Leishmaniasis
By Matthew Sweetman, Honors Biology, Period 6
Leishmaniasis (LEESH-MUH- NIGH-UH-SIS) is a pestilential parasitic disease spreading heavily throughout the world, leaving it's victims in anguish. This is most apparent in the countries of Pakistan, Afghanistan, India, and Brazil, to name a few. Leishmaniasis manifests in nearly a dozen forms, including cutaneous and visceral leishmaniasis, which are the most common. The quintessential symptom is lesions/ulcers on the hands, feet, arms, legs, face; almost anywhere on the skin. These can range from a minor annoyance to excrutiatingly painful, depending on location and severity. The disease is spread by the bite of insects, most commonly sandflies, and is highly infectious. Leishmaniasis is considered an emerging disease, with a plethora of health agencies and organizations stressing an imperative need for the general public to be informed about the disease, especially where it is most present.
Background info: Leishmaniasis is a menacing disease, with over 2 million new cases emerging worldwide annually and about a billion people being at a considerable risk for it(Peacock, 2007,1). It was first proposed and exemplified by two men(not working cooperatively) named Leishman and Donovan in 1903(Markle, 2004, 51). It is spread most commonly through the bite of the sandfly, either from the Phlebotomus papatasi, Phlebotomus sergenti, and Phlebotomus salehi genuses(Rahman, 2008, 33). Depending on what type of leishmaniasis you're infected with and the ability of your immune system to fight infection, the disease manifests itself in many different ways. For example, the cutaneous form may present with symptoms as minor as a innocuous sore near a gland or as serious as an excruciatingly painful ulcer on the skin(CDC, 2009, 69). Visceral Leishmaniasis can present with fever, weight loss, and hepatosplenomegaly(a concurrent growth of both the spleen and the liver within a person) (Markle, 2004, 51).
Here's how the Leishmania parasite works. The leishmania have 2 paramount life cycles in their terms of infection: Their time as a promastigote within the sandfly carrier, and living in phagolysosomal vesicles of the host organism as an amastigote( Landfear, 2008, 13). In terms of physical description, the promastigotes are slim, almost sunflower seed-like cells with one flagella whereas the amastigotes are tiny cells that lack a primary flagella, and therefore lack the agility of the promastigotes(Landfear, 2008, 14). The parasite begins infection by entering a macrophage attempting to destroy it, using binary fission to reproduce itself, and spreading to other cells by identical methods(Muneeb, 2006, 43).
Like all parasites, Leishmania is completely and unequivocally dependent on it's host organism for the necessties of life(Landfear, 2008, 15). They receive their nutrients from cells called transporters, which collect nutrients from the host cells and deliver them to the parasite cell(Landfear, 2008, 15). Another nutrient that the parasite microbe constantly needs is a purine; but seeing as the protozoa cannot produce purines themselves, they rely completely on the host for them.(Landfear, 2008, 17). This desperate need also presents a unique and possibly invaluable future treatment option; blocking the parasite from it's purine source, thus killing it.
Also, recent experiments have suggested that glucose is also extremely important for this protozoa. This conclusion was reached from a study in which a leishmania parasite was grown through its promastigote and amastigote stages in a lab, thus allowing the microbe to be mutated. In this case, the parasite was created as empty and purposeless, as it was unable to absorb glucose, fructose, maltose, etc. But because of this deprivation, the parasite could not make it past the amasitgote stage, and died. This experiment and its results suggest that depriving the cell of glucose in its promastigote stage can inhibit its growth and therefore, eradicate it(Landfear, 2008, 20).
