Biological rhythms in infections

The rodent malaria asexual cell stage cycle takes approximately 24hours. In synchronous species each cell stage occurs at a certain time of day

The developmental rhythm of many malaria parasite species is coordinated: parasites invade host red blood cells, replicate, and then release their progeny in a timed, synchronized burst. For several centuries, the species of malaria parasite infecting a patient was diagnosed by the regularity of fever (every 1, 2, or 3 days) resulting from synchronous bursting. Despite such ancient knowledge, why parasites that exclusively live within the bodies of other organisms have a daily rhythm has remained unanswered. 

 

Rhythms in the vector

Rhythms in the host

A C57/Bl6 mouse (Mus musculus) - frequently used as hosts in our experimental infections. (Credit: Sinclair Stammers)

An Anopheles stephensi mosquito taking a blood meal. (Credit: Sinclair Stammers)

Rhythms in parasite development are proposed to have evolved to enable the maturation (infectiousness) of sexual stages to coincide with mosquito biting activity. Data do not support this idea but mosquitoes do have circadian rhythms that are likely to influence parasite-vector interactions. Interactions could impact on transmission directly by affecting the prevalence or intensity of infections in mosquitoes and/or indirectly by affecting whether mosquitos live long enough to bite new hosts, and their biting rate. 

The discovery of biological rhythms in parasite behaviours and host immune responses suggests that timing matters for how hosts and parasites interact. We have revealed that when parasite schedules are perturbed to be out of synchrony with the host’s circadian rhythms, the replication and transmission of parasites is reduced and hosts suffer less severe infections. Rhythms in immune defence and parasite development could provide an evolutionary advantage to hosts, parasites or both, and either or both parties may control each other’s rhythms. 


  (credit: EviMalar, Jamie Hall, Edward Ross, Wellcome Trust)

(credit: EviMalar, Jamie Hall, Edward Ross, Wellcome Trust)

What next?

We would like to know whether parasites actively organise their rhythms, which could be achieved by using an endogenous clock or by responding to time-of-day cues resulting from the host circadian rhythm. Or whether circadian aspects of host physiology, such as innate immune responses, impose schedules on parasite development.

We would also like to uncover the nature of the benefits rhythms bring to parasite replication in the host and their potential for transmission. We are also investigating how rhythms in the parasite, vector, and host all interact to shape transmission from hosts to vectors, and from vectors to hosts. 

Growing evidence that the daily rhythms of malaria parasites can confer tolerance to antimalarial drugs, and that the use of bed nets is changing the biting time of the mosquitoes that transmit malaria, makes understanding how and why parasites exhibit daily rhythms increasingly urgent.