Relationship between body size of adult Anopheles gambiae s.l. and infection with the malaria parasite Plasmodium falciparum

The influence of adult female body size of Anopheles gambiae s.l. on development of midgut and salivary gland infections by the parasite Plasmodium falciparum was investigated in a field study carried out in Tanzania. The proportion of mosquitoes infected during a blood meal was independent of size. However, the number of oocysts harboured by infected mosquitoes increased with size of the mosquito. The proportion of mosquitoes with sporozoites, and thus potentially infective to humans, was highest in intermediate-sized mosquitoes, whereas the largest and smallest mosquitoes were less likely to have sporozoites. This pattern is interpreted as a combination of high survival rate of large, uninfected mosquitoes and of low survival rate of mosquitoes infected with many oocyst

Overloading the immunity of the mosquito Anopheles gambiae with multiple immune challenges

BACKGROUND: Melanisation – the production and deposition of a layer of melanin that encapsulates many pathogens, including bacteria, filarial nematodes and malaria parasites is one of the main immune responses in mosquitoes. Can a high parasite load overload this immune response? If so, how is the melanisation response distributed among the individual parasites? METHODS: We considered these questions with the mosquito Anopheles gambiae by inoculating individuals simultaneously with one, two or three negatively charged Sephadex beads, and estimating the melanisation as the darkness of the bead (which ranges from about 0 for unmelanised beads to 100 for the most melanised beads of our experiment). RESULTS: As the number of beads increased, the average degree to which beads were melanised decreased from 71 to 50. While the darkness of the least melanised bead in a mosquito decreased from an average of 71 to 35, the darkness of the most strongly melanised one did not change with the number of beads. CONCLUSIONS: As the number of beads increased, the mosquito’s immune response became overloaded. The mosquito’s response was to prioritise the melanisation of one bead rather than distributing its response over all beads. Such immune overloading may be an important factor underlying the evolution of resistance against vector-borne diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-016-1491-8) contains supplementary material, which is available to authorized users

Parasite Evolution and Life History Theory

Beth F. Kochin is with Emory University, James J. Bull is with UT Austin, Rustom Antia is with Emory University.As a group, parasites are extraordinarily diverse. Even closely related parasites may behave very differently, infecting different host species, causing different pathologies, or infecting different tissues. For example, Escherichia coli bacteria, a typically harmless inhabitant of the human gut, can, in different forms, cause diarrhea, intestinal bleeding, urinary tract infections, kidney bleeding, meningitis, and other diseases. Underlying this diversity is evolution.This work is supported by the National Institutes of Health and the Fannie and John Hertz Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Cellular and Molecular Biolog

Maternal environment shapes the life history and susceptibility to malaria of Anopheles gambiae mosquitoes

BACKGROUND: It is becoming generally recognized that an individual's phenotype can be shaped not only by its own genotype and environmental experience, but also by its mother's environment and condition. Maternal environmental factors can influence mosquitoes' population dynamics and susceptibility to malaria, and therefore directly and indirectly the epidemiology of malaria. METHODS: In a full factorial experiment, the effects of two environmental stressors - food availability and infection with the microsporidian parasite Vavraia culicis - of female mosquitoes (Anopheles gambiae sensu stricto) on their offspring's development, survival and susceptibility to malaria were studied. RESULTS: The offspring of A. gambiae s.s. mothers infected with V. culicis developed into adults more slowly than those of uninfected mothers. This effect was exacerbated when mothers were reared on low food. Maternal food availability had no effect on the survival of their offspring up to emergence, and microsporidian infection decreased survival only slightly. Low food availability for mothers increased and V. culicis-infection of mothers decreased the likelihood that the offspring fed on malaria-infected blood harboured malaria parasites (but neither maternal treatment influenced their survival up to dissection). CONCLUSIONS: Resource availability and infection with V. culicis of A. gambiae s.s. mosquitoes not only acted as direct environmental stimuli for changes in the success of one generation, but could also lead to maternal effects. Maternal V. culicis infection could make offspring more resistant and less likely to transmit malaria, thus enhancing the efficacy of the microsporidian for the biological control of malaria

Genetic variation of male reproductive success in a laboratory population of Anopheles gambiae

<p>Abstract</p> <p>Background</p> <p>For Anopheline mosquitoes, the vectors of human malaria, genetic variation in male reproductive success can have important consequences for any control strategy based on the release of transgenic or sterile males.</p> <p>Methods</p> <p>A quantitative genetics approach was used to test whether there was a genetic component to variation in male reproductive success in a laboratory population of <it>Anopheles gambiae</it>. Swarms of full sibling brothers were mated with a fixed number of females and their reproductive success was measured as (1) proportion of ovipositing females, (2) proportion of ovipositing females that produced larvae, (3) proportion of females that produced larvae, (4) number of eggs laid per female, (5) number of larvae per ovipositing female and (6) number of larvae per female.</p> <p>Results</p> <p>The proportion of ovipositing females (trait 1) and the proportion of ovipositing females that produced larvae (trait 2) differed among full sib families, suggesting a genetic basis of mating success. In contrast, the other measures of male reproductive success showed little variation due to the full sib families, as their variation are probably mostly due to differences among females. While age at emergence and wing length of the males were also heritable, they were not associated with reproductive success. Larger females produced more eggs, but males did not prefer such partners.</p> <p>Conclusion</p> <p>The first study to quantify genetic variation for male reproductive success in <it>A. gambiae </it>found that while the initial stages of male reproduction (i.e. the proportion of ovipositing females and the proportion of ovipositing females that produced larvae) had a genetic basis, the overall reproductive success (i.e. the mean number of larvae per female) did not.</p

