@article{FirdessaGoodAmstaldenetal.2015,
  author    = {Firdessa, Rebuma and Good, Liam and Amstalden, Maria Cecilia and Chindera, Kantaraja and Kamaruzzaman, Nor Fadhilah and Schultheis, Martina and R{\"o}ger, Bianca and Hecht, Nina and Oelschlaeger, Tobias A. and Meinel, Lorenz and L{\"u}hmann, Tessa and Moll, Heidrun},
  title     = {Pathogen- and host-directed antileishmanial effects mediated by polyhexanide (PHMB)},
  series = {PLoS Neglected Tropical Diseases},
  volume    = {9},
  journal   = {PLoS Neglected Tropical Diseases},
  number    = {10},
  doi       = {10.1371/journal.pntd.0004041},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148162},
  pages     = {e0004041},
  year      = {2015},
  abstract  = {Background Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. Methodology/Principal Findings Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB's DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. Conclusions Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators.},
  language  = {en}
}
@phdthesis{FirdessaFite2015,
  author    = {Firdessa Fite, Rebuma},
  title     = {Use of polyhexanide and nanomedicine approach for effective treatments of cutaneous leishmaniasis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115072},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2015},
  abstract  = {Despite huge suffering caused by cutaneous leishmaniasis (CL), there is no effective and affordable treatment strategy against CL and no licensed vaccines. The current treatments show limited efficacy and high toxicity. Improved therapies through discovery of novel drugs and/or an alternative treatment approaches are/is urgently needed. We aimed at identifying a novel antileishmanial agent and developing an innovative nanoparticle (NP) based platform for safe and effective treatments against CL. We discovered that polyhexanide (PHMB), a widely used antimicrobial polymer and wound antisepsis, shows an inherent antileishmanial activity at submicromolar concentrations. PHMB appears to kill L. major parasites via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation. However, host chromosomes binding appear to be limited by exclusion from mammalian cell nuclei. Moreover, we attempted to establish effective drug delivery systems that overcome the various shortcomings in the present treatment of CL. In this scenario, we initially studied the cellular interactions of NPs and their uptake mechanisms into mammalian cells before applying them in drug delivery system. We obtained clear evidence for the involvement of multiple endocytic routes to internalize NPs. Physicochemical properties of NPs, cell type, temperature and pathogenesis of the target diseases were shown to be determinant factors. Thereafter, a mechanism based host- and pathogen-directed combination therapy comprising PHMB and CpG ODN immunomodulator was established for overall synergistic effect against CL. It simultaneously targets the pathogen and the host immunity with effective delivery system. The results show that PHMB binds to CpG ODN and form stable nanopolyplexes for efficient cell entry and therapy. The nanopolyplexes displayed enhanced cellular uptake and antileishmanial potency while drastically reducing the toxicity against mammalian cells. In conclusion, our findings clearly indicate that PHMB can be used as effective candidate drug against CL and as non-viral delivery of immunomodulatorynucleic acids. Moreover, our proof-of concept study showed nanomedicine approaches are effective strategy to challenge CL and other human diseases.},
  subject      = {Leishmaniose},
  language  = {en}
}
@article{BergSchellingHailuetal.2015,
  author    = {Berg, Stefan and Schelling, Esther and Hailu, Elena and Firdessa, Rebuma and Gumi, Balako and Erenso, Girume and Gadisa, Endalamaw and Mengistu, Araya and Habtamu, Meseret and Hussein, Jemal and Kiros, Teklu and Bekele, Shiferaw and Mekonnen, Wondale and Derese, Yohannes and Zinsstag, Jakob and Ameni, Gobena and Gagneux, Sebastien and Robertson, Brian D and Tschopp, Rea and Hewinson, Glyn and Yamuah, Lawrence and Gordon, Stephen V and Aseffa, Abraham},
  title     = {Investigation of the high rates of extrapulmonary tuberculosis in Ethiopia reveals no single driving factor and minimal evidence for zoonotic transmission of Mycobacterium bovis infection},
  series = {BMC Infectious Diseases},
  volume    = {15},
  journal   = {BMC Infectious Diseases},
  number    = {112},
  doi       = {10.1186/s12879-015-0846-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143935},
  year      = {2015},
  abstract  = {Background: Ethiopia, a high tuberculosis (TB) burden country, reports one of the highest incidence rates of extra-pulmonary TB dominated by cervical lymphadenitis (TBLN). Infection with Mycobacterium bovis has previously been excluded as the main reason for the high rate of extra-pulmonary TB in Ethiopia. Methods: Here we examined demographic and clinical characteristics of 953 pulmonary (PTB) and 1198 TBLN patients visiting 11 health facilities in distinct geographic areas of Ethiopia. Clinical characteristics were also correlated with genotypes of the causative agent, Mycobacterium tuberculosis. Results: No major patient or bacterial strain factor could be identified as being responsible for the high rate of TBLN, and there was no association with HIV infection. However, analysis of the demographic data of involved patients showed that having regular and direct contact with live animals was more associated with TBLN than with PTB, although no M. bovis was isolated from patients with TBLN. Among PTB patients, those infected with Lineage 4 reported "contact with other TB patient" more often than patients infected with Lineage 3 did (OR = 1.6, CI 95\% 1.0-2.7; p = 0.064). High fever, in contrast to low and moderate fever, was significantly associated with Lineage 4 (OR = 2.3; p = 0.024). On the other hand, TBLN cases infected with Lineage 4 tended to get milder symptoms overall for the constitutional symptoms than those infected with Lineage 3. Conclusions: The study suggests a complex role for multiple interacting factors in the epidemiology of extra-pulmonary TB in Ethiopia, including factors that can only be derived from population-based studies, which may prove to be significant for TB control in Ethiopia.},
  language  = {en}
}