Plant-mediated effects on mosquito capacity to transmit human malaria

The ecological context in which mosquitoes and malaria parasites interact has received little attention, compared to the genetic and molecular aspects of malaria transmission. Plant nectar and fruits are important for the nutritional ecology of malaria vectors, but how the natural diversity of plant-derived sugar sources affects mosquito competence for malaria parasites is unclear. To test this, we infected Anopheles coluzzi, an important African malaria vector, with sympatric field isolates of Plasmodium falciparum, using direct membrane feeding assays. Through a series of experiments, we then examined the effects of sugar meals from Thevetia neriifolia and Barleria lupilina cuttings that included flowers, and fruit from Lannea microcarpa and Mangifera indica on parasite and mosquito traits that are key for determining the intensity of malaria transmission. We found that the source of plant sugar meal differentially affected infection prevalence and intensity, the development duration of the parasites, as well as the survival and fecundity of the vector. These effects are likely the result of complex interactions between toxic secondary metabolites and the nutritional quality of the plant sugar source, as well as of host resource availability and parasite growth. Using an epidemiological model, we show that plant sugar source can be a significant driver of malaria transmission dynamics, with some plant species exhibiting either transmission-reducing or -enhancing activities

Studying fitness cost of <it>Plasmodium falciparum</it> infection in malaria vectors: validation of an appropriate negative control

Abstract Background The question whether Plasmodium falciparum infection affects the fitness of mosquito vectors remains open. A hurdle for resolving this question is the lack of appropriate control, non-infected mosquitoes that can be compared to the infected ones. It was shown recently that heating P. falciparum gametocyte-infected blood before feeding by malaria vectors inhibits the infection. Therefore, the same source of gametocyte-infected blood could be divided in two parts, one heated, serving as the control, the other unheated, allowing the comparison of infected and uninfected mosquitoes which fed on exactly the same blood otherwise. However, before using this method for characterizing the cost of infection to mosquitoes, it is necessary to establish whether feeding on previously heated blood affects the survival and fecundity of mosquito females. Methods Anopheles gambiae M molecular form females were exposed to heated versus non-heated, parasite-free human blood to mimic blood meal on non-infectious versus infectious gametocyte-containing blood. Life history traits of mosquito females fed on blood that was heat-treated or not were then compared. Results The results reveal that heat treatment of the blood did not affect the survival and fecundity of mosquito females. Consistently, blood heat treatment did not affect the quantity of blood ingested. Conclusions The study indicates that heat inactivation of gametocyte-infected blood will only inhibit mosquito infection and that this method is suitable for quantifying the fitness cost incurred by mosquitoes upon infection by P. falciparum.</p

Host-seeking behaviors of mosquitoes experimentally infected with sympatric field isolates of the human malaria parasite Plasmodium falciparum: no evidence for host manipulation

International audiencePrevious studies have shown that Plasmodium parasites can manipulate mosquito feeding behaviors such as motivation and avidity to feed on vertebrate hosts, in ways that increase the probability of parasite transmission. These studies, however, have been mainly carried out on non-natural and/or laboratory based model systems and hence may not reflect what occurs in the field. We now need to move closer to the natural setting, if we are to fully capture the ecological and evolutionary consequences of these parasite-induced behavioral changes. As part of this effort, we conducted a series of experiments to investigate the long and short-range behavioral responses to human stimuli in the mosquito Anopheles coluzzii during different stages of infection with sympatric field isolates of the human malaria parasite Plasmodium falciparum in Burkina Faso. First, we used a dual-port olfactometer designed to take advantage of the whole body odor to gauge mosquito long-range host-seeking behaviors. Second, we used a locomotor activity monitor system to assess mosquito short-range behaviors. Compared to control uninfected mosquitoes, P. falciparum infection had no significant effect neither on long-range nor on short-range behaviors both at the immature and mature stages. This study, using a natural mosquito-malaria parasite association, indicates that manipulation of vector behavior may not be a general phenomenon. We speculate that the observed contrasting phenotypes with model systems might result from coevolution of the human parasite and its natural vector. Future experiments, using other sympatric malaria mosquito populations or species are required to test this hypothesis. In conclusion, our results highlight the importance of following up discoveries in laboratory model systems with studies on natural parasite–mosquito interactions to accurately predict the epidemiological, ecological and evolutionary consequences of parasite manipulation of vector behaviors

