12 results on '"MacHunter, B."'
Search Results
2. Bacteria and viruses in the nasopharynx immediately prior to onset of acute lower respiratory infections in Indigenous Australian children
- Author
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Smith-Vaughan, HC, Binks, MJ, Beissbarth, J, Chang, AB, McCallum, GB, Mackay, IM, Morris, PS, Marsh, RL, Torzillo, PJ, Wurzel, DF, Grimwood, K, Nosworthy, E, Gaydon, JE, Leach, AJ, MacHunter, B, Chatfield, MD, Sloots, TP, Cheng, AC, Smith-Vaughan, HC, Binks, MJ, Beissbarth, J, Chang, AB, McCallum, GB, Mackay, IM, Morris, PS, Marsh, RL, Torzillo, PJ, Wurzel, DF, Grimwood, K, Nosworthy, E, Gaydon, JE, Leach, AJ, MacHunter, B, Chatfield, MD, Sloots, TP, and Cheng, AC
- Abstract
Acute lower respiratory infection (ALRI) is a major cause of hospitalization for Indigenous children in remote regions of Australia. The associated microbiology remains unclear. Our aim was to determine whether the microbes present in the nasopharynx before an ALRI were associated with its onset. A retrospective case-control/crossover study among Indigenous children aged up to 2 years. ALRI cases identified by medical note review were eligible where nasopharyngeal swabs were available: (1) 0-21 days before ALRI onset (case); (2) 90-180 days before ALRI onset (same child controls); and (3) from time and age-matched children without ALRI (different child controls). PCR assays determined the presence and/or load of selected respiratory pathogens. Among 104 children (182 recorded ALRI episodes), 120 case-same child control and 170 case-different child control swab pairs were identified. Human adenoviruses (HAdV) were more prevalent in cases compared to same child controls (18 vs 7%; OR = 3.08, 95% CI 1.22-7.76, p = 0.017), but this association was not significant in cases versus different child controls (15 vs 10%; OR = 1.93, 95% CI 0.97-3.87 (p = 0.063). No other microbes were more prevalent in cases compared to controls. Streptococcus pneumoniae (74%), Haemophilus influenzae (75%) and Moraxella catarrhalis (88%) were commonly identified across all swabs. In a pediatric population with a high detection rate of nasopharyngeal microbes, HAdV was the only pathogen detected in the period before illness presentation that was significantly associated with ALRI onset. Detection of other potential ALRI pathogens was similar between cases and controls.
- Published
- 2018
3. The melioidosis agentBurkholderia pseudomalleiand related opportunistic pathogens detected in faecal matter of wildlife and livestock in northern Australia
- Author
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HÖGER, A. C. R., primary, MAYO, M., additional, PRICE, E. P., additional, THEOBALD, V., additional, HARRINGTON, G., additional, MACHUNTER, B., additional, CHOY, J. LOW, additional, CURRIE, B. J., additional, and KAESTLI, M., additional
- Published
- 2016
- Full Text
- View/download PDF
4. Stronger Activity of Human Immunodeficiency Virus Type 1 Protease Inhibitors against Clinical Isolates of Plasmodium vivax than against Those of P. falciparum
- Author
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Lek-Uthai, U., primary, Suwanarusk, R., additional, Ruengweerayut, R., additional, Skinner-Adams, T. S., additional, Nosten, F., additional, Gardiner, D. L., additional, Boonma, P., additional, Piera, K. A., additional, Andrews, K. T., additional, MacHunter, B., additional, McCarthy, J. S., additional, Anstey, N. M., additional, Price, R. N., additional, and Russell, B., additional
- Published
- 2008
- Full Text
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5. Stronger Activity of Human Immunodeficiency Virus Type 1 Protease Inhibitors against Clinical Isolates of Plasmodium vivaxthan against Those of P. falciparum
- Author
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Lek-Uthai, U., Suwanarusk, R., Ruengweerayut, R., Skinner-Adams, T. S., Nosten, F., Gardiner, D. L., Boonma, P., Piera, K. A., Andrews, K. T., MacHunter, B., McCarthy, J. S., Anstey, N. M., Price, R. N., and Russell, B.
