Infectious Disease

Infectious Disease US Medical PG Question 1: An 18-month-old boy presents to the emergency department for malaise. The boy’s parents report worsening fatigue for 3 days with associated irritability and anorexia. The patient’s newborn screening revealed a point mutation in the beta-globin gene but the patient has otherwise been healthy since birth. On physical exam, his temperature is 102.4°F (39.1°C), blood pressure is 78/42 mmHg, pulse is 124/min, and respirations are 32/min. The child is tired-appearing and difficult to soothe. Laboratory testing is performed and reveals the following: Serum: Na+: 137 mEq/L Cl-: 100 mEq/L K+: 4.4 mEq/L HCO3-: 24 mEq/L Urea nitrogen: 16 mg/dL Creatinine: 0.9 mg/dL Glucose: 96 mg/dL Leukocyte count: 19,300/mm^3 with normal differential Hemoglobin: 7.8 g/dL Hematocrit: 21% Mean corpuscular volume: 82 um^3 Platelet count: 324,000/mm^3 Reticulocyte index: 3.6% Which of the following is the most likely causative organism for this patient's presentation?

• A. Streptococcus pneumoniae (Correct Answer)
• B. Listeria monocytogenes
• C. Haemophilus influenzae
• D. Neisseria meningitidis
• E. Salmonella

Infectious Disease Explanation: ***Streptococcus pneumoniae*** - Patients with **sickle cell disease** (indicated by the beta-globin gene mutation) are functionally **asplenic** and highly susceptible to encapsulated bacteria, with *S. pneumoniae* being the most common cause of **sepsis** in this population. - The patient's presentation with **fever**, **hypotension**, **tachycardia**, and **leukocytosis** is consistent with **sepsis**, and the elevated reticulocyte index suggests a hemolytic process or bone marrow response, common in sickle cell crises exacerbated by infection. *Listeria monocytogenes* - This pathogen primarily affects **neonates**, **immunocompromised individuals**, and **elderly** patients, often presenting as meningitis or sepsis. - While it can cause sepsis, it is a less common cause of severe infection in a non-neonatal toddler with sickle cell disease compared to *S. pneumoniae*. *Haemophilus influenzae* - Although *H. influenzae* is an encapsulated bacterium that can cause severe infections in functionally asplenic patients, routine childhood vaccinations have significantly reduced its incidence. - While possible, it is less likely than *S. pneumoniae* in an 18-month-old, especially if vaccinated, and *S. pneumoniae* remains the leading cause of sepsis in sickle cell patients. *Neisseria meningitidis* - *N. meningitidis* is another encapsulated bacterium that can cause serious infections, including **meningitis** and **sepsis**, particularly in immunocompromised individuals like those with sickle cell disease. - However, the incidence of **meningococcal disease** is generally lower than **pneumococcal disease** in this age group, and the absence of classic meningeal signs or petechial rash makes it a less probable primary suspect compared to *S. pneumoniae*. *Salmonella* - *Salmonella* species can cause **osteomyelitis** and **sepsis** in patients with sickle cell disease, often presenting with gastrointestinal symptoms. - While a known pathogen in this population, the clinical picture of **rapidly progressive sepsis** without clear GI focus makes *S. pneumoniae* a more immediate and common concern.

Infectious Disease US Medical PG Question 2: A 13-month-old boy is referred to an immunologist with recurrent otitis media, bacterial sinus infections, and pneumonia, which began several months earlier. He is healthy now, but the recurrent nature of these infections are troubling to his parents and they are hoping to find a definitive cause. The boy was born at 39 weeks gestation via spontaneous vaginal delivery. He is up to date on all vaccines and is meeting all developmental milestones. The patient has five older siblings, but none of them had similar recurrent illnesses. Clinical pathology results suggest very low levels of serum immunoglobulin. As you discuss options for diagnosis with the patient’s family, which of the following tests should be performed next?

• A. CSF gram staining
• B. Urine protein screening
• C. Stool cultures
• D. Flow cytometry (Correct Answer)
• E. Genetic analysis

