Phlebotomines are the sole or principal vectors of Leishmania, Bartonella bacilliformis, and some arboviruses. The coevolution of sand flies with Leishmania species of mammals and lizards is considered in relation to the landscape epidemiology of leishmaniasis, a neglected tropical disease. Evolutionary hypotheses are unresolved, so a practical phlebotomine classification is proposed to aid biomedical information retrieval. The vectors of Leishmania are tabulated and new criteria for their incrimination are given. Research on fly-parasite-host interactions, fly saliva, and behavioral ecology is reviewed in relation to parasite manipulation of blood feeding, vaccine targets, and pheromones for lures. Much basic research is based on few transmission cycles, so generalizations should be made with caution. Integrated research and control programs have begun, but improved control of leishmaniasis and nuisance-biting requires greater emphasis on population genetics and transmission modeling. Most leishmaniasis transmission is zoonotic, affecting the poor and tourists in rural and natural areas, and therefore control should be compatible with environmental conservation.

Biology of Phlebotomine Sand Flies as Vectors of Disease Agents

Background 
Saliva of blood sucking arthropods contains compounds that antagonize their hosts' hemostasis, which include platelet aggregation, vasoconstriction and blood clotting; saliva of these organisms also has anti-inflammatory and immunomodullatory properties. Perhaps because hosts mount an active immune response against these compounds, the diversity of these compounds is large even among related blood sucking species. Because of these properties, saliva helps blood feeding as well as help the establishment of pathogens that can be transmitted during blood feeding.


Methodology/Principal Findings 
We have obtained 1,626,969 reads by pyrosequencing a salivary gland cDNA library from adult females Amblyomma maculatum ticks at different times of feeding. Assembly of this data produced 72,441 sequences larger than 149 nucleotides from which 15,914 coding sequences were extracted. Of these, 5,353 had >75% coverage to their best match in the non-redundant database from the National Center for Biotechnology information, allowing for the deposition of 4,850 sequences to GenBank. The annotated data sets are available as hyperlinked spreadsheets. Putative secreted proteins were classified in 133 families, most of which have no known function.


Conclusions/Significance 
This data set of proteins constitutes a mining platform for novel pharmacologically active proteins and for uncovering vaccine targets against A. maculatum and the diseases they carry.

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A Deep Insight into the Sialotranscriptome of the Gulf Coast Tick, Amblyomma maculatum

Leishmaniasis is a disease that ranges in severity from skin lesions to serious disfigurement and fatal systemic infection. WHO has classified the disease as emerging and uncontrolled and estimates that the infection results in two million new cases a year. There are 12 million people currently infected worldwide, and leishmaniasis threatens 350 million people in 88 countries. Current treatment is based on chemotherapy, which relies on a handful of drugs with serious limitations such as high cost, toxicity, difficult route of administration and lack of efficacy in endemic areas. Vaccination remains the best hope for control of all forms of the disease, and the development of a safe, effective and affordable antileishmanial vaccine is a critical global public-health priority. Extensive evidence from studies in animal models indicates that solid protection can be achieved by immunization with defined subunit vaccines or live-attenuated strains of Leishmania. However, to date, no such vaccine is available despite substantial efforts by many laboratories. The major impediment in vaccine design is the translation of data from animal models to human disease, and the transition from the laboratory to the field. Furthermore, a thorough understanding of protective immune responses and generation and maintenance of the immunological memory, the most important and least-studied aspect of antiparasitic vaccine development, during Leishmania infection is needed. This review focuses on recent findings in antileishmania vaccine field and highlights current difficulties facing vaccine development and implementation.

Leishmaniasis Vaccine: Where are We Today?

Contrary to previous models based on plasma, coagulation processes are currently believed to be mostly cell surface-based, including three overlapping phases: initiation, when tissue factor-expressing cells and microparticles are exposed to plasma; amplification, whereby small amounts of thrombin induce platelet activation and aggregation, and promote activation of factors (F)V, FVIII and FXI on platelet surfaces; and propagation, in which the Xase (tenase) and prothrombinase complexes are formed, producing a burst of thrombin and the cleavage of fibrinogen to fibrin. Thrombin exerts a number of additional biological actions, including platelet activation, amplification and self-inhibition of coagulation, clot stabilisation and anti-fibrinolysis, in processes occurring in the proximity of vessel injury, tightly regulated by a series of inhibitory mechanisms. "Classical" anticoagulants, including heparin and vitamin K antagonists, typically target multiple coagulation steps. A number of new anticoagulants, already developed or under development, target specific steps in the process, inhibiting a single coagulation factor or mimicking natural coagulation inhibitors.

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General mechanisms of coagulation and targets of anticoagulants (Section I). Position Paper of the ESC Working Group on Thrombosis--Task Force on Anticoagulants in Heart Disease.

In the honeybee, Apis mellifera, the queen larvae are fed with a diet exclusively composed of royal jelly (RJ), a secretion of the hypopharyngeal gland of young worker bees that nurse the brood. Up to 15% of RJ is composed of proteins, the nine most abundant of which have been termed major royal jelly proteins (MRJPs). Although it is widely accepted that RJ somehow determines the fate of a female larva and in spite of considerable research efforts, there are surprisingly few studies that address the biochemical characterisation and functions of these MRJPs. Here we review the research on MRJPs not only in honeybees but in hymenopteran insects in general and provide metadata analyses on genome organisation of mrjp genes, corroborating previous reports that MRJPs have important functions for insect development and not just a nutritional value for developing honeybee larvae.

Origin and function of the major royal jelly proteins of the honeybee (Apis mellifera) as members of the yellow gene family.

It has been surprisingly discovered that a sand fly salivary gland polypeptide, or a nucleic acid sequence encoding the polypeptide, can function as an anticoagulant. The present disclosure provides methods of treatment of disorders associated with abnormal coagulation of the blood utilizing compositions that include the sand fly salivary gland polypeptides of the disclosure.

Sand fly salivary proteins as novel factor xa inhibitors and methods of use

The three dimensional structure of an insec yellow/major royal jelly protein family member and its function in blood feeding by the Leishmania vector Lutzomyia longipalpis

It has been surprisingly discovered that a sand fly salivary gland polypeptide, or a nucleic acid sequence encoding the polypeptide, can function as an inhibitor of complement activation. The present disclosure provides for methods of treatment of disorders associated with an immune response associated with increased complement activation utilizing compositions comprising the sand fly salivary gland polypeptides of the disclosure. Also provided herein is the use of sand fly salivary gland anti-complement proteins to block transmission of parasites from sand flies to humans and animals.

Nicolas Collin

Papers

Sand fly salivary proteins as novel factor xa inhibitors and methods of use

The three dimensional structure of an insec yellow/major royal jelly protein family member and its function in blood feeding by the Leishmania vector Lutzomyia longipalpis

Sand fly salivary proteins with anti-complement activity and methods of their use