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Visceral Leishmaniasis in 4 US Army Soldiers
Abstract and Commentary
By Dean L. Winslow, MD, FACP, FIDSA, Chief, Division of AIDS Medicine, Santa Clara Valley Medical Center; Clinical Professor, Stanford University School of Medicine, Section Editor, HIV, is Associate Editor for Infectious Disease Alert.
Dr. Winslow serves as a consultant for Siemens Diagnostics, and is on the speaker's bureau for Boehringer-Ingelheim and GSK.
Synopsis: Cases of visceral leishmaniasis are described in 4 US Army soldiers who acquired their infections in Afghanistan or Iraq. All 4 patients presented with classical symptoms and signs. The 3 patients treated initially with liposomal amphotericin B were clinically cured but the patient treated with amphotericin B lipid complex experienced clinical relapse and was successfully retreated with sodium stibogluconate.
Source: Myles O, et al. Visceral leishmaniasis: Clinical observations in 4 US Army soldiers deployed to Afghanistan or Iraq, 2002-2004. Arch Intern Med. 2007;167:1899-1901.
The infectious diseases group at Walter Reed reported the clinical cases of 4 patients who acquired visceral leishmaniasis during deployments to either Afghanistan (two patients) or Iraq (two patients). The patients ranged in age from 23 to 39. Three patients were African-American and one was white. The median time to onset of symptoms after returning from deployment was 6 months, although one patient became ill during the 11th month of his tour of duty while still in Iraq. All patients presented with fever and splenomegaly, two had hepatomegaly, three were mildly leukopenic, and two had mild thrombocytopenia. All had elevated transaminases. All had antibody detected by the new rK39 dipstick test (which uses a recombinant L. chagasi antigen to identify antibodies to the parasite's dominant kinesin-like amastigote antigen), as well as high titers in the standard IFA assay. Liver biopsy was done in two patients, both of whom had histopathology consistent with VL; only one had a positive PCR. All four patients underwent bone marrow biopsy, two had histopathology consistent with VL, and PCR of bone marrow was positive in only one of the three patients in whom PCR was performed. Liposomal amphotericin B (Ambisome) treatment was successful in all three patients treated with this agent; one patient treated initially with amphotericin B lipid complex (Abelcet) failed and was successfully retreated with a 28-day course of sodium stibogluconate (Pentostam).
During my second (of three, soon to be four) Air Force deployment to Iraq, I had the pleasure of spending three days during the late summer/early fall of 2003 in An Nasiriyah, Iraq, with one of the authors of this paper, LTC Peter Weina, who at that time was commander of the US Army's Theater Army Medical Laboratory. Peter is one of the world's foremost experts in leishmaniasis, and I was able to see a handful of cutaneous leish cases with Peter (of the approximately 800 he saw during that year). His team did an amazing job defining the epidemiology of the disease in Coalition personnel, as well as characterizing the sand fly vector during that time. This particular area of southern Iraq (approximately half way between Baghdad in the center of Iraq and Basra in the south) had once been part of the extensive wetlands that existed in the south of Iraq between the Tigris and Euphrates rivers. During the early-mid 1990s, Saddam Hussein drained the wetlands (to punish the largely Shia Arab population which rose up in rebellion in the aftermath of the first Gulf War). Surprisingly, this seemed to, if anything, increase the population of sand flies in the area, based on the large numbers recovered in Peter's team's light traps. Since at that time in 2003 many of the US Army troops did not have air conditioned tents and were sleeping either in abandoned Iraqi buildings or out in the open or on their vehicles, some of the soldiers had sustained literally hundreds of intensely pruritic bites from these sand flies (which are smaller than mosquitoes), mainly at night. I know both of us wondered at that time whether we would later be seeing many cases of either visceral leishmaniasis (likely due to L. infantum) or viscerotropic disease due to the more common agent which generally causes cutaneous disease (L. major or L. tropica), as was seen in a handful of cases following the first Gulf War.1 It is hoped that the Walter Reed group will publish additional details on these four cases later to include species identification. (I also hope Peter's group publishes the full account of the excellent work his group did during austere combat conditions back in 2003. It is an impressive story.)
It is interesting that one of the four cases of VL described by the Walter Reed group in this paper did not travel outside the IZ ("Green Zone") in southeastern Baghdad. However, it does not surprise me too much, as I am relatively certain they have some sand flies there as well. Personnel stationed there would be expected to be at lower risk than troops out "beating the boonies," since everyone in the IZ now sleeps in an air conditioned building. We did find small numbers of sand flies in light traps at our base in western Baghdad when I was serving there in 2006, although I saw no cases of either cutaneous or visceral leish acquired on our base. Since the sand flies are poor fliers and do not seem to like air conditioned tents or buildings, it would be interesting to know if this particular soldier who never left the IZ spent significant amounts of time outside of his quarters at night.
This series of four cases of visceral disease is informative in describing the clinical presentation in these patients and pointing out the limitations of making a diagnosis of visceral leishmaniasis by histopathology and/or PCR on any one tissue (bone marrow or liver). Both the new rK39 dipstick antibody test and the IFA seemed to perform well. The clinical failure of amphotericin B lipid complex and the success of liposomal amphotericin B may be a reflection of the superior distribution of the latter agent in tissues of the reticuloendothelial system. Visceral leishmaniasis should be kept in mind in the differential diagnosis of fever in military personnel returning from duty in Southwest Asia, even in those personnel who have been home for several months.