PNG Institute of Medical Research

Madang, Papua New Guinea

PNG Institute of Medical Research

Madang, Papua New Guinea
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PubMed | Walter and Eliza Hall Institute of Medical Research, PNG Institute of Medical Research, National Health Research Institute, Wellcome Trust Sanger Institute and 2 more.
Type: Journal Article | Journal: PLoS neglected tropical diseases | Year: 2016

Elimination of Plasmodium vivax malaria would be greatly facilitated by the development of an effective vaccine. A comprehensive and systematic characterization of antibodies to P. vivax antigens in exposed populations is useful in guiding rational vaccine design.In this study, we investigated antibodies to a large library of P. vivax entire ectodomain merozoite proteins in 2 Asia-Pacific populations, analysing the relationship of antibody levels with markers of current and cumulative malaria exposure, and socioeconomic and clinical indicators. 29 antigenic targets of natural immunity were identified. Of these, 12 highly-immunogenic proteins were strongly associated with age and thus cumulative lifetime exposure in Solomon Islanders (P<0.001-0.027). A subset of 6 proteins, selected on the basis of immunogenicity and expression levels, were used to examine antibody levels in plasma samples from a population of young Papua New Guinean children with well-characterized individual differences in exposure. This analysis identified a strong association between reduced risk of clinical disease and antibody levels to P12, P41, and a novel hypothetical protein that has not previously been studied, PVX_081550 (IRR 0.46-0.74; P<0.001-0.041).These data emphasize the benefits of an unbiased screening approach in identifying novel vaccine candidate antigens. Functional studies are now required to establish whether PVX_081550 is a key component of the naturally-acquired protective immune response, a biomarker of immune status, or both.


Barnadas C.,PNG Institute of Medical Research | Barnadas C.,Case Western Reserve University | Barnadas C.,Walter and Eliza Hall Institute | Koepfli C.,Swiss Tropical and Public Health Institute | And 7 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2011

Plasmodium vivax intervention trials customarily report uncorrected treatment failure rates. Application of recrudescence-reinfection genotyping and drug resistance single-nucleotide polymorphism typing to a 4-arm comparative efficacy trial illustrated that molecular approaches can assist in understanding the relative contributions of true drug resistance (recurrent with same genotype) and new infections to treatment failure. The PCR-corrected adequate clinical and parasitologic response may constitute an informative secondary endpoint in future P. vivax drug trials. Copyright © 2011, American Society for Microbiology. All Rights Reserved.


Koepfli C.,Swiss Tropical and Public Health Institute | Koepfli C.,University of Basel | Koepfli C.,Walter and Eliza Hall Institute | Timinao L.,Swiss Tropical and Public Health Institute | And 10 more authors.
PLoS ONE | Year: 2013

Introduction:The importance of Plasmodium vivax in malaria elimination is increasingly being recognized, yet little is known about its population size and population genetic structure in the South Pacific, an area that is the focus of intensified malaria control.Methods:We have genotyped 13 microsatellite markers in 295 P. vivax isolates from four geographically distinct sites in Papua New Guinea (PNG) and one site from Solomon Islands, representing different transmission intensities.Results:Diversity was very high with expected heterozygosity values ranging from 0.62 to 0.98 for the different markers. Effective population size was high (12′872 to 19′533 per site). In PNG population structuring was limited with moderate levels of genetic differentiation. FST values (adjusted for high diversity of markers) were 0.14-0.15. Slightly higher levels were observed between PNG populations and Solomon Islands (FST = 0.16).Conclusions:Low levels of population structure despite geographical barriers to transmission are in sharp contrast to results from regions of low P. vivax endemicity. Prior to intensification of malaria control programs in the study area, parasite diversity and effective population size remained high. © 2013 Koepfli et al.


Mitja O.,Lihir Medical Center | Mitja O.,University of Barcelona | Paru R.,Lihir Medical Center | Selve B.,Newcrest Mining Ltd | And 4 more authors.
Malaria Journal | Year: 2013

Background: Plasmodium vivax and Plasmodium falciparum malaria remain highly endemic in the Pacific Islands including Lihir Island, Papua New Guinea. Lihir Gold Limited is conducting mining activities and funded an integrated vector control intervention within the villages surrounding the mine. The aim of this study was to assess the impact of such programme by comparing the epidemiological trends of malaria in different parts of the island. Methods. Two cross-sectional surveys were conducted before and after the intervention (2006-2010) to determine malaria prevalence in mine-impact (MI) and non-MI areas. Incidence of malaria was estimated for the Lihir Medical Centre catchment area using island population denominators and a health-centre passive case detection ongoing from 2006-2011. Results: A total of 2,264 and 1,653 children < 15 were surveyed in the cross-sectional studies. The prevalence of any malaria parasitaemia initially was 31.5% in MI areas and, 34.9% in non-MI (POR 1.17; 95 CI 0.97 - 1.39). After four years there was a significant reduction in prevalence in the MI areas (5.8%; POR 0.13, 95 CI 0.09-0.20), but reduction was less marked in non-MI areas (26.9%; POR 0.69, 95 CI 0.58-0.81).28,747 patients were included in the evaluation of incidence trends and overall malaria in local Lihirian population in MI areas declined over time, while it remained at similar high levels among migrants. The age-incidence analysis showed that for each higher age range the malaria incidence declines compared to that of the previous stratum. Conclusions: There was a substantial reduction in prevalence and incidence rates of both P. vivax and P. falciparum in the mining area following implementation of a malaria control intervention, which was not seen in the area outside the mining activities. © 2013 Mitjà et al.; licensee BioMed Central Ltd.


