Abstract
Background
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.
Methodology/principal findings
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.
Conclusions/significance
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.
Introduction
Leishmaniasis is a vector-borne disease caused by a protozoan parasite of the genus Leishmania, which transmitted to humans by the bite of infected female sandflies. The progression of infection is determined by the specific parasite-host cell interaction. Distinct balances between parasite replication dynamics and host immune responses across species [1–3] account for the broad spectrum of clinical manifestations in humans, which range from localized cutaneous lesions to severe and potentially fatal visceral disease.
Three Leishmania species coexist in Tunisia: Leishmania (L.) major, L. killicki, and L. infantum. L. major is the predominant species, occurring mainly in central and southern Tunisia. L. infantum and L. killicki occur sporadically, mainly in the north and south, respectively. Infections with Leishmania species manifest in various clinical forms. While L. major and L. killicki cause exclusively self-healing cutaneous leishmaniasis (CL), L. infantum is responsible for distinct clinical manifestations, ranging from cutaneous leishmaniasis to visceral leishmaniasis (VL), a potentially fatal disease if untreated. Although L. infantum primarily causes visceral leishmaniasis and sporadic cutaneous leishmaniasis, a recent report indicates that it can also rarely cause mucosal leishmaniasis in Tunisia [4]. This finding highlights the broader clinical spectrum of L. infantum infections and underscores the need for continued surveillance and updated epidemiological assessments.
In addition, leishmaniasis caused by L. infantum has long been restricted to the northern regions of Tunisia. In recent years, both human and canine leishmaniasis were spread to other areas [5–9]. It is therefore necessary to update the status of leishmaniasis due to L. infantum in order to monitor the extent of the disease in Tunisia.
Moreover, leishmaniasis is among the highest-priority neglected vector-borne tropical diseases worldwide [10,11]. Epidemiological studies of these parasitoses aim to identify the key components of the parasite cycle, including the vertebrate host (reservoir), the invertebrate host (vector), and the Leishmania parasite.
So far, the dog is the unique proven reservoir host for L. infantum, and P. perniciosus is the vector. However, recent evidence suggests that L. infantum has multiple transmission pathways involving various species as reservoir and vector hosts. The diversity of Leishmania species, vectors, and reservoirs contributes to the complex epidemiology of the disease. In addition, environmental and climatic factors, including temperature, humidity, and land use, significantly influence sandfly distribution and incidence of leishmaniasis [12].
Methods
This literature review was conducted to examine leishmaniasis due to L. infantum in Tunisia focusing on clinical and epidemiological parameters. Searches were performed in PubMed, Google Scholar, and Scopus, covering publications from 1904 to 2024, using keywords such as “leishmaniasis,” “Leishmania infantum,” “Tunisia,” “clinical forms,” “epidemiology,” “reservoir,” and “vector.” Inclusion criteria encompassed original research articles, reviews, and peer-reviewed studies that addressed L. infantum in Tunisia, as well as comparative analyses with other Mediterranean countries. Only studies published in English or French were considered. Exclusion criteria included papers unrelated to the topic (e.g., focused mainly on immunology or without available full text). We identified 153 records from PubMed, 182 from Scopus, and 255 from Google Scholar. After removal of duplicates, 398 records remained and were screened by title and abstract, leading to the exclusion of 258 records based on our exclusion criteria. About 140 full-text articles were assessed for eligibility, of which 58 were excluded, mainly because they lacked clinical or epidemiological data or had no accessible full text. Finally, around 82 studies were included in the qualitative synthesis. This approach was designed to provide a comprehensive update of knowledge about leishmaniasis due to L. infantum in Tunisia.
1. Visceral leishmaniasis in Tunisia
1.1. History and impact.
In Tunisia, VL is an old disease. The first documented case was described in Tunis in 1904 [13]. Although VL is less common than CL, its public health impact is significant. Prior to 2012, the annual incidence in Tunisia was estimated at approximately 89 cases [14]. However, over the past decade, the incidence of VL has increased, and its geographical range has expanded, particularly in central and northern regions, resulting in an increase in both disease burden and healthcare costs [5,15,16]. The expansion of VL foci is linked to environmental and ecological changes that favor the coexistence of reservoir hosts (mainly dogs) and competent sandfly vectors [17]. VL represents a major public health concern in Tunisia, not only because of its clinical severity but also due to its socioeconomic impact, particularly in rural areas where healthcare resources are limited. Timely diagnosis, effective treatment, and vector control measures remain essential for reducing morbidity and mortality.
1.2. Clinical forms.
In Tunisia, VL is predominantly known for its Mediterranean infantile form, developing in approximately 95% of cases in children under five years of age [18]. The common symptoms of VL are splenomegaly (97.9%), fever (79.9%), and hepatomegaly (47.3%). [19]. Nevertheless, adult cases were increasingly reported [20,21]. Since 2000, adult cases have risen to nearly 10% [22]. This shift in the epidemiological profile is primarily attributed to factors leading to immunosuppression, including viral infections such as Human Immunodeficiency Virus (HIV) and iatrogenic causes (e.g., corticosteroids, immunosuppressants, and anti-mitotic drugs) [21,23]. L. infantum acts as an opportunistic parasite favored by any cellular immunity deficit. In Tunisia, however, VL-HIV co-infection is rare [24,25].
1.3. Geographical breakdown.
In Tunisia, VL is distributed across humid, sub-humid, semi-arid and arid bioclimatic zones. It was historically endemic and widely distributed in the northern regions of the country before progressively expanding towards the center (Fig 1). Several Northern provinces are known to be endemic for this form of leishmaniasis [7,15,25,29,30]. In addition, autochthonous cases have been reported in central provinces [5,7,25,31–34].
Fig 1. Geographical distribution of human visceral leishmaniasis due to Leishmania infantum cases identified by isoenzymatic method between 2001 and 2008 in Tunisia [7,21,22,25,26–28].
Map created with Datawrapper using Natural Earth public domain basemap (https://www.naturalearthdata.com). The numbers next to the circles indicate the number of cases.
This expansion is likely driven by a combination of environmental, climatic, and anthropogenic factors, including increased human and animal mobility, agricultural development, and changes in land use that favor sandfly vector proliferation and reservoir host movement [17,35]. Such ecological shifts pose challenges for disease control programs, particularly in newly affected areas where surveillance, diagnostic infrastructure, and clinical expertise are often limited.
