Sand Flies, Disease of Destruction

Monday, November 23, 2009

Leishmaniasis is one of the top neglected diseases soldiers have been diagnosed with since deployment to Afghanistan or Iraq. Found in 88 countries worldwide, treatment is expensive and the availability of therapies is often scarce. A major outbreak in 2003 left deep ulcers caused by the parasites known as the "baghdad boil" among troops. Leishmaniasis is caused by a parasitic protozoans of the genus Leishmania, transmitted by the bites of sand flies. They infect white blood cells that normally would defend the body from such invaders. There are two forms of leishmaniasis. The more serious, called kala-azar or visceral leishmaniasis (black fever), affects the internal organs, causing fever, anemia, splenomegaly, and discoloration of the skin. Untreated, it can be fatal. The second, or cutaneous leishmaniasis, leaves deep, disfiguring sores at the site of the bite. The sand flies that spread the parasites are carried by animals including dogs and a species of gerbil, as well as people. The insects often breed on waste land and in rubbish.

People with cutaneous leishmaniasis have one or more sores on their skin. The sores can change in size and appearance over time. They may end up with a raised edge and central crater (ulcer). The sores can be painless or painful. Some people have swollen glands near the sores. People with visceral leishmaniasis usually have fever, weight loss, and an enlarged spleen and liver. They may have abnormal blood tests, low blood counts, including a low red blood cell count (anemia), low white blood cell count, and low platelet count. The complete 5284-nucleotide sequence of the double-stranded RNA genome of leishmania RNA virus 1 (LRV1) contains three open reading frames (ORFs) on the plus (+) (mRNA) strand. Similar to the RNA binding properties of synthetic and recombinant HIV-1 nucleocapsid protein (NCp7) and fragments observed in the 5'-HIV-1 RNA. ORFs may encode the major viral coat protein, overlapping ORF-3 by 71 nucleotides. The HIV viral genome mutates at a high rate. As the worldwide rate of HIV infection increases, the need for a leishmaniasis vaccine needs to becomes more urgent. In an IFA test, HIV antigen is mixed with a fluorescent compound and then with a sample of the patient's blood, testing were positive for Leishmania. Leishmaniasis accelerates the onset and worsens the course for people infected with HIV. Leishmaniasis is a spectrum of diseases, each distinctly manifested and all with potentially devastating consequences. Treatment of leishmaniasis requires the administration of toxic and poorly tolerated drugs.

In October 2002, well prior to the invasions of Iraq and Afghanistan, the US Defense Intelligence Agency's Armed Forces Medical Intelligence Center (AFMIC) warned that leishmaniasis would be a danger for troops. Insect repellant and bed nets were frequently in short supply, and commanders failed to emphasize the risk of Leishmaniasis. Almost all of the people in the United States who have leishmaniasis became infected while traveling or living in other countries. Over 90 percent of the cases of cutaneous leishmaniasis occur in parts of Afghanistan, Algeria, Iran, Iraq, Saudi Arabia, Syria, Brazil and Peru. Over 90 percent of the cases of visceral leishmaniasis occur in parts of India, Bangladesh, Nepal, Sudan, and Brazil. The World Health Organization estimates that 12 million people worldwide are infected with leishmaniasis. The WHO says that the public health impact of this disease has been grossly underestimated. During the past 10 years, endemic areas have been spreading, with 350 million people thought to be at risk of infection. Antiparasitic pentavalent antimonials, such as sodium stibogluconate (Pentostam) or meglumine antimoniate, are the mainstays of therapy.

Sodium stibogluconate was the only recommended treatment in the United States and was available only through the CDC, but amphotericin B in its liposomal form has recently been approved and is now considered to be the drug of choice for visceral leishmaniasis because of its shorter course and lower toxicity. Treatment of cutaneous leishmaniasis differs according to the etiology and geographic location of the infection. For certain types where the potential for mucosal spread is low, topical paromycin can be used. For more invasive lesions sodium stibogluconate, meglumine antimonate, or pentamidine can be used. Amphotericin B deoxycholate may be first-line therapy for advanced mucosal disease. Visceral leishmaniasis, treatment with a pentavalent antimonial compound usually is effective, outside of India. Transfusions may be necessary for severe bleeding or anemia. Antibiotics are indicated to treat intercurrent infectious conditions. A major advance has been the advent of liposomal formulations of amphotericin B, in which various alternative lipids have replaced deoxycholate. These formulations, which passively target amphotericin to macrophage-rich organs, are much more costly than conventional amphotericin B. Miltefosine, a chemotherapeutic agent, is the first extremely effective oral agent for visceral leishmaniasis.

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