Driving Reduced AIDS-associated Meningo-encephalitis Mortality

Integrating the Diagnosis and Management of HIV-associated Central Nervous System (CNS) Infections Into Routine Health Services in Low and Middle Income Countries (LMICs)

Sponsors

Lead Sponsor: St George's, University of London

Collaborator: European and Developing Countries Clinical Trials Partnership (EDCTP)
National Institute for Medical Research, Tanzania
University of North Carolina Project-Malawi (UNC Project)
French National Agency for Research on AIDS and Viral Hepatitis
Yaounde Central Hospital
Institut Pasteur

Source St George's, University of London
Brief Summary

The DREAMM project is investigating whether point of care tests within a diagnostic and treatment algorithm together with support and additional training of laboratory and clinical staff will reduce two and ten week all-cause mortality of HIV-associated meningo-encephalitis in LMICs.

Detailed Description

HIV-associated central nervous system (CNS) infection causes significant mortality and places a high burden on limited health care resources in Sub-Saharan Africa (SSA). Cohort and autopsy studies estimate that CNS infections cause up to 25% of HIV-related deaths.

Cryptococcal meningitis alone is estimated to account for up to 20% of HIV-related mortality and its' incidence in Africa, unlike in resource-rich settings, has remained high despite antiretroviral roll out.

In African low and middle income countries (LMICs) mortality associated with cryptococcal meningitis has been estimated at 70% at 3 months.

Tuberculous meningitis mortality also remains unacceptably high and is reported at over 70% in a study from Cameroon. Delays in diagnosis are key causes of poor patient outcomes for tuberculous and bacterial meningitis, and cryptococcal meningitis where patients present late and with advanced disease.

The aim of the DREAMM study is to drive down this unacceptably high mortality associated with HIV-associated meningo-encephalitis in LMICs.

A further aim is to provide capacity building in implementation research at each of the sites driven by the local African Principal Investigators (PIs) (Dr Cecilia Kanyama, Lilongwe, Malawi; Dr Charles Kouanfack, Yaounde, Cameroon; Dr Sayoki Mfinanga, NIMR, Dar Es Salaam Tanzania).

The project is in three phases:

1. Audit local clinical and laboratory procedures and practices and availability of essential drugs and diagnostic tests for routine care of HIV-associated meningo-encephalitis patients in three study sites. 75 patients in total will be recruited into the audit phase of DREAMM-25 patients from each study site.

2. Laboratory (led by Institut Pasteur) and clinical training program on HIV-associated meningitis in LMICs. Key clinical and laboratory personnel will be trained on the latest point of care diagnostic tests and safe administration of essential medicines for HIV-associated meningo-encephalitis such as amphotericin B deoxycholate. They will disseminate this knowledge to their hospital counterparts.

3. Implementation of algorithmic approach to diagnosis and treatment of HIV-associated meningitis with aggressive cryptococcal (urine, blood and CSF) and tuberculous (urine & CSF detection) microbiological detection in the three study sites. The aim is to reduce the time from patient presentation to diagnostic testing and administration of effective, microbiologically-driven treatment. Data from audit and algorithmic phases of study will be fed back to local ministries of health (MOH), and access to essential antifungal drugs and diagnostic tests for HIV-associated meningitis improved and finally, cohesive HIV-related meningitis guidelines for African LMICs developed.

Important sub-studies include a health economics evaluation study to determine the cost of the intervention and routine care costs. A new semi-quantitative cryptococcal antigen lateral flow assay (CrAg LFA) (CryptoPS, Biosynex, Strasburg, France) will be evaluated uniquely for the diagnosis of patients with meningo-encephalitis. New, point of care (POC) polyvalent tests (CrAg/HIV) and (CrAg/Streptococcus pneumoniae) will also be evaluated. Lastly, nanopore technology (MinION, Oxford Nanopore Technology, Oxford, UK) will be optimised for the diagnosis of HIV-associated meningo-encephalitis in African low and middle income countries (LMICs).

These point of care tests nested within algorithms and the new tests being evaluated have the potential to significantly reduce CNS infection-related mortality by reducing delays in proven diagnosis and initiation of effective treatments.

Overall Status Recruiting
Start Date April 23, 2016
Completion Date April 2020
Primary Completion Date October 2019
Study Type Observational
Primary Outcome
Measure Time Frame
All-cause mortality 2 weeks from enrolment
All-cause mortality 10 weeks from enrolment
Secondary Outcome
Measure Time Frame
Time to lumbar puncture (LP) or other appropriate diagnostic investigation. Up to 2 weeks from enrolment
Time to meningo-encephalitis treatment Up to 10 weeks from enrolment
Number of patients diagnosed with cryptococcal meningitis 10 weeks from enrolment
Number of patients diagnosed with tuberculous meningitis 10 weeks from enrolment
Number of patients diagnosed with toxoplasma meningo-encephalitis 10 weeks from enrolment
Number of patients diagnosed with bacterial meningitis 10 weeks from enrolment
Enrollment 450
Condition
Eligibility

Sampling Method: Non-Probability Sample

Criteria:

Inclusion Criteria:

1. Consecutive patients > 18 years with 1st episode of suspected meningo- encephalitis

2. Known to be HIV positive or willing to undertake an HIV test

3. Willing to agree to participate in the study

Exclusion Criteria:

1. Patients presenting with suspected relapse of HIV-associated meningo-encephalitis

2. Cerebral malaria confirmed on point of care test or thick/thin blood film, by clinical evaluation and further investigation, as required

3. HIV negative patients

4. Pregnant or lactating patients

Patients who are HIV negative or are diagnosed with cerebral malaria on hospital admission or after initial investigation will be excluded or withdrawn from the DREAMM study.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Angela Loyse, MD Principal Investigator St George's, University of London
Overall Contact

Last Name: Angela Loyse, MD

Phone: 020 8725 0443

Email: [email protected]

Location
Facility: Status: Contact:
Kamuzu Central Hospital | Lilongwe, Malawi Recruiting Cecilia Kanyama, MD
Amana Hospital | Dar es Salaam, Tanzania Recruiting Sayoki Mfinanga, MD
Location Countries

Malawi

Tanzania

Verification Date

January 2019

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Acronym DREAMM
Study Design Info

Observational Model: Other

Time Perspective: Other

Source: ClinicalTrials.gov