2. Cutaneous leishmaniasis due to L. infantum in Tunisia
2.1. History and impact.
L. infantum is primarily recognized as viscerotropic species responsible for VL in both the Old and New Worlds. However, cutaneous leishmaniasis (CL) caused by L. infantum was described for the first time in Tunisia in the early 20th century [36]. Since then, sporadic CL cases have been reported with only a few cases each year. In Tunisia, the average annual incidence is estimated at approximately 30 cases [37]. These cases often occur in areas where VL is also endemic, indicating overlapping transmission cycles.
2.2. Clinical forms.
The classic cutaneous lesion caused by L. infantum is usually localized and is characterized by a single, small, ulcerated or lupoid facial lesion, which may persist for several months to up to three years [38]. Unusual and atypical presentations, such as diffuse cutaneous leishmaniasis and lesions mimicking other dermatological conditions, have also been documented, highlighting the need for accurate differential diagnosis [39,40]
2.3. Geographical breakdown.
CL due to L. infantum is sporadically distributed in Tunisia, occurring in humid, sub-humid, and semi-arid bioclimatic conditions. This parasite is predominantly found in the north as the VL, supporting its dual role in visceral and cutaneous disease [37,41]. However, molecular and epidemiological surveys have indicated a progressive southward expansion; currently, L. infantum is also detected in central regions (Fig 2) [7,42,44]. Microsatellite analyses from Morocco and Algeria suggest possible genetic flow between neighboring foci, which may have implications for future spread in Tunisia [45]. Clinical, geographical repartition and Main challenges about L. infantum in Tunisia were summarized in Table 1.
Fig 2. Geographical distribution of cutaneous leishmaniasis due to Leishmania infantum cases identified by isoenzymatic method between 2001 and 2008 in Tunisia [26,28,37,42,43].
Map created with Datawrapper using Natural Earth public domain basemap (https://www.naturalearthdata.com). The numbers next to the circles indicate the number of cases.
Table 1. Clinical spectrum and geographical distribution of Leishmania infantum infections in Tunisia.
| Parameter | Visceral leishmaniasis (VL) | Cutaneous leishmaniasis (CL) |
| First description | 1904 [13] | 1918 [36] |
| Clinical aspects | mostly infantile form [18], rarely adults [20] | mostly a single, small, ulcerated or lupoid lesion on the face [38,44] with rare atypical forms [41,46] |
| Main endemic areas | North Tunisia: humid, subhumid, and semi-arid zones [7,15,25,29,30] | North Tunisia: humid, subhumid, and semi-arid zones [37,41] |
| Sporadic areas | Central Tunisia: arid and Saharan regions [5,7,25,31–33] | Central Tunisia: arid and Saharan regions [7,42,44] |
| Isoenzymatic variants | MON-1 (75.1%), MON-24 (21.4%), and MON-80 (3.5%) [21,22,25,26–28,37,42,43] | MON-24 (84.4%), MON-1 (13.1%), and MON-80 (2.5%) [21,22,25,26–28,37,42,43] |
| Main challenges | Monitoring the increasing incidence of VL among adults and potential spread of both CL and VL to previously non-endemic areas | |
| Integrating molecular tools alongside classical isoenzymatic methods for understanding of parasite dynamics | ||
Data compiled from published epidemiological and clinical studies between 1904 and 2024. Percentages reflect case distributions reported in cited studies. All references to specific information are cited in the corresponding places within the table.
3. Epidemiology of L. infantum in Tunisia
Epidemiological studies are conducted by analyzing all parameters of the L. infantum transmission cycle (parasite, vector, and reservoir)
3.1. Identifying the parasite.
In Tunisia, isoenzymatic analysis of L. infantum strains revealed three zymodemes (enzymatic variants): MON-1, MON-24, and MON-80. These zymodemes can cause both CL and VL. L. infantum zymodemes MON-1 and MON-80 mainly cause VL (91.3% and 72.7% of cases, respectively), while MON-24 is predominantly associated with CL (68.2%) [21,22,25,26–28,37,42,43]. Thus, there is no strict correlation between taxa and clinical appearance. These findings highlight the importance of integrating molecular tools, such as Multi-Locus Microsatellite Typing (MLMT) or genomic sequencing, alongside classical isoenzymatic methods for accurate epidemiological monitoring. While isoenzymatic analysis (zymodeme identification) remains the gold standard for species and strain designation, it has limited resolution to detect genetic recombination, hybrid strains, or population-level gene flow. Molecular methods complement this by uncovering such hidden genetic diversity and transmission dynamics, providing a more complete understanding of the parasite’s ecology and evolution, which is crucial for effective surveillance and control strategies [47].
3.2. The Reservoir.
Leishmania parasites are maintained mostly in animal reservoirs, which allow the survival of the parasite between two seasons of transmission. The transmission cycle of L. infantum is primarily zoonotic, with domestic dogs serving as the main reservoir hosts for L. infantum, as in all Mediterranean countries [6,26,28,48]. Canine infection with L. infantum is important as a cause of disease in dogs and as a reservoir for human leishmaniasis. A spatial correlation was confirmed between the occurrence of human VL and the high rate of Leishmania infection in Tunisian dogs. The detection of L. infantum in dogs confirmed an increase of the prevalence and an extension of the spatial repartition [6–8,16,49].
Besides dogs, other species have also been reported to be infected by L. infantum. Derghal et al. detected L. infantum DNA in hedgehogs (Atelerix algirus) and rodents (Meriones shawi) [50]. Further investigations need to be conducted to confirm their potential role in Leishmania transmission.
3.3. The vector.
In Tunisia, P. perniciosus was proven as the main vector of L. infantum [51], confirmed recently by uses of molecular methods [16,52–56]. P. perniciosus would be able to transmit both viscerotropic and dermotropic strains as supported by experimental evidence [57]. To fully understand the role of P. perniciosus in transmitting dermotropic L. infantum, further studies are needed by isolating and identifying Leishmania in naturally infected sandflies. Furthermore, morphological identifications must be coupled with molecular tools for precise species discrimination. This is particularly crucial given the phenotypic polymorphism observed in Tunisian P. perniciosus [58–60].