A Possible Mechanism for the Suppression of Plasmodium berghei Development in the Mosquito Anopheles gambiae by the Microsporidian Vavraia culicis

BACKGROUND: Microsporidian parasites of mosquitoes offer a possible way of controlling malaria, as they impede the development of Plasmodium parasites within the mosquito. The mechanism involved in this interference process is unknown. METHODOLOGY: We evaluated the possibility that larval infection by a microsporidian primes the immune system of adult mosquitoes in a way that enables a more effective anti-Plasmodium response. To do so, we infected 2-day old larvae of the mosquito Anopheles gambiae with one of 4 isolates of the microsporidian Vavraia culicis and reared one group as an uninfected control. Within each treatment, we fed half the adult females on a mix of P. berghei ookinetes and blood and inoculated the other half with a negatively charged CM-25 Sephadex bead to evaluate the mosquitoes' melanisation response. CONCLUSIONS: The microsporidian-infected mosquitoes were less likely to harbour oocysts (58.5% vs. 81.8%), harboured fewer oocysts (8.9 oocysts vs. 20.7 oocysts) if the malaria parasite did develop and melanised the Sephadex bead to a greater degree (73% vs. 35%) than the controls. While the isolates differed in the number of oocysts and in the melanisation response, the stimulation of the immune response was not correlated with either measure of malaria development. Nevertheless, the consistent difference between microsporidian-infected and -uninfected mosquitoes--more effective melanisation and less successful infection by malaria--suggests that microsporidians impede the development of malaria by priming the mosquito's immune system

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

<p>Abstract</p> <p>Background</p> <p>The 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 <it>Plasmodium berghei </it>through <it>Anopheles stephensi </it>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.</p> <p>Methods</p> <p>An 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.</p> <p>Results</p> <p>The 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.</p> <p>Conclusions</p> <p>A 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 <it>Plasmodium </it>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.</p

Challenges in Estimating Insecticide Selection Pressures from Mosquito Field Data

Insecticide resistance has the potential to compromise the enormous effort put into the control of dengue and malaria vector populations. It is therefore important to quantify the amount of selection acting on resistance alleles, their contributions to fitness in heterozygotes (dominance) and their initial frequencies, as a means to predict the rate of spread of resistance in natural populations. We investigate practical problems of obtaining such estimates, with particular emphasis on Mexican populations of the dengue vector Aedes aegypti. Selection and dominance coefficients can be estimated by fitting genetic models to field data using maximum likelihood (ML) methodology. This methodology, although widely used, makes many assumptions so we investigated how well such models perform when data are sparse or when spatial and temporal heterogeneity occur. As expected, ML methodologies reliably estimated selection and dominance coefficients under idealised conditions but it was difficult to recover the true values when datasets were sparse during the time that resistance alleles increased in frequency, or when spatial and temporal heterogeneity occurred. We analysed published data on pyrethroid resistance in Mexico that consists of the frequency of a Ile1,016 mutation. The estimates for selection coefficient and initial allele frequency on the field dataset were in the expected range, dominance coefficient points to incomplete dominance as observed in the laboratory, although these estimates are accompanied by strong caveats about possible impact of spatial and temporal heterogeneity in selection

Modelling the impact of intermittent preventive treatment for malaria on selection pressure for drug resistance

BACKGROUND: Intermittent preventive treatment (IPT) is a promising intervention for malaria control, although there are concerns about its impact on drug resistance. METHODS: The key model inputs are age-specific values for a) baseline anti-malarial dosing rate, b) parasite prevalence, and c) proportion of those treated with anti-malarials (outside IPT) who are infected. These are used to estimate the immediate effect of IPT on the genetic coefficient of selection (s). The scenarios modelled were year round IPT to infants in rural southern Tanzania, and three doses at monthly intervals of seasonal IPT in Senegal. RESULTS: In the simulated Tanzanian setting, the model suggests a high selection pressure for drug resistance, but that IPTi would only increase this by a small amount (4.4%). The percent change in s is larger if parasites are more concentrated in infants, or if baseline drug dosing is less common or less specific. If children aged up to five years are included in the Tanzanian scenario then the predicted increase in s rises to 31%. The Senegalese seasonal IPT scenario, in children up to five years, results in a predicted increase in s of 16%. CONCLUSION: There is a risk that the useful life of drugs will be shortened if IPT is implemented over a wide childhood age range. On the other hand, IPT delivered only to infants is unlikely to appreciably shorten the useful life of the drug used