In Tunisia, both cutaneous (CL) and visceral leishmaniases (VL) are historical diseases that have been described since the nineteenth century. Cutaneous form is more prevalent than the visceral one. It is caused by three taxa (Leishmania major, Leishmania infantum, and Leishmania killicki synonymous Leishmania tropica) and six zymodemes (MON-1, MON-8, MON-24, MON-25, MON-80, and MON-317). Among these dermotropic zymodemes, sand flies vectors and reservoir hosts were identified for only three ones. Transmission cycles of L. infantum MON-24 and MON-80 and L. killicki MON-317 are still unknown. Zoonotic CL is largely distributed and covers mainly the sub-arid and arid bioclimatic stages. Nevertheless, it has recently spread to the humid and sub-humid stages in northern Tunisia. Sporadic and chronic CL are less prevalent with limited geographical distribution. Visceral leishmaniasis (VL) is mainly infantile that affects children of <13 years. It is caused by the single taxon L. infantum. Transmission cycle of this parasite is zoonotic but not well elucidated. Three zymodemes are responsible for the genesis of VL (MON-1, MON-24 and MON-80). Only the transmission cycle of L. infantum MON-1 is identified. Geographically, VL is mainly distributed in the humid, sub-humid, and semi-arid bioclimatic stages of the country. Despite the large progress of knowledge in the ecoepidemiology of leishmaniases in Tunisia, many parameters of the transmission cycles of these taxa are still unknown and need further investigations to identify them.
- cutaneous leishmaniasis
- visceral leishmaniasis
In the Mediterranean basin region, both cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL) are well established diseases with an estimated annual incidence ranges from 239,500 to 393,600 and from 1200 to 2000 cases, respectively. In Tunisia (North Africa, South Mediterranean basin), leishmaniases are largely spread causing a serious public health problem. Clinically, both CL and VL are encountered in this region. Nevertheless, the cutaneous form is most prevalent and largely distributed. Visceral leishmaniasis is less prevalent in this region with a zoonotic transmission of the causative agent.
In Tunisia, leishmaniases are historical. Indeed, the first documented cutaneous case was reported in 1884, while the first VL case was in 1904. Nevertheless, these infectious diseases were stayed neglected for a long period and the epidemiological investigations were scarce. Indeed, an analysis of the published research on leishmaniases in Tunisia over about a century (1884–1980) showed around 20 published items. From the beginning of 1980s of the last century, the number of publications has increased from 5 publications (1981–1985), to 14 publications (1991–1995), 41 publications (2001–2005), and 85 publications (2011–2015).
The aim of this chapter is to review the history of leishmaniases in Tunisia and to present the new insights into the epidemiological features of this disease. This includes clinical forms, transmission cycles, and geographical distribution.
As many other regions of the Mediterranean basin, Tunisia is an endemic focus for both cutaneous and visceral leishmaniases. Each of these two clinical forms has its own epidemiological profile.
2.1. Cutaneous leishmaniases
Cutaneous leishmaniasis refers to a dermal lesion which appears at the site of the infected sand fly bite. The lesion is usually painless and characterized by a gradual evolution. It firstly appears as a tiny erythema, which then develops into a papule and nodule that can ulcerate within 2 weeks to 6 months. It heals gradually over months or years. Although CL is mild and not life threatening, its disfiguring lesions and scars with altered pigmentation severely affect the social and psychological functioning of the affected individuals causing anxiety, depression, decrease in body satisfaction, and low quality of life [1–3]. The clinical form of CL lesions varies between patients, reflecting different species of parasite, different virulence degree inside the same species or a difference in the immunological status of patients.
The first real documented case of CL in Tunisia date from 1884 in the region of Gafsa, south Tunisia [4, 5]. Indigenous people named it “Habb El Seneh” (sore of a year) or “Bess El Tmeur” (evil of the dates) related to their supposition that the disease is the result of the consumption of dates, sting of palms or the drinking of the water . In 1882, Achard, military physician in Gafsa, gave the infection the name of “Clou de Gafsa” (boil of Gafsa). It was only in 1905 that Nicolle and Cathoire made microbiological analysis of the sore scraping and reported the presence of small oval bodies sized of 4 μm similar to those already described by Wright in 1903 in the oriental sore [7–9]. While Wright proposed the name
Given that the Gafsa boil was almost observed on the uncovered parts of the body, that the infection was restricted to some cities of Gafsa near water sources, and that patients reported the bite of insects few days before the onset of the lesion, Billet supposed that the infection is transmitted by the bite of the mosquito Pyretophorus chaudoyei . It was only in 1921 that the brothers Sergent proved the transmission of CL by the female sand fly
Nevertheless, few were the data available on the incidence of the disease, its geographical distribution and the causative species. Since the 1980s of the last century and by the introduction of both biochemical and molecular tools, many research teams have investigated the epidemiology of CL in many regions of the country focusing on the characterization of the parasite and the identification of both reservoirs and phlebotomine sand fly hosts.
