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Leishmaniasis is the second and fourth highest cause of mortality and morbidity respectively among all tropical diseases. Recurrence in the onset of leishmaniasis is a major problem that needs to be addressed to reduce the case fatality rate and ensure timely clinical intervention. Here we are investigating the association of risk factors with recurrent cutaneous leishmaniasis to address this issue. Patients received by Nasser Ullah Khan Babar Hospital in Peshawar, Pakistan from March 2019 to July 2020 were enrolled in this study. Those patients who developed symptoms after completion of treatment were included in Group-A while those who had atypical scars like leishmaniasis but were negative for cutaneous leishmaniasis were included in the comparison group tagged as Group B. All those individuals who had completed six weeks of treatment for CL but had normal complete blood counts (CBC) were included to avoid other underlying immunological pathologies, while we excluded those participants who had co-morbidities like diabetes, liver disease, cardiac disease, and pregnant and lactating women through their history Association was tested between Group-A and Group-B with other explanatory variables through chi-square test. The regression model was proposed to determine the predictors. A total of 48 participants of both sexes were included in the study with a mean age of 32.2 ± 15.10. The data suggest that females are overrepresented among the patients with recurrent leishmaniasis [21(53.8 %,); p = 0.07]. Compared to patients; healthy participants had a higher proportion of adults (19–59 years) versus adolescents (13–18 years) [26(66.7 %) vs 07(17.9), p = 0.004]. Multivariate logistic regression analysis shows that females are 2.1 times more prone to infections among cases as compared to healthy individuals [unadjusted OR 2.20, 95 % confidence interval (CI) 1.5–10.6, p = 0.02; adjusted OR 2.1, 95 % CI 1.50–10.69, p = 0.02]. We propose that patients receiving intradermal were less likely to be infected as compared to those receiving intralesional injections [unadjusted OR 0.07.0, 95 % confidence interval (CI) 1.18–3.37, p = 0.03; adjusted OR 0.06, 95 % CI 1.18–3.38, p = 0.03]. Old age (adults) and sex (females) were the strongest predictors to be associated with recurrent leishmaniasis. Similarly, the choice of intradermal as compared to intralesional injection and the prolonged treatment duration were strongly associated with greater chances of recurrence. [ABSTRACT FROM AUTHOR]

Background: The IL-12/IFN-γ axis plays a vital role in the control of intramacrophagic pathogens including Leishmania infections. Objective: The aim of this study was to investigate genetic defects in the IL-12/IFN-γ axis in cutaneous leishmaniasis patients, using immunological and genetic evaluation. Methods: Enzyme-linked immunosorbent assay was used to quantify IFN-γ , while flow cytometry was performed to analyze surface IL-12Rβ1/IL-12Rβ2 expression and phosphorylation of signal transducers as well as the activator of transcription 4 (pSTAT4). Sequencing was carried out for genetic analysis. Results: The peripheral blood mononuclear cells from the two patients (P1 and P2) demonstrated impaired production of IFN-γ. Furthermore, abolishment of the surface expression of Il-12Rβ1 was observed in lymphocytes, with consequent impairment of STAT4 phosphorylation in the lymphocytes of P1 and P2. IL-12Rβ1 deficiency was identified, which was caused by a novel homozygous missense mutation (c.485>T/p.P162L) and a novel homozygous nonsense mutation (c.805G>T/P.E269*) in the IL-12R β 2 gene of P1 and P2, respectively. In silico analyses predicted these novel mutations as being pathogenic, causing truncated proteins, with consequent inactivation. Conclusion: Our data have expanded the phenotype and mutation spectra associated with IL-12Rβ1 deficiency, and suggest that patients with CL should be screened for mutations in genes of the IL-12/IFN-γ axis. [ABSTRACT FROM AUTHOR]