Fig. 2. : factors that influence malaria parasite development in the mosquito midgut lumen. When a female Anopheles mosquito feeds on a malaria-infected person, it ingests sexual forms of the parasite: male and female gametocytes (1). Some of these gametocytes may be dead or non-infectious to the mosquito due to exposure to cytokines or nitric oxide (NO) produced in the infected human host (2). After the gametes egress from the red blood cell (RBC) (3) they become exposed to factors from the human blood that may negatively affect parasite development. These include damage caused by serum cytokines and NO (4), phagocytosis by lymphocytes (5), inhibition of fertilisation by transmission-blocking (TB) antibodies (6) and the attack of the vertebrate complement system (7, 8). The attack by the complement system can be initiated by two mechanisms: activation of the classical pathway (CPC) by opsonising antibodies (against Pfs230) that bind to gamete surface proteins (7) or activation of the alternative pathway (APC) by binding of C3 to the surface of the gamete (8). In both cases, lysis occurs after the formation of a membrane-attack complex on the parasite membrane. To evade the activation of the alternative complement pathway, the parasite uses the surface protein PfGAP50 to recruit factor H from the blood serum, thus inhibiting further activation of the system (9). Proteins from the complement system are degraded approximately 6 h after blood-feeding (10). Parasites that escape further develop into ookinetes which shares its niche with the midgut bacteria that multiplied exponentially after the ingestion of the blood (11). These bacteria may secrete antimalarial compounds, including reactive oxygen species (ROS), which impact ookinete viability (12). The ookinetes that survive invade and traverse the midgut epithelium after which they form oocysts on the basal side of the midgut epithelium (13). RNS: reactive nitrogen species.