**7. References**

246 Current Topics in Tropical Medicine

cases diagnosed in our laboratory was as follows: 74 cases in 1992, 72 cases in 1993 and 83 cases in 2005. This is not surprising as nearly 50 % or more of VL cases originate from

Concerning CL, we have to point out that first SCL cases from central Tunisia were diagnosed in our laboratory in patients with clinical presentation found to be evocative of this form, and amastigotes, very suggestive of *L. infantum* as compared to *L. major* because of their small size (Ben Saïd et al., 2006). As mentioned in section 2, additional cases were further reported and the spread of SCL towards central and southern Tunisia confirmed. Similarly, the first CCL case originating from outside the original foci of Tataouine area was again diagnosed in our laboratory (Haouas et al., 2005); and CCL spread was further confirmed by additional reports leading to the revised geographical distribution of the disease (Bouratbine et al., 2005; Aoun et al., 2008). In our laboratory, we used to diagnose ZCL since 1986. Up to the late 1990s, the number of diagnosed cases was too moderate as compared to that of ZCL reported cases in the endemic regions (Figures 7 & 9). This, for at least, the two following reasons: **i)** at the beginning of the outbreak, many patients suffering from ZCL were only clinically diagnosed, so that only a few of them were addressed to the laboratory for parasitological confirmation, **ii)** from the 1990s, a great number of families originating from ZCL endemic areas migrated and settled in Sousse city and suburbs, where they progressively constituted a large community. Most of them used to return back to their home of origin for summer holidays where, because continuously exposed to phlebotomine bites, many of them contract leishmaniasis which is later addressed to us for diagnosis. It is worth mentioning that a high proportion of this community originates from Sidi Khelif in Ouled Haffouz delegation, Sidi Bouzid; and and many of them were contaminated there and were later diagnosed in our laboratory. From 2000 and onwards, the number of ZCL patients who attended our laboratory for diagnosis dramatically increased. We consider that since this date the activity of our laboratory indirectly but adequately reflects the actual status of ZCL in central Tunisia, namely in Sidi Bouzid, Mahdia, Kairouan and Sousse governorates. This is best illustrated by our findings in 2004 where > 400 ZCL cases were diagnosed in our laboratory. In the same year, the highest incidence of ZCL (> 15000 cases) was registered at the national level, because of the three epidemic peaks that occurred in Sidi Bouzid (Sidi Bouzid city, Regueb, Menzel Bouzayène), Gafsa (Gafsa city, Sned, Mdhilla) and Kairouan (Nasrallah, Hajeb Layoun, Chrarda) governorates (Anonymous). The peak we registered in 2001 was due to an outbreak that arose in Chahda, a small locality in Chorbène delegation (Mahdia governorate). Indeed, more than 50 % of cases we diagnosed in 2001 were from this locality. A similar peak in Sidi El Heni delegation (Sousse governorate) was registered in 2006, with 107 cases. This peak was followed by a noticeable decrease as soon as control activities were carried out in the area. Similarly the decrease in ZCL incidence shown in our study over the last 5 years can be attributed to an important decrease in the transmission in Sidi Bouzid region where control activities were launched in the mid 2000s (Figure 9). This decrease was reflected on the national level over the same period (Figure 7).

Kairouan governorate.

Last, our results confirm the seasonal occurrence of ZCL.

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**16** 

*1Germany 2Colombia 3USA* 

*Systems Biology, Heidelberg* 

**Current Advances in Computational Strategies** 

*3University of Texas Medical Branch/Department of Biochemistry and Molecular Biology* 

Leishmaniasis is a complex disease caused by several species of the *Leishmania* genus ranging in severity from cutaneous and mucocutaneous lesions to the chronic visceral form that if untreated adequately can cause death. It has a worldwide distribution in 98 countries and 85 out of 98 are developing or poor countries. One of the main problems in leishmaniasis is the limited number of drug options along with the adverse effects they can cause including death (Ahasan., et al. 1996; Sundar & Chakravarty 2010; Oliveira., et al. 2011). In addition, there are reports of treatment failures due to increased parasite resistance to the first drug of choice, the antimonials (Faraut-Gambarelli., et al. 1997; Goyeneche-Patino., et al. 2008). Second-choice drugs, such as amphotericin B, pentamidine, paromomycin, and more recently, miltefosine, have also toxic effects that require hospital management (Maltezou 2008; Oliveira., et al. 2011). Miltefosine, the only oral administered drug for leishmaniasis, has not been tested in many *Leishmania* species. Recently, a central nervous system toxicity was reported for liposomal amphotericin B therapy used to treat

In the search for new drug targets in *Leishmania*, a group of proteins have been proposed based mainly on their known function, the expression level, and localization, or because they are involved in important metabolic processes in the parasite. Topoisomerases (Das., et al. 2008), kinases (de Azevedo & Soares 2009), proteins localized or targeted to lysosomes (Carrero-Lerida., et al. 2009) are some potential *Leishmania* drug targets. However, none of these protein targets have been used to successfully develop new drugs that can substitute

Currently, the massive genome sequencing of many medically important microorganisms together with protein structure and drug databases and the development of new computational tools, will allow molecular targets and new drugs to be searched in a more rigorous manner. Three *Leishmania* genomes, *L. major*, *L. infantum* and *L. braziliensis*

**1. Introduction** 

the existing therapies.

cutaneous leishmaniasis (Glasser & Murray 2011).

*and the Sealy Center for Structural Biology and Molecular Biophysics, Galveston* 

**for Drug Discovery in Leishmaniasis** 

*1German Cancer Research Center (DKFZ)/ Division Theoretical* 

*2Universidad de Antioquia/Programa de Estudio y Control de* 

*Enfermedades Tropicales – PECET, Medellín* 

Andrés F. Flórez1,2, Stanley Watowich3 and Carlos Muskus2

