1. Feb 2011 Dr Guada Lopez Marti Pediatric Infectious Diseases Marshall University

2. Question 1 The parents of a healthy 4-year-old boy are seeking your advice regarding the need for additional measles vaccination for their son. In reviewing the boy’s vaccination history, you note that he has received one dose of measles vaccine (as measles-mumps- rubella [MMR]) at the age of 12 months. You inform the parents that he should receive a second dose of measles vaccine. Of the following, the MOST important reason to recommend a second dose of measles vaccine for this child is that: A. one dose of measles vaccine fails to induce immunity in approximately 5% of children B. one dose of measles vaccine is associated with a low antibody- mediated response C. one dose of measles vaccine is associated with a poor cell-mediated response D. one dose of measles vaccine is associated with significant loss of protection with time (waning immunity) E. the child received the first dose of vaccine prior to 15 months of age

3. Answer 1: A one dose of measles vaccine fails to induce immunity in approximately 5% of children The currently available and licensed measles vaccine in the United States is a live attenuated strain produced in chick embryo cell culture One dose of measles vaccine administered to children after their first birthdays immunologically mimics natural measles infection and induces excellent cell-mediated and antibody-mediated responses in 95% of vaccinees Primary vaccine failure, defined as a failure to seroconvert after vaccination, occurs in approximately 5% of individuals who receive one dose of measles vaccine at 12 to 15 months of age. Thus, antibodies to measles are detected in at least 95% of persons vaccinated at an age- appropriate time. Potential reasons for primary measles vaccine failures include the presence of neutralizing maternal antibody (in children younger than 12 months) or previous receipt of blood products, improperly stored vaccine, or genetic factors

4. Question 2 You are planning an immunization schedule for a 14-month-old girl who was treated for Kawasaki disease 3 months ago. According to her hospitalization records, she received 18 g (2 g/kg) of immune globulin intravenous (IGIV) as treatment for her disease. Review of her immunization records shows she is due to receive the following vaccines: 4th dose of pneumococcal conjugate vaccine (PCV), booster dose of H. influenzae type b conjugate (Hib) vaccine, 1 st doses of hepatitis A, measles-mumps- rubella (MMR) and varicella vaccines. Of the following, the MOST appropriate immunization schedule for this child is administration of: A. all needed vaccines at the next clinic visit B. all needed vaccines 6 months after IGIV was administered C. all needed vaccines at 11 months after IGIV was administered D. MMR and varicella vaccines at the next clinic visit and PCV, Hib, and hepatitis A vaccines at least 11 months after IGIV was administered E. PCV, Hib, and hepatitis A vaccines at the next clinic visit and MMR and varicella vaccines at least 11 months after IGIV was administered

5. Answer 2: E PCV, Hib, and hepatitis A vaccines at the next clinic visit and MMR and varicella vaccines at least 11 months after IGIV was administered Table: Suggested Interval Between Administration of HISG and Live-virus Vaccines (MMR and Varicella) Dose of HISG (mg/kg)Suggested Interval <40 3 months 40 to 80 6 months 80 to 400 8 months 1,000 to 2,000 11 to 12 months

6. Question 3 A mother calls you about her 18-year-old daughter, who is a student at a college where several students have been diagnosed with mumps. The mother does not know the immunization status of the infected individuals but states that her daughter is up to date on all her immunizations and, to the best of her knowledge, has received two doses of measles-mumps-rubella (MMR) vaccine. Her daughter has been asymptomatic, with no fever or other systemic complaints. Of the following, the MOST appropriate action is to: A. administer a dose of mumps immune globulin to her daughter B. confirm that her daughter has received two doses of MMR vaccine C. have her daughter stay out of classes for 9 days to observe for the development of symptoms D. vaccinate her daughter immediately with a monovalent mumps vaccine to prevent infection from this exposure E. vaccinate her daughter immediately with another dose of MMR to prevent infection from this exposure

7. Answer 3: B Confirm that her daughter has received two doses of MMR vaccine Protective efficacy of the vaccine is estimated to be 90% to 95%. In cases of exposure, such as described in the vignette, it is important to ensure that the exposed person has received the recommended number of doses of MMR vaccine because mumps outbreaks have occurred in persons in highly immunized populations who previously have received only a single dose of mumps-containing vaccine. In addition, even though the MMR is a good vaccine, it is not 100% efficacious. About 10% of individuals who receive both doses of the vaccine still remain susceptible to mumps. These factors, coupled with crowded living conditions (eg, college dormitories) and the influx and mixing of students from different geographic areas, increases the risk of susceptible young adults developing the disease once it is introduced into the environment. Therefore, the most appropriate action is to confirm that the daughter has received two doses of MMR vaccine. If she is found not to have received two doses, a second dose should be administered as soon as possible. Monovalent vaccine is not available and is not recommended.

