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)
Lead Sponsor: St George's, University of London
European and Developing Countries Clinical Trials Partnership (EDCTP)
|Source||St George's, University of London|
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.
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.
|Start Date||April 23, 2016|
|Completion Date||April 2020|
|Primary Completion Date||October 2019|
Sampling Method: Non-Probability Sample
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.
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
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.
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Last Name: Angela Loyse, MD
Phone: 020 8725 0443
Email: [email protected]
|Has Expanded Access||No|
|Study Design Info||
Observational Model: Other
Time Perspective: Other