Abstract
Leishmania major, transmitted in Iraq by the bite of a sand fly Phlebotomus papatasi, causes cutaneous leishmaniasis (CL). The sand fly saliva is immunogenic, with both systemic humoral and cellular human immune responses resulting from natural exposure. 248 Americans who developed L. major infection in Iraq were sex, race/ethnicity, year of Iraq deployment-matched to controls without CL. Using a case-control study design, we compared sand fly saliva-specific human IgG levels and recognized antigens between the two groups. Serologic responses to Ph. papatasi salivary gland homogenate were studied with ELISA and Western blot, using serial samples obtained from before travel, during CL treatment (CL) or at time of return to US (controls), as well as (for CL cases) six to 24 months after return to non-endemic US. The mean change in optical density (MCOD), reflecting the change in sand fly saliva-specific IgG before and after exposure in Iraq, was 0.296 (range -0.138 to 2.057) in cases and 0.151 (range -0.454 to1.085) in controls, p<0.001. Low levels of sand fly saliva specific antibody were noted in CL cases by 7-8 months after return to the US. The most frequently recognized Ph. papatasi salivary antigens were MW30 (PpSP32) and MW64, although other salivary proteins recognized were MW12/14, 15, 18, 28, 32, 36, 42, 44, 46, 52. Logistic regression suggested that MW15, 28 and 42 were associated with the largest effect on the MCOD. MW30 was the most frequently recognized antigen suggesting a role as biomarker for sand fly exposure and CL risk. Anti-Ph. papatasi saliva IgG waned within months of return to the US. We also discuss vector antigenic saliva proteins in the context of CL presentation and identify some salivary antigens that may correlate with less lesion area, ulcer versus papule/plaque, race among those with CL.
Highlights
Cutaneous leishmaniasis (CL) affects more than 4 million people worldwide and more than a billion individuals live in endemic regions and are potentially at risk of infection [1, 2]
We report the kinetics, frequency, duration of, and the Ph. papatasi saliva antigens recognized by- anti-Ph. papatasi IgG antibodies in a cohort of 496 deployed U.S military members who traveled to Iraq
We evaluate these vector saliva antibody responses in the context of cutaneous leishmaniasis clinical presentation and personal protection measures utilized
Summary
Cutaneous leishmaniasis (CL) affects more than 4 million people worldwide and more than a billion individuals live in endemic regions and are potentially at risk of infection [1, 2]. Leishmania (L.) major parasites, transmitted by the sand fly vector Phlebotomus papatasi, in North Africa, Middle East, and Southwest Asia countries cause CL in some areas of highest incidence including Iraq [2, 3]. Of the sand fly fauna in Iraq, Ph. papatasi, Ph. sergenti and Ph. alexandri represent the only abundant anthropophilic species reported from the country [4, 5], where they are considered the primary vectors of L. major, L. tropica, and L. infantum, respectively [4, 6]. Introducing many Ph. papatasi-unexposed individuals into the circumstances of rudimentary shelter during the first year of combat in endemic Iraq, uniquely allows investigation of the role of human immune responses to vector saliva upon the risk and presentation of CL. Seminal observations [15, 16] have demonstrated that mice initially immunized with sand fly saliva (no parasite), as well as select molecules of saliva such as SP15 [17, 18], had subsequent clinical disease that was markedly ameliorated after challenge with Leishmania-infected sand fly bites
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