- Abstract
ABSTRACTRecent studies using laboratory clones have demonstrated that several antiretroviral protease inhibitors (PIs) inhibit the growth of Plasmodium falciparumat concentrations that may be of clinical significance, especially during human immunodeficiency virus type 1 (HIV-1) and malaria coinfection. Using clinical isolates, we now demonstrate the in vitro effectiveness of two HIV-1 aspartic PIs, saquinavir (SQV) and ritonavir (RTV), against P. vivax(n= 30) and P. falciparum(n= 20) from populations subjected to high levels of mefloquine and artesunate pressure on the Thailand-Myanmar border. The median 50% inhibitory concentration values of P. vivaxto RTV and SQV were 2,233 nM (range, 732 to 7,738 nM) and 4,230 nM (range, 1,326 to 8,452 nM), respectively, both within the therapeutic concentration range commonly found for patients treated with these PIs. RTV was fourfold more effective at inhibiting P. vivaxthan it was at inhibiting P. falciparum, compared to a twofold difference in SQV sensitivity. An increased P. falciparum mdr1copy number was present in 33% (3/9) of isolates and that of P. vivax mdr1was present in 9% of isolates (2/22), but neither was associated with PI sensitivity. The inter-Plasmodiumsp. variations in PI sensitivity indicate key differences between P. vivaxand P. falciparum. PI-containing antiretroviral regimens may demonstrate prophylactic activity against both vivax and falciparum malaria in HIV-infected patients who reside in areas where multidrug-resistant P. vivaxor P. falciparumis found.
- Published
- 2008
- Full Text
- View/download PDF
6. Longitudinal ex vivo and molecular trends of chloroquine and piperaquine activity against Plasmodium falciparum and P. vivax before and after introduction of artemisinin-based combination therapy in Papua, Indonesia.
- Author
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Marfurt J, Wirjanata G, Prayoga P, Chalfein F, Leonardo L, Sebayang BF, Apriyanti D, Sihombing MAEM, Trianty L, Suwanarusk R, Brockman A, Piera KA, Luo I, Rumaseb A, MacHunter B, Auburn S, Anstey NM, Kenangalem E, Noviyanti R, Russell B, Poespoprodjo JR, and Price RN
- Subjects
- Chloroquine pharmacology, Chloroquine therapeutic use, Drug Resistance genetics, Humans, Indonesia epidemiology, Plasmodium falciparum genetics, Plasmodium vivax genetics, Protozoan Proteins genetics, Quinolines, Antimalarials pharmacology, Antimalarials therapeutic use, Artemisinins pharmacology, Artemisinins therapeutic use, Malaria, Falciparum drug therapy, Malaria, Falciparum epidemiology
- Abstract
Drug resistant Plasmodium parasites are a major threat to malaria control and elimination. After reports of high levels of multidrug resistant P. falciparum and P. vivax in Indonesia, in 2005, the national first-line treatment policy for uncomplicated malaria was changed in March 2006, to dihydroartemisinin-piperaquine against all species. This study assessed the temporal trends in ex vivo drug susceptibility to chloroquine (CQ) and piperaquine (PIP) for both P. falciparum and P. vivax clinical isolates collected between 2004 and 2018, by using schizont maturation assays, and genotyped a subset of isolates for known and putative molecular markers of CQ and PIP resistance by using Sanger and next generation whole genome sequencing. The median CQ IC
50 values varied significantly between years in both Plasmodium species, but there was no significant trend over time. In contrast, there was a significant trend for increasing PIP IC50 s in both Plasmodium species from 2010 onwards. Whereas the South American CQ resistant 7G8 pfcrt SVMNT isoform has been fixed since 2005 in the study area, the pfmdr1 86Y allele frequencies decreased and became fixed at the wild-type allele in 2015. In P. vivax isolates, putative markers of CQ resistance (no pvcrt-o AAG (K10) insertion and pvmdr1 Y967F and F1076L) were fixed at the mutant alleles since 2005. None of the putative PIP resistance markers were detected in P. falciparum. The ex vivo drug susceptibility and molecular analysis of CQ and PIP efficacy for P. falciparum and P. vivax after 12 years of intense drug pressure with DHP suggests that whilst the degree of CQ resistance appears to have been sustained, there has been a slight decline in PIP susceptibility, although this does not appear to have reached clinically significant levels. The observed decreasing trend in ex vivo PIP susceptibility highlights the importance of ongoing surveillance., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2021
- Full Text
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7. Bacteria and viruses in the nasopharynx immediately prior to onset of acute lower respiratory infections in Indigenous Australian children.
