Box 2.

Outstanding research questions of cryptic Plasmodium chronic infections

Are cryptic asexual blood stages during chronic infections hidden at plain sight?

Do they represent the main source of parasites during asymptomatic infections?

Are the bone marrow and spleen the main places for cryptic chronic infections?

Is there host/parasite intercellular communication facilitating establishment of cryptic niches?

What selective advantages are behind the evolution of cryptic hypnozoite dormant stages vs cryptic active stages in P. vivax?

What is the factual degree of sheltering of these cryptic niches, both in terms of evasion of immune responses and anti-malarial drugs?

What are the implications of these sheltered niches for malaria elimination?