Alongside P. perniciosus, additional sandfly species may play a secondary role in the transmission life cycle of L. infantum, highlighting the complexity of vector ecology in the region [16,53,55,61]. For example, L. infantum DNA has been detected in P. perfiliewi [54,61], P. longicuspis [53,54], and P. langeroni [62]. Analyzing all reported cases of L. infantum-infected sandflies, revealed that the protozoan is most commonly detected in P. perniciosus (64.1%) the confirmed vector, but it has also been identified in P. perfiliewi (13.4%), P. longicuspis (8.9%), and in P. langeroni (3%) (Table 2). However, the incrimination of a species of sand fly as a vector of leishmaniasis should be confirmed by other parameters as a significant anthropophilic behavior, vector capacity, the simultaneous presence of the vector and the disease, and the abundance of the vector [64]. In addition, infected sandflies belonging to Sergentomya genus, normally associated with the transmission of reptile Leishmania, have been detected in minuta and dreyfussi [63]. However, experimental infestation of S. schwetzi proved that this phlebotomine species is refractory to human Leishmania species [65].
Table 2. Reported cases of Leishmania infantum-infected sandflies observed in Tunisia.
| Species of Sandfly | Numbers of cases | Percentages |
|---|---|---|
| P. (Larroussius) perniciosus | 43 | 64.1 |
| P. (Larroussius) perfiliewi | 9 | 13.4 |
| P. (Larroussius) longicuspis | 6 | 8.9 |
| P. (Larroussius) langeroni | 2 | 3 |
| Total P. (Larroussius) | 60 | 89.5 |
| S. minuta | 4 | 5 |
| S. dreyfussi | 3 | 4.4 |
| Total Sergentomya | 7 | 10.5 |
| Total | 67 | 100 |
In addition, sandfly analysis is useful for investigate potential Leishmania reservoirs. The analysis of blood meals in sand flies aims to identify the trophic preferences of sand flies and then learn more about other potential reservoirs not yet proven. Thus, DNA from mammalian species has been detected in P. (Larrousius) spp blood meals. Species such as Homo sapiens (human), as well as domestic animals such as Bos taurus (cow), Capra hircus (goat), Ovis aries (sheep), Oryctolagus cuniculus (rabbit), and Equus caballus (horse) have been identified [53,54] (Table 3). Furthermore, equids and wild rabbits are potential reservoirs since infected cases have been detected worldwide [66–69]. Human would be the reservoir of cutaneous form since CL lesions can persist for up to three years. Unexpectedly, no DNA of dogs, a proven reservoir of L. infantum in Tunisia, has been found in sandfly blood meal analysis in Tunisia. The presence of broad host availability could probably explain this result in the vicinity of the traps confirming the opportunistic behavior of species of this subgenus. This observation highlights the importance of conducting investigations focused on identified species in blood meal of sandflies to analyze their implication in the transmission life cycle of leishmaniasis.
Table 3. Reported blood meal sources of Phlebotomus (Larroussius) spp. sandflies infected with Leishmania infantum in Tunisia.
| Sand flies species | Blood meal typing | |||||||
|---|---|---|---|---|---|---|---|---|
| Bos taurus | Homo sapiens | Ovis aries | Capra hircus | Equus caballus | Equus asinus africanus | Meleagris gallopavo | Total (%) | |
| P. perniciosus | 19 | 19 | 4 | 6 | 0 | 0 | 0 | 50 (40.3%) |
| P. perfiliewi | 37 | 10 | 4 | 1 | 0 | 0 | 0 | 56 (45.1%) |
| P. longicuspis | 5 | 7 | 2 | 0 | 1 | 1 | 1 | 18 (14.5%) |
| Total (%) |
51 (41.1%) |
26 (21%) |
10 (8%) |
7 (5.6%) |
1 (0.8%) |
2 (1.8%) |
1 (0.8%) |
124 |
Also, unexpected anthropophilic feeding behavior of Sergentomya suggests its implication in the transmission of mammalian Leishmania to human [63]. Table 4 summarizes epidemiological features of L. infantum in Tunisia.
Table 4. Key epidemiological parameters of the Leishmania infantum transmission cycle in Tunisia.
| Confirmed vector(s) | P. perniciosus [51] |
| Suspected vectors | P. perfiliewi, P. longicuspis, P. langeroni [53,54,61,62] |
| Known reservoirs | Domestic dogs [48] |
| suspected reservoirs | Species infected by L. infantum DNA: Atelerix algirus (hedgehog), Meriones shawi (rodent) [50] |
| Vertebrate species identified through the identification of the Blood meal origin of engorged P. perniciosus specimens: Bos taurus (cow), Capra hircus (goat), Ovis aries (sheep), Oryctolagus cuniculus (rabbit), and Equus caballus (horse) [53,54] | |
| Main challenges | Need for further integrated research to clarify transmission cycles, identify additional vectors and reservoirs among suspected ones. |
Data summarized from multiple epidemiological, molecular, and entomological studies conducted in Tunisia between 1904 and 2023. Table highlights the main confirmed and suspected vectors and reservoirs. All references to specific information are cited in the corresponding places within the table.
4. Comparative perspective with neighboring countries
The epidemiological situation of L. infantum leishmaniasis in Tunisia shares similarities with other Maghreb countries, but also presents distinctive features. In Algeria, visceral leishmaniasis remains highly endemic in the north and has also extended southwards, with L. infantum MON-1 being the predominant zymodeme [70,71], similar to Tunisia. However, cutaneous cases due to L. infantum are less frequently reported compared to Tunisia. In Morocco, L. infantum is responsible for both VL and sporadic CL, and multi-locus microsatellite typing studies suggest genetic flow across borders with Algeria and Tunisia [72], which may explain the spread of atypical cutaneous forms. In Libya, L. infantum is mainly associated with VL in coastal and sub-humid areas, but sporadic CL cases have also been described [73,74]. These comparisons highlight that L. infantum in North Africa shows consistent zoonotic transmission cycles with dogs as the primary reservoir and P. perniciosus as the main vector, but differences in clinical presentations and geographical expansion may reflect local ecological, climatic, and socio-economic factors [75].
