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New grant will allow U of M researchers to advance new diagnosis & treatment methods for meningitis

Researchers from the University of Minnesota Medical School’s Division of Infectious Diseases and International Medicine have received a $3.2 million grant to examine new cost-effective approaches for diagnosing and treating meningitis. The University will partner with Uganda’s Makerere University on the effort.

In the first of two programs supported by the new grant, University of Minnesota researchers will employ a tiered approach to diagnosing meningitis, employing a strategic approach that eliminates a full battery of testing when a more limited panel of stepwise testing can confirm infection.  The project will also explore new diagnostic tests for meningitis due to tuberculosis (TB).

The grant will also support a new clinical trial to test the antifungal properties of sertraline (Zoloft), an antidepressant with possible anti-fungal properties in mouse models. Because Zoloft went off patent in 2006, the medication could present a cheaper alternative in the fight against cryptococcal meningitis.

Cryptococcal meningitis primarily affects people with a weakened immune system and accounts for 20 to 25 percent of AIDS-related deaths in Africa. Due to the burden of HIV in Africa, cryptococcal meningitis is the most common cause of meningitis in adults in Africa.

“We’ve made progress in combating cryptococcal meningitis but international mortality rates for the infection still hover around 40 percent at the six month mark, so the need for better, inexpensive drugs is apparent,” said grant leader David R. Boulware, M.D., M.P.H., the Medical School’s associate director of Global Health Programs in Internal Medicine. “We believe that a more efficient system of diagnosis and new inexpensive medications can improve lives while saving health resources that could be deployed in other ways.”

According to Boulware, a new University-developed diagnostic checklist can help resource-limited areas improve diagnosis of cryptococcal meningitis by allowing for incremental testing.

“If initial testing – let’s call it Test A – is positive for cryptococcal meningitis then there’s really no need for a patient to undergo test B or C, but right now there’s a standard battery of routine testing that became the international standard before we saw the sweeping impact of HIV,” said Boulware. “The rise of HIV in Africa over the past two decades has meant a huge influx of HIV-related cryptococcal meningitis cases, and we’re at the point where adding new efficiencies could save public health resources in sub-Saharan Africa and elsewhere.”

Boulware adds that in addition to better diagnostic testing, new medication options will be critical to fight cryptococcal meningitis efficiently.

By exploring the efficacy of drugs already developed, on the market and off-patent, patients and providers could have new options to fight cryptococcal meningitis effectively and in a cost-effective way. Supported by their latest grant, Boulware and his colleagues hope to evaluate Zoloft’s antifungal properties in 480 patients over three to four years.

Traditional treatment for cryptococcal meningitis is a combination of intravenous therapy and oral medication that spans two weeks.

All evaluation will occur in Uganda in partnership with Makerere University. The University has had a relationship with Makerere for nearly a decade.

“The bottom line is we’re trying to improve outcomes while lowering the cost of care,” said Boulware. “Cost containment is a major health care issue and it can be exacerbated in places like sub-Saharan Africa. By taking new approaches to common problems the University of Minnesota hopes to make a meaningful impact and generate real change.”

Collaborators in this project will include Drs. David Meya, Joshua Rhein, Nathan Bahr, Kathy Huppler Hullsiek, Kirsten Nielsen, and Paul Bohjanen.

The project will be supported by grant no. R01NS086312 from the National Institutes of Health.

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