1. 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

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

3. 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.

4. 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

5. 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

6. 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).

7. 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:

8. Causes of AMS
Rwembera and Wilson, Tropical Doctor 2009; 39:

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

10. Case Report Forms

11. CSF Microbiology and Chemistry
Refer to Case Report Form

12. Clinical Data
Refer to Case Report Form

13. Constructing the Database

14. 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

15. 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)

16. 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 :
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:
Rwenbera J and Wilson T. Altered consciousness in Ugandan hospital admissions. Tropical Doctor 2009; 39: