Meningitis Surveillance and investigation of causes of altered mental status among Kamuzu Central Hospital admissions, Lilongwe, Malawi Charles Kyriakos Vorkas PGY2, Internal Medicine UNC Hospitals/UNC Project April 18, 2013

Evaluating altered mental status Identifying reversible causes of altered behavior early is essential to treating critically ill patients.

A recently initiated cryptococcal meningitis Phase III clinical trial will provide an opportunity to characterize causes of meningitis among Kamuzu Central Hospital inpatients as well as investigate non infectious etiologies of mental status changes.

ACTA (Advanced Cryptococcal Treatment for Africa) Trial Objective: To determine the best initial therapy for newly diagnosed cryptococcal meningitis in HIV+ patients not on ART. 3 arms: 2 weeks of Amphotericin B + fluconazole/flucytosine 1 week of Amphotericin B + fluconazole/flucytosine Oral fluconazole and flucytosine alone

ACTA Study Recruitment Among patients with suspected meningitis, lumbar punctures will be performed in the short stay and on the medical wards and cerebrospinal fluid (CSF) will be sent to UNC project for analysis. Screening labs: India ink; if negative, cryptococcal antigen LFA Cell Count and differential Glucose and Protein Gram stain and culture

Nested Observational Cohort India ink+ or cryptococcal antigen LFA+ samples will then be consented for the ACTA trial. All patients receiving lumbar punctures will enter a de-identified database which will include CSF study results and clinical data points to help determine etiologies of altered mental status (AMS).

Sparse data concerning AMS in Resource limited settings Investigators looked at 100 consecutive admissions with altered mental status. Primary causes of AMS included infection, with cerebral malaria and meningitis predominating. Mortality in the study was 44% Rwembera and Wilson, Tropical Doctor 2009; 39: 240-241

Causes of AMS Rwembera and Wilson, Tropical Doctor 2009; 39: 240-241

Data dictionary Tables, variables and parameters defined in tabular format.

Case Report Forms

CSF Microbiology and Chemistry Refer to Case Report Form

Clinical Data Refer to Case Report Form

Constructing the Database

Study progress Recruitment initiated on Monday, 15 April 2013 10 lumbar punctures performed for suspected meningitis 5 female, 7 HIV positive 1 known history cryptococcal meningitis 10 samples processed to date - All India ink negative, cryptococcal antigen negative -5 with 0 RBCs, 0 WBCs -1 with 15 WBCs, 20 RBCs -1 with 4 WBCs, 275 RBCs -1 sample with too many cells to count -2 sample clotted

Challenges Assuring LPs are performed on all suspected AMS cases Performing clinical questionnaires/chart review Data entry/Linking meningitis surveillance database with existing Med Admissions database Timely laboratory reporting Communicating results to KCH primary teams (eg, delivery vs. dropbox)

References ACTA Phase III Trial Protocol. 31 July 2013 Nussbaum J, Jackson A, Namarika D et al. Combination flucytosine and high dose fluconazole compared with high dose fluconazole alone for the treatment of cryptococcal meningitis: a randomized trial in Malawi. Clinical Infectious Diseases 2010. 50: 338-44. Jackson A, Nussbaum J, Phulusa J, et al. A phase II randomized controlled trial adding oral flucytosine to high-dose fluconazole with short-course amphotericin B for cryptococcal meningitis. AIDS 2012; 26: 1363-70 Rwenbera J and Wilson T. Altered consciousness in Ugandan hospital admissions. Tropical Doctor 2009; 39: 240-41