Koepfli C.,Swiss Tropical and Public Health Institute | Koepfli C.,University of Basel | Ross A.,Swiss Tropical and Public Health Institute | Ross A.,University of Basel | And 10 more authors.
PLoS Neglected Tropical Diseases | Year: 2011

Plasmodium vivax is highly endemic in the lowlands of Papua New Guinea and accounts for a large proportion of the malaria cases in children less than 5 years of age. We collected 2117 blood samples at 2-monthly intervals from a cohort of 268 children aged 1 to 4.5 years and estimated the diversity and multiplicity of P. vivax infection. All P. vivax clones were genotyped using the merozoite surface protein 1 F3 fragment (msp1F3) and the microsatellite MS16 as molecular markers. High diversity was observed with msp1F3 (HE = 88.1%) and MS16 (HE = 97.8%). Of the 1162 P. vivax positive samples, 74% harbored multi-clone infections with a mean multiplicity of 2.7 (IQR = 1-3). The multiplicity of P. vivax infection increased slightly with age (P = 0.02), with the strongest increase in very young children. Intensified efforts to control malaria can benefit from knowledge of the diversity and MOI both for assessing the endemic situation and monitoring the effects of interventions. © 2011 Koepfli et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Lin E.,PNG Institute of Medical Research | Kiniboro B.,PNG Institute of Medical Research | Gray L.,Case Western Reserve University | Dobbie S.,PNG Institute of Medical Research | And 13 more authors.
PLoS ONE | Year: 2010

Background: Where P. vivax and P. falciparum occur in the same population, the peak burden of P. vivax infection and illness is often concentrated in younger age groups. Experiences from malaria therapy patients indicate that immunity is acquired faster to P. vivax than to P. falciparum challenge. There is however little prospective data on the comparative risk of infection and disease from both species in young children living in co-endemic areas. Methodology/Principal Findings: A cohort of 264 Papua New Guinean children aged 1-3 years (at enrolment) were actively followed-up for Plasmodium infection and febrile illness for 16 months. Infection status was determined by light microscopy and PCR every 8 weeks and at each febrile episode. A generalised estimating equation (GEE) approach was used to analyse both prevalence of infection and incidence of clinical episodes. A more pronounced rise in prevalence of P. falciparum compared to P. vivax infection was evident with increasing age. Although the overall incidence of clinical episodes was comparable (P. falciparum: 2.56, P. vivax 2.46 episodes / child / yr), P. falciparum and P. vivax infectious episodes showed strong but opposing age trends: P. falciparum incidence increased until the age of 30 months with little change thereafter, but incidence of P. vivax decreased significantly with age throughout the entire age range. For P. falciparum, both prevalence and incidence of P. falciparum showed marked seasonality, whereas only P. vivax incidence but not prevalence decreased in the dry season. Conclusions/ Significance: Under high, perennial exposure, children in PNG begin acquiring significant clinical immunity, characterized by an increasing ability to control parasite densities below the pyrogenic threshold to P. vivax, but not to P. falciparum, in the 2nd and 3rd year of life. The ability to relapse from long-lasting liver-stages restricts the seasonal variation in prevalence of P. vivax infections. © 2010 Lin et al.


Barry A.E.,Walter and Eliza Hall Institute of Medical Research | Barry A.E.,University of Melbourne | Waltmann A.,Walter and Eliza Hall Institute of Medical Research | Waltmann A.,University of Melbourne | And 8 more authors.
Pathogens and Global Health | Year: 2015

Population genetic analysis ofmalaria parasites has the power to reveal key insights into malaria epidemiology and transmission dynamics with the potential to deliver tools to support control and elimination efforts. Analyses of parasite genetic diversity have suggested that Plasmodium vivax populations are more genetically diverse and less structured than those ofPlasmodiumfalciparumindicating thatP. vivaxmay be amore ancientparasite ofhumans and/or less susceptibletopopulationbottlenecks, aswell asmoreefficient atdisseminatingitsgenes. These population genetic insights into P. vivax transmission dynamics provide an explanation for its relative resilience to control efforts. Here, we describe current knowledge on P. vivax population genetic structure, its relevance to understanding transmission patterns and relapse and how this information can inform malaria control and elimination programmes. © W. S. Maney & Son Ltd 2015.