Integrating epidemiological data from the Maghreb region is essential to understand regional parasite dynamics, anticipate future expansion under climate change scenarios, and design cross-border surveillance and control strategies.
5. Challenges and future perspectives: drug resistance, climate change, and co-infections
5.1. Drug resistance.
Although antimonial drugs and amphotericin B remain the cornerstone treatments for visceral leishmaniasis in Tunisia, emerging evidence from the Mediterranean basin suggests decreasing efficacy of pentavalent antimonials and variable response to amphotericin formulations [76,77]. Reports from Algeria and Morocco indicate sporadic treatment failures, raising concerns that drug resistance may also emerge in Tunisia [78]. Continuous monitoring of treatment outcomes and the introduction of molecular markers of resistance are essential to guide clinical management and policy decisions.
5.2. Impact of climate change.
Climate change is expected to profoundly alter the distribution of sandfly vectors in North Africa [79]. Rising temperatures, changes in humidity, and expansion of irrigated agricultural zones may create suitable habitats for Phlebotomus species in areas previously free of leishmaniasis. Predictive models from North Africa suggest a north-to-south expansion of L. infantum foci, with Tunisia being particularly vulnerable due to its diverse bioclimatic zones [79,80]. This highlights the urgent need to integrate climate data into national surveillance and vector control programs.
5.3. Co-infections, particularly HIV.
While HIV co-infection with VL is still rare in Tunisia, it has been increasingly reported in other Mediterranean countries, such as Libya [81], Spain, and Italy, where L. infantum acts as an opportunistic pathogen in immunocompromised patients [82,83]. With the rising prevalence of HIV in North Africa, the possibility of increased VL–HIV co-infections cannot be excluded. Such cases are associated with atypical clinical presentations, higher relapses rates, and increased mortality. Enhanced clinical awareness and cross-screening for both diseases are therefore crucial.
Conclusion
Given the complexity of L. infantum from both an epidemiological and clinical perspective, this taxon requires further investigation in Tunisia. Its geographical distribution is extended from the north to the center regions of the country. Also, the transmission cycle of this parasite is not entirely known; many sandflies and mammalian species are suspected of being potential vectors and reservoirs. Further comprehensive and integrated epidemiological and entomological investigations are crucial to clearly elucidate the transmission cycles of L. infantum, identify potential new vectors or reservoirs, and guide targeted control strategies. Moreover, continued monitoring of climatic, environmental, and human-induced changes will be essential to predict emerging foci and adapt public health interventions accordingly.
Key learning points
Leishmaniasis is a vector-borne parasitic disease transmitted through the bite of infected female sandflies.
Leishmaniasis is an emerging and growing public health concern in Tunisia, particularly due to the increasing incidence of visceral leishmaniasis among adults and potential spread of both cutaneous and visceral leishmaniais to previously non-endemic areas.
Leishmaniasis due to Leishmania infantum is zoonotic, with the domestic dog confirmed as the main reservoir, while other potential mammalian hosts remain to be identified.
Phlebotomus perniciosus is the only confirmed vectors, although several other sandfly species are suspected to contribute to Leishmania infantum transmission.
Key papers
Gramiccia M, Ben-Ismail R, Gradoni L, Ben Rachid MS, Ben Said M. A Leishmania infantum enzymatic variant, causative agent of cutaneous leishmaniasis in north Tunisia. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1991;85:370–1.
Aoun K, Bouratbine A, Harrat Z, Guizani I, Mokni M, Ali S, et al. Données épidémiologiques et parasitologiques concernant la leishmaniose cutanée sporadique du nord tunisien Bulletin de la Societe de pathologie exotique. 2000;93(2):101–3.
Haouas N, Gorcii M, Chargui N, Aoun K, Bouratbine A, Akrout FM, et al. Leishmaniasis in central and southern Tunisia: current geographical distribution of zymodemes. Parasite (Paris, France). 2007;14(3):239–46.
Ben Salah A, Ben Ismail R, Amri F, Chlif S, Ben Rzig F, Kharrat H, et al. Investigation of the spread of human visceral leishmaniasis in central Tunisia. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2000;94(4):382–6.
Remadi L, Chargui N, Jimenez M, Molina R, Haouas N, Gonzalez E, et al. Molecular detection and identification of Leishmania DNA and blood meal analysis in Phlebotomus (Larroussius) species. PLoS Neglected Tropical Diseases. 2020;14(3):e0008077.
Funding Statement
The authors received no specific funding for this work.
