Papua New Guinea Institute for Medical Research

Goroka, Papua New Guinea

Papua New Guinea Institute for Medical Research

Goroka, Papua New Guinea
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Schmidt M.S.,University of Iowa | King C.L.,Case Western Reserve University | Siba P.M.,Papua New Guinea Institute for Medical Research | Sanuku N.,Papua New Guinea Institute for Medical Research | Fleckenstein L.,University of Iowa
Journal of Pharmaceutical and Biomedical Analysis | Year: 2014

A sensitive and selective liquid chromatographic method using mass spectrometric detection was developed for the determination of diethylcarbamazine (DEC) in human plasma. DEC and its stable isotope internal standard d3-DEC were extracted from 0.25mL of human plasma using solid phase extraction. Chromatography was performed using a Phenomenex Synergi 4μ Fusion-RP column (2mm×250mm) with gradient elution. The retention time was approximately 4.8min. The assay was linear from 4 to 2200ng/mL. Analysis of quality control samples at 12, 300, and 1700ng/mL (N=15) had interday coefficients of variation of 8.4%, 5.4%, and 6.2%, respectively (N=15). Interday bias results were -2.2%, 6.0%, and 0.8%, respectively. Recovery of DEC from plasma ranged from 84.2% to 90.1%. The method was successfully applied to clinical samples from patients with lymphatic filariasis from a drug-drug interaction study between DEC and albendazole and/or ivermectin. © 2014 Elsevier B.V.


John E.,PathWest Royal Perth Hospital | Christiansen F.T.,PathWest Royal Perth Hospital | Christiansen F.T.,University of Western Australia | Mueller I.,Walter and Eliza Hall Institute of Medical Research | And 6 more authors.
Tissue Antigens | Year: 2012

The frequency of the killer-cell immunoglobulin-like receptor (KIR) genes and transmembrane alleles of KIR2DL4 were studied in coastal (Mugil community) and inland (Ilaita community) communities in Papua New Guinea. Linkage disequilibria between KIR genes and between alleles of KIR2DL4 and the KIR genes were similar to those found in other populations suggesting conservation of the usual gene order in Papua New Guinean haplotypes. Significant differences in the frequency of KIR genes were found between the two populations despite being separated by only 300 km. Examples of individuals who lacked the KIR2DL4 gene and others whose KIR2DL4 allele appeared to have 11 adenines in the polyadenine tract in exon 6 were identified. A relatively low frequency of the KIR A haplotype was found in both populations and particularly in the inland community. The KIR gene frequencies were consistent with the inland Ilaita community being closely related to Australian Aborigines and southern Indians, whereas the KIR gene frequencies of the coastal Mugil community appeared to have been influenced either by recent or ancient admixture from populations with a higher frequency of the KIR A haplotype. © 2012 John Wiley & Sons A/S.


Ahmed M.S.,University of Texas Medical Branch | Aleksunes L.M.,Rutgers University | Boeuf P.,University of Melbourne | Boeuf P.,Melbourne Health | And 25 more authors.
Placenta | Year: 2013

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2012 there were twelve themed workshops, four of which are summarized in this report. These workshops related to various aspects of placental biology: 1) epigenetics and imprinting in the placenta; 2) growth factors and villous trophoblast differentiation; 3) role of the placenta in regulating fetal exposure to xenobiotics during pregnancy; 4) infection and the placenta.


PubMed | Papua New Guinea Institute for Medical Research, Case Western Reserve University and University of Iowa
Type: | Journal: Journal of pharmaceutical and biomedical analysis | Year: 2014

A sensitive and selective liquid chromatographic method using mass spectrometric detection was developed for the determination of diethylcarbamazine (DEC) in human plasma. DEC and its stable isotope internal standard d3-DEC were extracted from 0.25mL of human plasma using solid phase extraction. Chromatography was performed using a Phenomenex Synergi 4 Fusion-RP column (2mm250mm) with gradient elution. The retention time was approximately 4.8min. The assay was linear from 4 to 2200ng/mL. Analysis of quality control samples at 12, 300, and 1700ng/mL (N=15) had interday coefficients of variation of 8.4%, 5.4%, and 6.2%, respectively (N=15). Interday bias results were -2.2%, 6.0%, and 0.8%, respectively. Recovery of DEC from plasma ranged from 84.2% to 90.1%. The method was successfully applied to clinical samples from patients with lymphatic filariasis from a drug-drug interaction study between DEC and albendazole and/or ivermectin.


