Epidemiology of meningitis with a negative CSF Gram stain: under-utilization of available diagnostic tests.

Meningitis with a negative cerebrospinal fluid Gram stain (CSF-GS) poses a diagnostic challenge as more than 50% of patients remain without an aetiology. The introduction of polymerase chain reaction (PCR) and arboviral serologies have increased diagnostic capabilities, yet large scale epidemiological studies evaluating their use in clinical practice are lacking. We conducted a prospective observational study in New Orleans between November 1999 and September 2008 (early era) when PCR was not widely available, and in Houston between November 2008 and June 2013 (modern era), when PCR was commonly used. Patients presenting with meningitis and negative CSF-GS were followed for 4 weeks. All investigations, PCR used, and results were recorded as they became available. In 323 patients enrolled, PCR provided the highest diagnostic yield (24·2%) but was ordered for 128 (39·6%) patients; followed by serology for arboviruses (15%) that was ordered for 100 (31%) of all patients. The yield of blood cultures was (10·3%) and that of CSF cultures was 4%; the yield for all other tests was <10%. Overall, 65% of the patients remained without a diagnosis at 4 weeks: 72·1% in early era vs. 53·4% (P < 0·01) in modern era; this change was attributed to diagnosing more viral pathogens, 8·3% and 26·3% (P < 0·01), respectively. The introduction of PCR and arboviral serologies has improved the yield of diagnosing patients with meningitis and a negative CSF-GS, but both tests are being under-utilized.

Inhibitor development and successful immune tolerance in an HIV-infected patient with haemophilia A and after immune reconstitution with HAART.

This is the case of a 28-year-old man with severe congenital haemophilia A, who had a relatively mild bleeding course during early childhood, with limited factor VIII (FVIII) exposure. He was infected with HIV before the age of 7 years, and demonstrated profound immunodeficiency from childhood, with very low CD4+ cell counts for more than a decade. Following initiation of highly active anti-retroviral therapy (HAART) and gradually increasing CD4+ cells, he presented for the first time with a high-titre inhibitor at age 26, despite over 1000 previous FVIII exposures. Subsequently, his inhibitor was successfully eradicated with a standard immune tolerance protocol. It is likely that the effects of chronic HIV infection on T-lymphocyte pathways, and the partial immune reconstitution resulting from HAART, led to this patient's unusual inhibitor course. Such a case serves to augment knowledge gained in animal studies about the immunobiology of FVIII inhibitors.