In 2021, there were an estimated 650,000 HIV-related deaths globally. Central nervous system (CNS) infections, including meningitis, are one of the biggest killers of people with advanced HIV disease, with up to one third of deaths caused by this type of infection. In African Low- and- Middle- Income- countries (LMICs), the fungal infection cryptococcal meningitis alone is estimated to be the cause of around 20% HIV-related deaths every year. Other common causes of HIV-related CNS infection include tuberculous meningitis (when tuberculosis affects the CNS), bacterial meningitis, and cerebral toxoplasmosis (a parasitic infection of the brain). Mortality for these is very high, at around 70% within routine care services. Diagnoses are rarely confirmed, which means treating infections effectively is challenging. Access to essential tests and medicines is often lacking or limited, and when they are available, frontline healthcare workers and laboratory technicians may not feel confident in using these.The DREAMM implementation science project aimed to overcome these challenges and reduce deaths from HIV-related CNS infections in routine care services in Africa.

1. Empowerment of local leadership to design and implement all interventions
   
   

2. A health system strengthening approach for hospitals was adopted to deliver quality care through:
   
   a) An open access, co-designed education program for front-line healthcare workers and laboratory technicians
   
   b) Optimised clinical and laboratory pathways for rapid diagnosis and targeted treatment according to meningitis cause
   
   c) Joint clinical and laboratory communities of practice which provided clinical mentorship and ongoing laboratory capacity building

DREAMM’s main intervention: implementing a step-wise algorithm for the rapid diagnosis and targeted treatment of HIV-linked meningitis. Key features:

• using point of care rapid diagnostic tests (in parallel with traditional laboratory techniques) to speed up diagnosis
• targeted treatments in line with WHO recommended guidelines  

In 2021, there were an estimated 650,000 HIV-related deaths globally. Central nervous system (CNS) infections that include meningitis are one of the biggest killers of people with advanced HIV disease (defined in adults by the World Health Organisation as a CD4<200 cells/microL), with up to one third of deaths caused by this type of infection. In African Low- and- Middle- Income- countries (LMICs), cryptococcal meningitis (a fungal infection) alone is estimated to be the cause of around 20% HIV-related deaths annually. Other common causes of HIV-related CNS infection include tuberculous meningitis (when tuberculosis affects the CNS), bacterial meningitis and cerebral toxoplasmosis (a parasitic infection of the brain).  Associated mortality is very high at around 70% within routine care services. Diagnoses are rarely confirmed which means treating infections effectively is challenging.  Access to essential tests and medicines is often lacking or limited.  Where available, frontline healthcare workers and laboratory technicians may not feel confident in using these. The DREAMM implementation science project aimed to overcome these challenges and reduce mortality from HIV-related CNS infections within routine care services in Africa.

The project was divided into three phases: 1) Observation, 2) Training, and, 3) Implementation.  The main DREAMM intervention was the implementation of a step by step decision-making tool to rapidly diagnose and allow targeted treatment of HIV-related central nervous system infections, including meningitis. 

Two implementation strategies were devised during the observation and training phases:
1) Empowerment of local leadership to design and implement all interventions
2) Delivery of quality care for HIV-related CNS infection in resource limited settings. 

Quality care was delivered through:
a) A  laboratory and clinical programme tailored for front-line healthcare workers and laboratory technicians
b) Optimised, codesigned clinical and laboratory pathways
c) Joint clinical and laboratory communities of practice for ongoing mentorship and laboratory capacity building.

The team was led by the Chief Investigator Dr Angela Loyse, along with Principal Investigators (PIs) Dr Cecilia Kanyama, Prof Sayoki Mfinanga, Prof Charles Kouanfack and Dr Saulos Nyirenda. The DREAMM training programme and clinical and laboratory pathways were co-designed with the PIs, hospital directors, frontline healthcare workers, laboratory technicians, and Ministries of Health. From Institut Pasteur, Mme Aude Sturny-Leclere led the development and delivery of the DREAMM laboratory training programme; Dr Timothee Boyer-Chammard was a key member of the DREAMM Project Management Team;and Prof Olivier Lortholary was the ‘PI nord’ for the Cameroon DREAMM site and came up with the DREAMM name! 

To find out more about the DREAMM team check out About Us.

DREAMM drew on clinical trials, mixed methodology (social science, education, health economics), and health system engineering. Co-designing interventions and strategies with front-line health workers and their leaders, the project developed a new approach for resource-limited settings to save lives from HIV-linked meningitis. 

The observation phase aimed to identify barriers and facilitators for delivery of care for HIV-related CNS infection in African LMICs within routine care services. 

The main intervention was the implementation of a step-wise algorithm (or decision making tool) for HIV-related CNS infection. The four main causes of HIV-related CNS infection (cryptococcal meningitis, tuberculous and bacterial meningitis, and cerebral toxoplasmosis) were targeted. Key features of the DREAMM algorithm included bedside rapid diagnostic testing by clinical staff, performed alongside laboratory testing, which included standard microbiological techniques such as cerebrospinal fluid (CSF) culture. All participants received cryptococcal antigen lateral flow assay (CrAg LFA) in blood and CSF and urinary lipoarabinomannan (LAM) testing in line with WHO guidance on Advanced HIV Disease. A second important feature was the implementation of the 2018 WHO cryptococcal meningitis guidelines.

Between November 2016 and April 2019, the DREAMM observation phase took place in four public hospitals in Malawi, Cameroon, and Tanzania for two to three months at each site. Overall, very few investigations were conducted within routine care, so treatments were largely empirical, using available medicines. Indeed, only 10% had a CNS infection confirmed microbiologically, so most were treated with broad-spectrum antibiotics and fluconazole, a suboptimal treatment for cryptococcal meningitis (a fungal infection and the leading cause of HIV-related CNS infection). Observation phase outcomes were poor with 49% all-cause, two-week mortality.

After training, with the new clinical and laboratory pathways and communities of practice in place, nearly 90% participants received a lumbar puncture (LP), the gold standard procedure for detecting meningitis.  

For three quarters of participants with suspected cryptococcal and tuberculous meningitis, the LP was done within 90 minutes, and the median time to a targeted treatment was five hours. For almost all of those who did not receive a LP, this was because LP was not appropriate. This is the case in cerebral toxoplasmosis, where symptoms can include limb weakness and seizures, and so brain imaging, which was promoted by the project, is advised instead.  

Where possible, bedside testing meant that rapid therapeutic decisions could be made while waiting for the results of laboratory testing. Hospital laboratory teams had overall responsibility and oversight of bedside testing by nurses and doctors and this was key for quality assurance mechanisms.  

Overall, there were nearly 50% fewer deaths (24% all-cause two week mortality) in the implementation phase compared to the observation phase. 

he mortality results have just been published in The Lancet HIV, you can read the paper here. These results are accompanied by two comment pieces on the importance and impact of this work by leading global health experts in The Lancet HIV (hyperlink: ) and The Lancet Global Health. The DREAMM epidemiology results are due for publication by early 2024.

If you would like to support our work and its continuation as we seek to scale up the DREAMM model of care and create a movement around Africa-led health system strengthening, through DREAMM 2, please see more about Funding DREAMM 2 or Contact Us.

We devised our own training materials, all of which are available to be used for educational purposes and can be found here.