References
- 1.Costa CHN, Chang K-P, Costa DL, Cunha FVM. From infection to death: an overview of the pathogenesis of visceral leishmaniasis. Pathogens. 2023;12(7):969. doi: 10.3390/pathogens12070969 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Lodi L, Voarino M, Stocco S, Ricci S, Azzari C, Galli L, et al. Immune response to viscerotropic Leishmania: a comprehensive review. Front Immunol. 2024;15:1402539. doi: 10.3389/fimmu.2024.1402539 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Gradoni L, Gramiccia M. Leishmania infantum tropism: strain genotype or host immune status?. Parasitol Today. 1994;10(7):264–7. doi: 10.1016/0169-4758(94)90142-2 [DOI] [PubMed] [Google Scholar]
- 4.Chouaieb H, Akhoundi M, Omri ME, Ismail S, Khammari I, Bellazreg F, et al. Mucosal leishmaniasis in Tunisia: observations from a rare case report. Am J Trop Med Hyg. 2025;112(5):966–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Ben Salah AB, Ben Ismail R, Amri F, Chlif S, Ben Rzig F, Kharrat H, et al. Investigation of the spread of human visceral leishmaniasis in central Tunisia. Trans R Soc Trop Med Hyg. 2000;94(4):382–6. doi: 10.1016/s0035-9203(00)90112-3 [DOI] [PubMed] [Google Scholar]
- 6.Chargui N, Haouas N, Gorcii M, Akrout Messaidi F, Zribi M, Babba H. Increase of canine leishmaniasis in a previously low-endemicity area in Tunisia. Parasite. 2007;14(3):247–51. doi: 10.1051/parasite/2007143247 [DOI] [PubMed] [Google Scholar]
- 7.Haouas N, Chaker E, Chargui N, Gorcii M, Belhadj S, Kallel K, et al. Geographical distribution updating of Tunisian leishmaniasis foci: about the isoenzymatic analysis of 694 strains. Acta Trop. 2012;124(3):221–8. doi: 10.1016/j.actatropica.2012.08.012 [DOI] [PubMed] [Google Scholar]
- 8.Bouattour A, Amri A, Belkhiria JA, Rhim A, Fezaa O, Gantier J-C, et al. Canine leishmaniosis in Tunisia: growing prevalence, larger zones of infection. PLoS Negl Trop Dis. 2021;15(12):e0009990. doi: 10.1371/journal.pntd.0009990 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Haouas N, Babba H. Leishmaniasis in Tunisia: history and new insights into the epidemiology of a neglected disease. Epidemiology and Ecology of Leishmaniasis. InTech. 2017. doi: 10.5772/65000 [DOI] [Google Scholar]
- 10.Hotez PJ, Molyneux DH, Fenwick A, Ottesen E, Ehrlich Sachs S, Sachs JD. Incorporating a rapid-impact package for neglected tropical diseases with programs for HIV/AIDS, tuberculosis, and malaria. PLoS Med. 2006;3(5):e102. doi: 10.1371/journal.pmed.0030102 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.WHO. Global leishmaniasis surveillance updates 2023: 3 years of the NTD road map. Wkly Epidemiol Rec. 2024;45(99):653–69. [Google Scholar]
- 12.Burza S, Croft SL, Boelaert M. Leishmaniasis. Lancet. 2018;392(10151):951–70. [DOI] [PubMed] [Google Scholar]
- 13.Laveran A, Cathoire M. Présentation de parasite: Piroplasma donovani. Bulletin de l’Académie de Médecine. 1904;51:247–8. [Google Scholar]
- 14.Alvar J, Vélez ID, Bern C, Herrero M, Desjeux P, Cano J, et al. Leishmaniasis worldwide and global estimates of its incidence. PLoS One. 2012;7(5):e35671. doi: 10.1371/journal.pone.0035671 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Bouratbine A, Aoun K, Chahed MK, Ben Ismail R. Données épidémiologiques sur la leishmaniose viscérale infantile en Tunisie en 1993. Médecine et Maladies Infectieuses. 1998;28(5):446–7. doi: 10.1016/s0399-077x(98)80129-7 [DOI] [Google Scholar]
- 16.Chargui N, Haouas N, Slama D, Gorcii M, Jaouadi K, Essabbah-Aguir N, et al. Transmission of visceral leishmaniasis in a previously non-endemic region of Tunisia: detection of Leishmania DNA in Phlebotomus perniciosus. J Vector Ecol. 2013;38(1):1–5. doi: 10.1111/j.1948-7134.2013.12000.x [DOI] [PubMed] [Google Scholar]
- 17.Ready PD. Epidemiology of visceral leishmaniasis. Clin Epidemiol. 2014;6:147–54. doi: 10.2147/CLEP.S44267 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Belhadj S, Pratlong F, Mahjoub H, Toumi NH, Azaiez R, Dedet JP, et al. Infantile visceral leishmaniasis from Leishmania infantum MON-24: a reality in Tunisia. Bull Soc Pathol Exot. 2000;93(1):12–3. [PubMed] [Google Scholar]
- 19.Aissi W, Ben Hellel K, Habboul Z, Ben Sghaier I, Harrat Z, Bouratbine A, et al. Epidemiological, clinical and biological features of infantile visceral leishmaniasis at Kairouan hospital (Tunisia): about 240 cases. Bull Soc Pathol Exot. 2015;108(4):265–71. doi: 10.1007/s13149-015-0438-1 [DOI] [PubMed] [Google Scholar]
- 20.Essabbah Aguir N, Toumi A, Loussaïf C, Gorcii M, M’rad S, Ben Brahim H, et al. Visceral leishmaniasis in immunocompetent adults. About six cases. Pathol Biol (Paris). 2013;61(2):54–8. doi: 10.1016/j.patbio.2012.02.002 [DOI] [PubMed] [Google Scholar]
- 21.Aoun K, Kooli C, Bouratbine A, Romdhane N, Kaaroud H, Maéz HB, et al. Aspects épidémiologiques et cliniques de la leishmaniose viscérale de l’adulte en Tunisie. Journal de Médecine et Maladies Infectieuses. 2002;32(7):387–92. [Google Scholar]
- 22.Aoun K, Kaaroud H, Hamzaoui S, Siala E, Kooli C, Turki S, et al. Particularites de la leishmaniose viscerale de l’adulte non infecte par le VIH en Tunisie. Journal de Médecine tropicale. 2004;64(2):160–2. [PubMed] [Google Scholar]
- 23.Herne N, Hauteville D, Verdier M, Chagnon A, Abgrall J, Raillat A. Mediterranean kala-azar in 2 adults treated with immunosuppressive agents. Rev Med Interne. 1980;1(2):237–40. doi: 10.1016/s0248-8663(80)80041-5 [DOI] [PubMed] [Google Scholar]