Data from: Plant-mediated effects on mosquito capacity to transmit human malaria

The ecological context in which mosquitoes and malaria parasites interact has received little attention, compared to the genetic and molecular aspects of malaria transmission. Plant nectar and fruits are important for the nutritional ecology of malaria vectors, but how the natural diversity of plant-derived sugar sources affects mosquito competence for malaria parasites is unclear. To test this, we infected Anopheles coluzzi, an important African malaria vector, with sympatric field isolates of Plasmodium falciparum, using direct membrane feeding assays. Through a series of experiments, we then examined the effects of sugar meals from Thevetia neriifolia and Barleria lupilina cuttings that included flowers, and fruit from Lannea microcarpa and Mangifera indica on parasite and mosquito traits that are key for determining the intensity of malaria transmission. We found that the source of plant sugar meal differentially affected infection prevalence and intensity, the development duration of the parasites, as well as the survival and fecundity of the vector. These effects are likely the result of complex interactions between toxic secondary metabolites and the nutritional quality of the plant sugar source, as well as of host resource availability and parasite growth. Using an epidemiological model, we show that plant sugar source can be a significant driver of malaria transmission dynamics, with some plant species exhibiting either transmission-reducing or -enhancing activities

Intervention reducing malaria parasite load in vector mosquitoes: No impact on Plasmodium falciparum extrinsic incubation period and the survival of Anopheles gambiae.

In the fight against malaria, transmission blocking interventions (TBIs) such as transmission blocking vaccines or drugs, are promising approaches to complement conventional tools. They aim to prevent the infection of vectors and thereby reduce the subsequent exposure of a human population to infectious mosquitoes. The effectiveness of these approaches has been shown to depend on the initial intensity of infection in mosquitoes, often measured as the mean number of oocysts resulting from an infectious blood meal in absence of intervention. In mosquitoes exposed to a high intensity of infection, current TBI candidates are expected to be ineffective at completely blocking infection but will decrease parasite load and therefore, potentially also affect key parameters of vector transmission. The present study investigated the consequences of changes in oocyst intensity on subsequent parasite development and mosquito survival. To address this, we experimentally produced different intensities of infection for Anopheles gambiae females from Burkina Faso by diluting gametocytes from three natural Plasmodium falciparum local isolates and used a newly developed non-destructive method based on the exploitation of mosquito sugar feeding to track parasite and mosquito life history traits throughout sporogonic development. Our results indicate the extrinsic incubation period (EIP) of P. falciparum and mosquito survival did not vary with parasite density but differed significantly between parasite isolates with estimated EIP50 of 16 (95% CI: 15-18), 14 (95% CI: 12-16) and 12 (95% CI: 12-13) days and median longevity of 25 (95% CI: 22-29), 15 (95% CI: 13-15) and 18 (95% CI: 17-19) days for the three isolates respectively. Our results here do not identify unintended consequences of the decrease of parasite loads in mosquitoes on the parasite incubation period or on mosquito survival, two key parameters of vectorial capacity, and hence support the use of transmission blocking strategies to control malaria

No evidence for manipulation of Anopheles gambiae, An. coluzzii and An. arabiensis host preference by Plasmodium falciparum

We would like to thank all children and their parents for participating in this study, the local authorities for their support, as well as all the volunteers for the dual-port olfactometer assays. We are very grateful to the IRSS staff in Burkina Faso for technical assistance. We also thanks the editor and two anonymous referees for helpful and constructive comments.International audienceWhether malaria parasites can manipulate mosquito host choice in ways that enhance parasite transmission toward suitable hosts and/or reduce mosquito attraction to unsuitable hosts (i.e. specific manipulation) is unknown. To address this question, we experimentally infected three species of mosquito vectors with wild isolates of the human malaria parasite Plasmodium falciparum, and examined the effects of immature and mature infections on mosquito behavioural responses to combinations of calf odour, human odour and outdoor air using a dual-port olfactometer. Regardless of parasite developmental stage and mosquito species, P. falciparum infection did not alter mosquito activation rate or their choice for human odours. The overall expression pattern of host choice of all three mosquito species was consistent with a high degree of anthropophily, with infected and uninfected individuals showing higher attraction toward human odour over calf odour, human odour over outdoor air, and outdoor air over calf odour. Our results suggest that, in this system, the parasite may not be able to manipulate the early long-range behavioural steps involved in the mosquito host-feeding process. Future studies are required to test whether malaria parasites can modify their mosquito host choice at a shorter range to enhance transmission

