HISTORY OF LEISHMANIASIS IN US MILITARY
Parasites have been plaguing the United States military ever since the US was founded over two centuries ago. Because troops are sent to countries endemic to parasites not found at home, the military has had to diagnose and treat a much greater number of diseases than the average American must deal with in their lifetime. One example of a communicable disease affecting the military today is leishmaniasis. The disease was first documented in US troops during World War II. Over a thousand soldiers contracted cutaneous leishmaniasis in places ranging from Iran to North Africa to Panama. There were at least fifty cases of visceral leishmaniasis concentrated in soldiers stationed around the Mediterranean Sea which resulted in serious illness and one death.
In the Middle East, US soldiers are once again facing the threat of leishmaniasis infection. Beginning in the 1990s, an increasing number of soldiers have been sent to Iraq, Afghanistan, Kuwait and Saudi Arabia. All of these countries are endemic to the disease. During the Persian Gulf War from 1990-1991, there were few documented cases. Twenty soldiers contracted cutaneous leishmaniasis and another twelve were infected with visceral leishmaniasis.(4) Although leishmaniasis did not have a significant impact on the health of American troops in the first Gulf War, experience with infection prepared the military for its longer campaigns in Afghanistan and Iraq during 21st century.
At present, there have been over a thousand cases of leishmaniasis diagnosed in military personnel serving in Operation Iraqi Freedom in Iraq and Operation Enduring Freedom in Afghanistan, according to Walter Reed Army Medical Center (WRAMC) Chief of Infectious Disease, Dr. Glenn Wortmann.(5) With a growing incidence, it becomes more important to understand the disease itself and identify the capacity for treatment and prevention.
THE SPREAD OF LEISHMANIASIS IN THE MIDDLE EAST
Leishmaniasis is spread through its vector, the phlebotomine sand fly. According to the United States Center for Disease Control, a person becomes infected when a sand fly, carrying the infective stage of the protozoa, takes a blood meal. The promastigote enters the skin through the bite wound, is phagocytized by macrophages, and then circulates throughout the body. The lifecycle continues when the sand fly takes another blood meal and ingests the parasite once again.(6)
Click to view animation of Leishmania life cycle: http://www.who.int/tdr/diseases/leish/lifecycle.htm
Because the sand fly is the primary means of transmission, understanding its habits is vital to streamlining military efforts to prevent infection. Research on the vectors suggests the sandfly is most active during nighttime hours; therefore risk for infection is highest between dusk and dawn. Given the small size of the fly (2-3 mm) and its noiseless flight, humans are often unaware when the flies are present.(1,6) Military personnel often go outside to use the restroom during the night and return with hundreds of bites, never realizing they have come into contact with the sand fly until they return inside to see the bites. Because the flies are active from March through November, infection typically occurs during these times.(7)
Identifying the ideal conditions for vector breeding allows military personnel to determine the areas where the threat of infection is greatest. Sand fly eggs and larvae thrive in areas of heat in humidity.(1) In the Middle East where temperatures are consistently hot, especially during the season of vector activity, sand flies find ideal conditions for breeding. Poor sanitation also creates ideal breeding grounds for the flies who like to lay their eggs in the cracks of ruined buildings or in heaps of garbage.(8)
Determining the number of infected flies is also an important step in determining the degree of risk for leishmaniasis infection. When sampling sand flies in Iraq, researchers expected to find less than a half-percent of the flies infected with Leishmania. However, 0.06% to 2.78% were actually infected. With such a large number of sand flies carrying the parasite, it takes fewer insect bites than predicted to actually contract leishmaniasis. Preventing the bites becomes more and more important.
Figure 5In addition to infecting humans, animal reservoirs are also characteristic of the disease in the Middle East. In Old World infections, small rodents are typically reservoirs.(9) However, Dr. Wortmann identifies dogs as a primary reservoir in Iraq.(5) Control of the disease becomes much more difficult when animals harbor the parasite. Even though efforts to treat the disease might decrease the prevalence in the human population, the parasite survives in dogs. Outbreaks can reoccur if sand flies take a blood meal from an infected dog and then bites a human.
Three Types of Infection:
There are three types of leishmaniasis varying in prevalence and degree of infection.
Cutaneous Leishmaniasis: Figure 6
Cutaneous Leishmaniasis is the most common form of Leishmaniasis throughout the world, with nearly 1.5 million new cases each year.(10) Seven countries, including Afghanistan, account for 90% of all CL cases.(11) When a person becomes infected ulcers appear on the face arms, and legs. Although not fatal, the disease can cause a high number of lesions and result in scarring.(1)
Mucocutaneous Leishmaniasis: Figure 7
This type of leishmaniasis can cause permanent damage to the mucous membranes of the nose, mouth, and throat cavities.(1)
Visceral Leishmaniasis: Figure 8
Called kala azar, meaning “black fever”, visceral leishmaniasis has been recognized as a debilitating disease for many centuries.(6) The disease manifest itself through fever, weight loss, swelling of the spleen and liver, and anemia. By for the most serious form of infection, the WHO warns that “if left untreated, the fatality rate in developing countries can be as high as 100% within two years.”(1)
Since the beginning of the current conflict in the Middle East, over a thousand cases of leishmaniasis have been diagnosed in military personnel. Over 99% of these cases have presented as cutaneous leishmaniasis, the most treatable form of the disease.(5) Most of the cutaneous leishmaniasis has come as a result of infection by Leishmania major, the species that dominates both Iraq and Afghanistan. By contrast, the incidence of visceral leishmaniasis is very low. As of October 2006, there have been only five reported cases of visceral leishmaniasis among military personnel, all coming from the species Leishmania infantum-donovani which is found predominately in Afghanistan.(12) There are no reports of mucocutaneous infection.