- 24.Toumi A, Kilani B, Ammari L, Tiouiri H, Kanoun F, Belhadj S. Aspects épidémiologiques, cliniques et thérapeutiques de la leishmaniose viscérale de l’adulte à l’hôpital de la Rabta à Tunis (Tunisie) entre 1983 et 2002. Bulletin de la Societe de pathologie exotique. 2007;100(4):282–6. [PubMed] [Google Scholar]
- 25.Belhadj S, Pratlong F, Toumi NH, Kallel K, Mahjoub H, Babba H, et al. Visceral leishmaniasis in Tunisia: result of the isoenzymatic characterization of 65 Leishmania infantum strains. Trans R Soc Trop Med Hyg. 2002;96(6):627–30. doi: 10.1016/s0035-9203(02)90332-9 [DOI] [PubMed] [Google Scholar]
- 26.Aoun K, Amri F, Chouihi E, Haouas N, Bedoui K, Benikhlef R, et al. Epidemiology of Leishmania (L.) infantum, L. major and L. killicki in Tunisia: results and analysis of the identification of 226 human and canine isolates. Bull Soc Pathol Exot. 2008;101(4):323–8. doi: 10.3185/pathexo3201 [DOI] [PubMed] [Google Scholar]
- 27.Aoun K, Bouratbine A, Harrat Z, Belkaïd M, Bel Hadj Ali S. Particular profile of the zymodemes of Leishmania infantum causing visceral leishmaniasis in Tunisia. Bull Soc Pathol Exot. 2001;94(5):375–7. [PubMed] [Google Scholar]
- 28.Haouas N, Gorcii M, Chargui N, Aoun K, Bouratbine A, Messaadi Akrout F, et al. Leishmaniasis in central and southern Tunisia: current geographical distribution of zymodemes. Parasite. 2007;14(3):239–46. doi: 10.1051/parasite/2007143239 [DOI] [PubMed] [Google Scholar]
- 29.Ben Ismail R, Gradoni L, Gramiccia M, Bettini S, Ben Rachid MS, Garraoui A. Epidemic cutaneous leishmaniasis in Tunisia: biochemical characterization of parasites. Trans R Soc Trop Med Hyg. 1986;80(4):669–70. doi: 10.1016/0035-9203(86)90175-6 [DOI] [PubMed] [Google Scholar]
- 30.Khaldi F, Achouri E, Gharbi A, Debbabi A, Ben Naceur B. Leishmaniose viscérale de l’enfant. Etude des cas hospitalisés de 1974 à 1988 à l’Hôpital d’Enfants de Tunis. Médecine tropicale. 1991;51(2):143–8. [PubMed] [Google Scholar]
- 31.Ayadi A, Ben Ismail R, Ben Rachid MS. Spread of Leishmania infantum kala-azar transmission area towards central and southern Tunisia. Archives de l’Institut Pasteur de Tunis. 1991;68:269–73. [PubMed] [Google Scholar]
- 32.Besbes A, Pousse H, Ben Said M, Kharrat H, Ghenimi L. Leishmanioses viscérales infantiles du centre tunisien (221 cas). Médecine et Maladies Infectieuses. 1994;24(5):628–34. doi: 10.1016/s0399-077x(05)80704-8 [DOI] [Google Scholar]
- 33.Kallel K, Pratlong F, Haouas N, Kaouech E, Belhadj S, Anane S, et al. Isoenzymatic variability of Leishmania infantum in Tunisia concerning 254 human strains. Acta Trop. 2008;106(2):132–6. doi: 10.1016/j.actatropica.2008.02.006 [DOI] [PubMed] [Google Scholar]
- 34.Ben-Ahmed K, Aoun K, Jeddi F, Ghrab J, El-Aroui M-A, Bouratbine A. Visceral leishmaniasis in Tunisia: spatial distribution and association with climatic factors. Am J Trop Med Hyg. 2009;81(1):40–5. doi: 10.4269/ajtmh.81.1.40 [DOI] [PubMed] [Google Scholar]
- 35.Bounoua L, Kahime K, Houti L, Blakey T, Ebi KL, Zhang P, et al. Linking climate to incidence of zoonotic cutaneous leishmaniasis (L. major) in pre-Saharan North Africa. Int J Environ Res Public Health. 2013;10(8):3172–91. doi: 10.3390/ijerph10083172 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Nicolle C, Blanc G. Extension of the boil of Gafsa area in Tunisia. Archives de l’Institut Pasteur de Tunis. 1918;10:94. [Google Scholar]
- 37.Aoun K, Bouratbine A, Harrat Z, Guizani I, Mokni M, Ali S, et al. Données épidémiologiques et parasitologiques concernant la leishmaniose cutanée sporadique du nord tunisien Bulletin de la Societe de pathologie exotique. 2000;93(2):101–3. [PubMed] [Google Scholar]
- 38.Chaffai M, Rachid B, Ben-Ismail R, Osman A, Ben Makni N. Formes clinico-épidémiologiques des leishmanioses cutanées en Tunisie. Annales de Dermatologie et de Vénéréologie. 1988;115:1255–60. [PubMed] [Google Scholar]
- 39.Chargui N, Bastien P, Kallel K, Haouas N, Akrout FM, Masmoudi A, et al. Usefulness of PCR in the diagnosis of cutaneous leishmaniasis in Tunisia. Trans R Soc Trop Med Hyg. 2005;99(10):762–8. doi: 10.1016/j.trstmh.2005.06.002 [DOI] [PubMed] [Google Scholar]
- 40.Ben Salah A, Ben Messaoud N, Guedri E, Zaatour A, Ben Alaya N, Bettaieb J, et al. Topical paromomycin with or without gentamicin for cutaneous leishmaniasis. N Engl J Med. 2013;368(6):524–32. doi: 10.1056/NEJMoa1202657 [DOI] [PubMed] [Google Scholar]
- 41.Kallel K, Pratlong F, Belhadj S, Cherif F, Hammami M, Dedet JP, et al. Cutaneous leishmaniasis in Tunisia: results of the iso-enzymatic characterization of 71 strains. Ann Trop Med Parasitol. 2005;99(1):11–9. doi: 10.1179/136485905X19874 [DOI] [PubMed] [Google Scholar]
- 42.Kallel K, Haouas N, Pratlong F, Kaouech E, Belhadj S, Anane S. La leishmaniose cutanée due à Leishmania infantum MON-24 en Tunisie: extension du foyer vers le centre du pays. Bulletin de la Societe de pathologie exotique. 2008;101(1):30–1. [PubMed] [Google Scholar]
- 43.Aoun K, Bouratbine A, Harrat Z, Maherzi A, Belkaid M, Bousnina S. Confirmation de la présence de Leishmania infantum MON-80 en Tunisie. Bulletin de la Societe de pathologie exotique. 1999;92(1):29–30. [PubMed] [Google Scholar]
