The More Familiar Mosquito & the Less Familiar Sand Fly Operate as Disease Vectors Using Similar Strategies
Few people in the modern western world, especially in its northern latitudes, have heard of sand flies or Leishmaniasis (named after a Scottish medical researcher, William Leishman), but many more are likely to become aware of both of them, owing to some changes in the world’s medical geography and epidemiology.
Fortunately, by applying some of their understanding of the mosquito’s propensity for transmittal of malaria, one can gain a basic insight into why and how sand flies can transmit Leishmaniasis.
Most scientifically-literate people today understand that malaria is a disease carried by infected female mosquitoes, and transmitted to biting victims during the mosquito’s biting of humans and other warm-blooded animals, in their quest for a blood meal.
Female mosquitoes need that blood meal in order to have more vigorous eggs with protein supplies that are adequate for viability.
When setting up the bite, the mosquitoes initially transmit some enzymes that keep the victim’s blood flow going, so that the wound does not close off, clot, and prematurely deprive them of that necessary blood.
Coincidentally, during the biting and enzyme injection prior to the blood withdrawal, the mosquitoes also transfer any malarial protozoan parasites they have contracted on their travels from blood source to blood source.
Mosquitoes can certainly live and reproduce without the parasites, and not all mosquitoes are even capable of carrying these parasites.
But the more animals and humans that are around to be bitten that already have malarial parasites in their blood stream, the more likely it is that other animals and humans without the parasites, will get them once the mosquito bites the “wrong” victim before he gets to the uninfected victim, and bites him or her.
Sand Flies
Like the mosquitoes, not all sand flies can carry the disease of Leishmaniasis, and about a third of the known species of sand flies do not.
But those sand flies that can carry Lesihmaniasis are almost as ubiquitous as malaria-carrying mosquitoes.
Since sand flies are only about a third as large as mospquitoes, many of their victims do not initially notice that they have been bitten.
Many sites where humans have been bitten show no signs of a wheal such as are seen with mosquito bites, and those lesions that do develop often take weeks or months, although some people have an essentially allergic blistering reaction that is more obvious.
Both mosquitoes and sand flies favor hotter climates, although the sand fly does not need the abundance of water most commonly associated with mosquitoes and their larvae.
The primary areas of sand fly infestation in the Old World are Central Asia (including especially Iraq, Iran, & Afghanistan), portions of South East Asia, and Northern Africa.
However, Southern Europe, including Italy, Southern France, Spain, Portugal, and Greece, are seeing a resurgence of sand flies and Leishmaniasis, and even Northern & Central Europeans are coming down with it, after decades and indeed, sometimes centuries without cases in a given district.
The variety of sand flies that carry Leishmaniasis in the Old World are from the subfamily called the Phlebotominae.
Both of the Americas have sand flies, although Latin America, and especially Brazil, has the greatest concentration of both vectors and Leishmaniasis by far.
The variety of sand flies that carry Leishmaniasis in the New World are from the subfamily Lutzomyia.
The Varieties of Leishmaniasis
Despite the differences of insect variety and even species differences in the particular parasites, the major types, signs and symptoms of Leishmaniasis disease are essentially the same in both Hemispheres.
The most common type is cutaneous Leischmaniasis. About 1.5 million new cases are estimated worldwide each year of this type, and about 12 millions cases seem recurrent or chronic.
The typical manifestation of this disease are bulbous swelling and sometimes subsequent collapse and disfiguring erosion of the skin, much as seen in leprosy.
The lesions can look ghastly but many victims report that they are relatively painless, and even without medical treatment, a substantial portion of them resolve over the course of some months. (The painlessness of many cases is hypothesized to be owing to a mild neurotoxic effect of the sand fly salivary enzymes.)
Those that do not resolve typically have two follow-on courses.
The most common, and even more disfiguring sequelae or variant is muco-cutaneous Leishmaniasis. Here the mouth and nose become bulbous or cratered and less reversibly disfigured. Victims often become social pariah.
But by far the most serious type (and it is not clear that this must be preceded by the cutaneous type in many cases) is called visceral Lesihmaniasis. Unlike cutaneous and even muco-cutaneous Leishmaniasis, this type is very often fatal in the half a million cases that start anew each year.
