Abstract Details

Title Viral Causes of Meningitis Detected by Metagenomic Next-generation Sequencing in a Ugandan Tuberculous Meningitis Cohort

Topic Global Health and Neuroepidemiology

Presentation(s) S7 - Global Health (3:54 PM-4:06 PM)

Poster/Presentation
Number 003

Objective

To identify viral infections by metagenomic next-generation sequencing (mNGS) in Ugandan HIV-infected patients with presumed tuberculous meningitis (TBM).

Background

Most Ugandan patients with HIV infection and meningitis whose CSF tests negative for cryptococcal antigen are treated as presumed TBM. Viral meningitis masquerading as TBM needs to be considered.

Design/Methods

CSF was obtained from 71 patients at Kiruddu National Referral Hospital in Kampala, Uganda, who were classified according to the Uniform Case Definition as definite (n=16), probable (n=7), or possible TBM (n=48). After total RNA and DNA were extracted, and unbiased cDNA and DNA libraries were sequenced, viruses were identified using a custom bioinformatics pipeline.

Results Viruses other than HIV-1 were identified in 37 patients, of which 6 were likely pathogenic (measles virus (n=2), Wesselsbron virus (n=1), rubella virus (n=1), herpes simplex virus (HSV)-1 (n=1), and HSV-2 (n=1)). All (n=6) were in patients classified as possible TBM (definite and probable TBM, n=0). Only the HSV-2 infected patient received contemporaneous multiplex PCR testing given lack of clinical improvement on anti-tubercular therapy. The patient with HSV-1 presented with headache, fever, and focal neurologic deficits, followed by pneumonia and death. One patient with measles virus was co-infected with Cryptococcus neoformans and did not improve with antifungal treatment. The other measles virus-infected patient had seizures progressing to coma and death. The patient infected with rubella virus had cutaneous Kaposi Sarcoma and a milder presentation of meningism after initiating antiretrovirals. Wesselsbron virus, an endemic flavivirus, was found in a patient with meningism, confusion, and hepatomegaly, who died from respiratory failure despite anti-tubercular therapy.

Conclusions

The Uniform Case Definition of possible TBM, while sensitive, is not specific. mNGS of CSF identified alternate candidate viral etiologies in 12.5% (n=6) of possible TBM cases. Two infections (HSV-1, HSV-2) were treatable, and three (two measles virus and one rubella virus) were vaccine preventable.

Authors/Disclosures
Carson M. Quinn, MD (Mass General Brigham) PRESENTER	Dr. Quinn has nothing to disclose.
Prashanth S. Ramachandran, Jr., MBBS (Royal Melbourne Hospital)	Dr. Ramachandran has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Ramachandran has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merk.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Fiona Cresswell	No disclosure on file
David Meya	No disclosure on file
David R. Boulware, MD, MPH (University of Minnesota)	The institution of David R. Boulware, MD, MPH has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sfunga. David R. Boulware, MD, MPH has received publishing royalties from a publication relating to health care. David R. Boulware, MD, MPH has received personal compensation in the range of $0-$499 for serving as a Study Section with NIH.
Michael R. Wilson, MD, FAAN (University of California San Francisco)	Dr. Wilson has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Delve Bio. Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Cambridge Medical Experts. Dr. Wilson has stock in Delve Bio. The institution of Dr. Wilson has received research support from Genentech / Roche. The institution of Dr. Wilson has received research support from NIH. The institution of Dr. Wilson has received research support from Novartis. The institution of Dr. Wilson has received research support from National Multiple Sclerosis Society. The institution of Dr. Wilson has received research support from Fanconi Anemia Research Foundation. The institution of Dr. Wilson has received research support from Department of Defense. The institution of Dr. Wilson has received research support from Chan Zuckerberg Initiative. Dr. Wilson has received intellectual property interests from a discovery or technology relating to health care. Dr. Wilson has received intellectual property interests from a discovery or technology relating to health care. Dr. Wilson has received personal compensation in the range of $10,000-$49,999 for serving as a Expert Witness with US Dept of Justice.

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