Population biology of malaria within the mosquito: density-dependent processes and potential implications for transmission-blocking interventions

Abstract

BackgroundThe combined effects of multiple density-dependent, regulatory processes may have an important impact on the growth and stability of a population. In a malaria model system, it has been shown that the progression of Plasmodium berghei through Anopheles stephensi and the survival of the mosquito both depend non-linearly on parasite density. These processes regulating the development of the malaria parasite within the mosquito may influence the success of transmission-blocking interventions (TBIs) currently under development.MethodsAn individual-based stochastic mathematical model is used to investigate the combined impact of these multiple regulatory processes and examine how TBIs, which target different parasite life-stages within the mosquito, may influence overall parasite transmission.ResultsThe best parasite molecular targets will vary between different epidemiological settings. Interventions that reduce ookinete density beneath a threshold level are likely to have auxiliary benefits, as transmission would be further reduced by density-dependent processes that restrict sporogonic development at low parasite densities. TBIs which reduce parasite density but fail to clear the parasite could cause a modest increase in transmission by increasing the number of infectious bites made by a mosquito during its lifetime whilst failing to sufficiently reduce its infectivity. Interventions with a higher variance in efficacy will therefore tend to cause a greater reduction in overall transmission than a TBI with a more uniform effectiveness. Care should be taken when interpreting these results as parasite intensity values in natural parasite-vector combinations of human malaria are likely to be significantly lower than those in this model system.ConclusionsA greater understanding of the development of the malaria parasite within the mosquito is required to fully evaluate the impact of TBIs. If parasite-induced vector mortality influenced the population dynamics of Plasmodium species infecting humans in malaria endemic regions, it would be important to quantify the variability and duration of TBI efficacy to ensure that community benefits of control measures are not overestimated.

The biology of sexual development of Plasmodium: the design and implementation of transmission-blocking strategies

“…A second requirement is the need to recognize and define the recently recognized non-linearities in parasite dynamics [51,52] as they pass through the sequential phases of their life cycles, noting that these relationships may be subject to significant species-specific variations in host, parasite or vector.…”

The Allee Effect and Elimination of Neglected Tropical Diseases: A Mathematical Modelling Study

“…Hosteparasite systems that contain positive DDs have been widely studied and documented (see e.g. for onchocerciasis Churcher et al, 2005Churcher et al, , 2006Duerr et al, 2003), schistosomiasis (Spear, 2012), lymphatic filariasis (LF) (Gambhir et al, 2010b;Gambhir and Michael, 2008), malaria (Muriu et al, 2013;Churcher et al, 2010;White et al, 2011)) though few of these studies explicitly focus upon the possibility of extinction of the parasite at low-intensity levels (the paper by White et al (2011) is a notable exception, perhaps because malaria is a disease for which there is an eradication goal). The paper by Duerr et al (2005) has come Figure 1 The effective reproduction number profile.…”

Characterization of P lasmodium developmental transcriptomes in A nopheles gambiae midgut reveals novel regulators of malaria transmission

“…The ingested parasite populations suffer substantial losses during this stage resulting in very few oocysts and in most cases, termination of transmission. This stage is therefore a good target of interventions aiming to control disease transmission (Aly and Matuschewski, ; Churcher et al ., 2010; 2013; Griffin et al ., ). However, the relatively small number of proteins that have been characterized to date with established functions in these stages does not permit comprehensive understanding of the molecular processes that control this transition stage, which could in turn inform the development of respective interventions.…”