- 44.BenSaid M, Guerbouj S, Saghrouni F, Fathallah-Mili A, Guizani I. Occurrence of Leishmania infantum cutaneous leishmaniasis in central Tunisia. Trans R Soc Trop Med Hyg. 2006;100(6):521–6. doi: 10.1016/j.trstmh.2005.08.012 [DOI] [PubMed] [Google Scholar]
- 45.Amro A, Hamdi S, Lemrani M, Mouna I, Mohammed H, Mostafa S, et al. Moroccan Leishmania infantum: genetic diversity and population structure as revealed by multi-locus microsatellite typing. PLoS One. 2013;8(10):e77778. doi: 10.1371/journal.pone.0077778 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 46.Belhadj S, Pratlong F, Hammami M, Kallel K, Dedet JP, Chaker E. Human cutaneous leishmaniasis due to Leishmania infantum in the Sidi Bourouis focus (Northern Tunisia): epidemiological study and isoenzymatic characterization of the parasites. Acta Trop. 2003;85(1):83–6. doi: 10.1016/s0001-706x(02)00255-3 [DOI] [PubMed] [Google Scholar]
- 47.Chargui N, Amro A, Haouas N, Schönian G, Babba H, Schmidt S, et al. Population structure of Tunisian Leishmania infantum and evidence for the existence of hybrids and gene flow between genetically different populations. Int J Parasitol. 2009;39(7):801–11. doi: 10.1016/j.ijpara.2008.11.016 [DOI] [PubMed] [Google Scholar]
- 48.Nicolle C, Comte C. Origine canine du kala-azar. Bulletin de la Societe de pathologie exotique. 1908;1:299–301. [Google Scholar]
- 49.Chargui N, Haouas N, Gorcii M, Lahmar S, Guesmi M, Ben Abdelhafidh A, et al. Use of PCR, IFAT and in vitro culture in the detection of Leishmania infantum infection in dogs and evaluation of the prevalence of canine leishmaniasis in a low endemic area in Tunisia. Parasite. 2009;16(1):65–9. doi: 10.1051/parasite/2009161065 [DOI] [PubMed] [Google Scholar]
- 50.Derghal M, Tebai A, Balti G, Souguir-Omrani H, Chemkhi J, Rhim A. High-resolution melting analysis identifies reservoir hosts of zoonotic Leishmania parasites in Tunisia. Parasites Vectors. 2022;15(1):12. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 51.Ben Ismail R. Incrimination de Phlebotomus perniciosus comme vecteur de Leishmania infantum. Archives de l’Institut Pasteur de Tunis. 1993;70:91–110. [Google Scholar]
- 52.Fares W, Dachraoui K, Barhoumi W, Cherni S, Chelbi I, Zhioua E. Co-circulation of Toscana virus and Leishmania infantum in a focus of zoonotic visceral leishmaniasis from Central Tunisia. Acta Trop. 2020;204:105342. doi: 10.1016/j.actatropica.2020.105342 [DOI] [PubMed] [Google Scholar]
- 53.Chargui N, Slama D, Haouas N, Rmadi L, Babba H. Transmission cycle analysis in a Leishmania infantum focus: Infection rates and blood meal origins in sand flies (Diptera: Psychodidae). J Vector Ecol. 2018;43(2):321–7. doi: 10.1111/jvec.12316 [DOI] [PubMed] [Google Scholar]
- 54.Remadi L, Chargui N, Jiménez M, Molina R, Haouas N, González E, et al. Molecular detection and identification of Leishmania DNA and blood meal analysis in Phlebotomus (Larroussius) species. PLoS Negl Trop Dis. 2020;14(3):e0008077. doi: 10.1371/journal.pntd.0008077 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 55.Weslati M, Ghrab J, Benabid M, Souissi O, Aoun K, Bouratbine A. Diversity, Abundance and Leishmania infantum infection rate of phlebotomine sandflies in an area with low incidence of visceral leishmaniasis in northern Tunisia. Microorganisms. 2022;10(5):1012. doi: 10.3390/microorganisms10051012 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 56.Benabid M, Ghrab J, Rhim A, Ben-Romdhane R, Aoun K, Bouratbine A. Temporal dynamics and Leishmania infantum infection prevalence of Phlebotomus perniciosus (Diptera, Phlebotominae) in highly endemic areas of visceral leishmaniasis in Tunisia. PLoS One. 2017;12(9):e0184700. doi: 10.1371/journal.pone.0184700 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 57.Remadi L, Jiménez M, Chargui N, Haouas N, Babba H, Molina R. The vector competence of Phlebotomus perniciosus for Leishmania infantum zymodemes of Tunisia. Parasitol Res. 2018;117(8):2499–506. doi: 10.1007/s00436-018-5939-y [DOI] [PubMed] [Google Scholar]
- 58.Remadi L, Chargui N, Depaquit J, Randrianambinintsoa FJ, Chaâbane-Banaoues R, Babba H, et al. On abnormal Phlebotomus perniciosus (Diptera: Psychodidae: Phlebotominae) from the center of Tunisia. J Med Entomol. 2023;60(6):1418–25. doi: 10.1093/jme/tjad114 [DOI] [PubMed] [Google Scholar]
- 59.Boudabous R, Jaouadi K, Bounamous A, Babba H. Morphological and molecular investigations of population structure of Phlebotomus perniciosus and Phlebotomus longicuspis (Diptera: Psychodidae) in Tunisia. J Med Entomol. 2012;49(4):787–93. doi: 10.1603/me11110 [DOI] [PubMed] [Google Scholar]
- 60.Chaouch M, Chaabane A, Ayari C, Ben Othman S, Sereno D, Chemkhi J, et al. Investigation of natural infection of Phlebotomine (Diptera: Psychodidae) by Leishmania in Tunisian endemic regions. Parasite Epidemiol Control. 2021;14:e00212. doi: 10.1016/j.parepi.2021.e00212 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 61.Barhoumi W, Fares W, Cherni S, Derbali M, Dachraoui K, Chelbi I, et al. Changes of sand fly populations and Leishmania infantum infection rates in an irrigated village located in arid Central Tunisia. Int J Environ Res Public Health. 2016;13(3):329. doi: 10.3390/ijerph13030329 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 62.Guerbouj S, Chemkhi J, Kaabi B, Rahali A, Ben Ismail R, Guizani I. Natural infection of Phlebotomus (Larroussius) langeroni (Diptera: Psychodidae) with Leishmania infantum in Tunisia. Trans R Soc Trop Med Hyg. 2007;101(4):372–7. doi: 10.1016/j.trstmh.2006.07.007 [DOI] [PubMed] [Google Scholar]
