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Programme 1: Preventing death from severe infections

Malawi has one of the lowest life expectancies in the world (55yrs), with infectious diseases the leading cause of death in both adults and children. Programme 1 is founded on unique patient access with strong diagnostic and surveillance platforms for infection in the community and in hospital. The Programme aims to prevent deaths by generating evidence to support vaccination intervention strategies, behavioural modification, and improved clinical syndrome management.

The work is underpinned and driven by our excellent laboratories, particularly in diagnostic microbiology, molecular biology and immunology, as well as through close integration with the community and with the Clinical Investigation Unit. We are embedded in the clinical service in adult medicine and paediatrics in a large national acute and referral hospital (Queen Elizabeth Central Hospital, Blantyre). We have the capacity to deliver world-class clinical trials, such as those in pneumococcal disease, rotavirus, HIV therapy, and cryptococcal meningitis. 

Specific Objectives – Preventing Death from Infection

Over the next 5 years, we will target diarrhoea, meningitis, sepsis and pneumonia in adults and children, with particular attention to locally prevalent pathogens. We will evaluate vaccine-driven prevention strategies, changes in health care seeking and improved syndrome management. Re-search Groups collaborate across the Programme; areas of established expertise (shaded in blue) and areas of active research (yellow lozenge) are shown in the Figure below. Strategic choices for active research have been made on the basis of scientific importance, excellent opportunities and strengths within the Programme and translational potential. Certain areas of past success have been de-prioritised using the same criteria.

mlw prog1 imageProgramme 1 track record of excellence (blue rectangles) and prioritised research areas (yellow lozenges).

 

Programme 1 Key Deliverables Vaccine-related

  • Sentinel hospital surveillance, community sampling and mathematical modelling to investigate sustained evidence of vaccine effectiveness, herd protection and changes to disease epidemiology for rotavirus and pneumococcus (Funded BMGF).
  • Childhood diarrhoea
    • Novel rotavirus vaccine trial (RV3) to enhance early protection from severe rotavirus disease (Funded BMGF).
    • Characterise disease burden of norovirus and Shigella in severe diarrhoea to inform early phase vaccine trials (Funded Takeda).
  • Respiratory infection
    • Large scale pragmatic controlled trials nested within the infant immunisation schedule to evaluate alternate pneumococcal conjugate vaccine (PCV) schedules (2+1 and 1+1) and optimise herd protection. (French; BMGF invited proposal)
    • Factorial design trial of inactivated influenza vaccine and PCV in HIV infected pregnant women to prevent early infant respiratory morbidity and mortality (Bar-Zeev; seeking funding)
    • Establish pneumococcal CHIM -Experimental Human Pneumococcal Carriage model - for vaccine testing (novel vaccines targeting carriage) and pathogenesis studies using mucosal sampling. (Funded - MRC programme grant).
  • Enteric infection
    • Effectiveness studies with typhoid conjugate (Funded BMGF)
    • New phase 1/2 iNTS vaccines. (Gordon M; EDCTP application)

Behaviour modification

  • Roll-out and monitoring of improved health system referral pattern for severe childhood illness (funded) following successful pilot work. (Funded MRF and Scottish Government)

Syndrome management

  • Randomised Controlled Trial (RCT) of antibiotics in severe paediatric gastroenteritis to reduce diarrhoea deaths in the post-rotavirus vaccine era (Funded WHO).
  • RCT of shortened treatment regimen in cryptococcal meningitis (Funded AMBITION - EDCTP and JGHT).
  • Improved understanding of sepsis, impact of DRI and the context in which AMR pathogens colonise humans in urban and rural Africa (Funded Wellcome Seed, WTCPP Fellow- Lewis).
  • Published AMR surveillance and mechanism data leading to successful trials of antibiotic stewardship (Funded BMGF, WTCPP Fellow - Lester).
  • RCT of ventilation to reduce death in cerebral malaria (Funded NIH)