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Effects of liver-stage clearance by Primaquine on gametocyte carriage of Plasmodium vivax and P. falciparum.

Abstract Primaquine (PQ) is the only currently licensed antimalarial that prevents Plasmodium vivax (Pv) relapses. It also clears mature P. falciparum (Pf) gametocytes, thereby reducing post-treatment transmission. Randomized PQ treatment in a treatment-to-reinfection cohort in Papua New Guinean children permitted the study of Pv and Pf gametocyte carriage after radical cure and to investigate the contribution of Pv relapses.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title plos neglected tropical diseases
Publication Year Start




PMID- 28732068
OWN - NLM
STAT- MEDLINE
DA  - 20170721
DCOM- 20170810
LR  - 20170813
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Linking)
VI  - 11
IP  - 7
DP  - 2017 Jul
TI  - Effects of liver-stage clearance by Primaquine on gametocyte carriage of
      Plasmodium vivax and P. falciparum.
PG  - e0005753
LID - 10.1371/journal.pntd.0005753 [doi]
AB  - BACKGROUND: Primaquine (PQ) is the only currently licensed antimalarial that
      prevents Plasmodium vivax (Pv) relapses. It also clears mature P. falciparum (Pf)
      gametocytes, thereby reducing post-treatment transmission. Randomized PQ
      treatment in a treatment-to-reinfection cohort in Papua New Guinean children
      permitted the study of Pv and Pf gametocyte carriage after radical cure and to
      investigate the contribution of Pv relapses. METHODS: Children received radical
      cure with Chloroquine, Artemether-Lumefantrine plus either PQ or placebo. Blood
      samples were subsequently collected in 2-to 4-weekly intervals over 8 months.
      Gametocytes were detected by quantitative reverse transcription-PCR targeting
      pvs25 and pfs25. RESULTS: PQ treatment reduced the incidence of Pv gametocytes by
      73%, which was comparable to the effect of PQ on incidence of blood-stage
      infections. 92% of Pv and 79% of Pf gametocyte-positive infections were
      asymptomatic. Pv and to a lesser extent Pf gametocyte positivity and density were
      associated with high blood-stage parasite densities. Multivariate analysis
      revealed that the odds of gametocytes were significantly reduced in mixed-species
      infections compared to single-species infections for both species (ORPv = 0.39
      [95% CI 0.25-0.62], ORPf = 0.33 [95% CI 0.18-0.60], p<0.001). No difference
      between the PQ and placebo treatment arms was observed in density of Pv
      gametocytes or in the proportion of Pv infections that carried gametocytes. First
      infections after blood-stage and placebo treatment, likely caused by a relapsing 
      hypnozoite, were equally likely to carry gametocytes than first infections after 
      PQ treatment, likely caused by an infective mosquito bite. CONCLUSION: Pv
      relapses and new infections are associated with similar levels of gametocytaemia.
      Relapses thus contribute considerably to the Pv reservoir highlighting the
      importance of effective anti-hypnozoite treatment for efficient control of Pv.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT02143934.
FAU - Wampfler, Rahel
AU  - Wampfler R
AD  - Swiss Tropical and Public Health Institute, Basel, Switzerland.
AD  - University of Basel, Basel, Switzerland.
FAU - Hofmann, Natalie E
AU  - Hofmann NE
AD  - Swiss Tropical and Public Health Institute, Basel, Switzerland.
AD  - University of Basel, Basel, Switzerland.
FAU - Karl, Stephan
AU  - Karl S
AD  - Divison of Population Health and Immunity, The Walter and Eliza Hall Institute of
      Medical Research, Parkville, Australia.
AD  - Department of Medical Biology, University of Melbourne, Victoria, Australia.
FAU - Betuela, Inoni
AU  - Betuela I
AD  - Vector Borne Diseases Unit, PNG Institute of Medical Research, Goroka, Papua New 
      Guinea.
FAU - Kinboro, Benson
AU  - Kinboro B
AD  - Vector Borne Diseases Unit, PNG Institute of Medical Research, Goroka, Papua New 
      Guinea.
FAU - Lorry, Lina
AU  - Lorry L
AD  - Vector Borne Diseases Unit, PNG Institute of Medical Research, Goroka, Papua New 
      Guinea.
FAU - Silkey, Mariabeth
AU  - Silkey M
AD  - Swiss Tropical and Public Health Institute, Basel, Switzerland.
FAU - Robinson, Leanne J
AU  - Robinson LJ
AD  - Divison of Population Health and Immunity, The Walter and Eliza Hall Institute of
      Medical Research, Parkville, Australia.
AD  - Department of Medical Biology, University of Melbourne, Victoria, Australia.
AD  - Vector Borne Diseases Unit, PNG Institute of Medical Research, Goroka, Papua New 
      Guinea.
AD  - Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.
FAU - Mueller, Ivo
AU  - Mueller I
AD  - Divison of Population Health and Immunity, The Walter and Eliza Hall Institute of
      Medical Research, Parkville, Australia.
AD  - Department of Medical Biology, University of Melbourne, Victoria, Australia.
AD  - Malaria Parasites & Hosts Unit, Institut Pasteur, Paris, France.
FAU - Felger, Ingrid
AU  - Felger I
AUID- ORCID: http://orcid.org/0000-0003-1255-2606
AD  - Swiss Tropical and Public Health Institute, Basel, Switzerland.
AD  - University of Basel, Basel, Switzerland.
LA  - eng
PT  - Clinical Trial, Phase IV
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20170721
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
RN  - 0 (Antimalarials)
RN  - 0 (Artemisinins)
RN  - 0 (Drug Combinations)
RN  - 0 (Ethanolamines)
RN  - 0 (Fluorenes)
RN  - 0 (artemether-lumefantrine combination)
RN  - 886U3H6UFF (Chloroquine)
RN  - MVR3634GX1 (Primaquine)
SB  - IM
MH  - Antimalarials/*therapeutic use
MH  - Artemisinins/therapeutic use
MH  - Blood/parasitology
MH  - Child
MH  - Child, Preschool
MH  - Chloroquine/therapeutic use
MH  - Double-Blind Method
MH  - Drug Combinations
MH  - Ethanolamines/therapeutic use
MH  - Female
MH  - Fluorenes/therapeutic use
MH  - Humans
MH  - Liver/drug effects/parasitology
MH  - Malaria, Falciparum/*drug therapy
MH  - Malaria, Vivax/*drug therapy
MH  - Male
MH  - Multivariate Analysis
MH  - Papua New Guinea
MH  - Plasmodium falciparum/*drug effects
MH  - Plasmodium vivax/*drug effects
MH  - Primaquine/*therapeutic use
MH  - Recurrence
MH  - Regression Analysis
MH  - Risk Factors
PMC - PMC5540608
EDAT- 2017/07/22 06:00
MHDA- 2017/08/11 06:00
CRDT- 2017/07/22 06:00
PHST- 2017/03/27 [received]
PHST- 2017/06/27 [accepted]
PHST- 2017/08/02 [revised]
AID - 10.1371/journal.pntd.0005753 [doi]
AID - PNTD-D-17-00425 [pii]
PST - epublish
SO  - PLoS Negl Trop Dis. 2017 Jul 21;11(7):e0005753. doi:
      10.1371/journal.pntd.0005753. eCollection 2017 Jul.