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New drugs, vaccines needed for bacterial meningitis
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A new series in The Lancet highlights the need for new vaccines and drug treatments for bacterial meningitis.
In an accompanying editorial, Diederik van de Beek, MD, PhD, professor of neurology at the Academic Medical Center, University of Amsterdam, the Netherlands, said bacterial meningitis causes high rates of mortality and morbidity globally, but the disease burden is especially high in resource-poor countries.
Diederik van de Beek
Antibiotic resistance is also a concern, van de Beek said, as many inexpensive and widely available antibiotics are showing reduced effectiveness. There is a need for large randomized controlled trials for new drugs and vaccines.
“New antibiotics can have a role in these situations, but clinical data for these new drugs have not kept pace with the rise of resistance,” van de Beek wrote. “Because drug-development companies are generally not interested in a disease that affects mainly patients in resource-poor countries, preclinical and clinical studies will need to be funded by governments or charitable foundations.”
Rapid diagnosis
In the first paper, researchers highlight the need for improved diagnosis of acute community-acquired bacterial meningitis. Rapid diagnosis improves the mortality rate and the onset of neurological problems. However, diagnosis can be delayed by several factors.
Clinical symptoms of meningitis, such as rash, neck stiffness and impaired consciousness, often do not appear until the patient is in the hospital, if at all, according to data from several studies. The utility of these clinical symptoms is also compounded because there are predisposing disorders that may affect patients.
Lumbar puncture to withdraw cerebrospinal fluid is necessary to diagnose bacterial meningitis, but this can be delayed if the patients do not receive cranial imaging to determine the risk for brain herniation. In addition, cerebrospinal fluid may not always be effective because it can be varied according to cause, age, immune status and previous treatment.
“Clinical judgment of individual patients by their physicians remains the most important factor in the diagnosis of acute bacterial meningitis,” the researchers wrote.
Treatment advances
According to the researchers of the second paper in the series, initiating early antibiotic treatment in bacterial meningitis is critical to improving outcomes. However, the effectiveness of the available antibiotics is declining due to the emergence of multidrug-resistant bacteria. There are few data to support the use of new antibiotics, such as fluoroquinolones.
Another controversial issue is the use of adjunctive anti-inflammatory therapies to improve outcomes. According to the researchers, such treatments are ineffective in resource-poor regions, which is where the disease burden is highest. Other treatments, such as glycerol, paracetamol and hypothermia, are being examined.
“In the near future, controlled trials are needed to assess treatment modalities such as induction of hypothermia, intracranial pressure management and specific monoclonal antibodies,” they wrote. “However, the greatest effect on the burden of illness due to bacterial meningitis is likely to be achieved through widespread use of vaccinations.”
Vaccination
In the third paper of the series, the potential of vaccines to prevent bacterial meningitis is discussed. Most cases of acute bacterial meningitis are caused by one of three bacteria: Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis. All three can be prevented with conjugate vaccines.
Measurement of a vaccine for H. influenzae has been most reliable because one serotype and one age group comprise 90% of the cases of this type of meningitis, according to the researchers. This vaccine has had the most striking effect when compared with the other vaccines — with a reduction of cases of more than 95%. There has also been a near elimination of serogroup C meningococcal meningitis. The reduction of all-age pneumococcal meningitis has decreased by about 25%.
However, the researchers said these data are true of high-income countries, where the vaccines have been used the longest. There are a lack of data of vaccine efficacy among low- and middle-income countries, which may not have even been introduced to the vaccines.
“Widespread introduction of conjugate vaccines, especially where disease burden is greatest, will have incremental effects on the global burden of acute bacterial meningitis, but important challenges remain,” the researchers wrote. “These include delivery of potent vaccines to difficult-to-access populations at risk; appropriately designed studies of effect, which require adequate surveillance to be in place many years before vaccine introduction; and development and testing of improved vaccines.”
For more information:
Brouwer M. Lancet. 2012;380:1684-1692.
McIntyre P. Lancet. 2012;380:1703-1711.
van de Beek D. Lancet. 2012;380:1623-1624.
van de Beek D. Lancet. 2012;380:1693-1702.
Disclosure: One researcher reports financial relationships with GlaxoSmithKline, Merck, Pfizer and Sanofi-Pasteur.