Tegumentary leishmaniasis and coinfections other than HIV

Abstract

Background: Tegumentary leishmaniasis (TL) is a disease of skin and/or mucosal tissues caused by Leishmania parasites. TL patients may concurrently carry other pathogens, which may influence the clinical outcome of TL.

Methodology and principal findings: This review focuses on the frequency of TL coinfections in human populations, interactions between Leishmania and other pathogens in animal models and human subjects, and implications of TL coinfections for clinical practice. For the purpose of this review, TL is defined as all forms of cutaneous (localised, disseminated, or diffuse) and mucocutaneous leishmaniasis. Human immunodeficiency virus (HIV) coinfection, superinfection with skin bacteria, and skin manifestations of visceral leishmaniasis are not included. We searched MEDLINE and other databases and included 73 records: 21 experimental studies in animals and 52 studies about human subjects (mainly cross-sectional and case studies). Several reports describe the frequency of Trypanosoma cruzi coinfection in TL patients in Argentina (about 41%) and the frequency of helminthiasis in TL patients in Brazil (15% to 88%). Different hypotheses have been explored about mechanisms of interaction between different microorganisms, but no clear answers emerge. Such interactions may involve innate immunity coupled with regulatory networks that affect quality and quantity of acquired immune responses. Diagnostic problems may occur when concurrent infections cause similar lesions (e.g., TL and leprosy), when different pathogens are present in the same lesions (e.g., Leishmania and Sporothrix schenckii), or when similarities between phylogenetically close pathogens affect accuracy of diagnostic tests (e.g., serology for leishmaniasis and Chagas disease). Some coinfections (e.g., helminthiasis) appear to reduce the effectiveness of antileishmanial treatment, and drug combinations may cause cumulative adverse effects.

Conclusions and significance: In patients with TL, coinfection is frequent, it can lead to diagnostic errors and delays, and it can influence the effectiveness and safety of treatment. More research is needed to unravel how coinfections interfere with the pathogenesis of TL.

Fig 1. Flow diagram of record search and selection.

Fig 2. Immune responses during TL and the potential for interference through coinfection: A means to focus new research.

(A) Leishmania parasite transmission during sandfly bite initiates TL. Local phagocyte function (including neutrophils, macrophages, and dendritic cells) may be affected by coinfections affecting skin homeostasis. Furthermore, coinfection may affect the nature of preexisting immunity to sandfly saliva and/or the local response to sandfly/parasite proteins. (B) Innate immune mechanisms regulated by stromal cells, dendritic cells, and innate lymphoid cells may all be influenced by the microenvironment created by local or systemic coinfection. (C) Changes to innate immunity or immunological cross-reactivity may influence the balance between effector (Th1, Th2, and Th17) and regulatory (R) T-cell subsets, leading to altered control of parasite load and/or altered immunopathology. (D) Coinfections may directly or indirectly alter macrophage intracellular signalling, affecting the intracellular survival of Leishmania independently of any effects on the specific T-cell response. ILC, innate lymphoid cell; Th, T helper cell; TL, tegumentary leishmaniasis.