BackgroundThe 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 FindingsFrom 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.ConclusionsThese 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...

In a treatment re-infection study of 206 Papua New Guinean school children, we examined risk of reinfection and symptomatic malaria caused by different Plasmodium species. Although children acquired a similar number of polymerase chain reaction-detectable Plasmodium falciparum and P. vivax infections in six months of active follow-up (P. falciparum = 5.00, P. vivax = 5.28), they were 21 times more likely to develop symptomatic P. falciparum malaria (1.17/year) than P. vivax malaria (0.06/year). Children greater than nine years of age had a reduced risk of acquiring P. vivax infections of low-to-moderate (>150/microL) density (adjusted hazard rate [AHR] = 0.65 and 0.42), whereas similar reductions in risk with age of P. falciparum infection was only seen for parasitemias > 5,000/microL (AHR = 0.49) and symptomatic episodes (AHR = 0.51). Infection and symptomatic episodes with P. malariae and P. ovale were rare. By nine years of age, children have thus acquired almost complete clinical immunity to P. vivax characterized by a very tight control of parasite density, whereas the acquisition of immunity to symptomatic P. falciparum malaria remained incomplete. These observations suggest that different mechanisms of immunity may be important for protection from these malaria species.

The most effective regimens were artemether-lumefantrine against P. falciparum and dihydroartemisinin-piperaquine against P. vivax. The relatively high rate of treatment failure with dihydroartemisinin-piperaquine against P. falciparum may reflect cross-resistance between chloroquine and piperaquine. (Australian New Zealand Clinical Trials Registry number, ACTRN12605000550606.)

Background Plasmodium falciparum in pregnancy results in substantial poor health outcomes for both mother and child, particularly in young, primigravid mothers who are at greatest risk of placental malaria (PM) infection. Complications of PM include maternal anaemia, low birth weight and preterm delivery, which contribute to maternal and infant morbidity and mortality in coastal Papua New Guinea (PNG).MethodsPlacental biopsies were examined from 1451 pregnant women who were enrolled in a malaria prevention study at 14–26 weeks gestation. Clinical and demographic information were collected at first antenatal clinic visits and women were followed until delivery. Placental biopsies were collected and examined for PM using histology. The presence of infected erythrocytes and/or the malaria pigment in monocytes or fibrin was used to determine the type of placental infection.ResultsOf 1451 placentas examined, PM infection was detected in 269 (18.5%), of which 54 (3.7%) were acute, 55 (3.8%) chronic, and 160 (11.0%) were past infections. Risk factors for PM included residing in rural areas (adjusted odds ratio (AOR) 3.65, 95% CI 1.76–7.51; p ≤ 0.001), being primigravid (AOR 2.45, 95% CI 1.26–4.77; p = 0.008) and having symptomatic malaria during pregnancy (AOR 2.05, 95% CI 1.16–3.62; p = 0.013). After adjustment for covariates, compared to uninfected women, acute infections (AOR 1.97, 95% CI 0.98–3.95; p = 0.056) were associated with low birth weight babies, whereas chronic infections were associated with preterm delivery (AOR 3.92, 95% CI 1.64–9.38; p = 0.002) and anaemia (AOR 2.22, 95% CI 1.02–4.84; p = 0.045).ConclusionsAmong pregnant PNG women receiving at least one dose of intermittent preventive treatment in pregnancy and using insecticide-treated bed nets, active PM infections were associated with adverse outcomes. Improved malaria prevention is required to optimize pregnancy outcomes.

Abstractobjectives To assess the population prevalence of malaria in villages across Papua New Guinea (PNG) following the first roll-out of free long-lasting insecticidal nets (LLIN). results Malaria prevalence ranged from 0% to 49.7% with a weighted average of 12.1% (95% CI 9.5, 15.3) in the national sample. More people were infected with Plasmodium falciparum (7.0%; 95% CI 5.4, 9.1) than with P. vivax (3.8%; 95% CI 2.4, 5.7) or P. malariae (0.3%; 95% CI 0.1, 0.6). Parasitaemia was strongly age-dependent with a P. falciparum peak at age 5-9 years and a P. vivax peak at age 1-4 years, yet with differences between geographical regions. Individual LLIN use and high community coverage were associated with reduced odds of infection (OR = 0.64 and 0.07, respectively; both P < 0.001). Splenomegaly in children and anaemia were common morbidities attributable to malaria.conclusions Malaria prevalence across PNG is again at levels comparable to the 1970s. The strong association of LLIN use with reduced parasitaemia supports efforts to achieve and maintain high country-wide coverage. P. vivax infections will require special targeted approaches across PNG.