8. Question 4 A 1-month-old boy presents to his primary care physician with swelling and redness around his umbilical cord stump and a temperature of 39.0°C. His white blood cell (WBC) count is 71.0 x10 3 /mcL. He is admitted to the hospital and treated with IV antibiotics. Although his infection resolves slowly over 10 days, his WBC count remains persistently elevated at 61.0x10 3 /mcL. Of the following, the MOST likely cause of this child's persistent leukocytosis is: A. Chediak-Higashi syndrome B. chronic granulomatous disease C. hyper-immunoglobulin (Ig) E syndrome D. leukocyte adhesion defects E. myeloperoxidase deficiency

9. Answer 4: D Leukocyte adhesion defects The child described in the vignette has omphalitis and persistent leukocytosis, features that are suggestive of a leukocyte adhesion defect (LAD) Defects in proteins involved in leukocyte rolling, adhesion, and cytoskeletal regulation make up the group of phagocytic immunodeficiencies termed LADs Currently, three types of LADs are identified, each of which is due to a specific genetic defect All three types are characterized by poor wound healing, skin ulcers, gingivitis/periodontitis, delayed separation of the umbilical cord, leukocytosis, and bacterial or fungal infections. Leukocytosis (primarily polymorphonuclear cells) without infection is common When infection occurs, the leukocyte count elevates further. Patients who have LADs lack CD11 and CD18 on their neutrophils, documented by flow cytometry. Genetic testing is used to confirm the diagnosis.

10. 4 cont.  Chediak-Higashi syndrome is characterized by partial oculocutaneous albinism, variable neurologic deficits, and severe bacterial infections, especially with Staphylococcus aureus. The WBC count usually is decreased, and patients may have profound neutropenia during an accelerated phase of the disease. -Chronic granulomatous disease (CGD) is characterized by a defective or absent phagocyte respiratory burst in both polymorphonuclear and mononuclear phagocytes. As a result, the phagocytes fail to destroy intracellular pathogens, leading to granuloma formation in any organ. The WBC count in CGD typically is normal. The clinical presentation most often involves suppurative lymphadenitis, hepatic abscess, or pneumonia. -Hyper-IgE syndrome, also known as Job syndrome, is a multisystem autosomal dominant disorder characterized by extreme elevations of serum IgE, recurrent skin and sinopulmonary infections, and eczematous rashes. Patients often have coarse facial hair, retention of primary teeth, and candidiasis of mouth and nails. The WBC count is usually normal. -Myeloperoxidase deficiency is the most common inherited phagocytic defect and affects both polymorphonuclear and mononuclear phagocytes. Affected patients most often are asymptomatic but may have severe candidal infections. The WBC count is usually normal.

11. Question 5 While at a holiday gathering, a 3-year-old healthy girl whispers in a cat’s ear in a playful attempt to wake it. She is immediately bitten on her cheek and taken to the emergency department. The owner obtained the cat 1 month ago. She believes it is immunized but is not sure what types of vaccines have been administered. Of the following, the MOST important factor in the decision to initiate postexposure rabies prophylaxis for this girl is whether: A. a serum rabies antibody titer can be obtained for the cat within 2 to 3 days B. a veterinarian can provide a certificate of rabies vaccination C. the bite involved the oral mucous membranes in addition to skin D. the bite wound was washed with soap and water and disinfected with iodine E. the cat was adopted from a shelter

12. Answer 5: B A veterinarian can provide a certificate of rabies vaccination Because the incubation period for rabies is long, the decision to administer postexposure prophylaxis is not emergent and can await obtaining a registered certificated of vaccination from a veterinarian. Furthermore, if no certificate is available, the domestic cat can be confined and observed for signs of rabies If rabies is suspected in a dog or cat that has bitten a person, the animal should be confined and observed for 10 days. If signs of rabies develop in the dog or cat, it should be euthanized in a manner that preserves the brain for further evaluation. If the exposure is from a wild mammal suspected of having rabies, the animal should be euthanized at once and the brain submitted for examination (Table) If the wild animal cannot be captured, strong consideration should be given to immediate prophylaxis for the person who has been bitten.