Visceral Leishmaniasis is characterized by the swelling of organs under the the skin and massive bloating of body parts, particularly the liver and the spleen. Internal bleeding and multi-organ system failure are the proximate causes of death.
The theory of why some patients develop the cutaneous or muco-cutaneous forms while others develop the far more serious visceral type, tends to revolve around the types and amounts of very potent blood-clot busting salivary gland-produced enzyme, maxadilan, that are found in the particular species of sand fly that does the biting.
It seems that those species with the most maxadilan, or with the maxadilan molecular conformations that are the most potent, disproportionately cause the visceral type, while those with less maxadilan or with maxadilan of a milder conformation, seem to cause the cutaneous and muco-cutaneous types.
A curious connection has been found between areas of the world where aluminum ions are abundant in the soils and water, and either the sand flies or the victims, an increased incidence or severity of Leishmaniasis, but this is, as yet, a side show compared to other lines of investigation.
Prevention and Chemotherapy of Leishmaniasis
Much as is the case with malaria, an ounce of prevention of sand fly prevention is worth more than a pound of Leishmaniasis cure.
Owing to current military deployments today, the US Army and Marine Corps are perhaps the most aggressive researchers and practitioners of sand fly exposure reduction today. (see Vickery et al., 2008, cited below)
The most common Lesihmaniasis preventatives are the liberal use of bodily applications of DEET, and wearing clothing that covers as much of the body as the usually intense heat of the climate allows for.
Netting, which must be as much as 3x as fine in mesh, and treated with insecticide, has shown a good deal of efficiency.
Fortunately, sand flies have not developed as many cases of resistance to insecticides as have mosquitoes and a relatively wide assortment can still be sprayed to good effect.
Now, there is a great deal of interest in identifying sand fly pheromones and using them to trap the sand flies, keeping them out of homes and tents altogether.
The news has not been as good with drugs after infection.
Some critics suggests that this is because the overwhelming proportion of Lesihmaniasis sufferers are desperately poor individuals in Third World countries, who are unlikely to be able to repay the drug discovery companies for the cost of developing new and better drugs.
Nonetheless, new drugs do come out intermittently, when governments provide incentives to investigate and manufacture anti-Leishmanials under “orphan drug” incentives.
Traditionally, the most commonly used drugs involve antimony-containing compounds. They require admission to a clinic for safe administration, are potentially toxic, expensive and have begun to lose their effectiveness on some subtypes of Leishmaniasis.
The antibiotic amphotericin has become a second line choice, and its cost has come down. Nonetheless, it is still generally administered by IVs performed in clinics, making it still rather expensive for patients who must stop work and travel many miles, often over days.
Curiously, the particular effectiveness of amphotericin for Lesihmaniasis was discovered in patients with AIDS and opportunistic bacterial infections who coincidentally also had Leishmaniasis.
It has likewise proved useful for those IV drug addicts who contract Leishmaniasis through sharing needles.
Milotefosine is a follow-on drug that has received World Health Organization backing, and is taken orally. Its cost is yet even more reasonable, but it too has run into some resistance problems.
There is an acceleration of interest and research in developing vaccines, particularly those that short-circuit the salivary proteins whose enzymes keep the skin’s blood flow from clotting so that the sand fly can obtain its blood meal before it clots.
The process by which salivary maxadilan proteins are synthesized in the sand fly and its mechanism of dispersal in its victim are increasingly well understood, and targeting these processes on a proteomic or transcriptomic scale provides hope for the future.
Will Leishmaniasis become prevalent again in the Northern latitudes of the economically advanced world, for example, in the US?
A disproportionate number of cases of Leishmaniasis cases in Southern and Central Europe seem to involve natives who have returned from vacationing in Lesihmaniacal endemic hot zones, as well as the influx of recent immigrants from those areas.
Livestock, and companion animals, particularly dogs, also seem to be reservoirs of the parasites.
Once again, infected people or animals, provide a home for the parasite, and local sand flies can themselves become infected by “foreign Leishmaniasis” parasites through biting an infected person, and then pass it on to uninfected individuals through subsequent bites.