Infectious Disease Explanation: ***Flow cytometry*** - Flow cytometry is essential for evaluating **lymphocyte subsets** (B cells, T cells, NK cells) and their maturation, which is crucial for diagnosing **primary immunodeficiencies** like X-linked agammaglobulinemia (XLA). - Given the history of recurrent bacterial infections and **very low serum immunoglobulin levels**, assessing B cell numbers and T cell populations would directly help identify defects in humoral immunity. *CSF gram staining* - **CSF gram staining** is used to diagnose **bacterial meningitis** at the time of an active infection. - The patient is currently healthy, and the test would not identify the underlying cause of recurrent infections or low immunoglobulin levels. *Urine protein screening* - **Urine protein screening** is used to detect **kidney disease** or other conditions causing proteinuria. - It is not relevant to investigating recurrent bacterial infections or low serum immunoglobulin levels, which point towards an immune system defect. *Stool cultures* - **Stool cultures** are performed to identify **gastrointestinal infections** (e.g., bacterial, parasitic). - While infections can occur in immunodeficient patients, this test is not a primary diagnostic tool for the underlying **immunodeficiency** causing recurrent otitis media, sinus infections, and pneumonia. *Genetic analysis* - **Genetic analysis** can confirm certain **primary immunodeficiency diagnoses** once specific defects are suspected (e.g., mutations in *BTK* for XLA). - However, flow cytometry is typically the next step to broadly characterize the immune cell populations and narrowed down differential diagnoses before proceeding with targeted genetic testing.

Infectious Disease US Medical PG Question 3: A 12-month-old girl is brought to her pediatrician for a checkup and vaccines. The patient’s mother wants to send her to daycare but is worried about exposure to unvaccinated children and other potential sources of infection. The toddler was born at 39 weeks gestation via spontaneous vaginal delivery. She is up to date on all vaccines. She does not walk yet but stands in place and can say a few words. The toddler drinks formula and eats a mixture of soft vegetables and pureed meals. She has no current medications. On physical exam, the vital signs include: temperature 37.0°C (98.6°F), blood pressure 95/50 mm Hg, pulse 130/min, and respiratory rate 28/min. The patient is alert and responsive. The remainder of the exam is unremarkable. Which of the following is most appropriate for this patient at this visit?

• A. Meningococcal vaccine
• B. Gross motor workup and evaluation
• C. Rotavirus vaccine
• D. Referral for speech pathology
• E. MMR vaccine (Correct Answer)

Infectious Disease Explanation: ***MMR vaccine*** - The **measles, mumps, and rubella (MMR) vaccine** is recommended for administration at **12-15 months of age**. - This timing offers protection against these common childhood diseases, which is especially important for children attending **daycare**. *Meningococcal vaccine* - The routine **meningococcal vaccine (MenACWY)** is typically recommended for adolescents at **11-12 years of age**, with a booster at 16 years. - While there are specific circumstances for earlier vaccination (e.g., high-risk conditions), it is **not routine** for a 12-month-old. *Gross motor workup and evaluation* - The patient's motor development, standing in place but not yet walking, is **within the normal range** for a 12-month-old. - A definitive **gross motor workup** would generally be considered if there were more significant delays or regressions. *Rotavirus vaccine* - The **rotavirus vaccine** series is typically given at **2, 4, and 6 months of age**, with the final dose administered no later than **8 months of age**. - A 12-month-old is **outside the recommended age range** for initiating or completing this vaccine series. *Referral for speech pathology* - Saying "a few words" at 12 months is **within the normal developmental milestone** for expressive language at this age. - A referral for **speech pathology** would generally be indicated for more significant language delays.

Infectious Disease US Medical PG Question 4: A 30-year-old man is brought to the emergency department with complaints of fevers to 39.0℃ (102.2℉) and diarrhea for the past 12 hours. There is no history of headaches, vomiting, or loss of consciousness. The past medical history is unobtainable because the patient recently immigrated from abroad and has a language barrier, but his wife says that her husband had a motor vehicle accident when he was a teenager that required emergent surgery. He is transferred to the ICU after a few hours in the ED due to dyspnea, cyanosis, and hemodynamic collapse. There are no signs of a meningeal infection. The blood pressure is 70/30 mm Hg at the time of transfer. A chest X-ray at the time of admission shows interstitial infiltrates without homogeneous opacities. The initial laboratory results reveal metabolic acidosis, leukopenia with a count of 2000/mm3, thrombocytopenia (15,000/mm3), and a coagulation profile suggesting disseminated intravascular coagulation. A peripheral smear is performed as shown in the accompanying image. Despite ventilatory support, administration of intravenous fluids, antibiotics, and vasopressor agents, the patient dies the next day. The gram stain from the autopsy specimen of his lungs reveals gram-positive, lancet-shaped diplococci occurring singly and in chains. Which of the following organisms is the most likely cause for the patient’s condition?

