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Objective To investigate changes in malaria prevalence in Papua New Guinea after the distribution of long-lasting Insecticide-treated nets, starting in 2004, and the introduction of artemisinin-based combination therapy in 2011. Methods Two malaria surveys were conducted in 2010-2011 and 2013-2014. They included 77 and 92 randomly selected villages, respectively. In each village, all members of 30 randomly selected households gave blood samples and were assessed for malaria infection by light microscopy. In addition, data were obtained from a malaria survey performed in 2008-2009. Results The prevalence of malaria below 1600 m in altitude decreased from 11.1% (95% confidence interval, CI: 8.5-14.3) in 2008-2009 to 5.1% (95% CI 3.6-7.4) in 2010-2011 and 0.9% (95% CI 0.6-1.5) in 2013-2014. Prevalence decreased with altitude. Plasmodium falciparum was more common than P. vivax overall, but not everywhere, and initially the prevalence of P. vivax infection decreased more slowly than P. falciparum infection. Malaria infections were clustered in households. In contrast to findings in 2008-2009, no significant association between net use and prevalence was found in the later two surveys. The prevalence of both fever and splenomegaly also decreased but their association with malaria infection became stronger. Conclusion Large-scale insecticide-treated net distribution was associated with an unprecedented decline in malaria prevalence throughout Papua New Guinea, including epidemic-prone highland areas.The decline was accompanied by broader health benefits, such as decreased morbidity. Better clinical management of nonmalarial fever and research into residual malaria transmission are required. Objectif Etudier les changements observes a legard de la prevalence du paludisme en Papouasie-Nouvelle-Gulnee suite a la distribution, depuis 2004, de moustiquaires impregnees d'Insecticides de longue duree et a l'introduction, depuis 2011, d'une combinaison therapeutique a base d'artemisinine. Methodes Deux enquetes portant sur le paludisme ont ete menees en 2010-2011 et 2013-2014. Elles incluaient respectivement 77 et 92 villages, selectionnes d'une maniere aleatoire. Dans chacun de ces villages, tous les membres de 30 foyers selectionnes aleatoirement ont donne des echantillons sanguins et ete soumis a un test de depistage de l'infection palustre par microscopie optique. Des donnees ont par ailleurs ete tirees d'une enquete sur le paludisme realisee en 2008-2009. Resultats La prevalencedu paludisme a moins de 1600 m d'altitude est passee de 11,1 % (intervalle de confiance, IC, a 95%: 8,5-14,3) en 2008-2009 a 5,1 % (IC a 95%: 3,6-7,4) en 2010-2011 et 0,9% (IC a 95%: 0,6-1,5) en 2013-2014. La prevalence diminuait avec l'altitude. Plasmodium falciparum n'etait pas systematiquement plus courant que R vivax, mais l'etait dans l'ensemble et, dans un premier temps, la prevalence de l'infection a R vivax a diminue plus lentement que la prevalence de l'Infection a P. falciparum. Les infections palustres ont ete regroupees par foyers. Contrairement a ce qu'indiquaient les resultats obtenus en 2008-2009, aucune correlation significative entre l'utilisation d'une moustiquaire et la prevalence n'a ete constatee dans le cadre des deux dernieres enquetes. Les prevalences de la fievre et de la splenomegalle ont egalement diminue, mais leur correlation avec l'infection palustre est devenue plus forte. Conclusion La distribution a grande echelle de moustiquaires impregnees d'insecticides a ete associee a un declin sans precedent de la prevalence du paludisme dans l'ensemble de la Papouasie-Nouvelle-Guinee, et notamment dans les reglons montagneuses sujettes aux epidemies. Ce declin s'est accompagne d'autres bienfaits sur la sante, et notamment d'une diminution de la morbidite. Il est necessaire d'ameliorer la prise en charge clinique de la fievre non palustre ainsi que les recherches sur la transmission residuelle du paludisme. Objetivo Investigar los cambios en la prevalencia de la malaria en Papua Nueva Guinea tras la distribucion de mosquiteros tratados con insecticida de larga duracion, a partir de 2004, y la introduccion de terapias combinadas basadas en la artemisinina en 2011. Metodos Se llevaron a cabo dos encuestas sobre la malaria en 2010-2011 y 2013-2014. Incluian 77y 92 aldeas seleccionadas al