In the US, although there has always been a small number of Leishmaniasis cases in the Mid-South (e.g. Texas, Arkansas, Louisiana), a spike has been predicted owing to the number of veterans returning home form service in Iraq and Afghanistan.
1300 US soldiers and marines have already contracted Leishmaniasis in these countries and it cannot always be detected or treated before these troops return home.
However, in one of the most intriguing studies (Claborn et al., 2008, cited below) it was determined that between two forts where many soldiers return from tours of duty in Iraq and Afghanistan, one had an environment that was conducive to sand flies, while the other one did not.
Fort Bragg in North Carolina is surrounded by cultivated pine forest, and well-plowed farms. While the heat there is sufficient to sustain a significant sand fly population, these two types of ground cover do not.
By contrast, Fort Campbell in Kentucky is characterized by deciduous forests and prairie land, which are not only hot enough to sustain a sand fly population, but which both have the right vegetation and ground cover to help sand flies thrive.
Here’s hoping that biomedical librarians everywhere become increasingly proficient in the use of the first weapon against Leishmaniasis, credible scientific and clinical information.
Tony Stankus [email protected] Life Sciences Librarian & Professor
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Alvar, J. & Jimenez, M. (1994). Could infected drug-users be potential Leishmania infantum reservoirs? AIDS, 8, 854.
Alvar, J., Yactayo, & Bern, C. (2006). Leishmaniasis and poverty. Trends in Parasitology, 22, 552-7.
Andrade BB, de Oliveira CI, Brodskyn, C. , Barral, A., et al. (2007). Role of sand fly saliva in human and experimental Leishmaniasis: Current insights. Scand J Immunol. 66, (2-3), 122-7.
Bates PA. Transmission of Leishmania metacyclic promastigotes by phlebotomine sand flies. (2007). Int J Parasitol. 37(10):1097-106.
Bates, P. A. (2008). Leishmania sand fly interaction: Progress and challenges. Current Opinion in Microbiology, 11(4), 340-344.
Champagne, D.E. (2005). Antihemostatic molecules from saliva of blood-feeding arthropods. Pathophysiology of Haemostasis & Thrombosis, 34 (4-5), 221-7.
Claborn, D., Masuoka, P., Morrow, M. & Keep, L. (2008). Habitat analysis of North American sand flies near veterans returning from Leishmaniasis-endemic war zones. International Journal of Health Geographics, 7, article number 65.
Cortes, S., Afonso, M.O., Alves-Pires, C. & Campino, L. (2007). Stray dogs and Leishmaniasis in urban areas. Emerging Infectious Diseases, 13, 1431-2.
Croft, S.L., Sundar, S., Fairlamb, AH. 2006. Drug resistance in Leishmaniasis. Clinical Mircrobiological Reviews, 19, 111-6.
Dujardin JC, FAU - Campino, L., Campino L, Canavate, C., Dedet, J., et al. (2008). Spread of vector-borne diseases and neglect of Leishmaniasis, Europe. Emerg Infect Dis. 14, (7):1013-8.
Gomes, R., Teixeira, C., Teixeira, M.J., et al. (2008). Immunity to a salivary protein of a sand fly vector protects against the fatal outcomes of visceral Leishmaniasis in a hamster model. Proceedings of the National Academy of Sciences, 195, (22), 7845-7850.
Hamilton JG. (2008). Sand fly pheromones: Their biology and potential for use in control programs. Parasite 15(3):252-6.
Joshi A, FAU - Narain, J. P., Narain JP, Prasittisuk, C., Bhatia, R., et al. (2008). Can visceral Leishmaniasis be eliminated from Asia? J Vector Borne Dis. 45, (2):105-11.
Kassi M, FAU - Kasi, P. M., Kasi PM, FAU - Marri, S. M., Marri SM, FAU - Tareen, I., et al. 2008. Vector control in cutaneous leishmaniasis of the old world: A review of literature. Dermatol Online J. 14, (6):1.
Kedzierski L, Zhu, Y., Zhu Y, Handman, E., & Handman E. (2006). Leishmania vaccines: Progress and problems. Parasitology 133 Suppl., S87-112.
