# Epidemiology and clinical spectrum of leishmaniasis due to Leishmania infantum in Tunisia: Current status, challenges, and perspectives

## TL;DR

This paper reviews the current state of leishmaniasis caused by Leishmania infantum in Tunisia, highlighting its spread, clinical forms, and challenges in controlling the disease.

## Contribution

The paper provides an updated systematic review of L. infantum epidemiology, clinical manifestations, and zymodeme distribution in Tunisia, emphasizing recent geographic and demographic changes.

## Key findings

- VL is highly endemic in northern Tunisia but is expanding southward, while CL cases due to L. infantum are increasing.
- MON-1 is the predominant zymodeme in Tunisia, with MON-24 and MON-80 detected sporadically.
- Domestic dogs and Phlebotomus perniciosus are the main reservoir and vector for VL, while other hosts and vectors may be involved in CL.

## Abstract

This review focuses on leishmaniasis caused by Leishmania (L.) infantum in Tunisia, a vector-borne parasitic disease transmitted through the bite of infected female sandflies. Leishmaniasis manifests as a spectrum of clinical forms, ranging from benign cutaneous lesions, to a severe and potentially fatal visceral form. In Tunisia, L. infantum is the etiological agent of visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL). While CL typically manifests as a single, small facial lesion, atypical forms are sometimes observed. VL primarily affects children under the age of five and immunocompromised individuals, although an increasing number of cases have been reported in immunocompetent adults in recent years. Although neglected, leishmaniasis is an emerging and growing public health concern in Tunisia, particularly due to the increasing incidence of VL among adults and potential spread of both CL and VL to previously non-endemic areas. This expansion is demonstrated by the fact that L. infantum has a geographical distribution mainly in the humid, sub-humid and semi-arid regions of the north, but gradually spreading towards the central and southern parts of the country.

This literature review was conducted through a systematic search of PubMed, Scopus, and Google Scholar for studies published between 1904 and 2024, focusing on the clinical, epidemiological, molecular, and ecological aspects of L. infantum in Tunisia. In addition to its clinical variability, L. infantum presents a biochemical variability with three isoenzymatic variants (zymodemes) identified in Tunisia: MON-1 (predominantly associated with VL), MON-24 (predominantly associated with CL), and MON-80 (implicated in both forms). Our review found that VL remains highly endemic in northern Tunisia but has expanded southward in recent decades, while cutaneous cases due to L. infantum are increasingly recognized. Isoenzymatic and molecular studies confirm the predominance of the MON-1 zymodeme, with sporadic detection of MON-24 and MON-80. Domestic dogs remain the main reservoir, and Phlebotomus (P.) perniciosus is the principal vector for VL, though other Phlebotomus species have been implicated in CL transmission. These findings highlight the importance of integrating molecular tools alongside classical isoenzyme methods for a better understanding of parasite dynamics and epidemiological monitoring.

The transmission cycle of L. infantum is not fully elucidated, but domestic dogs and P. perniciosus are considered the primary reservoir and vector for VL, respectively, while, other potential mammalian hosts and sandflies vectors were suspected for CL. Comparative data from Algeria, Morocco, Libya, and southern Europe suggest both common patterns and local specificities in L. infantum transmission, underscoring the importance of regional collaboration. The epidemiological and clinical complexity of L. infantum, together with its expanding geographic distribution in Tunisia, underscores the need for further integrated research to clarify transmission cycles and implement effective prevention and control strategies.