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Drug resistance and treatment failure in leishmaniasis: A 21st century challenge.

Abstract Reevaluation of treatment guidelines for Old and New World leishmaniasis is urgently needed on a global basis because treatment failure is an increasing problem. Drug resistance is a fundamental determinant of treatment failure, although other factors also contribute to this phenomenon, including the global HIV/AIDS epidemic with its accompanying impact on the immune system. Pentavalent antimonials have been used successfully worldwide for the treatment of leishmaniasis since the first half of the 20th century, but the last 10 to 20 years have witnessed an increase in clinical resistance, e.g., in North Bihar in India. In this review, we discuss the meaning of "resistance" related to leishmaniasis and discuss its molecular epidemiology, particularly for Leishmania donovani that causes visceral leishmaniasis. We also discuss how resistance can affect drug combination therapies. Molecular mechanisms known to contribute to resistance to antimonials, amphotericin B, and miltefosine are also outlined.
PMID
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Authors

Mayor MeshTerms

Drug Resistance

Keywords
Journal Title plos neglected tropical diseases
Publication Year Start



 

PMID- 29240765
OWN - NLM
STAT- MEDLINE
DCOM- 20171219
LR  - 20171224
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Linking)
VI  - 11
IP  - 12
DP  - 2017 Dec
TI  - Drug resistance and treatment failure in leishmaniasis: A 21st century challenge.
PG  - e0006052
LID - 10.1371/journal.pntd.0006052 [doi]
AB  - Reevaluation of treatment guidelines for Old and New World leishmaniasis is
      urgently needed on a global basis because treatment failure is an increasing
      problem. Drug resistance is a fundamental determinant of treatment failure,
      although other factors also contribute to this phenomenon, including the global
      HIV/AIDS epidemic with its accompanying impact on the immune system. Pentavalent 
      antimonials have been used successfully worldwide for the treatment of
      leishmaniasis since the first half of the 20th century, but the last 10 to 20
      years have witnessed an increase in clinical resistance, e.g., in North Bihar in 
      India. In this review, we discuss the meaning of "resistance" related to
      leishmaniasis and discuss its molecular epidemiology, particularly for Leishmania
      donovani that causes visceral leishmaniasis. We also discuss how resistance can
      affect drug combination therapies. Molecular mechanisms known to contribute to
      resistance to antimonials, amphotericin B, and miltefosine are also outlined.
FAU - Ponte-Sucre, Alicia
AU  - Ponte-Sucre A
AD  - Department of Physiological Sciences, Laboratory of Molecular Physiology,
      Institute of Experimental Medicine, Luis Razetti School of Medicine, Universidad 
      Central de Venezuela, Caracas, Venezuela.
FAU - Gamarro, Francisco
AU  - Gamarro F
AD  - Department of Biochemistry and Molecular Pharmacology, Instituto de Parasitologia
      y Biomedicina Lopez-Neyra, Spanish National Research Council (IPBLN-CSIC),
      Granada, Spain.
FAU - Dujardin, Jean-Claude
AU  - Dujardin JC
AD  - Molecular Parasitology Unit, Department of Biomedical Sciences, Institute of
      Tropical Medicine, Antwerp, Belgium.
FAU - Barrett, Michael P
AU  - Barrett MP
AD  - Wellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and 
      Inflammation, University of Glasgow, Glasgow, United Kingdom.
FAU - Lopez-Velez, Rogelio
AU  - Lopez-Velez R
AD  - Department of Infectious Diseases, National Referral Unit for Tropical Diseases, 
      Ramon y Cajal University Hospital, Madrid, Spain.
FAU - Garcia-Hernandez, Raquel
AU  - Garcia-Hernandez R
AD  - Department of Biochemistry and Molecular Pharmacology, Instituto de Parasitologia
      y Biomedicina Lopez-Neyra, Spanish National Research Council (IPBLN-CSIC),
      Granada, Spain.
FAU - Pountain, Andrew W
AU  - Pountain AW
AD  - Wellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and 
      Inflammation, University of Glasgow, Glasgow, United Kingdom.
FAU - Mwenechanya, Roy
AU  - Mwenechanya R
AD  - Department of Biomedical Sciences, School of Veterinary Medicine, University of
      Zambia, Lusaka, Zambia.
FAU - Papadopoulou, Barbara
AU  - Papadopoulou B
AUID- ORCID: http://orcid.org/0000-0002-6697-9739
AD  - Research Center in Infectious Diseases, CHU de Quebec Research Center and
      Department of Microbiology-Infectious Disease and Immunology, University Laval,
      Quebec, Canada.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20171214
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
RN  - 0 (Antiprotozoal Agents)
RN  - 107-73-3 (Phosphorylcholine)
RN  - 53EY29W7EC (miltefosine)
RN  - 7XU7A7DROE (Amphotericin B)
SB  - IM
MH  - Amphotericin B/pharmacology/therapeutic use
MH  - Antiprotozoal Agents/pharmacology/therapeutic use
MH  - *Drug Resistance
MH  - Drug Therapy, Combination
MH  - Humans
MH  - Leishmania/*drug effects/genetics/*pathogenicity
MH  - Leishmania donovani/drug effects/pathogenicity
MH  - Leishmaniasis/*drug therapy/immunology/parasitology
MH  - Leishmaniasis, Cutaneous/drug therapy
MH  - Leishmaniasis, Visceral/drug therapy/parasitology
MH  - Molecular Epidemiology
MH  - Phosphorylcholine/analogs & derivatives/pharmacology/therapeutic use
MH  - Treatment Failure
PMC - PMC5730103
EDAT- 2017/12/15 06:00
MHDA- 2017/12/20 06:00
CRDT- 2017/12/15 06:00
PHST- 2017/12/15 06:00 [entrez]
PHST- 2017/12/15 06:00 [pubmed]
PHST- 2017/12/20 06:00 [medline]
AID - 10.1371/journal.pntd.0006052 [doi]
AID - PNTD-D-17-01203 [pii]
PST - epublish
SO  - PLoS Negl Trop Dis. 2017 Dec 14;11(12):e0006052. doi:
      10.1371/journal.pntd.0006052. eCollection 2017 Dec.