The precise characterization of the parasite circulating in Tunisia started in 1981 using the gold standard method (isoenzymatic analysis) . Since then, many research teams have been involved in the isoenzymatic analysis of
2.1.1. Cutaneous leishmaniasis due to
Zoonotic cutaneous leishmaniasis (ZCL) due to
In 1908, an extension of the Gafsa boil occurred from the southwest (Gafsa) to the west (Feriana, Kasserine) and southeast (Aioun, Tataouine) regions. Since then, the endemic area did not go beyond Kasserine (Sbeitla) . The Tunisian Centre has been free from ZCL until a major outbreak in 1982 in the Sidi Saad Region (Kairouan) [21, 22]. Then, ZCL has spread to many foci in centre and south of Tunisia [23, 24]. Ruiz Postigo 2010  reported an annual incidence of 2750 new case of ZCL. Nevertheless, the true incidence of this noso-geographical form of CL is underestimated due to multiple factors including the increasing prevalence of the disease, the unrecorded cases, and the expanding areas of endemicity.
184.108.40.206. Clinical forms
This clinical polymorphism seems to be rather high, which could reflect the complexity of the disease involving several factors related to the parasite (virulence, parasitic load, and the presence of other pathogens), the type and duration of clinical lesion, the geographic location, the disease reservoir, and the host immune status [28, 29].
220.127.116.11. Causative species
The precise characterization of the parasite circulating in Tunisia foci started only in 1981 . Since then, many research teams have been involved in the isoenzymatic analysis of
18.104.22.168. Transmission cycle
In 1987, Ben Ismail et al.  proved that
22.214.171.124. Geographical distribution
Zoonotic CL due to
2.1.2. Cutaneous leishmaniasis due to
126.96.36.199. Clinical forms
Unfortunately, the low prevalence of sporadic CL (SCL) as well as the absence of published data concerning the clinical polymorphism of this noso-geographical form of CL prevents us to make a define description of the lesion. Previous studies reported that in over 80% of cases, CL caused by
188.8.131.52. Causative species
The precise identification of the causative agent of SCL using the golden standard method has been started in the beginning of the 1990s of the last century. Thus, three zymodemes of the
184.108.40.206. Transmission cycle
The transmission cycle of
220.127.116.11. Geographical distribution
Geographical distribution of SCL is apparently restricted to the humid and sub-humid bioclimatic areas. Its distribution overlaps with that of VL in north and central Tunisia. Indeed, Haouas et al. reported that 95.3% of dermotropic
2.1.3. Cutaneous leishmaniasis due to
Leishmania killicki(synonymous L. tropica)
Chronic cutaneous leishmaniasis (CCL) due to
The taxonomic status of
18.104.22.168. Clinical forms
22.214.171.124. Causative species
The first description of CL due to
126.96.36.199. Transmission cycle
In the last century, the transmission cycle of
188.8.131.52. Geographical distribution
2.2. Visceral leishmaniases
Visceral leishmaniasis refers to the dissemination of the parasite
The first case of VL in Tunisia was reported by Laveran and Cathoire in 1904  in the region of La Goulette, north of the country. Between 1904 and 1908, Charles Nicolle reported two new VL cases of children living in Tunis (north of the country). Since this date and till 1935, Charles Nicolle and collaborators reported 120 new VL cases mainly distributed in the north (Tunis, Bizerte, Zaghouan, Grombalia, Beja, and El Kef), the centre (Sousse and Kairouan) with one case in Tozeur (south of Tunisia) . Some outbreaks of VL were reported in centre Tunisia mainly Kairouan where 247 cases were reported between 1984 and 1996 .
Since the description of VL in Tunisia, the annual incidence has increased progressively going from three cases in beginning of the twentieth century to 57 in the 1980s of the same century . Currently, VL in Tunisia shows a stable incidence of about 100 cases per year [67, 68].
2.2.2. Clinical forms
As many other Mediterranean basin countries, LV in Tunisia has an infantile form affecting mainly children under 5 years. Indeed, the age of infected children ranged from 2 months to 13 years with a median, 18 months. The most common clinical symptoms at admission were splenomegaly, fever, and hepatomegaly. The principal biological disturbances were anemia, thrombocytopenia, and leucopenia .
While infantile VL is the most common form in Tunisia, cases of VL in both immunocompetent and immunocompromised (with HIV infection) adults were also reported in Tunisia . Twenty-two (22) cases of adult VL (including six patients infected with HIV virus) were recorded over a period of 20 years . Within this group, the triad of VL symptoms (fever, anemia, and splenomegaly) was less stable.
2.2.3. Causative species
The isoenzymatic identification of the isolated parasite have revealed three zymodemes of a single taxon
2.2.4. Transmission cycle
The domestic dog has been incriminated in the transmission of VL since the first report of canine leishmaniasis in 1908 . By the introduction of the isoenzymatic analysis, all strains isolated from infected dogs throughout the country were identified as
At the middle of the twentieth century,
2.2.5. Geographical distribution
Until 1980s, geographical distribution of VL in Tunisia was limited to the humid, sub-humid, and semi-arid bioclimatic stages. The main endemic foci were localized in the north of the country including Zaghouan, Kef, Jendouba, Seliana, Nabeul, Beja, and Tunis [24, 74, 75]. However, more recently, VL has extended to the arid areas in central and southern Tunisia including Kairouan, Monastir, Kasserine, Sfax, Gabes, Sidi Bouzid, and Tozeur [24, 41, 66, 75–77] (Figure 6). Such extension could be the result of many factors including the travel of the reservoir host and the environmental changes sustaining sand flies populations.
Both cutaneous and visceral leishmaniases are old infectious diseases in Tunisia. Over more than a century since the discovery of the disease, we have witnessed an extraordinary progress in the knowledge of the epidemiology of