Arnott A.,Burnet Institute | Arnott A.,Walter and Eliza Hall Institute of Medical Research | Arnott A.,University of Melbourne | Wapling J.,Burnet Institute | And 12 more authors.
Malaria Journal | Year: 2014

Background: As Plasmodium falciparum and Plasmodium vivax co-exist in most malaria-endemic regions outside sub-Saharan Africa, malaria control strategies in these areas must target both species in order to succeed. Population genetic analyses can predict the effectiveness of interventions including vaccines, by providing insight into patterns of diversity and evolution. The aim of this study was to investigate the population genetics of leading malaria vaccine candidate AMA1 in sympatric P. falciparum and P. vivax populations of Papua New Guinea (PNG), an area of similarly high prevalence (Pf = 22.3 to 38.8%, Pv = 15.3 to 31.8%). Methods. A total of 72 Pfama1 and 102 Pvama1 sequences were collected from two distinct areas, Madang and Wosera, on the highly endemic PNG north coast. Results: Despite a greater number of polymorphic sites in the AMA1 genes of P. falciparum (Madang = 52; Wosera = 56) compared to P. vivax (Madang = 36, Wosera = 34), the number of AMA1 haplotypes, haplotype diversity (Hd) and recombination (R) was far lower for P. falciparum (Madang = 12, Wosera = 20; Hd ≤0.92, R ≤45.8) than for P. vivax (Madang = 50, Wosera = 38; Hd = 0.99, R = ≤70.9). Balancing selection was detected only within domain I of AMA1 for P. vivax, and in both domains I and III for P. falciparum. Conclusions: Higher diversity in the genes encoding P. vivax AMA1 than in P. falciparum AMA1 in this highly endemic area has important implications for development of AMA1-based vaccines in PNG and beyond. These results also suggest a smaller effective population size of P. falciparum compared to P. vivax, a finding that warrants further investigation. Differing patterns of selection on the AMA1 genes indicate that critical antigenic sites may differ between the species, highlighting the need for independent investigations of these two leading vaccine candidates. © 2014 Arnott et al.; licensee BioMed Central Ltd.


Arnott A.,Burnet Institute | Mueller I.,Barcelona Center for International Health Research | Mueller I.,Walter and Eliza Hall Institute of Medical Research | Mueller I.,University of Melbourne | And 9 more authors.
PLoS Neglected Tropical Diseases | Year: 2013

Background:The Plasmodium vivax Apical Membrane Antigen 1 (PvAMA1) is a promising malaria vaccine candidate, however it remains unclear which regions are naturally targeted by host immunity and whether its high genetic diversity will preclude coverage by a monovalent vaccine. To assess its feasibility as a vaccine candidate, we investigated the global population structure of PvAMA1.Methodology and Principal Findings:New sequences from Papua New Guinea (PNG, n = 102) were analysed together with published sequences from Thailand (n = 158), India (n = 8), Sri Lanka (n = 23), Venezuela (n = 74) and a collection of isolates from disparate geographic locations (n = 8). A total of 92 single nucleotide polymorphisms (SNPs) were identified including 22 synonymous SNPs and 70 non-synonymous (NS) SNPs. Polymorphisms and signatures of balancing (positive Tajima's D and low FST values) selection were predominantly clustered in domain I, suggesting it is a dominant target of protective immune responses. To estimate global antigenic diversity, haplotypes comprised of (i) non-singleton (n = 40) and (ii) common (≥10% minor allele frequency, n = 23) polymorphic amino acid sites were then analysed revealing a total of 219 and 210 distinct haplotypes, respectively. Although highly diverse, the 210 haplotypes comprised of only common polymorphisms were grouped into eleven clusters, however substantial geographic differentiation was observed, and this may have implications for the efficacy of PvAMA1 vaccines in different malaria-endemic areas. The PNG haplotypes form a distinct group of clusters not found in any other geographic region. Vaccine haplotypes were rare and geographically restricted, suggesting potentially poor efficacy of candidate PvAMA1 vaccines.Conclusions:It may be possible to cover the existing global PvAMA1 diversity by selection of diverse alleles based on these analyses however it will be important to first define the relationships between the genetic and antigenic diversity of this molecule. © 2013 Arnott et al.


Jennison C.,Walter and Eliza Hall Institute of Medical Research | Jennison C.,University of Melbourne | Arnott A.,Walter and Eliza Hall Institute of Medical Research | Arnott A.,University of Melbourne | And 13 more authors.
PLoS Neglected Tropical Diseases | Year: 2015

Introduction: The human malaria parasite, Plasmodium vivax, is proving more difficult to control and eliminate than Plasmodium falciparum in areas of co-transmission. Comparisons of the genetic structure of sympatric parasite populations may provide insight into the mechanisms underlying the resilience of P. vivax and can help guide malaria control programs. Methodology/Principle findings:P. vivax isolates representing the parasite populations of four areas on the north coast of Papua New Guinea (PNG) were genotyped using microsatellite markers and compared with previously published microsatellite data from sympatric P. falciparum isolates. The genetic diversity of P. vivax (He = 0.83–0.85) was higher than that of P. falciparum (He = 0.64–0.77) in all four populations. Moderate levels of genetic differentiation were found between P. falciparum populations, even over relatively short distances (less than 50 km), with 21–28% private alleles and clear geospatial genetic clustering. Conversely, very low population differentiation was found between P. vivax catchments, with less than 5% private alleles and no genetic clustering observed. In addition, the effective population size of P. vivax (30353; 13043–69142) was larger than that of P. falciparum (18871; 8109–42986). Conclusions/Significance: Despite comparably high prevalence, P. vivax had higher diversity and a panmictic population structure compared to sympatric P. falciparum populations, which were fragmented into subpopulations. The results suggest that in comparison to P. falciparum, P. vivax has had a long-term large effective population size, consistent with more intense and stable transmission, and limited impact of past control and elimination efforts. This underlines suggestions that more intensive and sustained interventions will be needed to control and eventually eliminate P. vivax. This research clearly demonstrates how population genetic analyses can reveal deeper insight into transmission patterns than traditional surveillance methods. © 2015 Jennison et al.


