Text: CHUV
Photo: Ivàn Bravo

A genetic biomarker for mortality in bacterial meningitis

A study was conducted by the Department of Infectious Diseases at Lausanne University Hospital, led by Prof. Thierry Calandra, in collaboration with a team of scientists from the Netherlands. Results were published in Proceedings of the National Academy of Sciences of the United States of America (PNAS) on March 14, 2016.

Pneumococcal meningitis is the most common form of bacterial meningitis. It is often associated with severe complications and carries a high mortality rate among patients that contract it. Professor Thierry Calandra and his team from the Department of Infectious Diseases at Lausanne University Hospital have collaborated with a Dutch team of meningitis specialists to determine the presence of any genetic markers capable of predicting the likelihood of complications from this infection.

The study of a cohort of patients with pneumococcal meningitis enabled the team to identify genetic variations (polymorphisms) of a particular pro-inflammatory molecule of the cytokine family. Produced by the immune cells, these polymorphisms constitute a genetic marker for an adverse clinical outcome.

Corroborating the results of the genetic study, high levels of this molecule – called the macrophage migration inhibitory factor (MIF) – in the cerebrospinal fluid of patients with meningitis were associated with disease severity and high mortality rates. These observations are consistent with the adverse consequences of an excessive inflammatory response, which can lead to acute cerebral oedema and irreversible neural damage in cases of bacterial meningitis.

These results provide strong evidence that polymorphisms in the MIF gene constitute genetic markers for the morbidity and mortality of pneumococcal meningitis. They also offer new avenues of investigation for the development of immunomodulatory therapies aimed at reducing complications and mortality in these brutal infections.