Localized cutaneous leishmaniasis caused by Leishmania major is polymorphic in its clinical presentation and evolution. Clinical and parasitologic features and disease evolution of 112 Tunisian patients was evaluated. The expression of interleukin (IL)-4, IL-6, IL-10, IL-12 (p40), interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha mRNA was analyzed by reverse transcription-polymerase chain reaction in 73 biopsies. Cytokine mRNA expression varied individually over a wide range; TNF-alpha, IL-6, and IFN-gamma were detectable in >90% of lesions, IL-12 and IL-10 in 40% and 70%, respectively, and IL-4 in only 9%. Statistical analysis demonstrated positive association between the level of IL-12 and IFN-gamma and the presence of parasites in the lesions. Unfavorable evolution of the lesions was positively associated with high IL-10, IL-12, and IFN-gamma mRNA expression. These results indicate that an unfavorable clinical outcome was not related to an inadequate Th1 cell response and suggest that the macrophage-activating effect of IFN-gamma may be inhibited by the concomitant expression of IL-10.

The gp63 encoding genes were characterized by PCR-RFLP in 35 isolates representative of the Leishmania donovani complex (L. infantum, L. donovani, L. archibaldi and L. chagasi), with special attention to Mediterranean L. infantum from different geographical origins, and in separate groups from Old World Leishmania (L. major, L. tropica and L. aethiopica). The aim was to evaluate how the possible selective pressure by the host on these important surface proteins would influence structuring of our sample. Comparison was carried out with the structure obtained (i) from reported isoenzyme data, characters supposed to vary neutrally, and (ii) from PCR-RFLP analysis of gp63 inter-genic regions, containing nontranslated spacers and regulatory genes. Polymorphism within the gp63-encoding region, was much higher than in gp63 inter-genic regions. In the gp63 intra-genic dendrogram, the 4 species of L. donovani complex were discriminated and quite distinct from outgroups. Within L. infantum, geographical structuring was observed and did not overlap with the structure built-up from isoenzymes and inter-genic data. These results support the idea of a strong host-selection on gp63, at vector level but most of all at vertebrate (human or dog) immunological level. Furthermore, they illustrate how the nature of genetic characters may influence the perception of population structuring.

The epidemiology, clinical patterns, and spatial spread of Mediterranean visceral leishmaniasis were retrospectively studied in central Tunisia. The clinical profile of the disease was typical of the Mediterranean infantile form. Malnutrition and associated infectious diseases were observed in 62.5% and 55% of cases, respectively. The case-fatality rate was 6.2% and resistance to meglumine antimonate was observed in 1.6% of patients. The annual incidence of cases increased from approximately 10 cases per year before 1991 to approximately 50 cases per year between 1992 and 1994. The cumulative incidence was 133.7/100,000 among children aged < 15 years. This increase was preceded by 3 years of high mean annual rainfall in the region. The spatial distribution of the incidence of the infection through time showed an aggregation of cases in the northern part of the area where intensive agriculture projects took place during the last 10 years, leading to the establishment of a stable Leishmania infantum transmission cycle below the Atlas mountain chains, and an evident tendency to a progressive extension to the south.

To accurately quantify the different outcomes of Leishmania major infection and to evaluate the fraction of zoonotic cutaneous leishmaniasis (ZCL) cases prevented by naturally acquired leishmanin skin test (LST) reactivity, a cohort of 470 children was followed up in 2 endemic foci, Remada and Dhiba, in southern Tunisia. During May 1997, before the ZCL emergence season, LST was performed, and results were reassessed 12 months later. Active case detection during the ZCL emergence season showed a high incidence of ZCL: 57.0% in Remada and 13.7% in Dhiba. The preventive fraction of ZCL conferred by LST reactivity increased proportionally with the reaction size before the emergence season, revealing a dose-response effect of approximately 70%. In addition, asymptomatic L. major infection appeared to be a significant form of natural immunization, particularly in the context of relatively low transmission. These findings may help in the design and evaluation of vaccines.

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