# name
Strategies for Understanding and Reducing the Plasmodium vivax
                and Plasmodium ovale Hypnozoite Reservoir in Papua New Guinean
                Children: A Randomised Placebo-Controlled Trial and Mathematical
                Model

# metadata.dc.description.abstract[].value
BACKGROUND: The undetectable hypnozoite reservoir for relapsing
                Plasmodium vivax and P. ovale malarias presents a major
                challenge for malaria control and elimination in endemic
                countries. This study aims to directly determine the
                contribution of relapses to the burden of P. vivax and P. ovale
                infection, illness, and transmission in Papua New Guinean
                children. METHODS AND FINDINGS: From 17 August 2009 to 20 May
                2010, 524 children aged 5-10 y from East Sepik Province in Papua
                New Guinea (PNG) participated in a randomised double-blind
                placebo-controlled trial of blood- plus liver-stage drugs
                (chloroquine [CQ], 3 d; artemether-lumefantrine [AL], 3 d; and
                primaquine [PQ], 20 d, 10 mg/kg total dose) (261 children) or
                blood-stage drugs only (CQ, 3 d; AL, 3 d; and placebo [PL], 20
                d) (263 children). Participants, study staff, and investigators
                were blinded to the treatment allocation. Twenty children were
                excluded during the treatment phase (PQ arm: 14, PL arm: 6), and
                504 were followed actively for 9 mo. During the follow-up time,
                18 children (PQ arm: 7, PL arm: 11) were lost to follow-up. Main
                primary and secondary outcome measures were time to first P.
                vivax infection (by qPCR), time to first clinical episode, force
                of infection, gametocyte positivity, and time to first P. ovale
                infection (by PCR). A basic stochastic transmission model was
                developed to estimate the potential effect of mass drug
                administration (MDA) for the prevention of recurrent P. vivax
                infections. Targeting hypnozoites through PQ treatment reduced
                the risk of having at least one qPCR-detectable P. vivax or P.
                ovale infection during 8 mo of follow-up (P. vivax: PQ arm
                0.63/y versus PL arm 2.62/y, HR = 0.18 [95% CI 0.14, 0.25], p
                < 0.001; P. ovale: 0.06 versus 0.14, HR = 0.31 [95% CI 0.13,
                0.77], p = 0.011) and the risk of having at least one clinical
                P. vivax episode (HR = 0.25 [95% CI 0.11, 0.61], p = 0.002). PQ
                also reduced the molecular force of P. vivax blood-stage
                infection in the first 3 mo of follow-up (PQ arm 1.90/y versus
                PL arm 7.75/y, incidence rate ratio [IRR] = 0.21 [95% CI 0.15,
                0.28], p < 0.001). Children who received PQ were less likely
                to carry P. vivax gametocytes (IRR = 0.27 [95% CI 0.19, 0.38], p
                < 0.001). PQ had a comparable effect irrespective of the
                presence of P. vivax blood-stage infection at the time of
                treatment (p = 0.14). Modelling revealed that mass screening and
                treatment with highly sensitive quantitative real-time PCR, or
                MDA with blood-stage treatment alone, would have only a
                transient effect on P. vivax transmission levels, while MDA that
                includes liver-stage treatment is predicted to be a highly
                effective strategy for P. vivax elimination. The inclusion of a
                directly observed 20-d treatment regime maximises the efficiency
                of hypnozoite clearance but limits the generalisability of
                results to real-world MDA programmes. CONCLUSIONS: These results
                suggest that relapses cause approximately four of every five P.
                vivax infections and at least three of every five P. ovale
                infections in PNG children and are important in sustaining
                transmission. MDA campaigns combining blood- and liver-stage
                treatment are predicted to be a highly efficacious intervention
                for reducing P. vivax and P. ovale transmission. TRIAL
                REGISTRATION: ClinicalTrials.gov NCT02143934.

# metadata.dc.relation.isformatof[].value
Reproducció del document publicat a:
                http://dx.doi.org/10.1371/journal.pmed.1001891

# metadata.dc.source[].value
Articles publicats en revistes (ISGlobal)

# metadata.dc.title[].value
Strategies for Understanding and Reducing the Plasmodium vivax
                and Plasmodium ovale Hypnozoite Reservoir in Papua New Guinean
                Children: A Randomised Placebo-Controlled Trial and Mathematical
                Model