- Author
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Smith-Vaughan HC, Binks MJ, Beissbarth J, Chang AB, McCallum GB, Mackay IM, Morris PS, Marsh RL, Torzillo PJ, Wurzel DF, Grimwood K, Nosworthy E, Gaydon JE, Leach AJ, MacHunter B, Chatfield MD, Sloots TP, and Cheng AC
- Subjects
- Acute Disease epidemiology, Australia epidemiology, Bacteria classification, Bacteria genetics, Case-Control Studies, Child, Preschool, Cross-Over Studies, Female, Hospitalization, Humans, Infant, Male, Moraxella catarrhalis genetics, Moraxella catarrhalis isolation & purification, Native Hawaiian or Other Pacific Islander, Polymerase Chain Reaction, Prevalence, Respiratory Tract Infections epidemiology, Retrospective Studies, Streptococcus pneumoniae genetics, Streptococcus pneumoniae isolation & purification, Viruses genetics, Bacteria isolation & purification, Nasopharynx microbiology, Nasopharynx virology, Respiratory Tract Infections microbiology, Respiratory Tract Infections virology, Viruses isolation & purification
- Abstract
Acute lower respiratory infection (ALRI) is a major cause of hospitalization for Indigenous children in remote regions of Australia. The associated microbiology remains unclear. Our aim was to determine whether the microbes present in the nasopharynx before an ALRI were associated with its onset. A retrospective case-control/crossover study among Indigenous children aged up to 2 years. ALRI cases identified by medical note review were eligible where nasopharyngeal swabs were available: (1) 0-21 days before ALRI onset (case); (2) 90-180 days before ALRI onset (same child controls); and (3) from time and age-matched children without ALRI (different child controls). PCR assays determined the presence and/or load of selected respiratory pathogens. Among 104 children (182 recorded ALRI episodes), 120 case-same child control and 170 case-different child control swab pairs were identified. Human adenoviruses (HAdV) were more prevalent in cases compared to same child controls (18 vs 7%; OR = 3.08, 95% CI 1.22-7.76, p = 0.017), but this association was not significant in cases versus different child controls (15 vs 10%; OR = 1.93, 95% CI 0.97-3.87 (p = 0.063). No other microbes were more prevalent in cases compared to controls. Streptococcus pneumoniae (74%), Haemophilus influenzae (75%) and Moraxella catarrhalis (88%) were commonly identified across all swabs. In a pediatric population with a high detection rate of nasopharyngeal microbes, HAdV was the only pathogen detected in the period before illness presentation that was significantly associated with ALRI onset. Detection of other potential ALRI pathogens was similar between cases and controls.
- Published
- 2018
- Full Text
- View/download PDF
8. Pediatric melioidosis in Sarawak, Malaysia: Epidemiological, clinical and microbiological characteristics.
- Author
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Mohan A, Podin Y, Tai N, Chieng CH, Rigas V, Machunter B, Mayo M, Wong D, Chien SL, Tan LS, Goh C, Bantin R, Mijen A, Chua WY, Hii KC, Wong SC, Ngian HU, Wong JS, Hashim J, Currie BJ, and Ooi MH
- Subjects
- Adolescent, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Malaysia epidemiology, Male, Prospective Studies, Rain, Retrospective Studies, Time Factors, Melioidosis epidemiology, Melioidosis pathology
- Abstract
Background: Melioidosis is a serious, and potentially fatal community-acquired infection endemic to northern Australia and Southeast Asia, including Sarawak, Malaysia. The disease, caused by the usually intrinsically aminoglycoside-resistant Burkholderia pseudomallei, most commonly affects adults with predisposing risk factors. There are limited data on pediatric melioidosis in Sarawak., Methods: A part prospective, part retrospective study of children aged <15 years with culture-confirmed melioidosis was conducted in the 3 major public hospitals in Central Sarawak between 2009 and 2014. We examined epidemiological, clinical and microbiological characteristics., Findings: Forty-two patients were recruited during the 6-year study period. The overall annual incidence was estimated to be 4.1 per 100,000 children <15 years, with marked variation between districts. No children had pre-existing medical conditions. Twenty-three (55%) had disseminated disease, 10 (43%) of whom died. The commonest site of infection was the lungs, which occurred in 21 (50%) children. Other important sites of infection included lymph nodes, spleen, joints and lacrimal glands. Seven (17%) children had bacteremia with no overt focus of infection. Delays in diagnosis and in melioidosis-appropriate antibiotic treatment were observed in nearly 90% of children. Of the clinical isolates tested, 35/36 (97%) were susceptible to gentamicin. Of these, all 11 isolates that were genotyped were of a single multi-locus sequence type, ST881, and possessed the putative B. pseudomallei virulence determinants bimABp, fhaB3, and the YLF gene cluster., Conclusions: Central Sarawak has a very high incidence of pediatric melioidosis, caused predominantly by gentamicin-susceptible B. pseudomallei strains. Children frequently presented with disseminated disease and had an alarmingly high death rate, despite the absence of any apparent predisposing risk factor.
