The development of new drugs to disrupt malaria transmission
requires the establishment of an in vivo model to address the
biology of Plasmodium falciparum sexual stages (gametocytes).
Herein we show that chemically immune-modulated NSG mice grafted
with human erythrocytes support complete sexual development of
P. falciparum parasites and generate high gametocytemia.
Immunohistochemistry and RT-qPCR analyses indicate an enrichment
of immature gametocytes in the bone marrow and the spleen,
suggesting a sequestration mechanism reminiscent to that
observed in humans. Upon primaquine treatment, elimination of
gametocytes from peripheral blood and from sequestration sites
was observed, providing a proof of concept that these mice can
be used for testing drugs. Therefore, this model allows the
investigation of P. falciparum sexual commitment, gametocyte
interactions with the bone marrow and spleen and provides the
missing link between current in vitro assays and Phase I trials
in humans for testing new malaria gametocytidal drugs