• A. Neisseria meningitidis
• B. Non-typeable H. influenzae
• C. Streptococcus pneumoniae (Correct Answer)
• D. Staphylococcus aureus
• E. Streptococcus pyogenes

Infectious Disease Explanation: ***Streptococcus pneumoniae*** - The patient's history of a prior **motor vehicle accident (MVA) with emergent surgery** as a teenager suggests a possible **splenectomy**, making him susceptible to infections by **encapsulated organisms**. - The presentation with **sepsis**, profound **leukopenia** and **thrombocytopenia**, **DIC**, **interstitial infiltrates** on CXR, and **gram-positive, lancet-shaped diplococci** in lung tissue is classic for severe **pneumococcal sepsis** in an asplenic individual. *Streptococcus pyogenes* - While *S. pyogenes* can cause severe infections, it typically presents with conditions like **necrotizing fasciitis** or **streptococcal toxic shock syndrome**, which would involve different clinical features. - It is a **coccus** that grows in **chains**, but the characteristic **lancet-shape** and **diplococci** are not typical for *S. pyogenes*. *Neisseria meningitidis* - Although an encapsulated organism that can cause severe sepsis in asplenic patients, it is typically a **gram-negative diplococcus**. - Symptoms often include **meningitis** (though not always present) and a **petechial rash**, neither of which are described here. *Non-typeable H. influenzae* - This is a **gram-negative coccobacillus** and would not present as gram-positive, lancet-shaped diplococci. - While it can cause pneumonia, it is less commonly associated with the fulminant sepsis and DIC seen here, especially in an asplenic patient. *Staphylococcus aureus* - *S. aureus* is a **gram-positive coccus** that typically clusters, not as lancet-shaped diplococci or chains. - While it can cause severe sepsis and DIC, the morphology described in the Gram stain is inconsistent with *S. aureus*.

Infectious Disease US Medical PG Question 5: A father brings his 3-year-old son to the pediatrician because he is concerned about his health. He states that throughout his son's life he has had recurrent infections despite proper treatment and hygiene. Upon reviewing the patient's chart, the pediatrician notices that the child has been infected multiple times with S. aureus, Aspergillus, and E. coli. Which of the following would confirm the most likely cause of this patient's symptoms?

• A. Increased IgM, Decreased IgG, IgA, and IgE
• B. Negative nitroblue-tetrazolium test (Correct Answer)
• C. Positive nitroblue-tetrazolium test
• D. Normal dihydrorhodamine (DHR) flow cytometry test
• E. Increased IgE and IgA, Decreased IgM

Infectious Disease Explanation: ***Negative nitroblue-tetrazolium test*** - A **negative nitroblue-tetrazolium (NBT) test** indicates an inability of phagocytes to produce a respiratory burst, which is characteristic of **Chronic Granulomatous Disease (CGD)**. - CGD patients suffer from recurrent infections with catalase-positive organisms such as *Staphylococcus aureus*, *Aspergillus*, and *E. coli*, consistent with the patient's history. *Increased IgM, Decreased IgG, IgA, and IgE* - This pattern of immunoglobulin levels is characteristic of **X-linked hyper-IgM syndrome**, where there is a defect in CD40L on T cells. - While it also causes recurrent infections, the typical pathogens differ from those stated in the question, often including *Pneumocystis jirovecii*. *Positive nitroblue-tetrazolium test* - A **positive NBT test** indicates that phagocytes are capable of producing a respiratory burst and forming superoxide, thus ruling out CGD. - This result would be expected in a healthy individual or someone with an immunodeficiency not affecting the phagocytic oxidative burst. *Normal dihydrorhodamine (DHR) flow cytometry test* - A **normal DHR flow cytometry test** indicates that neutrophils can produce reactive oxygen species (ROS) effectively, meaning the respiratory burst is intact. - This result would rule out CGD, as CGD patients have an abnormal (decreased) DHR test. *Increased IgE and IgA, Decreased IgM* - This specific pattern of immunoglobulin abnormalities is not typically associated with a single, well-defined primary immunodeficiency that would present with the described infections. - **Hyper-IgE syndrome (Job's syndrome)**, for example, features very high IgE levels but usually a normal IgM.

Infectious Disease Flashcard 1 of 5

Question: Which RNA virus presents with rash of 3-days duration?_____

Answer: Rubella

Infectious Disease Flashcard 2 of 5

Question: When does common variable immunodeficiency typically present? _____

Answer: After age 2

Infectious Disease Flashcard 3 of 5

Question: Which childhood exanthem is known as second disease?_____

Answer: Scarlet fever (Step pyogenes - GAS)

Infectious Disease Flashcard 4 of 5

Question: What is the most common cause of pneumonia in infants?_____

Answer: Respiratory synctial virus (RSV)

Infectious Disease Flashcard 5 of 5

Question: What is the treatment of Haemophilus influenzae meningitis?_____

Answer: Ceftriaxone