Epidemiology: Leishmaniasis is a rapidly growing disease, although mostly in third world and/or developing countries such as Pakistan, Afghanistan, Sudan, Peru, Bangladesh, India, and Syria(CDC, 2009, 55). You may have noticed that these are all fairly warm-weathered countries, but this is not suspected to be a factor. The reason for this being that the sandflies, the organisms that spread the disease, are generally not active during the hotter parts of the day, but more between sunset and sunrise, when it tends to be cooler(CDC, 2009, 56). This disease in found endemically in about 88 different countries around the world, almost invariably in specific areas, not the country as a whole(Muneeb,2006, 40). Although within these areas, the amount of infections is usually tremendous. The amount of novel cases per year in the world is put at around 2 million; 1.5 million for cutaneous leishmaniasis, and 500,000 for visceral(CDC, 2009, 67). This disease also has no quintessential age range, it can manifest itself into any person, at any age, at any area (where an appropriate vector is present), at any time.
Diagnosis: This disease shares traits with many other diseases, making it very tricky to diagnosis. Leishmaniasis and its variants are commonly mistaken for: blastomycosis( a fungal skin infection), histoplasmosis( a fungal disease of the lungs), Wegener's granulomatosis( a vasculital inflammation of blood vessels), paracoccidioidomycosis( a more severe form of blastomycosis), and eczema( a simple allergic reaction causing bumps on the skin), to name a few(Markle, 2004, 70). Due to it's characteristics, such as ulcers, lesions, unexplained bumps, and other dermatological symptoms, Leishmaniasis is also mistaken for many cancers and autoimmune diseases. These reasons and many others just like it are why venerable physicians and/or dermatologists are imperatively needed to diagnose the disease correctly. This can prevent toxicity and other, more serious problems from mistreatment.
The methods by which leishmaniasis is diagnosed include biopsy of infected area, needle aspirate, monoclanal antibodies, and a slit-skin smear (Muneeb, 2006, 71). A biopsy for leishmaniasis consists of the cleaning of a selected lesion with a 70% ethyl alcohol or .9% saline solution, a shot of adrenaline(epinephrine) and 2% lidocaine to supress pain for the patient, and then the actual sample is extracted (Muneeb, 2006, 46). Once the sample is taken, the sample is carefully rubbed against a microscope a few times, dried, and set in 95% ethanol for a minute or 2 (Muneeb, 2006, 47). It is then marked with a Giemsa or H & E solution and visually scanned under a microscope by the physician for the amastigotes of the parasite.
Treatment: Leishmaniasis has many different treatments, all which vary in their efficacy and practicality, seeing as how the majority of cases occur in areas that are not very privileged in the field of medicine. Seeing as how the cutaneous form commonly heals itself, the focus for new medicines is put more on treatment of the more severe visceral form and infection in the immuno-compromised populations. Sodium Stibogluconate and Meglumine Antimoniate, two medicines invented in France in the 1940's, are the archetypal treatments of visceral leishmaniasis in the more poverty-stricken areas of the world, as they are cheap and usually affective( Muneeb, 2006, 48). These medicines are given through intravenous injection, a process that takes 2 weeks in order to achieve full efficacy, but they can be and usually are significantly toxic (Muneeb, 2006, 72). The symptoms from toxicity from these medicines can include: anorexia (decreased appetite) , myalgia (muscle pains), and malaise (general discomfort); which can lead to chemical pancreatitis (inflammation of the pancreas) , leukopenia (loss of some white blood cells) , and thrombocytopenia (a decrease in blood platelets) (Muneeb, 2006, 72). These symptoms are normally nothing to be overly concerned about, but they are much more serious to leishmaniasis victims. The reason being that the ulcers and lesions that leishmaniasis bring provide an entry point for opportunistic infections, and having a secondary infection while having these symptoms can be virulent.
There are also many experimental treatments (seeing as how this disease is endemic in over 80 countries in a world with little more than 200) in development such as rifamipicin, aminosidine, pentamidine, ketoconazole, and miltefosine (Muneeb, 2006, 73). The most seemingly effective of which is miltefosine, which proved itself in a study in Colmbia, in which 2 groups infected with leishmaniasis were given 133 mg and 150 mg per day, every day for 4 weeks (Muneeb, 2006, 74). Of those treated with 133 mg, 100% were cured, with 89% for the 150 mg (Muneeb, 2006, 74).