13. 5 cont Table: Rabies Postexposure Prophylaxis Guide

14. Question 6 You are meeting with a family who plans to travel to southeast Asia in the next 2 weeks. There are two children in the family, a 10-month-old infant and a 21-month-old child to whom you just administered the second dose of hepatitis A vaccine. The parents ask how they can best protect their children from hepatitis during their overseas trip. Of the following, the MOST appropriate protective steps are: A. administration of hepatitis A vaccine to the infant and counseling the family to exercise caution about the food and water they consume B. administration of immune globulin to both children and counseling the family to exercise caution about the food and water that they consume C. administration of immune globulin to the infant and counseling the family to exercise caution about the food and water that they consume D. counseling the family only to boil their drinking water while overseas E. no further intervention because the older child is immunized and the infant only eats canned baby food

15. Answer 6: C Administration of immune globulin to the infant and counseling the family to exercise caution about the food and water that they consume

16. Question 7 A 2-year-old boy presents to his primary care physician for a health supervision visit in November. The boy’s mother says he is scared of needles and she has heard that there is an influenza vaccine that is given by a spray. Of the following, the MOST appropriate reason to recommend the injectable influenza vaccine rather than the intranasal vaccine for this child is: A. allergies to feathers and cat dander for the boy B. grandmother who lives with the family receiving chemotherapy C.history of wheezing in the past year for the boy D. mother who is 4 months pregnant E. sister who had a bone marrow transplant for leukemia 1 year ago

17. Answer 7: C History of wheezing in the past year for the boy

18. Question 8 A 15-year-old girl who has systemic lupus erythematosus recently began treatment with high-dose steroids and tumor necrosis factor-alpha blockers. Her skin test and chest radiograph prior to initiating therapy were negative for tuberculosis. She presents today to the emergency department with a 2-week history of fevers that seem to have become progressively worse. She reports having cough and weight loss along with night sweats. On physical examination, the extremely pale girl has tachypnea and bilateral cervical, axillary, and inguinal lymphadenopathy. Chest radiograph shows bilateral diffuse pulmonary infiltrates. She is transferred to the intensive care unit and you are consulted regarding further evaluation. On talking with the family, you learn that they recently moved from Ohio. Of the following, the MOST sensitive test to yield the diagnosis for this patient is: A. antigen detection B.lymph node biopsy C.polymerase chain reaction D.serology E.tissue or body fluid cultures

19. Answer 8: A antigen detection The fever, malaise, headache, weakness, and dry cough described for the girl in the vignette, who has impaired cell-mediated immunity, are suggestive of disseminated histoplasmosis. Another clue to the diagnosis is that her family lived in Ohio Remember to always think about clinical presentation AND epidemiologic history of the patient!

20. Question 9 You are asked to evaluate a 5-year-old boy who presents with 1 month of diarrhea that has worsened over the past 3 days. His symptoms started 1 month after he returned from a trip to rural Mexico with complaints of crampy abdominal pain, diarrhea, poor appetite, and weight loss. His parents believe he has had fever off and on during this illness but have not measured his temperature. They deny any antibiotic use in the past 2 months. His initial symptoms have persisted, and recent stools contain blood and mucus (Fig. 1). You admit him to the hospital.