azar, respectivamente. En cada aldea, todos los miembros de 30 hogares seleccionados al azar dieron muestras de sangre y se evaluaron de infeccion de malaria con microscopio optico. Ademas, se obtuvieron datos de la encuesta sobre la malaria realizada en 2008-2009. Resultados La prevalencia de la malaria por debajo de 1600 m de altitud descendio del 11.1% (intervalo de confidencia (IC) del 95%: 8.5-14.3) en 2008-2009 al 5.1% (95% IC 3.6-7.4) en 2010-2011 y 0.9% (95% IC 0.6-1.5) en 2013-2014. La prevalencia descendia con la altitud. Plasmodium falciparum fue mas comun que P. vivax en general, pero no en todas partes e inicialmente la prevalencia de la infeccion P. vivax descendio mas lentamente que la infeccion P. falciparum. Las infecciones de malaria se agruparon en los hogares. Al contrario que los hallazgos en 2008-2009, no se encontro ninguna asociacion significativa entre el uso del mosquitero y la prevalencia en las dos ultimas encuestas. La prevalencia tanto de la fiebre como de la esplenomegalia tambien descendio, pero su asociacion con la infeccion de malaria se hizo mas fuerte. Conclusion La distribucion de mosquiteros tratados con insecticida a gran escala se asocio con un descenso sin precedentes en la prevalencia de la malaria en toda Papua Nueva Guinea, incluidas las areas altas con propension a causar epidemias. El descenso estuvo acompanado de beneficios saludables mas amplios, como el descenso de la morbilidad. Se requieren una mejor gestion clinica de la fiebre no relacionada con la malaria y la Investigacion de la transmision residual de la malaria., Introduction Historically, malaria has been endemic throughout Papua New Guinea, except in highland areas over 1600 m, where temperatures are low and there is no stable local transmission, though imported [...]

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, Introduction Renewed intensification of global malaria control efforts over the last 15 years have been successful in significantly reducing the global burden of malaria, with many countries in the Asia-Pacific [...]

Background: Intermittent preventive treatment in infants (IPTi) has been shown in randomized trials to reduce malaria- related morbidity in African infants living in areas of high Plasmodium falciparum (Pf) transmission. It remains unclear whether IPTi is an appropriate prevention strategy in non-African settings or those co-endemic for P. vivax (Pv). Methods and Findings: In this study, 1,121 Papua New Guinean infants were enrolled into a three-arm placebo-controlled randomized trial and assigned to sulfadoxine-pyrimethamine (SP) (25 mg/kg and 1.25 mg/kg) plus amodiaquine (AQ) (10 mg/kg, 3 d, n = 374), SP plus artesunate (AS) (4 mg/kg, 3 d, n = 374), or placebo (n = 373), given at 3, 6, 9 and 12 mo. Both participants and study teams were blinded to treatment allocation. The primary end point was protective efficacy (PE) against all episodes of clinical malaria from 3 to 15 mo of age. Analysis was by modified intention to treat. The PE (compared to placebo) against clinical malaria episodes (caused by all species) was 29% (95% CI, 10-43, p [less than or equal to] 0.001) in children receiving SP-AQ and 12% (95% CI, -11 to 30, p = 0.12) in those receiving SP-AS. Efficacy was higher against Pf than Pv. In the SP-AQ group, Pf incidence was 35% (95% CI, 9-54, p = 0.012) and Pv incidence was 23% (95% CI, 0-41, p = 0.048) lower than in the placebo group. IPTi with SP-AS protected only against Pf episodes (PE = 31%, 95% CI, 4-51, p = 0.027), not against Pv episodes (PE = 6%, 95% CI, -24 to 26, p = 0.759). Number of observed adverse events/serious adverse events did not differ between treatment arms (p>0.55). None of the serious adverse events were thought to be treatment-related, and the vomiting rate was low in both treatment groups (1.4%-2.0%). No rebound in malaria morbidity was observed for 6 mo following the intervention. Conclusions: IPTi using a long half-life drug combination is efficacious for the prevention of malaria and anemia in infants living in a region highly endemic for both Pf and Pv. Trial registration: ClinicalTrials.gov NCT00285662 Please see later in the article for the Editors' Summary., Introduction Malaria and anemia are major causes of morbidity and mortality in children in tropical countries [1]. Several preventive strategies have proven to be effective in reducing this burden, such [...]