Plasmodium oocysts respond with dormancy to crowding and nutritional stress

Abstract

Malaria parasites develop as oocysts in the mosquito for several days before they are able to infect a human host. During this time, mosquitoes take bloodmeals to replenish their nutrient and energy reserves needed for flight and reproduction. We hypothesized that these bloodmeals are critical for oocyst growth and that experimental infection protocols, typically involving a single bloodmeal at the time of infection, cause nutritional stress to the developing oocysts. Therefore, enumerating oocysts disregarding their growth and differentiation state may lead to erroneous conclusions about the efficacy of transmission blocking interventions. Here, we examine this hypothesis in Anopheles coluzzii mosquitoes infected with the human and rodent parasites Plasmodium falciparum and Plasmodium berghei, respectively. We show that oocyst growth and maturation rates decrease at late developmental stages as infection intensities increase; an effect exacerbated at very high infection intensities but fully restored with post infection bloodmeals. High infection intensities and starvation conditions reduce RNA Polymerase III activity in oocysts unless supplemental bloodmeals are provided. Our results suggest that oocysts respond to crowding and nutritional stress with a dormancy-like strategy, which urges the development of alternative methods to assess the efficacy of transmission blocking interventions.

Frequency matters: How successive feeding episodes by blood-feeding insect vectors influences disease transmission

“…In addition to the impacts on immune recognition of Plasmodium oocysts associated with an additional blood meal, several recent studies have demonstrated that an additional feeding can also influence parasite growth [ 26 , 32 , 33 ]. In mosquitoes receiving an additional blood meal, P .…”

“…In mosquitoes receiving an additional blood meal, P . falciparum oocysts display increased size [ 26 , 32 , 33 ] as a result of the added nutrient resources provided with feeding, which overcome nutritional dormancy to promote parasite growth [ 33 ]. The resulting increased growth translates into an accelerated sporozoite invasion of the mosquito salivary glands, reducing the EIP and increasing the likelihood of malaria transmission [ 32 ] ( Fig 2 ).…”

“…Oocyst size was unchanged when provided an additional blood meal at 4 days postinfection [ 26 ], yet P . berghei oocysts display an increase in growth when an additional feed is delayed and provided later in parasite development (7 days postinfection) [ 33 ]. Evidence suggests that an additional feeding overcomes a dormancy-like state in P .…”

“…berghei similar to P . falciparum [ 33 ], yet further experiments are required to determine any potential influence of additional blood meal on vectorial capacity.…”

The need for practical insecticide-resistance guidelines to effectively inform mosquito-borne disease control programs

“…For example, insecticide resistance is expected to reduce insecticide-induced mosquito mortality and thus increase the transmission potential of diseases. However, delayed mortality due to insecticide exposure has frequently been observed across different mosquito species (see for instance, Agnew et al, 2004 ; Martins et al, 2012 ) and may result in a reduced disease transmission given malaria parasites’ relatively long incubation time within the mosquito host (ranging from 7 days to several weeks, depending on temperature [ Mordecai et al, 2013 ; Paaijmans et al, 2009 ] and frequency of blood-meal intake [ Habtewold et al, 2021 ; Shaw et al, 2020 ]). Alarmingly though, recent observations of highly pyrethroid-resistant mosquito populations from Burkina Faso show a lack of such delayed mortality in some populations ( Hughes et al, 2020 ).…”