21. Fig 1

22. Question 9 cont… Of the following, the cause of his infection is MOST likely to be determined by: A. routine stool culture B. stool culture incubated at 42.0°C C. stool examination for ova and parasites D. stool examination for white blood cells E. toxin assay on stool

23. Answer 9: C Stool examination for ova and parasites The mucus-containing, bloody, frequent small stools described for the boy in the vignette are strongly suggestive of dysentery, which often is associated with fever, abdominal pain, and tenesmus Blood or white blood cells are seen in the stool with dysentery, the infectious causes of which include Shigella, Clostridium difficile, enterohemorrhagic or enteroinvasive Escherichia coli, Entamoeba histolytica, and less often, Campylobacter, Salmonella, Yersinia, Vibrio, Aeromonas, Plesiomonas shigelloides, and others The length of time since travel to a high-risk area, the subacute course of the diarrhea, and the absence of significant fever described for the boy suggests that his dysentery is caused by Entamoeba histolytica infection, which is diagnosed by an examination of his stool for ova and parasites

24. Question 10 A 5-year-old boy presents with the sudden onset of vomiting, temperature to 39.5°C, and headache. Lumbar puncture reveals 1,530 white blood cells/mm 3, 85% segmented neutrophils and 15% lymphocytes, glucose of 5 mg/dL, and protein of 220 mg/dL. A Gram stain is obtained (Figure).

25. Question 10 cont… The boy’s parents report that he had meningitis due to the same organism when he was 3 years old. The child responds well to treatment. Of the following, the MOST appropriate test to order for this child before discharge is: A. enzyme-linked immunosorbent assay to human immunodeficiency virus B. magnetic resonance imaging of the lumbosacral spine C. repeat lumbar puncture D. total hemolytic complement assay (CH 50 ) E. total immunoglobulin assessment

26. Answer 10: D total hemolytic complement assay (CH 50 ) The Gram stain obtained for the child described in the vignette reveals gram-negative intracellular diplococci. Accordingly, he has had recurrent bacterial meningitis due to Neisseria meningitidis. The boy likely has a deficiency of the terminal complement components (C5 through C9) Activation of these components results in the normal assembly of the membrane attack complex C5b-9, which is capable of bactericidal activity against gram-negative bacteria, such as N meningitidis. Recurrent invasive neisserial infection suggests a deficiency in these components

27. Question 11 The parents of a 6-month-old boy who has sickle cell anemia consult you about their son’s childhood immunization. He has not received any of the routine childhood vaccines because his parents are concerned about the potential adverse effect the vaccines may have on his development. They would prefer to delay all vaccines until after his second birthday. The mother asks if there are any other measures that can help reduce his risk of severe infections. Of the following, the action that is MOST likely to decrease his risk of severe infections is to administer: A. all childhood vaccines by the recommended catch-up schedule for age and start daily oral penicillin prophylaxis B. all childhood vaccines when he is 2 years old and start daily oral penicillin prophylaxis C. all childhood vaccines when he is 2 years old and start monthly transfusions with human immune serum globulin D. all vaccines containing viral antigens when he is 2 years old and start oral penicillin prophylaxis E. only age-appropriate pneumococcal and Haemophilus influenzae vaccines by the recommended catch-up schedule and defer other vaccines until he is 2 years old

28. Answer 11: A All childhood vaccines by the recommended catch-up schedule for age and start daily oral penicillin prophylaxis

29. Question 12 A 14-month-old female infant is referred to you for further evaluation of frequent episodes of otitis media and upper respiratory tract infections. Her parents state that she has had six episodes of ear infections since 6 months of age, with the last episode occurring 1 month ago, and she always seems to have nasal congestion and a runny nose. Birth and developmental histories are normal. The child is breastfed and does not attend child care. Her immunizations are up to date through 12 months of age, including three doses of conjugate pneumococcal vaccine. She has no history of pneumonia, meningitis, urinary tract infection, or sepsis. The only physical examination findings of note are some mild nasal congestion and shotty cervical lymphadenopathy. Previously obtained laboratory evaluation of serum immunoglobulin (Ig) concentrations show a low IgG of 100 mg/dL (1,000 mg/L), a normal IgM of 85 mg/dL (850 mg/L), and a normal IgA of 45 mg/dL (450 mg/L). Tetanus and diphtheria antibody titers are normal, but pneumococcal antibody titers are decreased. B- and T-cell flow cytometry yields normal results.

30. Question 12 cont… Of the following, the MOST likely diagnosis in this patient is: A. Bruton agammaglobulinemia B. common variable immunodeficiency C. hyper-IgM syndrome D. severe combined immunodeficiency E. transient hypogammaglobulinemia of infancy

31. Answer 12: E Transient hypogammaglobulinemia of infancy