The discovery of small non-coding RNAs has revolutionized our understanding of regulatory networks governing multiple functions in animals and plants. However, our knowledge of mosquito small RNAs is limited. We discuss here the state of current knowledge regarding the roles of small RNAs and their targets in mosquitoes, and describe the ongoing efforts to understand the role of the RNA interference (RNAi) pathway in mosquito antiviral immunity and transposon silencing. Providing a clear picture into the role of small RNAs in mosquito vectors will pave the way to the utilization of these small molecules in developing novel control approaches that target mosquito immunity and/or reproductive events. Elucidation of the functions of small RNAs represents a new frontier in mosquito biology.

Blood-protein digestion is a key physiological process providing essential nutrients for ticks and is a prerequisite for the transmission of tick-borne pathogens. Recently, substantial progress has been made in determining the proteolytic machinery in tick gut tissue, which is based on a dynamic multienzyme network capable of processing a vast amount of host blood. In this article we summarize our current knowledge of the molecular mechanisms of tick hematophagy and their similarities to those of Platyhelminthes, nematodes, and Plasmodium. Future research perspectives, including the potential for rational control of ticks and transmitted diseases, are also discussed.

The association of contemporary hosts and their parasites might reflect either cospeciation or more recent shifts among existing hosts. Cospeciation implies that lineages of hosts and parasites diverge in parallel at the same time, but testing this prediction requires time-calibrated phylogenies, which are particularly difficult to obtain in organisms that leave few fossils. It has successively become clear that host shifts have been frequent in the evolutionary history of malaria parasites, but dating these host shifts cannot be done without calibrated phylogenies. Hence, it remains unresolved how long contemporary hosts and vectors have been coevolving with their malaria parasites. This review addresses conflicting rate estimates of molecular evolution and suggests research directions to aid dating diversification events in malaria parasites.

The definition of artemisinin resistance is becoming one of a prolonged parasite clearance phenotype, although this variable is a complex function of both host and parasite characteristics. We discuss some of the limitations of this definition of artemisinin resistance, particularly because of its potential global impact. This opinion article reviews the mechanisms underlying parasite clearance after artemisinin treatment and how these might relate to in vitro methods to assay for resistance. It revisits criteria for defining artemisinin resistance that are not currently being applied and suggests the term 'treatment failure of artemisinin combination therapy' (TFACT) as a more accurate description of most cases of 'artemisinin resistance'.

The development of a continuous Plasmodium vivax blood cycle in vitro was first attempted 100 years ago. Since then, and despite the use of different methods, only short-term cultures have been achieved so far. The available literature has been reviewed in order to provide a critical overview of the currently available knowledge on P. vivax blood cycle culture systems and identify some unexplored ways forward. Results show that data accumulated over the past century remain fragmented and often contradictory, making it difficult to draw conclusions. There is the need for an international consortium on P. vivax culture able to collect, update, and share new evidence, including negative results, and thus better coordinate current efforts towards the establishment of a continuous P. vivax culture.

So far, the best immunization strategies to achieve high levels of protection against malaria are based on whole parasites. Complete sterile protection can be obtained in rodent models after immunization with sporozoites and chemoprophylaxis, or with sporozoites attenuated either genetically or by radiation. These approaches target specific stages, with arrests occurring at different time-points of the parasite life cycle. Here, we review these different approaches in relation to their capacity to induce protection in both Plasmodium berghei and Plasmodium yoelii models. The combined data suggest that maximal liver-stage exposure without further development into blood stages may induce the most efficient protection in mice.

The clonal theory of parasitic protozoa has been recently challenged by researchers stating that recombination in Kinetoplastida is much more frequent than previously believed, or that selfing and homogamy should be distinguished from 'strict' clonality. These researchers and many others show that the concept of clonality proposed by us is not correctly understood. A recapitulation of the clonal theory will thus be addressed herein. Comparisons with various other pathogens evidence general features among them and enhance our understanding of Trypanosoma and Leishmania population genetics. The relevance is considerable not only for our knowledge of the basic biology of these organisms but also for applied research: molecular epidemiology (strain-typing), clinical research, vaccine and drug design, and experimental evolution.

Epidemiological studies have demonstrated an association between malaria and invasive non-typhoid Salmonella (NTS) infections, especially in children. We explore the role of iron as a possible cofactor in this association. Malarial disease, among others, is associated with enhanced erythrophagocytosis and inflammation, which increases the iron content of macrophages and thereby also the survival of Salmonella spp. within macrophages. Whether iron supplementation programs augment the risk of invasive NTS infections in malaria-endemic regions is an important global health issue that still needs to be determined.

Bloodstream-form cells of Trypanosoma brucei exhibit massively increased endocytic activity relative to the insect midgut stage, enabling rapid recycling of variant surface glycoprotein and antibody clearance from the surface. In addition, recent advances have identified a role for receptor-mediated endocytosis in the uptake of the antitrypanosomal drug, suramin, via invariant surface glycoprotein 75, and in the uptake of trypanosome lytic factor 1 via haptoglobin-haemoglobin receptor. Here, we argue that receptor-mediated endocytosis represents both a validated drug target and a promising route for the delivery of novel therapeutics into trypanosomes.

The complex biological relationships underlying malaria transmission make it difficult to predict the impact of interventions. Mathematical models simplify these relationships and capture essential components of malaria transmission and epidemiology. Models designed to predict the impact of control programs generally infer a relationship between transmission intensity and human infectiousness to the mosquito, requiring assumptions about how infectiousness varies between individuals. A lack of understanding of human infectiousness precludes a standard approach to this inference, however, and field data reveal no obvious correlation between transmission intensity and human population infectiousness. We argue that model assumptions will have important consequences for predicting the impact of control programs.