16.5 Gametocytes and Infectiousness

In Ross’s models, everyone who is infected is also infectious. This is clearly wrong, but it may not be a terrible assumption under most circumstances. The Garki Model made the extreme assumption that semi-immune individuals are not infectious at all. There is now copious evidence that adults do transmit parasites to mosquitoes, but they are not as infectious. This decline in infectiousness occurs for two reasons: first, the densities of asexual-stage parasites in adults are controlled by immunity, so they are lower. Since a fraction of asexual parasites becomes gametocytes, the densities of gametocytes are also lower in adults. Second, gametocyte densities are modulated by an immune response that affects malaria parasites in mosquitoes, which is called gametocyte-stage transmission blocking immunity. The dynamics of gametocyte-stage immunity change with age and exposure, and we will need to understand how this form of immunity waxes and wanes.

There are some other important details about malaria infections that might be relevant in some contexts. First, P. falciparum gametocytes take 8-12 days to mature. When combined with the 6 days in the liver, we must acknowledge that the latent period is at least 2 weeks. Because gametocytes must reach densities high enough to be transmitted, the effective latent period for humans is probably closer to 20 days. Since the parasites also need 10 days or more to mature in mosquitoes, the shortest parasite generations are probably at least a month long.

Another feature of gametocytes that matters is that gametocyte populations are not always affected by anti-malarial drugs, so after taking drugs that clear all the asexual-stages, some people will remain infectious to mosquitoes for quite a while after being treated with some drugs.

Ross’s assumption may serve most needs, but the models must be good enough to guide policies, such as MDA or malaria elimination, when details about gametocytes and infectiousness can affect the outcomes of policies.