- Published
- 2017
- Full Text
- View/download PDF
9. Improved multilocus sequence typing of Burkholderia pseudomallei and closely related species.
- Author
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Price EP, MacHunter B, Spratt BG, Wagner DM, Currie BJ, and Sarovich DS
- Subjects
- Anion Transport Proteins genetics, DNA Primers, Genes, Bacterial, Burkholderia classification, Burkholderia genetics, Genotype, Multilocus Sequence Typing methods
- Abstract
The Burkholderiapseudomallei multilocus sequence typing (MLST) database (http://pubmlst.org/bpseudomallei/) contains the largest global sequence repository for B. pseudomallei and its closest genetic relatives. Using conventional MLST and in silico MLST data derived from publicly available whole-genome sequences, we first defined the phylogenetic relatedness of B. pseudomallei and its nearest neighbours. Based on this analysis, we propose that the recently described B. pseudomallei complex (Bpc) should be expanded to encompass B. pseudomallei, Burkholderiahumptydooensis (proposed), Burkholderiamallei, Burkholderiaoklahomensis, Burkholderiathailandensis and three unassigned Burkholderia Clades A, B and C (represented by type strains BDU 5, BDU 8 and MSMB0265, respectively). Of note, the MLST narK locus is present in all Bpc species but is missing in all other Burkholderia spp., including all Burkholderiacepacia complex species, with the exception of most Burkholderiaubonensis strains, which contain narK but encode genetically distinct sequences. The presence of narK is thus indicative of a Bpc strain. Next, we revisited in silico the performance of the existing MLST primers, which prompted redesign of primers targeting the gmhD, lepA, lipA, narK and ndh loci to encompass genetic diversity among Bpc strains and to address amplification/sequencing issues. We show in silico and in vitro that the redesigned primers yield good-quality amplification and sequencing results for the gmhD, lepA, lipA, narK and ndh loci in Bpc species. These primers provide an alternative for amplification and sequencing of MLST loci in Bpc species in cases when poor-quality amplification or sequencing data are obtained using the original MLST primers.
- Published
- 2016
- Full Text
- View/download PDF
10. Unprecedented Melioidosis Cases in Northern Australia Caused by an Asian Burkholderia pseudomallei Strain Identified by Using Large-Scale Comparative Genomics.
- Author
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Price EP, Sarovich DS, Smith EJ, MacHunter B, Harrington G, Theobald V, Hall CM, Hornstra HM, McRobb E, Podin Y, Mayo M, Sahl JW, Wagner DM, Keim P, Kaestli M, and Currie BJ
- Subjects
- Animals, Asia, Australia epidemiology, DNA, Bacterial genetics, Genetic Variation, Genomics methods, Genotype, Humans, Melioidosis epidemiology, Melioidosis transmission, Phylogeny, Polymorphism, Single Nucleotide, Sequence Analysis, DNA, Burkholderia pseudomallei genetics, Burkholderia pseudomallei isolation & purification, Genome, Bacterial, Melioidosis microbiology
- Abstract
Melioidosis is a disease of humans and animals that is caused by the saprophytic bacterium Burkholderia pseudomallei. Once thought to be confined to certain locations, the known presence of B. pseudomallei is expanding as more regions of endemicity are uncovered. There is no vaccine for melioidosis, and even with antibiotic administration, the mortality rate is as high as 40% in some regions that are endemic for the infection. Despite high levels of recombination, phylogenetic reconstruction of B. pseudomallei populations using whole-genome sequencing (WGS) has revealed surprisingly robust biogeographic separation between isolates from Australia and Asia. To date, there have been no confirmed autochthonous melioidosis cases in Australia caused by an Asian isolate; likewise, no autochthonous cases in Asia have been identified as Australian in origin. Here, we used comparative genomic analysis of 455 B. pseudomallei genomes to confirm the unprecedented presence of an Asian clone, sequence type 562 (ST-562), in Darwin, northern Australia. First observed in Darwin in 2005, the incidence of melioidosis cases attributable to ST-562 infection has steadily risen, and it is now a common strain in Darwin. Intriguingly, the Australian ST-562 appears to be geographically restricted to a single locale and is genetically less diverse than other common STs from this region, indicating a recent introduction of this clone into northern Australia. Detailed genomic and epidemiological investigations of new clinical and environmental B. pseudomallei isolates in the Darwin region and ST-562 isolates from Asia will be critical for understanding the origin, distribution, and dissemination of this emerging clone in northern Australia., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
