Project description:Papua New Guinean populations have one of the highest genetic diversity of the world. Our dataset provides genomic data covering most of the Papua New Guinean territory (n=58).
Project description:High-coverage whole genome sequences were collected to study patterns of genomic variation across the broad geography of Papua New Guinea. This region has experienced an extremely complex demographic history, including repeated bouts of admixture with archaic and modern human groups. This dataset reports whole genome sequences for 163 individuals from different regions (Mt Wilhelm, Daru, Port Moresby). Particular attention has been paid in the original study to genomic signals that are informative for population history, and adaptive history, including admixture with archaic hominins and the role of modern human admixture during the late Pleistocene and Holocene.
Project description:The settlement of Sahul, the lost continent of Oceania, remains one of the most ancient and debated human migrations. Modern New Guineans inherited a unique genetic diversity tracing back 50,000 years, and yet there is currently no model reconstructing their past population dynamics. We generated 58 new whole-genome sequences from Papua New Guinea, filling geographical gaps in previous sampling, specifically to address alternative scenarios of the initial migration to Sahul and the settlement of New Guinea. Here, we present the first genomic models for the settlement of northeast Sahul considering one or two migrations from Wallacea. Both models fit our data set, reinforcing the idea that ancestral groups to New Guinean and Indigenous Australians split early, potentially during their migration in Wallacea where the northern route could have been favored. The earliest period of human presence in Sahul was an era of interactions and gene flow between related but already differentiated groups, from whom all modern New Guineans, Bismarck islanders, and Indigenous Australians descend. The settlement of New Guinea was probably initiated from its southeast region, where the oldest archaeological sites have been found. This was followed by two migrations into the south and north lowlands that ultimately reached the west and east highlands. We also identify ancient gene flows between populations in New Guinea, Australia, East Indonesia, and the Bismarck Archipelago, emphasizing the fact that the anthropological landscape during the early period of Sahul settlement was highly dynamic rather than the traditional view of extensive isolation.
Project description:We examined genetic affinities of Aboriginal Australian and New Guinean populations by using nucleotide variation in the two hypervariable segments of the mtDNA control region (CR). A total of 318 individuals from highland Papua New Guinea (PNG), coastal PNG, and Aboriginal Australian populations were typed with a panel of 29 sequence-specific oligonucleotide (SSO) probes. The SSO-probe panel included five new probes that were used to type an additional 1,037 individuals from several Asian populations. The SSO-type data guided the selection of 78 individuals from Australia and east Indonesia for CR sequencing. A gene tree of these CR sequences, combined with published sequences from worldwide populations, contains two previously identified highland PNG clusters that do not include any Aboriginal Australians; the highland PNG clusters have coalescent time estimates of approximately 80,000 and 122,000 years ago, suggesting ancient isolation and genetic drift. SSO-type data indicate that 84% of the sample of PNG highlander mtDNA belong to these two clusters. In contrast, the Aboriginal Australian sequences are intermingled throughout the tree and cluster with sequences from multiple populations. Phylogenetic and multidimensional-scaling analyses of CR sequences and SSO types split PNG highland and Aboriginal Australian populations and link Aboriginal Australian populations with populations from the subcontinent of India. These mtDNA results do not support a close relationship between Aboriginal Australian and PNG populations but instead suggest multiple migrations in the peopling of Sahul.
Project description:Introductionsubacute sclerosing panencephalitis (SSPE) is a late, rare and usually fatal complication of measles infection. Although a very high incidence of SSPE in Papua New Guinea (PNG) was first recognized 20 years ago, estimated measles vaccine coverage has remained at ≤ 70% since and a large measles epidemic occurred in 2002. We report a series of 22 SSPE cases presenting between November 2007 and July 2009 in Madang Province, PNG, including localized clusters with the highest ever reported annual incidence.Methodology/principal findingsas part of a prospective observational study of severe childhood illness at Modilon Hospital, the provincial referral center, children presenting with evidence of meningo-encephalitis were assessed in detail including lumbar puncture in most cases. A diagnosis of SSPE was based on clinical features and presence of measles-specific IgG in cerebrospinal fluid and/or plasma. The estimated annual SSPE incidence in Madang province was 54/million population aged <20 years, but four sub-districts had an incidence >100/million/year. The distribution of year of birth of the 22 children with SSPE closely matched the reported annual measles incidence in PNG, including a peak in 2002.Conclusions/significanceSSPE follows measles infections in very young PNG children. Because PNG children have known low seroconversion rates to the first measles vaccine given at 6 months of age, efforts such as supplementary measles immunisation programs should continue in order to reduce the pool of non-immune people surrounding the youngest and most vulnerable members of PNG communities.
