This literature marketed report was received from the authors of a published article, and refers to a 53 year old male patient. The patient past medications included 13-valent conjugate pneumococcal vaccine. On an unknown date, the patient was vaccinated with pneumococcal vaccine, polyvalent (23-valent) (manufacturer unknown) injection (dose, route of administration, vaccination site, lot # and expiry date were not specified) for prophylaxis. The previously healthy and HIV-negative patient presented with vertigo, unstable gait, paranoia, disorientation, and short term memory deficits. Two months after presentation, the patient was diagnosed with Cryptococcal meningoencephalitis (CM) due to Cryptococcus neoformans (Cn) by cerebrospinal fluid (CSF) culture. Clinical immunological evaluation demonstrated persistent CD4+ lymphopenia and expansion of terminal effector memory cells relative to naive T-cell subsets and evidence of elevated activation markers such as increased numbers of HLA-DR% cells. Bone marrow biopsy revealed oligoclonal TCR gene rearrangement but no evidence of hematological malignancy by flow cytometry and cytogenetics. He responded well to 4 weeks of liposomal amphotericin with negative CSF cultures, but his course was subsequently complicated by hemolytic anemia that worsened over time (hemoglobin = 10.7 g/dL, mean cell volume = 100.3 femtoliters, reticulocyte percentage = 5.12, iron saturation percentage = 17, lactate dehydrogenase = 285 U/L, platelets = 171 K/micro-L, white blood cells = 2.62 K/micro-L, absolute neutrophil count = 1.82 K/micro-L, absolute lymphocyte count = 0.48 K/micro-L, absolute monocyte count = 0.27 K/micro-L) responsive to splenectomy and pulmonary emboli with an associated lupus anticoagulant. On an unknown date, the patient demonstrated normal Ig levels but had a suboptimal response to the pneumococcal vaccine, polyvalent (23-valent) given 2 months after 13-valent conjugate pneumococcal vaccine with less than 8 serotypes responding. Immunoglobulin (Ig) assessment was as follows: Pneumococcal serotype 1 =1.1 mcg/ml, Pneumococcal serotype 2 = 0.2 mcg/ml, Pneumococcal serotype 3 = 0.3, Pneumococcal serotype 4 = 0.2 mcg/ml, Pneumococcal serotype 5 = 1.7 mcg/ml, Pneumococcal serotype 8 = 0.8 mcg/ml, Pneumococcal serotype 9N = 0.5 mcg/ml, Pneumococcal serotype 12F = 0.1 mcg/ml, Pneumococcal serotype 14 = less than 0.7 mcg/ml, Pneumococcal serotype 17F = 2 mcg/ml, Pneumococcal serotype 19F = 1.5 mcg/ml, Pneumococcal serotype 20 = 0.2 mcg/ml, Pneumococcal serotype 22F = 2 mcg/ml, Pneumococcal serotype 23F = 1.6 mcg/ml, Pneumococcal serotype 6B = less than 0.6 mcg/ml, Pneumococcal serotype 10A = 1 mcg/ml, Pneumococcal serotype 11A = 1 mcg/ml, Pneumococcal serotype 7F = 0.6 mcg/ml, Pneumococcal serotype 15B = 1.1 mcg/ml, Pneumococcal serotype 18C = 0.3 mcg/ml, Pneumococcal serotype 19A = 0.9 mcg/ml, Pneumococcal serotype 9V = 1.2 mcg/ml and Pneumococcal serotype 33F = 0.6 mcg/ml. Autoantibodies to Granulocyte-macrophage colony-stimulating factor and interferon gamma were negative, but genetic analysis demonstrated a G169A IKBKG (accession number: Q9Y6K9) X-linked hemizygous mutation (E57K NEMO), although he possessed no clinical features of anhidrotic ectodermal dysplasia reported with this mutation. The patient recovered from his infectious course, and his hemolytic anemia remained stable at 18 months, but idiopathic CD4+ lymphopenia (ICL) persisted; partial recovery of CD8 + T-cell counts after splenectomy suggested that a direct genetic effect for his lymphopenia was less likely. The outcome of the event was unknown. The authors considered the event to be related to pneumococcal vaccine, polyvalent (23-valent) (manufacturer unknown). Upon internal review, the event of suboptimal response to the pneumococcal vaccine, polyvalent (23-valent) was determined to be medically significant.