hyperphosphorylated tau protein**, especially when forming **neurofibrillary tangles**, is a strong indicator of **neurodegeneration** [2]. - **Tauopathy** is a key pathological feature in AD and other neurodegenerative diseases [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1292-1294. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Manifestations Of Central And Peripheral Nervous System Disease, pp. 721-722.

Question 7: Molecular genetic testing is used to detect all of the following except?

A. Deletion
B. Translocation (Correct Answer)
C. Amplification
D. Point mutation

Explanation: ***Translocation*** - **Translocations** are chromosomal rearrangements that were historically detected primarily by **cytogenetic methods** (karyotyping, conventional FISH), rather than by traditional molecular genetic testing methods focused on DNA sequencing [3]. - While modern molecular techniques like **RT-PCR for fusion transcripts** (e.g., BCR-ABL), **NGS-based fusion detection**, and **targeted breakpoint sequencing** can now detect translocations, the classic distinction is that translocations involve large-scale structural chromosomal changes better visualized by cytogenetics [2], [3]. - In the traditional classification, molecular genetic testing referred primarily to **sequence-based methods** (PCR, Sanger sequencing) that detect smaller-scale DNA changes rather than gross chromosomal rearrangements. *Deletion* - **Deletions** are readily detected by molecular genetic testing using PCR, Sanger sequencing, MLPA (Multiplex Ligation-dependent Probe Amplification), and NGS [5]. - These techniques identify missing DNA sequences by analyzing changes in fragment size, read depth, or absence of expected amplification products [2], [5]. *Amplification* - **Amplification** (increased gene copy number) is detected by molecular methods including **quantitative PCR (qPCR)**, **digital PCR**, and **NGS-based copy number analysis** [4]. - These techniques quantify gene copy numbers to identify amplifications like HER2 amplification in breast cancer. *Point mutation* - **Point mutations** are the primary target of classic molecular genetic testing [1]. - Detected by **Sanger sequencing**, **allele-specific PCR**, **NGS panels**, and other sequence-based methods that identify single nucleotide changes in DNA [1], [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, p. 185. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 185-186. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 342-343. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 344. [5] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 183-184.

Question 8: Molecular genetic testing is used to detect all of the following except?

A. Translocation (Correct Answer)
B. Point mutation
C. Amplification
D. Deletion

Explanation: ***Translocation*** - This is the **intended answer** for this question, based on a distinction between traditional molecular genetic testing and cytogenetic methods. - Historically, **large-scale chromosomal translocations** were primarily identified by **conventional cytogenetic methods** like **karyotyping**. - However, in modern practice, translocations **can be detected** by molecular techniques including **FISH (fluorescence in situ hybridization)**, **RT-PCR** for specific fusion genes (e.g., BCR-ABL), and **next-generation sequencing** [3], [4]. - The distinction is becoming less clear as molecular cytogenetic techniques bridge both fields. *Point mutation* - **Single nucleotide changes** (point mutations) are the **classic target** of molecular genetic testing [1]. - Readily detected by **Sanger sequencing**, **next-generation sequencing**, **PCR-based methods**, and **allele-specific assays** [3]. - These tests specifically identify alterations in individual DNA bases. *Amplification* - **Gene amplifications** (increased copy number) are routinely detected using molecular genetic techniques. - Methods include **quantitative PCR (qPCR)**, **digital PCR**, **FISH**, and **array comparative genomic hybridization (aCGH)** [2]. - Example: HER2 amplification testing in breast cancer. *Deletion* - **Deletions** ranging from single nucleotides to whole genes are readily detectable by molecular genetic testing [1]. - Techniques include **multiplex ligation-dependent probe amplification (MLPA)**, **aCGH**, **next-generation sequencing**, and **deletion-specific PCR** [2], [3]. - Small and large deletions are both within the scope of modern molecular diagnostics [1], [3]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 183-184. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 186-187. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 185-186. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 342-343.

Question 9: Dent's disease is characterized by all except:

A. Nephrolithiasis
B. Defect in limb of Loop of Henle (Correct Answer)
C. Males are affected
D. Chloride channel defect

Explanation: Dent's disease is characterized by all except: ***Defect in limb of Loop of Henle*** - Dent's disease is primarily a **proximal tubule dysfunction** characterized by low molecular weight proteinuria, hypercalciuria, and nephrocalcinosis, not a defect in the limb of the Loop of Henle. - The disease involves mutations in the *CLC-5* gene, which encodes a **chloride channel** located in the proximal tubule and thick ascending limb, but the dominant pathology stems from proximal tubule dysfunction. *Chloride channel defect* - Dent's disease is indeed caused by mutations in the **CLC-5 chloride channel**, which is critical for endosomal acidification and protein reabsorption in the renal tubules. - The defective chloride channel leads to impaired intracellular trafficking and function of other transporters, predominantly in the proximal tubule. *Males are affected* - Dent's disease is an **X-linked recessive disorder**, meaning that males are predominantly affected because they only have one X chromosome. - Females who are carriers typically exhibit milder symptoms or are asymptomatic due to having a second functional X chromosome. *Nephrolithiasis* - **Hypercalciuria**, a hallmark of Dent's disease, leads to an increased risk of calcium stone formation and deposition in the kidneys. [1] - This often results in recurrent **nephrolithiasis** and progressive chronic kidney disease. [2]

Question 10: A patient with native aortic valve disease presents with right hemiparesis. What is the most appropriate management to prevent further strokes?

A. Both antiplatelet and anticoagulant
B. One dose of low molecular weight heparin sub-cutaneously followed by dual antiplatelet therapy
C. Antiplatelet only
D. Anticoagulant only (Correct Answer)

Explanation: ***Anticoagulant only*** - Patients with **native aortic valve disease** and **embolic stroke (like right hemiparesis)** are at high risk for further strokes if the emboli are cardiogenic in origin, often from valvular vegetations or abnormalities [1]. **Anticoagulants** are superior to antiplatelets in preventing recurrent **systemic embolization** from cardiac sources. - While the specific cause of the aortic valve disease isn't stated (e.g., infective endocarditis, nonbacterial thrombotic endocarditis, or calcific aortic stenosis with mobile thrombus), **anticoagulation** is generally the preferred strategy in this context to prevent further **thromboembolic events**. *Antiplatelet only* - **Antiplatelet agents** (e.g., aspirin, clopidogrel) primarily prevent arterial clots formed on atherosclerotic plaques and are less effective for preventing **cardiogenic emboli** originating from valvular disease. - Relying solely on antiplatelet therapy in this scenario would leave the patient at a higher risk for recurrent strokes from the underlying **cardiac source** [1]. *Both antiplatelet and anticoagulant* - While some conditions warrant combination therapy (e.g., after certain cardiac procedures or in specific acute coronary syndromes), adding an **antiplatelet agent** to an **anticoagulant** significantly increases the risk of **bleeding** without providing substantial additional benefit for preventing stroke in the context of native aortic valve disease as the primary stroke mechanism. - The increased **bleeding risk** generally outweighs the potential benefit for preventing future strokes when the primary etiology points to cardiogenic embolism. *One dose of low molecular weight heparin sub-cutaneously followed by dual antiplatelet therapy* - A single dose of **LMWH** provides short-term anticoagulation and is not sufficient for long-term stroke prevention in a patient with ongoing risk from native aortic valve disease. - **Dual antiplatelet therapy (DAPT)** is indicated in other contexts (e.g., after stent placement) but is not the appropriate long-term strategy for preventing **cardiogenic strokes** from valvular disease, where anticoagulation is paramount.

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