Table 2. Issues highlighted for any potential CHIM studies in Malawi.

Potential benefits	Challenges
Accelerating or streamlining vaccines/treatment relevant to the national health burden. Building local capacity in: clinical facilities; laboratory diagnostics; experimental medicine; clinical governance; and regulatory confidence. Opportunity to construct Malawi’s regulatory framework to suit its own needs rather than adopting one from the EU/US. Improving science capacity through work-based training and mentorship of local scientists. Understanding key scientific questions relevant to public health in Malawi, including the effect of genetics, endemic infectious disease and co-infections, immune status, and environmental factors. These unique combinations of effects cannot be correctly understood in a model run elsewhere.	Current infrastructure and clinical facilities may not be ready for CHIM (specifically, monitoring and supporting adverse events e.g. on intensive care units). Inherent vulnerabilities may hamper fully informed consent in the local context (languages, assessment understanding, participant criteria suitability, cultural family/group consenting). Poor community hygiene and sanitation infrastructure could prevent effective control measures (e.g. typhoid in out- patient settings). Production of challenge stain locally may have QA issues, but “international” strains may be less relevant - resulting long supply chains need careful management. Consensus on appropriate compensation for monetary and opportunity costs is lacking: the balance between appropriate recompense and incentivisation is difficult and locally variable. Malawi has not yet hosted Phase 1 studies, or those including healthy volunteers who are expected to become symptomatic due to the research protocol; there is a relative shortage of skills and experience

Potential benefits

Challenges

Accelerating or streamlining vaccines/treatment relevant to
the national health burden.

Building local capacity in: clinical facilities; laboratory
diagnostics; experimental medicine; clinical governance; and
regulatory confidence.

Opportunity to construct Malawi’s regulatory framework to
suit its own needs rather than adopting one from the EU/US.

Improving science capacity through work-based training and
mentorship of local scientists.

Understanding key scientific questions relevant to public
health in Malawi, including the effect of genetics, endemic
infectious disease and co-infections, immune status, and
environmental factors. These unique combinations of effects
cannot be correctly understood in a model run elsewhere.

Current infrastructure and clinical facilities may not be
ready for CHIM (specifically, monitoring and supporting
adverse events e.g. on intensive care units).

Inherent vulnerabilities may hamper fully informed consent
in the local context (languages, assessment understanding,
participant criteria suitability, cultural
family/group consenting).

Poor community hygiene and sanitation infrastructure
could prevent effective control measures (e.g. typhoid in out-
patient settings).

Production of challenge stain locally may have QA issues,
but “international” strains may be less relevant - resulting
long supply chains need careful management.

Consensus on appropriate compensation for monetary
and opportunity costs is lacking: the balance between
appropriate recompense and incentivisation is difficult and
locally variable.

Malawi has not yet hosted Phase 1 studies, or those
including healthy volunteers who are expected to become
symptomatic due to the research protocol; there is a relative
shortage of skills and experience