PubMed | PNG Institute of Medical Research, Walter and Eliza Hall Institute of Medical Research and University of Melbourne
Type: Journal Article | Journal: PLoS neglected tropical diseases | Year: 2016

Major gaps in our understanding of Plasmodium vivax biology and the acquisition of immunity to this parasite hinder vaccine development. P. vivax merozoites exclusively invade reticulocytes, making parasite proteins that mediate reticulocyte binding and/or invasion potential key vaccine or drug targets. While protein interactions that mediate invasion are still poorly understood, the P. vivax Reticulocyte-Binding Protein family (PvRBP) is thought to be involved in P. vivax restricted host-cell selectivity.We assessed the binding specificity of five members of the PvRBP family (PvRBP1a, PvRBP1b, PvRBP2a, PvRBP2b, PvRBP2-P2 and a non-binding fragment of PvRBP2c) to normocytes or reticulocytes. PvRBP2b was identified as the only reticulocyte-specific binder (P<0.001), whereas the others preferentially bound to normocytes (PvRBP1a/b P0.034), or showed comparable binding to both (PvRBP2a/2-P2, P = 0.38). Furthermore, we measured levels of total and IgG subclasses 1, 2, 3 and 4 to the six PvRBPs in a cohort of young Papua New Guinean children, and assessed their relationship with prospective risk of P. vivax malaria. Children had substantial, highly correlated (rho = 0.49-0.82, P<0.001) antibody levels to all six PvRBPs, with dominant IgG1 and IgG3 subclasses. Both total IgG (Incidence Rate Ratio [IRR] 0.63-0.73, P = 0.008-0.041) and IgG1 (IRR 0.56-0.69, P = 0.001-0.035) to PvRBP2b and PvRBP1a were strongly associated with reduced risk of vivax-malaria, independently of age and exposure.These results demonstrate a diversity of erythrocyte-binding phenotypes of PvRBPs, indicating binding to both reticulocyte-specific and normocyte-specific ligands. Our findings provide further insights into the naturally acquired immunity to P. vivax and highlight the importance of PvRBP proteins as targets of naturally acquired humoral immunity. In-depth studies of the role of PvRBPs in P. vivax invasion and functional validation of the role of anti-PvRBP antibodies in clinical immunity against P. vivax are now required to confirm the potential of the reticulocyte-binding PvRBP2b and PvRBP1a as vaccine candidate antigens.


Baker A.,James Cook University | Tahani D.,James Cook University | Gardiner C.,James Cook University | Bristow K.L.,CSIRO | And 3 more authors.
Applied and Environmental Microbiology | Year: 2011

Burkholderia pseudomallei is a saprophytic bacterium which is the causative agent of melioidosis, a common cause of fatal bacterial pneumonia and sepsis in the tropics. The incidence of melioidosis is clustered spatially and temporally and is heavily linked to rainfall and extreme weather events. Clinical case clustering has recently been reported in Townsville, Australia, and has implicated Castle Hill, a granite monolith in the city center, as a potential reservoir of infection. Topsoil and water from seasonal groundwater seeps were collected around the base of Castle Hill and analyzed by quantitative real-time PCR targeting the type III secretion system genes for the presence of B. pseudomallei. The organism was identified in 65% (95% confidence interval [CI], 49.5 to 80.4) of soil samples (n =40) and 92.5% (95% CI, 83.9 to 100) of seasonal groundwater samples (n =40). Further sampling of water collected from roads and gutters in nearby residential areas after an intense rainfall event found that 88.2% (95% CI, 72.9 to 100) of samples (n =16) contained viable B. pseudomallei at concentrations up to 113 CFU/ml. Comparison of isolates using multilocus sequence typing demonstrated clinical matches and close associations between environmental isolates and isolates derived from clinical samples from patients in Townsville. This study demonstrated that waterborne B. pseudomallei from groundwater seeps around Castle Hill may facilitate exposure to B. pseudomallei and contribute to the clinical clustering at this site. Access to this type of information will advise the development and implementation of public health measures to reduce the incidence of melioidosis. © 2011, American Society for Microbiology.


Makaen J.,PNG Institute of Medical Research | Maure T.,PNG Institute of Medical Research
Laboratory Medicine | Year: 2014

The conventional method of processing sputum for acid fast bacilli microscopy has been a primary tool for laboratory diagnosis of pulmonary tuberculosis in Papua New Guinea. In routine preparation, untreated sputum is directly smeared on a glass slide without undergoing any stage of processing. Mounting evidence suggests that direct smearing is less sensitive and, to a certain degree, compromises infection control. A few alternatives for processing sputum have been recommended in the literature; however, their consumables are not easily accessible and are expensive for wide use in rural laboratories. The bleach concentration and processing method appears to be the most preferable choice because bleach is inexpensive, readily available, and has bactericidal properties.

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