Case Study - Finding the Unidentified Perpretrator of Recurrent Infection

Finding the Unidentified Perpetrator: A Curious Case of Recurrent Infections Case study adapted from Dr. Monika Esser, Head of Division of Immunology, N.H.L.S. Coastal Branch, Tygerberg Hospital in Cape Town, South Africa An 8-month-old child was presented at the hospital with recurrent and frequent infections. The child had received all vaccination up to this point; this was confirmed with laboratory results that indicated the presence of protective antibodies. However, further blood tests showed the child had severe lymphopenia (a decrease in white blood cells). An ELISA test was used to detect the presence of antibodies against human immunodeficiency virus (HIV), but no antibodies were detected. Given the variable composition of antibodies in the child’s blood, it was presumed many of the antibodies were passively given through the mother’s breastmilk. The child was diagnosed with severe-combined immunodeficiency disorder (SCID), then treated for his infection, as well as isolated and barrier nursed, which is standard protocol for someone who has SCID. Watch the following video about the Bubble Boy, David Vetter: https://youtu.be/E7hd_etqKdM?si=iFAZqXOUawOe-QNF Watch the following video about the development of HIV: https://youtu.be/FDVNdn0CvKI?si=oCHaIk0BZ0xGJNQb Questions: 1. (2 points) What is the primary cause of SCID? What treatments were available at the time when David Vetter was born? - SCID is primarily caused by an adenosine deaminase deficiency - Bone marrow transplant 2. (1 point) How does HIV affect the immune system? - HIV kills immune system cells rendering the system either not as effective or not effective at all 3. (2 points) What similarities do the two diseases have? What are some differences? - Both diseases have fungal origin and often an early fatal outcomes - SCID is often found in infants, whereas HIV is usually found in adults 4. (2 points) What kinds of treatments are available now or in development that could treat either of these diseases?

- SCID can be treated by a bone marrow transplant and a stem cell transplant - HIV can be treated by antiretroviral therapy (taking medication every day, won’t cure but will alleviate symptoms) 2 months later, the mother was screened as a potential bone marrow donor for her child. During the screening process, she tested positive for HIV. In light of this finding, a PCR test for HIV was used to determine whether the child also had HIV. The PCR result was positive for the child, so HAART therapy was started to treat the HIV infection. After 6 months of HAART therapy, the child’s lymphocyte profile increased (see Table 1), with antibody levels returning to normal levels. No viral presence was detected via PCR. The child did not develop any more recurring infections, and an HIV ELISA test remained negative after one year. Immune 9 18 2yrs, 1 months old Reference markers months old months old averages and ranges CD3 139 cells/μL 1,624 2,579 cells/μL 655– 2,823 cells/μL cells/μL CD4 21 cells/μL 499 1,287 cells/μL 321– 1,389 cells/μL cells/μL CD8 119 cells/μL 1,055 1,446 cells/μL 220– cells/μL 1,664 cells/μL NK 26 cells/μL 202 369 cells/μL 82–594 cells/μL cells/μL B cell 29 cells/μL 917 2,117 cells/μL 959–3644 cells/μL cells/μL Table 1: Levels of different immune cells and immune-stimulating molecules over time. CD3: molecule on CD4 and CD8 T cells that helps activate the cells, indicates mature T cells CD4: type of T cell that leads the immune system attack by helping other immune cells CD8: type of T cell that kills cells invaded by intracellular pathogens NK (natural killer): immune cell that kills infected or cancerous cells B cell: immune cell responsible for antibody production A subsequent review of his hospital records revealed the child had been previously admitted with pneumonia at 4 months old, 4 months before being admitted at 8 months old. During this admission, a PCR test for HIV had been run, resulting in a positive result (see Table 2). Moderate lymphopenia was also noted at this admission. 4mths 8mths 10mths 11mths 12mths 14mths 16mths 25mths (Start of HAART) ELISA (-) (-) (-) (-) (-) PCR (+) (+) Viral Log 5.93 Log 3.8 Undetectable

Questions: 5. (1 point) Looking at Tables 1 and 2, how did immune cell count and viral load change over time for the patient? - Cell count grew exponentially 6. (2 points) What might be the cause of this child having a negative ELISA in the face of a positive HIV PCR? Give two possible reasons. - The child could have been infected perinatally before maternal seroconversion - The test could have been taken in the first few weeks after infection 7. (2 points) Posit two possible scenarios that help explain how the child could have contracted HIV from his mother. - Children can get HIV from their mother during pregnancy or childbirth - They can also get it from brestfeeding 8. (2 points) What is HAART therapy? What viral mechanism is prevented when HAART therapy is used? Given the nature of HIV infection, how long will the child need this drug therapy? - HAART therapy is taking HIV medication everyday in order to help alleviate symptoms and live a healthier life - The HAART therapy uses inhibitors to half the HIV viral replication - At minimum 1 year 9. (1 point) How would the child’s treatment have been impacted had the previous visit’s records had been available? - A patient’s medical history is important because medical professionals would have been able to see how treatments have worked in the past and how the patient responded to specific medication