- Published
- 2015
- Full Text
- View/download PDF
11. Effective preparation of Plasmodium vivax field isolates for high-throughput whole genome sequencing.
- Author
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Auburn S, Marfurt J, Maslen G, Campino S, Ruano Rubio V, Manske M, Machunter B, Kenangalem E, Noviyanti R, Trianty L, Sebayang B, Wirjanata G, Sriprawat K, Alcock D, Macinnis B, Miotto O, Clark TG, Russell B, Anstey NM, Nosten F, Kwiatkowski DP, and Price RN
- Subjects
- Humans, Malaria, Vivax diagnosis, Plasmodium vivax isolation & purification, Real-Time Polymerase Chain Reaction, DNA, Protozoan genetics, DNA, Protozoan isolation & purification, Genome, Protozoan, High-Throughput Nucleotide Sequencing methods, Malaria, Vivax parasitology, Plasmodium vivax genetics
- Abstract
Whole genome sequencing (WGS) of Plasmodium vivax is problematic due to the reliance on clinical isolates which are generally low in parasitaemia and sample volume. Furthermore, clinical isolates contain a significant contaminating background of host DNA which confounds efforts to map short read sequence of the target P. vivax DNA. Here, we discuss a methodology to significantly improve the success of P. vivax WGS on natural (non-adapted) patient isolates. Using 37 patient isolates from Indonesia, Thailand, and travellers, we assessed the application of CF11-based white blood cell filtration alone and in combination with short term ex vivo schizont maturation. Although CF11 filtration reduced human DNA contamination in 8 Indonesian isolates tested, additional short-term culture increased the P. vivax DNA yield from a median of 0.15 to 6.2 ng µl(-1) packed red blood cells (pRBCs) (p = 0.001) and reduced the human DNA percentage from a median of 33.9% to 6.22% (p = 0.008). Furthermore, post-CF11 and culture samples from Thailand gave a median P. vivax DNA yield of 2.34 ng µl(-1) pRBCs, and 2.65% human DNA. In 22 P. vivax patient isolates prepared with the 2-step method, we demonstrate high depth (median 654X coverage) and breadth (≥89%) of coverage on the Illumina GAII and HiSeq platforms. In contrast to the A+T-rich P. falciparum genome, negligible bias was observed in coverage depth between coding and non-coding regions of the P. vivax genome. This uniform coverage will greatly facilitate the detection of SNPs and copy number variants across the genome, enabling unbiased exploration of the natural diversity in P. vivax populations.
- Published
- 2013
- Full Text
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12. Ex vivo drug susceptibility of ferroquine against chloroquine-resistant isolates of Plasmodium falciparum and P. vivax.
- Author
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Marfurt J, Chalfein F, Prayoga P, Wabiser F, Kenangalem E, Piera KA, Machunter B, Tjitra E, Anstey NM, and Price RN
- Subjects
- Drug Resistance, Metallocenes, Aminoquinolines pharmacology, Antimalarials pharmacology, Chloroquine pharmacology, Ferrous Compounds pharmacology, Plasmodium falciparum drug effects
- Abstract
Ferroquine (FQ; SSR97193), a ferrocene-containing 4-aminoquinoline derivate, has potent in vitro efficacy against chloroquine (CQ)-resistant Plasmodium falciparum and CQ-sensitive P. vivax. In the current study, ex vivo FQ activity was tested in multidrug-resistant P. falciparum and P. vivax field isolates using a schizont maturation assay. Although FQ showed excellent activity against CQ-sensitive and -resistant P. falciparum and P. vivax (median 50% inhibitory concentrations [IC(50)s], 9.6 nM and 18.8 nM, respectively), there was significant cross-susceptibility with the quinoline-based drugs chloroquine, amodiaquine, and piperaquine (for P. falciparum, r = 0.546 to 0.700, P < 0.001; for P. vivax, r = 0.677 to 0.821, P < 0.001). The observed ex vivo cross-susceptibility is likely to reflect similar mechanisms of drug uptake/efflux and modes of drug action of this drug class. However, the potent activity of FQ against resistant isolates of both P. falciparum and P. vivax highlights a promising role for FQ as a lead antimalarial against CQ-resistant Plasmodium and a useful partner drug for artemisinin-based combination therapy.
- Published
- 2011
- Full Text
- View/download PDF
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