TY  - JOUR
A1  - Firdessa, Rebuma
A1  - Good, Liam
A1  - Amstalden, Maria Cecilia
A1  - Chindera, Kantaraja
A1  - Kamaruzzaman, Nor Fadhilah
A1  - Schultheis, Martina
A1  - Röger, Bianca
A1  - Hecht, Nina
A1  - Oelschlaeger, Tobias A.
A1  - Meinel, Lorenz
A1  - Lühmann, Tessa
A1  - Moll, Heidrun
T1  - Pathogen- and host-directed antileishmanial effects mediated by polyhexanide (PHMB)
JF  - PLoS Neglected Tropical Diseases
N2  - 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.
KW  - resistance
KW  - activation
KW  - dendritic cells
KW  - Cutaneous leishmaniasis
KW  - topical treatment
KW  - biocide polyhexamethylene biguanide
KW  - experimental visceral leishmaniasis
KW  - drug-delivery systems
KW  - therapy
KW  - paromomycin
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148162
VL  - 9
IS  - 10
ER  - 
TY  - JOUR
A1  - Berg, Stefan
A1  - Schelling, Esther
A1  - Hailu, Elena
A1  - Firdessa, Rebuma
A1  - Gumi, Balako
A1  - Erenso, Girume
A1  - Gadisa, Endalamaw
A1  - Mengistu, Araya
A1  - Habtamu, Meseret
A1  - Hussein, Jemal
A1  - Kiros, Teklu
A1  - Bekele, Shiferaw
A1  - Mekonnen, Wondale
A1  - Derese, Yohannes
A1  - Zinsstag, Jakob
A1  - Ameni, Gobena
A1  - Gagneux, Sebastien
A1  - Robertson, Brian D
A1  - Tschopp, Rea
A1  - Hewinson, Glyn
A1  - Yamuah, Lawrence
A1  - Gordon, Stephen V
A1  - Aseffa, Abraham
T1  - 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
JF  - BMC Infectious Diseases
N2  - 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.
KW  - zoonotic
KW  - Mycobacterium
KW  - Ethiopia
KW  - tuberculosis
KW  - Bovis
KW  - pulmonary
KW  - extrapulmonary
KW  - lymphadenitis
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143935
VL  - 15
IS  - 112
ER  -