PubMed | Burnet Institute, Swiss Tropical and Public Health Institute, Walter and Eliza Hall Institute of Medical Research and Papua New Guinea Institute for Medical Research
Type: Journal Article | Journal: PLoS neglected tropical diseases | Year: 2015

The human malaria parasite, Plasmodium vivax, is proving more difficult to control and eliminate than Plasmodium falciparum in areas of co-transmission. Comparisons of the genetic structure of sympatric parasite populations may provide insight into the mechanisms underlying the resilience of P. vivax and can help guide malaria control programs.P. vivax isolates representing the parasite populations of four areas on the north coast of Papua New Guinea (PNG) were genotyped using microsatellite markers and compared with previously published microsatellite data from sympatric P. falciparum isolates. The genetic diversity of P. vivax (He = 0.83-0.85) was higher than that of P. falciparum (He = 0.64-0.77) in all four populations. Moderate levels of genetic differentiation were found between P. falciparum populations, even over relatively short distances (less than 50 km), with 21-28% private alleles and clear geospatial genetic clustering. Conversely, very low population differentiation was found between P. vivax catchments, with less than 5% private alleles and no genetic clustering observed. In addition, the effective population size of P. vivax (30353; 13043-69142) was larger than that of P. falciparum (18871; 8109-42986).Despite comparably high prevalence, P. vivax had higher diversity and a panmictic population structure compared to sympatric P. falciparum populations, which were fragmented into subpopulations. The results suggest that in comparison to P. falciparum, P. vivax has had a long-term large effective population size, consistent with more intense and stable transmission, and limited impact of past control and elimination efforts. This underlines suggestions that more intensive and sustained interventions will be needed to control and eventually eliminate P. vivax. This research clearly demonstrates how population genetic analyses can reveal deeper insight into transmission patterns than traditional surveillance methods.


Howes R.E.,University of Oxford | Patil A.P.,University of Oxford | Piel F.B.,University of Oxford | Nyangiri O.A.,Kenya Medical Research Institute | And 10 more authors.
Nature Communications | Year: 2011

Blood group variants are characteristic of population groups, and can show conspicuous geographic patterns. Interest in the global prevalence of the Duffy blood group variants is multidisciplinary, but of particular importance to malariologists due to the resistance generally conferred by the Duffy-negative phenotype against Plasmodium vivax infection. Here we collate an extensive geo-database of surveys, forming the evidence-base for a multi-locus Bayesian geostatistical model to generate global frequency maps of the common Duffy alleles to refine the global cartography of the common Duffy variants. We show that the most prevalent allele globally was FY*A, while across sub-Saharan Africa the predominant allele was the silent FY*BES variant, commonly reaching fixation across stretches of the continent. The maps presented not only represent the first spatially and genetically comprehensive description of variation at this locus, but also constitute an advance towards understanding the transmission patterns of the neglected P. vivax malaria parasite. © 2011 Macmillan Publishers Limited. All rights reserved.


Chidlow G.R.,PathWest Laboratory Medicine WA | Chidlow G.R.,University of Western Australia | Laing I.A.,University of Western Australia | Harnett G.B.,PathWest Laboratory Medicine WA | And 9 more authors.
Journal of Clinical Virology | Year: 2012

Background: Acute lower respiratory tract infections (ALRI) commonly result in fatal outcomes in the young children of Papua New Guinea (PNG). However, comprehensive studies of the viral aetiology of ALRI have not been conducted in PNG for almost 30 years. Objectives: To determine the viruses associated with ALRI among children living in the PNG highlands using sensitive molecular detection techniques. Study design: Pernasal swabs were collected routinely between 1 week and 18 months of age and also during episodes of ALRI, as part of a neonatal pneumococcal conjugate vaccine trial. A tandem multiplex real-time PCR assay was used to test for a comprehensive range of respiratory viruses in samples collected from 221 young children. Picornavirus typing was supported by DNA sequence analysis. Results: Recognized pathogenic respiratory viruses were detected in 198/273 (73%) samples collected from children with no evidence of ALRI and 69/80 (86%) samples collected during ALRI episodes. Human rhinoviruses (HRV) species A, B and C were detected in 152 (56%) samples from non-ALRI children and 50 (63%) samples collected during ALRI episodes. Partial structural region sequences for two new species C rhinoviruses were added to the GenBank database. ALRI was associated with detection of adenovirus species B (p< 0.01) or C (p< 0.05), influenza A (p< 0.0001) or respiratory syncytial virus (p< 0.0001). Multiple viruses were detected more often during ALRI episodes (49%) than when children displayed no symptoms of ALRI (18%) (p< 0.0001). Conclusions: The burden of infection with respiratory viruses remains significant in young children living in the PNG highlands. © 2012 .

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