DOI: 10.5061/dryad.m1n03
title: Data from: 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

description: 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 &lt; 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 &lt; 0.001). Children who received PQ
 were less likely to carry P. vivax gametocytes (IRR = 0.27 [95% CI 0.19,
 0.38], p &lt; 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.
description: Data repository analyses
 presented in Robinson et al. 2015 PLoS Medince1) Albinama_Table1.dta:
 Baseline characteristics of cohort; 2) Albinama_Table2_Po: Survival
 analyses of risk of P. ovale infections; 3) Albinama_Table2_Pv_clin:
 Survival analyses of incidence risk of P. vivax clinical episodes; 4)
 Albinama_Table2_Pv_LM: survival analyses of incidence risk of
 light-microscopically positive P. vivax infections; 5)
 Albinama_Table2_Pv_PCR: survival analyses of incidence risk of PCR
 positive P. vivax infections; 6)Albinama_Table2_Pvg: survival analyses of
 incidence risk of gametocyte positive P. vivax infections; 7)
 Albinama_Table3_0-3mo: incidence of malaria endpoints for first 3 months
 of follow-up; 8) Albinama_Table3_4-8mo: incidence of malaria endpoints for
 months 4-8 of follow-up; 9) Albinama_Table3_0-8mo: incidence of malaria
 endpoints for entire 8 months follow-up; 10) Albinama_Table4_Pf_clin:
 Survival analyses of incidence risk of P. falciparum clinical episodes;
 11) Albinama_Table4_Pf_LM: survival analyses of incidence risk of
 light-microscopically positive P. falciparum infections; 12)
 Albinama_Table4_Pf_PCR: survival analyses of incidence risk of PCR
 positive P. falciparum infections; 13)Albinama_Table4_Pm_PCR: survival
 analyses of incidence risk of PCR positive P. malariae
 infections;Albinama data
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