Khatami A, FAU - Firooz, A., Firooz A, Gorouhi, F., Gorouhi F, Dowlati, Y., et al. Treatment of acute old world cutaneous Leishmaniasis: A systematic review of the randomized controlled trials. J Am Acad Dermatol. 57, (2):335.e1-29.
Kumari, S., Kumar, A., Samant, M. et al. (2008). Proteomic approaches for discovery and new targets for vaccine and therapeutics against visceral Lesihmaniasis. Proteomics: Clinical Applications, 2, (3), 372-386.
Lerner EA, Iuga, A. O., Iuga AO, & Reddy VB. 2007. Maxadilan, a PAC1 receptor agonist from sand flies. Peptides 28, (9):1651-4.
Lines, J. Chikununya in Italy: Globalisation is to blame, not climate change. BMJ, 335, 576.
Maingnon, R., Khela, A., Sampson, C. et al. (2008). Aluminum: A natural adjuvant in Leishmania transmission via sand flies? Transactions of the Royal Societyof Tropical Medicine & Hygiene, 102 (11), 1140-2.
Malik, A.N.J., John, L. Bryceson, A.D.M. & Lockwood, D.N.J. (206). Changing pattern of visceral leishmaniasis, UK, 1985-2004. Emerging Infectious Disease, 12, 1257-9.
Milon, G. (2008). Leishmania parasites: Could we consider them as living organisms per se? Microbes and Infection, 10(9), 1077-1081.
Oliveira, LF., Jochim, R.C., Valenzuela, J.G. et al. 2009. Sand flies, Leishmania, and transcriptome-borne solutions. Parasitology International, 58, (1), 1-5.
Prates, D.B., Santos, L.D., Miranda, J.C. et al. (2008). Changes in the amounts of total salivary gland proteins of Lutomyia longipalpis (Diptera: Psychodidae) according to age and diet. Journal of Medical Entomology, 45, (3), 409-413.
Rando, D. G., Avery, M. A., Tekwani, B. L., Khan, S. I., & Ferreira, E. I. (2008). Antileishmanial activity screening of 5-nitro-2-heterocyclic benzylidene hydrazides. Bioorganic & Medicinal Chemistry, 16(14), 6724-6731.
Ready, P. D. (2008). Leishmaniasis emergence and climate change. Revue Scientifique et Technique-Office International Des Epizooties, 27, (2), 399-412.
Reddy VB, FAU - Li, Y., Li Y, & Lerner EA. (2008). Maxadilan, the PAC1 receptor, and leishmaniasis. J Mol Neurosci., 36(1-3):241-4.
Reithinger R, FAU - Dujardin, J., Dujardin JC, FAU - Louzir, H., Louzir H, FAU - Pirmez, C., et al. (2007). Cutaneous leishmaniasis. Lancet Infect Dis., 7, (9), 581-96.
Valenzuela, J.G., Garfield, M., Rowton, E.D. & Pham, V.M. (2004). Identification of the most abundantly secreted proteins from the salivary glands of the sand fly, Lutzomyia longipalpis, vector of Leishmania chagasi. Journal of Experimental Biology, 207, (21), 3717-3729.
Vickery, J.P., Tribble, D.R., Putnam, S.D., McGraw, T., Sanders, J.W., Armstrong, A.W., & Riddle, M.S. (2008). Factors associated with the use of protective measures against vector-borne diseases among troops deployed to Iraq and Afghanistan. Military Medicine, 173, (11), 1060-1067.
Volf, P., Hostomska, J., & Rohousova, I. (2008). Molecular crosstalks in Leishmania-sand-fly-host relationships. Parasite, 15(3), 237-243.
Wheat, W. H., Pauken, K. E., Morris, R. V., & Titus, R. G. (2008). Lutzomyia longipalpis salivary peptide maxadilan alters murine dendritic cell expression of CD80/86, CCR7, and cytokine secretion and reprograms dendritic cell-mediated cytokine release from cultures containing allogeneic T cells. Journal of Immunology, 180, (12), 8286-8298.
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