Possible effects of the disease: Leishmaniasis results vary from full recovery to cataclysmic consequences and even death, especially the visceral manifestations. These results can include but are not limited to: a self-healing ulcer and/or dermatological lesion(s), scars from healed lesions, hepatosplenmegaly, severe weight loss, multiple organ failures, cancers, coma, and even death(Markle, 2004, 51). Relapses of all types of Leishmaniasis are very common about 3-6 months after the primary infection, and are often worse than the initial infection, leading to a need for a meticulous subsequent treatment(Muneeb, 2006, 49).
Prevention: Leishmaniasis is a fairly easy disease to prevent. Because sandflies are most active between dusk and dawn, activity during those hours while in a country where the disease is prevalent is not advised. Also, it is wise to keep your skin as least exposed as you possibly can, and regularly use insect repellents (preferably those that use the chemical DEET) (CDC, 2009, 58). When indoors, stay in cooler areas, spray the aforementioned repellents onto any and all living areas, and do not wear clothes after 5 washes. Also, learn to appreciate the fact that sand flies( the insects that spread the disease) are much smaller than mosquitoes, and can therefore can fit into smaller spaces (CDC, 2009, 59).
New treatments: Because Leishmaniasis poses such a daunting threat, newer, more effective treatments are seriously needed. The newest of which include a gene targeting of the DNA of the parasite, Leishmania, and using peptidases as growth and malignancy inhibitors in Leishmaniasis. The former of which includes identifying genes and their functions, then determining which genes are most paramount, and finally, inhibiting those genes. This is made easy because a recent study has shown that even though there are over 8,000 genes in the leishmania genome, only about 20 are delineated between the separate species ( Peacock, 2007,2). For example, the CFAS (cyclopropane fatty acid synthase) enzyme, which probably functions in the creation of the plasma membrane of the microbe, is a possible target for inhibition. (Peacock, 2007,5).
The use of peptidases to inhibit growth and virulence in Leishmaniasis is also a developing treatment. This process consists of studying the functions and routines of petidases in the parasite and using natural inhibitors on these peptidases. For example, an inhibitor of the Cytesine peptidase is being researched. If successful, this inhibitor will disable the connection between the host and the parasite, ending the parasite's life within days or even hours ( Mottram, 2010, 12).
FAQs: The possibility of having Leishmaniasis can be pretty scary, but with the right information and a well-informed public, it can be treated quicker and much more effectively. Some of the most frequently asked questions (FAQs) include but are not limited to the following:
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1. Q: What are the types of Leishmaniasis?
A: Leishmanisis presents in many shapes and forms. The two most common are by far and wide the cutaneous and visceral forms (CDC, 2009, 68) Other types include mucocutaneous, viscerotopic, and post-kala-azar dermal leishmaniasis.
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2. Q: What are the symptoms of leishmaniasis?
A: Symptoms of leishmaniasis differ from case to case. But generally, someone with cutaneous leishmaniasis showcases lesions, ulcers, and/or lacerations (either painful or painless) on the surface of the skin, some of which can penetrate into the deeper layers (Muneeb, 2006, 75). However, visceral leishmaniasis is much more severe. Symptoms include fever, hepatosplenomegaly (simultaneous enlargment of spleen and liver), systematic failure of multiple organs, coma, and fatality (Markle, 2004, 51).
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3. Q: How serious is the disease?
A: Leishmaniasis, if contracted in the states, is relatively harmless due to wide availability of effective treatments, but if it is contracted abroad, it can be much more serious, for reasons inverse to the aforementioned.
Conclusion: To sum up, Leishmaniasis is a malignant threat to the contemporary world, especially that which is considered "expendable" by the more fortunate populations. This fact, although incontrovertibly apparent, does not alleviate the responsibility of those who are privileged enough to help. Those who have the ability to assist the less fortunate have the responsibility to assist the less fortunate. Only through acts of sincere magnanimity and kindness will threats like this disease be eradicated from the world.