- 63.Remadi L, Farjallah D, Chargui N, Belgacem S, Baba H, Zrieq R, et al. Blood meal analysis and molecular detection of mammalian Leishmania DNA in wild-caught Sergentomyia spp. from Tunisia and Saudi Arabia. Parasitol Res. 2023;122(9):2181–91. doi: 10.1007/s00436-023-07919-y [DOI] [PubMed] [Google Scholar]
- 64.Killick-Kendrick R. Phlebotomine vectors of the leishmaniases: a review. Med Vet Entomol. 1990;4(1):1–24. doi: 10.1111/j.1365-2915.1990.tb00255.x [DOI] [PubMed] [Google Scholar]
- 65.Sadlova J, Dvorak V, Seblova V, Warburg A, Votypka J, Volf P. Sergentomyia schwetzi is not a competent vector for Leishmania donovani and other Leishmania species pathogenic to humans. Parasit Vectors. 2013;6(1):186. doi: 10.1186/1756-3305-6-186 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 66.Mhadhbi M, Sassi A. Infection of the equine population by Leishmania parasites. Equine Vet J. 2020;52(1):28–33. doi: 10.1111/evj.13178 [DOI] [PubMed] [Google Scholar]
- 67.Ortega-García MV, Salguero FJ, García N, Domínguez M, Moreno I, Berrocal A. Equine infection with Leishmania spp. in Costa Rica: study of five cases. Vet Med Sci. 2021;7(6):2234–9. doi: 10.1002/vms3.587 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 68.Martín-Sánchez J, Torres-Medina N, Morillas-Márquez F, Corpas-López V, Díaz-Sáez V. Role of wild rabbits as reservoirs of leishmaniasis in a non-epidemic Mediterranean hot spot in Spain. Acta Trop. 2021;222:106036. doi: 10.1016/j.actatropica.2021.106036 [DOI] [PubMed] [Google Scholar]
- 69.Jiménez M, González E, Martín-Martín I, Hernández S, Molina R. Could wild rabbits (Oryctolagus cuniculus) be reservoirs for Leishmania infantum in the focus of Madrid, Spain?. Vet Parasitol. 2014;202(3–4):296–300. doi: 10.1016/j.vetpar.2014.03.027 [DOI] [PubMed] [Google Scholar]
- 70.Benikhlef R, Harrat Z, Tchoua R, Dedet JP, Mâaza S, Aoun K. Detection of Leishmania infantum MON-1 in a dog from a northern region of Algeria. Bulletin de la Société de Pathologie Exotique. 2014;107(2):101–4. [Google Scholar]
- 71.Harrat Z, Tchoua R, Belkaid M, Debruyne M, Dedet JP. Visceral leishmaniasis in the Algerian population: a review of the literature. Bulletin de la Société de Pathologie Exotique. 2009;102(4):208–13. [Google Scholar]
- 72.Amro A, Hamdi S, Lemrani M, Mouna I, Mohammed H, Mostafa S, et al. Moroccan Leishmania infantum: genetic diversity and population structure as revealed by multi-locus microsatellite typing. PLoS One. 2013;8(10):e77778. doi: 10.1371/journal.pone.0077778 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 73.Amro A, Gashout A, Al-Dwibe H, Zahangir Alam M, Annajar B, Hamarsheh O, et al. First molecular epidemiological study of cutaneous leishmaniasis in Libya. PLoS Negl Trop Dis. 2012;6(6):e1700. doi: 10.1371/journal.pntd.0001700 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 74.Amro A, Al-Dwibe H, Gashout A, Moskalenko O, Galafin M, Hamarsheh O, et al. Spatiotemporal and molecular epidemiology of cutaneous leishmaniasis in Libya. PLoS Negl Trop Dis. 2017;11(9):e0005873. doi: 10.1371/journal.pntd.0005873 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 75.Aoun K, Bouratbine A. Cutaneous leishmaniasis in North Africa: a review. Parasite. 2014;21:14. doi: 10.1051/parasite/2014014 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 76.Croft SL, Olliaro P. Leishmaniasis chemotherapy – challenges and opportunities. Clin Microbiol Infect. 2011;17(10):1478–83. doi: 10.1111/j.1469-0691.2011.03630.x [DOI] [PubMed] [Google Scholar]
- 77.Rijal S, Sundar S, Mondal D, Das P, Alvar J, Boelaert M. Treatment of visceral leishmaniasis in the Indian subcontinent: current status and future prospects. BMJ. 2019;364:k5224. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 78.Harrat Z, Boubidi SC, Pratlong F, Benikhlef R, Selt B, Dedet JP, et al. Description of a dermatropic Leishmania close to L. killicki (Rioux, Lanotte & Pratlong 1986) in Algeria. Trans R Soc Trop Med Hyg. 2009;103(7):716–20. doi: 10.1016/j.trstmh.2009.04.013 [DOI] [PubMed] [Google Scholar]
- 79.Bounoua L, Kahime K, Houti L, Blakey T, Ebi KL, Zhang P, et al. Linking climate to incidence of zoonotic cutaneous leishmaniasis (L. major) in pre-Saharan North Africa. Int J Environ Res Public Health. 2013;10(8):3172–91. doi: 10.3390/ijerph10083172 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 80.Ready PD. Epidemiology of visceral leishmaniasis. Clin Epidemiol. 2014;6:147–54. doi: 10.2147/CLEP.S44267 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 81.Amro A, Al-Dwibe H, Lashhab A. Cutaneous leishmaniasis mimicking sarcoidosis in Libyan patient: a case report. J Microbiol Exp. 2020;8(5):171–4. [Google Scholar]
- 82.Desjeux P, Alvar J. Leishmania/HIV co-infections: epidemiology in Europe. Ann Trop Med Parasitol. 2003;97 Suppl 1:3–15. doi: 10.1179/000349803225002499 [DOI] [PubMed] [Google Scholar]
- 83.Alvar J, Aparicio P, Aseffa A, Den Boer M, Cañavate C, Dedet J-P, et al. The relationship between leishmaniasis and AIDS: the second 10 years. Clin Microbiol Rev. 2008;21(2):334–59, table of contents. doi: 10.1128/CMR.00061-07 [DOI] [PMC free article] [PubMed] [Google Scholar]