Because treatments for leishmaniasis infection exist, diagnosis is an important step in preventing the debilitating affects of the disease. A cutaneous leishmaniasis diagnosis usually begins when an individual notices slow-healing ulcerations on the surface of his skin. It is current practice in the Middle East to treat these wounds initially with a course of amoxicillin-clavulanate. If the wounds are from a bacterial infections, the antibiotics will heal them. However, if the wound has not healed after more than three weeks and the antibiotics do not work, it is likely that the patient does indeed have leishmaniasis.(13)
To verify the diagnosis, skin cultures from the sores can be taken to identify the parasite. Such samples can be retrieved in two ways: a skin scraping or a punch biopsy.
The following is a video clip of the skin scraping procedure: http://www.pdhealth.mil/downloads/Leish%20Dx%20Scraping%20Video.wmv
Although doctors in Iraq can initially use a sample to diagnose leishmaniasis in a field laboratory, it is much more reliable and also required that they send the sample back to the US to confirm the results, do further testing and research, and to put in the registry. In this way, the Leishmania Diagnostics Lab at Walter Reed Army Institute of Research (WRAIR) can continue to find ways to protect soldiers against the ill-effects of infection.(14)
Visceral leishmaniasis will first present with fever, hepatosplenomegaly, cytopenia, and hypergammaglobulinemia. If these symptoms are present and visceral leishmaniasis is suspected, an rK39 serological test can be done to confirm the diagnosis.
Cutaneous leishmaniasis often is self-limited and as a result, heals on its own. Oftentimes, if it is known that Leishmania major caused the lesions, the sores will be left alone to heal untreated. The problem with this, however, is that the lesions take much longer to heal than normal wounds and leave large conspicuous scars.(7) Such scars are especially unwanted on the face and hands because of the cosmetic consequences and on the joints because range of motion might be compromised. Small lesions that merit treatment, but are not on the face, hands or joints, will be remedied with ThermoMed, a heating device that kills heat-sensitive Leishmania with a second-degree burn.(15) This method is attractive because it only has to be completed once and it has been shown to be very effective. Also, military personnel that need ThermoMed treatment do not need to be completely evacuated, but rather can go to their designated theater treatment facility and then return to their unit after only a short time. There is a risk of infection and scarring from this treatment, but as long as the burns are taken care of with Gentamicin ointment and dressings are frequently changed, they should heal.
If the lesions are larger than about 2.5 cm or are on the face, hands, or joints, they will be treated with Pentostam, a drug given intravenously. Although Pentostam has been used in Europe for over half a century, the Food and Drug Administration (FDA) still has not approved it for use in the United States. However, it is 95% effective in speeding the lesion-healing process so the military has access to Pentostam under a research protocol.(7) Use is limited to the Walter Reed Army Medical Center, forcing military personnel needing treatment with the drug to be returned to the US for treatment. The drug is highly toxic, with a number of side effects presenting during the 10-20 day treatment period. Side effects include headache, rash, pancreatitis, arthralgias, myalgias, fatigue, electrocardiographic changes, and reactivation of herpes virus infections.(13)
Cutaneous leishmaniasis is considered cured if after 60-90 days the lesions heal and no new ones present.(15)
Visceral leishmaniasis is a much more serious disease than cutaneous leishmaniasis because it is fatal if not treated. The most effective drug is amphotericin B, which has a 95% success rate. However, it is also very toxic. AmBisome has also been approved by the FDA, but can only be used in patients who are not immunocompromised.(13) Because of the severity of visceral leishmaniasis, military personnel with the disease are sent to Walter Reed Army Medical Center for treatment as soon as they are diagnosed.
Current prevention methods in the US military are focused primarily on self-protection to reduce the number of sand fly bites, therefore reducing the chance of infection. The US Army Center for Health Promotion and Preventive Medicine (USACHPPM) provides a thorough overview of prevention strategies and even distributes pocket cards to military personnel that describe ways to reduce sand fly bites. H
As depicted above, there are three primary self-protection methods:
1. Topical insect repellents: Must to contain between 20-50% DEET. Cover all exposed skin, including the face. Repellent with 33% DEET can last up to twelve hours but needs to be reapplied if it is washed off by sweat or water.
2. Permethrin-treated uniforms and bednets: Use an Individual Dynamic Absorption (IDA) kit, which contains 40% permethrin, to apply enough repellent to last the lifetime of the uniform. Otherwise use permethrin aerosol spray, which is on 0.5% permethrin, so it will only last through 5-6 washes. Standard bednets have holes that are large enough for sand flies to travel through, but if they are sprayed with permethrin, they become effective. Also, finer bednets already treated with permethrin are available in some areas.
3. Correct uniform attire: If uniforms are worn correctly, they will be able to keep sand flies from being able to enter under the clothing and reach the skin.(10)
In addition, staying inside from dusk until dawn is important. This is the time of day that sand flies are most active and most likely to bite. Also, keep living areas clear of stray dogs and rodents, as such mammals also carry Leishmania parasites and can pass them on to humans. Overall, if each of these methods is applied, the number of sand fly bites and the risk of contracting leishmaniasis will dramatically decrease.
If used consistently, these methods can drastically reduce the chances of being bitten frequently by sand flies. However, due to the nature of the current conflict, military personnel do not always have access to insect repellents or bednets. In a survey done at Walter Reed Army Medical Center on leishmaniasis patients, “80% had used topical repellents, but 26% noted that these were unavailable at some times during their deployment, 17% had never treated their uniforms with permethrin, and only 10% had slept under a bednet.”(13)