Meningitis: Burden, Causes, Screening and Prevention in Rural Northern Uganda

This study will investigate the burden, causes, diagnostics, treatments and preventive measures related to meningitis in northern Uganda. We hypothesize that understanding the burden of meningitis, risk factors, diagnostics, treatments and the preventive measures will provide information regarding the gaps in care that can be addressed in order to improve the continuum of meningitis care. we hypothesize that our data will support the advocacy for the implementation of routine vaccination for the prevention of bacterial meningitis and improving guidelines for Cryptococcal antigen (CrAg) screening for prevention of cryptococcal meningitis, which will save lives in Uganda.

Aim 1: To prospectively collect data on all patients with meningitis and meningitis symptoms who were admitted to Lira Regional Referral Hospital (LRRH) to assess burden, etiologies, pathogenesis, and outcomes of meningitis using modern diagnostic testing not previously available in Uganda.

Aim 2: To perform CrAg screening of 10,000 HIV-positive patients to determine the prevalence of cryptococcal antigenemia (infection) and conduct a case control study to compare risk factors and outcomes among CrAg-positive patients and matched CrAg-negative controls based on age, sex, TB status, ART experience, CD4 count, and viral load.

Study Overview

• Status: Recruiting
• Conditions: Meningitis
• Intervention / Treatment: Diagnostic test: Pastorex Latex Agglutination Test; Diagnostic test: Biofire PCR for meningitis; Diagnostic test: Immy CrAg Lateral Flow Assay

• Study Type: Interventional
• Enrollment (Estimated): 10400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Paul Bohjanen, MD; Email: paul_bohjanen@urmc.rochester.edu

Study Locations

• Uganda
  • Lira, Uganda, 224180000
    • Recruiting
    • Lira Regional Referral Hospital
    • Contact: Edward Kumakech, PhD; Email: edward.kumakech77@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All patients who present with meningitis or meningitis symptoms, regardless of age or vulnerably status is eligible for meningitis testing.
• Approximately 10,000 HIV-infected patients presenting to the LRRH HIV Clinic (LIDC), regardless of age or vulnerability status, are eligible for CrAg screening.

Exclusion Criteria:

• Patients who are found not to have meningitis after initial evaluation, or are found to have other alternative diagnoses that explain their symptoms, will be excluded.
• CrAg-negative HIV-infected patients who have other active opportunistic infections will be excluded from enrollment in the control group.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants who are HIV negative; Patients who are assessed at Lira Regional Referral Hospital emergency room or are admitted to the pediatric, male or female medical wards at Lira Regional Referral Hospital with meningitis symptoms (defined as headache or irritability in combination with fever, confusion or Glasgow coma scale (GCS) <14, photophobia, neck pain/stiffness, seizure or bulging fontanel) will be approached to participate in the study.	Diagnostic test: Pastorex Latex Agglutination Test; Rapid diagnosis of bacterial meningitis; Diagnostic test: Biofire PCR for meningitis; Rapid diagnosis of multiple forms of meningitis
Experimental: Participants who are HIV positive, CrAg positive; All HIV-infected patients of any age, who receive care at the Lira Infectious Disease Center will be approached for screening for cryptococcal antigen. Those who test positive using the CrAg test will be included in this arm.	Diagnostic test: Immy CrAg Lateral Flow Assay; Rapid diagnosis of cryptococcal meningitis
Sham Comparator: Participants who are HIV positive, CrAg negative; All HIV-infected patients of any age, who receive care at the Lira Infectious Disease Center will be approached for screening for cryptococcal antigen. Those who test negative using the CrAg test will be included in this arm. All HIV-infected patients of any age, who receive care at the Lira Infectious Disease Center will be approached for screening for cryptococcal antigen. Those who test positive using the CrAg test will be included in this arm.	Diagnostic test: Immy CrAg Lateral Flow Assay; Rapid diagnosis of cryptococcal meningitis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
number of participants with meningitis who died during hospitalization	duration of hospitalization, approximately 2 weeks
number of participants with meningitis who died during the first 6 months of hospital admission	6 months
number of participants who were screened using the CrAg diagnostic test who were cryptococcal antigen positive	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of participants who develop overt cryptococcal meningitis	Overt cryptococcal meningitis is defined as symptomatic meningitis.	2 years
Number of participants with overt cryptococcal meningitis who die		2 years

Collaborators and Investigators

• Sponsor: University of Rochester
• Collaborators: Fogarty International Center of the National Institute of Health; Infectious Disease Institute at Makerere University; Lira University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: August 9, 2022
• First Submitted That Met QC Criteria: August 9, 2022
• First Posted (Actual): August 11, 2022

Study Record Updates

• Last Update Posted (Actual): September 5, 2023
• Last Update Submitted That Met QC Criteria: August 30, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neuroinflammatory Diseases; Meningitis
• Other Study ID Numbers: STUDY00007296; R21TW012439 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No