*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 [69].

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 [24]. Twenty-two (22) cases of adult VL (including six patients infected with HIV virus) were recorded over a period of 20 years [70]. 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 *L. infantum*: The zymodeme MON-1 is the most identified one (89.12% of the VL cases). It was isolated in both infantile and adult VL cases [24]. The second zymodeme responsible for VL is *L. infantum* MON-24. The first case of VL due to this zymodeme was reported in 2000 [71]. Currently, *L. infantum* MON-24 is responsible for 8.08% of VL cases in Tunisia [24]. Finally, *L. infantum* MON-80 was identified in some sporadic VL cases in centre Tunisia (Zaghouan and Kairouan). It is responsible for 2.07% of VL cases [24].

#### *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 [72]. By the introduction of the isoenzymatic analysis, all strains isolated from infected dogs throughout the country were identified as *L. infantum* MON-1 [24, 30]. This result confirms the dog as the reservoir host of zoonotic VL caused by the zymodeme MON-1. In 2009, Benikhlef reported three cases of canine VL in Tunisia due to *L. infantum* MON-80; nevertheless, their role as reservoir for this zymodeme is still discussed [42].

At the middle of the twentieth century, *P. perniciosus* has been reported to be the vector of *L. infantum* MON-1 and the complete life cycle was demonstrated [73]. However, the vector hosts of the two other zymodemes MON-24 and MON-80 are still unknown (**Figure 5**). Recently, *L. infantum* DNA was detected in the sand flies mid gut of the *Larroussius* (*P. langeroni, P. longi‐ cuspis, P. perfiliewi*) and *Phlebotomus* (*P. papatasi*) subgenera as well as the *Sergentomyia* genus (*S. minuta*) [45, 46]. However, neither parasite isolation from these sand flies species nor *L. infantum* isoenzymatic identification were carried out in Tunisia yet to confirm their role as vector of *L. infantum* zymodemes.

**Figure 5.** Transmission cycles of the viscerotropic *Leishmania infantum* zymodemes in Tunisia. (Laboratory of Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia).

#### *2.2.5. Geographical distribution*

*2.2.1. History*

126 The Epidemiology and Ecology of Leishmaniasis

*2.2.2. Clinical forms*

*2.2.3. Causative species*

*2.2.4. Transmission cycle*

thrombocytopenia, and leucopenia [69].

anemia, and splenomegaly) was less stable.

The first case of VL in Tunisia was reported by Laveran and Cathoire in 1904 [64] 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) [65]. Some outbreaks of VL were reported in centre Tunisia

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 [66]. Currently, VL in Tunisia shows a stable incidence of about 100 cases per year [67, 68].

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,

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 [24]. Twenty-two (22) cases of adult VL (including six patients infected with HIV virus) were recorded over a period of 20 years [70]. Within this group, the triad of VL symptoms (fever,

The isoenzymatic identification of the isolated parasite have revealed three zymodemes of a single taxon *L. infantum*: The zymodeme MON-1 is the most identified one (89.12% of the VL cases). It was isolated in both infantile and adult VL cases [24]. The second zymodeme responsible for VL is *L. infantum* MON-24. The first case of VL due to this zymodeme was reported in 2000 [71]. Currently, *L. infantum* MON-24 is responsible for 8.08% of VL cases in Tunisia [24]. Finally, *L. infantum* MON-80 was identified in some sporadic VL cases in centre

The domestic dog has been incriminated in the transmission of VL since the first report of canine leishmaniasis in 1908 [72]. By the introduction of the isoenzymatic analysis, all strains isolated from infected dogs throughout the country were identified as *L. infantum* MON-1 [24, 30]. This result confirms the dog as the reservoir host of zoonotic VL caused by the zymodeme MON-1. In 2009, Benikhlef reported three cases of canine VL in Tunisia due to *L. infantum* MON-80; nevertheless, their role as reservoir for this zymodeme is still discussed [42].

Tunisia (Zaghouan and Kairouan). It is responsible for 2.07% of VL cases [24].

mainly Kairouan where 247 cases were reported between 1984 and 1996 [66].

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.

**Figure 6.** Geographical distribution of viscerotropic *Leishmania infantum* zymodemes [24].