Project description:Studies are available that assess the risk of malaria in accordance to the body's iron store and the systematic iron supplementation of preschool children. However, only a few studies evaluated the temporal association between hemoglobin and malaria and their results are opposing. A total of 1,650 3-month-old Papua New Guinean infants were enrolled in this study and followed-up for 12 months. The risk of malaria was assessed in all children every 3 months and with each episode of fever. The incidence of clinical malaria between 3 and 15 months of age was 249 cases per 1,000 infants per year. After adjustment for potential confounding factors, a decrease of 1 g/dL of hemoglobin was associated with a nonsignificant increase of 11% for risk of malaria infection (hazard ratio, 1.11, 95% confidence interval; CI, 0.99-1.25, P = 0.076). Only children with severe anemia (hemoglobin < 8.0 g/dL) at baseline were at higher risk of malaria infection (hazard ratio, 1.72, 95% CI, 1.08-2.76, P = 0.023) during the follow-up year compared with the control group (Hemoglobin > 10.0 g/dL). This association was not statistically significant if only clinical malaria episodes were taken into account (hazard ratio, 1.42, 95% CI, 0.77-2.61, P = 0.26). Our study suggests that infants with lower hemoglobin levels are not protected against malaria infection. Further research that examines the risk of malaria in relation to both hemoglobin and iron store levels would be important to better understand this complex interaction.
Project description:AimsThe aim of the present study was to investigate the safety, tolerability and pharmacokinetics of coadministered azithromycin (AZI) and piperaquine (PQ) for treating malaria in pregnant Papua New Guinean women.MethodsThirty pregnant women (median age 22 years; 16-32 weeks' gestation) were given three daily doses of 1 g AZI plus 960 mg PQ tetraphosphate with detailed monitoring/blood sampling over 42 days. Plasma AZI and PQ were assayed using liquid chromatography-mass spectrometry and high-performance liquid chromatography, respectively. Pharmacokinetic analysis was by population-based compartmental models.ResultsThe treatment was well tolerated. The median (interquartile range) increase in the rate-corrected electrocardiographic QT interval 4 h postdose [12 (6-26) ms(0) (.5) ] was similar to that found in previous studies of AZI given in pregnancy with other partner drugs. Six women with asymptomatic malaria cleared their parasitaemias within 72 h. Two apararasitaemic women developed late uncomplicated Plasmodium falciparum infections on Days 42 and 83. Compared with previous pregnancy studies, the area under the concentration-time curve (AUC0-∞ ) for PQ [38818 (24354-52299) μg h l(-1) ] was similar to published values but there was a 52% increase in relative bioavailability with each dose. The AUC0-∞ for AZI [46799 (43526-49462) μg h l(-1) ] was at least as high as reported for higher-dose regimens, suggesting saturable absorption and/or concentration-dependent tissue uptake and clearance from the central compartment.ConclusionsAZI-PQ appears to be well tolerated and safe in pregnancy. Based on the present/other data, total AZI doses higher than 3 g for the treatment and prevention of malaria may be unnecessary in pregnant women, while clearance of parasitaemia could improve the relative bioavailability of PQ.
Project description:BackgroundApproximately 826,000 children, mostly young infants, die annually from invasive pneumococcal disease. A 6-10-14-week schedule of pneumococcal conjugate vaccine (PCV) is efficacious but neonatal PCV may provide earlier protection and better coverage. We conducted an open randomized controlled trial in Papua New Guinea to compare safety, immunogenicity and priming for memory of 7-valent PCV (PCV7) given in a 0-1-2-month (neonatal) schedule with that of the routine 1-2-3-month (infant) schedule.MethodsWe randomized 318 infants at birth to receive PCV7 in the neonatal or infant schedule or no PCV7. All infants received 23-valent pneumococcal polysaccharide vaccine (PPV) at age 9 months. Serotype-specific serum IgG for PCV7 (VT) serotypes and non-VT serotypes 2, 5 and 7F were measured at birth and 2, 3, 4, 9, 10 and 18 months of age. Primary outcomes were geometric mean concentrations (GMCs) and proportions with concentration ? 0.35 µg/ml of VT serotype-specific pneumococcal IgG at age 2 months and one month post-PPV.ResultsWe enrolled 101, 105 and 106 infants, respectively, into neonatal, infant and control groups. Despite high background levels of maternally derived antibody, both PCV7 groups had higher GMCs than controls at age 2 months for serotypes 4 (p<0.001) and 9V (p<0.05) and at age 3 months for all VTs except 6B. GMCs for serotypes 4, 9V, 18C and 19F were significantly higher (p<0.001) at age 2 months in the neonatal (one month post-dose2 PCV7) than in the infant group (one month post-dose1 PCV7). PPV induced significantly higher VT antibody responses in PCV7-primed than unprimed infants, with neonatal and infant groups equivalent. High VT and non-VT antibody concentrations generally persisted to age 18 months.ConclusionsPCV7 is well-tolerated and immunogenic in PNG neonates and young infants and induces immunologic memory to PPV booster at age 9 months with antibody levels maintained to age 18 months.Trial registrationClinicalTrials.gov NCT00219401.