Mosquito aging modulates the development, virulence and transmission potential of pathogens

&lt;p&gt;Host age variation is a striking source of heterogeneity that can shape the evolution and transmission dynamic of pathogens. Compared to vertebrate systems, our understanding of the impact of host age on invertebrate-pathogen interactions remains limited. We examined the influence of mosquito age on key life-history traits driving human malaria transmission. Females of &lt;em&gt;Anopheles coluzzii&lt;/em&gt;, a major malaria vector, belonging to three age classes (4, 8, and 12 day-old), were experimentally infected with &lt;em&gt;Plasmodium falciparum&lt;/em&gt; field isolates. Our findings revealed reduced competence in 12-day-old mosquitoes, characterized by lower oocyst/sporozoite rates and intensities compared to younger mosquitoes. Despite shorter median longevities in older age classes, infected 12-day-old mosquitoes exhibited improved survival, suggesting that the infection might act as a fountain of youth for older mosquitoes specifically. The timing of sporozoite appearance in the salivary glands remained consistent across mosquito age classes, with an extrinsic incubation period of approximately 13 days. Integrating these results into an epidemiological model revealed a lower vectorial capacity for older mosquitoes compared to younger ones, albeit still substantial due to extended longevity in the presence of infection. Considering age heterogeneity provides valuable insights for ecological and epidemiological studies, informing targeted control strategies to mitigate pathogen transmission.&lt;/p&gt;&lt;p&gt;Funding provided by: Agence Nationale de la Recherche&lt;br&gt;Crossref Funder Registry ID: https://ror.org/00rbzpz17&lt;br&gt;Award Number: grant no.11-PDOC-006-01&lt;/p&gt;&lt;p&gt;Funding provided by: Agence Nationale de la Recherche&lt;br&gt;Crossref Funder Registry ID: https://ror.org/00rbzpz17&lt;br&gt;Award Number: grant no.16-CE35-0007&lt;/p&gt

Field evidence for manipulation of mosquito host selection by the human malaria parasite, Plasmodium falciparum

This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (https://dx.doi.org/10.24072/pci.evolbiol.100057).International audienceWhether the malaria parasite Plasmodium falciparum can manipulate mosquito host choice in ways that enhance parasite transmission toward humans is unknown. We assessed the influence of P. falciparum on the blood-feeding behaviour of three of its major vectors (Anopheles coluzzii, An. gambiae and An. arabiensis) in Burkina Faso. Host preference assays using odour-baited traps revealed no effect of infection on mosquito long-range anthropophily. However, the identification of the blood meal origin of mosquitoes showed that females carrying sporozoites, the mature transmissible stage of the parasite, displayed a 24% increase in anthropophagy compared to both females harbouring oocysts, the parasite immature stage, and uninfected individuals. Using a mathematical model, we further showed that this increased anthropophagy in infectious females resulted in a > 250% increase in parasite transmission potential, everything else being equal. This important epidemiological consequence highlights the importance of vector control tools targeting infectious females

Relationship between parasite density and EIP.

(a) EIP (the time between the infectious blood meal and the detection of P. falciparum in mosquito saliva collected from cotton balls) as a function of gametocytemia (the number of gametocytes per microliter of blood in each of the dilution groups: 24, 45, 48, 72, 91, 98, 136, 261 and 784 gametocytes/μl of blood, note that to avoid overlapping of the x-axis labels, the concentrations of 48 and 91 gam/μl are not indicated). Each colored circle represents an infected mosquito from which EIP was measured (red: parasite isolate A with an initial gametocytemia of 72, green: parasite isolate B with initial gametocytemia of 136, and blue: parasite isolate C with an initial gametocytemia of 784). The x-axis is on a log10 scale. (b) EIP as a function of 1/Ct in mosquito infected heads/thoraxes extracts (the higher the 1/Ct value, the higher the infection intensity). For each cotton ball, 1/Ct value is the average over 3 technical replicates. The colored lines in panels (a) and (b) represent the linear relationship for each parasite isolate. (c) Kaplan–Meier curves representing the temporal dynamics of sporozoite detection in cotton balls used to collect saliva from individual mosquitoes fed on each parasite isolate.</p